Each Administration of Cyclosporin A Enhances Skin Microvascular Reactivity in Renal Transplant Recipients

Abstract

Both impaired and enhanced microvascular function have been described in humans on cyclosporin A (CsA) therapy. In the present study we investigated the acute microvascular effects of a single CsA administration in renal transplant recipients on maintenance CsA therapy. Fourteen renal transplant recipients, median age 48 years (range 24–63 years), transplanted 4–12 weeks earlier, were included in this placebo-controlled, double-blinded, crossover study. All recipients had stable renal function; median serum creatinine was 116 μmol/L (range 80–184 μmol/L). Immunosuppressive therapy consisted of CsA, prednisolone, and either azathioprine or mycophenolate. Microvascular function was assessed by laser Doppler flowmetry in combination with acetylcholine (endothelium dependent) stimulation and the postocclusive reactive hyperemia test. Measurements were performed before (control) and 2.5 h following administration of CsA (Neoral) or matching placebo and repeated with reversed medication after at least 6 days. Vasodilative responses to acetylcholine stimulation were significantly higher following CsA ingestion compared with placebo. The mean change in AUC1.5 (area under the flux versus time curve) from control to 2.5 h was 100 ±145 for CsA and −292 ± 140 AU × min for placebo (P = 0.047, n = 10). The postocclusive hyperemic response AUCrh was also significantly higher following CsA intake (39 ± 4 AU × min) compared to placebo (30 ± 4 AU × min) (P = 0.006, n = 12). This study shows that each dose of CsA induces a transient increase in skin microvascular reactivity in renal transplant recipients. We speculate that this might be due to the potentiation of one or several endothelial-dependent compensatory vasodilative mechanisms in the microvascular bed.