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Atorvastatin improves endothelial function in renal-transplant recipients
A Asberg1, A Hartmann, E Fjeldså
1Laboratory for Renal Physiology, Section of Nephrology, Medical Department, The National Hospital, N-0027 Oslo, Norway.
Insights
Atorvastatin significantly reduced cholesterol and improved endothelial function in kidney transplant patients. This suggests a potential protective effect via the endothelial-nitric oxide pathway.
Area of Science:
- Cardiology
- Nephrology
- Pharmacology
Background:
- Hyperlipidemia and endothelial dysfunction are common in cyclosporin A (CsA)-treated renal transplant recipients.
- These conditions increase the risk of atherosclerosis and cardiovascular mortality.
- Statins may improve endothelial function beyond cholesterol reduction.
Purpose of the Study:
- To assess the effects of atorvastatin on serum lipids and endothelial function.
- To evaluate atorvastatin's impact in CsA-treated renal transplant recipients.
Main Methods:
- Pilot study involving 22 renal transplant recipients on CsA and prednisolone.
- 4-week open trial of 10 mg/day atorvastatin.
- Assessment of forearm skin microvasculature endothelial function using acetylcholine and laser Doppler flowmetry.
- Measurement of serum lipids, endothelin-1 (ET-1), nitric oxide (NO), and von Willebrand factor (vWF).
Main Results:
- Significant reductions in total cholesterol (26.8%) and LDL cholesterol (41.5%) after 4 weeks.
- Significant improvement in endothelial function (AUC(ACh): 538 to 682 AU x min, P=0.042).
- Borderline significant increase in plasma NO levels (49 to 57 micromol/l, P=0.051).
- No significant changes in plasma ET-1 or vWF levels.
Conclusions:
- Atorvastatin effectively lowers cholesterol and improves endothelial function in renal transplant recipients.
- Increased NO levels suggest a potential endothelial protective effect through the NO pathway.
- Atorvastatin may offer cardiovascular benefits in this patient population.
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.
Conclusion:
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".