Atorvastatin improves endothelial function in renal-transplant recipients.
BACKGROUND
Hyperlipidaemia and endothelial dysfunction are common features in cyclosporin A (CsA)-treated renal transplant recipients. Endothelial dysfunction may contribute to the risk of premature atherosclerosis and cardiovascular death in these patients. A beneficial effect of statin therapy beyond cholesterol lowering may be an improvement of endothelial function. The present study was designed to assess the effect of atorvastatin on serum lipids and endothelial function in CsA treated renal transplant recipients.


METHODS
This pilot study was an open trial of 4 weeks atorvastatin (10 mg per day) treatment in renal transplant recipients (n=22). All patients received a CsA- and prednisolone-based immunosuppressive regimen. Endothelial function was assessed in the forearm skin microvasculature by acetylcholine stimulation and laser Doppler flowmetry, before and after atorvastatin treatment. Serum lipids, plasma endothelin-1 (ET-1), nitric oxide (NO), and von Willebrand factor (vWF) were also measured.


RESULTS
Both total and LDL cholesterol were significantly reduced by 26.8 +/- 8.4 and 41.5 +/- 11.0% respectively, after 4 weeks of treatment. Endothelial function was significantly improved during atorvastatin treatment, area under the flux versus time curve (AUC)(ACh) was 538 +/- 362 AU x min before and 682 +/- 276 AU x min after treatment (P=0.042). Plasma NO levels also showed a borderline significant increase from 49 +/- 30 to 57 +/- 37 micromol/l during the treatment period (P=0.051), though plasma ET-1 (0.37+/-0.08 vs 0.37+/-0.12 fmol/ml) and vW (196+/-57 vs 197+/-37%) were unchanged.


CONCLUSIONS
Atorvastatin lowered serum cholesterol significantly and improved endothelial function in renal transplant recipients after 4 weeks of treatment. Plasma NO levels were increased during atorvastatin treatment, indicating a possible endothelial protective effect through an "endothelial-NO pathway".
Asberg
A
A
Laboratory for Renal Physiology, Section of Nephrology, Medical Department, The National Hospital, N-0027 Oslo, Norway.
Hartmann
A
A
Fjeldså
E
E
Holdaas
H
H
D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D005260:Female; D005542:Forearm; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008055:Lipids / Q000097:blood; D008297:Male; D008833:Microcirculation / Q000502:physiology; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D010865:Pilot Projects; D011758:Pyrroles / Q000627:therapeutic use*; D012867:Skin / Q000098:blood supply
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011758:Pyrroles; D009569:Nitric Oxide; D000069059:Atorvastatin