Transtubular Potassium Concentration Gradient Research Articles

Urine osmolality predicts worsening renal function and poor prognosis in acute decompensated heart failure

Abstract Background/Purpose Worsening renal function (WRF) can sometimes occur in the patients with acute decompensated heart failure (ADHF) and increase the risk of morbidity and mortality (1). In a previous study, it was reported that fractional excretion of sodium (FENa) reflects net sodium reabsorption from nephron segments and predicts WRF during treating ADHF (2). On the other hand, recently the new drugs which approach urine concentration mechanism and affect urine osmolality (U-OSM), such as tolvaptan and sodium-glucose cotransporter-2 inhibitor, have begun to be widely used as treatment of heart failure. Thus, we focused on U-OSM, which reflects not only sodium handling but also water excretion controlled by the collecting duct, and evaluated the association between WRF and U-OSM. Moreover, previous studies have demonstrated that FENa, fractional excretion of urea nitrogen and transtubular potassium concentration gradient are markers for long-term prognosis in patients with ADHF (3–5). Therefore, we also studied whether U-OSM can predict prognosis in ADHF. Methods A total of 157 patients admitted to our hospital because of a primary diagnosis of ADHF from February 2020 through July 2021 were retrospectively reviewed. U-OSM in the spot urinary samples were examined within 72 hours after admission. U-OSM was calculated based on the following validated formula (6): U-OSM = 1.07 × {2 × [urine sodium (mEq/L)] + [urine urea nitrogen (mg/dL)]/2.8 + [urine creatinine (mg/dl)] × 2/3} + 16.2. The primary outcome was the occurrence of WRF during hospitalization. WRF was defined as increased serum creatinine ≥0.3 mg/dL from baseline (7). The secondary outcome was the occurrence of ADHF readmission and all-cause death within 180 days after discharge. Results Primary Outcome. WRF developed in 46% of all patients. In the patients that developed WRF during hospitalization, U-OSM was significantly lower than in the patients without WRF (366±106 mOsm/L versus 430±128 mOsm/L; P<0.001). Receiver operating characteristic curve analysis revealed the optimal cutoff values of U-OSM was 403 mOsm/L (AUC 0.64; 95% CI: 0.56–0.72; P<0.001) to predict the WRF (Figure 1). On multivariable logistic regression analysis, U-OSM (OR, 1.99, 95% CI: 1.27–3.12; p=0.003) and serum creatinine (OR, 1.00, 95% CI: 0.99–1.00; P=0.009) were independent predictors of WRF. Secondary Outcome. There were 34 patients (22%) readmitted and 9 patients (6%) died within 180 days after discharge. ROC curve analysis revealed the optimal cutoff values of U-OSM as 349 mOsm/L (C-statistic 0.74; 95% CI: 0.65–0.83; P<0.001) to predict ADHF readmission and all-cause death within 180 days (Figure 2A). On Kaplan-Meier analysis, the secondary outcome was significantly higher in patients with U-OSM<349 mOsm/L (u-OSM≥349, 57%, U-OSM<349, 43%; HR, 0.99; 95% CI: 0.99–1.00, P<0.001) (Figure 2B). Conclusion U-OSM on admission may be a predictor of WRF and a prognostic marker in ADHF patients. Funding Acknowledgement Type of funding sources: None.

Effect of empagliflozin as add-on therapy on transtubular potassium concentration gradient in patients with type 2 diabetes hospitalized for acute decompensated heart failure

Abstract Background The transtubular potassium concentration gradient (TTKG) has been reported to be a marker of renal aldosterone bioactivity, and has been shown to be a surrogate of arterial underfilling in patients with acute decompensated heart failure (ADHF). Moreover, high TTKG at discharge has been shown to be associated with poor prognosis in ADHF patients. Empagliflozin, one of the sodium glucose cotransporter 2 inhibitors, has been shown to reduce the risk of cardiovascular mortality in patients with type 2 diabetes mellitus (T2D) and cardiovascular disease. However, little is known about the effect of empagliflozin as add-on therapy on TTKG in T2D patients with ADHF. Purpose We sought to elucidate the effect of empagliflozin as add-on therapy on TTKG in T2D patients with ADHF. Methods We enrolled 58 consecutive T2D patients admitted for ADHF. On admission, enrolled patients were randomly assigned in a 1:1 ratio to either empagliflozin add-on therapy (EMPA(+)) or conventional glucose-lowering therapy (EMPA(−)). All patients in EMPA(+) group received empagliflozin (10 mg/day) throughout the study period. Left ventricular ejection fraction (LVEF) was measured at baseline using echocardiography. Body weight and vital signs, such as blood pressure and heart rate, were measured, and blood and urine samples were collected at baseline and 1, 2, 3 and 7 days after randomization. The TTKG was measured using the first morning urine samples collected on each day. TTKG was calculated according to the following equation: TTKG = (Ku/Ks)×(plasma osmolality/urine osmolality), where Ku is urine potassium concentration and Ks is serum potassium concentration, as previously reported. Results Thirty patients were assigned to the EMPA(+) group, and 28 patients were assigned to the EMPA(−) group. There were no significant baseline differences in LVEF, plasma B-type natriuretic peptide (BNP) level, body mass index, or serum creatinine level between the EMPA(+) and EMPA(−) groups. TTKG did not significantly differ between the two groups at baseline. However, seven days after randomization, plasma BNP level was significantly lower in the EMPA(+) group than in the EMPA(−) group (median 227 [IQR 114–381] pg/mL vs 362 [227–554] pg/mL, p=0.0294). Furthermore, TTKG of the EMPA(+) group was significantly lower at 2, 3 and 7 days after randomization (Figure). Conclusions This study demonstrated that empagliflozin as add-on therapy can lower TTKG in T2D patients with ADHF. Figure 1 Funding Acknowledgement Type of funding source: None

Diagnostic value of parameters from a spot urine sample for renal potassium loss in hypokalemia

BackgroundWe assessed the value of 1) a spot urine test for diagnosing hypokalemia caused by renal potassium loss, and 2) actual 24-hour urine potassium excretion (24 hUK-actual) for diagnosing hypokalemia caused by renal potassium loss in patients treated with potassium supplementation. The study population was from Southwest China. MethodsPatients with hypokalemia were divided into 2 groups: hypokalemia caused by renal potassium loss (n = 67) and hypokalemia caused by extrarenal potassium loss (n = 63). Urine potassium concentration (UK), urine creatinine concentration (UCr), urine potassium-creatinine ratio (UK/UCr), fractional excretion of potassium (FEK), transtubular potassium concentration gradient (TTKG), and 24-h urine potassium excretion (24 hUK-calculated) were derived from spot urine samples collected on admission, before initiation of therapy. Patients received intravenous potassium chloride 0.4 or 0.6 g/h. 24 hUK-actual was detected in patients whose serum potassium did not return to normal after 24 h of therapy. ResultsPatients with hypokalemia caused by renal potassium loss had significantly higher UK, UK/UCr, FEK, TTKG and 24 hUK-calculated compared to patients with hypokalemia caused by extrarenal potassium loss (P < 0.05). FEK predicted renal potassium loss in hypokalemia with high accuracy at a cut-off of 9.29% (sensitivity, 80.6%; specificity, 85.7%). The area under the curve for 24 hUK-actual in predicting renal potassium loss in patients with hypokalemia treated with low or high-dose potassium chloride infusion were 0.939 or 0.956, respectively. On the spot urine test, FEK showed the highest correlation with 24 hUK-actual during low or high dose potassium chloride infusion (r = 0.831, p < 0.001 or r = 0.764, p < 0.001). ConclusionsFEK from a spot urine sample represents a convenient and reliable parameter to predict renal potassium loss in patients with hypokalemia.

A Practical Approach for Pathophysiological Diagnosis of Refractory Hypokalemia

Hypokalemia is a common finding in hospitalized patients. In most cases the cause will be obvious. However, in a subgroup of patients the cause is occasionally uncertain and establishing the diagnosis may present difficulties and can become a challenge. In such cases, measurement of urinary indices e.g. trans-tubular potassium gradient [TTKG] and random urine potassium/creatinine concentrations along with blood acid/base parameters and assessment of urinary excretion of potassium, chloride, calcium and creatinine have been employed in the differential diagnosis. TTKG and urine potassium/creatinine ratio are used as a rapid appropriate index of potassium excretion and to establish a proper diagnosis and management in this medical emergency. It helps to differentiate between hypokalemia caused by redistribution or renal potassium wasting. Urinary chloride excretion and urinary calcium/creatinine ratio in conjunction with plasma acid/base values, aldosterone, renin and cortisol values are used for narrowing the differential diagnosis of refractory hypokalemia. Conclusions: Calculating the trans-tubular potassium concentration gradient, urinary potassium/creatinine ratio, urinary chloride excretion and urinary calcium/creatinine ratio in conjunction with plasma acid/base values provided simple and reliable tests for differential diagnosis of causes of refractory hypokalemia and to provide a proper management in the intensive care unit and in the emergency until advanced further tests to be done.

144The transtubular potassium concentration gradient as a predictive index of clinical tissue hypoperfusion in patients with acute decompensated heart failure

144The transtubular potassium concentration gradient as a predictive index of clinical tissue hypoperfusion in patients with acute decompensated heart failure

A case report of distal RTA presenting as hypokalaemic periodic paralysis in young male

A 21-year-old normotensive male presented with acute onset flaccid paralysis with the history of a similar episode a few months back. Clinical and laboratory evaluation revealed lower motor neuron type of flaccid quadriparesis with hypokalaemia, normal anion gap metabolic acidosis, bicarbonaturia, and transtubular potassium concentration gradient (TTKG) more than 7. Subsequently urine acidification test (by NH4CI challenge test) was done and diagnosis of distal renal tubular acidosis was established. The patient responded to conservative management (Sohl's solution).

A case report of recurrent hypokalaemic periodic paralysis in a young male patient

A 21-year-old normotensive male patient presented with acute-onset flaccid paralysis with the history of a similar episode a few months back. Clinical and laboratory evaluation revealed lower motor neuron type of flaccid quadriparesis with hypokalaemia, normal anion gap metabolic acidosis, bicarbonaturia and transtubular potassium concentration gradient more than 7. Subsequently, urine acidification test (by ammonium chloride challenge test) was performed and diagnosis of renal tubular acidosis was established. The patient ultrasound did not show nephrocalcinosis, and history of recurrent diarrhoea preceding the attack revealed that the patient also had coeliac disease. The patient responded to conservative management (Sohl’s solution) and gluten-free diet.

P114 – 2576: Hypokalemic periodic paralysis: A case report based on clinical and genetic findings

Objectives Hypokalemic periodic paralysis (HPP) is a rare channelopathy characterized by episodes of acute muscle weakness associated with hypokalemia. The classification of this disorder is based on anamnesis, biochemical study and molecular genetic testing. Our aim is to present a patient with HPP confirmed by genetic study. Methods Case description providing the results of complementary tests. Results A 14-year-old male presented with several episodes of sudden weakness of all four limbs that prevents him from walking, always on waking and without any triggers. No relevant personal or familial history, except for delayed tooth eruption and oligodontia. During the attack the examination revealed weakness predominantly in lower limbs with hyporeflexia; laboratory tests showed severe hypokalaemia (1.8 mmol/l) and increased creatinine kinase levels; blood gases, biochemical analysis of urine and thyroid hormones where normal; electrocardiogram showed a slight flattening of the T wave with no other abnormalities. Admission to the PICU was necessary twice in order to receive intravenous potassium infusion. Other episodes where satisfactorily treated with oral supplements. Genetic investigations showed a heterozygous mutation in the SCN4A gene (c.1582C>G), compatible with HPP diagnosis. The patient is currently being treated with oral potassium supplements and acetazolamide, achieving a reduction in the number of episodes. Conclusion HPP is a condition in which affected individuals may experience flaccid paralytic episodes with concomitant hypokalemia. In primary HPP caused by a genetic ion channel defect (CACNA1S gene for the majority of cases), hypokalemia is caused by intracellular muscular shift of potassium, so transtubular potassium concentration gradient and potassium-creatinine ratio during paralytic attack is key to distinguish primary HPP from hypokalemia caused by urinary losses. Associated hyperthyroidism must be ruled out. It's important to differentiate between the acute and preventive treatment. The response varies depending on the type of mutation.

Circadian rhythm of urinary potassium excretion during treatment with an angiotensin receptor blocker

We have reported that the circadian rhythm of urinary potassium excretion (U(K)V) is determined by the rhythm of urinary sodium excretion (U(Na)V) in patients with chronic kidney disease (CKD). We also reported that treatment with an angiotensin receptor blocker (ARB) increased the U(Na)V during the daytime, and restored the non-dipper blood pressure (BP) rhythm into a dipper pattern. However, the circadian rhythm of U(K)V during ARB treatment has not been reported. Circadian rhythms of U(Na)V and U(K)V were examined in 44 patients with CKD undergoing treatment with ARB. Whole-day U(Na)V was not altered by ARB whereas whole-day U(K)V decreased. Even during the ARB treatment, the significant relationship persisted between the night/day ratios of U(Na)V and U(K)V (r=0.56, p<0.0001). Whole-day U(K)V/U(Na)V ratio (p=0.0007) and trans-tubular potassium concentration gradient (p=0.002) were attenuated but their night/day ratios remained unchanged. The change in the night/day U(K)V ratio correlated directly with the change in night/day U(Na)V ratio (F=20.4) rather than with the changes in aldosterone, BP or creatinine clearance. The circadian rhythm of U(K)V was determined by the rhythm of UNaV even during ARB treatment. Changes in the circadian U(K)V rhythm were not determined by aldosterone but by U(Na)V.

Electrolyte disturbances in acute pyelonephritis

The aim of this study was to determine whether renal unresponsiveness to aldosterone associated with hyperkalemia is present in infants with acute pyelonephritis in the absence of significant urinary tract anomalies and to describe the clinical characteristics of patients presenting an inadequate renal response to hyperkalemia. The patient cohort comprised 113 infants with acute pyelonephritis (APN), based on the criteria of a temperature >38°C and significant bacteriuria. Serum and urine electrolytes, creatinine, osmolality, and renal tubular function tests were performed at diagnosis. The findings were compared to those present in 75 children who had fever without significant bacteriuria. Hyperkalemia (>5.5 mmol/L) was observed in infants with an APN diagnosis, who exhibited a lower transtubular potassium concentration gradient (TTKG) and a higher fractional sodium excretion. We defined inadequate renal response to hyperkalemia as the combination of hyperkalemia and TTKG below the normal range established for the age of the subject. Infants presenting an inadequate response to hyperkalemia were younger and associated more frequently with an APN diagnosis. This alteration could be explained by the renal interstitial inflammation present in acute pyelonephritis and the immaturity of the renal tubular responsiveness to aldosterone due to infancy in the absence of urinary tract infection or obstruction.

サイアザイドによる降圧加療により意識障害を伴う低ナトリウム血症で緊急入院した2症例

The salt intake of the Japanese is among the highest in the world, leading to a high prevalence of salt-sensitive hypertension. To prevent this, salt restriction, suppression of the rennin-angiotensin-aldosterone system, and natriuresis are important. Therefore, the use of a combination of an angiotensin II receptor blocker and thiazide diuretics is used for antihypertensive treatment. Some randomized controlled studies suggested that thiazide diuretics are useful not only to lower blood pressure, but also to prevent cardiovascular events and improve prognosis in the elderly, who are prone to being salt-sensitive. We encountered 2 elderly patients referred to our emergency room because of severe hyponatremia and consciousness disturbance, who had been treated with thiazide diuretics for 1 and 2 months, respectively. In both, hypernatriuria despite hyponatremia, slight dehydration, and refractory antidiuretic hormone (ADH) excess were observed, but activation of the rennin-angiotensin-aldosterone system was absent. Thyroid and adrenal functions were unremarkable. Theses phenomena have much in common with the condition called mineralcorticoid-responsive hyponatremia of the elderly (MRHE). Several weeks after discontinuation of diuretics, serum sodium values returned to normal levels, but transtubular potassium concentration gradient (TTKG) values were depleted despite slight hyperkalemia, and relative ADH excess was sustained, which suggested mineralocorticoid dysfunction and distal renal tubulointerstitial injury. Distal tubulointerstitial dysfunction is one of the most important causes of MRHE. On the basis of these 2 cases, we speculated whether distal tubulointerstitial injury may accelerate hyponatremia in the elderly. We need to check not only serum potassium, but also sodium levels, especially in elderly persons with suspected tubulointerstitial injury.

Conn's Syndrome with an Unusual Presentation of Rhabdomyolysis Secondary to Severe Hypokalemia

Conn's syndrome is one of the major causes of secondary hypertension. Premature hypertension, metabolic alkalosis, and hypokalemia usually lead clinicians to suspect the diagnosis. We describe a case of Conn's syndrome in a 28-year-old woman with an unusual presentation of rhabdomyolysis secondary to hypokalemia and complete bilateral lower limb paralysis. An elevated transtubular potassium concentration gradient, asymptomatic severe hypertension, and metabolic alkalosis pointed to possible primary hyperaldosteronism, which was confirmed by a decrease in plasma renin activity (PRA), elevation in plasma aldosterone level and elevation of the plasma aldosterone to PRA ratio. Computed tomography showed an adrenal tumor in the adrenal gland. Her blood pressure, hypokalemia, and plasma aldosterone level returned to normal after left adrenalectomy, further confirming the diagnosis. Histologic examination showed an adrenal gland adenoma.

An Unusual Cause of Hypokalemia in an Elderly Man with Hypertension

Hypokalemia in the elderly usually results from gastrointestinal loss or the use of diuretics. However, primary aldosteronism should be considered in hypertensive patients with metabolic alkalosis and unexplained hypokalemia with hyperkaliuresis. We report a 63 year-old hypertensive man with such metabolic findings. The transtubular potassium concentration gradient and serum aldosterone level were higher than normal. Abdominal computed tomography showed bilaterally enlarged adrenal glands, and a nuclear medicine study supported the diagnosis of bilateral adrenal hyperplasia.

Transtubular potassium concentration gradient: comparison between healthy old people and chronic renal failure patients

Transtubular potassium concentration gradient (TTKG) is an index of potassium secretory activity in the distal tubule. Since water reabsorption takes place in the distal tubule as well, urine potassium concentration is a less accurate index evaluating distal K+ secretion because the effect of water is not taken into account on urine potassium concentrations. Potassium secretion and water reabsorption are strongly related to age and renal function. As a consequence, TTKG would be altered in both elderly individuals, as well as in patients with chronic renal failure (CRF). The aim of this study was to assess and compare TTKG in these two groups. A total of 55 individuals were studied, 12 of them were patients with CRF and 43 healthy elderly subjects with normal renal function. Informed consent was obtained from all patients. Patients with diabetes mellitus, cardiac failure, cirrhosis, obstructive uropathy, hyperkalemia, hypokalemia, or taking any medication that could alter the potassium balance were excluded from the study. All subjects were on a diet containing 50 mmol of potassium intake daily (documented by a three-day dietary record). Plasma potassium, creatinine, urea, glucose and osmolality were measured in all as well. 24 h creatinine clearance (CrCl ) and TTKG were calculated. Statistical analysis was made using Student's t-test. TTKG was significantly lower in the elderly group (4.2+/-1.9 vs 6.2+/-1.8 , P 0.005)Both groups had a significantly lower TTKG when compared to healthy young people (8+/-2). Plasma and urine potassium levels, as well as plasma osmolality were similar in the two groups. Only urine osmolality was lower in the CRF group (382+/-141 vs. 514+/-180, P=0.01) Both old age and renal impairment lead to a reduced TTKG in comparison with young healthy people. Furthermore, TTKG is significantly lower in elderly healthy subjects compared to patients with CRF.

Laboratory tests to determine the cause of hypokalemia and paralysis.

Hypokalemia and paralysis may be due to a short-term shift of potassium into cells in hypokalemic periodic paralysis (HPP) or due to a large deficit of potassium in non-HPP. Failure to make a distinction between HPP and non-HPP may lead to improper management. Therefore, we evaluated the diagnostic value of spot urine tests in patients with hypokalemia and paralysis during 3 years. Before therapy, the urine potassium concentration, potassium-creatinine ratio, and transtubular potassium concentration gradient were determined in a second voided urine sample. Forty-three patients with hypokalemia and paralysis were identified: 30 had HPP and 13 had non-HPP. There was no significant difference in the plasma potassium or bicarbonate concentrations and in the pH of arterial blood between the 2 groups. All but 2 patients in the non-HPP group had urine potassium concentration values less than 20 mmol/L. Although the potassium concentration was significantly lower in the HPP group, there was some overlap. In contrast, the transtubular potassium concentration gradient and potassium-creatinine ratio differentiated patients with HPP vs non-HPP. Although only a mean +/- SD of 63 +/- 36 mmol of potassium chloride was administered in the patients with HPP, rebound hyperkalemia (>5 mmol/L) occurred in 19 (63%) of these 30 patients. Calculating the transtubular potassium concentration gradient and potassium-creatinine ratio provided a simple and reliable test to distinguish HPP from non-HPP. Minimal potassium chloride supplementation should be given to avoid rebound hyperkalemia in patients with HPP.

Effect of Low-Molecular-Weight Heparin on Potassium Homeostasis

Background: Low-molecular-weight heparins (LMWHs) are being preferred to unfractionated heparin (UFH) because of their superior convenience and a comparable or slightly better toxicity profile. Whether LMWH has an inhibitory effect on aldosterone that causes hyperkalemia is yet uncertain. Methods: Twenty-eight patients (all male; mean age: 70 years, range 52–87 years) placed on LMWH therapy (40 mg subcutaneously every 12 h) for deep venous thrombosis prophylaxis after an operation were included in the study. Transtubular potassium concentration gradient (TTKG) was calculated 1 day prior to LMWH therapy and again after 4 days of treatment. Of the 28 patients enrolled in the study, we were able to calculate the TTKG in only 19 patients: 9 had a urinary osmolarity (either before or after LMWH therapy) less than the serum osmolarity, making the TTKG calculation unreliable. The Wilcoxon signed-rank test was used to analyze differences in the median serum potassium levels and TTKG before and after LMWH therapy. Results: All patients had adequate renal function (creatinine clearance >90 ml/min). Mean (± SD) serum potassium concentration before LMWH was 4.25 (± 0.40) mmol/dl. It increased to 4.35 (± 0.41) mmol/dl after initiating LMWH therapy (p = 0.09). Similarly, the mean (± SD) TKKG calculated was 5.52 (± 2.33) before and 5.97 (± 3.06) after 4 days of LMWH (p = 0.54). Conclusions: Unlike UFH, LMWH (Lovenox^®) in doses used for postoperative prophylaxis against deep venous thrombosis does not seem to have a significant effect on potassium homeostasis.

Transtubular potassium concentration gradient in preterm neonates

To determine the postnatal changes in mineralocorticoid action on the cortical distal nephron in preterm neonates, we evaluated the transtubular potassium gradient (TTKG) and its relationship to other renal and non-renal parameters in 16 preterm neonates during the first 5 weeks of life. Preterm neonates were divided into two groups according to their gestational age: the first group (group A, n=9) had a gestational age less than 30 weeks and the second group (group B, n=7) had a gestational age over 30 weeks. TTKG in both groups increased significantly with postnatal age, and TTKG in group A was significantly lower than that in group B (P=0.0003; two-way repeated analysis of variance). TTKG in group A was significantly lower during the 2 weeks of postnatal life than that in full-term neonates [TTKG during 1st week (mean+/-SD) 3.73+/-1.32, P<0.00001; during 2nd week 7.77+/-3.60, P=0.0096 versus full-term neonates (n=19); 11.56+/-3.23]. TTKG in group B was significantly lower only during the 1st week of life (6.55+/-2.71, P=0.0013) compared with full-term neonates. Plasma aldosterone concentration did not correlate with TTKG value. Stepwise regression analysis showed that postnatal age, cortical lumen sodium concentration (CLNa), and clinical condition requiring the use of mechanical ventilation were independent variables that correlated significantly with TTKG. We postulate that the low TTKG level in preterm neonates might reflect the prematurity of renal function (early postnatal age, CLNa) and the condition(s), relating to immaturity, such as the use of mechanical ventilation.

Renal and adrenal mechanisms in cyclosporine-induced hyperkalaemia after renal transplantation.

CsA associated hyperkalaemia was investigated in 24 renal transplant recipients 6 months after transplantation. 51Cr-EDTA-, PAH-, lithium and sodium clearances, 24 h urinary creatinine and potassium excretions, plasma renin activity and aldosterone concentrations were measured. Transtubular potassium concentration gradient (TTKG) was calculated. An ACTH test was performed to document adrenal function. Eleven patients had hyperkalaemia. The TTKGs were low normal or reduced in both normo- and hyperkalaemic patients implying inhibition of K+ secretion. The hyperkalaemic patients received more CsA (mean dose 21.3 vs. 9.7 mg kg-1d-1, P = 0.01), and had lower lithium clearances (mean 9.9 vs. 17.0 mL min-1 1.73 m-2, P < 0.05). Adrenal function had no clear effect. Serum potassium concentration correlated with CsA dose (r = 0.773, P < 0.001) and inversely with lithium clearance (r = -0.568, P < 0.01) suggesting that CsA induced decrease in distal tubular flow rate reduced K+ excretion. Hyperkalaemia was not fully explained by renal mechanisms.

What is responsible for the diurnal variation in potassium excretion?

Potassium excretion exhibits a diurnal pattern, with most excretion occurring close to noon in humans. Each component of the K+ excretion rate [urinary K+ concentration ([K+]) and flow rate] was measured and back-calculated to reflect events in the cortical collecting duct (CCD). Our purpose was to determine to what extent each component contributed to this diurnal variation in each 2-h portion of the day. In humans, K+ excretion rose threefold from nadir (0600 h) to peak (1200-1400 h), 18 h after the principal intake of K+. The variation in K+ excretion was due almost exclusively to changes in [K+] in the terminal CCD ([K+]CCD) rather than via changes in flow rate. In rats, the bulk of K+ excretion occurred shortly after eating. Both components of K+ excretion rose after meals; the rise in the [K+]CCD (3.3-fold) predominated at earlier times, and the rise in flow rate occurred later and was primarily a result of a higher rate of excretion of urea. The rise in [K+]CCD did not correlate with aldosterone levels or administration. A very large rise in the [K+]CCD only occurred in the presence of bicarbonaturia; the transtubular potassium concentration gradient was now close to 15 in the morning and evening.

Renal electrolyte and water handling in normal pregnancy: possible role of endothelin-1

The study was carried out to determine the urinary excretion of endothelin-1 (ET-1) in normal pregnancy and to define its possible role in mediating the renal response to aldosterone and arginine vasopressin (AVP). Measurements were performed in 12 healthy pregnant women serially in the 20th, 24th, 28th, 32nd and 36th weeks of pregnancy. Urinary ET-1, plasma and urinary aldosterone and AVP levels (RIA methods) as well as plasma and urine sodium, potassium, creatinine and osmolality were measured; creatinine clearance (C cr), osmolar clearance (C osm) and free water clearance (CH 2O) calculated. Fractional sodium excretion (FE Na), urine sodium/potassium ratio ( Na K ) and transtubular potassium concentration gradient (TTKG) were also determined. It was demonstrated that urinary ET-1 excretion was higher in pregnant than in non-pregnant women and it increased further as the pregnancy progressed from 34.8 ± 4.0 pmol/day in week 20 to 44.1 ± 3.2 pmol/day in week 36 ( P < 0.01). Daily ET-1 excretion significantly correlated with AVP ( r = 0.39, P < 0.005) and aldosterone excretion ( r = 0.62, P < 0.0001). Furthermore, there was a significant positive relationship between ET-1 excretion and urine flow rate ( r = 0.67, P < 0.0001), C CR ( r = 0.40, P < 0.0025), C osm ( r = 0.58, P < 0.001), sodium ( r = 0.56, P < 0.001) and potassium excretion ( r = 0.42, P < 0.001). However, such a relationship could not be established between ET-1 excretion and FE Na, TTKG and Na K . It is concluded that the activated reninangiotensin-aldosterone system, the augmented AVP secretion and the reduced renal medullary tonicity might contribute to the increased renal ET-1 production in pregnancy, which might modulate the renal response to aldosterone and AVP.