Nephrol Dial Transplant (2001) 16: 2152-2157
© 2001 European Renal Association-European Dialysis and Transplant Association
Effect of simvastatin on renal function in autosomal dominant polycystic kidney disease
1 Department of Nephrology, 2 Department of General Internal Medicine, 3 Department of Clinical Chemistry, Leiden University Medical Center, Leiden and 4 Department of General Internal Medicine, St Elisabeth Hospital, Tilburg, The Netherlands
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±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±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.
Keywords: acetylcholine; autosomal dominant polycystic kidney disease; renal blood flow; renal function; simvastatin; vascular reactivity
Correspondence and offprint requests to: M. A. van Dijk, Department of Nephrology, Leiden, University Medical Center, Albinusdreef 2, PO Box 9600, 2300 RC Leiden, The Netherlands. Email: marjanvd{at}hotmail.com
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