Academic literature on the topic 'TTKG TransTubular Potassium Gradient'

Background: In primary aldosteronism (PA), kidney function impairment could be concealed by relative hyperfiltration and emerge after adrenalectomy. We hypothesized transtubular gradient potassium gradient (TTKG), a kidney aldosterone bioactivity indicator, could correlate to end organ damage and forecast kidney function impairment after adrenalectomy. Methods: In the present prospective study, we enrolled lateralized PA patients who underwent adrenalectomy and were followed up 12 months after operation in the Taiwan Primary Aldosteronism Investigation (TAIPAI) registry from 2010 to 2018. The clinical outcome was kidney function impairment, defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 at 12 months after adrenalectomy. End organ damage is determined by microalbuminuria and left ventricular mass. Results: In total, 323 patients [mean, 50.8 ± 10.9 years old; female 178 (55.1%)] were enrolled. Comparing pre-operation and post-operation data, systolic blood pressure, serum aldosterone, urinary albumin to creatinine ratio and eGFR decreased. TTKG ⩾ 4.9 correlated with pre-operative urinary albumin to creatinine ratio >50 mg/g [odds ratio (OR) = 2.42; p = 0.034] and left ventricular mass (B = 20.10; p = 0.018). Multivariate logistic regression analysis demonstrated that TTKG ⩾ 4.9 could predict concealed chronic kidney disease (OR = 5.42; p = 0.011) and clinical success (OR = 2.90, p = 0.017) at 12 months after adrenalectomy. Conclusions: TTKG could predict concealed kidney function impairment and cure of hypertension in PA patients after adrenalectomy. TTKG more than 4.9 as an adverse surrogate of aldosterone and hypokalaemia correlated with pre-operative end organ damage in terms of high proteinuria and cardiac hypertrophy.

1. The purpose of this study was to evaluate the renal mechanisms which lead to a high urine [K+] in adrenalectomized (ADX) rats devoid of aldosterone. 2. By dividing the urine [K+] by the urine to plasma osmolality ratio, the [K+] in the cortical collecting duct luminal fluid can be estimated; dividing this value by the plasma [K+] yields an index of the transtubular [K+] gradient (TTKG) in vivo. 3. The TTKG was close to 7 in aldosterone deficient ADX rats while on a normal K+ diet and fell towards unity when amiloride or a low K+ diet was administered to these rats. 4. With a longer time on a low K+ diet, the TTKG was less than 1 in ADX rats. This suggests that K+ was reabsorbed in the medullary collecting duct under these conditions. 5. Hyperkalemia appears to have an ‘aldosterone-like’ action in the cortical collecting duct in vivo in the absence of aldosterone in ADX rats. This action of hyperkalemia permits normal K+ excretion rates despite the absence of mineralocorticoids.

In assessing disorders of potassium excretion, urine composition is used to calculate the transtubular gradient (TTKG), as an estimate of tubule fluid concentration, at a point when the fluid was last isotonic to plasma, namely, within the cortical collecting duct (CCD). A mathematical model of the CCD has been developed, consisting of principal cells and α- and β-intercalated cells, and which includes Na+, K+, Cl−, HCO[Formula: see text], CO2, H2CO3, phosphate, ammonia, and urea. Parameters have been selected to achieve fluxes and permeabilities compatible with data obtained from perfusion studies of rat CCD under the influence of both antidiuretic hormone and mineralocorticoid. Both epithelial (flat sheet) and tubule models have been configured, and model calculations have focused on the determinants of the TTKG. Using the epithelial model, luminal K+ concentrations can be computed at which K+secretion ceases (0-flux equilibrium), and this luminal concentration derives from the magnitude of principal cell peritubular uptake of K+ via the Na-K-ATPase, relative to principal cell peritubular membrane K+ permeability. When the model is configured as a tubule and examined in the context of conditions in vivo, osmotic equilibration of luminal fluid produces a doubling of the initial K+ concentration, which, depending on delivered load, may be substantially greater than the zero-flux equilibrium value. Under such circumstances, the CCD will be a site for K+ reabsorption, although the relatively low permeability ensures that this reabsorptive flux is likely to be small. Osmotic equilibration may also raise luminal NH3 concentrations well above those in cortical blood. In this situation, diffusive reabsorption of NH3 provides a mechanism for base reclamation without the metabolic cost of active proton secretion.

Background: Bartter's syndrome refers to a group of genetic disorders that affect the renal tubular system, which is responsible for reabsorbing various substances such as sodium, potassium, and chloride from the urine into the blood. This study aimed to present a clinical case related to Bartter syndrome.
 Case presentation: A 52-year-old male patient in the internal medicine department of Dr. M. Djamil General Hospital Padang with the main complaint of weakness in both legs increasing since 1 day ago. On laboratory examination, the patient found potassium 1.7 mmol/L, indicating hypokalemia. Renal function examination showed normal kidney function. Examination of blood gas analysis showed results of metabolic alkalosis. Examination of urine potassium obtained potassium levels of 22 mmol/day, urine osmolarity of 140 mOsm/kgH2O at serum osmolarity of 274 mOsm/kgH2O, with TTKG (transtubular potassium gradient) = 28. The patient was diagnosed with Bartter syndrome. Treatment is carried out by administering KSR tablets 3x600 mg orally while monitoring electrolytes regularly.
 Conclusion: This patient has hypokalemia, metabolic alkalosis, normal magnesium and calcium, and hypercalciuria. This patient is diagnosed with Bartter syndrome.

Abstract Abstract 5151 Background: Along with hydroxyurea, anagrelide has been widely used for the treatment of myeloproliferative neoplasms (MPNs). In contrast to hydroxyurea, anagrelide selectively inhibits megakaryocyte colony development and its cytoreductive effect relatively limited to platelets, hence, it usually used as a first line therapy for the patients with essential thrombocytosis (ET). The frequently reported adverse events of anagrelide are palpitation, headache, edema, and vague abdominal symptoms. Renal insufficiency as a complication of anagrelide treamtent is not well recognized. Some studies suggested that anagrelide has a possible relationship to renal failure, especially in the patients with preexisting renal diseases. A few cases of acute interstitial nephritis or renal tubular necrosis were reported sporadically. However, the relationship between anagrelide and renal insufficiency remain unclear, and its mechanism remains to be further elucidated. In the present study, we investigated the incidence and the characteristics of renal impairment in anagrelide-treated patients with MPNs. Methods: Total 335 patients with thrombocythemia due to MPNs who showed normal renal function before starting treatment were enrolled. They were serially assessed renal function and serum potassium levels. Treatment modalities such as anagrelide, hydroxyurea, phlebotomy or combination were decided by the characteristics of presenting cytosis and patients' tolerability. If the patients showed renal impairment during the treatment period, other parameters such as co-morbidities, combined medication history, electrolytes imbalance, urine analysis, and imaging studies were fully assessed in order to find the existing causes of renal failure. Results: Of total enrolled 335 patients, 54.0% with ET, 33.4% with polycythemia vera (PV), 3.3% with primary myelofibrosis, 0.6% with chronic neutrophilic leukemia (CNL), and 6.6% with MPN, unclassifiable. Others were diseases categorized as a myelodysplastic (MDS)/MPN (1.5% with atypical chronic myeloid leukemia and 0.6% with chronic myelomonocytic leukemia). In terms of treatment modalities, 56.7% were anagrelide group (anagrelide alone, anagrelide+hydroxyurea, and anagrelide+phlebotomy), whereas 43.3% were non-anagrelide group (hydroxyurea alone and hydroxyurea+phlebotomy). The median age of anagrelide group was 61 years (ranges; 19–84 years) and non-anagrelide group was 57 years (ranges: 14–84 years). In anagrelide group, the median serum creatinine levels before starting treatment was 0.8 mg/dL (ranges: 0.5–1.3 mg/dL). In non-anagrelide group, median serum creatinine was 0.9 mg/dL (ranges: 0.4–1.3 mg/dL). After addressing the treatment, forty-six (24.2%) in anagrelide group revealed increases of serum creatinine (median: 1.5 mg/dL, ranges: 1.4–2.3) above the normal reference ranges. Median estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation in these patients was 39.5 mL/min/1.73 m2 (ranges; 21.0–56.0). On the other hand, in non-anagrelide group, only 7.6% showed increases of serum creatinine (median 1.5 mg/dL, ranges: 1.4–2.0) and decreases of eGFR (median; 43 mL/min/1.73 m2, ranges: 32–53) (P=0.000). The relative risk ratio (RR) for renal impairment of anagrelide use was 3.89 (C.I.: 1.94–7.83) (P=0.000). Median time to develop renal impairment from the start of anagrelide was 13.8 months (ranges; 0.2–53.4 months). In anagrelide group, 8.4% have diagnosed as diabetes mellitus (DM) before starting the anagrelide, however, the preexisting DM was not significantly related to the development of renal failure (RR=1.26, P=0.649). Of total 46 patients who showed renal impairment after anagrelide use, mild to moderate proteinuria (grade 1 or 2) were revealed in ten patients (21.7%). Furthermore, nine patients (19.6%) showed the features of hyperkalemic renal tubular acidosis which was charaterized by metabolic acidosis, hyperkalemia, and low transtubular potassium gradient (TTKG < 5). Conclusions: In the present study, we suggested the possible casual relationship between anagrelide therapy and renal impairment. Although large randomized studies and more detailed analyses to find the underlying mechianisms may be warranted, caution and serial follow-up of renal function should be indicated in MPN patients with anagrelide treatment. Disclosures: No relevant conflicts of interest to declare.

Hyperkalemia is commonly encountered in patients who receive a renal transplant and the immunosuppressive drug, cyclosporine. There is also a high incidence of hypertension (which is thought to be due to expansion of the extracellular fluid volume) and hyperchloremic metabolic acidosis in this group of patients. This constellation of findings led to the suspicion of the possibility that their basis might be type II hypoaldosteronism. To test this hypothesis, 12 patients with hyperkalemia (plasma K+, 5.1 +/- 0.2 mmol/L at the time of study) while receiving cyclosporine were studied. Patients who had diabetes mellitus, those receiving drugs known to cause hyperkalemia (e.g., beta blockers, angiotensin-converting enzyme inhibitors, K(+)-sparing diuretics), or those with a serum creatinine greater than 200 mumol/L were excluded. The renal response to hyperkalemia was inappropriate because the transtubular K+ concentration gradient (TTKG) was only 4.3 +/- 0.4 compared with a TTKG of 13 +/- 1, 2 h after 50 mmol of KCl was given to normal subjects. The TTKG, after administration of 200 micrograms of fludrocortisone, was still very low (5.6 +/- 0.6) in the patients compared with that of controls (12 +/- 1). After administration of 250 to 500 mg of acetazolamide to increase the delivery of bicarbonate to the distal nephron, the TTKG rose significantly to 11 +/- 1 in patients on cyclosporine, compared with 17 +/- 1 in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)