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)

Recent experimental data has implicated growth hormone in the development of glomerular sclerosis. In this study, we have examined the development and progression of glomerular and tubulointerstitial scarring in Wistar and Dwarf rats, selectively growth hormone-deficient, following subtotal nephrectomy. Wistar rats showed progressive proteinuria, hypertension and renal failure as well as severe renal scarring 120 days after subtotal nephrectomy. In contrast, growth hormone-deficient Dwarf rats had minimal proteinuria, mild renal functional impairment and moderate renal histological scarring. The difference in these functional and structural parameters between the two strains is highly significant, although both experimental groups had comparable food consumption and systemic blood pressure. The significantly smaller glomeruli and limited kidney hypertrophy over 120 days observed in Dwarf rats may account for some of the protection against glomerular sclerosis and tubulointerstitial scarring observed in that strain.
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PMID:Role of growth hormone in the development of experimental renal scarring. 192 Nov 52

Recent experiments have shown that the kidney adapts to chronic variations in urine concentration. Glomerular filtration rate (GFR), kidney weight relative to body weight, thickness of inner stripe of the outer medulla, volume of epithelium in early thick ascending limb, and internephron heterogeneity are all decreased by chronic water diuresis and increased by chronic stimulation of urine concentration. It was further shown that the intrarenal pattern of hypertrophy observed after high protein (HP) intake, but not that observed after compensatory hypertrophy or normal growth with age, is exactly similar to that observed after chronic stimulation of urine concentration. Since solute-free water reabsorption (TcH2O) is markedly enhanced by HP diet, this suggests that the increases in GFR and renal mass observed after HP intake are, at least in part, an adaptive response of the kidney to increased urinary concentrating activity. The beneficial effects are induced by protein restriction in chronic renal failure (CRF) could thus be due, in part, to the reduction of this concentrating activity. This hypothesis was confirmed by an experiment performed in rats with experimental chronic renal failure (CRF) in which a chronic increase in water intake, reducing urine osmolality and TcH2O, without any change in food composition or consumption, reduced proteinuria, systemic hypertension, kidney hypertrophy, incidence of glomerulosclerosis, and mortality.
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PMID:Vasopressin-dependent kidney hypertrophy: role of urinary concentration in protein-induced hypertrophy and in the progression of chronic renal failure. 204 45

Spontaneously hypertensive rats (SHR) were uninephrectomized (UNX) at 6 wk of age and given either standard chow (CON), low-sodium chow (LSC), or standard chow and hydrochlorothiazide (HCTZ) added to the drinking water. Severe hypertension developed in all three groups. Forty-two weeks after UNX, proteinuria and glomerular sclerosis were significantly lower in LSC than in CON or HCTZ. The protective effect of salt restriction did not depend upon alterations in plasma renin concentration or glomerular hemodynamics. Micropuncture revealed that glomerular pressure was high in all three groups. Renal hypertrophy assessed by kidney weight, kidney-to-body weight ratio, glomerular volume, and glomerular capillary radius were reduced by salt restriction. These findings suggest that, in the setting of glomerular hypertension, hypertrophy promotes sclerosis. Salt restriction inhibits compensatory kidney growth and protects the kidney.
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PMID:Superiority of salt restriction over diuretics in reducing renal hypertrophy and injury in uninephrectomized SHR. 219 43

The effect of long-term treatment with either enalapril or high dose verapamil on survival, proteinuria, blood pressure and renal morphology was studied in female Wistar rats with markedly reduced renal mass. Four weeks were allowed for remnant kidney hypertrophy before determining the response to renal ablation of individual animals regarding proteinuria and hypertension. At this time, five groups of 18 rats were formed with equal levels of proteinuria and hypertension. Groups E1 and E2 were treated with enalapril, groups V1 and V2 with verapamil, and one group served as control. The daily food allowance was 14 g/rat of a standard rat diet, containing 30% protein and 100 mmol NaCl/kg food in groups E1 and V1. NaCl content was reduced to 20 mmol/kg food in groups E2, V2 and control. The drugs were added to the drinking water, enalapril at a dose of 0.1 g/liter, verapamil at 0.5 to 0.7 g/liter. Drug intake thus amounted to 10 to 25 mg/kg for enalapril and 50 to 140 mg/kg for verapamil. Treatment was continued for 15 weeks. Three of the 18 control rats did not survive up to 15 weeks. Mortality was lower in the enalapril treated groups with a single nonsurvivor in group E1. In contrast, mortality was higher in the verapamil treated animals with seven nonsurvivors in group V1 and eight in group V2. Blood pressure control was excellent in both enalapril treated groups. and proteinuria decreased in most animals of group E1 and all of group 22. Glomerulosclerosis did not develop in the majority of the enalapril treated animals. Despite the high dose, verapamil barely lowered blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term enalapril and verapamil in rats with reduced renal mass. 255 83

A 4-day drug schedule was used to explore the efficacy and simultaneous toxicity of cisplatin and 30 other platinum (II) amines given IP to PVG x Lew F1 hybrid rats at cumulative doses of 10-300 mumol/kg. Toxic effects monitored were stomach enlargement, kidney hypertrophy with tubular necrosis and proteinuria, evident visceral mucin, and lymphoid involution (thymus, spleen). Immunosuppressive effects were monitored as inhibition of the lymph node hypertrophy induced by grafting PVG spleen cells into each paw of F1 hybrids. No significant activity/toxicity was observed with 'platinum-(pyrimidine) blues'. N-alkyl derivatives of cisplatin were less active/toxic and some had no immunosuppressant effect, though they are reported as effective antitumour agents (in mice). mu-Hydroxobridged aminoplatinum (II) dimers were highly toxic, effective immunosuppressants and their toxicity profiles were distinct from the dihalo or diaquo diaminoplatinum species. 1,2-Diaminocyclohexane platinum derivatives showed a wide range of potency, all being much less nephrotoxic than cisplatin.
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PMID:Platinum drugs: combined anti-lymphoproliferative and nephrotoxicity assay in rats. 743 27

In Wistar rats just after weaning, 5/6 of renal parenchyma were removed surgically. Thereafter, the rats were fed either a "high-protein" (21%) or two types of a "low-protein" (6%) diet; in one of the latter the lack of protein was substituted by saccharide, in the other by fat, making the substitution "isocaloric" in either case. In all three diet groups, subgroups were formed drinking either tap water or water containing either the ACE inhibitor enalapril (Ena) or the calcium antagonist diltiazem (Dil), or both (Ena + Dil). In the high-protein diet group, increases in the weight of kidney remnants, in proteinuria and in systolic blood pressure (SBP) were seen. This was prevented by feeding either type of the low-protein diet but also by Ena and Ena + Dil. Ena and Ena + Dil not only prevented the increase in SBP but actually lowered it significantly. Dil alone also had a SBP-lowering action but offered no protection from kidney hypertrophy and proteinuria. No additive protective action of Ena + Dil or Ena + low protein or Ena + Dil + low protein was seen, suggesting that a bottom limit of these protective action was reached by the low-protein diet alone. There was no substantial difference between either type of the low-protein diet except a small and transient decrease in body weight in the first week of fat-rich diet administration.
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PMID:A comparison of the effect of feeding a low-protein diet and of pharmacological intervention on the course of ablation nephropathy in the rat. 777 Jun 41

Cell cycle regulation in diabetic nephropathy. Renal hypertrophy is one of the earliest abnormalities of diabetic nephropathy. Although selected cell populations. such as tubulointerstitial fibroblasts, may undergo sustained proliferation in the diabetic environment, most renal cells such as mesangial cells are arrested in the G1-phase of the cell cycle after actively leaving G0-phase and some self-limited early proliferation. High glucose, transforming growth factor-beta (TGF-beta), angiotensin II, and probably other factors induce inhibitors of cyclin-dependent kinases (CDK) including p21Cip1 and p27KiP1. These CDK-inhibitors bind to and inactivate G1-phase cyclin/CDK complexes. The consequence is a lack in kinase activity, underphosphorylation of the retinoblastoma gene protein, and a failure to initiate the G1-S-phase transit. The half-life of CDK-inhibitors may also be increased by serine phosphorylation mediated through activated MAP kinases. Treatment of diabetic rats with angiotensin-converting enzyme inhibitors attenuates glomerular hypertrophy and abolishes the glomerular expression of the CDK-inhibitors p16INK4 and p27KiP1, thus indicating that the cell cycle arrest can be therapeutically influenced. Cell cycle proteins may also be involved in these molecular events, leading to a limited degree of tubular apoptosis, which is a feature of diabetic nephropathy. Although not definitively proven, accumulating evidence suggests that early hypertrophy of renal cells may act as pacemaker for subsequent irreversible structural changes, such as glomerulosclerosis and tubulointerstitial fibrosis. Therefore, a better understanding of altered processes of cell cycle regulation is necessary to develop novel therapeutic strategies to prevent diabetic nephropathy. The recent observation that glomerular hypertrophy and proteinuria do not develop in diabetic p21CiP1 knockout mice indicates that this approach is feasible.
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PMID:Cell cycle regulation in diabetic nephropathy. 1099 92

This study was designed to investigate the effect of hyperglycemia and angiotensin II (AngII) on renal hypertrophy and proteinuria in the pregnant diabetic rat. Secondary objectives were to evaluate changes in components of the renin-angiotensin axis and the effects of administration of losartan on pregnancy outcome. Fifty-three pregnant rats were allocated to 6 groups (1) nondiabetic controls (n = 12), (2) nondiabetic controls administered losartan (70-80 mg/kg/day; n = 10), (3) rats in which intravenous streptozotocin (STZ) was used to induce diabetes (55 mg/kg on day 10 of pregnancy; n = 10), (4) diabetic rats treated with losartan (n = 7), (5) diabetic rats treated with insulin (4 U/day; n = 7), and (6) diabetic rats treated with insulin and losartan (n = 7). Urinary protein excretion measured 4 days after STZ was 4 times greater in the rats with STZ-induced diabetes and significantly less in diabetic rats given losartan, insulin, or both. Postpartum kidney weight was greater in the rats with STZ-induced diabetes (2.04 +/- 0.21 g) than in the controls (1.37 +/- 0.14 g; P <.05) and reduced in the diabetic rats given losartan, insulin, or both (1.57 +/- 0.22, 1.73 +/- 0.13, and 1.51 +/- 0.14 g, respectively; P <.05). Plasma levels of angiotensin II in rats given losartan were more than 3.5 times greater than those in controls (749 +/- 436, 596 +/- 323, 567 +/- 349, and 159 +/- 28 pg/mL; P <.001). Postpartum activity of angiotensin-converting enzyme was increased in the untreated diabetic rats compared with that in control rats (162 +/- 12 vs 117 +/- 16 nmol/mL/min; P <.05). This increase was abolished by treatment with losartan or insulin. The number of newborns and mean weight of each newborn was similar in all groups. In summary, administration of losartan or insulin prevented, in part, kidney hypertrophy and protein excretion in the diabetic pregnant rat. Losartan did not affect the number or weight of newborns. Because angiotensin II receptor-blockers are contraindicated in pregnancy, good control of diabetes through the use of insulin should be advantageous.
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PMID:Insulin and losartan reduce proteinuria and renal hypertrophy in the pregnant diabetic rat. 1453 4

The Diabetic Nephropathy Committee recommends the use of revised criteria for the early diagnosis of diabetic nephropathy in Japan. The new criteria are as follows: 1) Urinary albumin should be determined by immunoassay using a morning spot urine sample in diabetic patients without proteinuria or with dipstick-positive(+ 1) proteinuria. 2) A urinary albumin-to-creatinine ratio ranging from 30 to 299 mg/ gCr in 2 or more of 3 specimens may be diagnosed as microalbuminuria. 3) Two alternatives, i.e. the urinary albumin excretion rate of 30-299 mg/24hr in 24hr urine collection or 20-199 microg/min in timed urine collection can be used to detect microalbuminuria. 4) Renal hypertrophy and elevated urinary type IV collagen may indicate the existence of diabetic renal disease. 5) Microalbuminuria originating in non-diabetic diseases should be excluded.
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PMID:[Revised criteria for the early diagnosis of diabetic nephropathy]. 1629 6

Obesity is a major risk factor in the development of chronic renal failure. Rimonabant, a cannabinoid CB1 receptor antagonist, improves body weight and metabolic disorders; however, its effect on mortality and chronic renal failure associated with obesity is unknown. Obese Zucker rats received either rimonabant or vehicle for 12 months and were compared to a pair-fed but untreated group of obese rats. Mortality in the obese rats was significantly reduced by rimonabant along with a sustained decrease in body weight, transient reduction in food intake, and an increase in plasma adiponectin. This was associated with significant reduction in plasma total cholesterol, low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio, triglycerides, glucose, norepinephrine, plasminogen activator inhibitor 1, and preservation of pancreatic weight and beta-cell mass index. The cannabinoid antagonist attenuated the increase in proteinuria, urinary N-acetylglucosaminidase excretion, plasma creatinine, and urea nitrogen levels while improving creatinine clearance. Renal hypertrophy along with glomerular and tubulointerstitial lesions were reduced by rimonabant. Although the drug did not modify hemodynamics, it normalized the pressor response to angiotensin II. Our study suggests that in a rat model of chronic renal failure due to obesity, rimonabant preserves renal function and increases survival.
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PMID:Blockade of cannabinoid CB1 receptors improves renal function, metabolic profile, and increased survival of obese Zucker rats. 1788 51


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