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

Lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A inhibitor, was given to 14 patients with unremittent nephrotic syndrome (heavy proteinuria with hyperlipidaemia) for 6 months. Treatment was started at an initial dose of 20 mg/day, increasing to a maximum of 80 mg/day. Treatment was well tolerated except in two patients: one developed rhabdomyolysis and one severe hypertriglyceridaemia requiring an additional antihyperlipidaemic agent. Lovastatin was effective in reducing serum cholesterol, LDL-C and apolipoprotein B in the remaining 12 patients. Cholesterol was reduced by 31% from 8.24 +/- 0.49 mmol/l (mean +/- SEM) to 5.7 +/- 0.18 mmol/l after 6 months (P less than 0.001). LDL-C was normalized to 3.26 +/- 0.21 mmol/l from a pretreatment value of 5.76 +/- 0.48 mmol/l (P less than 0.001), a decrease of 43%. Serum apolipoprotein B was also normalized to 1.11 +/- 0.09 g/l from a basal level of 1.51 +/- 0.10 g/l (P less than 0.05). Triglyceride, HDL-C and apolipoprotein A1 concentrations were unchanged. Proteinuria as well as renal albumin clearance were unchanged. GFR by plasma radioisotope Cr-EDTA clearance for the whole group was unaltered by treatment. However, among those with relatively good pretreatment renal function (GFR greater than 70 ml/min per 1.73 m2), GFR increased at the end of 6 months' treatment (118.2 +/- 15 ml/min per 1.73 m2 versus 77.6 +/- 8.4 ml/min per 1.73 m2 in wash-out phase).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Lovastatin in glomerulonephritis patients with hyperlipidaemia and heavy proteinuria. 131 86

Dahl salt-sensitive (S) rats fed a high salt diet develop hypertension, hyperlipidemia, and progressive renal disease. Previous studies have suggested that lipids may be important in the pathogenesis of glomerulosclerosis in Dahl S rats. To investigate this possibility, Dahl S rats fed 4% NaCl chow were treated chronically with the cholesterol synthesis inhibitor lovastatin. After 22 weeks, lovastatin-treated rats had a 38% reduction in serum cholesterol, a 76% reduction in urine albumin excretion, and one-sixth the incidence of focal glomerulosclerosis compared with vehicle-treated control rats. Blood pressure in lovastatin-treated rats was significantly (p < 0.05) lower than that in vehicle-treated rats both early in the study (4 weeks of treatment) and at the end of the protocol. Lovastatin had no effect on glomerular filtration rate or glomerular ultrafiltration dynamics. The efficacy of angiotensin converting enzyme inhibitors in attenuating proteinuria and experimental glomerular disease may be dependent on sodium intake. Thus, we also investigated the effects of long-term enalapril treatment on glomerular injury in Dahl S rats fed high salt chow. Enalapril treatment (50 or 200 mg/l drinking water) significantly lowered blood pressure in Dahl S rats, but did not significantly affect albuminuria or glomerulosclerosis. Enalapril also had no effect on glomerular hemodynamics. These results suggest that lipids may be important in the development of both glomerular disease and hypertension in Dahl S rats and that angiotensin converting enzyme inhibition may not affect the course of renal disease in a setting of high salt intake.
 ...
PMID:Lovastatin but not enalapril reduces glomerular injury in Dahl salt-sensitive rats. 142 16

The nephrotic syndrome was induced in uninephrectomized Sprague-Dawley rats using repeated injections of puromycin and protamine sulfate. Preliminary studies demonstrated that the administration of lovastatin (4 mg/kg body weight [BW] subcutaneously [SC] daily) was effective at lowering plasma cholesterol over a 63-day period, although not to normal values. Subsequently, two groups of rats that had been made nephrotic were studied; one group (n = 8) received lovastatin, the other (n = 9) received the vehicle alone. Blood and urine collections were made at days 0, 23, and 60. Clearance studies and renal histology were obtained at day 60. Lovastatin-treated rats had significantly lower cholesterol at day 23 and 60 than vehicle-treated rats (270.5 +/- 39.7 v 501.7 +/- 81.9 and 148.2 +/- 10.7 v 268.2 +/- 40.8 mg/dL, P less than 0.05). Both groups of rats developed equivalent degrees of proteinuria and hypoalbuminemia. At day 60, the lovastatin-treated rats had a lower urea: 18.3 +/- 4.1 v 55.8 +/- 9.6 mmol/L (blood urea nitrogen [BUN] 51.2 +/- 111.5 v 156.2 +/- 27.0 mg/dL, P less than 0.02) and greater unulin clearance (1.83 +/- 0.42 v 0.82 +/- 0.41 mL/min/kg BW, P less than 0.05) than the vehicle-treated rats. Neither group was hypertensive and the blood pressure (BP) was similar in both groups. The percentage of glomeruli showing no changes or minimal histological changes was significantly greater in the lovastatin-treated group (26.5% +/- 5.7% v 8.33% +/- 3.33%, P less than 0.02), and there were more glomeruli with global sclerosis in the vehicle-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Lovastatin ameliorates the development of glomerulosclerosis and uremia in experimental nephrotic syndrome. 229 29

The efficacy and safety of lovastatin as a hypolipidemic agent were evaluated in ten adult patients with secondary hypercholesterolemia due to proteinuria (greater than 2 g/d) and (in seven patients) concurrent corticosteroid therapy. Patients were on a low-cholesterol diet throughout the study. After a 4-week baseline period, patients were randomized to receive either placebo or 10 mg lovastatin twice daily for a period of 6 weeks. The dose of lovastatin was increased to 20 mg twice daily for 6 weeks, and 40 mg twice daily for 6 weeks in the latter group. Those patients who received placebo for the first 6 weeks subsequently received 10, 20, and 40 mg of lovastatin twice daily in a stepped dose regimen, with each dose given for 6 weeks. Lovastatin was well tolerated by all patients and none withdrew from the study. Baseline plasma cholesterol concentrations (390 +/- 20 mg/dL; mean +/- SEM) decreased 22% (P less than 0.003) at the lowest dose of 10 mg twice daily, 27% at 20 mg twice daily, and 33% at 40 mg twice daily. Baseline plasma triglycerides decreased by 25% (P less than 0.05) at the highest dosage. Concentrations of low-density lipoprotein (LDL) cholesterol fell by 29%, 34%, and 45% on doses of 10, 20, and 40 mg of lovastatin twice daily. Concentrations of high-density lipoprotein (HDL) cholesterol increased slightly. Serum creatinine concentrations and proteinuria were not affected by lovastatin therapy. We conclude that lovastatin was a well-tolerated and extremely effective hypocholesterolemic agent in patients with persistent secondary hypercholesterolemia associated with proteinuria or proteinuria and concurrent corticosteroid therapy.
 ...
PMID:Lovastatin in the treatment of multifactorial hyperlipidemia associated with proteinuria. 265 May 39

The nephrotic syndrome is characterized by proteinuria, hypoalbuminemia, and hypercholesterolemia. Hypertriglyceridemia often is present as well. In this study, the kinetics of plasma lipoproteins were investigated in four patients with nephrotic hyperlipidemia, and repeat studies were carried out in three of these patients during therapy with lovastatin. Before lovastatin therapy, the patients had an extremely delayed catabolism of very low density lipoproteins (VLDL) without evidence of overproduction of lipoproteins in this fraction. Three of four patients had elevated levels of low density lipoprotein (LDL) that were due mainly to increased production rates for LDL. In the three patients treated with lovastatin, the drug therapy lowered plasma concentrations of total cholesterol, triglycerides, VLDL-cholesterol, and LDL-cholesterol, and raised high density lipoprotein (HDL)-cholesterol. Lovastatin therapy decreased VLDL-triglycerides primarily by enhancing their catabolism, and lowered LDL-cholesterol levels mainly by reducing input rates for LDL. Overall, lovastatin appears to be an effective drug for the treatment of hyperlipidemia in the nephrotic syndrome.
 ...
PMID:Lovastatin therapy in nephrotic hyperlipidemia: effects on lipoprotein metabolism. 316 83