Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The N-phenylsuccinimides are being evaluated as experimental agricultural fungicides. The purpose of this study was to examine the relationship between the electron withdrawing or electron donating properties of phenyl ring substituents on meta-substituted N-phenylsuccinimide (NPS) derivatives and the nephrotoxic potential of the corresponding fungicides. Male Fischer 344 rats were administered a single intraperitoneal injection of a succinimide (0.4 or 1.0 mmol/kg) or vehicle (sesame oil, 2.5 ml/kg), and renal function monitored at 24 and 48 hr. Non-halogen-substituted NPS derivatives produced little evidence of nephrotoxicity at the doses used in this study. Among the meta-halogen derivatives of NPS, N-(3-chlorophenyl)succinimide (NCPS) was the most nephrotoxic. NCPS-induced nephrotoxicity was characterized by diuresis, proteinuria, hematuria, elevated blood urea nitrogen (BUN) concentration, decreased organic ion accumulation and proximal tubular necrosis. However, all renal effects produced by NCPS were mild to moderate. These results suggest that the electron withdrawing or donating property of a functional group is not a good predictor of the nephrotoxic potential for the corresponding fungicide. In addition, lipophilicity did not correlate with nephrotoxic potential for the meta-substituted NPS derivatives evaluated in this study.
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PMID:Structure-nephrotoxicity relationships for meta-substituted N-phenylsuccinimides. 362 73

Ibuprofen-associated, acute, reversible renal failure with hyperkalemia, tubular necrosis, and proteinuria developed in a patient who had no predisposing underlying disease. A renal biopsy specimen revealed mesangial hypercellularity without glomerular crescent formation. A profound interstitial nephritis with focal inflammatory cell infiltrates of predominantly mononuclear cells and neutrophils as well as focal tubular destruction was seen. Vasculitis was not observed. Ultrastructural studies confirmed the light microscopic diagnosis of a tubulointerstitial nephritis and, in addition, indicated the presence of electron-dense mesangial and subepithelial deposits. Direct immunofluorescence examination showed diffuse mesangial IgM and C3 deposition as well as vascular C3 deposition. Renal failure rapidly resolved after discontinuation of ibuprofen therapy and initiation of steroid therapy, with return to normal levels of serum creatinine, urea nitrogen, potassium, and sodium. Proteinuria also resolved.
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PMID:Ibuprofen-associated renal dysfunction. Pathophysiologic mechanisms of acute renal failure, hyperkalemia, tubular necrosis, and proteinuria. 368 62

Previous studies have shown that the experimental agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) produces acute nephrotoxicity via a reactive intermediate in Sprague-Dawley and Fischer-344 rats. The purpose of this study was to examine if an arene oxide intermediate is a toxic metabolite contributing to NDPS-induced nephropathy in rats. N-(3,4,5-Trichlorophenyl)succinimide (NTPS) was prepared to prevent arene oxide formation of NDPS, and its nephrotoxic potential was determined in Sprague-Dawley and Fischer-344 rats. Rats were administered a single intraperitoneal injection of NTPS (0.4 or 1.0 mmol/kg) or sesame oil (2.5 ml/kg), and renal function was monitored at 24 and 48 h. NTPS (0.4 or 1.0 mmol/kg) administration produced diuresis, proteinuria, glucosuria, hematuria, decreased accumulation of p-aminohippurate (PAH) and tetraethylammonium (TEA), and increased blood urea nitrogen (BUN) and kidney weight in both strains. Extensive proximal tubular necrosis was observed in both strains of rat. The magnitude of these effects was similar to those previously reported for NDPS-induced nephrotoxicity in Sprague-Dawley and Fischer-344 rats. It was concluded that an arene oxide metabolite does not contribute to the nephrotoxic potential of NDPS. The results of the present study indicate that lipophilic character alone is not a good predictor of the nephrotoxic potential for NDPS and NTPS.
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PMID:Acute N-(3,4,5-trichlorophenyl)succinimide-induced nephrotoxicity in Sprague-Dawley and Fischer-344 rats. 372 98

Deuterium labelling of the succinimide ring of N-(3,5-dichlorophenyl) succinimide (NDPS) markedly reduced the acute nephrotoxicity produced by NDPS administration to Fischer 344 rats. Administration of the deuterium-labelled derivative, NDPS-d4, to male Fischer 344 rats failed to produce the marked diuresis, increased proteinuria, glucosuria, hematuria, elevated blood urea nitrogen (BUN) concentration and kidney weight, decreased basal p-aminohippurate (PAH) accumulation, and proximal tubular necrosis which are characteristic of NDPS-induced nephrotoxicity. However, lactate-stimulated PAH and tetraethylammonium (TEA) accumulation were decreased by NDPS-d4 (1.0 mmol/kg). The lack of nephrotoxicity produced by NDPS-d4 suggests that oxidation at the carbon-carbon bridge of the succinimide ring is an important biotransformation step in the generation of the nephrotoxic species of NDPS.
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PMID:Deuterium isotope effect in acute N-(3,5-dichlorophenyl)succinimide-induced nephrotoxicity. 376 9

Deisopropylngaione (DIN) is one of a family of hepatotoxic furanosesquiterpenoid essential oils which is found in small amounts (5%) in the leaves of some specimens of the Australian plant Myoporum deserti. DIN differs from other furanoid myoporaceous essential oils in that it also causes lesions in the lungs and kidneys. At the near LD50 dose rate of 150 mg kg-1 given by intraperitoneal injection, DIN is able to cause lethal renal proximal tubular necrosis without causing significant injury to the liver and lungs in adult male mice. Following dosing, there is an increase in kidney weight due mainly to increase in water content which reaches a maximum within 16-24 h. This is accompanied by degeneration and necrosis of the proximal tubular epithelium, with proteinuria and glucosuria lasting up to 9 days in non-lethally affected mice. Marked body weight loss due to the intoxication causes a marked increase in the kidney weight:body weight ratio lasting between 9 and 18 days. Residual lesions are still present in the kidneys at 32 days, but recovery is eventually complete. DIN is structurally similar to the sweet potato toxic furan 4-ipomeanol and, like the latter, is probably injurious to the kidneys through toxic metabolism by the cytochrome-P450-containing monooxygenases of the proximal tubular epithelium. Although slight renal injury is occasionally observed in livestock poisoned by myoporaceous plants, it is unlikely that DIN is the cause. So far, DIN, like 4-ipomeanol, appears to be unequivocally nephrotoxic only for the male mouse.
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PMID:The nephrotoxicity for mice of deisopropylngaione, a minor furanoid component of toxic myoporaceous essential oils. 398 17

A case of fatal acute renal failure during treatment with 1,1-diaminomethyl cyclohexane sulphato platinum II (TNO-6) is reported. Pathologic investigation showed focal tubular necrosis with interstitial infiltration and edema. Despite the development of proteinuria no changes of the glomeruli were found, either by light or electron microscopic investigation. The pathologic changes caused by TNO-6 are similar to those found in renal failure caused by cisplatin (CDDP).
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PMID:TNO-6-induced acute renal failure. A case report. 402 87

Renal structural changes were studied sequentially between 1 hour and 6 days in rats treated with D-serine. Extensive necrosis of proximal straight tubules was rapid in onset and was followed by complete tubular regeneration 6 days post-treatment. The apparent progression of cellular changes was initial shrinkage, followed either by swelling and loss of apical cytoplasm or immediate lysis of cytoplasmic and nuclear contents. Tubular damage left only the basement membrane as a barrier between interstitial and luminal fluids. In similarly treated rats, proteinuria and glucosuria developed at the onset of tubular necrosis and disappeared when the tubules were completely relined by epithelium suggesting that they are due to diffusion of protein and glucose from interstitium into tubular fluid across the denuded basement membranes and that epithelial cells, under normal conditions, act as a barrier to diffusion of certain substances between the interstitium and tubular fluid.
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PMID:The nature of D-serine--induced nephrotoxicity. 444 30

1. Administration of frusemide or ethacrynic acid to cephaloridine-treated mice increased both the incidence and extent of proximal renal tubular necrosis compared with that obtained in cephaloridine-treated control mice.2. Administration of frusemide to cephaloridine-treated rats produced significant changes in urine output, electrolyte excretion and proteinuria, and plasma urea nitrogen and creatinine values were significantly increased compared with controls or rats that received frusemide or cephaloridine alone.3. Histological examination of the kidneys showed a higher incidence and greater extent of tubular necrosis in rats that received both frusemide and cephaloridine.4. It is suggested that this adverse drug interaction may have contributed to the deterioration in renal function observed in some patients treated with diuretics and cephaloridine concurrently.
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PMID:Enhancement by potent diuretics of renal tubular necrosis induced by cephaloridine. 549 95

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

Rapidly progressive renal failure developed in four patients with silica exposure. Three presented with manifestations of a connective tissue disorders. All had abnormal proteinuria, hypoalbuminemia and active urinary sediments. Histologically, a distinct constellation of findings was present, consisting of glomerular hypercellularity and sclerosis, crescents, interstitial cellular infiltrates and tubular necrosis with red cell casts as seen on light microscopy. On electron microscopy there was foot process obliteration, characteristic cytoplasmic dense lysosomes, microtubules and dense deposits. Despite vigorous treatment, two patients died of the systemic illness and one is on hemodialysis. The fourth is improved after pulse methylprednisolone therapy. We propose that silica induced this multisystem disease through activation of the immune system and a direct tissue toxic effect.
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PMID:Rapidly progressive silicon nephropathy. 627 74


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