Effect of simvastatin on renal function in autosomal dominant polycystic kidney disease

Background. In animal models, HMG-CoA reductase inhibitors were able to improve renal function and endothelium-dependent vascular reactivity. In various experimental renal diseases, including autosomal dominant polycystic kidney disease (ADPKD), HMG-CoA reductase inhibitors improved the rate of decline in renal function. We studied the effect of simvastatin on ADPKD patients. Methods. In a double-blind cross-over study, 10 normocholesterolaemic ADPKD patients were treated in random order for 4 weeks with 40 mg simvastatin or placebo daily. After each treatment period, we investigated the effect of simvastatin on renal blood flow and endothelium-dependent vascular reactivity. These periods were separated by a 4-week wash-out period. Results. After treatment with simvastatin. glomerular filtration rate (GFR) significantly increased from 124 +/- 4 ml/min to 132 +/- 6 ml/min (P < 0.05). Simultaneously, effective renal plasma flow (ERPF) increased significantly from 494 <plus/minus> 30 ml/min to 619 +/- 67 ml/min after simvastatin treatment (P < 0.05). These renal effects were accompanied by a significantly enhanced vasodilator response to acetylcholine in the forearm after simvastatin treatment. Total serum cholesterol levels were significantly reduced after treatment with simvastatin. from 4.24 <plus/minus> 0.32 to 3.17 +/- 0.22 mmol/l (P < 0.001). Conclusion. We concluded that simvastatin treatment can ameliorate renal function in ADPKD patients, by increasing renal plasma flow, possibly via improvement of endothelial function. Long-term clinical trials with HMG-CoA reductase inhibitors are needed to confirm these results and to establish a chronic inhibiting effect of HMG-CoA reductase inhibitors on the progression towards end-stage renal disease in ADPKD patients.