Proteinuria as complication of simvastatin treatment

Deslypère, J.P.; Delanghe, Joris; Vermeulen, A

doi:10.1016/0140-6736(90)93164-k

Cited by 35 publications

(21 citation statements)

References 4 publications

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“…This finding indicates that, at least in the RMR model, rosuvastatin tends to enhance urinary protein excretion. Of note, recent evidence demonstrated that also in hypercholesterolemic patients with normal renal function statin therapy [15, 16], particularly rosuvastatin [18], was sometimes associated with episodes of mild proteinuria. Nevertheless, the underlying mechanism(s) remains poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…The renoprotective properties of statins have been, however, challenged by recent observations that, given at high doses to hypercholesterolemic subjects with normal renal function, these drugs may enhance urinary protein excretion rate [15,16,17,18,19]. Episodes of proteinuria – usually early after starting treatment – were transient, most frequently related to high doses of rosuvastatin (80 mg), and apparently not associated with worsening of renal function [20].…”

Section: Introductionmentioning

confidence: 99%

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Effects of Rosuvastatin on Glomerular Capillary Size-Selectivity Function in Rats with Renal Mass Ablation

Corna

Sangalli

Cattaneo³

et al. 2007

Am J Nephrol

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Background: Evidence is accumulating that statins can reduce proteinuria and disease progression in chronic kidney disease. However, some safety concerns have been recently raised on the use of these agents, mainly due to transient episodes of proteinuria observed in patients receiving high doses of rosuvastatin. Methods: We investigated in rats with renal mass ablation (RMR) whether rosuvastatin (5 or 20 mg/day) worsens proteinuria as compared to untreated RMR animals. Moreover, we also examined whether rosuvastatin-induced changes in proteinuria would be due to the effect of the drug on permselective properties of glomerular capillary barrier, measured by the fractional clearance of graded-size Ficoll molecules and/or by proximal tubular mechanisms, by assessing urinary excretion of β₂-microglobulin. Results: RMR rats given rosuvastatin for 28 days showed a progressive increase in proteinuria, with values numerically but not significantly higher than those in RMR animals given the vehicle. In RMR rats, rosuvastatin did not significantly affect the fractional clearance of Ficoll as compared to vehicle-treated RMR animals. A significant correlation was found between urinary protein and β₂-microglobulin excretion in rats treated with rosuvastatin (r = 0.936, p < 0.001), but not in those given vehicle. Renal function, glomerular and tubulointerstitial injury were comparable in rosuvastatin-treated and untreated RMR rats at the end of the 28-day follow-up. Conclusion: In rats with RMR, rosuvastatin mildly enhances urinary protein excretion rate. This, however, was not the result of further changes in the size-permselective function of glomerular capillary barrier.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of Rosuvastatin on Glomerular Capillary Size-Selectivity Function in Rats with Renal Mass Ablation

Corna

Sangalli

Cattaneo³

et al. 2007

Am J Nephrol

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“…Rabelink et al 22 showed that simvastatin substantially reduced albuminuria in hypercholesterolemic nondiabetic patients. In contrast, Deslypere et al 23 reported that simvastatin induced proteinuria on one or more occasions in 10 of 120 hypercholesterolemic patients. The discrepancy could be explained by different patient population, implying different patterns of renal pathology.…”

Section: Previous Studiesmentioning

confidence: 92%

Effect of Pravastatin on Proteinuria in Patients With Well-Controlled Hypertension

2002

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Abstract-Proteinuria is an important risk factor for cardiovascular and renal morbidity and mortality. The effects of 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitor (statin) therapy on proteinuria in normolipidemic patients with well-controlled hypertension have not been studied. A total of 63 normolipidemic (total cholesterol Ͻ240 mg/dL) and proteinuric (300 to 3000 mg/d) patients with well-controlled blood pressure (Ͻ140/90 mm Hg) were randomized to receive either placebo (nϭ32) or pravastatin (10 mg/d; nϭ31) after a 3-month placebo period. Pravastatin lowered proteinuria after 6 months by 54% (PϽ0.0001). Creatinine clearance was stable throughout the study in the 2 groups. Despite unchanged plasma endothelin-1 levels throughout the study, urinary excretion of the peptide was decreased and significantly correlated with improvement in urinary protein excretion in pravastatin-treated patients (rϭ0.64, Pϭ0.001). The urinary excretion of retinol-binding protein decreased after pravastatin administration, probably reflecting an improvement in tubular function. In contrast, the urinary excretion of IgG did not change significantly throughout the study in either group. Multivariate analysis revealed that proteinuria was only significantly correlated with statin use (PϽ0.0001, R 2 ϭ0.66). Linear regression analysis in the statin-treated group did not show any correlation between changes in lipid profiles and proteinuria regression. Thus, in addition to their primary function of antilipidemia, the addition of pravastatin to treatment for well-controlled hypertension may have an additive effect on reducing proteinuria independent of hemodynamics and lipid-lowering effects, possibly through inhibiting renal endothelin-1 synthesis and improving tubular function.

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“…Nonetheless, statins should be prescribed with caution since high doses of these agents can lead to renal and extrarenal complications. For instance, proteinuria can occur in some patients when treated with a high dose of simvastatin (40 mg/day), regress following discontinuation, and recur with the resumption of the drug [132]. The mechanism by which rosuvastatin and occasionally other statins cause proteinuria is not entirely clear.…”

Section: Effect Of Statins On Progression Of Ckdmentioning

confidence: 99%

Dyslipidemia in Chronic Kidney Disease and Nephrotic Syndrome

Vaziri

2015

Dyslipidemias

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Proteinuria as complication of simvastatin treatment

Cited by 35 publications

References 4 publications

Effects of Rosuvastatin on Glomerular Capillary Size-Selectivity Function in Rats with Renal Mass Ablation

Effects of Rosuvastatin on Glomerular Capillary Size-Selectivity Function in Rats with Renal Mass Ablation

Effect of Pravastatin on Proteinuria in Patients With Well-Controlled Hypertension

Dyslipidemia in Chronic Kidney Disease and Nephrotic Syndrome

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