Effects of simvastatin on lipoprotein (a) and lipoprotein composition in patients with nephrotic syndrome

Abstract

dicates that young children (< 2 years) have a different bladder shape than older children and need to be assessed by a specific formula to improve the accuracy of ultrasonographic estimation of their bladder volume. The influence of simvastatin, a competitive inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A reductase, on quantitative and qualitative changes in lipoprotein metabolism was investigated in 18 patients (group I, 10 with primary kidney disease and group II, 8 with diabetic nephropathy) with nephrotic syndrome. Nephrotic patients exhibited severe hyperlipidemia (serum cholesterol 390+_ 17 mg/dl an triglyceride 335-+42 mg/dl; mean -+ SEM) and had significantly higher lipoprotein (a) [Lp(a)] levels (54_+12 mg/dl; median 31 mg/dl, p <0.01) compared with 20 healthy subjects (mean 12_+ 1.8 mg/dl; median 7 mg/dl). Fifty-six percent of the patients and 15% of the controls had values greater than 30 mg/dl. Treatment with simvastatin in increasing doses over a period of three months (13 patients received 40 mg/day and 5 patients 20 mg/day at the end of the third month) reduced LDL-cholesterol in both groups of patients (35% and 54%) as well as apolipoprotein B (apoB) (31% and 46%) significantly, but Lp (a) levels were not influenced (57_+21 vs 59___20 and 50_+14 vs 53 _+ 16 mg/dl, respectively). On the other hand a complex change in lipoprotein composition occurred. The ratio of LDL apoB/LDL cholesterol-ester increased significantly (0.75_+0.03 to 0.84+_0.03 and 0.80 __ 0.03 to 1.02 ___ 0.1, respectively) and cholesterol concentration in VLDL (64 _+ 16 to 39 _+ 7 and 74 _+ 18 to 55 _+ 74 mg/dl, respectively) was reduced. Therefore, the ratio of triglycerides/cholesterol in VLDL increased (2.89_+0.32 vs 4.10_+0.50 and 3.56_+0.30 to 5.86_+0.97, respectively), indicating VLDL formation poor in cholesterol and rich in triglycerides. The data show that simvastatin profoundly influences the composition of triglyceride and cholesterol rich lipoproteins in patients with nephrotic syndrome. Although these alterations in lipoprotein composition appear to be favorable, the strikingly elevated levels of the atherogenic lipoprotein(a) were not influenced.

Efficiency of 1-Year Treatment with Fluvastatin in Hyperlipidemic Patients with Nephrotic Syndrome

“…In comparison to studies with different HMGCoA reductase inhibitors, there are no major differences concerning correction of the lipid profile. The extent of lowering total cholesterol, LDL cholesterol, and triglycerides seems comparable to the previously reported efficiency of simvastatin and lovastatin [6,11].…”

“…HDL cholesterol and Lp(a) remained unchanged. These findings are similar to those described in studies using other HMGCoA reductase inhibitors in patients with nephrotic syndrome [5,6].…”

“…Even so, we did not measure very-low-density lipoprotein, this explanation for reduction of the triglyceride concentration has been reported before and during treatment of hyperlipidemia in nephrotic syndrome with simvastatin [6]. The plasma concentrations of Lp(a) did not change during treatment with fluvastatin.…”

“…Besides the increased risk of atherosclerotic vascular complications [2], an accelerated progression of renal disease has been postulated [3,4]. 3-Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are considered to be the treatment of choice of the disturbed lipoprotein and apolipoprotein profile of patients with nephrotic syndrome [1,5,6]. In short-term trials HMG-CoA reductase inhibitors proved to be effective in lowering serum lipids with only few side effects [5,6].…”

Effect of statins on lipoprotein (a) in dyslipidemic patients

“…Contradictory findings have been reported concerning variations in Lp(a) levels after statin treatment. [15][16][17][18] This calls for a better understanding of statin monotherapies on Lp(a) levels.…”