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 (micromol/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.