Histopathological study of renal transplant artery stenosis: Role of rejection and cold ischaemia time in the pathogenesis of intimal hyperplasia in an arterial allograft

Introduction: Intimal hyperplasia of renal allograft arteries is a cause of hypertension and graft loss and the predisposing factors are poorly understood. We performed a histopathological study focusing on cold ischaemia time and immunological factors and their effect on the donor artery. Methods: Primary renal artery branches were obtained from patients undergoing transplant nephrectomy for chronic rejection. Non-transplant patients undergoing nephrectomy served as controls. Clinical information including immunosuppression and rejection episodes, cold ischaemia time and graft survival were collected from the patients' charts. Collagen, smooth muscle cells, T cells, macrophages, and neutrophils were quantified using immunohistochemistry. The intima to media ratio was also calculated using imaging software. Statistical analysis was performed using linear regression and the Mann-Whitney test with P < 0.05 significant. Results: Nine transplant patients and five controls were included. All transplant patients received maximum immunosuppression according to clinical standards. The median number of acute rejection episodes was 1 (range 0-5). Cold ischaemia time was 24.3 ± 9.6 h (mean ± SD). Mean allograft longeviy was 87.4 ± 72.9 months (mean ± SD). The intima/media ratio in the transplant group was higher as compared with the control (P = 0.002). The same was true for intima collagen content (P = 0.001) and intima smooth muscle content (P = 0.036). Cold ischaemia time was 19.6 ± 11.1 h (mean ± SD) and did not correlate with intima/media ratio. Also the number of rejection episodes did not correlate with the intima/media ratio. Conclusion: Intimal hyperplasia in the allograft artery has a multifactorial aetiology. We were not able to establish an association between intimal hyperplasia and acute rejection episodes or length of cold ischaemia time. It appears that immunosuppression does not prevent the development of intimal hyperplasia.