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

Abstract

Background: Chronic allograft nephropathy (CAN) leads to chronic allograft dysfunction and loss. Regular renal transplant biopsies may be useful to find risk factors for CAN.

Methods: 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.

Results: 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.

Conclusion: 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.