Hypokalemic Nephropathy Research Articles

Tubulointerstitial macrophage infiltration in a patient with hypokalemic nephropathy and primary Sjögren’s syndrome

We report a case of hypokalemic nephropathy associated with primary Sjögren's syndrome (SS). The patient presented with profound and persistent hypokalemia secondary to distal renal tubular acidosis (RTA). A renal biopsy exhibited tubular degeneration, marked interstitial fibrosis and intense macrophage infiltration. Hypokalemia has been reported to induce macrophage infiltration in experimental animal models but not in humans. This is the first report of intense tubulointerstitial macrophage infiltration in a patient with hypokalemic nephropathy associated with SS.

“End-stage kidney” in longstanding bulimia nervosa

The extent of renal damage over long-term binge/purges has not been well documented in bulimia nervosa (BN). We describe a 52-year-old woman with longstanding BN subsequent to an 8-year history of anorexia nervosa (AN). The patient showed chaotic binge/purges and chronic severe hypokalemia after recovery from AN at age 26 years, and renal biopsy showed juxtaglomerular hyperplasia, which was diagnosed as pseudo-Bartter's syndrome. Over the following 26 years, the patient's eating behaviors remained chaotic, and her renal function gradually deteriorated. After the patient died of pneumonia and sepsis at age 52 years, autopsy of her kidney showed chronic interstitial nephritis, proximal tubular swelling, and diffuse glomerular sclerosis, suggesting chronic glomerular injury associated with long-term binge/purges. To our knowledge, this is the first case report of a patient with BN with long-term binge/purges who developed an eventual "end-stage kidney" characterized by hypokalemic nephropathy and diffuse glomerulosclerosis.

Supplement nephropathy due to long-term, high-dose ingestion of ascorbic acid, calcium lactate, vitamin D and laxatives

A 48-year-old Japanese woman previously in good health was found to have severe proximal tubular dysfunction with a high serum level of ascorbic acid (57.3 microg/ml, reference range: 1.9 - 15.0 microg/ml). Renal biopsy specimen showed marked tubulointerstitial damage, i.e. tubular atrophy, dilatation of tubular lumen with flattened tubular epithelial cells, vacuolization of proximal and distal tubular epithelial cells, and severe interstitial fibrosis with mild infiltration of mononuclear cells. Calcified lesions, which caused tubular obstruction or stenosis, were also seen in interstitial area adjacent to degenerated proximal tubuli. Hypokalemic nephropathy, probably due to long-term use of laxatives, was clearly shown. However, calcified lesions seemed to be caused by inappropriate excessive daily ingestion of ascorbic acid (6 000 mg/day), calcium lactate, and vitamin D because of the patient's misunderstanding that these supplements could keep her in a good health. This condition may be clinically called "supplement nephropathy".

Proximal renal tubular dysfunction in primary distal renal tubular acidosis

Low-molecular-weight (LMW) proteinuria has been described in patients with primary distal renal tubular acidosis (dRTA). However, other proximal renal tubular dysfunctions have rarely been reported. In this report we describe reversible and multiple proximal renal tubular cell dysfunctions in a patient with dRTA. A 4-year-old girl was admitted to our hospital for investigation of short stature and proteinuria. Laboratory studies revealed a hyperchloremic metabolic acidosis without aciduria, hypokalemia, hypouricemia with uricosuria, hypercalciuria, LMW proteinuria, phosphaturia, and generalized aminoaciduria. The patient was diagnosed as having dRTA with multiple proximal renal tubular dysfunctions. All proximal renal tubular dysfunction subsided 1.5 years after starting alkali therapy. The precise pathogenic mechanisms underlying the development of multiple proximal renal tubular dysfunctions in dRTA remained unclear. However, proximal renal tubular endosomal dysfunction resulting from a profound intracellular acidosis caused by vacuolar H+-ATPase dysfunction or hypokalemic nephropathy might contribute to the development of proximal renal tubular dysfunctions in patients with dRTA.

Endothelin a receptor blockade and endothelin B receptor blockade improve hypokalemic nephropathy by different mechanisms.

Hypokalemia causes renal tubulointerstitial injury with an elevation in renal endothelin-1 (ET-1). It was hypothesized that hypokalemic tubulointerstitial injury is ameliorated by the blockade of ET-A receptors (ETA), whereas ET-B receptor (ETB) antagonism may exacerbate the injury, because ETB is thought to mediate vasodilation. Rats were fed a K(+)-deficient diet alone (LC) or with an ETA-selective antagonist ABT-627 (LA) or an ETB-selective antagonist A-192621 (LB) for 8 wk. Control rats were on a normal K(+) diet alone or with the ETA-selective or ETB-selective antagonists. The severity of hypokalemia was not significantly different among LA, LB, and LC. LC developed tubulointerstitial injury with an elevation of renal preproET-1 mRNA level. There was an increase in tubular osteopontin expression, macrophage infiltration, collagen accumulation, and tubular cell hyperplasia. ETA blockade significantly ameliorated all parameters for renal injury in the cortex without suppressing local ET-1 and ETA expression. By contrast, ETB blockade significantly reduced local ET-1 and ETA expression and improved the injury to a similar extent in the cortex. In the medulla, ETA or ETB blockade only partially blocked renal injury. ETA blockade did not affect BP in normokalemic or hypokalemic rats. ETB blockade induced a BP elevation with a decrease in urinary Na(+) excretion in normokalemic but not in hypokalemic rats. These results indicate that ET-1 can mediate hypokalemic renal injury in two different ways: by directly stimulating ETA and by locally promoting endogenous ET-1 production via ETB. Thus, ETA as well as ETB blockade may be renoprotective in hypokalemic nephropathy.

The role of growth factors and ammonia in the genesis of hypokalemic nephropathy

Hypokalemia is a common electrolyte abnormality encountered in clinical practice. It can be identified in an asymptomatic patient undergoing routine electrolyte screening or can manifest itself as part of a number of functional abnormalities in a variety of organs and systems. Among the most commonly recognized complications are profound effects on the cardiovascular and neuromuscular systems, together with abnormalities in acid–base regulation. In humans, hypokalemia contributes to the development of hypertension and predisposes patients to a variety of ventricular arrhythmias, including ventricular fibrillation. Commonly recognized neuromuscular complications include weakness, cramping, and myalgia. Hypokalemia also affects systemic acid–base homeostasis by interfering with multiple components of the renal acid–base regulation and is a frequent cause of metabolic alkalosis. Less known, however, is the role of potassium deficiency in causing progressive renal failure. In animals, potassium deficiency stimulates renal enlargement because of cellular hypertrophy and hyperplasia. If potassium deficiency persists, interstitial infiltrates appear in the renal interstitial compartment, and eventually tubulointerstitial fibrosis develops. In humans, longstanding hypokalemia is associated with the development of renal cysts, chronic interstitial nephritis, and progressive loss of renal function, the so-called hypokalemic nephropathy. This review focuses on the potential mechanisms involved in the development of the hypokalemic nephropathy with emphasis on the role of ammonia and growth factors in its pathogenesis. © 2002 by the National Kidney Foundation, Inc.

Expression of Bcl-2 and Bax in Hypokalemic Nephropathy in Rats

Objectives: Potassium depletion results in hyperplasia of renal tubular and interstitial cells in humans and animals, and potassium repletion induces rapid regression of hyperplasia. Apoptosis participates importantly in this reduction of cell number, although we have observed tubular and interstitial apoptosis in rats during potassium depletion as well. Methods: To investigate mechanisms of apoptosis in this model, we assessed expression of Bcl-2 and Bax, using immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). Results: Cell proliferation identifiable by labeling with 5-bromo 2′-deoxyuridine was prominent in tubular and interstitial cells of the cortex and outer medulla (OM) 7 days after potassium depletion. Simultaneously present apoptotic cells identified by light microscopy, electron microscopy, and nick end labeling were located mainly in the OM. Seven days after potassium repletion, apoptotic cells increased again but proliferating cells decreased. Bcl-2 protein distributed in the tubules of the OM was significantly decreased in potassium-depleted and potassium-repleted rats compared with control rats, while immunoreactivity for Bax protein tended to increase above control levels in potassium-depleted rats. RT-PCR for bcl-2 and bax demonstrated a significant decrease in levels of bcl-2 mRNA in potassium-depleted and potassium-repleted rats relative to those in controls. Expression of bax mRNA in potassium-depleted and potassium-repleted rats tended to increase, while ratios of bcl-2 mRNA to bax mRNA significantly decreased. Conclusions: These results suggest that apoptosis is associated with progression and regression of cellular proliferation in hypokalemic nephropathy, and a decrease in Bcl-2 may be involved in promoting this apoptotic process.

Hypokalemia induces renal injury and alterations in vasoactive mediators that favor salt sensitivity.

We investigated the hypothesis that hypokalemia might induce renal injury via a mechanism that involves subtle renal injury and alterations in local vasoactive mediators that would favor sodium retention. To test this hypothesis, we conducted studies in rats with diet-induced K+ deficiency. We also determined whether rats with hypokalemic nephropathy show salt sensitivity. Twelve weeks of hypokalemia resulted in a decrease in creatinine clearance, tubulointerstitial injury with macrophage infiltration, interstitial collagen type III deposition, and an increase in osteopontin expression (a tubular marker of injury). The renal injury was greatest in the outer medulla with radiation into the cortex, suggestive of an ischemic etiology. Consistent with this hypothesis, we found an increased uptake of a hypoxia marker, pimonidazole, in the cortex. The intrarenal injury was associated with increased cortical angiontensin-converting enzyme (ACE) expression and continued cortical angiotensin II generation despite systemic suppression of the renin-angiotensin system, an increase in renal endothelin-1, a decrease in renal kallikrein, and a decrease in urinary nitrite/nitrates and prostaglandin E(2) excretion. At 12 wk, hypokalemic rats were placed on a normal-K+ diet with either high (4%)- or low (0.01%)-NaCl content. Despite correction of hypokalemia and normalization of renal function, previously hypokalemic rats showed an elevated blood pressure in response to a high-salt diet compared with normokalemic controls. Hypokalemia is associated with alterations in vasoactive mediators that favor intrarenal vasoconstriction and an ischemic pattern of renal injury. These alterations may predispose the animals to salt-sensitive hypertension that manifests despite normalization of the serum K+.

Expression of insulin-like growth factor-I and transforming growth factor-β in hypokalemic nephropathy in the rat

Potassium deficiency (KD) in the rat retards body growth but stimulates renal enlargement caused by cellular hypertrophy and hyperplasia, which is most marked in the outer medulla. If hypokalemia persists, interstitial infiltrates appear and eventually fibrosis. Since early in KD insulin-like growth factor-I (IGF-I) levels in the kidney are elevated, suggesting that it may be an early mediator of the exaggerated renal growth, and as transforming growth factor-beta (TGF-beta) promotes cellular hypertrophy and fibrosis, we examined the renal expression of these growth factors in prolonged KD. Rats were given a K-deficient diet or were pair fed or ad libitum fed a K-replete diet for 21 days. Growth factor mRNA levels were measured in whole kidney and protein expression localized by immunohistochemistry. KD rats weighed less than pair-fed controls, while the kidneys were 49% larger. Their serum IGF-I and kidney IGF-I protein levels were depressed, as were their IGF-I mRNA levels in liver, kidney, and muscle. These changes can largely be attributed to decreased food intake. In contrast, kidney IGF binding protein-1 (IGFBP-1) mRNA and TGF-beta mRNA levels were increased significantly. Histology of outer medulla revealed marked hypertrophy and adenomatous hyperplasia of the collecting ducts and hypertrophy of the thick ascending limbs of Henle with cellular infiltrates in the interstitium. Both nephron segments immunostained strongly for IGF-I and IGFBP-1, but only the nonhyperplastic enlarged thick ascending Henle limb cells immunostained for TGF-beta, which was strongly positive. Prominent interstitial infiltrates with ED1 immunostained monocytes/macrophages were present. These findings are consistent with a sustained role for IGF-I in promoting the exaggerated renal growth of KD and appear to be mediated through local trapping of IGF-I by the overexpressed IGFBP-1, which together with IGF-I can promote renal growth. The selective localization of TGF-beta to hypertrophied nonhyperplastic nephron segments containing IGF-I raises the possibility that TGF-beta may be serving to convert the mitogenic action of IGF-I into a hypertrophic response in these segments. It is also conceivable that TGF-beta may be a cause of the tubulointerstitial infiltrate. Finally, the low circulating IGF-I levels likely contribute to the impaired body growth.

Licorice‐induced hypokalemic myopathy and hypokalemic renal tubular damage in anorexia nervosa

A patient with a history of anorexia nervosa developed licorice-induced hypokalemic myopathy. With potassium replacement, high CPK blood level and myopathic signs returned to normal. However, the patient manifested persistent hypokalemia and impaired renal function to concentrate and acidify the urine. Renal biopsy demonstrated intense degeneration and vacuolation of tubules with a normal glomerus which was consistent with hypokalemic nephropathy. Prolonged hypokalemia in anorexia nervosa is sometimes attributed to surreptitious purging or taking diuretics, but it is necessary to check the urine pH, the urine-specific gravity, and the urine potassium level in order to find underlying renal damage even after hypokalemic myopathy is treated successfully. © 1999 John Wiley & Sons, Inc. Int J Eat Disord 26: 111–114, 1999.

Albuminuria in untreated patients with primary aldosteronism or essential hypertension

The determinants and significance of urinary albumin excretion have been studied in normal subjects and in hypertensive patients; however, they are unknown in patients with primary aldosteronism. From a population of 114 patients with documented primary aldosteronism, we selected 23 never-treated patients (12 males, 11 females; 11 tumoral, 12 non-tumoral) and compared them to patients with never-treated essential hypertension with low renin (supine plasma renin activity <1 ng/ml per h, n = 23) or normal renin (supine plasma renin activity between 1 and 4 ng/ml per h, n = 23), matched for age, body mass index, mean arterial pressure, renal function and known duration of hypertension. The patients with primary aldosteronism had lower serum potassium and higher plasma aldosterone concentrations than those with essential hypertension. Urinary albumin and beta2-microglobulin excretion were greater in untreated patients with primary aldosteronism than in those with low- or normal-renin essential hypertension. Among the patients with essential hypertension, the renin activity was not a determinant of albuminuria. These findings indicate that primary aldosteronism is associated with excessive urinary albumin excretion. This albuminuria could be due to impairment of proximal tubular reabsorption caused by hypokalemic nephropathy and/or by high levels of circulating aldosterone; however, it could be an indicator of target-organ damage associated with primary aldosteronism.

Mineralocorticoid hypertension and congenital deficiency of 11β‐hydroxysteroid dehydrogenase in a family with the syndrome of‘apparent’mineralocorticoid excess

The so-called syndrome of 'apparent mineralocorticoid excess' (AME) is a rare cause of endocrine hypertension thought to result from a defect in the peripheral conversion of cortisol to cortisone. Less than 30 cases have been described. From a consanguineous marriage we present a family comprising 2 and probably 3 affected cases of AME. The index case is a 4-year-old boy with mineralocorticoid hypertension, short stature, failure to thrive, hypokalaemic nephropathy and osteopenia. The ratio of the urinary excretion of tetrahydrocortisone/tetrahydrocortisols was reduced at 0.05 (reference range 1.77-2.11), and the plasma half-life of 3H-11 alpha-cortisol elevated at 152 minutes (reference range 30-50) indicative of severe 11 beta-hydroxysteroid dehydrogenase deficiency. Plasma cortisol concentrations were normal and daily secretion rate reduced. Dexamethasone administration induced a natriuresis in keeping with the observation that cortisol itself is the implicated mineralocorticoid. Treatment with amiloride lowered blood pressure, increased potassium levels, and resulted in an increase in growth rate. The boy's twin brother died at the age of 3.5 years following a trivial diarrhoeal illness and was almost certainly affected. AME was also diagnosed in a younger brother (age 17 months), but both parents are normal. Congenital deficiency of 11 beta-hydroxysteroid dehydrogenase should be considered in any child with mineralocorticoid hypertension and failure to thrive. As cortisol is the 'offending' mineralocorticoid in this condition, the term 'apparent' mineralocorticoid excess is perhaps obsolete.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of potassium deficiency and gossypol on urinary N-acetyl-β-glucosaminidase excretion in the rat

Some men receiving gossypol in China developed elevated urinary N-acetyl-β-glucosaminidase (NAG) levels and hypokalemia. Since idiopathic hypokalemia occurs in China, hypokalemic nephropathy may have caused the elevated NAG levels. To learn if gossypol is directly nephrotoxic, we treated rats with a normal or low potassium diet with or without gossypol. The low potassium diet produced high NAG levels rather than the gossypol. This indicates the importance of differentiating hypokalemic nephropathy from drug nephrotoxicity in regions where idiopathic hypokalemia occurs.

Sleep Apnea Syndrome and End-stage Renal Disease: Cure After Renal Transplantation

We report two patients undergoing maintenance hemodialysis who presented with sleep apnea syndrome (SAS). The first patient is a 36-year-old man with a terminal Berger's glomerulopathy and associated obstructive sleep apnea syndrome (OSAS) (apnea-hypopnea index [AHI] = 80). He was receiving home hemodialysis and was treated by nasal continuous positive airway pressure (CPAP). After successful renal transplantation, his symptoms completely disappeared, and control polysomnography greatly improved (AHI = 9). The second patient had hypokalemic nephropathy with severe, uncontrolled hypertension and hypertensive myocardiopathy. He was receiving home dialysis and showed a central sleep apnea syndrome with an AHI of 51. He also was successfully treated by nasal CPAP. After renal transplantation, his sleep improved, insomnia disappeared, and polysomnography showed great improvement (AHI = 5). We discuss the role of periodic breathing related to end-stage renal disease associated metabolic abnormalities, as a pathogenetic factor of these SASs. Respiratory correction of chronic metabolic acidosis, "uremic toxins," "middle molecules," and hemodialysis are all evoked as etiologic factors and their own roles are discussed.

Selective zonal change of the renomedullary interstitial cells in hypokalemic rats.

Electron microscopic morphometry was undertaken to quantitate the morphological change of the renomedullary interstitial cells (RIC) of hypokalemic rats by using large montages. Two weeks of potassium depletion resulted in an increase of the RIC, which were restricted to the interbundle region of the inner stripe of the outer medulla. The increase of the RIC is characterized by a preferential increase in volume density (+340.0%; P < 0.01) and numerical density (+61.4%; P < 0.01) in the interbundle region but not in the vascular bundle of the inner stripe or in the inner medulla. The increased RIC in the interbundle region of the inner stripe demonstrated an increase of lipid droplets, which are known to contain prostaglandin precursors. The selective zonal change of RIC with increased lipid droplets is a characteristic lesion of hypokalemic rats and suggests an enhanced vasoactive function of RIC associated with hypokalemic nephropathy.

Increased Ammoniagenesis as a Determinant of Progressive Renal Injury

Loss of renal mass evokes increased ammoniagenesis in surviving nephrons, which in turn enables net acid excretion by the kidney. However, this compensatory increase in ammonia production in surviving nephrons triggers the alternative complement pathway, thereby instigating progressive tubulointerstitial injury. Ammonia has recently been identified as a stimulus to renal growth. Enhanced renal growth may serve as a forerunner for renal injury. The growth-promoting properties of ammonia may provide another mechanism through which augmented ammoniagenesis may underlie the enhancement of renal growth and injury observed in such models as the remnant kidney, hypokalemic nephropathy, high protein feeding, experimental diabetes nephropathy, and dietary deficiency of antioxidants.

Hypokalemic nephropathy in the rat. Role of ammonia in chronic tubular injury.

Chronic potassium deficiency results in progressive tubulointerstitial injury, associated with augmented renal ammoniagenesis. We investigated the role of elevated renal ammonia levels and the interaction of ammonia with the complement system in this injury. Potassium deficiency was induced in rats by feeding a low potassium diet. Experimental animals received 150 mM NaHCO3 or equimolar NaCl, as drinking water. After 3 wk, NaHCO3 supplemented rats demonstrated decreased ammonia production, less renal hypertrophy, less histologic evidence of injury, and less proteinuria. In in vitro studies on normal cortical tubular fragments, the addition of ammonia to serum in concentrations comparable to renal cortical levels in potassium-deficient animals significantly increased tubular deposition of C3 as quantitated by a radiolabeled antibody binding technique. Thus, alkali supplementation reduced chronic tubulointerstitial disease in a rat model of hypokalemic nephropathy. We propose that increased cortical ammonia levels contribute to hypokalemic nephropathy through ammonia-mediated activation of the alternative complement pathway.

Medical consequences of eating disorders.

While much has appeared in the recent literature about various psychotherapeutic techniques used to treat eating disorders, little attention has been paid to the medical complications. Prominent among these are heart damage, failure of the endocrine system, infarction and perforation of the stomach after acute dilatation, multiple suicide attempts, aspiration, injury or rupture of the esophagus, severe bleeding per rectum causing anemia due to laxative abuse, hypokalemic nephropathy, depressive disorders due to starvation, and severe erosion of the enamel of the teeth resulting in extensive loss of teeth. I decry the sudden trend of nonmedically trained personnel rushing into the treatment of eating disorders, particularly anorexia nervosa and bulimia, because they know little about the possibly fatal consequences of their failure to attend to some of these medical phenomena. I also note with grave concern the identification of the medical profession with the "thin is better" mentality of our culture, which blinds them to the serious medical consequences of eating disorders.

In common clinical usage nonsteroidal anti-inflammatory drugs infrequently produce adverse effects on the kidney.

EACH DAY, well over 5 million people are exposed to various nonsteroidal antiinflammatory drugs (NSAIDs) in the United States. This figure derives from data on naproxen, sulindac, indomethacin, ibuprofen, benoxaprofen, piroxicam and other nonsteroidal drugs. 1 The number is clearly an underestimate since it does not include aspirin. Moreover, we know that about one percent of the population have rheumatoid arthritis (2.3 million) while another one percent has spondylarthritis. 2 Of the several million more who have degenerative joint disease, many are receiving daily NSAIDs. To these must be added the many individuals who regularly take aspirin for poorly defined reasons, ingesting, together, hundreds of tons per year. In one recent survey, some ten percent of patients admitted over a one-week period to a Veterans Administration Hospital were taking NSAIDs.3 How many of these individuals are at risk for nephrotoxicity from these agents? Opinion is roughly divided between those who assume the risk is virtually nil (they divide the vast denominator at risk by the tiny number of case reports) and those who consider that nonsteroidals are guilty, (they rememeber the anecdotes and have a particularly sensitive appreciation of renal physiology) until proved innocent! Few people take the middle ground. In this debate, we are more fortunate than in many other biomedical discussions. We do have the facts. It is now well-recognized that prostaglandins are important modulators of the hemodynamic and excretory functions of the kidney. These unsaturated fatty acids are synthesized from arachidonate precursors, a process regulated by intrarenal factors, circulating angiotensin II, catecholamines, vasopressin, bradykinin and, no doubt, other chemicals (4). Salt and water excretion is modified by the effects of prostaglandins on glomerular filtration rate, proximal tubal fluid reabsorption, medullary solute gradients, and the water and ion reabsorptive properties of distal nephron segments. Likewise, prostaglandins mediate renin release under normal conditions and, particularly, in response to intravascular volume depletion. In a variety of clinical disorders, renal prostaglandins are considered to be abnormal. These processes include hypertension, ureteral obstruction, Bartter's syndrome, hypokalemic nephropathy, and drug-induced disorders of water metabolism. Nevertheless, it should be stressed that there is not a consensus concerning the physiologic importance of the prostaglandin system on renal function. This results from the technical and physiological problems in defining the role of renal prostaglandins. 5 At issue is the role of prostaglandins in the maintenance of normal renal function in normal individuals, as compared to their action to maintain renal function in individuals with renal compromise. Most investigators agree that the prostaglandins become progressively more active with deteriorating renal function. What role do NSAIDs have in complicated clinical situations? The renal effects of drugs that inhibit prostaglandin synthesis have been debated for several years. It must be remembered that it is dangerous to extrapolate from the in vitro situation to the in vivo condition, or from extrarenal location to the kidney. For example, acetylsalicylic acid acetylates platelet cyclooxygenase irreversibly, resulting in inhibition for the life of the cell. By contrast, renal cyclooxygenase turnover, is rapid and aspirinmediated inhibition disappears within 48 hr. fi The other NSAIDs inhibit cyclo-oxygenase reversibly and disassociate from the cyclooxygenase molecule resulting in inhibitory effects that are progressively attenuated over

Arachidonic acid metabolism, prostaglandins and the kidney

Renal prostaglandins are gaining increasing recognition as important modulators of hemodynamics and excretory function in the mammalian kidney. Synthesis of these unsaturated fatty acids from arachidonate precursors is closely regulated by intrarenal factors, and circulating angiotensin II, catecholamines, arginine vasopressin and bradykinin. Endogenous prostaglandins exert little influence on renal blood flow and glomerular filtration rate in the basal state, but inhibition of arachidonate metabolism when renal perfusion is impaired causes marked alterations in these parameters. Renal salt and water excretion is modified by the effects of prostaglandins on glomerular filtration rate, proximal tubule fluid reabsorption, medullary solute gradients, and the intrinsic water and ion reabsorptive properties of distal nephron segments. Prostaglandins also mediate renin release under basal conditions and in response to intravascular volume depletion. Abnormalities of renal prostaglandins are evident in various clinical disorders of renal function including hypertension, ureteral obstruction, Bartter syndrome, hypokalemic nephropathy and drug-induced disorders of water metabolism. Appropriate clinical use of nonsteroidal anti-inflammatory agents requires consideration of the potential renal consequences of inhibiting prostaglandin biosynthesis.