Cyclosporin A Toxicity of the Renal Allograft – a Late Complication and Potentially Reversible

Abstract

Cyclosporin A (CsA) has improved patient and organ graft survival, but the dichotomy of benefit and toxicity is still an issue. In a retrospective analysis of 392 renal transplant recipients we documented CsA nephrotoxicity (striped fibrosis, arteriolar wall hyalinosis) in 28 (7.1%) patients (23 male/5 female) in a follow-up of more than one year post transplantation. Median age at renal transplantation was 41 years (13–60) and the period between transplantation and graft biopsy was 42 months (12–122). Median CsA trough levels (ng/ml) at 12 months post transplantation, at time of graft biopsy and at last follow-up were: 114 (71–265), 130 (78–285), 66 (24–115). The following parameters were assessed at 12 months post transplantation, at time of biopsy and at last follow-up: s-creatinine (µmol/l), Doppler resistive index, systolic and diastolic blood pressure (mm Hg) and the number of antihypertensives. Median s-creatinine at 12 months post transplantation was 150.3 (94.6–247.5), at biopsy 225.4 (121.1–353.6) and at last follow-up 160.0 (106.1–247.5) (p < 0.001 for biopsy vs. last follow-up). Resistive index decreased from 0.70 (0.64–0.88) to 0.68 (0.51–0.84) (p < 0.005), systolic blood pressure from 137 (100–168) to 130 (105–144) (p < 0.05) and the number of patients with more than 4 antihypertensives from 10 to 6 between biopsy and last follow-up, with no acute rejection episodes after modification of immunosuppressive therapy (50% of previous CsA trough level and addition of azathioprine or mycophenolate mofetil). Conclusion: CsA nephrotoxicity occurs late after renal transplantation with increased systolic blood pressure and Doppler resistive index. Reduction of CsA improves renal function, reduces graft resistive index and systolic blood pressure.