Influence of nifedipine on interstitial fibrosis in renal transplant allografts treated with cyclosporin A.

Abstract

To compare the degree of interstitial fibrosis in renal transplant biopsy specimens from immunosuppressed patients using conventional doses of cyclosporin with and without calcium channel blockade with a combination of low dose cyclosporin and azathioprine; to correlate the degree of interstitial fibrosis with the glomerular filtration rate. A single blind histomorphometric assessment was done of cortical interstitial volume fraction from biopsy specimens taken intraoperatively and at one, six, and 12 months after transplantation from three prospectively randomised groups of patients: (A) conventional dose cyclosporin; (B) conventional dose cyclosporin plus nifedipine; (C) low dose cyclosporin plus azathioprine. Interstitial volume increased with time in all groups. No differences in interstitial volume were present at operation or at one month, but at six months interstitial volume was significantly less in group B than group A (p < 0.001) or group C (p < 0.05). More grafts failed in group A than group B leaving only small numbers for comparison at 12 months. At 12 months the differences persisted but did not reach significance. These results strongly reflected the clinical findings, where glomerular filtration rate was significantly lower in group A than groups B or C at six and 12 months; no differences in glomerular filtration rate were found at one month. In a direct comparison glomerular filtration rate showed a significant negative correlation with interstitial volume fraction. These findings suggest that calcium channel blockade with nifedipine slows the development of interstitial fibrosis in renal transplant recipients treated with cyclosporin. When clinical data are considered, it is suggested that calcium channel blockade may have a mitigating effect on the long term nephrotoxic effects of cyclosporin and should be considered as adjunctive treatment in patients requiring this immunosuppressant following renal transplantation.