Risk factors for chronic allograft nephropathy after renal transplantation: a protocol biopsy study.

Abstract

Chronic allograft nephropathy (CAN) leads to chronic allograft dysfunction and loss. Regular renal transplant biopsies may be useful to find risk factors for CAN. We carried out 688 protocol biopsies in 258 patients at 6, 12, and 26 weeks after renal transplantation. Patients with signs of CAN in the biopsy 3 (N= 70, CAN group), and those without (N= 120, non-CAN group), were compared. Chronic tubulointerstitial changes increased from biopsy 1 to 3 (5% vs. 37%, P < 0.0001). Fifty-six of 190 patients had acute rejection within 6 months (30%), 33 of which were found in protocol biopsies (17%). On univariate analysis, the CAN group had CAN more often at biopsy 2 than the non-CAN group (23% vs. 4%, P < 0.0001), had a lower calculated creatinine clearance at biopsy 1 and 2 (49.4 +/- 25.8 vs. 57 +/- 20.2 mL/min, P= 0.01; 47.3 +/- 21.2 vs. 57.9 +/- 19.5 mL/min, P= 0.001, respectively), had a living donor less often than a brain dead donor (7% vs. 18%, P= 0.045), had a longer cold ischemia time (17.4 +/- 7 vs. 14.9 +/- 8.1 hours, P= 0.04), and had arterionephrosclerosis more often (24% vs. 12%, P= 0.02). On multivariate analysis, the differences in CAN at biopsy 2 (P= 0.001) and lower GFR at biopsy 2 (P= 0.002) were confirmed; in addition, nephrocalcinosis (P= 0.006) and acute rejection (P= 0.046) were found to occur more often. Chronic tubulointerstitial changes develop early after renal transplantation and are associated with reduced kidney function. Risk factors for CAN are arterionephrosclerosis (donor-related), nephrocalcinosis (related to preexisting hyperparathyroidism), a long cold-ischemia time (ischemia-perfusion-related), and acute rejection. Renal functional decline precedes morphologic changes of CAN, expressed as tubular atrophy and interstitial fibrosis.