Aldosterone in congestive heart failure: analysis of determinants and role in sodium retention.

In patients with congestive heart failure (CHF), the role of aldosterone in the abnormal sodium (Na+) retention and the determinants of plasma aldosterone (PA) including plasma atrial natriuretic factor (hANF), plasma renin activity (PRA), and plasma potassium (K+) have not been fully elucidated. We therefore studied the effect of the specific aldosterone antagonist, spironolactone, on urinary Na+ and K+ excretion and plasma hormone responses in 6 Na(+)-retaining CHF patients. After withdrawal of diuretics 4 days prior to the study, the CHF patients were placed on a Na+ intake of 100 mmol/day for 9 days. Spironolactone, 200 mg p.o. bid, was administered for the last 4 days of the 9-day study period. PRA and norepinephrine increased with spironolactone treatment (both p less than 0.05). Plasma hANF before spironolactone was significantly elevated and decreased during spironolactone therapy (p less than 0.05). Urinary Na+ excretion significantly increased during spironolactone administration and the positive Na+ balance was reversed in the CHF patients. Moreover, the urine Na+:K+ concentration ratio significantly increased during spironolactone administration. Analysis of the relationship between PA, plasma K+, PRA, and plasma hANF indicated that PRA is the primary determinant of PA in patients with CHF. Thus, the present results indicate that the renin-angiotensin-aldosterone system is an important mediator of Na+ retention in CHF, as evidenced by the reversal of the positive Na+ balance with a specific aldosterone antagonist. This natriuretic effect can be demonstrated in the presence of potential antinatriuretic influences including stimulation of the renin-angiotensin and sympathetic nervous systems and a decrease in plasma hANF.     

Functional relationships in the nephrotic syndrome

An analysis of 70 observations in patients with the nephrotic syndrome (NS) on a low sodium diet is presented. The following parameters were determined: plasma volume, plasma renin activity, plasma aldosterone concentration, serum albumin, urinary sodium and protein excretion, and creatinine clearance. In 41 instances glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined on the basis of 51Cr-EDTA and 125I-hippuran clearances, and the filtration fraction (FF) was calculated. The results in patients with minimal lesions (ML) and those with histological glomerular lesions (HL) were compared to determine whether these groups can be separated on the basis of signs of hypovolemia and primary renal sodium retention. Although a higher proportion of the ML patients showed extreme sodium retention and elevated plasma renin and aldosterone levels, these values tended to overlap and no differences were found for blood volume, blood pressure, and overall renal function between the groups. FF was markedly and equally depressed in both groups: 13.5 +/- 1.6% in the ML and 14.2 +/- 1.1% SEM in the HL group (NS). Analysis of the within-group relationships between the parameters under study revealed relatively few correlations, which supports the hypothesis that primary impairment of renal water and salt excretion is an important if not overruling factor in patients with the NS.     

Collecting duct is a site of sodium retention in PAN nephrosis: a rationale for amiloride therapy

Micropuncture studies of the distal nephron and measurements of Na,K-ATPase activity in microdissected collecting tubules have suggested that renal retention of sodium in puromycin aminonucleoside (PAN) nephrotic rats originates in the collecting duct. The present study demonstrated this hypothesis by in vitro microperfusion and showed that amiloride was able to restore sodium balance. Indeed, isolated perfused cortical collecting ducts from PAN-treated rats exhibited an abnormally high transepithelial sodium reabsorption that was abolished by amiloride, and in vivo administration of amiloride fully prevented decreased urinary sodium excretion and positive sodium balance in nephrotic rats. As expected from the aldosterone independence of Na(+) retention in PAN nephrotic rats, blockade of aldosterone receptor by potassium canrenoate did not alter urinary Na(+) excretion, Na(+) balance, or ascites formation in PAN nephrotic rats.     

Suppression of surgical hyperaldosteronism by potassium canrenoate during gynecologic surgery under sevoflurane anesthesia

BACKGROUND: Surgical hyperaldosteronism leads to sodium and water retention during surgery and often causes postoperative edema. This study investigated the effect of potassium canrenoate (PC) on pituitary adrenocortical function in lower abdominal surgery under sevoflurane anesthesia. METHODS: Twenty patients were randomized to receive 400 mg of PC (the PC group, n=10) or saline (the control group, n=10) intravenously. The following parameters were determined: plasma aldosterone, adrenocorticotropic hormone (ACTH), plasma renin activity (PRA), serum sodium and potassium, urinary sodium and potassium, and urine output. RESULTS: The aldosterone and ACTH levels showed significant increases in the control group during surgery. Plasma ACTH also increased significantly in the PC group, but plasma aldosterone levels were unchanged during surgery. The urine Na/K ratio of the PC group was significantly higher than that of the control group. CONCLUSION: The present study suggested that PC suppresses the increase of plasma aldosterone caused by surgical stress. That may prevent sodium retention and potassium excretion during surgery.     

Collecting duct (Na+/K+)-ATPase activity is correlated with urinary sodium excretion in rat nephrotic syndromes

In puromycin aminonucleoside (PAN)-treated nephrotic rats, sodium retention is associated with increased (Na+/K+)-ATPase activity in the cortical collecting ducts (CCD). This study was undertaken to determine whether stimulation of (Na+/K+)-ATPase in the CCD is a feature of other experimental nephrotic syndromes, whether it might be responsible for renal sodium retention, and whether it is mediated by increased plasma vasopressin levels or activation of calcineurin. For this purpose, the time courses of urinary excretion of sodium and protein, sodium balance, ascites, and (Na+/K+)-ATPase activities in microdissected CCD were studied in rats with PAN or adriamycin nephrosis or HgCl2 nephropathy. The roles of vasopressin and calcineurin in PAN nephrosis were evaluated by measuring these parameters in Brattleboro rats and in rats treated with cyclosporin or tacrolimus. Despite different patterns of changes in urinary sodium and protein excretion in the three nephrotic syndrome models, there was a linear relationship between CCD (Na+/K+)-ATPase activities and sodium excretion in all three cases. The results also indicated that there was no correlation between proteinuria and sodium retention, but ascites was present only when proteinuria was associated with marked reduction of sodium excretion. Finally, the lack of vasopressin in Brattleboro rats or the inhibition of calcineurin by administration of either cyclosporin or tacrolimus did not prevent development of the nephrotic syndrome in PAN-treated rats or stimulation of CCD (Na+/K+)-ATPase. It is concluded that stimulation of Na(+/K+)-ATPase in the CCD of nephrotic rats might be responsible for sodium retention and that this phenomenon is independent of proteinuria and vasopressin and calcineurin activities.     

Early and late adjustment to potassium loading in humans

We studied the adaptation to early (72 hr) and late (20 days) K loading (400 mmol/day, 4 equal meals every 6 hour) in six healthy humans. Throughout the study, each single K meal was followed by an acute transient rise in plasma K, aldosterone and kaliuresis. "K balance" (urinary K excretion approximately 80% of intake) was achieved in the second 24 hour period of K loading. This was associated with elevated plasma K and aldosterone, slightly negative sodium (Na) balance and stimulated plasma renin activity. At 20 days of K loading Na loss had been compensated. Plasma renin activity and aldosterone had returned to baseline, although the latter kept increasing after each single K meal. Compared to the first K meal, the K meals at 72 hours and 20 days of K loading were followed by more kaliuresis, while the natriuretic effect had disappeared. Abrupt discontinuation of K loading was followed by negative K balance, lasting only 24 hour, and by Na retention, lasting 72 hours. In conclusion, switching to a high K diet in humans is immediately followed by increased renal K excretion, and by Na loss. K excretion increases over a few days, while Na loss is halted. This can be explained by the rise in plasma aldosterone, secondary to elevated plasma K and renin activity. After weeks, renal adaptation forms an additional factor promoting K excretion and preventing natriuresis. The latter appears specifically from the Na retention which occurs after discontinuation of K loading in the absence of persistent aldosterone stimulation.     

Urine kallikrein excretion in relation to renal sodium handling in minimal change nephrotic syndrome.

Twenty-four-hour urine kallikrein excretion (Uka), urine protein excretion, renal sodium handling, and the activity of the renin-angiotensin-aldosterone system were serially studied in 11 children at three different stages of the minimal change nephrotic syndrome (MCNS)-edema forming state, proteinuric steady state in which a relapse of the disease was just starting but no edema as yet and remission. The value for Uka was significantly increased in the edema forming state in contrast to the normal values of proteinuric steady state and remission. Serum sodium concentration was only decreased in the edema forming state and the degree of hypoalbuminemia and proteinuria did not differ between the edema forming and proteinuric steady states. Urine volume, absolute and fractional sodium excretion were significantly decreased in the edema forming and proteinuric steady states as compared with those in remission, suggesting that sodium retention was present in both states of the disease although the change in these parameters was more profound in the edema forming state than in the proteinuric steady state. Creatinine clearance did not differ among each stage of the disease. Plasma renin activity and plasma aldosterone concentration were significantly increased in the edema forming state as compared with those in the proteinuric steady state and remission. Plasma renin activity and plasma aldosterone concentration were significantly correlated directly with Uka and plasma aldosterone concentration was correlated inversely with urine sodium excretion. No relation was noted between Uka and other variables.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pathogenesis of edema formation in the nephrotic syndrome

Based on observations in 110 children with nephrotic syndrome (NS) and data from the literature, existing concepts on the pathogenesis of edema formation in the NS have been modified. The data suggest that the basic abnormality is a primary disturbance in renal sodium excretion. Depending on the stage in the development of the NS, the rate of progression in the development of hypoproteinemia, and the absolute levels of plasma oncotic pressure, functional hypovolemia may develop, resulting in stimulation of hemostatic mechanisms and secondary sodium retention. This applies as much to patients with minimal change NS as to patients with histological lesions. Alterations in kidney function (glomerular filtration rate, renal plasma flow, filtration fraction) in the NS cannot be explained by hypo- or hypervolemia, but reflect variations in plasma oncotic pressure and glomerular basement membrane permeability. These abnormalities will also influence sodium excretion. Evaluation of the presence of functional hypovolemia will have therapeutic consequences. A quick diagnosis can be made by assessment of FE_Na ⁺ and U_K ⁺/ (U_K ⁺+U_Na ⁺) Sodium retention associated with increased distal Na/K exchange indicates functional hypovolemia, and may be treated by albumin infusion if clinically required. Received: 20 August 1999 / Revised: 20 September 2000 / Accepted: 21 September 2000     

Sodium and potassium status, plasma renin and aldosterone profiles in normotensive and hypertensive Johannesburg blacks

Many studies have suggested that there is an association between the sodium status, plasma renin and aldosterone profile and essential hypertension. We measured serum, urine and red blood cell (RBC) sodium and potassium, plasma renin and aldosterone levels in normotensive Whites, normotensive Blacks, mildly hypertensive Blacks, severely hypertensive Blacks and Blacks with malignant hypertension. There were no important differences between the groups studied as regarded the serum sodium, serum potassium and urinary sodium excretion values. However, the urinary potassium excretion was significantly lower in normotensive and hypertensive Blacks than in Whites. RBC sodium concentrations showed no significant differences in the mean values across the range of degrees of hypertension in Blacks, although they tended to be higher in the more severely hypertensive groups. Blacks with mild-to-moderate hypertension as well as the severely hypertensive group had significantly lower plasma renin levels than the normotensive group; only in the malignant hypertensives with advanced renal failure did the plasma renin and aldosterone levels rise.     

Epidural Analgesia Inhibits the Renin and Aldosterone Response to Surgery

Renin activity and aldosterone concentration in plasma and excretion of sodium and potassium in urine were measured during a period of 24 hours in 12 patients undergoing hysterectomy under general anaesthesia or epidural analgesia. Analgesia extended from T4 to S5 and was effective throughout the study. The normal stress-induced increase in plasma renin activity and aldosterone was inhibited by epidural analgesia. Urinary excretion of potassium was significantly lower in the epidural group, but sodium and water retention showed no difference between groups. It is concluded that neurogenic stimuli from the surgical area are important release mechanisms of the renin-aldosterone response to surgery. The results suggest that post-operative sodium retention is caused by factors other than the mineralocorticoid system.     

Observations on sodium retention related to insulin treatment of experimental diabetes.

Streptozotocin (STZ)-diabetic rats regularly retained sodium (Na+), and tended to retain potassium (K+) as well, in response to insulin. Diabetic patients have also been reported to exhibit antinatriuresis and antikaliuresis early in the course of insulin therapy. Insulin-related Na+ retention can occur without a marked reduction in blood glucose level and does not appear to be attributable to preexisting Na+ depletion, mineralocorticoid effect, or suppression of glucosuria. The decrease in urinary Na+ excretion (UNaV) in the rats incident to insulin administration was appreciably greater than the decrease in chloride (Cl-) or water excretion. The significance of this observation is uncertain. It may be, in part, a consequence of the nephrotoxicity of STZ. Insulin-related Na+ retention may be closely related pathogenetically to the Na+ retention of refeeding and may reflect a direct renal action of insulin or, less likely, an alteration of renal tubular metabolism in response to insulin-mediated changes in sytemic metabolism.     

Hyperkalemic distal renal tubular acidosis associated with Rett syndrome

Renal function was studied in a 7-year-old girl with Rett syndrome (RS) complicated by persistent hyperchloremic hyperkalemic metabolic acidosis. The acidosis was associated with a urine pH above 5.5, positive urinary anion gap and decreased potassium excretion. Plasma renin activity, aldosterone and cortisol levels were normal. Therapy with sodium bicarbonate failed to lower urine pH below 5.5 or increase potassium excretion. Hydrochlorothiazide administration resulted in a fall in urine pH below 5.5 and an increase in potassium excretion as a result of increased distal sodium delivery and increased sodium reabsorption in the distal nephron. We conclude that a voltage-dependent type of derangement in the distal nephron, rather than aldosterone deficiency, is responsible for the impairment in urinary acidification observed in this patient. Early detection of impaired renal acidification in RS may prevent or slow the progression of growth failure.     

Sodium retention in nephrotic syndrome is due to an intrarenal defect: evidence from steroid-induced remission

There is increasing evidence that the sodium retention of nephrotic syndrome is directly due to an intrarenal mechanism and not to a low blood volume stimulating the renin-angiotensin-aldosterone system. However the mechanism of the natriuresis that occurs during remission is not known. Patients with nephrotic syndrome were therefore studied during steroid-induced remission. At the onset of natriuresis, blood volume and plasma albumin were low and did not change. Plasma renin activity and plasma aldosterone were initially high and both fell during the natriuresis. At the end of the natriuresis when patients had lost their oedema, plasma renin activity and plasma aldosterone rose to high levels, plasma albumin and blood volume remained low, and yet the patients were no longer retaining sodium and were in sodium balance. These observations suggest that the natriuresis of remission is due to the correction of an intrarenal mechanism causing the sodium retention. This study raises two major unanswered questions. Firstly, when the presumed intrarenal mechanism is corrected, what tells the kidney to excrete large amounts of sodium when the blood volume remains low? Secondly, why do the patients come back into sodium balance when the blood volume is low, and plasma renin activity and plasma aldosterone are elevated?     

Hyperaldosteronemia and activation of the epithelial sodium channel are not required for sodium retention in puromycin-induced nephrosis

Edema and ascites in nephrotic syndrome mainly result from increased Na+ reabsorption along connecting tubules and cortical collecting ducts (CCD). In puromycin aminonucleoside (PAN)-induced nephrosis, increased Na+ reabsorption is associated with increased activity of the epithelial sodium channel (ENaC) and Na+,K+-ATPase, two targets of aldosterone. Because plasma aldosterone increases in PAN-nephrotic rats, the aldosterone dependence of ENaC activation in PAN nephrosis was investigated. For this purpose, (1) the mechanism of ENaC activation was compared in nephrotic and sodium-depleted rats, and (2) ENaC activity in PAN-nephrotic rats was evaluated in the absence of hyperaldosteronemia. The mechanism of ENaC activation was similar in CCD from nephrotic and sodium-depleted rats, as demonstrated by (1) increased number of active ENaC evaluated by patch clamp, (2) recruitment of ENaC to the apical membrane determined by immunohistochemistry, (3) shift in the electrophoretic profile of gamma-ENaC, and (4) increased abundance of beta-ENaC mRNA. Corticosteroid clamp fully prevented all PAN-induced changes in ENaC but did not alter the development of a full-blown nephrotic syndrome with massive albuminuria, amiloride-sensitive sodium retention, induction of CCD Na+,K+-ATPase, and ascites. It is concluded that in PAN-nephrosis, (1) ENaC activation in CCD is secondary to hyperaldosteronemia, (2) sodium retention and induction of Na+,K+-ATPase in CCD are independent of hyperaldosteronemia, and (3) ENaC is not necessarily limiting for sodium reabsorption in the distal nephron.     

Role of aldosterone in the sodium retention of patients with nephrotic syndrome

The role of aldosterone in the abnormal sodium retention in patients with nephrotic syndrome has been debated. In fact, studies using a converting enzyme inhibitor to lower plasma aldosterone have rejected such a role. We therefore studied 5 nephrotic patients and 6 control subjects by using the more specific aldosterone antagonist, spironolactone. After withdrawal of diuretics 5 days prior to the study, the nephrotic patients and control subjects were placed on a high-sodium diet (285 +/- 6 mEq/day) for 8 days. After 4 days, spironolactone 200 mg p.o., b.i.d., was given for the remaining 4 days. Plasma renin activity and plasma aldosterone levels were similar in both nephrotic patients and control subjects before the study, after sodium loading and after spironolactone had been given. After 4 days of high sodium intake control subjects were in sodium balance, but the nephrotic patients were in a positive sodium balance (approx. 80 mEq/day; p less than 0.01). On days 3 and 4 of spironolactone, the nephrotic patients exhibited an increase in urinary sodium excretion (205 +/- 20 vs. 312 +/- 13 mEq/day; p less than 0.005) but not the control subjects (279 +/- 16 vs. 286 +/- 13 mEq/day; NS). It is therefore concluded that aldosterone is a significant contributor to the sodium retention in patients with nephrotic syndrome.     

Effects of indomethacin on the renal function and renin-aldosterone system in chronic glomerulonephritis

The effects of indomethacin on plasma renin activity (PRA), plasma and urine aldosterone levels and on renal function were studied in 37 patients with chronic glomerulonephritis (GN). Indomethacin produced a significant decrease in PRA, in plasma and urinary aldosterone levels and an increase in serum potassium levels. In 4 patients indomethacin induced the clinical syndrome of hyporeninemic hypoaldosteronism with hyperkalemia, which developed during the first weeks of treatment, persisted during treatment and disappeared without any additional drugs when indomethacin was stopped. In 14 patients with chronic GN, indomethacin caused a decrease in glomerular filtration rate (GRF). Their pretreatment PRA was significantly higher than that of patients with unchanged or increased GFR and most of them had prominent sclerotic changes on biopsy. Indomethacin considerably depressed diuresis and urinary sodium excretion. The antidiuretic and antinatriuretic effects of indomethacin were more pronounced in patients with the nephrotic syndrome. The results suggest that indomethacin exerts an effect on the renin-aldosterone axis, may be a cause of drug-induced hyporeninemic hypoaldosteronism and may cause a decrease in GFR in patients with high PRA.     

Plasma atrial natriuretic peptide and natriuretic response to water immersion in patients with nephrotic syndrome.

Eight nonnatriuretic (daily Na excretion less than 50 mEq), 4 natriuretic (daily Na excretion greater than 50 mEq), and 4 steroid-responsive nephrotic patients, and 12 normal controls were studied with a 4-hour water immersion with measurements of electrolytes, plasma atrial natriuretic peptide (ANP), plasma renin activity (PRA), and plasma aldosterone (PA) [corrected]. Four nonnatriuretic patients further received 25 g albumin infusion, with a subsequent 2-hour water immersion study. The results are as follows: (1) In the nonnatriuretic patients, the extremely low basal Na excretion rate, high PRA, and PA levels indicated a state of active Na retention. In spite of the water-immersion induced suppression of PRA and PA and a comparable magnitude of plasma ANP increment, the natriuretic response to water immersion was blunted in the nonnatriuretic patients. (2) In the natriuretic patients, water immersion resulted in a similar magnitude of natriuresis but a higher degree of plasma ANP increment in comparison to the normal controls. (3) Natriuretic and plasma ANP responses to water immersion were not different between the steroid-responsive patients and normal controls. (4) The increase in plasma ANP and the suppression of PRA and PA after 25 g albumin infusion did not result in natriuresis until the further suppression of PRA and PA and the further stimulation of plasma ANP by subsequent water immersion. The above results indicate that the natriuretic and plasma ANP responses to water immersion are related to the basal Na status in nephrotic patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hyperkalemia in patients infected with the human immunodeficiency virus: involvement of a systemic mechanism.

BACKGROUND: The appearance of hyperkalemia has been described in human immunodeficiency virus (HIV)-positive patients treated with drugs with amiloride-like properties. Recent in vitro data suggest that individuals infected with HIV have alterations in transcellular K+ transport. METHODS: With the objective of examining the presence of alterations in transmembrane K+ equilibrium in HIV-positive patients, we designed a prospective, interventional study involving 10 HIV-positive individuals and 10 healthy controls, all with normal renal function. An infusion of L-arginine (6%, intravenously, in four 30-min periods at 50, 100, 200, and 300 ml/hr) was administered, and plasma and urine electrolytes, creatinine, pH and osmolality, total and fractional sodium and potassium excretion, transtubular potassium gradient, plasma insulin, renin, aldosterone, and cortisol were measured. RESULTS: A primary disturbance consisting of a significant rise in plasma [K+] induced by L-arginine was detected in only the HIV patients but not in the controls (P < 0.001 between groups). A K+ redistribution origin of the hyperkalemia was supported by its rapid development (within 60 min) and the lack of significant differences between HIV-positive individuals and controls in the amount of K+ excreted in the urine. The fact that the HIV-positive individuals had an inhibited aldosterone response to the increase in plasma K+ suggested a putative mechanism for the deranged K+ response. CONCLUSIONS: These results reveal that HIV-infected individuals have a significant abnormality in systemic K+ equilibrium. This abnormality, which leads to the development of hyperkalemia after the L-arginine challenge, may be related, in part, to a failure in the aldosterone response to hyperkalemia. These results provide a new basis for understanding the pathogenesis of hyperkalemia in HIV individuals, and demonstrate that the risk of HIV-associated hyperkalemia exists even in the absence of amiloride-mimicking drugs or overt hyporeninemic hypoaldosteronism.     

Draining the edema: a new role for aquaretics?

Investigations into edema formation in nephrotic syndrome have mostly focused on the primary role of sodium. While there is controversy about whether sodium retention is an inherent aspect of nephrotic syndrome (overfill hypothesis) or a secondary consequence (underfill hypothesis), the critical role of sodium in driving fluid retention is generally accepted. Consequently, treatment of edema is based on enhancing renal sodium excretion, using saluretics to block tubular reabsorption of sodium. However, there is also evidence of renal water retention: urine in nephrotic patients is typically highly concentrated (unless urinary concentrating ability is impaired by loop diuretics), and vasopressin levels are commonly elevated. Consequently, aquaretics, i.e., drugs that inhibit renal water reabsorption, may constitute effective treatments for nephrotic edema. In fact, these drugs are already approved for the treatment of non-nephrotic edematous states, such as those encountered in congestive heart or liver failure. In this edition of Pediatric Nephrology, two case reports raise the possibility that aquaretics may also be helpful in the treatment of nephrotic edema. These case reports provide no solid evidence for such treatment, and there clearly are serious concerns about inducing critical hypovolemia with potentially catastrophically consequences, such as thrombosis and shock. Yet these concerns similarly apply to saluretics, which clinicians routinely use in the treatment of edema. In addition, the described powerful effect of aquaretics with respect to the resolution of edema, as well as our understanding of the underlying physiology, argue for a more systematic, yet careful assessment of these drugs in the treatment of nephrotic syndrome.     

Renal function derangements induced by portacaval anastomosis in normal rats.

The purpose of this study was to determine the renal function derangements that portacaval shunting caused in previously normal rats. Eight rats suffered a surgical portacaval shunt (PCS) and another 8 a sham operation (SHAM). Renal function was investigated by determining urinary volume, sodium, potassium, creatinine and aldosterone excretion, in basal conditions and after sodium overload. Plasma renin concentration and urinary excretion of PGE2, 6-keto-PGF1 alpha and TXB2 were also determined in basal conditions. PCS rats showed increased urinary volume, creatinine excretion and endogenous creatinine clearance, either in basal conditions or after sodium load. After the latter, PCS animals also showed sodium retention and hyperaldosteronuria. PCS caused in basal conditions a striking diminution in urinary excretion of all prostaglandins and no changes in plasma renin. In conclusion, PCS in the normal rat caused a renal dysfunction consisting of polyuria, possibly related to ADH disfunction and an inability to manage a sodium load.