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El-Khoury, Joe M. "Chronic Kidney Disease: Vitamin D Treatment Regimens and Novel Assay Development for Kidney and Cardiovascular Function Biomarkers." Cleveland State University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=csu1343914060.
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Masconi, Katya. "The occurance of genetic variations in the MYH9 gene and their association with CKD in a mixed South African population." Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/71697.
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Thesis (MScMedSc)--Stellenbosch University, 2012.ENGLISH ABSTRACT: The purpose of this study was to investigate the association of the selected MYH9 single nucleotide polymorphisms (SNPs) with chronic kidney disease (CKD) and its related co-morbidities in the South African mixed ancestry population residing in Bellville South, Cape Town. In 2008, two landmark studies identified SNPs in the MYH9 gene which explained most of the increased risk for non-diabetic CKD in African Americans. These polymorphisms were later found to be weakly associated with diabetic nephropathy. Three SNPs that exhibited independent evidence for association with CKD were selected (rs5756152, rs4821480 and rs12107). These were genotyped using a Taqman genotyping assay on a BioRad MiniOpticon and confirmed by sequencing in 724 subjects from Bellville South, Cape Town, South Africa. Prevalent CKD was defined based on the estimated glomerular filtration rate calculated using the modification of diet in renal disease (MDRD) formula. Chronic kidney disease was present in 214 subjects (29.6%), 96.3% were stage 3 and only 8 subjects were stage 4. In additive allelic models, adjusted for age and gender, rs5756152 demonstrated an association with kidney function whereby each G allele of rs5756152 increased eGFR by 3.67 ml/min/1.73, reduced serum creatinine by 4.5% and increased fasting plasma glucose by 0.51 mmol/L. When an interaction model was used, the effect of rs5756152 on serum creatinine, eGFR and blood glucose levels was retained, and enhanced, but only in diabetic subjects. In addition, rs4821480 T allele increased eGFR while rs12107 A allele decreased glucose levels in diabetic subjects. In contrast to reports that MYH9 SNPs are strongly associated with non-diabetic end stage renal disease, our study demonstrated that rs5756152 and rs4821480 are associated with early kidney function derangements in type 2 diabetes whilst rs12107 is associated with glucose metabolism. Our findings, along with previous reports, suggest that the MYH9 gene may have a broader genetic risk effect on different types of kidney diseases than previously thought.
AFRIKAANSE OPSOMMING: Hierdie studie het ondersoek ingestel na die verband tussen drie gekose MYH9-enkelnukleotied-polimorfismes (SNP’s) en chroniese niersiekte (hierna ‘niersiekte’), wat verwante ko-morbiditeite insluit, onder ’n Suid-Afrikaanse populasie van gemengde afkoms in Bellville-Suid, Kaapstad. Twee rigpuntstudies het in 2008 op SNP’s in die MYH9-geen afgekom wat verklaar het waarom Afro-Amerikaners ’n hoër risiko vir niediabetiese niersiekte toon. Later is bevind dat hierdie polimorfismes ook ’n swak verband met diabetiese nefropatie het. Drie SNP’s wat elk onafhanklik bewys gelewer het van ’n verband met niersiekte is vervolgens gekies (rs5756152, rs4821480 en rs12107). Die SNP’s is daarná met behulp van die Taqman-toets op ’n BioRad MiniOpticon aan genotipering onderwerp, en is toe deur middel van reeksbepaling by 724 proefpersone van Bellville-Suid, Kaapstad, Suid-Afrika, bevestig. Die voorkoms van niersiekte is bepaal op grond van die geraamde glomerulêre filtrasietempo (eGFR), wat aan die hand van die ‘niersiekte-dieetveranderings’- (MDRD-)formule bereken is. Daar is bevind dat 214 proefpersone (29,6%) aan chroniese niersiekte ly – 96,3% was in fase 3 en slegs agt proefpersone in fase 4. In toegevoegde alleliese modelle wat vir ouderdom en geslag aangepas is, het rs5756152 ’n verband met nierfunksie getoon: Elke G-allel van rs5756152 het eGFR met 3,67 ml/min/1,73 verhoog, serumkreatinien met 4,5% verlaag en vastende plasmaglukose met 0,51 mmol/L verhoog. Toe ’n interaksiemodel gebruik is, is die effek van rs5756152 op serumkreatinien, eGFR en bloedglukosevlakke behou en versterk, hoewel slegs by diabetiese proefpersone. Daarbenewens het die T-allel van rs4821480 eGFR verhoog, terwyl die A-allel van rs12107 ook glukosevlakke by diabetiese proefpersone verlaag het. In teenstelling met bewerings dat MYH9-SNP’s ’n sterk verband met niediabetiese eindstadiumniersiekte toon, het hierdie studie bewys dat rs5756152 en rs4821480 met vroeë nierfunksieversteurings by tipe 2-diabetes verband hou, terwyl rs12107 weer met glukosemetabolisme verbind word. Tesame met vorige studies, doen hierdie navorsingsbevindinge dus aan die hand dat die MYH9-geen dalk ’n groter genetiese risiko-effek op verskillende tipes niersiekte het as wat voorheen vermoed is.
Cape Peninsula University of Technology Research Fund
University of Stellenbosch Merit Bursary
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Amagwu, Anthony C. "Management of Chronic kidney Disease by Advanced Practice Nurses." ScholarWorks, 2018. https://scholarworks.waldenu.edu/dissertations/4832.
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Despite best available care, uncontrolled chronic kidney disease (CKD) - a complex disease that impacts millions in the United States, will eventually progress to end stage renal disease which is associated with high morbidity and mortality. New evidence suggests management of earlier stages of CKD is effective in delaying disease progression. This project evaluated the impact of a CKD class, led by a nephrology nurse practitioner, on preventing disease progression in advanced CKD patients with diabetes and hypertension. The purpose of the class was to validate the need for the advanced practice nurse (APN) in the care continuum of CKD. CKD education is a quality improvement project based on the chronic illness trajectory nursing model by Corbin and Strauss. Using a case-control method and a simple descriptive statistic to compare the mean values, retrospective data from 52 patients were analyzed. Twelve non-participating patients had a mean 7% increase in serum creatinine levels at the 1-year mark. Forty participating patients saw a mean decrease of 30% serum creatinine. With significant evidence suggesting that disease progression is delayed and renal function is improved in all study markers for patients who participated in a CKD education class led by a nephrology nurse practitioner and who received usual care - an argument can be made for updating the APN role in the continuum of care for those with CKD. The results may contribute to social change by providing improved access to quality care that addresses the socioeconomic devastation of end stage renal disease.
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So, Beng Hock. "Chronic kidney disease : determining chronicity, prevalence, variation and survival in a community chronic kidney disease (CKD) cohort." Thesis, University of Glasgow, 2018. http://theses.gla.ac.uk/30671/.
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Chronic kidney disease (CKD) is insidious and most cases are diagnosed through opportunistic serum creatinine (SCr) testing before symptoms develop. However, efforts to accurately assess prevalence have been hampered by the lack of a universally agreed definition of SCr thresholds for the diagnosis of CKD. At the turn of the millennium, two crucial developments occurred. The first was the description of the Modification of Diet in Renal Disease estimated Glomerular Filtration Rate (eGFR) which closely correlated to cumbersome measured GFR and could be used instead in daily clinical practice. The second was the publication of the Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guideline for the evaluation, classification and stratification of CKD detailing a new definition of CKD based on GFR thresholds. Together, these two developments formed the basis of CKD as we know it today. Prevalence of CKD varies, and accurate prevalence estimates are difficult to obtain especially with respect to fulfilling the chronicity criterion (reduced eGFR ≥ 90 days). Traditional risk factors for CKD are well described and non-traditional risk factors such as socio-economic status (SES), health literacy and rurality are gaining interest. SCr sampling patterns in the community mean that most individuals with CKD are tested routinely every year. This information may not be considered in its entirety by primary care providers (PCP) which may explain inaccuracies in PCP CKD registers. Accurate identification is important to direct evidence based clinical interventions to this patient group. In chapter 2, a novel algorithm for detecting CKD and confirming chronicity from a laboratory database was developed to identify a CKD cohort of the population served by NHS Ayrshire & Arran. Data linkage of additional laboratory data, Scottish Morbidity Records for co-morbidity, statin dispensing information from Prescribing Information Scotland, area SES, rurality and deaths from Information Services Division Scotland enriched the cohort. Patients on renal replacement therapy were identified and excluded through the Scottish Renal Registry. Multiple imputations were applied where appropriate to address missing values. There were 21,037 individuals from 2010 to 2012 fulfilling the definition of CKD stage 3 – 5. Prevalence of adults with CKD was 5.6% – 5.8%. Average age (± SD) of the cohort was 75 ± 11 years. 64.6% were female and average eGFR for the cohort was 47.32 ± 11.53 mL/min/1.73m2. In chapter 3, laboratory ascertainment of CKD identified 7% more cases than PCP CKD registers. Furthermore, around 25% of patients on PCP CKD registers may be wrongly coded as having CKD. There was a 3.9-fold variation in CKD prevalence amongst PCPs, ranging from 2.8% - 11.0%. Variation fell to 3-fold with laboratory ascertainment, ranging from 3.0% - 9.1%. This fell further with age and gender stratification. Stratified laboratory CKD prevalence was positively associated with SES and rurality, a novel finding, but in multivariate linear regression, only SES, in addition to age and gender, were significant predictors for CKD prevalence. Chapter 4 explored the association between SES, eGFR and all-cause mortality. One-way ANOVA demonstrates a linear relationship between eGFR and SES (F (4,15078) = 2.52, p = 0.039) with a mean difference in eGFR of 0.83 mL/min/1.73m2 between the lowest and the highest SES quintile. However, linear regression modelling found proteinuria, hypertension, peripheral arterial disease, age, gender and serum albumin to be significant predictors for eGFR, but not SES. After adjustment for age and gender imbalance, survival demonstrated substantial influence by SES, but weakened in effect with full adjustment with only Scottish Index of Multiple Deprivation (SIMD) quintile 3 demonstrating a 13% increased risk (HR 1.13, 95% CI 1.03 to 1.24) with no progressive increase in risk associated with lower levels of SES. As a quality of care marker, the dispensing of statin was examined in chapter 5. Having another diagnosis where statins are indicated, male gender, higher serum albumin, CKD stage 3B and age between 65 – 80 were associated with higher odds ratio for statin dispensing. 64% of the cohort was dispensed a statin in 2010, but the proportion fell by 5% to 58% in 2012. This fall in dispensing disproportionately affected younger and less co-morbid CKD patients who were all eligible for a statin. SES and gender did not appear to be a factor in falling dispensing rates. Average LDL levels were lower in the statin group by (mean difference) 0.78 mmol/L (95% CI 0.74 to 0.81) in 2010 and 0.93 mmol/L (0.90 to 0.97) in 2012. 37.2% of all statin prescriptions was for Simvastatin 40 mg. Statins reduce cardiovascular events and mortality in CKD. However, in older patients typical of CKD, evidence is lacking. Chapter 6 examines survival in those dispensed a statin. Those dispensed a statin were younger, more likely to be male, had higher serum albumin and more co-morbid. After full adjustment, statin dispensing was associated with a 24% lower risk of death (HR 0.76, 95% CI 0.71 to 0.83) overall, 18% benefit for primary prevention (no prior coronary heart disease or cerebrovascular disease) (0.82, 0.74 to 0.91), 32% benefit in secondary prevention (0.68, 0.60 to 0.77), 22% benefit in younger (< 76 years) CKD patients (0.78, 0.67 to 0.92) and 22% benefit in the older (≥ 76 years) CKD patients (0.78, 0.71 to 0.85) over 4.5 years follow-up. To illustrate absolute risk reduction, the number needed to treat to avoid one death for all patients is 15.8 (95% CI 12.3 to 22.2) and 12.4 (9.3 to 18.5) for older CKD patients. This thesis demonstrates that centralised ascertainment of CKD is better at case finding, than existing PCP CKD registers. The linkage of additional, routinely collated healthcare data can develop CKD registers into a powerful tool for monitoring quality of care, efficacy of therapy and hypothesis generation which can, and should be, integrated into clinical IT systems with the appropriate information governance oversight in place.
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Tangkiatkumjai, Mayuree. "Herbal and dietary supplement use in Thai patients with chronic kidney disease (CKD) and their association with progression of CKD." Thesis, University of Nottingham, 2014. http://eprints.nottingham.ac.uk/27736/.
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The primary objective of this thesis was to determine any associations between herbal and dietary supplement (HDS) use and the fast progression of chronic kidney disease (CKD) in Thai outpatients with CKD. The secondary objectives were to determine any associations between HDS use and CKD complications, and the prevalence and reasons for HDS use. A survey recruited 421 outpatients with stages 3 to 5 CKD from two kidney clinics in Thailand, from January to June 2012. A prospective cohort study followed up these respondents, in particular noting their serum creatinine, as well as serum levels of potassium and phosphate, for 12 months. Such data were extracted from patients’ medical notes. Three hundred and fifty-seven respondents were followed up. The exposed group was defined as the current and regular users of HDS, and the primary outcome of the cohort study was defined as either a decline in the estimated glomerular filtration rate of at least 5 ml/min/1.73m2/year or the initiation of renal replacement therapy. Sixteen HDS users were recruited from the survey to be interviewed about their reasons for using HDS, using open-ended questions to elicit information in the qualitative study. Exclusion criteria were those with had received renal replacement therapy before recruitment. Univariate and multivariate analyses were performed to determine the associations using Chi-squared tests and multiple logistic regressions. Tests were 2-tailed and a p-value < 0.05 was considered statistically significant. The prevalence of HDS use during the previous year in Thai patients with CKD was 45% (95%CI 40%-50%). The most frequently reported influences on HDS use in the survey and the qualitative study were family members, friends and perception of benefits gained from using HDS. An association between HDS use and CKD progression was not found (adjusted OR 1.16, 95%CI 0.66 – 2.03). Two respondents (0.6%) had acute kidney injury, which may be related to the use of unknown Chinese herbal medicines or river spiderwort combined with diclofenac; issues which were reported by their doctor in their medical note. HDS use was associated with uncontrolled hyperphosphatemia (adjusted OR 3.53, 95%CI 1.20 – 10.43), possibly due to the HDS used in the cohort study which contained phosphate or vitamin D. Health care providers should closely monitor CKD patients using Chinese herbal medicine, river spiderwort or HDS containing phosphorus or vitamin D. Further studies need to examine renal adverse effects of specific herbal medicines, particularly in relation to acute kidney injury.
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Eyre, Heather. "Urotensin II in the development of experimental chronic kidney disease." Thesis, University of Manchester, 2015. https://www.research.manchester.ac.uk/portal/en/theses/urotensin-ii-in-the-development-of-experimental-chronic-kidney-disease(e12bed8b-1bef-4bd1-9b19-5546ce7e1af9).html.
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Urotensin II (UII) is a potent peptide hormone with a complex species and vessel-dependent vascular profile. UII and the homologous UII-related peptide (URP) bind to the g-protein coupled urotensin II receptor (UT) with high affinity. The peptide ligands and receptor have been detected in numerous human and rat tissues including heart, brain and kidney. The kidney is a major source of UII, which appears to act as both an endocrine and paracrine mediator of renal function. UII has been shown to influence renal blood flow, glomerular filtration rate and sodium handling in the renal tubules. More speculative actions of UII as a pro-fibrotic mediator include the activation of fibroblasts and promotion of collagen synthesis. Abnormally elevated UII, URP and UT expression has been highlighted in a number of cardio-renal disease states; particularly end stage renal disease, diabetes and diabetic nephropathy (DN). This work aims to investigate the role of the UII system in the development and progression of CKD using an experimental model of CKD in rodents. The first aim of the current work involved establishing the surgical 5/6th subtotal nephrectomy (SNx) model of chronic kidney disease (CKD) in the laboratory and forming a profile of UII expression in late stage experimental CKD to complement UII clinical data which are exclusively from patients in the later stages of disease. UII/URP and UT were substantially over-expressed in the kidneys of SNx rats in late stage CKD. This novel insight complements the clinical profile of CKD/DN where over expression of the UII system is routinely reported. In a second study the 5/6th SNx rat model was used to explore the effects of chronic UT receptor antagonism on the progression of CKD. Although there were no discernible differences in kidney mass or histological profile between the treatment groups at the end of the study, there was a small delay in the development of albuminuria and in the onset of systolic blood pressure elevation in the UT antagonist treated cohort. The study did not produce clear-cut evidence defining the potential therapeutic value of UT-antagonism in the treatment of CKD. Despite this the results are encouraging and suggest that the role of UT-inhibition in CKD is worth considering further.
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Ferrer, Lucas Manuel. "ROLE OF CKD AND CASPASE-1 IN NEOINTIMAL HYPERPLASIA DEVELOPMENT." Master's thesis, Temple University Libraries, 2014. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/300901.
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Public HealthM.S.
Vascular access dysfunction is a cause of morbidity and mortality in chronic kidney disease (CKD) patients that require hemodialysis. The major cause of vascular access failure is venous stenosis due to neointimal hyperplasia (NH). Vascular smooth muscle cells (VSMC) are critical for the development of NH lesions, as they have the ability to modulate their phenotype from a "contractile" to a "synthetic" phenotype in the presence of uremia, through the regulation of sensor genes for uremia danger signals and VSMC-specific differentiation genes. Recent research indicates that Caspase-1 (casp-1) activation plays an essential role in sensing metabolic danger signal-associated molecular patterns and initiating vascular inflammation. Carbamylated LDL, a uremic toxin that has been shown to be found in higher levels in patients with CKD and in CKD murine models when compared to controls, and could play a role in casp-1 activation. Therefore, the goal of this project is to examine the role of cLDL/CKD-driven casp-1 activation in VSMC and CKD-related NH. We have established a CKD mouse model and published on CKD-associated vascular remodeling. We exposed wild type and caspase-1 knockout mice to our CKD model, analyzed and quantified the NH lesion formed. We also examined in vitro and ex-vivo changes in VSMC-specific differentiation genes when exposed to uremic serum and cLDL, in the presence or absence of caspase-1 inhibitor. We found that CKD serum induces with casp-1 activation and phenotypic changes in VSMCs from a "contractile" to a "synthetic" phenotype, which are reversed with casp-1 inhibition. In an ex-vivo model using relative quantification we found that VSMC contractile markers α -Actin, Calponin, SM-22, and Smoothelin gene expression of CKD mouse carotid VSMC were higher in casp-1 knockout mice when compared to wild-type (1.40, 1.28, 1.22, 1.41 respectively). Also using an in-vivo model, relative quantification of α-actin decreased from 1.0 to 0.329 when VSMCs were exposed to uremic serum and but increased back to 0.588 when Caspase-1 inhibitor is added. The relative quantification of Calponin also decreased from 1.0 to 0.394 when exposed to uremic serum and increased back to 0.601 with caspase-1 inhibitor. We also found that caspase-1 deficiency significantly reversed CKD-related vascular remodeling in casp-1 knockout mice and reduced NH volume by 50% from 1,440,023in wild-type mice to 71,069 µm2 in casp-1 knockouts (p-value 0.002). This evidence provides evidence that casp-1 plays a critical role in NH formation. Furthermore our results provide a novel insight over the therapeutic potential of casp-1 inhibitors for CKD induced NH and other inflammation induced vascular remodeling.
Temple University--Theses
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Lim, Kenneth Jia-En. "Role of Klotho in the development of vascular calcification in patients with chronic kidney disease (CKD)." Thesis, University of Warwick, 2012. http://wrap.warwick.ac.uk/50202/.
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Background: Cardiovascular disease is the leading cause of mortality in patients with Chronic Kidney Disease (CKD). Vascular calcification is a significant contributor to cardiovascular mortality in CKD. Klotho is a 130kDa transmembrane protein with cardiovasculo-protective properties and also functions as a co-factor for the phosphatonin, fibroblast growth factor (FGF)-23 at the kidney. FGF-23 levels rise in CKD despite progression of accelerated vascular calcification (VC). There are currently conflicting data on whether FGF-23 may exhibit direct vasculo-protective effects in CKD. Methods and results: In this study, we describe for the first time endogenous Klotho expression in human arteries and human aortic smooth muscle cells (HASMCs). We show that CKD is a state of vascular Klotho deficiency promoted by chronic circulating stress factors, including pro-inflammatory, uremic and disordered metabolic conditions. Mechanistic studies demonstrated that Klotho knockdown potentiated the development of accelerated calcification through a Runx2 and myocardin-SRF dependent pathway. Klotho knockdown studies further revealed that vascular cells are a Klotho-dependent target tissue for FGF-23. FGF-23 mediated cellular activation of p-ERK, p-AKT and cellular proliferative effects, which were abrogated following Klotho knockdown. We next showed that vascular Klotho deficiency driven by pro-calcific stressors could be restored by vitamin D receptor (VDR) activators, in vitro and further confirmed using human arterial organ cultures from CKD patients, in vivo. Furthermore, restoration of Klotho by vitamin D receptor (VDR) activators conferred HA-SMCs FGF-23 responsive and unmasked its anticalcific effects. Conclusions: Chronic metabolic stress factors found in CKD promote vascular Klotho deficiency. Mechanistic studies revealed a bi-functional role for local vascular Klotho, first as an endogenous inhibitor of VC and second, as a co-factor required for vascular FGF-23 signalling. Furthermore, VDR activators can restore Klotho expression and unmask FGF-23 anti-calcific effects.
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Lomas, Amy. "The renal effects of nonsteroidal anti-inflammatory drugs (NSAIDS) in dogs with chronic kidney disease (CKD)." Thesis, Kansas State University, 2013. http://hdl.handle.net/2097/20475.
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Master of ScienceDepartment of Clinical Sciences
Gregory F. Grauer
Prostaglandins play many important roles in the kidney including regulation of renal blood flow, glomerular filtration, renin release, and sodium excretion. Upon activation of the renin angiotensin aldosterone system (RAAS), prostaglandin upregulation becomes critical to offset the vasoconstrictive effects of norephinephrine, angiotensin II, and vasopressin. Nonsteroidal anti-inflammatory drugs (NSAIDs) produce both their beneficial and detrimental effects through inhibition of the cyclooxygenase enzyme and subsequent interference with prostaglandin production. Healthy canine kidneys express both COX-1 and COX-2, although basal COX-2 expression in dogs is significantly higher than in other species. Nonsteroidal anti-inflammatory drugs that spare COX-1 have exhibited less gastrointestinal toxicity, but no NSAID has been proven safe for the kidney. The kidney is the organ with the second highest reports of adverse drug events, which is usually manifested as functional changes. However, structural changes including renal papillary necrosis, can occasionally be observed. Dogs with chronic kidney disease could be expected to be at increased risk for NSAID-related adverse drug effects. As nephrons and renal reserve are lost in chronic kidney disease, the canine kidney becomes more dependent on COX-2 for production of prostaglandins. Inasmuch as the prevalence of both CKD and OA increases with age, it is expected that many dogs being treated with NSAIDs for OA will have loss of renal reserve and/or early stage CKD. If administration of an NSAID is required for long term treatment of osteoarthritis, frequent monitoring of blood pressure and renal parameters, as well as hepatic enzymes are recommended.
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Miller, Matthew Scott. "The effect of calcifediol supplementation on renin-angiotensin-aldosterone system mediators in dogs with chronic kidney disease." The Ohio State University, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1618829782648424.
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Hadeiba, Tareg Hadi Ahmed. "The role of iron in oxidative stress accelerated endothelial dysfunction in chronic kidney disease." Thesis, University of Bradford, 2015. http://hdl.handle.net/10454/14325.
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Chronic kidney disease (CKD) is growing global public health problem affecting 1 in 10 adults in developed countries and recognised as an important risk factor for cardiovascular disease (CVD) development. CVD is the main cause of death among CKD patients. Endothelial injury and dysfunction are critical steps in atherosclerosis, a major CVD. Oxidative stress (increased level of reactive oxygen species, ROS) has been associated with CVD development. Intravenous (IV) iron preparations are widely used in the management of CKD mediated anaemia, and have been associated with increased oxidative stress and cellular dysfunction. This study examined the effect of pharmacologically-relevant concentrations of IV Venofer (iron sucrose) or IV Ferinject (Ferric carboxymaltose, FCM) on primary human umbilical vein endothelial cell (HUVEC) activation/damage and on intracellular ROS generation as well as studying the potential mechanisms responsible. Data from TUNEL assay and Annexin V-FITC/PI staining showed that, IV FCM had no effect, but IV iron sucrose increased HUVEC apoptosis at 24hr. IV iron sucrose inhibited cell proliferation and reduced cell viability. Both compounds induced EC activation through sustained activation of p38 MAPK and up-regulation of ICAM-1 and VCAM-1. Additionally, the compounds induced significant increase in total ROS and superoxide anion production, which was attenuated by the anti-oxidant N-acetylcysteine (NAC). P38 MAPK showed up-regulation of pro-apoptotic protein Bax and down-regulation of antiapoptotic Bcl-2 protein in HUVEC treated with IV iron sucrose and p38 inhibition reversed these effects. In summary, these results suggest that IV iron sucrose causes more severe EC injury than IV FCM. However, both IV iron preparations induced intracellular ROS and superoxide anion generation in HUVEC leading to EC activation/dysfunction, providing a potential explanation for vascular damage in CKD patients.
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Rudomanova, Valeriia. "Unraveling the Secrets of Kidney Disease: Novel Molecular Mechanisms of Acute and Chronic Kidney Injury." University of Cincinnati / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1623250686588821.
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Alderson, Helen. "Investigation of chronic kidney disease related biomarkers in association with clinical characteristics and outcomes in a large prospective CKD cohort." Thesis, University of Manchester, 2017. https://www.research.manchester.ac.uk/portal/en/theses/investigation-of-chronic-kidney-disease-related-biomarkers-in-association-with-clinical-characteristics-and-outcomes-in-a-large-prospective-ckd-cohort(de946dd2-b3b6-4466-a8f4-9d5f212d81e2).html.
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Chronic Kidney Disease (CKD) is common and is associated with increased risk of progression to end stage renal disease, cardiovascular disease and death. CKD is a heterogeneous condition and accurately predicting an individual’s risk for adverse outcomes remains a challenge. Over the past decade there has been a focus on the identification of novel biomarkers that may help improve risk stratification and the prediction of clinical endpoints in this population. The overall aim of this research project was to investigate a series of novel biomarkers in patients from the Chronic Renal Insufficiency Standards Implementation Study (CRISIS), a prospective observational study of outcome in all cause non-dialysis dependent CKD 3-5. The biomarkers selected for this project were Anti-Apolipoprotein A-1 (Anti-apoA-1 IgG), fetuin-A, fibroblast growth factor-23 (FGF23), high sensitivity cardiac troponin T (HS-cTnT), kidney injury molecule-1 (KIM-1), N-terminal pro-brain natriuretic peptide (NT-proBNP), neutrophil gelatinase associated lipocalin (NGAL) and osteoprotegerin (OPG). These biomarkers were chosen to address the three clinical endpoints of progression, cardiovascular disease and death with biomarkers considered both individually and as groups of related markers. The first aim of this project was to examine associations between the novel biomarkers and the clinical characteristics of the CRISIS population. The second aim was to investigate the associations between novel biomarkers and the study endpoints. In the case of FGF23 longitudinal measurements were analysed and in all other cases associations between baseline levels of the markers and clinical outcomes were considered. The third aim was to consider whether the biomarkers investigated in this project actually improve parameters of risk stratification and model discrimination, thereby demonstrating a potential to improve the prediction of outcome events in the CKD population. Many of the biomarkers were independently associated with one or all of the clinical outcomes considered. Despite these associations, it was more difficult to demonstrate clear improvement in risk classification or the prediction of clinical endpoints. Baseline models of standard biochemical and clinical parameters performed very well so even biomarkers that were strongly associated with clinical outcomes resulted in only small incremental improvements in the prediction of outcome events. It is now important to focus on defining how biomarkers may fit into clinical decision pathways.
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Hossain, Mohammad Parvez. "Chronic kidney disease (CKD) : natural history and impact of socio-economic factors as well as health service provisions." Thesis, University of Sheffield, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.574569.
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Background: Worldwide, the rapidly rising prevalence of chronic kidney disease (CKO) and the impact of adverse outcomes including endstage renal disease (ESRO) on renal replacement therapy (RRT) and cardiovascular rnorbiditv and mortalitv are an increasing public health burden. Aims: To investigate the natural history of CKO; the predictors of progression and regression of CKO in a clinic population, including demographic, clinical and socio-economic factors and explore the implications for health services of variations in prevalence and severity Methods: A retrospective cohort was established and data collected using clinic records and postal questionnaires Models were developed of the predictors of outcomes in CKO patients attending a single clinic and by using geographical information system (GIS), to investigate socioeconomic inequalities in terms of workload for primary care at area level in Sheffield, UK Results: In a cohort of 918 patients, 22% of the patients had regression 44~'O remained stable, only 34% experienced progression. This was despite of the vast majority presenting with late stages of CKO; mainly stages 3 and 4. In the multivariare model. beyond the expected predictors that reflected reversal of traditional risk of progression such as lower baseline SBP and lower proteinuria, we observed that lower baseline. eGFR and serum phosphorous, higher haemoglobin and not using ACEi/ARB were independent predictors of regression CKO patients from the most deprived areas experienced a higher proportion of progression as well as a faster rate of progression of CKD compared to those lived in the least deprived areas (lMO quintile 5 44% progression and 13%) rapid progression; IMD quintile 1. 13% progression and 6% fast progression). Furthermore, we found those who living in more deprived areas, a strong independent risk for presentations with heavy proteinuria and progression and rapid progression of CKD. We also found, there was significant clustering of ('KO patients referred to the hospital in the most deprived areas Both the prevalence of CKO and associated conditions (OM, HTN, CHO, and Obesity) and case load per general practitioner (GP) were significantly higher in deprived areas. Conclusions: Predictors of progression and regression need to be better understood in order to inform prognosis and clinical practice Health commissioners and providers need to ensure that high quality services for early identification and active management of CKO are available, particularly in relatively deprived areas.
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Malanda, Eufrásia Maria de Oliveira. "Tradução para português de “Chronic Kidney Disease (CKD): clinical practice recommendations for primary care physicians and healthcare providers”." Master's thesis, Universidade de Évora, 2018. http://hdl.handle.net/10174/30055.
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A presente dissertação concilia a tradução da obra intitulada – “Chronic Kidney Disease (CKD): Clinical Practice Recommendations for Primary Care Physicians and Healthcare Providers”, publicada por Gregory e Jerry em 2015 – e a elaboração de uma proposta de glossário bilingue (inglês/português) sobre Doença Renal Crónica.
Ancorado em pressupostos teóricos das áreas de Estudos de Tradução e Terminologia, o trabalho desenvolvido visa contribuir para a disseminação do conhecimento científico; Abstract:
A Portuguese Translation of “Chronic Kidney Disease (CKD): Clinical Practice Recommendations for Primary Care Physicians and Healthcare Providers”
This dissertation combines the translation of the book – “Chronic Kidney Disease (CKD): Clinical Practice Recommendations for Primary Care Physicians and Healthcare Providers”, published by Gregory and Jerry Yee in 2015 – and a proposal to create a bilingual (EN-PT) glossary of terms for chronic kidney disease.
Grounded in theoretical paradigms of both Translation Studies and Terminology, the work developed aims at contributing to the dissemination of scientific knowledge.
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Yarkiner, Zalihe. "Developing longitudinal models for monitoring chronic diseases in computerised general practice (GP) records : a case study in chronic kidney disease (CKD)." Thesis, Kingston University, 2015. http://eprints.kingston.ac.uk/34536/.
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Analysis of longitudinal data is a rapidly growing field of statistical analysis, in response to the increasing availability of longitudinal datasets in many disciplines. Longitudinal studies are becoming more popular as they allow investigation of the same individuals over time, and where both within-individual and between-individual differences can be examined. Since the study of change over time is necessary in many areas, longitudinal studies and meaningful analysis of longitudinal data is essential. The health sector is one such area where longitudinal research is playing an increasingly important role. The aim of this research is to examine statistical methodologies for the analysis of longitudinal medical data, specifically General Practice (GP) records. All General Practices (GPs) in England and Wales are now computerized and routinely record detailed patient information, hence providing a rich longitudinal dataset. This research investigates new techniques and adaptations of existing methodologies to understand and explain patterns of change and the natural development and treatment of chronic diseases within routinely collected GP data. The data used here, although taken from a raw sample of 129 General Practice records, have been subjected to some cleaning and recoding in places, hence it should be considered as a secondary data source. Through out the data driven applications presented, different sub¬samples of the original dataset have been used. For the main part the full cleaned sample of 876951 patients is used where possible. Smaller samples ranging between 472 and 58675 patients are used depending on the outcome of interest and the availability of valid observations for the various applications employed. Mainly regression-based techniques, in two broad categories, were used to analyse the repeated measurements from each patient in our dataset. Firstly, linear and generalized mixed modelling approaches were used, whereas in the second phase of the project, the applications of semi-parametric and non-parametric approaches were investigated. The case study of particular interest in this research project is the incidence and progression of chronic kidney disease (CKD). There is a lack of knowledge and understanding of the natural history ofCKD and its progression over time. This project aims to address these issues. The advanced statistical models used in this research quantify how kidney function, assessed using estimated Glomerular Filtration Rate (eGFR), changes with respect to time and how other factors, including other related medical conditions (known as co-morbidities of CKD), affect kidney function and its change over time. The techniques and approaches used in this study are motivated by mixed model designs. The decline of kidney function as time progresses for typical CKD patients is observed to be non-linear. The type of nonlinear mixed models developed in this project do not assume that the decline of eGFR over time is linear, and hence are better able to model the progression of CKD than more traditional linear models. As a consequence, the proportion of the total variation in the outcome that can be explained by considering the patient level factors is tripled through the use of these non-linear models, showing they have much greater explanatory power than previous, simpler statistical models. The disease under study is Chronic Kidney Disease (CKD) but the methodologies should also be applicable other chronic, progressive diseases.
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Mirza, Majd A. I. "The role of fibroblast growth factor-23 in chronic kidney disease-mineral and bone disorder." Doctoral thesis, Uppsala universitet, Medicin, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-130339.
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Fibroblast growth factor-23 (FGF23) was initially identified as the causative factor of autosomal dominant hypophosphatemic rickets. Further studies confirmed that FGF23 is predominantly expressed in the osteocytes and osteoblasts of bone and that circulating FGF23 acts on the kidney to inhibit renal phosphate reabsorption and 1,25(OH)2D3 hydroxylation. With the progression of chronic kidney disease (CKD), the kidneys become insufficient to maintain a normal systemic mineral homeostasis, resulting in various abnormalities of bone and mineral metabolism, generally referred to as Chronic Kidney Disease – Mineral and Bone Disorders (CKD-MBD). FGF23 increases early in the course of CKD in order to maintain normal serum phosphate levels; long before a significant increase in serum phosphate can be detected. Recent studies suggest that increased FGF23 levels are associated with progression of CKD, mortality, and the development of refractory secondary hyperparathyroidism. Because FGF23 is the very earliest marker of CKD-MBD, it is of particular interest to evaluate the relation between FGF23 and CKD-MBD abnormalities, in the setting of early CKD and also in individuals with normal renal function. In the present work, we show that FGF23 is linked to several dynamic measurements of vascular function, including endothelial dysfunction, arterial stiffness, and atherosclerosis. FGF23 is also positively associated with left ventricular mass index and an increased risk of having left ventricular hypertrophy. All associations were independent of serum phosphate and were strengthened in subjects with diminished renal function. Furthermore, we found significant evidence for an association between higher FGF23 and increased fat mass and dyslipidemia, which could represent a novel pathway linking FGF23 to cardiovascular disease. Finally, we show that FGF23 is a significant predictor of future fracture risk. Although these associations could be reflecting the increased risk associated with hyperphosphatemia and calcitriol deficiency, current evidence points towards FGF23 being more than an innocent bystander. At the very least, FGF23 holds promise of being a bio-marker of cardiovascular status and phosphate-related toxicity both in CKD and in the general population, and might be a therapeutic target that could improve the fatal prognosis in CKD patients.
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Geneen, Louise. "Resistance (exercise) training in non-dialysis dependent chronic kidney disease (CKD stage 3) and validation of ultrasound in the measurement of muscle size and structure in haemodialysis patients (CKD stage 5)." Thesis, Queen Margaret University, 2014. https://eresearch.qmu.ac.uk/handle/20.500.12289/7416.
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Aim: This thesis set out to make an original contribution to knowledge with regard to methods of assessing muscle size and architecture in the CKD and ESRD population, and to assess the ability to improve the muscle size and architecture, and symptoms of uraemia, by implementing an anabolic intervention (resistance exercise training) in the CKD population. Outcome measures: Ultrasound was shown to have high validity (against gold standard MRI measures; ICCs: VLACSA 0.96, VL depth 0.99, fat depth 0.98) and intra-rater reliability (ICCs: VL depth 0.98, total muscle depth 0.97, fat depth 0.99; MDC: VL depth 0.14cm, total muscle depth 0.19cm, fat depth 0.22cm) in measuring regional body composition at the mid-VL site in the CKD population. There were significant (p<0.01) correlations between US-derived measures of (mid-VL) muscle size and architecture with strength and function (larger muscle mass and/or pennation angle positively correlated with higher strength and/or functional performance). Patient-reported uraemic symptoms were worse (p<0.01) in those with reduced strength and/or function. Intervention results: An anabolic (resistance training) intervention (12-weeks, randomized to once [RT1 n=7] or three times [RT3 n=10] per week, 80%1RM) brought about significant improvements over time (p<0.01) in all measures of muscle size and architecture (VL depth, total muscle depth, VLACSA, pennation angle). Interaction effects (group*time) were only seen in pennation angle (p<0.05) and VLACSA (p<0.01) where RT3 gains were greater than RT1 from week 8 onwards. All measures of strength, function, and uraemic symptoms improved over time (p<0.01) with no interaction effects (no difference from greater training frequency/ volume). Clinical and research implications: The intervention results suggest implementing a RT form of “prehabilitation” in early stage (CKD3) patients just once per week is sufficient to bring about statistically and clinically important changes in strength and function that benefit the patient through reduced frequency and/or intrusiveness of uraemic symptoms (improved health-related quality of life), with minimal time-commitment. Further research should examine if there is additional benefit to the significantly greater increases in VLACSA and pennation angle observed in RT3, with regards to long-term maintenance of functional improvements, and whether an RT1 or RT3 programme delays the progression of CKD, the need for RRT, and patient mortality.
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Eddington, Helen. "Improving the outcomes of patients with chronic kidney disease-mineral bone disorder." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/improving-the-outcomes-of-patients-with-chronic-kidney-disease--mineral-bone-disorder(0c72d2af-4523-43c4-a1f9-95ecb304e5ac).html.
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Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) is a systemic disorder which includes abnormal bone chemistry, vascular or soft tissue calcification, and abnormal bone formation. Many of the parameters of CKD-MBD have been associated with an increased mortality risk in renal patients. There were three main facets to this research project. The first aim of this research was to perform two different studies using the Chronic Renal Insufficiency Standards Implementation Study (CRISIS) data. This prospective epidemiological study is designed to identify factors associated with renal progression and survival in the pre-dialysis CKD population. We have shown that for each 0.323mmol/L (1mg/dL) increase in serum phosphate there was a significant stepwise increased risk of death. (HR1.3 (1.1, 1.5) P=0.01). The association of baseline phenotypic data against vascular stiffness measurements was also investigated. Augmentation index measured at the radial artery was associated with a raised systolic blood pressure but no association with biochemical abnormalities was found.We hypothesised that the phosphate effect on survival was related to the effects within the CKD-MBD spectrum and therefore control of secondary hyperparathyroidism would improve bone and cardiovascular parameters. Therefore for the second part of this research we performed a randomised controlled trial to examine the effects of cinacalcet with standard therapy compared to standard therapy alone on bone and cardiovascular parameters in haemodialysis patients with uncontrolled hyperparathyroidism. The change of biochemical parameters and cardiovascular markers were also further explored in secondary analyses alongside survival data. The primary end point of change in vascular calcification at 52 weeks showed no significant difference between arms. As equivalent control of phosphate and iPTH was achieved in both arms secondary analyses were performed. This showed a significant regression of left ventricular hypertrophy and carotid intima-media thickness associated with phosphate but not iPTH reduction. Patients whose phosphate reduced during the study had a survival advantage when followed for 5 years (HR=10.2 (1.1, 104.5) P=0.049). The third part of this research was to investigate iPTH assay variability. We explored the variation in iPTH assays across the North West and paired this with regional audit data. This study showed that despite there being significant variation among iPTH assays across the region the variation in clinical management was still accounting for some variation in achieving PTH targets.In conclusion, serum phosphate, within the normal laboratory range, is associated with an increased mortality in CKD patients. Haemodialysis patients may have improvement of cardiovascular outcomes with tight control of secondary hyperparathyroidism, by whichever therapeutic means. Intact PTH assays variation may alter our clinical management but variation in practice still affects guideline achievement.
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Prieto, Roseanne. "Preventing Progression of End Stage Renal Disease: A Systematic Review of Patient-Provider Communication in Primary Care." Diss., The University of Arizona, 2016. http://hdl.handle.net/10150/612943.
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Background: Chronic kidney disease (CKD) affects approximately 26 million individuals in the United States and is a top priority in the objectives for Healthy People 2020. Despite efforts to improve awareness, discussion of CKD is often minimal or ineffective in the primary care setting. This leads to a lack of patient awareness and knowledge of self-care skills to prevent or slow progression of the disease. A lack of communication of has been attributed to the provider's lack of confidence and knowledge to discuss CKD and to avoid unnecessary stress. Purpose: The purpose of the DNP project is to provide a systematic review of patient-provider communication processes used to influence self-management or behavioral change in primary care and propose a tool to enhance communication and slow progression of CKD. Methods: A systematic review was conducted following the method guidelines of the Cochrane Collaboration. Six electronic databases were searched. Inclusion criteria were adult humans, primary research studies, systematic and literature reviews, focus on communication of self-management or behavioral change strategies, primary outcomes of improving self-management and/or patient outcomes and availability of full-text online or by request. Outcomes: Of the 5765 articles initially identified, 28 studies met inclusion criteria. The studies revealed a lack of evidence directed towards CKD and communication was not directly addressed in a majority of the studies. Interventions most successful in improving patient outcomes were individualized, elicited collaboration or interaction with the patient and provider, were motivational or encouraging and aided in barrier identification and problem solving. A communication tool was developed from the evidence in order to stimulate more meaningful conversation between the patient and provider.
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Takaori, Koji. "Severity and Frequency of Proximal Tubule Injury Determines Renal Prognosis." Kyoto University, 2018. http://hdl.handle.net/2433/232126.
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Laville, Solène. "Optimisation de la prise en charge thérapeutique des patients avec une maladie rénale chronique : étude de pharmacoépidémiologie dans la cohorte CKD-REIN Evaluation of the adequacy of drug prescriptions in patients with chronic kidney disease : results from the CKD-REIN cohort Adverse drug reactions in patients with chronic kidney disease." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASR004.
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La maladie rénale chronique (MRC) touche entre 8 et 15 % de la population adulte mondiale et jusqu’à un tiers des personnes âgées. Par rapport à la population ayant une fonction rénale normale, les patients avec une MRC présentent un risque majoré d’hospitalisation, d’effets indésirables médicamenteux (EIM) et de mortalité. Les données des résumés des caractéristiques des produits relatifs aux médicaments sont limitées chez les patients ayant une fonction rénale altérée, car cette population est exclue de la grande majorité des essais thérapeutiques. La MRC entraine une modification de la pharmacocinétique et de la pharmacodynamique d’un grand nombre de médicaments nécessitant des contre-indications et des adaptations de posologie à la fonction rénale.À partir des données de la cohorte CKD-REIN, ce travail de thèse a permis d’apporter de nouvelles informations concernant l’utilisation des médicaments dans la population de patients atteints de maladie rénale chronique modérée à avancée, suivie en néphrologie.CKD-REIN est une étude de cohorte prospective représentative réalisée dans 40 consultations de néphrologie en France. L’étude a inclus 3033 patients atteints de MRC modérée à avancée , dont 65% d’hommes, avec une médiane d’âge de 69 ans [écart interquartile (EI), 60-76]. A l’inclusion, 45% avait un débit de filtration glomérulaire estimé (DFGe) à moins de 30 mL/min/1,73m2.La plupart des patients étaient polymédiqués à l’entrée dans CKD-REIN. Le nombre médian de médicaments prescrits par patient était de 8 [EI, 5-10]. De plus, nous avons mis en évidence que plus de la moitié des patients inclus (52%) recevaient au moins une prescription qui était contre-indiquée ou dont la posologie était surdosée par rapport à leur fonction rénale. L’équation permettant d’estimer la fonction rénale du patient au moment de la prescription avait une grande importance dans l’évaluation du caractère approprié ou non des prescriptions. La baisse du DFGe et le nombre de médicaments étaient les principaux facteurs de risque d’exposition aux prescriptions inappropriées.L’étude des EIM ont montré qu’ils étaient fréquents chez les patients atteints de MRC, qu’ils soient graves ou non (taux d’incidence : 14,4 % personnes-années (PA) [intervalle de confiance (IC)95%, 12,6–16,5] pour les EIM (toute gravité confondue) et de 2,7 %PA [IC95%, 1,7–4,3] pour les EIM graves). Des médicaments tels que les inhibiteurs du système rénine-angiotensine, les antithrombotiques ou encore les diurétiques, fréquemment prescrits dans cette population, étaient les classes les plus pourvoyeuses d’EIM. Un DFGe diminué, un nombre de médicaments supérieur à 10 et une mauvaise observance thérapeutique étaient des facteurs de risque importants de survenue d’EIM.Enfin, nous nous sommes focalisés sur l’évaluation des risques associés à l’utilisation des antithrombotiques oraux dans cette population atteinte de MRC. Le risque d’hémorragie chez les patients recevant un anticoagulant oral était deux fois et demie supérieur à celui des patients ne recevant aucun antithrombotique oral (rapport de risque de 2,36 [IC95%, 1,44 ; 3,85]) et ce risque était majoré lorsque la prise d’anticoagulant oral s’accompagnait d’une prise d’antiagrégant plaquettaire (rapport de risque de 4,01[IC95%, 2,23 ; 7,20]). Un risque augmenté d’insuffisance rénale aiguë a également été mis en évidence avec la prise d’anticoagulant oral (rapport de risque de 1,89 [IC95%, 1,46; 2,44]). En revanche, nous n’avons pas retrouvé d’association significative entre la prise d’antithrombotique oral et la progression de la maladie rénale chronique vers l’insuffisance rénale terminale traitée (rapport de risque de 1,37 [IC95%, 0,92 ; 2,04]).Ce travail de thèse rend compte que la prise en charge thérapeutique des patients atteints de MRC est complexe. Il met en lumière de nombreuses pistes pour optimiser la prise en charge thérapeutique des patients atteints de MRC modérée à avancéeChronic kidney disease (CKD) affects between 8% and 15% of the world's adult population and up to one third of the elderly. Compared to the population with normal kidney function, patients with CKD are at increased risk of hospitalization, adverse drug reactions (ADRs) and mortality. Data in summaries of product characteristics are limited in patients with impaired renal function as this population is excluded from the vast majority of clinical trials. CKD greatly alters the pharmacokinetics and pharmacodynamics of a large number of drugs that require contraindications and dosage adjustments with regard to kidney function.Based on data from the CKD-REIN cohort study, this thesis made it possible to provide new information about the use of drugs in the population of patients with moderate to advanced CKD under nephrology care.CKD-REIN is a representative prospective cohort study, based on 40 nationally public and private facilities. The CKD-REIN study included 3,033 patients with moderate to advanced CKD, 65% of whom were men, with a median age of 69 years [interquartile range (IQR), 60-76]. At baseline, 45% had an estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73m2.Polypharmacy concerned most of the patients in CKD-REIN at baseline. The median number of drugs prescribed per patient was 8 [IQR, 5-10]. In addition, we have shown that more than half of the patients included (52%) received at least one prescription that was contraindicated or with an overdosed dosage according to their renal function. The equation used to estimate the patient's eGFR at the time of prescription was of great importance in assessing the appropriateness of prescriptions. A low eGFR and the number of drugs were the main risk factors for exposure to inappropriate prescriptions.The study on ADRs showed that they were common in patients with CKD, whether serious or not (incidence rate: 14.4% person-years (PA) [confidence interval (CI) 95%, 12.6–16.5] for ADRs (all severity) and 2.7% PA [95%CI, 1.7–4.3] for serious ADRs). Drugs such as inhibitors of the renin-angiotensin system, antithrombotics or diuretics, frequently prescribed in this population, were the pharmacological classes with the most ADRs. Decreased eGFR, receiving more than 10 drugs, and poor treatment adherence were significant risk factors for undergoing ADRs.Finally, we focused on assessing the risks associated with the use of oral antithrombotics in this population with CKD. The risk of hemorrhage in patients receiving an oral anticoagulant was two and a half times greater than that in patients not receiving any oral antithrombotic (hazard ratio (HR) of 2.36 [95%CI, 1.44; 3.85]) and this risk was increased when taking concomitantly an oral anticoagulant and an antiplatelet agent (HR of 4.01 [95%CI, 2.23; 7.20]). An increased risk of acute kidney injury has also been associated with the take of an oral anticoagulant (HR of 1.89 [95%CI, 1.46; 2.44]). On the other hand, we did not find a significant association between taking oral antithrombotic medication and end-stage renal disease (HR of 1.37 [95%CI, 0.92; 2.04]).This thesis shows that the therapeutic management of patients with CKD is complex. It highlights many opportunities for optimizing the therapeutic management of patients with moderate to advanced CKD
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Della, Bella Elena <1983>. "Progenitori endoteliali nei pazienti con Chronic Kidney Disease - Mineral and Bone Disorder (CKD-MBD) in fase uremica: effetti del trattamento con vitamina D." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amsdottorato.unibo.it/4636/.
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L'insufficienza renale cronica (CKD) è associata ad un rischio cardiovascolare più elevato rispetto alla popolazione generale: fattori come uremia, stress ossidativo, età dialitica, infiammazione, alterazioni del metabolismo minerale e presenza di calcificazioni vascolari incidono fortemente sulla morbosità e mortalità per cause cardiovascolari nel paziente uremico.
Diversi studi hanno verificato il coinvolgimento dei progenitori endoteliali (EPC) nella malattia aterosclerotica ed è stato dimostrato che esprimono osteocalcina, marcatore di calcificazione. Inoltre, nella CKD è presente una disfunzione in numero e funzionalità delle EPC. Attualmente, il ruolo delle EPC nella formazione delle calcificazioni vascolari nei pazienti in dialisi non è stato ancora chiarito.
Lo scopo della tesi è quello di studiare le EPC prelevate da pazienti con CKD, al fine di determinarne numero e fenotipo. È stato anche valutato l'effetto del trattamento in vitro e in vivo con calcitriolo e paracalcitolo sulle EPC, dato il deficit di vitamina D dei pazienti con CKD: il trattamento con vitamina D sembra avere effetti positivi sul sistema cardiovascolare. Sono stati valutati: numero di EPC circolanti e la relativa espressione di osteocalcina e del recettore della vitamina D; morfologia e fenotipo EPC in vitro; effetti di calcitriolo e paracalcitolo sull’espressione di osteocalcina e sui depositi di calcio.
I risultati dello studio suggeriscono che il trattamento con vitamina D abbia un effetto positivo sulle EPC, aumentando il numero di EPC circolanti e normalizzandone la morfologia. Sia calcitriolo che paracalcitolo sono in grado di ridurre notevolmente l’espressione di OC, mentre solo il paracalcitolo ha un effetto significativo sulla riduzione dei depositi di calcio in coltura. In conclusione, il trattamento con vitamina D sembra ridurre il potenziale calcifico delle EPC nell’uremia, aprendo nuove strade per la gestione del rischio cardiovascolare nei pazienti affetti da CKD.Chronic Kidney Disease (CKD) is associated to an increased cardiovascular risk compared to the general population: factors like uremia, oxidative stress, dialytic vintage, inflammation, mineral metabolism dysregulation and vascular calcifications greatly affect cardiovascular morbidity and mortality in CKD. Several papers reported the involvement of endothelial progenitor cells (EPCs) in atherosclerosis: it was also demonstrated their expression of osteocalcin, a marker of calcification. Moreover, a dysfunction in number and functionality of EPCs is also detectable in CKD. Currently, the role of EPCs in the pathogenesis of vascular calcifications in patients with CKD is not clear. The project presented herein aimed to study EPCs from CKD patients and determine their number and phenotype. Moreover, it was evaluated the effect of treatment with calcitriol and paricalcitol on EPCs, both in vivo and in vitro, because CKD patients suffer from vitamin D deficiency and it was reported that vitamin D has beneficial effects on the cardiovascular system. The number of circulating EPCs and their expression of osteocalcin and vitamin D receptor, morphology and phenotype of EPC in vitro, effects of calcitriol and paricalcitol on expression of osteocalcin and calcium deposition where evaluated. The results suggest that treatment with vitamin D has beneficial effects on EPCs, by increasing their number and improving morphology. Both calcitriol and paricalcitol could strongly reduce the expression of osteocalcin by EPCs, whereas only paricalcitol was able to reduce the deposition of calcium in cell cultures. In conclusion, treatment of CKD patients with vitamin D seems to reduce the calcific potential of EPCs in uremia, highlighting a putative protective role of vitamin D therapy against vascular calcifications.
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Simba, Kudakwashe. "The impact of vascular calcification among dialysis dependent South African CKD patients. A five year follow up study. Cardiovascular mortality and morbidity, ethnic variation and hemodynamic correlates." Master's thesis, Faculty of Health Sciences, 2019. http://hdl.handle.net/11427/31257.
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BACKGROUND
Vascular calcification is a major risk factor for cardiovascular morbidity and mortality in patients with end stage renal disease (ESRD). In Western countries, Blacks with ESRD appear to have lesser degrees of vascular calcification compared to non-Blacks. However, there is no published data on the association of ethnic differences in vascular calcification and survival in ESRD from Sub-Saharan Africa.
METHODS
This study assessed the 5-year change in vascular calcification and mortality in a previously published cohort of patients with ESRD. Vascular calcification was assessed by abdominal aortic calcification score (lateral abdominal radiograph) and vascular stiffness by pulse wave velocity.
RESULTS
Sixty-six of the original 74 participants, studied a baseline, were identified. The median age was 46.6 years (37.6-59.2) and 57.6% were women. Abdominal aortic calcification showed no progression among Blacks [baseline range 0-5, follow up range 0-8 (p=1.00)], but a nonsignificant trend to progression among non-Blacks [baseline range 0-19, follow up range 0-22 (p=0.066)]. Black participants did not display a survival advantage (p=0.870). Overall, sepsis was the most common cause of mortality (64% of those with an identifiable cause of death). Non-Blacks had higher parathyroidectomy rates than Blacks with 9/30 cases compared to 2/36 (p=0.036). After adjustment for parathyroidectomy at follow up, the odds ratio of having abdominal vascular calcification score of ≥1 amongst non-Blacks was 8.6-fold greater compared to Blacks (p= 0.03). Central aortic systolic pressures (CASP) and pulse wave velocities (PWV) were higher in the study population than age matched normative values. At follow up, a positive correlation (r=0.3) was observed between PWV and abdominal aortic calcification (p=0.04). Elevated baseline coronary artery calcification score and FGF-23 level at baseline were not associated with a difference in mortality.
CONCLUSION
There was no significant progression in vascular calcification among Blacks. After adjusting for increased parathyroidectomy rates, there was a greater progression of vascular calcification amongst non-Blacks compared to Blacks highlighting possible ethnic differences in calcium phosphate metabolism in patients with ESRD. The lack of vascular calcification progression in Blacks was not however associated with improved survival, but the sample size was small.
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Jackson, Ashley R. "Significance of Renal Urothelium During Development and Disease." The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1459778047.
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Righi, Samuel. "Increased Circulatory Lipopolysaccharide From a High Fat Diet Aggravates Inflammation and Exacerbates Renal Failure." VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/3444.
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Kidney failure is frequently associated with the risk factors linked to metabolic syndrome. Lipopolysaccharide (LPS) is a potent inflammatory molecule, which has increased absorption from the gut into blood circulation following a high fat and high-energy diet. We hypothesized that LPS from a high fat diet can amplify inflammation, thereby exacerbating chronic kidney disease and associated disorders. We have found that adding a high fat diet to renal insufficient mice significantly progressed their kidney disease as well as associated disorders, compared to both a high fat diet and renal insufficiency alone. Additionally, we were able to demonstrate in vitro that the combination of LPS and palmitic acid, a marker of high fat diet, induced inflammatory pathways significantly more than either LPS or palmitic acid alone. These results provide insight into connection between a high fat diet and the progression of chronic kidney disease as well as associated disorders.
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Contreras, Macazana Roxana Milagros. "Estimación de la tasa de filtración glomerular usando las ecuaciones CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) y MDRD 4 (Modification of Diet in Renal Disease) en pacientes diabéticos tipo 2 atendidos en HNERM." Bachelor's thesis, Universidad Nacional Mayor de San Marcos, 2014. https://hdl.handle.net/20.500.12672/8961.
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Publicación a texto completo no autorizada por el autorDetermina la correlación y el grado de concordancia entre la ecuación de CKD-EPI y MDRD con la depuración de creatinina en orina de 24 horas para la estimación de la tasa de filtrado glomerular en pacientes diabéticos tipo 2, mayores de edad que acuden al servicio de Patología Clínica sección Bioquímica depuración de creatinina del HNERM, en el periodo octubre a diciembre 2013. Es un estudio Analítico comparativo, prospectivo observacional. Se obtuvo una muestra de 152 pacientes diabéticos, se aplicó el test de correlación de spearman, se aplicó el coeficiente de correlación de concordancia, y para determinar el bias respecto a la DCC se utilizó la gráfica de Blant altman. Se evaluó las ecuaciones CKD EPI, MDRD 4 con la DCC respectivamente la ecuación CKD EPI tuvo mejor correlación R 0.86, se evaluó el grado de concordancia con el índice Kappa k 0.69 (muy bueno) IC 0.61-0.78, y la ecuación MDRD 4, 0.63, IC 0.56 y 0.71. Se evalúo el bias entre los métodos y se observa en toda la población que la ecuación CKD EPI y MDRD 4 sobrestiman la TFG en relación a la DCC, en -3.1 y -8.1 respectivamente, siendo la ecuación CKD EPI la que tiene menor error sistemático. Se concluye que la ecuación CKD EPI es comparable con la DCC en orina de 24 horas, tiene un mejor desempeño y correlación que la ecuación MDRD 4.
Trabajo académico
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Cheddani, Lynda. "Comparaison du risque cardiovasculaire et de la mortalité entre patients transplantés rénaux et malades rénaux chroniques à fonction rénale équivalente. Uremic Toxins and Clinical Outcomes: The Impact of Kidney Transplantation Higher mortality risk among kidney transplant recipients than among estimated glomerular filtration rate-matched patients with CKD – preliminary results Less arterial stiffness in kidney transplant recipients than chronic kidney disease patients matched for renal function." Thesis, université Paris-Saclay, 2021. http://www.theses.fr/2021UPASR006.
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La maladie rénale chronique(MRC) s’associe à un très haut risque cardiovasculaire(CV), et les maladies CV représentent après greffe une des principales causes de décès avec greffon fonctionnel. Le débit de filtration glomérulaire(DFG) influe sur le risque CV. L’objectif de ce travail était de comparer pour la 1ère fois patients MRC et transplantés rénaux(TR) à même niveau de DFG sur 1) le risque de mortalité; 2) le niveau de rigidité aortique (évaluée par la vitesse de l’onde de pouls carotido-fémorale, CF-VOP). Le 3ème objectif visait à comparer l’évolution de la pression pulsée (PP) selon le devenir rénal (dialyse ou transplantation rénale préemptive, TRP) des patients MRC inscrits préemptivement sur liste de greffe. Méthodes. Ce travail est basé sur l’analyse de plusieurs cohortes. Pour l’objectif 1, les données étaient issues de CKD-REIN et DIVAT. CKD-REIN est une cohorte prospective réalisée dans 40 consultations de néphrologie en France, incluant 3033 patients avec MRC modérée à sévère. Le registre DIVAT recense prospectivement les données de patients transplantés de 8 centres français, notre étude concernait le registre nantais. L’objectif 2 était étudié au sein d’une partie de la cohorte prospective parisienne NephroTEST de patients MRC adressés pour bilan standardisé au service des Explorations Fonctionnelles de l’Hôpital Tenon (Paris), et de la cohorte rétrospective TransplanTEST de patients TR également évalués dans ce service (168 patients TR à l’Hôpital Foch-Suresnes). Pour ces objectifs, les patients TR et MRC étaient appariés sur un score de propension qui incluait notamment le DFG. Le 3ème objectif concernait les patients de CKD-REIN inscrits préemptivement sur liste de greffe: le niveau de PP et son évolution étaient comparés selon le type de suppléance rénale (SR) initié au cours du suivi (dialyse ou TRP). Résultats. Dans notre 1ère étude, la TR était associée à une augmentation du risque de mortalité relativement aux patients MRC appariés (HR: 2,6[1,54- 4,56], p=0,001 après ajustement sur l’âge, le DFG et le ratio protide/creatinine urinaire). L’augmentation du risque apparaissait davantage liée à une fréquence accrue des infections sévères et cancers qu’à une augmentation du risque CV. Il n’a pas été mis en évidence de différence concernant le risque de survenue de ≥ 1 événement CV non létal au cours du suivi (HR : 0,8[0,44-1,50], p=0,501). Dans la 2ème étude, les patients TR présentaient à 12 mois de la greffe une CF-VOP significativement plus basse que les patients MRC appariés (10,1m/s vs 11,0m/s, p=0,008), contrairement à l’évaluation réalisée à 3 mois de greffe (10,5m/s vs 11,0m/s, p=0,242). L’amélioration survenant au cours de la 1ère année de greffe conférait aux patients TR évalués à 12 mois un moindre niveau de rigidité aortique relativement aux patients MRC de même DFG. Après ajustement sur l’âge, la pression artérielle moyenne, le DFG mesuré, l’indice de masse corporelle, le statut diabétique et le niveau de PTH sérique, la TR s’associait à une réduction de 60% du risque de CF-VOP>10,6m/s (médiane) à 12 mois de la greffe (OR: 0,4[0,23-0,68]). Enfin, les résultats (préliminaires) de notre 3ème étude n’ont pas retrouvé d’association entre le type de SR et les modalités d’évolution de la PP au cours des 6 mois suivant l’initiation, chez les patients inscrits préemptivement sur liste de greffe. La dégradation du DFG dans l’année précédant la SR était plus rapide dans le groupe ayant évolué vers la dialyse (à étiologies de MRC comparables). Conclusion. Nos résultats confortent l’idée qu’une remise à zéro du risque de mortalité et d’événement CV des patients MRC n’est pas rendu possible, même après TR, de même qu’un retour au niveau d’un patient MRC comparable. Les complications CV post TR apparaissent différer de celles des patients MRC de même DFG. Les stratégies de prévention et de ralentissement de la progression de la MRC doivent par conséquent constituer une priorité en néphrologieChronic kidney disease (CKD) is associated with a very high cardiovascular (CV) risk, and CV disease is one of the main causes of death with a functioning transplant after kidney transplantation. Glomerular filtration rate (GFR) influences CV risk. The objective of this work was to compare for the first time CKD-patients and renal transplant recipients (RTR) with similar GFR level: 1) on the risk of overall mortality; 2) on aortic stiffness level (assessed by carotid-femoral pulse wave velocity, CF-PWV), a CV risk biomarker. The third objective was to compare pulse pressure (PP) and its evolution according to renal replacement therapy modality (dialysis or preemptive renal transplantation, PRT) in CKD patients pre-emptively registered on the kidney transplant waiting list.Methods. This work is based on the analysis of several cohorts. For the first objective, data came from CKD-REIN and DIVAT. CKD-REIN is a French prospective cohort performed in 40 nephrology consultations, including 3033 patients with moderate to severe CKD. The DIVAT register prospectively collects data of transplant recipients from 8 French centers, our study focused on the Nantes’ register. The second objective was studied in part of the prospective Parisian NephroTEST cohort of CKD-patients who were referred to the Physiology Unit of Tenon Hospital (Paris) for a one-day standardized evaluation, and of the RTR TransplanTEST cohort (retrospective cohort of 168 TR patients at Foch Hospital-Suresnes) evaluated in the same Physiology Unit. For these two objectives, RTR and CKD-patients were matched on a propensity score which included GFR among others. For the third objective, CKD-REIN patients who were pre-emptively registered on the kidney transplant waiting list were compared on PP level and on its evolution, according to the renal replacement therapy (RRT) modality initiated during the follow-up (dialysis or PRT). Results. In our first study, RTR was associated with an increased risk of overall mortality relative to the matched CKD-patients (HR: 2.6 [1.54-4.56], p=0.001 after adjusting for age, GFR and protide/creatinine urinary ratio). The increased risk appeared to be more related to an increased frequency of severe infections and neoplasms than to an increased CV risk. There was no difference between the two groups concerning the occurrence of at least one non-fatal CV event during the follow-up (HR: 0.8 [0.44-1.50], p=0.501). On the other hand, in the second study, RTR presented a significantly lower CF-PWV at 12-months after kidney transplant than the CKD-matched patients (10.1m/s vs 11.0m/s, p=0.008), unlike the evaluation performed at 3 months post-transplant (10.5m/s vs 11.0m/s, p=0.242). The improvement occurring within the 1st year of RT conferred to RTR assessed at 12 months a lower aortic stiffness level in comparison to the CKD-matched patients with similar GFR. After adjustment for age, mean arterial pressure, measured GFR, body mass index, diabetic status and serum PTH level, RT was associated with a 60% reduction in the risk of CF-VOP > 10.6m/s (median) at 12 months after RT (OR: 0.4 [0.23-0.68]). Finally, our latest (preliminary) results (third study) did not find any association between the RRT modality and PP evolution within the 6 months following RRT initiation in patients who were pre-emptively registered on the kidney transplant waiting list. The GFR decline in the year prior to RRT initiation was faster in-group of patients who initiate dialysis (with comparable CKD etiologies). Conclusion. Our results support the idea that, RT does not offset the excess mortality risk observed in CKD patients. At the same level of GFR, post-TR CV complications appear to be different from CV complications in CKD patients. Therefore, we believe that prevention and slowing CKD progression strategies must remain a priority in nephrology
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Hoibian, Elsa. "Impact de l'insuffisance rénale chronique et de l'urémie sur la motilité et la perméabilité intestinale." Thesis, Lyon, 2018. http://www.theses.fr/2018LYSEI066.
Full textAbstract:
L’Insuffisance Rénale Chronique (IRC) résulte de la destruction progressive et irréversible des reins. Elle est associée à une rétention de toxines urémiques à l’origine des nombreuses complications de la maladie rénale chronique (cardiovasculaires, osseuses ou métaboliques). Nos travaux se sont focalisés sur l’impact de la dysfonction rénale et de l’urémie sur la fonction barrière de l’intestin et la motilité intestinale. Deux modèles d’IRC ont été implémentés : un modèle animal, chez la souris, par néphrectomie chimique (régime alimentaire enrichi en adénine) et un modèle cellulaire d’urémie en incubant des cellules coliques Caco-2 avec 10% de plasma de patients hémodialysés (HD). Le transit, la motilité, la perméabilité intestinale et la régulation des protéines des jonctions serrées ont été explorés. Les animaux urémiques présentent un transit gastro-intestinal ralenti et une perméabilité intestinale augmentée associés à une dérégulation de l’expression et de l’abondance des protéines des jonctions serrées dans le côlon (surexpression de la Claudine 1). La perméabilité de la monocouche cellulaire de Caco-2 incubées avec du plasma HD est significativement augmentée et est associée à une augmentation de l’expression et de l’abondance de la Claudine-1. En IRC, la motilité digestive et la fonction barrière de l’intestin sont significativement altérées. Ces dysfonctions pourraient contribuer à la production intestinale et l’absorption des toxines urémiques accélérant ainsi la progression du syndrome urémique et installant un véritable « cercle vicieux »Chronic Kidney Disease (CKD) result from a progressive kidney dysfunction. CKD is associated with an increase in the concentration of uremic toxins inducing CKD-associated metabolic alterations. Our work focused on the impact of renal dysfunction on gut permeability and gut motility. In vivo, CKD was induced in mice by chemical nephrectomy (adenine-enriched diet); In vitro, Caco-2 cells were incubated for 24h with 10% (v/v) of uremic plasma to mimic the uremic environment. Gastrointestinal transit time, gut motility, intestinal permeability and expression of tight junction proteins were explored. In vivo, kidney failure was associated with an impaired gastrointestinal transit and an increased intestinal permeability associated with a dysregulation of tight junction proteins (mainly claudine-1 overexpression). The Caco-2 monolayer permeability was significantly increased in cell monolayers incubated with uremic plasma. Claudine-1 expression and abundance was increased. In CKD, gut motility and gut permeability (e.g. « leaky » gut) are significantly impaired. Generally speaking, these gut dysfunctions could promote the production and the absorption of uremic toxins contributing to the uremic syndrom
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Soita, David Jonah. "Cardiovascular disease risk profile of the South-African mixed ancestry population with high incidence of diabetes mellitus: baseline and three year follow-up." Thesis, Cape Peninsula University of Technology, 2013. http://hdl.handle.net/20.500.11838/1519.
Full textAbstract:
THESIS SUBMITED IN FULFILMENT OF THE REQUIREMENT FOR THE
AWARD OF THE DEGREE OF DOCTOR OF TECHNOLOGY OF BIOMEDICAL
TECHNOLOGTY IN THE FACULTY OF HEALTH AND WELLNESS SCIENCES
AT THE CAPE PENINSULA UNIVERSITY OF TECHNOLOGY
SUPERVISORS: PROF T.E. MATSHA
PROF R.T. ERASMUS
DR A. ZEMLIN
SUBMITED DECEMBER 2013Introduction: Cardiovascular diseases (CVD) have become the leading cause of morbidity and mortality amongst the global population. Originally thought to be a health burden of high income countries, the prevalence is rapidly increasing in developing countries. For example, in 2008, an estimated 17.3 million died from CVD, and 80% of these (13.8 mil) were from low to middle income countries. Epidemiological data on CVD in Africa is scanty and of poor quality and national vital registration is available in only 5% of Africa’s 53 countries. Furthermore, data on CVD risk amongst the South African population and specifically the mixed ancestry community is poorly described. The increasing global population of people with CVD has been largely attributed to increasing rates of determinants and risk factors which include obesity, metabolic syndrome (MetS), type 2 diabetes mellitus (DM) and chronic kidney diseases (CKD). The prevalence of DM in South Africa is known to be on the rise with more affected communities being South African Asians followed by coloureds. Aims and objectives: The aim of this study was to determine the CVD risk profile of the Bellville South community during a baseline and three year follow-up study, by assessment of known risk factors, MetS, type 2 DM, obesity and CKD. Methods: Participants for this study were drawn from an urban community of the Bellville South suburb of Cape Town. At baseline (January 2008 and March 2009) 946 individuals aged 16 to 95 participated. All participants received a standardized interview and physical examination during which anthropometric measurements were performed three times and their average used for analysis: weight (kg), height (cm), waist (cm) and hip (cm) circumferences. Body Mass Index (BMI) was calculated as weight per square metre (kg/m2). A blood sample was obtained from all participants after an overnight fast for the determination of biochemical profiles: glucose, glycated haemoglobin, creatinine, total cholesterol, high density lipoprotein cholesterol (HDL-C), triglycerides and low density lipoprotein cholesterol (LDL-C) which was calculated using Friedewald’s formula. Kidney function test was assessed through estimated glomerular filtration rate (eGFR) using the cockcroft-Gault and MDRD equations. Blood pressure was measured according to the World Health Organisation (WHO) guidelines. Participants with no history of doctor diagnosed DM underwent a 75 g oral glucose tolerance test as recommended by the WHO. Metabolic syndrome was determined using JIS, NCEP ATPIII and IDF criteria. The follow-up examination was conducted in 2011 (3 years from vii baseline) using similar procedures. A total of 198 participants formed the follow-up cohort whose measurements were compared to those of the baseline. Finally, the prediction and processes/progression of the risk factors were determined. Results: At both baseline and follow-up studies, females had a higher BMI compared to their male counterparts. The crude prevalence of type 2 DM, including the previously diagnosed type 2 DM was 28.59% (age-adjusted = 33.5%, 95%CI: 30.01 – 36.92), and that of undiagnosed type 2 DM was 17.8% (age-adjusted = 12.4%, 95%CI: 9.8 – 14.8). The overall prevalence of CKD was 28.7% (269) and was higher in females (31.4%) compared to 20.2% in males. MetS was present in 46.5% of the participants. Gender-specific prediction for CVD risk calculated using the 30-year CVD interactive risk calculator showed that high CVD risk was present in normoglycaemic and younger subjects (under 35 years). At follow-up, the cumulative incidence of progression in glucose tolerance status was: 16.2% (32 participants including 11 with new-onset diabetes), and increased in a stepwise fashion with the number of components of MetS. Between baseline and 3-year evaluation glomerular filtration rate (eGFR) increased by 8.7 ml/min (95% confidence interval: 6.9-10.7), reflecting variables trajectories across baseline strata of kidney functions. Conclusion: Given the findings of this study and the estimated increases in the determinants and risk factors of CVD in the mixed ancestry population of South Africa this trend may continue to worsen if current trajectories do not change.
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Krajisnik, Tijana. "Fibroblast growth factor-23 and Klotho in bone/mineral and parathyroid disorders." Doctoral thesis, Uppsala universitet, Medicin, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-107456.
Full textAbstract:
Fibroblast growth factor-23 (FGF23) is a novel, bone-produced hormone that regulates renal phosphate (Pi) reabsorption and calcitriol metabolism. Disorders of mineral and bone metabolism, such as autosomal dominant hypophosphatemic rickets (ADHR) and hyperostosis-hyperphosphatemia syndrome (HHS), witness the importance of well-balanced serum levels of FGF23. Patients with chronic kidney disease (CKD) are highly morbid due to Pi retention/hyperphosphatemia and calcitriol deficiency, which lead to elevated serum levels of parathyroid hormone (PTH) and secondary hyperparathyroidism (sHPT). As a response to hyperphosphatemia, CKD patients have also remarkably high serum FGF23 levels, which are associated with cardiovascular risk factors and increased mortality in CKD. The overall aim of this dissertation was to discern a possible role of FGF23 in parathyroid biology. Our in vitro experiments on isolated bovine parathyroid cells demonstrate that FGF23 directly and dose-dependently suppresses the PTH production and secretion, while increasing the expression of the 25-hydroxyvitamin D3-activating enzyme 1α-hydroxylase. We investigated possible expressional changes in the FGF23 receptor co-factor Klotho in hyperparathyroid disorders and found that Klotho expression is decreased or absent and inversely correlated to serum calcium (Ca) in adenomas of primary HPT (pHPT). In the hyperplastic parathyroid glands of sHPT, Klotho expression declines in parallel with the kidney function and correlates with the glomerular filtration rate. Moreover, Klotho expression is suppressed by Ca and FGF23, increased by calcitriol, but unaffected by Pi and PTH in vitro. Finally, we identified a novel missense mutation in the gene encoding GALNT3, which is normally involved in the post-translational glycosylation of FGF23, as the cause of aberrant FGF23 processing in a patient with HHS. In summary, we provide evidence for a novel bone/parathyroid axis in which FGF23 functions as a direct, negative regulator of the PTH production. High extracellular Ca is a major determinant of the Klotho expression in pHPT, whereas the Klotho levels in sHPT may be attributed to a combination of the high FGF23 and Ca, and low calcitriol levels associated with CKD. Hence, the decreased Klotho expression in sHPT could explain the concomitantly high FGF23 and PTH levels, as well as the failure of FGF23 to prevent or mitigate the development of sHPT in CKD.
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Belding, Emily. "A review of the implications of chronic kidney disease in pregnancy on maternal and fetal outcomes." Thesis, 2020. https://hdl.handle.net/2144/41185.
Full textAbstract:
The prevalence of pregnancies complicated by chronic kidney disease (CKD) is increasing. Yet, CKD in pregnancy tends to be under-diagnosed, as women of childbearing age are not regularly screened for renal dysfunction, nor is screening incorporated into routine pregnancy follow up. Further, renal dysfunction has significant implications for maternal and fetal outcomes, with degree of renal dysfunction at conception being the most important prognostic factor. It is established that the risk for poorer renal, maternal and fetal outcomes, increases incrementally with severity of CKD, with intrauterine death and progression to end-stage renal disease (ESDR) associated with severe CKD. However, it is difficult to predict which CKD pregnancies will lead to poor outcomes as the definition of CKD in pregnancy is not uniform between studies, nor are measurement parameters. This paucity of data prevents the establishment of a standard of care protocol and leaves clinicians ill-equipped to care for and manage this complex patient cohort. This review discusses renal, maternal and fetal outcomes in CKD pregnancies as presented by the literature, in order to demonstrate the contradictions in data and gaps in knowledge surrounding this topic, as well as the need for a general management algorithm.
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Lu, Hsin-Ying, and 呂欣穎. "Protective Effects of Exercise for Doxorubicin-induced Chronic Kidney Disease (CKD)." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/20231891256729319569.
Full textAbstract:
碩士中國醫藥大學
物理治療學系復健科學碩士班
99
Chronic kidney disease (CKD) is a worldwide public health problem. CKD eventually leads to permanent loss of kidney function indicates that patients inevitably suffer from end stage renal disease (ESRD) and require renal replacement therapies such as dialysis and/or transplantation. According to United States Renal Data System (USRDS), the prevalence of ESRD for 2007 was the highest in Taiwan. The incidence and prevalence of CKD rise steadily and cause many public health problems and huge expenditure of National Health Insurance program. CKD may develop some complications such as high blood pressure, anemia, osteodystrophy, poor nutritional health and nerve damage. Also, CKD increases the risk of morbidity and mortality. Death of CKD is commonly caused by cardiovascular disease. Renal fibrosis is always the ultimate result of CKD. Glomerulosclerosis is a common characteristic in patients with progressive CKD. Fibrosis is caused by a series of events, including: (1) injury to the capillary epithelial/endothelial cells; (2) release of TGF-β1, the major fibrogenic cytokine which has been identified as the main inducer of epithelial mesenchymal transition (EMT) and disruption of the underlying tubular basement membrane (TBM) by MMPs; (3) recruitment of inflammatory cells and cytokine, such as helper T cell, IL-6 and TNF-α; (4) increase in of reactive oxygen species (ROS); and (5) activate collagen production/accumulation . Regular physical exercise tends to ameliorate a diversity of endothelial functions by preventing the bone loss and minimizing the attack from radical oxygen species, hence it has become a non-pharmacological intervention for treating the metabolic syndrome. Most patients suffering from CKD are inactive and tend to have reduced physical function and performance, and result in poor quality of life, or need dialysis. In this study, CKD was induced in Sprague-Dawley (SD) rats by injection of s.c. 8.5 mg/kg of Doxorubicin (DR) and the beneficial effect of treadmill running exercise was evaluated. SD rats were divided into 3 groups each for control (n=18) and CKD-induced groups (n=24). Among three groups of both control and experimental, one group was not subjected to physical exercise. Second group was subjected to 30 min/day exercise and the third group was subjected to 60 min/day. The speed of the treadmill was 30m/min. The exercises were carried out three times a week for the duration of 3 months. Results showed that regular running significantly decreased levels of cholesterol, triglyceride and increase serum albumin in a dose-responsive manner. In addition, regular running exercise for 60 min significantly decrease the urine protein levels, the oxidative, inflammatory stress and fibrogenesis. In summary, regular running exercise can be an alternative treatment or an adjuvant remedy for treating CKD.
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Ying-Hsia and 施瑩霞. "The study of the benefits analysis after nutrition support on chronic kidney disease (CKD) patients." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/05211344936514823964.
Full textAbstract:
碩士中山醫學大學
營養學系碩士班
98
It is a large population of patients with hemodialysis in Taiwan. Nutritional support is important for these patients. This study was aimed to understand the effect of dietary guide twice per year upon nutritional status for these patients in Show-Chung hospital. Results showed after one-year interventional program, albumin, BUN, creatinine, hemoglobin, uric acid, TG, cholesterol, phosphorus and dietary protein were significantly changed (p<0.001), in which MDRD-GFR was negatively correlated with BUN, creatinine and phosphours (p<0.001). This study found that dietary guide for chronic kidney disease patients twice per year was beneficial.
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Teng, Chien-Wen, and 鄧傑文. "DSP Arteriosclerosis Assessment System and It's Application in early stage of Chronic Kidney Disease(CKD)." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/90364042989034664363.
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碩士國立東華大學
電機工程學系
97
The incidence of Chronic Kidney Diseases (CKD) in Taiwan is ranked first in the world and prevalence is ranked second. Almost 1.5 million people suffer from the CKD around Taiwan currently, but 90% of people do not know that they have the disease. For this reason, how to detect CKD is a very important topic to discuss. From the studies, we realized that Cardiovascular Disease (CVD) and CKD have a causal relationship. Furthermore, after the statistical analysis presented in this paper, we also found that arteriosclerosis is a risk factor for CKD. Using the pulse wave velocity (PWV) measurement instrument research and development from Medical Information and Technology Lab at Department of Electrical Engineering in National Dong Hwa University, there is significant negative correlation(r=-0.354, p<0.01) between PWV and Glomerular Filtration Rate (GFR). As the existing instrument of PWV must match computer or laptop and hence makes it inconvenient to carry. Therefore, another point of thesis is try to use the operation ability of TI C6000 chip and the C6000 platform, to provide a perfect integration development tool (Code Composer Studio, CCS), and to experiment with simulation and development. Based on the assignment of microprocessor and DSP, this thesis used MSP430F169 as the Host，DSK6416 as the Slave，HPI (Host Port Interface to communication, through real-time with parallel transmission. This thesis also used handshaking to exchange information and to reduce error, to ensure it is accurate of the PWV result.
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Bibi, Asima. "Calreticulin in kidney function and disease: chronic low level of calreticulin impairs Ca2+ homeostasis leading to mitochondrial dysfunction and chronic renal injury." Doctoral thesis, 2012. http://hdl.handle.net/11858/00-1735-0000-000D-EF88-D.
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Nwosu, Novelia Rawlins, and 諾立亞. "Knowledge Attitudes and Practices (KAP) among Chronic Kidney Disease (CKD) patients in St. Kitts and Nevis." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/16209274221030341915.
Full textAbstract:
碩士國立臺北護理健康大學
護理研究所
105
Background: The Caribbean developing countries are experiencing an increase in chronic kidney diseases and related incidences. As a small developing state St. Kitts and Nevis has recognize the vast impact of chronic kidney disease and records one of the highest incidences of renal disease in the northern Caribbean. An integral part of chronic kidney disease is patient education about nutrition management, increased physical activity, and improvements of lifestyle choices. However, regardless of the availability of information, there remains a limited understanding of people’s knowledge, attitudes, and practices associated with chronic kidney disease in St Kitts Nevis. Methods: This descriptive correlational study designed, looked at patient’s knowledge attitude and practices of chronic kidney disease. Data was collected from 114 patients with chronic kidney disease stages 1-4 were referred and interviewed between July – September 2016, at the Eureka Health Services Medical Clinic in Nevis and the Out Patient Clinic at the JNF Hospital in St. Kitts using the chronic kidney diseases Screening Index Tool structured questionnaire. Results: Participants knowledge, attitudes and practices mean scores regarding CKD were knowledge 13.67 (58%), attitudes 53.79 (72%) and practices 46.66 (77%). Among demographics education and employment was associated with knowledge, age and marital status was associated with attitudes whilst, education and marital status associated with practices. The interrelationship between the variables showed knowledge and attitudes have positive correlation to practices, however, participants’ knowledge was not associated with attitudes. Regarding hierarchical regression analysis, attitude was the most important predictor of practices among the study participants, it predicted 12% of total variance. Implications for Practice: Efforts should be made provide more information about chronic kidney disease focusing on the factors associated with knowledge attitude and behavioral practices, management and controlling of early stage of chronic kidney disease, the importance of diet and exercise, and adhering to medical treatment. The CKD Screening Index tool is one avenue that hospital institutions collaborating with the health promotion unit can explore to screen persons who may be at risk for CKD thus increasing the awareness and to detect CKD at an earlier stage so that appropriate preventive measures can be implemented.
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Malindisa, Sibusiso Tebogo. "Genetic insights on the role of telomere dynamics in Chronic Kidney Disease (CKD) regardless of HIV status." Thesis, 2016. http://hdl.handle.net/10539/21009.
Full textAbstract:
A dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of requirements for the degree of Master of Science in the School of Molecular and Cell Biology. Johannesburg, 2016.Telomeres play significant roles in maintaining genome stability, regulating cell proliferation and apoptosis. The role of telomere biology and telomerase reactivation has been studied extensively in cancers. Telomerase has been previously associated with driving chronic kidney disease (CKD) advancement and most frequently due to HIV infection. However, the mechanism by which telomerase activation contributes towards disease progression beyond its canonical function of telomere maintenance is poorly understood. Telomerase is a ribonucleoprotein whose main function is telomere maintenance. Telomerase activity is dependent on expression of the rate-limiting human telomerase reverse transcriptase (hTERT) component. In addition to telomere maintenance, hTERT is implicated in other non-telomere related functions that promote cellular proliferation. Expression of hTERT is predominantly regulated at the transcription level where variation in promoter and minisatellite (MNS16A) sequences alter its expression. This variation has been implicated to confer susceptibility to diseases such as cancer and ageing disorders in non-African populations. Data on variation and pathogenicity of telomere-associated genes in African populations is limited and warrants further research. Thus bioinformatics analysis was performed to elucidate variation within the human TERT gene and promoter in different populations. The promoter, MNS16A and relative telomere length (RTL) were also evaluated in 159 African study participants with and without CKD. TERT common variants are equally distributed across populations with limited data on connection to the effects of the variants in African populations. Further bioinformatics analyses revealed significant difference (p<0.0001) in distribution of promoter variant rs2853669 between African and non-African populations. No common promoter mutations were identified in our study population. Interestingly, the long MNS16A variant suggested to increase TERT expression was significantly overrepresented in individuals with CKD regardless of HIV status. For the first time, a strong association of the long MNS16A variant with CKD regardless of HIV status is reported, implicating MNS16A as a potential risk factor in CKD.
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Chang, Hsien-Cheng, and 張賢政. "A Population-Based Study of the Association between Betel-Quid Chewing and Chronic Kidney Disease (CKD) in Men." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/18479774388825094243.
Full textAbstract:
碩士國立臺灣大學
預防醫學研究所
98
Background The incidence and prevalence of end-stage-renal-disease (ESRD) on dialysis in Taiwan are highest over the world. It is crucial to emphasize on chronic kidney disease (CKD) which is the earlier disease state and is much more prevalent. Clinical guidelines recommend screening CKD in high risk groups and early intervention to delay renal function deterioration and related complication. In addition to well known risk factors, it is also important to identify special risk factors for Taiwanese. The betel-quid chewing is highly prevalent in Taiwan and is found to be the risk factor of diabetes and cardiovascular disease. The purpose of this study is to explore the association between betel quid chewing and CKD in men. Materials and methods A total of 32238 men attended the Keelung community-based integrated screening (KCIS) between 1999 and 2005. Population registration data including age and sex, questionnaire questions including educational level, past medical history, and habits of betel-quid chewing, alcohol, and smoking were collected. Anthropometric measurements included blood pressure, body height, body weight, and body mass index(BMI) calculation. Venous blood was sampled after fasting for biochemistry data. Urinary protein was also checked by urine stick. The definition of each chronic disease was based on either the measurement or laboratory abnormal result or the past medical history. Proteinuria was defined as one or more plus urine protein. Glomerular filtration rate was estimated (eGFR) by MDRD study equation. Men with either proteinuria or low eGFR less than 60 mL/min/1.73m2 were defined as CKD. Multi-variate logistic regression model was used for analysis the association between betel quid chewing and CKD in men. Dose response effect of betel-quid chewing was also evaluated by test for trend. Results The prevalence of betel-quid chewing in this study population was 16.47%, including 8.02% who quitted and 8.45% who were current chewers. Of 18946 men with complete urinary protein and eGFR data, 2769 CKD cases were noted. The prevalence was 14.62% (95% confidence interval (CI) 14.07-15.16). The prevalence and 95% CI of stage 1 to stage 5 CKD were 1.60%(1.42-1.78), 5.54%(5.21-5.88), 7.06%(6.68-7.44), 0.36%(0.27-0.44), and 0.05%(0.02-0.09) respectively. A total of 7.47%(7.08-7.86) study population were CKD stage 3 to 5. After age standardized to Taiwan population in 2006, the prevalence of CKD in Taiwanese men was 10.11%(9.69-10.54) with 4.68%(4.42-4.94) as stage 3 to 5. The prevalence and percentage of later stage both increased by age. Old age, diabetes, hypertension, hyperlipidemia, hyperuricemia, and obesity were identified as independent risk factors of CKD. The highest educational level with more than 12 school years was independent protective factor. Compared to non-chewers, the age adjusted odds ratio for CKD of betel-quid chewer was 1.285 (95%CI 1.110-1.487). It was still significant if we divided the chewers to ex-users and current users. After adjusted for all confounding factors, the adjusted odds ratio of betel-quid chewers was 1.147(95%CI 0.979-1.345). It was also more than 1 but insignificant if we divided the chewers to ex-users and current users. Regarding the dose response effect of daily dose, duration, and cumulative dose, all the adjusted odds ratios increased as the dose of betel-quid increase. But they were insignificant by test for trend . The result was similar when proteinuria was modeled as outcome variable. Betel-quid chewing was not risk factor when modeled with low eGFR<60 mL/min/1.73m2 as outcome. Conclusion The prevalence of CKD in Taiwan was high. In addition to well known high risk groups those screening were recommended, betel-quid chewing might also be a risk factor for CKD and proteinuria. But the association was insignificant after adjusting to other risk factors in our study. In the context of no other laboratory data of other risk factors available, betel-quid chewing might be a surrogate factor for CKD and might need screening. The cohort study should be considered for confirming the association between betel-quid and CKD and for exploring the mechanism. Cost-benefit analysis should also be performed if screening would be recommended.
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Wang, Tzu-Wen, and 王姿文. "A Retrospective Study To Evaluate The Effect Of Renin Inhibitor On Patients With Hypertension And Chronic Kidney Disease(CKD)." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/65735293222121673769.
Full textAbstract:
碩士亞洲大學
健康產業管理學系健康管理組碩士在職專班
100
Background: Proteinuria and hypertension are both important risk factors for progression of renal diseases. Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are RAAS(Renin-Angiotensin-Aldosterone-System) blockade agents which have been shown to be effective therapeutic approaches for controlling of hypertension and prevention of renal damages in patients with hypertension. In the rate-limiting step of the RAAS cascade, renin is the main determinant of RAAS activity and has been considered the optimal target for RAAS suppression. Aliskiren is the first-in-class direct rennin inhibitor as oral antihypertensive agents which was approved in 2008 for the treatment of hypertension in Taiwan, however, clinical data in Taiwanese population is still lacking after launch in Taiwan. The major objective of our study is to compare the blood pressure lowering efficacy, anti-proteinuria potential, and the effect on renal function by renin inhibition in hypertensive patients, with and without diabetes, and in subgroups with eGFR<60ml/min/1.73m2 and with eGFR>60ml/min/1.73m2. The secondary objective is to assess changes of serum potassium and serum creatinine concentration in various subgroups from safety perspectives. Methods: This study is a retrospective analysis which collect clinical data of adult patients(above 18 year-old) who were diagnosed with hypertension and accepted direct renin inhibitor, alikiren treatment for at least three months from April 2010 to October 2011 in Central of regional hospital, using the t test statistical method. Results: Clinical data of a total of 219 adults from April 2010 to October 2011 were analyzed in this retrospective study, and among all the patients 50% of them were diagnosed with diabetes mellitus. Patients treated with Aliskiren for 3 months showed 8.1 mmHg (p<0.001) decrease of systolic blood pressure, and 4.3mmHg (p<0.001) decrease of diastolic blood pressure. The average reduction of UACR (urine serum albumin-creatinine ratio) was 202.2mg / g (p=0.034) which is statistically significant. The results showed 3.3 ml/min/1.73m2 increase of GFR in diabetic patients but 4.4 ml/min/1.73m2 (p=0.002) decrease in non-diabetic patients. In subgroups with various GFR, the results also showed 2.1 ml/min/1.73m2 increase of GFR in patient subset with eGFR<60ml/min/1.73m2, and 5.7 ml/min/1.73m2 decrease of GFR in patient subset with eGFR>60ml/min/1.73m2 (p=0.031). No significant changes of serum potassium were observed in this analysis. Conclusions: The results of this study showed that with the blood pressure lowering efficacy and anti-proteinuria potential, Aliskiren may result in different effects on renal function in various patient populations. The decline of eGFR in hypertensive patient subgroups with non-diabetic group or with renal function eGFR> 60ml/min/1.73m2 suggested that the physicians should monitor a number of indicators to assess changes of renal function while patient with hypertension are treated with Aliskiren. The present study only assessed surrogate marker of proteinuria, UACR, and suggested that further studies to establish more stringent evaluation of renal function and renal protection effect are still necessary.
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HUANG, TE-CHIH, and 黃得誌. "Impact of Tw-DRGs-based payments on health care providers with simulation Model: The Example of Chronic kidney disease, CKD(MDC5, MDC10, MDC11)." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/qn9raf.
Full textAbstract:
碩士嘉南藥理大學
醫務管理系
107
Objectives: In 2018, the National Health Insurance (NHI) Administration announced the Tw-DRGs (Taiwan Diagnosis-Related Groups) its full draft implementation. However, most of the Tw-DRGs implemented in the second stage were based on surgical divisions. Among the hospital specialties that have yet to implement Tw-DRGs, internal medicine is a specialty that deals with diseases that are often highly complex. In particular, the classification of CKD as a high-risk disease. In the past, CKD has become one of the 10 leading causes of death in Taiwan, as well as the costliest disease among the country’s top of medical resource utilization and expenses. Based on the aforementioned factors, CKD was selected as the subject matter of this study, while the impacts and effects of the Tw-DRGs 4.0 payment system on hospitals were examined through a model simulation of the system. Method: An experimental design approach was adopted in this study, collect a case hospital data (January 2017 to December 2017), and total 910 CKD data. Based on the relevant literature summarized and analyzed, with revised and verified by experts. A system simulation framework was developed in this study; subsequently, the relevant variables within the framework were used to collect and archive the data. A simulation based on the new Tw-DRGs 4.0 system was then performed and the results were compared with the actual medical expenses data. Results: (1) In terms of fixed benefits and medical resource utilization, a statistically significant difference with respect to case-mix groups was only observed between patients with only high blood pressure and patients with only diabetes. (2) In terms of the effects of CKD severity on fixed benefits and medical resource utilization, a statistically significant difference was only observed in the MDC11 group. (3) In terms of the predictive power of the overall system simulation framework, the explanatory power of the model was 56% while the explanatory power of the single MDC11 sample was 89%. Conclusion: The results of this study indicated that the simulated Tw-DRGs 4.0 system had statistically significant effects on medical facilities, including differences in fixed benefits due to arising complications. Regarding the effects of disease severity, it was shown that CKD severity was linked to the cost differences in the MDC11 group. In this study indicating that the selected variables were appropriate for the CKD samples. However, the selection of variables must be revised if one intends to apply the system simulation framework to the MDC5 and MDC10 groups, so as to enhance the predictive power of simulation results.
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Guimarães, Serafim Miguel de Sousa Barreto. "Patient reported outcome measures in chronic kidney disease: analysis of self-reported indicators of experiencing chronic disease." Doctoral thesis, 2019. http://hdl.handle.net/10773/27993.
Full textAbstract:
There is often a discrepancy between clinical data, including laboratory tests, and the patients’ experience of being ill. The goal of this work was to search for Key Performance Indicators (KPI) of disease other than the usual numeric data. As research model, we have used Chronic Kidney Disease (CKD). Those indicators should express
the experience of living with the disease and be sensible to medical decisions so that they can be targeted for intervention. In chapter 2, a contextualization of CKD is made, presenting an extensive list of the standard indicators that currently drive physicians’ decisions. A general approach to chronic diseases is presented in chapter 3, highlighting models of interventions. Some existing indicators are also covered.
The experimental work is presented in chapter 4. Our hypothesis was based on a conceptual model which postulated that a given Patient Reported Outcome Measure (PROM) would be suitable for daily use in the clinical context provided that it would link predictors (demographic variables, comorbidity indices, estimates of Glomerular
Filtration Rate – eGFR - and untoward events of the previous year) to Endpoints (death, dialysis, hospitalizations and emergency episodes) with statistically significant relationships and serve as indicator as surrogate of well-being. We conducted an observational study and recruited 60 patients with CKD to whom several questionnaires
of PROM were administered: Short Physical Performance Battery (SPPB), World Health Organization Disability Assessment Schedule (WHODAS), Satisfaction With Life Scale (SWLS) and Kidney Disease Quality of Life (KDQoL). Follow-up period was 24 months. Lastly, we wanted to know the relevancy of the endpoints to the patients. For that, they were asked to rank six endpoints according to what they think their physician’s priority should be (avoid death, avoid dialysis, avoid worsening of lab tests, prevent further deterioration of medical condition, avoid hospital admissions and avoid emergency episodes). We conclude that: 1) SPPB could predict death, dialysis and hospital
admissions. 2) WHODAS could predict death and dialysis. 3) Physical Functioning domain of KDQoL could predict death and hospital admissions. 4) Role Emotional domain of KDQoL could predict death. 5) Energy/Vitality domain of KDQoL could predict hospital admissions. 6) Role Physical domain of KDQoL could predict dialysis. 7) Mental Health domain of KDQoL could predict hospital admissions and emergency episodes. 8) Pain, Social Function and General Health domains of KDQoL, and SWLS were not useful in predicting any of the proposed endpoints. 9) The Cockcroft-Gault (CG) formula to compute eGFR is the only that could predict mortality. 10) All eGFR formulae predicted beginning of dialysis. 11) Only the CG formula could predict the scores of some PROM scales: SPPB, Physical Function domain of KDQoL and WHODAS. 12) Both the Charlson comorbidity scales (1987 and 2011) are useful for
the prediction of studied endpoints: the first predicts death and hospital admissions while the second predicted mortality, dialysis, hospitalizations and emergency episodes. 13) The highest priority of patients is that their physician’s main concern should be to “Avoid death” whereas options “Avoid dialysis” and “Avoid worsening of laboratory tests” came next, in a tie. 14) Patients ranked “Avoid hospitalization” and “Avoid emergency episodes” in the last places, after all the others. Finally, 15) Eight possible schemes were drawn from the analysis of the
conceptual model. Four of them have shown to have clinical utility. Longitudinal exploration of these PROM is needed in order to reinforce their clear place at office and bedside and in disease management.Há frequentemente uma discrepância entre os dados clínicos, incluindo análises laboratoriais, e a experiência de se estar doente. O objetivo deste trabalho foi procurar indicadores-chave de desempenho de doença para além dos dados numéricos habituais. Como modelo de investigação, utilizamos a Doença Renal Crónica (DRC). Esses indicadores devem traduzir a experiência de viver com a doença e serem sensíveis às decisões médicas, para que possam ser alvo de intervenção. No capítulo 2, é feita uma contextualização da DRC, apresentando-se uma extensa lista dos indicadores que actualmente orientam as decisões dos médicos. No capítulo 3, faz-se uma abordagem geral das doenças crónicas, destacando modelos de gestão da doença crónica. Alguns indicadores actualmente usados também são referidos. O trabalho experimental é apresentado no capítulo 4. A nossa hipótese baseou-se num modelo conceptual que postulava que uma determinada medida de resultados autorelatados pelos doentes (PROM: Patient Reported Outcome Measures) seria adequada para uso diário em contexto clínico se tivesse uma correlação estatisticamente significativa entre os preditores (variáveis demográficas, índices de comorbilidade, estimativas de Taxa de Filtração Glomerular - TFGe - e eventos adversos do ano anterior) e os resultados (morte, diálise, hospitalizações e idas ao serviço de urgência), servindo assim como indicador de bem-estar. Realizámos um estudo observacional, tendo recrutado 60 doentes renais crónicos que responderam a vários questionários de PROM: “Short Physical Performance Battery” (SPPB), “World Health Organization Disability Assessment Schedule” (WHODAS), “Satisfaction With Life Scale” (SWLS) e “Kidney Disease Quality of Life” (KDQoL). O período de acompanhamento foi de 24 meses. Finalmente, estudámos a relevância dos resultados para os doentes. Para isso, foi-lhes pedido que classificassem seis desfechos, de acordo com o que acham que deveria ser a prioridade do seu médico (“evitar a morte”, “evitar a diálise”, “evitar o agravamento dos exames laboratoriais”, “evitar a deterioração do seu estado geral”, “evitar internamentos hospitalares” e “evitar idas ao serviço de urgência”). Os resultados permitiram concluir que: 1) O SPPB previu morte, diálise e hospitalizações. 2) O WHODAS previu morte e diálise. 3) O domínio Função Física do KDQoL previu morte e hospitalizações. 4) O domínio Saúde Mental do KDQoL previu morte. 5) O domínio Energia/vitalidade do KDQoL previu hospitalizações. 6) O domínio físico do KDQoL previu diálise. 7) Domínio de Saúde Mental do KDQoL previu hospitalizações e idas ao serviço de urgência. 8) Os domínios Dor, Função Social e Saúde Geral do KDQoL, bem como o SWLS não foram úteis na previsão de nenhum dos resultados propostos. 9) A fórmula de Cockcroft-Gault (CG) para calcular a TFGe é a única que previu a morte. 10) Todas as fórmulas de cálculo da TFGe previram o início da diálise. 11) Apenas a fórmula de CG pôde prever a pontuação de algumas escalas do PROM: SPPB, domínio da Função Física do KDQoL e WHODAS. 12) Ambas as escalas de comorbilidade de Charlson (de 1987 e 2011) são úteis para a predição dos resultados estudados: a primeira prevê mortes e internamentos hospitalares, enquanto a segunda prediz morte, diálise, hospitalizações e idas ao serviço de urgência. 13) A principal prioridade dos doentes é que a principal preocupação do seu médico seja “evitar a morte”, enquanto as opções “evitar diálise” e “evitar o agravamento dos exames laboratoriais” vêm a seguir, empatadas. 14) Os doentes classificaram as opções “evitar hospitalização” e “evitar episódios de urgência” nos últimos lugares, depois de todas as demais. Finalmente, 15) O modelo conceptual proposto permitiu identificar oito possibilidades diferentes de relação entre preditores, PROM e resultados. Quatro deles mostraram ter utilidade clínica. São necessários estudos longitudinais com PROM para reforçar o seu papel no consultório e na enfermaria, e também na gestão da doença.
Programa Doutoral em Ciências e Tecnologias da Saúde
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Peiskerová, Martina. "Oxidační a karbonylový stres, mikrozánět a kardiovaskulární riziko u pacientů s onemocněním ledvin." Doctoral thesis, 2015. http://www.nusl.cz/ntk/nusl-333780.
Full textAbstract:
Short summary: Background: High cardiovascular risk in patients with chronic kidney disease is partly due to mineral dysbalance, microinflammation and oxidative stress. CKD patients accumulate traditional and non-traditional CV risk factors. FGF23, MMPs and PlGF belong among these non-traditional biomarkers of CV risk. FGF23 is a phosphaturic hormone and inhibitor of calcitriol synthesis. It is associated with vascular calcifications. Matrix-metalloproteinases (e.g. MMP-2, MMP-9) are proteolytic, proinflammatory enzymes, contributing to myocardial remodelation. Placental growth factor (PlGF) is a proangiogenic cytokine that is associated with LV hypertrophy in animal model. Plasmatic FGF23, MMPs and PlGF are elevated in CKD. Aim: We aimed to describe dynamic changes between several novel biomarkers of CV risk (FGF23, MMP-2, MMP-9 and PlGF) in CKD stages 1-5, to describe their mutual correlations and possible association with traditional CV risk markers. We studied possible association of laboratory and echocardiographic parameters in patients with CKD stages 2-4. Methods: In a cross-sectional study we evaluated 80 patiens with CKD 1-5 and 44 healthy controls. In a prospective study we evaluated echocardiographic and laboratory parameters in 62 patients with CKD 2-4 for an average study period of 36±10...