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1
Chaabane, Wassim, Françoise Praddaude, Marie Buleon, et al. "Renal functional decline and glomerulotubular injury are arrested but not restored by release of unilateral ureteral obstruction (UUO)." American Journal of Physiology-Renal Physiology 304, no. 4 (2013): F432—F439. http://dx.doi.org/10.1152/ajprenal.00425.2012.
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Murine unilateral ureteral obstruction (UUO), a major model of progressive kidney disease, causes loss of proximal tubular mass and formation of atubular glomeruli. Adult C57BL/6 mice underwent a sham operation or reversible UUO under anesthesia. In group 1, kidneys were harvested after 7 days. In group 2, the obstruction was released after 7 days, and a physiological study of both kidneys was performed 30 days later. Renal blood flow (RBF), glomerular filtration rate (GFR), urine protein, and albumin excretion were measured after ligation of either the left or right ureter. Glomerular volume (periodic acid-Schiff), glomerulotubular integrity and proximal tubular mass ( Lotus tetragonolobus lectin), and interstitial collagen (Sirius red) were measured by histomorphometry. Obstructed kidney weight was reduced by 15% at 7 days but was not different from sham after a 30-day recovery. Glomerular volume and proximal tubular area of the obstructed kidney were reduced by 55% at 7 days, but normalized after 30 days. Interstitial collagen deposition increased 2.4-fold after 7 days of UUO and normalized after release. However, GFR and RBF were reduced by 40% and urine albumin/protein ratio was increased 2.8-fold 30 days after release of UUO. This was associated with a 50% reduction in glomerulotubular integrity despite a 30-day recovery ( P < 0.05 for all data). We conclude that release of 7-day UUO can arrest progression but does not restore normal function of the postobstructed kidney. Although the remaining intact nephrons have hypertrophied, glomerular injury is revealed by albuminuria. These results suggest that glomerulotubular injury should become the primary target of slowing progressive kidney disease.
2
Figliuzzi, Marina, Barbara Bonandrini, and Andrea Remuzzi. "Decellularized Kidney Matrix as Functional Material for whole Organ Tissue Engineering." Journal of Applied Biomaterials & Functional Materials 15, no. 4 (2017): e326-e333. http://dx.doi.org/10.5301/jabfm.5000393.
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Renal transplantation is currently the most effective treatment for end-stage renal disease, which represents one of the major current public health problems. However, the number of available donor kidneys is drastically insufficient to meet the demand, causing prolonged waiting lists. For this reason, tissue engineering offers great potential to increase the pool of donated organs for kidney transplantation, by way of seeding cells on supporting scaffolding material. Biological scaffolds are prepared by removing cellular components from the donor organs using a decellularization process with detergents, enzymes or other cell lysing solutions. Extracellular matrix which makes up the scaffold is critical to directing the cell attachment and to creating a suitable environment for cell survival, proliferation and differentiation. Researchers are now studying whole intact scaffolds produced from the kidneys of animals or humans without adversely affecting extracellular matrix, biological activity and mechanical integrity. The process of recellularization includes cell seeding strategies and the choice of the cell source to repopulate the scaffold. This is the most difficult phase, due to the complexity of the kidney. Indeed, no studies have provided sufficient results of complete renal scaffold repopulation and differentiation. This review summarizes the research that has been conducted to obtain decellularized kidney scaffolds and to repopulate the scaffolds, evaluating the best cell sources, the cell seeding methods and the cell differentiation in kidney scaffolds.
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Kellerman, P. S., R. A. Clark, C. A. Hoilien, S. L. Linas, and B. A. Molitoris. "Role of microfilaments in maintenance of proximal tubule structural and functional integrity." American Journal of Physiology-Renal Physiology 259, no. 2 (1990): F279—F285. http://dx.doi.org/10.1152/ajprenal.1990.259.2.f279.
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To determine the selective effect of microfilament disruption on both cellular structure and function, microfilament-specific doses of cytochalasin D (10 microM) were used in an isolated perfused kidney system. Structurally, cytochalasin D resulted in extensive disruption of the apical surface with blebbing, vacuolization, and patchy loss and fusion of microvilli. Functionally, cytochalasin D resulted in an initial decrease in glomerular filtration rate (300.8 +/- 29.9 vs. 541.6 +/- 51 microliters.min-1.g-1, P less than 0.05) with subsequent stabilization throughout the duration of the perfusion. In contrast, the tubular reabsorption of sodium decreased significantly in a linear fashion from 97.1 +/- 0.7 to 64.3 +/- 7.0% over the duration of the perfusion. Similarly, the tubular reabsorption of lithium decreased linearly from 74.8 +/- 2.6%, before the addition of cytochalasin, to 33.6 +/- 6.8% by the end of the perfusion. Correlation of the decrements in percent tubular reabsorption of sodium and lithium for individual kidneys was 0.87 (P less than 0.01), suggesting the effect of microfilament disruption on tubular reabsorption of sodium was localized primarily to the proximal tubule. Because ischemic injury is characterized by time-dependent structural alterations in the apical membrane of proximal tubule cells, we set out to determine whether microfilament disruption occurs during ischemic acute renal failure. Utilizing indirect immunofluorescence with an anti-actin antibody, control kidneys demonstrated intact circumferential apical immunofluorescence representing brush-border and terminal web actin staining. Fifteen minutes of ischemia resulted in multiple large gaps in the terminal web, and 50 min of ischemia caused diffuse redistribution of actin immunofluorescence throughout the cytoplasm.(ABSTRACT TRUNCATED AT 250 WORDS)
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Lovisa, Sara, Eliot Fletcher-Sananikone, Hikaru Sugimoto, et al. "Endothelial-to-mesenchymal transition compromises vascular integrity to induce Myc-mediated metabolic reprogramming in kidney fibrosis." Science Signaling 13, no. 635 (2020): eaaz2597. http://dx.doi.org/10.1126/scisignal.aaz2597.
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Endothelial-to-mesenchymal transition (EndMT) is a cellular transdifferentiation program in which endothelial cells partially lose their endothelial identity and acquire mesenchymal-like features. Renal capillary endothelial cells can undergo EndMT in association with persistent damage of the renal parenchyma. The functional consequence(s) of EndMT in kidney fibrosis remains unexplored. Here, we studied the effect of Twist or Snail deficiency in endothelial cells on EndMT in kidney fibrosis. Conditional deletion of Twist1 (which encodes Twist) or Snai1 (which encodes Snail) in VE-cadherin+ or Tie1+ endothelial cells inhibited the emergence of EndMT and improved kidney fibrosis in two different kidney injury/fibrosis mouse models. Suppression of EndMT limited peritubular vascular leakage, reduced tissue hypoxia, and preserved tubular epithelial health and function. Hypoxia, which was exacerbated by EndMT, resulted in increased Myc abundance in tubular epithelial cells, enhanced glycolysis, and suppression of fatty acid oxidation. Pharmacological suppression or epithelial-specific genetic ablation of Myc in tubular epithelial cells ameliorated fibrosis and restored renal parenchymal function and metabolic homeostasis. Together, these findings demonstrate a functional role for EndMT in the response to kidney capillary endothelial injury and highlight the contribution of endothelial-epithelial cross-talk in the development of kidney fibrosis with a potential for therapeutic intervention.
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Weidenbusch, Marc, Severin Rodler, and Hans-Joachim Anders. "Interleukin-22 in kidney injury and regeneration." American Journal of Physiology-Renal Physiology 308, no. 10 (2015): F1041—F1046. http://dx.doi.org/10.1152/ajprenal.00005.2015.
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Interleukins have become well-known regulators of innate and adaptive immunity-related tissue inflammation. Recently, IL-22 has gained a lot of interest for its unique functions in maintaining and regaining epithelial integrity. IL-22 is exclusively secreted by different immune cell subsets, while IL-22 receptors are mainly expressed by epithelial cells. As the kidney is largely an epithelial organ, the functional role of IL-22 in the kidney deserves to be explored in detail. Here, we briefly summarize the key features of IL-22 biology and review the available data on its expression and functional roles in kidney injury and kidney regeneration. Furthermore, we provide suggestions on how to explore this evolving field in the future.
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Martinez-Maldonado, M., J. M. Lopez-Novoa, E. Fernandez-Repollet, C. Baldizon, S. Opava-Stitzer, and J. E. Benabe. "Functional studies in experimental renal cortical necrosis in the rat." American Journal of Physiology-Renal Physiology 257, no. 6 (1989): F925—F936. http://dx.doi.org/10.1152/ajprenal.1989.257.6.f925.
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Necrosis of the outer two-thirds of the cortex (CN) was induced with boiling water in the left kidney of rats. Two days afterward, morphological damage was shown to be limited to the superficial cortex; deep nephron population was well-preserved. Glucose reabsorption under basal and glucose loading conditions, and extraction of p-aminohippurate, used as indices of proximal tubule integrity, were normal in control and experimental kidneys 48 h after cortical necrosis. Basal fractional water and electrolyte excretion did not differ between control and experimental kidneys. Calculated mean single-nephron glomerular filtration rate (GFR) and plasma flow for superficial (SupGFR and SupNPF) and juxtamedullary nephrons (JMGFR and JMPF) were similar to those obtained by micropuncture and Hanssen's technique for SupGFR, and for JMGFR by Hanssen's. Volume expansion led to a 27% increase in calculated SupGFR, but no change in JMGFR. The JMPF increased by 81%, whereas SupNPF increased by only 23%, suggesting that, in this model, GFR of deep nephrons may be independent of plasma flow. The results indicate that deep nephrons retain their functional integrity 48 h after cortical necrosis. After volume expansion fractional excretion of sodium was greater, and fractional water reabsorption less, in CN than in control kidneys. Thus handling of sodium and water by superficial and deep nephrons under basal conditions was similar, but reabsorptive capacity for deep nephrons of CN was lower during volume expansion. The present studies suggest that deep nephrons can maintain relatively normal function in cortical necrosis.
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Herath, Sanjeeva, Amy Y. M. Au, Kylie M. Taylor, Natasha Kapoor-Kaushik, Zoltán H. Endre, and Jonathan H. Erlich. "Long-Term Functional and Structural Renoprotection After Experimental Acute Kidney Injury in Subclinical Chronic Kidney Disease In Vivo." International Journal of Molecular Sciences 26, no. 10 (2025): 4616. https://doi.org/10.3390/ijms26104616.
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Subclinical chronic kidney disease (sCKD) predisposes one to acute kidney injury (AKI) and chronic kidney disease (CKD). Reduced kidney functional reserve (KFR) detects sCKD in preclinical studies and predicts AKI after cardiac surgery. We evaluated renal protection in a rat model of kidney injury where ischaemia–reperfusion injury (IRI) was induced after sCKD. Dual treatment boosting nicotinamide adenine dinucleotide (NAD) by nicotinamide riboside (NR) combined with the mitochondria-targeted antioxidant SkQR1 protected the KFR and reduced structural kidney damage, including markers of vascular integrity and the relative blood volume (rBV). The dual treatment upregulated Sirt1 and Nrf2, increased the nuclear localisation of the mitochondrial biogenesis regulator PGC-1α and the mitochondrial protein marker COX4, and upregulated the antioxidant gene NOQ1. These observations suggest mitochondrial protection and modulation of the cellular redox state provided long-term structural and functional protection against kidney injury superimposed on background sCKD.
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LeNoble, L. M., R. W. Lappe, M. J. Brody, H. A. Struyker Boudier, and J. F. Smits. "Selective efferent chemical sympathectomy of rat kidneys." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 249, no. 4 (1985): R496—R501. http://dx.doi.org/10.1152/ajpregu.1985.249.4.r496.
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Surgical denervation of kidneys results in interruption of both afferent and efferent renal nerves. We attempted selective efferent renal denervation in rats by slow infusions of 6-hydroxydopamine (6-OHDA) into the right renal artery. Integrity of efferent renal nerves was assessed by chemical and physiological methods and by measuring responses of mean arterial blood pressure (MAP) and heart rate (HR) to intrarenal (ir) infusion of bradykinin in conscious rats. Results were compared with those in surgically denervated and ir saline-infused rats. Surgical denervation of left kidney reduced renal norepinephrine (NE) to 58 and 14% of control levels at 1 and 7 days, respectively, after surgery. Increase in left renal resistance during posterior hypothalamus (PH) stimulation was only 70 +/- 28% (n = 5) compared with 289 +/- 69% (n = 6) in control animals. Response in opposite kidney was unchanged. Although 0.1 mg 6-OHDA ir caused considerable reduction of NE levels in both kidneys, responses to PH stimulation were unchanged. 6-OHDA (1 mg) reduced NE levels in infused and control kidney and atria. Functional evidence for denervation was only obtained in the kidney infused with 6-OHDA. Responses of MAP and HR to ir bradykinin were unchanged 7 days after 1 mg 6-OHDA. The data suggest that ir 6-OHDA results in functional efferent sympathectomy without affecting afferent renal nerves.
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You, Y., D. J. Hirsch, and N. S. Morgunov. "Functional integrity of proximal tubule cells: effects of temperature and preservation solutions." Journal of the American Society of Nephrology 3, no. 12 (1993): 1900–1912. http://dx.doi.org/10.1681/asn.v3121900.
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Electrophysiologic and morphologic changes during cooling and perfusion with preservation solutions in isolated perfused proximal straight tubules from Swiss white mice were investigated. In standard Ringer-substrate solution, cooling from 37 degrees C to 22 and 4 degrees C depolarized both transepithelial potential and basolateral cell membrane potential. Basolateral k+ transference number and cell membrane conductances were also significantly reduced. An increase in intracellular Na+ activity was observed only during cooling from 37 to 4 degrees C. No cell swelling was detected when tubules were perfused with Ringer-substrate solution at all three temperatures up to 1 h. Perfusion with Euro-Collins' (EC) solution at 37 degrees C resulted in rapid cell swelling, associated with rapid deterioration of transepithelial potential. Substitution of glucose with mannitol abolished the damaging effect of EC solution at 37 degrees C. EC perfusion at 22 degrees C also led to cell swelling and deterioration of transepithelial potential, but after a 10-min delay. In comparison, perfusion with University of Wisconsin (UW) solution at 22 or 37 degrees C had no effect on cell volume. Less damage to transepithelial potential was observed after the UW perfusion. It was concluded that EC solution is more damaging than UW solution to kidney tubules at 22 and 37 degrees C. The presence of EC solution in the renal interstitium during the rewarming phase may contribute significantly to reperfusion injuries in kidney transplantation.
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Bhati, Yogendra, Biswaranjan Mohanty, and Manashree Mane. "Research on Whole Organ Decellularization Protocols for Kidney Transplantation and Vascular Integrity Evaluation." Seminars in Medical Writing and Education 2 (December 30, 2023): 144. https://doi.org/10.56294/mw2023144.
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The shortage of donor kidneys highlights the need for innovative approaches to transplantation. Whole-organ decellularization creates acellular scaffolds suitable for recellularization with recipient-derived cells, reducing the risk of immune rejection. A key challenge is preserving vascular integrity during decellularization to ensure organ functionality. This aims to compare three decellularization protocols, detergent-based, enzyme-based, and a combined approach, for their effectiveness in maintaining vascular integrity (VI), ECM retention, and perfusion capacity. Additionally, factors influencing VI are analyzed using statistical techniques. Kidneys were processed using the three protocols. VI was measured using parameters such as ECM retention percentage, vascular leakage rates, and perfusion capacity. Pearson correlation analysis determined correlations between parameters such as decellularization time and vascular outcomes. One-way ANOVA contrasted protocol performance, and logistic regression determined predictors of preservation of VI. There were significant differences in ECM retention between protocols. The detergent-based process showed superior ECM retention and reduced vascular leakage compared to other processes. Logistic regression found decellularization time and solution concentration were important predictors of vascular preservation. The detergent-based protocol better maintained VI and ECM retention, thus holding potential for future clinical use in kidney transplantation. Additional optimization might further improve scaffold quality and functional results.
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Lakhe-Reddy, Sujata, Vincent Li, Thomas D. Arnold, Shenaz Khan та Jeffrey R. Schelling. "Mesangial cell αvβ8-integrin regulates glomerular capillary integrity and repair". American Journal of Physiology-Renal Physiology 306, № 12 (2014): F1400—F1409. http://dx.doi.org/10.1152/ajprenal.00624.2013.
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αvβ8-Integrin is most abundantly expressed in the kidney, brain, and female reproductive organs, and its cognate ligand is latent transforming growth factor (LTGF)-β. Kidney αvβ8-integrin localizes to mesangial cells, and global β8-integrin gene ( Itgb8) deletion results in embryonic lethality due to impaired placentation and cerebral hemorrhage. To circumvent the lethality and better define kidney αvβ8-integrin function, Cre-lox technology was used to generate mesangial-specific Itgb8-null mice. Platelet-derived growth factor-β receptor ( PDGFBR)- Cre mice crossed with a reporter strain revealed functional Cre recombinase activity in a predicted mesangial pattern. However, mating between two different PDGFBR-Cre or Ren1 d -Cre strains with Itgb8 flox/− mice consistently resulted in incomplete recombination, with no renal phenotype in mosaic offspring. Induction of a renal phenotype with Habu snake venom, a reversible mesangiolytic agent, caused exaggerated glomerular capillary microaneurysms and delayed recovery in Cre+/− PDGFRB flox/− mice compared with Cre+/− PDGFRB flox/+ control mice. To establish the mechanism, in vitro experiments were conducted in Itgb8-null versus Itgb8-expressing mesangial cells and fibroblasts, which revealed β8-integrin-regulated adhesion to Arg-Gly-Asp (RGD) peptides within a mesangial-conditioned matrix as well as β8-integrin-dependent migration on RGD-containing LTGF-β or vitronectin matrices. We speculate that kidney αvβ8-integrin indirectly controls glomerular capillary integrity through mechanical tension generated by binding RGD peptides in the mesangial matrix, and healing after glomerular injury may be facilitated by mesangial cell migration, which is guided by transient β8-integrin interactions with RGD ligands.
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Nkanu, EE, K. Dasofunjo, UP Ujong, and EE Amaku. "Physiological and biochemical implications of prenatal exposure to acetaminophen and Piliostigma thonningii extract on the renal function indices of female rats." GSC Biological and Pharmaceutical Sciences 12, no. 1 (2020): 015–24. https://doi.org/10.5281/zenodo.4269337.
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N-Acetyl-p-Aminophenol (APAP), also known as acetaminophen, is the most commonly used over-the counter analgesic and antipyretic medication. However, its overdose leads to both liver and kidney damage. This research work assessed the effect of prenatal exposure to <em>Piliostigma thonningii</em> on some renal function indices following acetaminophen induced toxicity. The leaves of <em>P. thonningii</em> were collected and air dried for 14 days until constant weight was obtained. Twenty-five (25) pregnant female rats (180 - 200) g was grouped on the bases of their weight to five (5) groups of 5 rats each. Animals in group A served as control while groups B-E served as the treated groups. Group B was administered with 200 mg/kgb.wt of acetaminophen, Group C was administered 200 mg/kgb. wt of <em>P. thonningii</em>, Group D was administered with 100 mg/kgb. wt of <em>P. thonningii</em> + 200 mg/kgb . wt of acetaminophen, while group E was administered 200 mg/kgb. wt of <em>P. thonningii</em> + 200 mg/kgb. wt of acetaminophen. The administration was done for 28days/till parturition. The dams were fed for 21day and five from each group were sacrificed and blood collected by cardiac puncture in sterile plane tubes for prenatal renal function assessment. The result shows (p<0.05) significant increase in Na<sup>+</sup> concentration of groups administered with acetaminophen alone, with evidence of significant decrease in groups administered with <em>P.thonningii</em> alone. The result also show that prenatal exposure to <em>P.thonningii </em>produced no significant difference on serum K<sup>+</sup>,Cl<sup>-</sup>,HCO<sub>3</sub><sup>-</sup>,urea,creatinine, ALT,AST and ALP. It was speculated that prenatal exposure to acetaminophen produced no assault on the functional integrity of the kidney but with an evidence of hypernatremia which may be due to increase in aldosterone level.
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Albrahim, Tarfa. "Effect of Blueberry Supplement on Alleviating Aged-Associated Kidney Dysfunction in Rats." Current Research in Nutrition and Food Science Journal 13, no. 1 (2025): 200–217. https://doi.org/10.12944/crnfsj.13.1.13.
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The study investigated the possible benefits of supplementing with blueberry extract (BBE) to mitigate age-related kidney alterations and oxidative stress in a murine model. As aging is related to structural and functional changes in the kidneys, the study aimed to determine whether the implementation of a BBE-enriched diet could alleviate these negative consequences. In this study, 4-week administration with a BBE to 24-month-old male Wistar rats orally (100 mg/kg) was investigated in aging-induced alterations in kidney biochemistry including kidney function (blood urea nitrogen, creatinine, and calcium ions levels), oxidants/antioxidants status [lipid peroxidation, nitric oxide, glutathione, total antioxidant capacity, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and nuclear factor erythroid 2-related factor 2 (Nrf2)], and inflammation status (tumor necrosis factor-α, interleukin-1β, and interleukin-10), in addition to the kidney structure. The study revealed significant changes in different kidney parameters in aging rats, including increased serum urea and creatinine levels, decreased blood calcium levels, increased MMP-9, inflammatory cytokines, oxidative stress, and decreased antioxidant enzyme activity. However, including BBE in the diet of aged rats resulted in several positive outcomes. Histopathological investigation revealed age-related structural alterations in the kidneys, which were partially mitigated by BBE, notably in terms of the preservation of glomerular integrity. Finally, the study reveals that BBE has therapeutic potential in combating age-related renal oxidative stress and inflammation, making it a promising diet intervention for maintaining kidney health in aging individuals.
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Faria, João, Sabbir Ahmed, Dimitrios Stamatialis, et al. "Bioengineered Kidney Tubules Efficiently Clear Uremic Toxins in Experimental Dialysis Conditions." International Journal of Molecular Sciences 24, no. 15 (2023): 12435. http://dx.doi.org/10.3390/ijms241512435.
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Patients with end-stage kidney disease (ESKD) suffer from high levels of protein-bound uremic toxins (PBUTs) that contribute to various comorbidities. Conventional dialysis methods are ineffective in removing these PBUTs. A potential solution could be offered by a bioartificial kidney (BAK) composed of porous membranes covered by proximal tubule epithelial cells (PTECs) that actively secrete PBUTs. However, BAK development is currently being hampered by a lack of knowledge regarding the cytocompatibility of the dialysis fluid (DF) that comes in contact with the PTECs. Here, we conducted a comprehensive functional assessment of the DF on human conditionally immortalized PTECs (ciPTECs) cultured as monolayers in well plates, on Transwell® inserts, or on hollow fiber membranes (HFMs) that form functional units of a BAK. We evaluated cell viability markers, monolayer integrity, and PBUT clearance. Our results show that exposure to DF did not affect ciPTECs’ viability, membrane integrity, or function. Seven anionic PBUTs were efficiently cleared from the perfusion fluid containing a PBUTs cocktail or uremic plasma, an effect which was enhanced in the presence of albumin. Overall, our findings support that the DF is cytocompatible and does not compromise ciPTECs function, paving the way for further advancements in BAK development and its potential clinical application.
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Willinger, Christian C., Herbert Schramek, Kristian Pfaller, Michael Joannidis, Peter Deetjen, and Walter Pfaller. "Ultrapure Polymerized Bovine Hemoglobin Improves Structural and Functional Integrity of the Isolated Perfused Rat Kidney." Kidney and Blood Pressure Research 18, no. 6 (1995): 288–305. http://dx.doi.org/10.1159/000173929.
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Garcia-Dominguez, Ximo, César D. Vera-Donoso, Eric Lopez-Moncholi, Victoria Moreno-Manzano, José S. Vicente, and Francisco Marco-Jiménez. "Sildenafil Citrate Enhances Renal Organogenesis Following Metanephroi Allotransplantation into Non-Immunosuppressed Hosts." Journal of Clinical Medicine 11, no. 11 (2022): 3068. http://dx.doi.org/10.3390/jcm11113068.
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In order to harness the potential of metanephroi allotransplantation to the generation of a functional kidney graft on demand, we must achieve further growth post-transplantation. Sildenafil citrate (SC) is widely known as a useful inductor of angiogenesis, offering renoprotective properties due to its anti-inflammatory, antifibrotic, and antiapoptotic effects. Here, we performed a laparoscopic metanephroi allotransplantation after embedding sildenafil citrate into the retroperitoneal fat of non-immunosuppressed adult rabbit hosts. Histology and histomorphometry were used to examine the morphofunctional changes in new kidneys 21 days post-transplantation. Immunofluorescence of E-cadherin and renin and erythropoietin gene expression were used to assess the tubule integrity and endocrine functionality. After the metanephroi were embedded in a 10 µM SC solution, the new kidneys’ weights become increased significantly. The E-cadherin expression together with the renin and erythropoietin gene expression revealed its functionality, while histological mature glomeruli and hydronephrosis proved the new kidneys’ excretory function. Thus, we have described a procedure through the use of SC that improves the outcomes after a metanephroi transplantation. This study gives hope to a pathway that could offer a handsome opportunity to overcome the kidney shortage.
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Pyatchenkov, M. O., A. G. Markov, and A. Sh Rumyantsev. "Structural and functional intestinal barrier abnormalities and chronic kidney disease. Literature review. Part I." Nephrology (Saint-Petersburg) 26, no. 1 (2022): 10–26. http://dx.doi.org/10.36485/1561-6274-2022-26-1-10-26.
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The gut microbiota is an essential part of the human organism, which plays a crucial role in maintaining its homeostasis. Peaceful coexistence with trillions of microorganisms mainly depends on the normal functioning of cellular and extracellular components of the intestinal mucosa, often called the "intestinal barrier". This barrier protects the organism against pathogenic infections while and at the same time satisfying its requirements for digestion and absorption of nutrients. It is not surprising that structural and functional intestinal barrier abnormalities are involved in the pathogenesis of many diseases including various nephropathies. The pathogenetic interconnection between the intestine and the kidneys is bidirectional. On the one hand, uremia affects the microbiota composition and the integrity of the intestinal epithelium. On the other hand, uremic toxins translocation, formed as a result of abnormal microbial metabolism, from the intestine into circulation through the ultra-permeable barrier contributes to the progression of renal dysfunction. Furthermore, according to a number of researchers, dysbiosis and the leaky gut syndrome are considered as one of the possible causes of anemia, nutritional disorders, cardiovascular and many other complications, often diagnosed in patients with chronic renal disease. The first part of the review reflects modern data about normal intestinal barrier structure and physiology, as well as methods for studying the intestinal wall integrity and permeability. The significant role of microbiota in the regulation of the barrier properties of the intestinal mucous and epithelial layer is emphasizing. The main differences between the intestinal microflora of patients with nephropathies from healthy people are presented, possible causes of their occurrence are discussed.
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Pirola, C. J., A. L. Alvarez, M. S. Balda, S. Finkielman, and V. E. Nahmod. "Evidence for cholinergic innervation in dog renal tissue." American Journal of Physiology-Renal Physiology 257, no. 5 (1989): F746—F754. http://dx.doi.org/10.1152/ajprenal.1989.257.5.f746.
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Denervation procedures that affect the sympathetic system of the kidney, as demonstrated by norepinephrine depletion of renal tissue, increased urine volume, fractional sodium excretion, and free water clearance in anesthetized water-loaded dogs. These increases were reduced by atropine, which also blocked the increase above those basal functional levels produced by acetylcholine in both innervated and denervated kidneys. An in vitro tubular cell preparation of innervated kidneys corresponding to the outer cortex showed [3H]quinuclidinyl benzilate (QNB) binding parameters characteristic of muscarinic receptors. Denervation did not change either [3H]QNB binding parameters or the ability of inner and outer cortex cells to perform the hemicholinium-3-inhibitable, sodium-dependent choline uptake and conversion of [3H]choline to [3H]acetylcholine. This cell membrane behavior is similar to that observed in tissues where cholinergic neuronal structures are present, suggesting the existence of a cholinergic innervation of the kidney, independent of the integrity of vessel-traveling nerves. Similarly, the finding of choline acetyltransferase in renal tissue, unaffected by sympathetic denervation, seems to confirm the presence of cholinergic nerve terminals. The cholinergic system may thus contribute to the regulation of tubular reabsorption of sodium and water in some conditions.
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Xushvaqtov, Ilyos Shodiqul o'g'li, Mahliyo Zokir qizi Turdimurodova, Muhayyo Boboniyozovna Xuramova, Dilshoda Abdulla qizi Xurramova, and Shaxina Ilxomovna Rajabova. "PATHOPHYSIOLOGY OF KIDNEY DISEASES. DISORDERS OF URINE PRODUCTION AND EXCRETION. CHARACTERISTICS OF CHILDREN." Multidisciplinary Journal of Science and Technology 3, no. 4 (2023): 210–14. https://doi.org/10.5281/zenodo.10207071.
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Chronic kidney disease (CKD) is a condition in which an initial injury is superseded by a more gradual, chronic process of decreasing function that, in the most extreme cases, ultimately leads to the need for renal replacement therapy. An important consideration is that, while the initiating causes are quite varied, as CKD progresses the mechanisms involved become increasingly similar, so that eventually a set of common events contributes to inexorable loss of functional nephron mass. The mechanisms that are involved can be described as those that disrupt normal renal physiology and those by which decreasing structural integrity renders such disruption irreversible. Thus, the key to understanding progression is examining how function becomes dysregulated and how this dysfunction interacts with the process of renal scarring. This chapter will review these mechanisms.
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Sequeira-Lopez, Maria Luisa S., Vidya K. Nagalakshmi, Minghong Li, Curt D. Sigmund, and R. Ariel Gomez. "Vascular versus tubular renin: role in kidney development." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 309, no. 6 (2015): R650—R657. http://dx.doi.org/10.1152/ajpregu.00313.2015.
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Renin, the key regulated enzyme of the renin-angiotensin system regulates blood pressure, fluid-electrolyte homeostasis, and renal morphogenesis. Whole body deletion of the renin gene results in severe morphological and functional derangements, including thickening of renal arterioles, hydronephrosis, and inability to concentrate the urine. Because renin is found in vascular and tubular cells, it has been impossible to discern the relative contribution of tubular versus vascular renin to such a complex phenotype. Therefore, we deleted renin independently in the vascular and tubular compartments by crossing Ren1 c fl/fl mice to Foxd1-cre and Hoxb7-cre mice, respectively. Deletion of renin in the vasculature resulted in neonatal mortality that could be rescued with daily injections of saline. The kidneys of surviving mice showed the absence of renin, hypertrophic arteries, hydronephrosis, and negligible levels of plasma renin. In contrast, lack of renin in the collecting ducts did not affect kidney morphology, intra-renal renin, or circulating renin in basal conditions or in response to a homeostatic stress, such as sodium depletion. We conclude that renin generated in the renal vasculature is fundamental for the development and integrity of the kidney, whereas renin in the collecting ducts is dispensable for normal kidney development and cannot compensate for the lack of renin in the vascular compartment. Further, the main source of circulating renin is the kidney vasculature.
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Bricker, N. S., P. A. Morrin, and S. W. Kime. "The pathologic physiology of chronic Bright's disease. An exposition of the "intact nephron hypothesis"." Journal of the American Society of Nephrology 8, no. 9 (1997): 1470–76. http://dx.doi.org/10.1681/asn.v891470.
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Clinical and experimental data relating to the functional capacity of the surviving nephrons of the chronically diseased kidney for the most part support the thesis that these nephrons retain their essential functional integrity regardless of the nature of the underlying form of chronic Bright's disease. There are instances in which specific alterations of function correlate with pathologic involvement of a particular site of the nephron but these appear to represent the exceptions, and in general the more advanced the disease becomes, the less evident are the differentiating features. Studies on dogs with unilateral renal disease indicate that the functional capacity of the nephrons of the diseased kidney parallels that of the nephrons of the contralateral normal kidney. These data tend to exclude widespread intrinsic damage to the functioning nephrons by the underlying pathologic processes. From these observations, as well as from certain supporting clinical and experimental observations, it is suggested that the majority of surviving nephrons in the patient with bilateral renal disease similarly are functionally intact. Concepts of the pathologic physiology of the kidney, based on the "intact nephron hypothesis", are presented. Within the framework of this hypothesis it is concluded that (1) the diseased kidney consists of a diminished number of nephrons, most of which retain essentially normal functional abilities; (2) certain of the apparent abnormalities in function in bilateral renal disease may relate to adaptive changes imposed by the decreased nephron population and the attendant derangements in body fluids rather than to structural distortion of nephrons; (3) the over-all flexibility of the diseased kidney decreases as the number of constituent nephrons decreases; but (4) there is an orderly and predictable pattern of excretion for all substances.
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Elwakiel, Ahmed, Akash Mathew, and Berend Isermann. "The role of endoplasmic reticulum–mitochondria-associated membranes in diabetic kidney disease." Cardiovascular Research 119, no. 18 (2023): 2875–83. http://dx.doi.org/10.1093/cvr/cvad190.
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Abstract Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide. The pathomechanisms of DKD are multifactorial, yet haemodynamic and metabolic changes in the early stages of the disease appear to predispose towards irreversible functional loss and histopathological changes. Recent studies highlight the importance of endoplasmic reticulum–mitochondria-associated membranes (ER-MAMs), structures conveying important cellular homeostatic and metabolic effects, in the pathology of DKD. Disruption of ER-MAM integrity in diabetic kidneys is associated with DKD progression, but the regulation of ER-MAMs and their pathogenic contribution remain largely unknown. Exploring the cell-specific components and dynamic changes of ER-MAMs in diabetic kidneys may lead to the identification of new approaches to detect and stratify diabetic patients with DKD. In addition, these insights may lead to novel therapeutic approaches to target and/or reverse disease progression. In this review, we discuss the association of ER-MAMs with key pathomechanisms driving DKD such as insulin resistance, dyslipidaemia, ER stress, and inflammasome activation and the importance of further exploration of ER-MAMs as diagnostic and therapeutic targets in DKD.
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Cybulsky, Andrey V., Joan Papillon, Julie Guillemette, Natalya Belkina, Genaro Patino-Lopez, and Elena Torban. "Ste20-like kinase, SLK, a novel mediator of podocyte integrity." American Journal of Physiology-Renal Physiology 315, no. 1 (2018): F186—F198. http://dx.doi.org/10.1152/ajprenal.00238.2017.
Full textAbstract:
SLK is essential for embryonic development and may play a key role in wound healing, tumor growth, and metastasis. Expression and activation of SLK are increased in kidney development and during recovery from ischemic acute kidney injury. Overexpression of SLK in glomerular epithelial cells/podocytes in vivo induces injury and proteinuria. Conversely, reduced SLK expression leads to abnormalities in cell adhesion, spreading, and motility. Tight regulation of SLK expression thus may be critical for normal renal structure and function. We produced podocyte-specific SLK-knockout mice to address the functional role of SLK in podocytes. Mice with podocyte-specific deletion of SLK showed reduced glomerular SLK expression and activity compared with control. Podocyte-specific deletion of SLK resulted in albuminuria at 4–5 mo of age in male mice and 8–9 mo in female mice, which persisted for up to 13 mo. At 11–12 mo, knockout mice showed ultrastructural changes, including focal foot process effacement and microvillous transformation of podocyte plasma membranes. Mean foot process width was approximately twofold greater in knockout mice compared with control. Podocyte number was reduced by 35% in knockout mice compared with control, and expression of nephrin, synaptopodin, and podocalyxin was reduced in knockout mice by 20–30%. In summary, podocyte-specific deletion of SLK leads to albuminuria, loss of podocytes, and morphological evidence of podocyte injury. Thus, SLK is essential to the maintenance of podocyte integrity as mice age.
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Kelam, Nela, Marin Ogorevc, Ivona Gotovac та ін. "Analysis of Kallikrein 6, Acetyl-α-Tubulin, and Aquaporin 1 and 2 Expression Patterns During Normal Human Nephrogenesis and in Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)". Genes 16, № 5 (2025): 499. https://doi.org/10.3390/genes16050499.
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Background/Objectives: The human kallikrein-related peptidase 6 (KLK6), a serine protease with trypsin-like properties, belongs to the 15-member kallikrein (KLK) gene family and is predominantly recognized for its role in oncogenesis, neurodegenerative disorders, and skin conditions. Aquaporins (AQPs) are integral membrane proteins that facilitate water transport across cell membranes. AQP1 is constitutively active in the kidneys and plays a crucial role in reabsorbing filtered water, while AQP2 is regulated by vasopressin and is essential for maintaining body fluid homeostasis. The primary objective of the present study is to investigate the spatio-temporal expression patterns of KLK6, AQP1, and AQP2 throughout normal human nephrogenesis and congenital kidney and urinary tract (CAKUT) abnormalities: duplex kidneys, horseshoe kidneys, and dysplastic kidneys. Methods: An immunofluorescence analysis of KLK6, AQP1, and AQP2 was performed on 37 paraffin-embedded fetal kidney samples. The area percentage of KLK6 in the kidney cortex was calculated in normal developing samples during developmental phases 2, 3, and 4 and compared with CAKUT samples. Results: KLK6 exhibits distinct spatiotemporal expression patterns during human kidney development, with consistent localization in proximal tubules. Its subcellular positioning shifts from the basolateral cytoplasm in early phases to the apical cytoplasm in later stages, which may be strategically positioned to act on its substrate in either the peritubular space or the tubular fluid. KLK6 expression followed a quadratic trajectory, peaking at Ph4. This marked increase in the final developmental phase aligns with its strong expression in mature kidneys, suggesting a potential role in proximal tubule differentiation and functional maturation through facilitating extracellular matrix remodeling and activating proteinase-activated receptors, modulating the signaling pathways that are essential for tubular development. In duplex kidneys, structural abnormalities such as ureteral obstruction and hydronephrosis may upregulate KLK6 as part of a reparative response, while its downregulation could impair epithelial remodeling and cytoskeletal integrity, exacerbating dysplastic phenotypes. Conclusions: These findings highlight the potential of KLK6 involvement in normal kidney development and the pathology of CAKUT.
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Liu, Zhiwen, Ying Wang, Shaoqun Shu, Juan Cai, Chengyuan Tang, and Zheng Dong. "Non-coding RNAs in kidney injury and repair." American Journal of Physiology-Cell Physiology 317, no. 2 (2019): C177—C188. http://dx.doi.org/10.1152/ajpcell.00048.2019.
Full textAbstract:
Acute kidney injury (AKI) is a major kidney disease featured by a rapid decline of renal function. Pathologically, AKI is characterized by tubular epithelial cell injury and death. Besides its acute consequence, AKI contributes critically to the development and progression of chronic kidney disease (CKD). After AKI, surviving tubular cells regenerate to repair. Normal repair restores tubular integrity, while maladaptive or incomplete repair results in renal fibrosis and eventually CKD. Non-coding RNAs (ncRNAs) are functional RNA molecules that are transcribed from DNA but not translated into proteins, which mainly include microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), small nucleolar RNAs (snoRNAs), and tRNAs. Accumulating evidence suggests that ncRNAs play important roles in kidney injury and repair. In this review, we summarize the recent advances in the understanding of the roles of ncRNAs, especially miRNAs and lncRNAs in kidney injury and repair, discuss the potential application of ncRNAs as biomarkers of AKI as well as therapeutic targets for treating AKI and impeding AKI-CKD transition, and highlight the future research directions of ncRNAs in kidney injury and repair.
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Huang, G. Steven, and Meng-Yen Hong. "Functional and Molecular Characterization for the Damp-Obstructed Rat Model in Chinese Medicine." American Journal of Chinese Medicine 34, no. 02 (2006): 323–40. http://dx.doi.org/10.1142/s0192415x06003862.
Full textAbstract:
Functional and molecular characterization was performed on the major organs of damp-obstructed rats by applying expression datasets of microarray experiments and real-time RT-PCR. Gene ontology repertoires, i.e. cellular component, molecular function, and biological process were used to classify differentially expressed genes in the major organs of rats upon treatment of dampness. As to the cellular component, over-expression of genes associated with the plasma membrane was observed in the stomach, spleen, kidney, heart, liver, and lung. Genes associated with translational machinery, endoplasmic recticulum membrane, Golgi apparatus, and nuclear envelope were down-regulated in the stomach. Concerning the molecular function, genes associated with oxidoreductase activity were up-regulated in the stomach, spleen, kidney, lung, and brain. Channel activity, membrane receptor, and electron transporter activity were up-regulated in stomach, kidney, and lung. Regarding the biological process, genes associated with signal transduction were up-regulated in the stomach, while genes associated with biosynthesis and ATP metabolism were down-regulated. In the spleen, melanin biosynthesis was up-regulated while hormone-related activities were down-regulated. In the kidney, genes associated with nucleotide biosynthesis and ATP metabolism were depressed. In the heart and liver, apoptosis was up-regulated while immune response and RAS signal transduction were down-regulated. Interestingly, genes associated with oncogenesis were up-regulated in the stomach and kidney. Functional fingerprints indicated that dampness weakened membrane structures, depressed metabolic activity (especially ATP metabolism), damaged matrix proteins, enhanced signal transduction, and revealed a positive association with oncogenesis. To quantify the functional impact at the molecular level, mRNA levels of key genes were determined by real-time RT-PCR. The results indicated that ATP storage in kidney, spleen, and stomach was depleted in damp-obstructed rats. We propose that oxidative stress, membrane integrity, melanin biosynthesis, ion channel activity, and ATP metabolism might be hallmarks for damp-obstructed rats. Our results also suggested dampness as a pathogenic factor in rats which is possibly associated with enhanced liabilities of cancer.
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Abbate, Mauro, Dennis Brown, and Joseph V. Bonventre. "Expression of NCAM recapitulates tubulogenic development in kidneys recovering from acute ischemia." American Journal of Physiology-Renal Physiology 277, no. 3 (1999): F454—F463. http://dx.doi.org/10.1152/ajprenal.1999.277.3.f454.
Full textAbstract:
Recovery of the kidney from acute renal failure relies on a sequence of events including epithelial cell dedifferentiation and proliferation followed by differentiation and restoration of the functional integrity of the nephron. The factors responsible for, and the significance of, reversion to a less differentiated cell phenotype and its relationship to the proliferative response after ischemia are poorly understood. In an attempt to identify adhesion molecules that may be influential in the recovery process, the expression of neural cell adhesion molecule (NCAM) and markers of epithelial differentiation and proliferation were analyzed at various times after an ischemic insult. In maturing nephrons, NCAM is detectable by immunohistochemistry in renal vesicles, S-shaped bodies, and early tubules. There is minimal cellular NCAM expression in normal tubules of the adult kidney. In contrast, in postischemic kidneys, NCAM expression is abundant in S3 proximal tubule cells 5 days after reperfusion. As in developing tubules, NCAM is concentrated in basal and lateral aspects of cells that have no apical gp330 or dipeptidyl peptidase IV detectable on their brush border. The expression of NCAM is preceded by disassembly of the brush border and proliferation of surviving S3 cells, which is most prominent at 2 days postischemia. NCAM expression persists in some flattened and dedifferentiated cells for up to 7 wk after ischemia. Thus proximal tubule epithelial cells of the postischemic kidney express NCAM in a pattern that recapitulates the expression of NCAM in the developing kidney. Such reversion of phenotype extends at least back to the early stages of renal vesicle formation, and this reversion may represent a critical step in the reestablishment of a normal tubule. NCAM-matrix interactions may mediate the motogenic and mitogenic responses of the dedifferentiated epithelium that are critical to reestablishment of a functional proximal tubule.
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Rodriguez, Patricia Q., Asmundur Oddsson, Lwaki Ebarasi, et al. "Knockdown of Tmem234 in zebrafish results in proteinuria." American Journal of Physiology-Renal Physiology 309, no. 11 (2015): F955—F966. http://dx.doi.org/10.1152/ajprenal.00525.2014.
Full textAbstract:
Podocytes are highly specialized epithelial cells located at the outer aspects of the glomerular capillary tuft and critical components of the kidney filtration barrier. To maintain their unique features, podocytes express a number of proteins that are only sparsely found elsewhere in the body. In this study, we have identified four (Tmem234, Znf185, Lrrc49, and Slfn5) new highly podocyte-enriched proteins. The proteins are strongly expressed by podocytes, while other parts of the kidney show only weak or no expression. Tmem234, Slfn5, and Lrrc49 are located in foot processes, whereas Znf185 is found in both foot and major processes. Expressional studies in developing kidneys show that these proteins are first expressed at the capillary stage glomerulus, the same stage when the formation of major and foot processes begins. We identified zebrafish orthologs for Tmem234 and Znf185 genes and knocked down their expression using morpholino technology. Studies in zebrafish larvae indicate that Tmem234 is essential for the organization and functional integrity of the pronephric glomerulus filtration barrier, as inactivation of Tmem234 expression results in foot process effacement and proteinuria. In summary, we have identified four novel highly podocyte-enriched proteins and show that one of them, Tmem234, is essential for the normal filtration barrier in the zebrafish pronephric glomerulus. Identification of new molecular components of the kidney filtration barrier opens up possibilities to study their role in glomerulus biology and diseases.
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Begum, Sajidah, and Gladys O. Latunde-Dada. "Anemia of Inflammation with An Emphasis on Chronic Kidney Disease." Nutrients 11, no. 10 (2019): 2424. http://dx.doi.org/10.3390/nu11102424.
Full textAbstract:
Iron is vital for a vast variety of cellular processes and its homeostasis is strictly controlled and regulated. Nevertheless, disorders of iron metabolism are diverse and can be caused by insufficiency, overload or iron mal-distribution in tissues. Iron deficiency (ID) progresses to iron-deficiency anemia (IDA) after iron stores are depleted. Inflammation is of diverse etiology in anemia of chronic disease (ACD). It results in serum hypoferremia and tissue hyperferritinemia, which are caused by elevated serum hepcidin levels, and this underlies the onset of functional iron-deficiency anemia. Inflammation is also inhibitory to erythropoietin function and may directly increase hepcidin level, which influences iron metabolism. Consequently, immune responses orchestrate iron metabolism, aggravate iron sequestration and, ultimately, impair the processes of erythropoiesis. Hence, functional iron-deficiency anemia is a risk factor for several ailments, disorders and diseases. Therefore, therapeutic strategies depend on the symptoms, severity, comorbidities and the associated risk factors of anemia. Oral iron supplements can be employed to treat ID and mild anemia particularly, when gastrointestinal intolerance is minimal. Intravenous (IV) iron is the option in moderate and severe anemic conditions, for patients with compromised intestinal integrity, or when oral iron is refractory. Erythropoietin (EPO) is used to treat functional iron deficiency, and blood transfusion is restricted to refractory patients or in life-threatening emergency situations. Despite these interventions, many patients remain anemic and do not respond to conventional treatment approaches. However, various novel therapies are being developed to treat persistent anemia in patients.
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Pollack, Anne L., Gerard Apodaca, and Keith E. Mostov. "Hepatocyte growth factor induces MDCK cell morphogenesis without causing loss of tight junction functional integrity." American Journal of Physiology-Cell Physiology 286, no. 3 (2004): C482—C494. http://dx.doi.org/10.1152/ajpcell.00377.2003.
Full textAbstract:
Hepatocyte growth factor (HGF) induces mitogenesis, motogenesis, and tubulogenesis of cultured Madin-Darby canine kidney (MDCK) epithelial cells. We report that in addition to these effects HGF stimulates morphogenesis of tight, polarized MDCK cell monolayers into pseudostratified layers without loss of tight junction (TJ) functional integrity. We tested TJ functional integrity during formation of pseudostratified layers. In response to HGF, the TJ marker ZO-1 remained in morphologically complete rings and functional barriers to paracellular diffusion of ruthenium red were maintained in pseudostratified layers. Transepithelial resistance (TER) increased transiently two- to threefold during the morphogenetic transition from monolayers to pseudostratified layers and then declined to baseline levels once pseudostratified layers were formed. In MDCK cells expressing the trk/met chimera, both HGF and NGF at concentrations of 2.5 ng/ml induced scattering. However, 2.5 ng/ml HGF did not affect TER. The peak effect of HGF on TER was at a concentration of 100 ng/ml. In contrast, NGF at concentrations as high as 25 μg/ml had no effect on TER or pseudostratified layer morphogenesis of trk/met-expressing cultures. These results suggest that altered presentation of the stimulus, such as through HGF interaction with low-affinity sites, may change the downstream signaling response. In addition, our results demonstrate that HGF stimulates pseudostratified layer morphogenesis while inducing an increase in TER and maintaining the overall tightness of the epithelial layer. Stimulation of epithelial cell movements by HGF without loss of functional TJs may be important for maintaining epithelial integrity during morphogenetic events such as formation of pseudostratified epithelia, organ regeneration, and tissue repair.
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Stițiuc, Irina, and Sasu Boris. "ASSESSING KIDNEY FUNCTION IN ELDERLY." Deutsche internationale Zeitschrift für zeitgenössische Wissenschaft 53 (April 3, 2023): 61–63. https://doi.org/10.5281/zenodo.7796143.
Full textAbstract:
In recent years, due to the increase in life expectancy in Western societies, there has been such an unprecedented phenomenon - a sharp increase in the proportion of elderly people aged 65 years and older. The main direction that will significantly affect the daily professional life of nephrologists in the 21st century is the progressive aging of the world's population. Therefore, plans to integrate nephrology with gerontology and geriatrics will allow these sciences to adapt to this inevitable phenomenon of increasing demographic pressure and manage health and care at all levels - from the individual patient to the general population and global health systems. Aim of the study: To study the prevalence and characteristics of functional changes in the kidneys in elderly and senile people for the early implementation of preventive actions.
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Jobst-Schwan, Tilman, Karl X. Knaup, Rikke Nielsen, et al. "Renal uptake of the antiapoptotic protein survivin is mediated by megalin at the apical membrane of the proximal tubule." American Journal of Physiology-Renal Physiology 305, no. 5 (2013): F734—F744. http://dx.doi.org/10.1152/ajprenal.00546.2012.
Full textAbstract:
The inhibitor of apoptosis protein survivin is a bifunctional molecule that regulates cellular division and survival. We have previously shown that survivin protein can be found at high concentrations in the adult kidney, particularly in the proximal tubules. Here, survivin is localized primarily at the apical membrane, a pattern that may indicate absorption of the protein. Several proteins in primary urine are internalized by megalin, an endocytosis receptor, which is in principle found in the same localization as survivin. Immunolabeling for survivin in different species confirmed survivin signal localizing to the apical membrane of the proximal tubule. Immunoelectron microscopy also showed apical localization of survivin in human kidneys. Furthermore, in polarized human primary tubular cells endogenous as well as external recombinant survivin is stored in the apical region of the cells. Costaining of survivin and megalin by immunohistochemistry and immunoelectron microscopy confirmed colocalization. Finally, by surface plasmon resonance we were able to demonstrate that survivin binds megalin and cubilin and that megalin knockout mice lose survivin through the urine. Survivin accumulates at the apical membrane of the renal tubule by reuptake, which is achieved by the endocytic receptor megalin, collaborating with cubilin. For this to occur, survivin will have to circulate in the blood and be filtered into the primary urine. It is not known at this stage what the functional role of tubular survivin is. However, a small number of experimental and clinical reports implicate that renal survivin is important for functional integrity of the kidney.
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Wilson, P. D. "Epithelial cell polarity and disease." American Journal of Physiology-Renal Physiology 272, no. 4 (1997): F434—F442. http://dx.doi.org/10.1152/ajprenal.1997.272.4.f434.
Full textAbstract:
The establishment and maintenance of epithelial polarity is essential for the integrity and function of epithelial organs and is particularly critical in the kidney, where vectorial reabsorption and secretion are effected in different segments of the nephron by the differential polarized insertion of channels, transporters, and related proteins into apical membranes lining the tubule lumen or basolateral membranes adjacent to the interstitium and blood space. Faulty intracellular delivery and polarization of membrane proteins can lead to serious diseases such as cystic fibrosis, I cell disease, and renal cystic diseases. The best understood disease of epithelial polarity is autosomal dominant polycystic kidney disease (ADPKD) caused by mutations in a >462-kDa, developmentally regulated membrane protein, “polycystin.” ADPKD cysts are characteristically lined by a single layer of structurally polarized epithelial cells with normal functional intercellular tight junctions but with aberrant polarization of some important membrane proteins. Abnormal apical membrane polarity of biochemically active, ouabain-sensitive Na-K-adenosinetriphosphatase (Na-K-ATPase) in ADPKD cyst epithelia leads to abnormal sodium ion secretion and provides a mechanism for aberrant fluid secretion. In addition, apically mislocated, functional epidermal growth factor (EGF) receptors on cyst epithelia, together with EGF synthesis and secretion into cyst lumens, provide a mechanism for autocrine regulation of increased epithelial cell proliferation in ADPKD. Underlying mechanisms for these abnormalities in polarized distribution of membrane proteins include the aberrant expression of fetal gene products, such as the beta2-subunit of Na-K-ATPase, in ADPKD kidneys. Overexpression of polycystin protein in ADPKD cyst epithelia, low levels restricted to medullary collecting tubules in normal adult kidneys, and high levels in ureteric bud-derived structures in human fetal kidneys further suggest a failure of downregulation of fetal genes as a mechanism for the polarity abnormalities that characterize ADPKD.
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.B, Ashika. "IDENTIFICATION OF CHRONIC RENAL ILLNESS USING RENAL STONE PICTURE AND VALUES." International Scientific Journal of Engineering and Management 04, no. 05 (2025): 1–9. https://doi.org/10.55041/isjem03878.
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Abstract - The escalating global prevalence of kidney stones necessitates innovative methodologies for precise detection and comprehensive functional assessment. This study leverages cutting-edge deep learning techniques, particularly Visual Geometry Group16 (VGG16), to enhance diagnostic accuracy and generalizability. By utilizing a diverse CT image dataset, the proposed model effectively discerns kidney stones while integrating advanced image processing techniques to refine predictive performance. Beyond mere identification, the framework incorporates a multifaceted functional analysis, evaluating critical factors such as obstruction, perfusion dynamics, and tissue integrity, thereby providing deeper clinical insights. The methodological approach encompasses rigorous model training on a meticulously curated dataset, followed by robust validation using key performance metrics, including sensitivity and specificity. The anticipated outcomes of this research include the development of a highly sophisticated AI-driven diagnostic system, fostering early intervention and optimizing patient outcomes. By seamlessly integrating artificial intelligence into renal healthcare, this study aims to redefine clinical paradigms, enhancing both diagnostic precision and therapeutic efficacy Key words - Chronic renal illness-CNN-VGG16-Deep Learning-Image classification
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Ojiako, Okey A., Paul C. Chikezie, Doris I. Ukairo, Chiedozie O. Ibegbulem, and Reginald N. Nwaoguikpe. "Functional assessments and histopathology of hepatorenal tissues of rats treated with raw and processed herbs." European Journal of Biological Research 7, no. 3 (2017): 172–90. https://doi.org/10.5281/zenodo.823220.
Full textAbstract:
The present study ascertained the functional integrity of hepatic and renal tissues, concurrently with blood lipid patterns, of Wistar rats infused with CCl<sub>4</sub> and treated with raw and hydrothermal processed herbs, namely, <em>Monodora myristica</em>, <em>Chromolaena odorata</em>, <em>Buccholzia coriacea</em> and <em>Sphenostylis stenocarpa</em>. Measurement of phytochemical contents of the herbs was according to standard methods. The rats were randomly designated on the bases of diets and treatments received for 28 consecutive days. Fibrosis was induced in the Wistar rats by single dose intra-peritoneal injection of CCl<sub>4</sub> for 2 consecutive days. Liver and kidney function tests and serum lipid profile were measured using spectrophotometric methods. Renal and hepatic tissues were subjected to histopathological examinations. The concentrations of alkaloids in the four herbal extracts were within the range of 4.83±0.03 - 31.33±0.29 mg/100 g sample, whereas the concentrations of saponins varied within a relatively narrow range: 0.33±0.09 - 4.33±0.02 mg/100 g dry sample; <em>p </em>> 0.05. The activity ratios of AST to ALT of the rat groups were generally less than 1.0 unit. Atherogenic indices of fibrotic rats were within the following ranges: TAG/HDL-C ratio (3.59±0.03 - 6.76±0.06), TC/HDL-C ratio (3.72±0.02 - 6.94±0.05) and LDL-C/HDL-C ratio (2.00±0.01 - 4.59±0.02). Losses in phytochemical contents following hydrothermal processing of the herbs did not substantially affect their overall therapeutic scores against morphological and functional impairments of hepatic and renal tissues following CCl<sub>4</sub> intoxication of the rats.
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Gonzalez, Claudio D., María Paula Carro Negueruela, Catalina Nicora Santamarina, Roxana Resnik, and Maria I. Vaccaro. "Autophagy Dysregulation in Diabetic Kidney Disease: From Pathophysiology to Pharmacological Interventions." Cells 10, no. 9 (2021): 2497. http://dx.doi.org/10.3390/cells10092497.
Full textAbstract:
Diabetic kidney disease (DKD) is a frequent, potentially devastating complication of diabetes mellitus. Several factors are involved in its pathophysiology. At a cellular level, diabetic kidney disease is associated with many structural and functional alterations. Autophagy is a cellular mechanism that transports intracytoplasmic components to lysosomes to preserve cellular function and homeostasis. Autophagy integrity is essential for cell homeostasis, its alteration can drive to cell damage or death. Diabetic kidney disease is associated with profound autophagy dysregulation. Autophagy rate and flux alterations were described in several models of diabetic kidney disease. Some of them are closely linked with disease progression and severity. Some antidiabetic agents have shown significant effects on autophagy. A few of them have also demonstrated to modify disease progression and improved outcomes in affected patients. Other drugs also target autophagy and are being explored for clinical use in patients with diabetic kidney disease. The modulation of autophagy could be relevant for the pharmacological treatment and prevention of this disease in the future. Therefore, this is an evolving area that requires further experimental and clinical research. Here we discuss the relationship between autophagy and Diabetic kidney disease and the potential value of autophagy modulation as a target for pharmacological intervention.
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Ergin, Bülent, Sakir Akin, and Can Ince. "Kidney Microcirculation as a Target for Innovative Therapies in AKI." Journal of Clinical Medicine 10, no. 18 (2021): 4041. http://dx.doi.org/10.3390/jcm10184041.
Full textAbstract:
Acute kidney injury (AKI) is a serious multifactorial conditions accompanied by the loss of function and damage. The renal microcirculation plays a crucial role in maintaining the kidney’s functional and structural integrity for oxygen and nutrient supply and waste product removal. However, alterations in microcirculation and oxygenation due to renal perfusion defects, hypoxia, renal tubular, and endothelial damage can result in AKI and the loss of renal function regardless of systemic hemodynamic changes. The unique structural organization of the renal microvasculature and the presence of autoregulation make it difficult to understand the mechanisms and the occurrence of AKI following disorders such as septic, hemorrhagic, or cardiogenic shock; ischemia/reperfusion; chronic heart failure; cardiorenal syndrome; and hemodilution. In this review, we describe the organization of microcirculation, autoregulation, and pathophysiological alterations leading to AKI. We then suggest innovative therapies focused on the protection of the renal microcirculation and oxygenation to prevent AKI.
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Bronas, Ulf. "EFFECT OF A 6-MONTH HOME-BASED WALKING PROGRAM ON COGNITIVE FITNESS IN OLDER ADULTS WITH CHRONIC KIDNEY DISEASE." Innovation in Aging 6, Supplement_1 (2022): 394–95. http://dx.doi.org/10.1093/geroni/igac059.1553.
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Abstract We have previously demonstrated that cognitive status and white matter integrity are highly associated with physical fitness in older adult patients with chronic kidney disease (CKD). We present data from a two group RCT determining effect of a 6-month home-based walking intervention on physical and cognitive fitness compared to usual care. The intervention included use of a wearable activity monitor, weekly didactic phone meetings, interactive tools and monthly coach-delivered feedback. The intervention group had a 78% compliance rate to the 6-month exercise program (159.9 (149.2) minutes/week). Executive function composite score and global cognitive for intervention group &gt; than control group. Additionally, global white matter integrity and functional connectivity improved in the intervention group and declined in the usual care group. We conclude that a home-based physical activity intervention can have significant improvement on cognitive health and neuroplasticity in older adults with CKD and lowering their risk of developing AD/ADRD
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Gnemmi, Viviane, Qiubo Li, Qiuyue Ma, et al. "Asymptomatic Hyperuricemia Promotes Recovery from Ischemic Organ Injury by Modulating the Phenotype of Macrophages." Cells 11, no. 4 (2022): 626. http://dx.doi.org/10.3390/cells11040626.
Full textAbstract:
Acute organ injury, such as acute kidney injury (AKI) and disease (AKD), are major causes of morbidity and mortality worldwide. Hyperuricemia (HU) is common in patients with impaired kidney function but the impact of asymptomatic HU on the different phases of AKI/AKD is incompletely understood. We hypothesized that asymptomatic HU would attenuate AKD because soluble, in contrast to crystalline, uric acid (sUA) can attenuate sterile inflammation. In vitro, 10 mg/dL sUA decreased reactive oxygen species and interleukin-6 production in macrophages, while enhancing fatty acid oxidation as compared with a physiological concentration of 5 mg/dL sUA or medium. In transgenic mice, asymptomatic HU of 7–10 mg/dL did not affect post-ischemic AKI/AKD but accelerated the recovery of kidney excretory function on day 14. Improved functional outcome was associated with better tubular integrity, less peritubular inflammation, and interstitial fibrosis. Mechanistic studies suggested that HU shifted macrophage polarization towards an anti-inflammatory M2-like phenotype characterized by expression of anti-oxidative and metabolic genes as compared with post-ischemic AKI-chronic kidney disease transition in mice without HU. Our data imply that asymptomatic HU acts as anti-oxidant on macrophages and tubular epithelial cells, which endorses the recovery of kidney function and structure upon AKI.
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Mitsas, Angelos C., Mohamed Elzawawi, Sophie Mavrogeni, et al. "Heart Failure and Cardiorenal Syndrome: A Narrative Review on Pathophysiology, Diagnostic and Therapeutic Regimens—From a Cardiologist’s View." Journal of Clinical Medicine 11, no. 23 (2022): 7041. http://dx.doi.org/10.3390/jcm11237041.
Full textAbstract:
In cardiorenal syndrome (CRS), heart failure and renal failure are pathophysiologically closely intertwined by the reciprocal relationship between cardiac and renal injury. Type 1 CRS is most common and associated with acute heart failure. A preexistent chronic kidney disease (CKD) is common and contributes to acute kidney injury (AKI) in CRS type 1 patients (acute cardiorenal syndrome). The remaining CRS types are found in patients with chronic heart failure (type 2), acute and chronic kidney diseases (types 3 and 4), and systemic diseases that affect both the heart and the kidney (type 5). Establishing the diagnosis of CRS requires various tools based on the type of CRS, including non-invasive imaging modalities such as TTE, CT, and MRI, adjuvant volume measurement techniques, invasive hemodynamic monitoring, and biomarkers. Albuminuria and Cystatin C (CysC) are biomarkers of glomerular filtration and integrity in CRS and have a prognostic impact. Comprehensive “all-in-one” magnetic resonance imaging (MRI) approaches, including cardiac magnetic resonance imaging (CMR) combined with functional MRI of the kidneys and with brain MRI are proposed for CRS. Hospitalizations due to CRS and mortality are high. Timely diagnosis and initiation of effective adequate therapy, as well as multidisciplinary care, are pertinent for the improvement of quality of life and survival. In addition to the standard pharmacological heart failure medication, including SGLT2 inhibitors (SGLT2i), renal aspects must be strongly considered in the context of CRS, including control of the volume overload (diuretics) with special caution on diuretic resistance. Devices involved in the improvement of myocardial function (e.g., cardiac resynchronization treatment in left bundle branch block, mechanical circulatory support in advanced heart failure) have also shown beneficial effects on renal function.
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Peerapanyasut, Wachirasek, Anongporn Kobroob, Siripong Palee, Nipon Chattipakorn, and Orawan Wongmekiat. "Activation of Sirtuin 3 and Maintenance of Mitochondrial Integrity by N-Acetylcysteine Protects Against Bisphenol A-Induced Kidney and Liver Toxicity in Rats." International Journal of Molecular Sciences 20, no. 2 (2019): 267. http://dx.doi.org/10.3390/ijms20020267.
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Mitochondrial impairment ensuing from oxidative imbalance is related to adverse consequences of bisphenol A (BPA), a globally utilized industrial chemical. Recent evidence reveals sirtuin 3 (SIRT3) as a key regulator of mitochondrial homeostasis; however, its role in BPA toxicity remains unidentified. This study explored the potential benefits of N-acetylcysteine (NAC), an effective antioxidant, against BPA toxicity in the kidney and liver, and examined whether SIRT3 was involved in this condition. Male Wistar rats were fed with vehicle, BPA (5, 50 mg/kg), BPA (50 mg/kg) plus NAC (100 mg/kg) and were evaluated after 5 weeks. NAC treatment significantly diminished BPA-induced kidney and liver functional disorders, histopathological alterations, oxidative stress, and apoptosis. The increased mitochondrial reactive oxygen species, the disrupted membrane potential, the swelling, and the impaired mitochondrial fission caused by BPA were also mitigated upon concurrent treatment with NAC. The benefits of NAC were associated with enhanced AMPK-PGC-1α-SIRT3 signaling protein expressions, which led to decreased acetylation of superoxide dismutase 2 (SOD2) and increased expression of mitochondrial antioxidant manganese superoxide dismutase (MnSOD). The findings demonstrate the efficacy of NAC in protecting BPA-induced kidney and liver injury, which, in part, is mediated by activating SIRT3 and improving mitochondrial function, dynamics, and oxidative imbalance.
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Bidet, M., M. Tauc, J. Merot, A. Vandewalle, and P. Poujeol. "Na+-H+ exchanger in proximal cells isolated from rabbit kidney. I. Functional characteristics." American Journal of Physiology-Renal Physiology 253, no. 5 (1987): F935—F944. http://dx.doi.org/10.1152/ajprenal.1987.253.5.f935.
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The purpose of this study was to investigate the characteristics of the Na+-H+ exchange in isolated proximal cells from rabbit kidney cortex. The cells were prepared by mechanical dissociation and sequential passages through nylon meshes. The intracellular pH (pHi) was measured in a bicarbonate-free medium [extracellular pH (pHe) = 7.30], using the fluorescent dye 2,7-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF). Resting pHi was 7.13 +/- 0.04 (n = 11) at 20-22 degrees C. Cells were acid loaded with nigericin in choline solution and H+ efflux, induced by extracellular Na+ (Nae), was calculated using a buffering power of 23.6 +/- 0.6 mmol.1-1.pH unit-1 (n = 19) estimated by NH4Cl exposure. In isolated proximal cells, the Na+-H+ antiporter had an apparent Km for Nae of 86.7 +/- 1.5 mM (n = 4) and was competitively inhibited by amiloride with a Ki of 33.3 +/- 6.4 X 10(-6) M (n = 3). Lowering pHe, inhibited the Na+-H+ exchanger. This inhibition was not purely competitive and the Ki was 40.4 +/- 12.7 nM (n = 3). The Na+-H+ exchange was greatly activated when the cytoplasm was acidified. The intracellular H+ concentration dependence did not follow simple Michaelis-Menten kinetics. Of the different cations tested on pHi recovery, such as Li+, choline+, K+, and tetramethylammonium, only Li+ induced an alkalinization of acidified cells similar to that of Na+. 22Na influx measurements indicated that cellular depletion of Na+ stimulated Na+-H+ exchange. The results permit the conclusion that the isolation procedures did not impair the main features of the Na+-H+ antiporter, at least as compared with those previously described in renal brush-border membrane vesicles or in other cellular systems. The integrity of the transporter in isolated proximal cells would permit the direct study of its hormonal and metabolic control.
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Peer, Victoria, Ramzia Abu Hamad, Sylvia Berman, and Shai Efrati. "Renoprotective Effects of DNAse-I Treatment in a Rat Model of Ischemia/Reperfusion-Induced Acute Kidney Injury." American Journal of Nephrology 43, no. 3 (2016): 195–205. http://dx.doi.org/10.1159/000445546.
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Background: Massive DNA destruction/accumulation of cell-free DNA debris is a sensitive biomarker of progressive organ/tissue damage. Deleterious consequences of DNA debris accumulation are evident in cardiac ischemia, thrombosis, auto-inflammatory diseases, SLE-induced lupus nephritis and cystic fibrosis. In case of renal pathologies, degradation and elimination of DNA debris are suppressed, due to downregulated DNAse-I activity within the diseased kidneys. The aim of the current study was to evaluate whether exogenous DNAse-I administration might exert renoprotective effects in the setting of acute kidney injury (AKI or acute renal failure). Methods: Sprague-Dawley rats underwent unilateral nephrectomy, with simultaneous clamping of contralateral kidney artery. The treated group received DNAse-I injection before discontinuing anesthesia. Positive (ischemic) controls received saline injection. Negative (non-ischemic) controls were either non-operated or subjected to surgery of similar duress and duration without ischemia. Renal perfusion was evaluated using the Laser-Doppler technique. Blood was procured for evaluating DNAse-I activity, renal functioning, renal perfusion. The kidneys were allocated for histopathologic examinations and for the evaluation of renal hypoxia, intra-renal apoptosis and proliferation. Results: Contrary to the situation in untreated ischemic rats, renal perfusion was significantly improved in DNAse-treated animals, concomitantly with significant amelioration of damage to renal functioning and tissue integrity. Treatment with DNAse-I significantly decreased the ischemia-induced renal hypoxia and apoptosis, simultaneously stimulating renal cell proliferation. Exogenous DNAse-I administration accelerated the clearance of intra-renal apoptotic DNA debris. Conclusion: Functional/histologic hallmarks of renal injury were ameliorated, renal functioning improved, intra-renal hypoxia decreased and intra-renal regeneration processes were activated. Thus, DNAse-I treatment protected the kidney from deleterious consequences of ischemia-induced AKI.
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Sung, Chih-Chien, Min-Tser Liao, and Chia-Ter Chao. "Independent Determinants of Appetite Impairment among Patients with Stage 3 or Higher Chronic Kidney Disease: A Prospective Study." Nutrients 13, no. 8 (2021): 2863. http://dx.doi.org/10.3390/nu13082863.
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Protein-energy wasting (PEW) is an important complication resulting from chronic kidney disease (CKD). Appetite impairment contributes significantly to PEW in these patients, but risk factors associated with having appetite impairment in patients with CKD remain elusive. Patients with an estimated glomerular filtration rate <60 mL/min/1.73 m2 for ≥2 times at least three months apart were prospectively enrolled during 2017, with their demographic features, comorbidities, anthropometric parameters, physical and performance indices, functional status, frailty, sensory organ integrity, and laboratory data collected. Their appetite status was measured using the Council on Nutrition Appetite Questionnaire (CNAQ). We examined independent determinants of appetite impairment in these CKD patients using multiple regression analyses. Among 78 patients with CKD, 42.3% had CNAQ-identified impaired appetite. Those with an impaired appetite also had poorer physical performance, a higher degree of functional impairment, higher frail severities, lower serum sodium levels, less intact oral cavity, and a trend toward having less intact nasal structures than those without. Multiple regression analyses revealed that a higher frail severity, in the forms of increasing Study of Osteoporotic Fractures (SOF) scores (odds ratio (OR), 2.74; 95% confidence interval (CI), 1.15–6.57) and a less intact nasal structure (OR, 0.96; 95% CI, 0.92–0.995) were associated with a higher probability of having an impaired appetite, while higher serum sodium (OR, 0.76; 95% CI, 0.6–0.97) correlated with a lower probability. Based on our findings, in patients with CKD, the severity of frailty, serum sodium, and nasal structural integrity might modify appetite status. Therapies targeting these factors might be beneficial for appetite restoration in patients with CKD.
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Chang, Cheng-Yi, Ping-Ho Pan, Jian-Ri Li, et al. "Glycerol Improves Intracerebral Hemorrhagic Brain Injury and Associated Kidney Dysfunction in Rats." Antioxidants 10, no. 4 (2021): 623. http://dx.doi.org/10.3390/antiox10040623.
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In stroke patients, the development of acute kidney injury (AKI) is closely linked with worse outcomes and increased mortality. In this study, the interplay between post-stroke and AKI and treatment options was investigated in a rodent model of hemorrhagic stroke. Intrastriatal collagenase injection for 24 h caused neurological deficits, hematoma formation, brain edema, apoptosis, blood–brain barrier disruption, oxidative stress, and neuroinflammation in Sprague Dawley rats. Elevation of serum blood urea nitrogen, serum creatinine, urine cytokine-induced neutrophil chemoattractant-1, and urine Malondialdehyde, as well as moderate histological abnormality in the kidney near the glomerulus, indicated evidence of kidney dysfunction. The accumulation of podocalyxin DNA in urine further suggested a detachment of podocytes and structural deterioration of the glomerulus. Circulating levels of stress hormones, such as epinephrine, norepinephrine, corticosterone, and angiotensin II were elevated in rats with intracerebral hemorrhage. Osmotic agent glycerol held promising effects in alleviating post-stroke brain injury and kidney dysfunction. Although the detailed protective mechanisms of glycerol have yet to be determined, the intrastriatal collagenase injection hemorrhagic stroke model in rats allowed us to demonstrate the functional and structural integrity of glomerulus are targets that are vulnerable to post-stroke injury and stress hormones could be surrogates of remote communications.
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Zaidan, Nadim, and Lama Nazzal. "The Microbiome and Uremic Solutes." Toxins 14, no. 4 (2022): 245. http://dx.doi.org/10.3390/toxins14040245.
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Uremic retention solutes, especially the protein-bound compounds, are toxic metabolites, difficult to eliminate with progressive renal functional decline. They are of particular interest because these uremic solutes are responsible for the pathogenesis of cardiovascular and chronic kidney diseases. Evidence suggests that the relation between uremic toxins, the microbiome, and its host is altered in patients with chronic kidney disease, with the colon’s motility, epithelial integrity, and absorptive properties also playing an important role. Studies found an alteration of the microbiota composition with differences in species proportion, diversity, and function. Since uremic toxins precursors are generated by the microbiota, multiple therapeutic options are currently being explored to address dysbiosis. While an oral adsorbent can decrease the transport of bacterial metabolites from the intestinal lumen to the blood, dietary measures, supplements (prebiotics, probiotics, and synbiotics), and antibiotics aim to target directly the gut microbiota composition. Innovative approaches, such as the modulation of bacterial enzymes, open new perspectives to decrease the plasma level of uremic toxins.
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Rehman, Saif Ur, Sara Jamil Khan, Shahnaz Bano, Saadia Zainab, Sadia Kazi, and Palwasha Abbasi. "Comparative Analysis of Metformin and Empagliflozin in Male Wistar Rats with Non-Diabetic Chronic Kidney Disease." Journal of Saidu Medical College, Swat 15, no. 1 (2025): 105–9. https://doi.org/10.52206/jsmc.2025.15.1.1006.
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Background: Chronic kidney disease has been identified as one of the greatest challenges faced by global public health. It is very important to highlight that T2DM (Type 2 Diabetes Mellitus) is an important driver of Chronic Kidney Disease, and its number is increasing due to this causative relationship. Objective: To determine the differences in the effectiveness of Metformin and Empagliflozin on kidney function in the different stages of chronic kidney disease development without diabetes in male Wistar rats.Materials and Method: In this experimental study, 54 male Wistar rats were included in this study. The rats were housed under standardized environmental conditions. Metformin and Empagliflozin were fed daily orally by gavage, with dosages determined according to the dosage adjustment principles for kidney failure. Rats were randomly distributed into three groups, including a control group. The study employed serum creatinine levels, as well as creatinine clearance, to ascertain kidney function. The study spread over nine weeks and ended with integrity being approached.Results: Serum creatinine levels showed a decrease in Metformin groups for a duration of 4 and 5 weeks, which is different from the moderate impact of Empagliflozin exposure. Creatinine clearance showed an appreciable increase in the Metformin groups, which is remarkable evidence of its nephroprotective properties. Empagliflozin yet produced less effect.Conclusion: The study reports that the low-dose Metformin (200 mg/kg) has the potential to manage Chronic Kidney diseases in male Wistar rats, mainly when applied for a longer duration. Significant differences in functional outcomes amongst the patients were ascertained, though empagliflozin did not meet statistical significance.Keywords: Chronic Kidney Disease, Empagliflozin, Kidney Function, Metformin, Type 2 Diabetes Mellitus.
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Seo-Mayer, Patricia W., Gunilla Thulin, Li Zhang, et al. "Preactivation of AMPK by metformin may ameliorate the epithelial cell damage caused by renal ischemia." American Journal of Physiology-Renal Physiology 301, no. 6 (2011): F1346—F1357. http://dx.doi.org/10.1152/ajprenal.00420.2010.
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Alterations in epithelial cell polarity and in the subcellular distributions of epithelial ion transport proteins are key molecular consequences of acute kidney injury and intracellular energy depletion. AMP-activated protein kinase (AMPK), a cellular energy sensor, is rapidly activated in response to renal ischemia, and we demonstrate that its activity is upregulated by energy depletion in Madin-Darby canine kidney (MDCK) cells. We hypothesized that AMPK activity may influence the maintenance or recovery of epithelial cell organization in mammalian renal epithelial cells subjected to energy depletion. MDCK cells were ATP depleted through a 1-h incubation with antimycin A and 2-deoxyglucose. Immunofluoresence localization demonstrated that this regimen induces mislocalization of the Na-K-ATPase from its normal residence at the basolateral plasma membrane to intracellular vesicular compartments. When cells were pretreated with the AMPK activator metformin before energy depletion, basolateral localization of Na-K-ATPase was preserved. In MDCK cells in which AMPK expression was stably knocked down with short hairpin RNA, preactivation of AMPK with metformin did not prevent Na-K-ATPase redistribution in response to energy depletion. In vivo studies demonstrate that metformin activated renal AMPK and that treatment with metformin before renal ischemia preserved cellular integrity, preserved Na-K-ATPase localization, and led to reduced levels of neutrophil gelatinase-associated lipocalin, a biomarker of tubular injury. Thus AMPK may play a role in preserving the functional integrity of epithelial plasma membrane domains in the face of energy depletion. Furthermore, pretreatment with an AMPK activator before ischemia may attenuate the severity of renal tubular injury in the context of acute kidney injury.
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Vandorpe, David H., Sabine Wilhelm, Lianwei Jiang, et al. "Cation channel regulation by COOH-terminal cytoplasmic tail of polycystin-1: mutational and functional analysis." Physiological Genomics 8, no. 2 (2002): 87–98. http://dx.doi.org/10.1152/physiolgenomics.00092.2001.
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Polycystin-1 (PKD1) mutations account for ∼85% of autosomal dominant polycystic kidney disease (ADPKD). We have shown previously that oocyte surface expression of a transmembrane fusion protein encoding part of the cytoplasmic COOH terminus of PKD1 increases activity of a Ca2+-permeable cation channel. We show here that human ADPKD mutations incorporated into this fusion protein attenuated or abolished encoded cation currents. Point mutations and truncations showed that cation current expression requires integrity of a region encompassing the putative coiled coil domain of the PKD1 cytoplasmic tail. Whereas these loss-of-function mutants did not exhibit dominant negative phenotypes, coexpression of a fusion protein expressing the interacting COOH-terminal cytoplasmic tail of PKD2 did suppress cation current. Liganding of the ectodomain of the PKD1 fusion protein moderately activated cation current. The divalent cation permeability and pharmacological profile of the current has been extended. Inducible expression of the PKD1 fusion in EcR-293 cells was also associated with activation of cation channels and increased Ca2+ entry.
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Verkoelen, Carl F., Burt G. Van Der Boom, Adriaan B. Houtsmuller, Fritz H. Schröder, and Johannes C. Romijn. "Increased calcium oxalate monohydrate crystal binding to injured renal tubular epithelial cells in culture." American Journal of Physiology-Renal Physiology 274, no. 5 (1998): F958—F965. http://dx.doi.org/10.1152/ajprenal.1998.274.5.f958.
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The retention of crystals in the kidney is considered to be a crucial step in the development of a renal stone. This study demonstrates the time-dependent alterations in the extent of calcium oxalate (CaOx) monohydrate (COM) crystal binding to Madin-Darby canine kidney (MDCK) cells during their growth to confluence and during the healing of wounds made in confluent monolayers. As determined by radiolabeled COM crystal binding studies and confirmed by confocal-scanning laser microscopy, relatively large amounts of crystals (10.4 ± 0.4 μg/cm2) bound to subconfluent cultures that still exhibited a low transepithelial electrical resistance (TER < 400 Ω ⋅ cm2). The development of junctional integrity, indicated by a high resistance (TER > 1,500 Ω ⋅ cm2), was followed by a decrease of the crystal binding capacity to almost undetectable low levels (0.13 ± 0.03 μg/cm2). Epithelial injury resulted in increased crystal adherence. The highest level of crystal binding was observed 2 days postinjury when the wounds were already morphologically closed but TER was still low. Confocal images showed that during the repair process, crystals selectively adhered to migrating cells at the wound border and to stacked cells at sites were the wounds were closed. After the barrier integrity was restored, crystal binding decreased again to the same low levels as in undamaged controls. These results indicate that, whereas functional MDCK monolayers are largely protected against COM crystal adherence, epithelial injury and the subsequent process of wound healing lead to increased crystal binding.