Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032617 (polyuria)
 3,056 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of cadmium intoxication on renal transport systems for various amino acids were studied. Subcutaneous injections of CdCl2, at a dose of 2 mg Cd/kg.day for 2 weeks, resulted in polyuria, proteinuria, glycosuria, phosphaturia, and aminoaciduria, as observed in chronic cadmium-intoxicated humans and experimental animals. The nature of aminoaciduria was nonspecific, including iminoacid as well as almost all species of neutral, acidic, and basic amino acids. In renal cortical brush border membrane vesicles isolated from cadmium-intoxicated rats, Na(+)-dependent transport of L-proline, L-alanine, and L-lysine was markedly attenuated, whereas the amino acid transport in the basolateral membrane vesicle was not significantly affected. Similar results were obtained in the normal membrane vesicles directly exposed to inorganic cadmium. These results indicate that cadmium intoxication impairs various Na(+)-amino acid cotransport systems in the renal brush border membrane, which leads to panaminoaciduria.
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PMID:Alteration of renal amino acid transport system in cadmium-intoxicated rats. 225 75

Effects of cadmium intoxication on renal transport systems for various organic compounds were studied. Subcutaneous injections of CdCl2 (2 mg Cd/kg.day) for two to three weeks induced marked polyuria, glycosuria, and proteinuria without altering glomerular filtration rate. In renal cortical brush border membrane vesicles (BBMV) isolated from cadmium treated rats, Na(+)-dependent D-glucose uptake was markedly attenuated, and this was due to reduction in Vmax and not Km. Likewise, Na(+)-driven L-glutamate transport and H(+)-driven tetraethylammonium transport were significantly reduced. In renal cortical basolateral membrane vesicles (BLMV) of cadmium intoxicated rats, Na(+)-dependent succinate transport was drastically reduced. These results indicate that cadmium intoxication impairs various transport systems for organic compounds in the brush border and basolateral membranes of proximal renal tubules.
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PMID:Transport of organic compounds in renal plasma membrane vesicles of cadmium intoxicated rats. 240 86

A study was conducted to investigate nephritogenic tubular basement membrane antigens common to human and rat kidneys. Brown Norway (BN) rats were immunized with human renal basement membrane in complete Freund's adjuvant simultaneously with Bordetella pertussis vaccine. The immunized rats developed polyuria and increased levels of serum creatinine one week after the second immunization. Renal histology at this time revealed marked, acute tubulointerstitial nephritis with linear deposition of IgG and C3 along the tubular basement membrane and Bowman's capsule, but not along the glomerular basement membrane. Rats with this tubulointerstitial nephritis rapidly developed antibodies against renal antigens from normal BN rats such as tubular basement membrane and proximal tubule brush border, however antibodies to glomerular basement membrane appeared later. Western blotting using the same rat sera detected a 145-kDa antigen from 8 M urea-solubilized human renal basement membrane and 120-kDa, 135-kDa and 145-kDa antigens from 8 M urea-solubilized BN rat renal basement membrane. This suggests that renal basement membranes of human and rat origin have common antigens involved in the pathogenesis of tubulointerstitial nephritis.
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PMID:Induction of interstitial nephritis in rats by basement membrane of human origin. 268 56

In exploratory studies aimed at elucidating CNS effects due to heavy metal toxicity, signs of compromised renal function were seen in rats. The studies reported here describe the sequential steps of the development of nephrotoxicity by trimethyltin chloride (TMT) in rats. Single doses of 12.25 mg/kg TMT administered orally to 150- to 175-g Long-Evans rats elicited overt signs of toxicity including behavioral abnormalities and marked weight loss. Concurrent with the development of these signs, nephrotoxicity was manifested as functional kidney compromise and associated histopathologic evidence of tubular damage. Pathological changes in the kidneys from treated rats were hyaline droplet inclusions, attenuated brush border, basolateral vacuolization, and eosinophilic granular casts in the proximal tubule cells. These lesions were detected as early as 2 days post-treatment and progressed with time in an orderly and sequential fashion. Renal lesions between 5 and 8 days were mild to severe cortical tubular dilatation, hydropic degeneration, and diffuse hyaline droplet deposition in the lower nephron tubules. Medullary edema and exfoliation of degenerated tubular epithelial cells with cast formation followed from 8 to 11 days. The morphological changes were accompanied by marked elevation of blood urea nitrogen, parallel with polyuria at Day 2 and oliguria by Day 14. Behavioral abnormalities as well as weight loss correlated well with the time course and severity of renal dysfunction and progression of morphological changes. A second experiment compared the effects of TMT in rats of different weights. Heavier rats were more sensitive than lighter rats to the nephrotoxic effects of TMT. These effects were independent of recognizable neurotoxic effects of TMT in the hippocampus.
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PMID:The pathogenesis of trimethyltin chloride-induced nephrotoxicity. 355 27

Chronic administration of cyclosporin A (CyA) to animals and humans results in renal damage characterized by tubulointerstitial lesions and renal insufficiency. This nephrotoxicity limits the use of CyA in the management of graft rejection. Despite recent investigations in this area, relatively few studies correlate structural and functional abnormalities in animals undergoing long-term CyA treatment. The authors therefore treated 30 rats with CyA at the dose of 40 mg/kg/48 hr for up to 5 months. An additional group of 30 rats was given the vehicle alone and was considered as a control group. Renal morphology and function were studied. For evaluation of the effect of drug withdrawal, a third group of 25 animals received CyA for 3 months and was followed for another 2 additional months after drug withdrawal. The results show that the chronic administration of CyA to rats induced complex renal morphologic changes, associated with renal insufficiency, polyuria, and enhanced sodium excretion. Withdrawal of the drug resulted in almost complete normalization of morphologic and functional parameters. The early morphologic expression of CyA nephrotoxicity was isometric vacuolization and loss of brush border involving the proximal tubular cells, followed by a peculiar lesion in distal tubular cells due to glycogen accumulation. Glomerular and interstitial damage was mild and appeared only after 3 months of CyA administration. No vascular abnormalities were found in rats treated with CyA for 5 months. A CyA-induced decrease in the glomerular filtration rate (GFR) correlates with brush border loss but not with isometric vacuolization. The distal tubular glycogen accumulation was associated with the development of polyuria and enhanced sodium excretion. Given the high blood sugar level and severe glycosuria in animals treated chronically with CyA, it is also concluded that CyA possesses a diabetogenic effect which is likely to be responsible for glycogen accumulation at the tubular level.
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PMID:Renal injury induced by long-term administration of cyclosporin A to rats. 359 4

Two young siblings had a syndrome of growth retardation, severe rickets, anemia, renal insufficiency, and renal tubular dysfunction, the last including acidosis, aminoaciduria, and polyuria. There was moderate psychomotor developmental delay. Neither child had cystinosis. Renal biopsy in the older child revealed severe glomerular abnormalities, with capillary wall thickening reminiscent of the hemolytic-uremic syndrome. The proximal convoluted tubules were lined with short, cuboidal cells containing mildly abnormal mitochondria. There was also thinning of brush border microvilli and basolateral infoldings, perhaps as the result of regressive changes, and interstitial fibrous tissue was moderately increased. The etiology of the tubular and glomerular changes is uncertain. We believe these patients represent a previously unreported hereditary syndrome sharing certain clinical features with severe nephropathic cystinosis.
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PMID:A familial syndrome of growth retardation, severe Fanconi-type renal disease and glomerular changes--a new entity? 372 23

Antibiotics are the principal cause of drug-associated nephropathy. They are responsible for acute interstitial nephropathy (AIN) or acute tubulo-interstitial nephropathy (ATIN) due to two different pathophysiologic mechanisms: a drug-induced immunologic process and direct action due to drug accumulation. 1) Ain of immunologic origin. These are rare and are induced either by beta-lactamines or by rifampicin. Among the beta-lactamines, methicillin is the most often responsible, while penicillin and ampicillin are less often, and only rarely are carbenicillin, oxacillin, nafcillin, cephalothin and cephalexin. Macroscopic hematuria occurring 10 to 15 days after initiation of treatment usually reveals the renal involvement. It is associated with or preceded by fever, skin eruption and blood eosinophilia. Renal insufficiency (RI) is not severe and rarely requires hemodialysis (HD). The course is usually favorable. Rifampicin-induced AIN is observed in two circumstances, either during intermittent treatment or when previous treatment is resumed. Macroscopic hematuria is rare and RI often severe. Anti-rifampicin anti-bodies are usually found. 2) ATIN due to direct toxicity. Several classes of antibiotics may be responsible: cephalosporins, polymyxins or cyclins, but it is usually observed with aminoglycosides (AG). The incidence of renal involvement due to the latter group is estimated to be 4 to 10%. Nephrotoxicity is initially reflected by polyuria, tubular proteinuria and increased enzymuria, followed by cylindruria and reduced glomerular filtration. HD is rarely required. The proximal tubule is predominantly affected; pathological findings are disappearance of the brush border and tubular necrosis. Electronic microscopy shows lysosomal alterations with numerous myelinic bodies. Tubular regeneration occurs within 15 to 30 days.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antibiotic nephrotoxicity. 610 Jan 74

Insulin stimulates reabsorption of phosphate (Pi) in the renal proximal tubule. Previous studies have shown that vanadate can mimic the action of insulin on various tissues. In the present study, we tested the action of vanadate on renal Pi transport both in control rats and in rats made diabetic by injection of streptozotocin. Vanadate was administered orally for 4 days by inclusion in drinking water (0.7 mg/ml). By the 4th day, vanadate treatment of control rats did not change acid-base status, plasma glucose or the filtered load of Pi, but the urinary excretion of Pi was reduced to 2.5 +/- 0.9 compared with 17.6 +/- 3.5 mumol/mg creatine (P < 0.02) in untreated control rats. However, Na+/Pi cotransport by isolated brush border membrane vesicles was not different between the two groups. Findings in parathyroidectomized rats were similar. By the 4th day of vanadate treatment of diabetic rats, there was reversal of polyuria, polydipsia and hyperglycemia with no change in acid-base status. The filtered load of Pi was decreased by vanadate, and urinary Pi excretion also tended to decrease but not significantly. The values for Pi excretion were 21.4 +/- 7.6 in vanadate treated diabetics and 36.1 +/- 4.5 mumol/mg creatinine in untreated diabetics. In contrast to vanadate, daily injections of insulin did not change the filtered load of Pi but reduced urinary Pi excretion in diabetic rats to 15.6 +/- 2.2 mumol/mg creatinine (P < 0.02). These findings suggest that vanadate stimulated tubular Pi reabsorption in control rats but not in diabetic rats. Vanadate treatment of diabetic rats may tend to decrease tubular Pi reabsorption in contrast to the action of insulin.
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PMID:Vanadate action on renal phosphate transport. 793 28

The discovery of aquaporin-1 (AQP1) by Agre and associates answered the longstanding biophysical question of how water specifically crosses biological membranes. In the kidney at least 7 aquaporins are expressed at distinct sites. AQP1 is extremely abundant in the proximal tubule and descending thin limb and is essential for urinary concentration. AQP2 is exclusively expressed in the principal cells of the connecting tubule and collecting duct and is the predominant vasopressin-regulated water channel. AQP3 and AQP4 are both present in the basolateral plasma membrane of collecting duct principal cells and represent exit pathways for water reabsorbed apically via AQP2. Studies in patients and transgenic mice have shown that both AQP2 and AQP3 are essential for urinary concentration. Three additional aquaporins are present in the kidney. AQP6 is present in intracellular vesicles in collecting duct intercalated cells and AQP8 are present intracellularly at low abundance in proximal tubules and collecting duct principal cells but the physiological function of these 2 channels remain undefined. AQP7 is abundant in the brush border of proximal tubule cells and is likely to be involved in proximal tubule water reabsorption. A series of studies have underscored crucial roles of aquaporins for regulation of renal water metabolism and hence body water balance. Moreover it has become clear that dysregulation of aquaporins, and especially AQP2 is critically involved in many water balance disorders. Lack of functional AQP2 is seen in primary forms of diabetes insipidus, and reduced expression and targeting is seen in several diseases associated with urinary concentrating defects such as acquired nephrogenic diabetes insipidus, postobstructive polyuria, as well as acute and chronic renal failure. In contrast, in conditions with water retention such as severe congestive heart failure, pregnancy and SIADH both AQP2 expression levels and apical plasma membrane targetting is increased suggesting a role for AQP2 in the development of water retention. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiology and pathophysiology of water balance and water balance disorders.
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PMID:Physiology and pathophysiology of renal aquaporins. 1132 Apr 86

The discovery of aquaporin-1 (AQP1) answered the long-standing biophysical question of how water specifically crosses biological membranes. In the kidney, at least seven aquaporins are expressed at distinct sites. AQP1 is extremely abundant in the proximal tubule and descending thin limb and is essential for urinary concentration. AQP2 is exclusively expressed in the principal cells of the connecting tubule and collecting duct and is the predominant vasopressin-regulated water channel. AQP3 and AQP4 are both present in the basolateral plasma membrane of collecting duct principal cells and represent exit pathways for water reabsorbed apically via AQP2. Studies in patients and transgenic mice have demonstrated that both AQP2 and AQP3 are essential for urinary concentration. Three additional aquaporins are present in the kidney. AQP6 is present in intracellular vesicles in collecting duct intercalated cells, and AQP8 is present intracellularly at low abundance in proximal tubules and collecting duct principal cells, but the physiological function of these two channels remains undefined. AQP7 is abundant in the brush border of proximal tubule cells and is likely to be involved in proximal tubule water reabsorption. Body water balance is tightly regulated by vasopressin, and multiple studies now have underscored the essential roles of AQP2 in this. Vasopressin regulates acutely the water permeability of the kidney collecting duct by trafficking of AQP2 from intracellular vesicles to the apical plasma membrane. The long-term adaptational changes in body water balance are controlled in part by regulated changes in AQP2 and AQP3 expression levels. Lack of functional AQP2 is seen in primary forms of diabetes insipidus, and reduced expression and targeting are seen in several diseases associated with urinary concentrating defects such as acquired nephrogenic diabetes insipidus, postobstructive polyuria, as well as acute and chronic renal failure. In contrast, in conditions with water retention such as severe congestive heart failure, pregnancy, and syndrome of inappropriate antidiuretic hormone secretion, both AQP2 expression levels and apical plasma membrane targetting are increased, suggesting a role for AQP2 in the development of water retention. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiology and pathophysiology of water balance and water balance disorders.
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PMID:Aquaporins in the kidney: from molecules to medicine. 1177 13


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