Background: Chronic allograft nephropathy (CAN) is defined and graded in the Banff '97 scheme by the severity of interstitial fibrosis and tubular atrophy. It has been denoted that chronic rejection can be diagnosed if the typical vascular lesions are seen, consisting of fibrointimal thickening. We observed several patients who developed CAN without vascular changes or signs of cyclosporine toxicity. Therefore, we assessed the risk factor profiles of CAN with and without transplant vasculopathy.
Methods: A cohort of 654 cadaveric renal transplants performed between 1983 and 1997 that functioned for more than 6 months was studied. Fifty-four transplants had CAN defined by a significant decline in renal function together with interstitial fibrosis and tubular atrophy without signs of cyclosporine nephrotoxicity or recurrent disease. Using the Banff chronic vascular (CV) score, 23 of 54 cases (43%) had a chronic vasculopathy score of 0 or 1 whereas 31 cases (57%) had a CV score of 2 or 3. Applying multivariate logistic regression, predictor variables of the two groups were compared with 231 transplants with a stable function for at least 5 yr.
Results: Graft histology was obtained at a mean of 2.4 and 2.9 yr after transplantation in the group with or without vasculopathy, respectively. Acute rejection episodes (AREs) after 3 months post-transplantation were the strongest risk factor for both forms of CAN, odds ratio (OR) 14.7 (6.0-36.0). CAN with vasculopathy was also associated with transplants performed in the 1980s, OR 4.95 (1.65-14.9) and with creatinine clearance at 6 months, OR 0.58 (0.44-0.75) per 10 mL/min increase. In contrast, young recipient age, OR 0.69 (0.47-0.99) per 10-yr increase, and the presence of panel reactive antibodies at the time of transplantation, OR 1.26 (1.08-1.47) per 10% increase, were independent risk factors for CAN without vasculopathy.
Conclusions: After exclusion of cyclosporine toxicity or recurrent disease CAN occurred without moderate or severe transplant vasculopathy in 43% of the cases. The correlation with young recipient age, sensitization and late ARE suggest an immune pathogenesis, consistent with chronic rejection.