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+/-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).


CONCLUSIONS
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.
van Dijk
M A
MA
Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands. marjanvd@hotmail.com
Kamper
A M
AM
van Veen
S
S
Souverijn
J H
JH
Blauw
G J
GJ
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005542:Forearm / Q000098:blood supply; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D016891:Polycystic Kidney, Autosomal Dominant / Q000188:drug therapy* / Q000503:physiopathology*; D012079:Renal Circulation / Q000187:drug effects; D019821:Simvastatin / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014665:Vasodilator Agents; D002784:Cholesterol; D019821:Simvastatin; D000109:Acetylcholine