title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nephrology; and Department of Pathology, Hannover Medical School, Hannover, Germany. schwarz.anke@mh-hannover.de
authors.forename: Anke
authors.initials: A
authors.lastname: Schwarz
authors.forename: Michael
authors.initials: M
authors.lastname: Mengel
authors.forename: Wilfried
authors.initials: W
authors.lastname: Gwinner
authors.forename: Joerg
authors.initials: J
authors.lastname: Radermacher
authors.forename: Marcus
authors.initials: M
authors.lastname: Hiss
authors.forename: Hans
authors.initials: H
authors.lastname: Kreipe
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
mesh_terms: D001284:Atrophy; D001706:Biopsy; D002908:Chronic Disease; D002985:Clinical Protocols; D005260:Female; D005355:Fibrosis; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013997:Time Factors; D014184:Transplantation, Homologous