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 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

Genetically diabetic mice (db/db) were given 50 mg/kg body weight/day substance L, a nontoxic basic amino acid and compared to control diabetic mice without treatment. The oral administration of the compound was started at the age of 3 months and the animals were sacrificed at the age of 7 months. No adverse effects were observed in animals given the substance L. Total food consumption, drinking water intake and body weight were comparable between the groups. Nonenzymatic glycosylation of serum proteins and hemoglobin was not significantly different in the groups. Renal pathological lesions in the control diabetic mice showed glomerular mesangial expansion and on electron microscopy thickened glomerular basement membranes with a mean thickness of 3,204 +/- 186 A. Treated animals showed significantly less mesangial crescents and thinner glomerular basement membrane thickness of 2,520 +/- 252 A (p less than 0.01). The experimental animals showed in addition a lower mean kidney weight. Glomerular but not tubular proteinuria was reduced in the treated group. Basement membrane collagen type IV isolated from kidneys of experimental animals was more soluble in acidity and showed a lower degree of cross-linking as evaluated by SDS-polyacrylamide gel electrophoresis. We conclude that substance L is beneficial to diabetic renal changes. We suggest that this positive effect could be due to the inhibition of glucose-mediated abnormal cross-linking of collagenous structures by the interaction of substance L with reactive carbonyl residues of glycosylation adducts of collagen. Other possible mechanisms are discussed.
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PMID:The effect of substance L on glucose-mediated cross-links of collagen in the diabetic db/db mouse. 207 11

Previous studies have demonstrated that inhibition of thromboxane A2-dependent platelet aggregation by the thromboxane A2 synthase inhibitor, OKY 1581, ameliorated the progressive kidney disease of rats with subtotal renal ablation. OKY 1581 also decreased the excessive renal thromboxane A2 synthesis and lowered systemic blood pressure. In the same model, a low dose aspirin and a specific thromboxane A2 receptor antagonist failed to influence proteinuria, glomerulosclerosis, and hypertension, thus excluding a role for either platelet or renal thromboxane A2 in renal disease progression. The aims of this study were to establish (1) whether a thromboxane A2 synthase inhibitor different from OKY 1581 could retard the progression of glomerular disease in rats with remnant kidney and (2) whether this effect was associated with an increase in renal synthesis of the vasodilatory prostacyclin. Treatment of rats with renal mass ablation with FCE 22178 (100 mg/kg by gavage and 200 mg/kg in the drinking water) for 35 days starting 10 days after surgical ablation was associated with an improvement in renal function in comparison with rats receiving the vehicle alone. Proteinuria was significantly lower, and rats were partially protected from the development of glomerulosclerosis. Systolic blood pressure was significantly lower than in animals given the vehicle. Urinary thromboxane B2 excretion was significantly decreased, and urinary 6-keto-prostaglandin F1 alpha increased in respect to vehicle-treated rats. We conclude that FCE 22178 limits glomerular injury in rats with remnant kidney.
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PMID:Thromboxane synthesis inhibition increases renal prostacyclin and prevents renal disease progression in rats with remnant kidney. 213 29

There is evidence to suggest that thromboxane synthesis inhibition will attenuate the hypertension and proteinuria associated with subtotal renal ablation. In the present study, the thromboxane receptor antagonist, daltroban, (30 mg/kg/day i.p.) or vehicle was administered to rats for 3 weeks starting 2 weeks after partial renal ablation (right uninephrectomy and ligation of approximately two-thirds of the blood supply to the left kidney). Renal ablation was associated with proteinuria and increased systolic blood pressure. Neither the proteinuria nor the hypertension was affected by daltroban administration. Histological examination of the remaining kidney demonstrated no beneficial effect of daltroban. In a second study, it was determined that, 2 weeks after renal ablation, urinary thromboxane excretion was significantly increased, and subsequent administration of daltroban for 2 weeks resulted in significant blockade of the effects of the thromboxane mimetic, U46619. In a third study, enalapril (50 mg/l in the drinking water) resulted in a significant attenuation of the proteinuria, hypertension and glomerular lesions associated with partial renal ablation. The data indicate that enalapril, but not daltroban, protects against the development of renal disease associated with reduced renal mass.
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PMID:Effect of enalapril or the thromboxane receptor antagonist, daltroban, in rats with subtotal renal ablation. 213 68

Cisplatin is currently one of the most used agents in the treatment of cancer and it is essential in the treatment of germ cell cancer. The use of the drug is hampered by side effects - especially renal toxicity which is dose limiting. The present work was undertaken to elucidate the pathophysiological mechanisms involved in cisplatin induced nephrotoxicity. Immediately after administration of cisplatin to dogs, renal blood flow (RBF) and glomerular filtration rate (GFR) remained unchanged, while proximal reabsorption rates decreased significantly. The cisplatin induced nephrotoxicity is thus initiated by an acute, mainly proximal tubular impairment, preceding alterations in renal hemodynamics. These data were confirmed in a micropuncture study in rats. At 48 to 72 hours after administration of cisplatin depressed renal function could be attributed to impairment of proximal as well as distal tubular reabsorptive capacities, now associated with increased renal vascular resistance. After administration of 4 cycles of 20 mg cisplatin/m2 d. for 5 days in humans, a small but significant decrease in 51Cr-EDTA clearance was observed. In the high-dose cisplatin group (40 mg/m2 d. for 5 days) a severe progressive decrease in GFR was observed during treatment and GFR remained decreased for up to 2 years after termination of treatment. The observation of an acute increase in N-acetyl-beta-D-glucosaminidase and beta-2-microglobulin indicates a primary tubular effect of cisplatin also in humans. A marked reduction of proximal tubular reabsorptive capacities of sodium and water was also observed in this group, together with a decrease in distal tubular function. These changes persist for at least 6 months after treatment. In the high-dose group proteinuria developed. This was mainly of tubular origin during cisplatin infusion and of glomerular origin between treatment cycles. Cisplatin remains one of the most potent antineoplastic agents ever developed. Further work should be performed to reduce its potential for renal toxicity.
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PMID:Cisplatin nephrotoxicity: experimental and clinical studies. 217 84

Thirty-six male Lewis rats rendered diabetic using alloxan received syngeneic pancreaticoduodenal grafts. Seven days prior to and 7, 30, and 90 days posttransplantation, the animals were housed in metabolic cages for periods of 48 hours. During this time, body weight, water intake, food intake, urine output, and fecal output were recorded every 24 hours. Blood sugar, plasma insulin, glucosuria, and proteinuria were determined at 3-month intervals prior to the transplant and at monthly intervals posttransplantation. These parameters were also concurrently recorded for diabetic control rats. Pancreaticoduodenal transplantation produces immediate relief of hyperglycemia, glucosuria, polyuria, polyphasia, and polydypsia, resulting in good health of the animals until the time of sacrifice. A significantly increased insulin level was also recorded. The transplanted animals showed a weight gain reflecting that of a normal growth curve.
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PMID:Metabolic effect of pancreas transplantation on long-term diabetic rats. 219 25

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 objective of the work was to evaluate the basic parameters of zinc metabolism, i.e. serum levels and urinary excretion of zinc (Zn) in insulin dependent diabetes. The authors investigated a group of diabetics with normal renal function (DM) and with chronic renal insufficiency as a result of diabetic nephropathy (RIDM). Two control groups were formed by healthy volunteers (C) and non-diabetic subjects with chronic renal insufficiency (RI). In diabetics without impaired renal functions (DM) the Zn serum levels did not differ significantly from controls, urinary excretion was significantly raised. The authors did not reveal a correlation of serum Zn levels with parameters of compensation of diabetes nor with the insulin dose. Urinary Zn output correlated positively with proteinuria and the average blood sugar level during the collection of urine. The authors did not find a correlation with diuresis, fractional water excretion, glycosuria or urea excretion. The fractional Zn clearance in diabetic subjects was significantly raised and correlated with the mean blood sugar level. This finding suggests a decline of the tubular Zn absorption in hyperglycaemia. In diabetics with renal failure (RIDM) the results did not differ from non-diabetics with the same degree of renal insufficiency: serum Zn levels were, as compared with healthy controls, in both groups significantly reduced, the urinary excretion being normal. Thus insulin dependent diabetes nor its metabolic compensation do not influence in a marked way serum Zn levels but lead to higher urinary Zn losses.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Serum levels and urinary excretion of zinc in patients with insulin-dependent diabetes]. 220 24

The effects of dietary protein intake on the progression of renal insufficiency were studied in daunomycin (DMC) induced nephrotic rats (DMC rats) and also patients with chronic renal diseases. In the first study, the author examined which treatment among enalapril (E) and indomethacin (I) and dietary protein restriction was the most effective to prevent proteinuria and glomerulosclerosis, and then the effect of dietary protein restriction on renal content of malondialdehyde (MDA) and superoxide dismutase (SOD) in DMC rats. These rats were divided into four groups as follows: group PL and group PH were isocaloric diets containing either 5% or 24% protein, respectively and group PE and PI were given orally E (100 mg/l drinking water) or I (50 mg/l drinking water) with diets of 24% protein, respectively. In group PL, urinary protein excretion (U-Protein) rates and renal damage index were significantly lower than those in other three groups. In group PE, renal damage index was significantly improved although U-Protein showed no reduction in contrast with these in group PH. Renal MDA in group PL was lower than that in group PH was significantly lower than that in group PL. In this study dietary protein restriction was the most effective treatment for the prevention of progressive renal insufficiency. In the second study, patients with chronic renal diseases were divided into two groups according to their Ccr: group I; Ccr greater than or equal to 60 ml/min, group II; Ccr less than 60 ml/min. All patients orally received diets of high protein (1.4 g/kgBW) and subsequently of low protein (0.7 g/kgBW). Ccr, U-Protein, serum MDA and serum SOD were estimated at the end of each dietary period. In group I, Ccr was significantly lower on low protein diet than that on high protein diet, although these were no significant changes in Ccr in group II. The low protein diet caused a significant decrease in U-Protein in both groups. Serum MDA in group I was significantly lower on low protein diet than that on high protein diet, but not in group II. Serum SOD activity showed no changes. It is suggested that dietary protein restriction might reduce oxidant stress to the kidney, in addition to renal hemodynamic changes induced by prostaglandin and renin-angiotensin system, resulting in the prevent of progress of renal insufficiency.
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PMID:[Study on the pathogenetic factors of the progression of renal insufficiency, with special reference to the effects of dietary protein intake]. 221 17

The pathophysiology of the nephrotic syndrome (NS), characterized by protenuria, edema, sodium retention and hyperlipidemia, is not clear. We studied the role of some systemic factors on sodium retention in an experimental model of NS. NS was induced in rats by a single subcutaneous injection of puromycin aminonucleoside (PA) (15 mg/100 g); control animals received vehicle. All rats were kept in metabolic cages for 24 days (3 days before and 21 days after PA-injection). Urine was collected daily. Blood samples were obtained every day until day 10, and then every other day up to the end of the study. The rats showed the following alterations after PA injection: a) a rise in serum angiotensin converting enzyme activity (ACEA) and plasma aldosterone (PAldo) at day 1; b) a rise in urinary aldosterone (UAaldoV), azotemia and sodium retention at day 2; c) massive proteinuria (UProt) and decrease in plasma angiotensinogen concentration (PAC) at day 4; d) increases in plasma renin activity (PRA), plasma renin concentration (PRC) and serum creatinine as well as hypoproteinemia, hypercholesterolemia, hypertriglyceridemia, ascitis and edema at day 5; e) increase in urine volume at day 6. PAldo became normal at day 7; urine sodium (UNaV), PRA and PRC at day 8; UAldoV at day 9; serum urea and ACEA at day 10; urinary volume at day 11; PAC, serum total protein and creatinine at day 12. The edema disappeared at day 11. UProt, hypercholesterolemia and hypertriglyceridemia persisted, though they decreased substantially by the end of the study (day 21). Light microscopy studies revealed normal glomerular morphology, but electron microscopy showed fusion of podocytes before proteinuria. These data suggest that: a) sodium retention was not a consequence of proteinuria or hypoproteinemia; b) sodium retention seems non-related to renin secretion, but may be partially mediated by a fall in glomerular filtration rate or by an increased tubular resabsorption secondary to other factors; c) the increase in PAldo, UAldoV and ACEA are non-related to renin secretion: all occurred before PRA rose; d) water retention, increase in PRA and PRC, hypercholesterolemia and hypertriglyceridemia are secondary to the hypoproteinemia.
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PMID:Pathophysiology of experimental nephrotic syndrome induced by puromycin aminonucleoside in rats. I. The role of proteinuria, hypoproteinemia, and renin-angiotensin-aldosterone system on sodium retention. 223 72


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