Beyond the transtubular potassium gradient: Alternative urinary markers for diagnosing hypoaldosteronism.

Effect of mineralocorticoid activity on transtubular potassium gradient, urinary [K]/[Na] ratio, and fractional excretion of potassium

SUMMARY The influence of induced chronic renal failure on 24- hour urinary excretion and fractional excretion of sodium and potassium was studied in cats. Induction of chronic renal failure significantly increased fractional excretion of potassium (P < 0.0001) and sodium (P < 0.05); however, 24-hour urinary excretion of sodium and potassium decreased slightly following induction of chronic renal failure. Fractional excretion and 24-hour urinary excretion of sodium and potassium were compared by linear regression in clinically normal cats, cats with chronic renal failure, and clinically normal and affected cats combined. In clinically normal cats, linear regression revealed only moderate correlation between fractional excretion and 24- hour urinary excretion for sodium and potassium. Linear regression of these same relationships in cats with chronic renal failure, and in clinically normal cats and cats with chronic renal failure combined, indicated low correlation. Fractional excretions of sodium and potassium were not reliable indicators of 24-hour urinary excretion of these electrolytes in cats with chronic renal failure or unknown glomerular filtration rate. Fractional excretion of potassium and sodium correlated only moderately with 24-hour urinary excretion in clinically normal cats.

Children born with growth retardation (GR) have a smaller nephron number and are at increased risk for the development of renal disease and hypertension in adult life. Data on the immediate post-natal development of renal function in neonates born with GR are limited and data on the effects of aminoglycosides (AGs) on renal function in these infants are lacking. This was a prospective study of 81 preterm neonates with a mean gestational age of 32.5 weeks, 40 born with GR (small for gestational age, SGA) and 41 without GR (appropriate for gestational age, AGA). The infants were classified into 4 groups. Groups A (n = 21) and B (n = 20) consisted of AGA and SGA neonates, respectively, who received AGs, and groups C (n = 20) and D (n = 20) of AGA and SGA neonates, respectively, who did not receive AG treatment. Indices of renal function were: serum creatinine (SeCr), the fractional excretion of sodium (FENa), potassium (FEK), phosphorus (FEP), magnesium and uric acid (FEUA), the urinary calcium/creatinine ratio and the transtubular potassium gradient (TTKG). No differences were observed in the parameters examined between SGA and AGA neonates who did not receive AGs. Conversely, SGA infants who received AGs after birth (group B) exhibited higher values of SeCr 2 months later. Specifically, their mean +/- SD value of SeCr (micromol/l) was 42 +/- 05 compared with 33 +/- 08 in group D, 35 +/- 04 in group A and 33 +/- 04 in group C (P < 0.01). These infants also had significantly higher values of TTKG than SGA infants without AG treatment (22 +/- 9 vs 13 +/- 3 in group D) and FEUA (60 +/- 23 vs 35 +/- 14 in group D). Their FENa and FEP were also inappropriately high despite having lower serum levels of Na and P. Preterm SGA infants who had no need of AG treatment after birth have similar renal functional maturation than AGA preterm infants at 2 months of life, but preterm SGA infants who received AGs had indications of impaired glomerular and tubular function at this age.

While recent literature data suggest that a primary impairment in sodium excretion is the basic abnormality in the pathogenesis of edema formation in the nephrotic syndrome, there is ample evidence that functional hypovolemia contributes to stimulation of renal sodium and fluid retention. Vasoactive hormones such as renin and aldosterone are involved in this process. Discrimination between both mechanisms would be possible by assessment of aldosterone bioactivity and will have therapeutical consequences by indicating the need for administration of i.v. albumin or diuretics. In this paper, several indices of aldosterone bioactivity were assessed in 85 patients with minimal lesion nephrotic syndrome (118 measurements were performed in patients while in remission and 210 following relapses), and in 41 nephrotic patients with different types of nephropathy and were related to plasma renin and aldosterone levels. A better correlation was found between log aldosterone and U(K+)/U(Na+) + U(K+) ratio than with other parameters measuring renal potassium handling such as transtubular potassium gradient, fractional excretion of potassium and urine K+/urine Na+ or urine K+ creatinine ratios. In patients with renal sodium retention (FE(Na)% less than 0.5), an U(K+)/U(Na+) + U(K+) ratio higher than 0.60 identifies patients with increased aldosterone levels and indicates functional hypovolemia. This index may therefore be used to assess which patients will benefit from i.v. albumin administration.

Twenty-nine psoriasis patients on 5 mg/kg cyclosporin A (CyA) therapy were studied for 3 months using the furosemide test. Five of them (17%) showed an abnormal renal acidification capacity after furosemide administration: The urinary pH did not sink under 5.3 after furosemide, while the ammonium and titrable acid levels were significantly low. There were no significant differences from controls regarding the serum potassium or fractional potassium excretion. Nevertheless, the transtubular potassium gradient was lower in patients with an abnormal furosemide test result. We conclude that some patients treated with a low dose CyA therapy developed an abnormality in the distal tubular acidification.

Twenty-nine psoriasis patients on 5 mg/kg cyclosporin A (CyA) therapy were studied for 3 months using the furosemide test. Five of them (17 %) showed an abnormal renal acidification capacity after furosemide administration: The urinary pH did not sink under 5.3 after furosemide, while the ammonium and titrable acid levels were significantly low. There were no significant differences from controls regarding the serum potassium or fractional potassium excretion. Nevertheless, the transtubular potassium gradient was lower in patients with an abnormal furosemide test result. We conclude that some patients treated with a low dose CyA therapy developed an abnormality in the distal tubular acidification.

Growth Restriction at Birth and Kidney Function During Childhood

The renal handling of sodium and potassium in environmental cadmium-exposed subjects with renal dysfunction

Función tubular renal en el muy anciano

1) To determine the incidence and severity of hyperkalemia during trimethoprim therapy. 2) To test the hypothesis that trimethoprim inhibits renal potassium excretion by blocking sodium channels in the mammalian distal nephron. Thirty consecutive patients who were treated with trimethoprim-containing drugs. All patients included in the study had the acquired immunodeficiency syndrome (AIDS). Thirty-nine male Sprague-Dawley rats receiving normal rat chow and tap water (allowed free access). Humans: high dose (20 mg/kg per day) of trimethoprim therapy. Rats: trimethoprim (9.6 mg/h per kg body weight) was infused intravenously or into the renal distal tubules (1 mmol/L). Humans: Serum and urine electrolyte levels, serum creatinine, renin, aldosterone, and cortisol levels were measured, and the transtubular potassium gradient was calculated. Rats: The effects of trimethoprim infusion on urinary sodium, chloride, and potassium concentration and urine volume were measured. Sodium, chloride, potassium, and inulin concentrations were measured in fluid samples obtained from kidney distal tubules. The voltage across the wall of the distal tubule was measured. Humans: Trimethoprim increased the serum potassium concentration by 0.6 mmol/L (95% Cl, 0.29 to 0.95 mmol/L) despite normal adrenocortical function and glomerular filtration rate. Serum potassium levels greater than 5 mmol/L were observed during trimethoprim treatment in 15 of 30 patients. Rats: Intravenous trimethoprim inhibited renal potassium excretion by 40% (Cl, 21% to 60%) and increased renal sodium excretion by 46% (Cl, 9% to 83%). Trimethoprim (1 mmol/L) in tubule fluid inhibited distal tubule potassium secretion by 59% (Cl, 26% to 92%) and depolarized the lumen-negative transepithelial voltage by 66% (Cl, 46% to 85%). Trimethoprim (an organic cation) acts like amiloride and blocks apical membrane sodium channels in the mammalian distal nephron. As a consequence, the transepithelial voltage is reduced and potassium secretion is inhibited. Decreased renal potassium excretion secondary to these direct effects on kidney tubules leads to hyperkalemia in a substantial number of patients being treated with trimethoprim-containing drugs.

To investigate the role of potassium on blood pressure we measured serum potassium, urinary excretion of potassium and sodium, fractional excretion of potassium, urinary sodium:potassium ratio, plasma renin activity, aldosterone, and norepinephrine during dynamic maneuvers in normotensive and hypertensive subjects. After baseline measurements, we expanded intravascular volume with infusion of intravenous saline and then induced sodium and volume depletion by diuretic administration during a low sodium salt diet. These studies were performed in 431 normotensive and 478 hypertensive subjects enabling evaluation of the effects of age, race, and sex, as well as blood pressure, on the results. Among normotensives, we found that white subjects had significantly P less than 0.05) higher levels of serum and urine potassium, fractional potassium excretion and lower urinary sodium:potassium ratios than black subjects and that males had the same patterns of differences compared to females. Similar, but less consistent racial differences were seen among the hypertensive subjects. We also observed significant (P less than .05) correlations between urinary potassium excretion and body weight in both normal and hypertensive groups. In normal subjects, a significant correlation was observed between the urinary sodium:potassium ratio and blood pressure that was not seen in the hypertensives. The latter, however, displayed a significant (P less than .05) inverse relationship between serum potassium and blood pressure. Multiple regression analysis revealed that urinary potassium excretion was influenced by age, race, sex, body weight, blood pressure, creatinine clearance, renin, and aldosterone. These observations reveal important relationships between potassium homeostasis and blood pressure control that deserve further study.

Perinatal taurine exposure alters renal hemodynamics and sodium excretion in adult rats. This study further tests the effect of perinatal taurine on renal potassium excretion in adult conscious rats. Female Sprague‐Dawley rats were fed normal rat chow and given water alone (C), 3% beta‐alanine in water (taurine depletion, TD) or 3% taurine in water (taurine supplementation, TS), either from conception until delivery (fetal period; TDF or TSF) or from delivery until weaning (lactation period; TDL or TSL). In Experiment 1, after weaning, male offspring were fed normal rat chow and tap water. In Experiment 2, female pups were treated similarly, but from conception until weaning. At 7–8 weeks of age, renal potassium excretion at rest and after an acute saline load (5% of body weight) was studied in conscious, restrained rats. All male groups displayed similar renal potassium excretion. TSF increased fractional potassium excretion at rest but not in response to saline load, whereas TDF did the opposite. Plasma potassium levels were lower only at rest in TSF but at rest and during the challenge in TDF. Their glomerular filtration rates did not significantly different among groups. In female offspring, perinatal taurine supplementation decreased renal potassium excretion, glomerular filtration rate, and plasma potassium concentration at rest and after the saline load. It is unlikely that increased tubular reabsorption caused these effects, since the fractional potassium excretion significantly increased, especially at rest. Perinatal taurine depletion had no significant effect on renal potassium excretion in the female offspring. The present data suggest that perinatal taurine exposure influences renal potassium excretion in the adult rats.

Senescence and chronic renal failure bring about a progressive glomerular filtration reduction. Moreover, a reduction in glomerular filtration usually modifies the potassium renal excretion. In the present study, we compared the renal potassium handling between old and chronic renal disease populations. Fifty-five volunteers were studied, 43 of them were healthy old persons and 12 were predialysis chronic renal disease patients. Exclusion criteria were: presence of altered plasma potassium (Kp), diabetes mellitus, obstructive uropathy, drugs that could alter plasma potassium levels. All volunteers were on a diet with a potassium content around 50 mmol/day (3-day dietary register). We measured potassium, creatinine, urea in plasma and 24 hours urine. We also measured creatinine clearance (CrCl) and fractional excretion of potassium (FEK), and we studied the relationship between these parameters. Statistical analysis was made using Student's test. Slopes of the correlation curves between CrCl and FEK. [Table: see text]. The relationship between creatinine clearance and fractional excretion of potassium in old and chronic renal disease groups were different with the excretion of potassium being lower in the elderly.

To investigate biomarkers of acute renal injury in Wistar rats, subjected to left renal ischemia for 10 minutes, and then compare reperfusion at 24 hours, and at 5, 7, 14 and 21 days after the procedure. Eight female and male rats between 60 and 81 days old were used in the Central Animal Facility of the UFMS. Assessed biomarkers included urine protein, urea, creatinine, glucose, sodium, potassium, urine alkaline phosphatase and gamma-glutamyl transferase activities, and protein-to-creatinine ratio; and in serum: urea, creatinine, sodium and potassium, fractional excretion of sodium, potassium, urine flow and creatinine clearance. Greater variance was observed in the parameters at 24 hours and at five days (p<0.05) after reperfusion. On the 21st day, these parameters approximated those obtained for the control group. Renal ischemia for 10 minutes was sufficient to raise urine levels of protein, glucose, fractional excretion of potassium, urea, creatinine clearance, urine activity of gamma-glutamyltransferase and alkaline phosphatase enzymes in the first 24 hours, up to five days after reperfusion, which may indicate risk of acute kidney injury, according to the RIFLE classification.

Sickle cell disease causes microvascular occlusion in different vascular beds. In kidneys, it leads to occult glomerular dysfunction causing asymptomatic microalbuminuria, proximal tubulopathy causing hyposthenuria and increased free water loss and distal tubulopathy causing poor urine acidification. We studied the prevalence of various types of renal dysfunction, the ability of different tests to detect it at an early stage and the correlation of these parameters in children receiving hydroxyurea (HU). Fifty-six children (sample size calculated using SAS9.2 package) attending paediatric clinical services in a tertiary care hospital between 2 and 12 years of age diagnosed by high-performance liquid chromatography (HPLC) were enrolled. Their demographic and laboratory data including renal and urine parameters were collected. Parameters like fractional excretion of sodium (FeNa), trans tubular potassium gradient (TtKg) and free water clearance (TcH2O) were derived by calculations. Data were analysed using IBM SPSS Version 21.0 and Microsoft Office Excel 2007. We found a significant number of children to have microalbuminuria (17.8%), hyposthenuria (30.4%) and impaired renal tubular potassium excretion (TtKg) (81.3%). A significant correlation was found between the dose of HU with urine osmolality (p < 0.0005) and free water clearance (p = 0.002), while all parameters showed a significant correlation with compliance with HU. Derangement in urine microalbumin and TcH2O correlated significantly with low mean haemoglobin levels (<9 g/dl). Renal dysfunction is common in children with SCD and can be detected early using simple urine parameters and can be prevented with an early and appropriate dosage of HU with good compliance.