Patterns of chronic injury in pediatric renal allografts.
BACKGROUND
In pediatric recipients, the pathophysiology of chronic renal allograft injury is poorly understood.


METHODS
We studied the evolution and determinants of tubulointerstitial, vascular, and glomerular injury in 240 pediatric protocol renal allograft biopsies during the first 5 years posttransplant.


RESULTS
Chronic tubulointerstitial injury (ci, ct) developed predominantly during the first 12 months posttransplant, whereas chronic vascular damage (cv, and arteriolar hyalinosis [ah]) and global glomerulosclerosis (gs) became increasingly prevalent at 25 to 36 months and beyond. Chronic interstitial lesions were associated with acute rejection and borderline histology (odds ratio [OR] 2.3, P<0.04), recipient body surface area less than 1.0 m2 (OR 3.6, P<0.05), and obesity (OR 2.0, P<0.03). Determinants of ct were acute rejection (OR 2.6, P=0.02) and acute tubular necrosis (OR 2.8, P<0.04). Vascular fibrous intimal thickening and ah were associated with donor hypertension (OR 3.6, P=0.001) and recipient body surface area less than 1.0 m (OR 2.6, P=0.02), respectively. The severity of ah correlated with the incidence of gs (r=0.32, P<0.0001), with 7.8% gs for ah0, 14.3% gs for ah1, 60.0% gs for ah2, and 95.5% gs for ah3 (median values). Antibody induction conferred protection from ci (OR 0.31, P=0.008), ct (OR 0.33, P=0.002), and ah (OR 0.12, P<0.001) progression.


CONCLUSIONS
By 5 years posttransplant, pediatric renal allografts manifest a substantial burden of tubulointerstitial and microvascular injury. These lesions are associated with donor hypertension, acute inflammation, renal hypoperfusion, obesity, and calcineurin inhibitor toxicity. The pervasiveness and rapid progression of microvascular lesions at 25 to 36 months suggest that attempts at reducing calcineurin inhibitor exposure should be made before two years posttransplant.
Department of Pediatrics, University of Manitoba, Winnipeg, MB, Canada.
Allison B
AB
Dart
Albrecht
A
Schall
Ian W
IW
Gibson
Tom D
TD
Blydt-Hansen
Patricia E
PE
Birk
D000208:Acute Disease; D001706:Biopsy; D002648:Child; D003404:Creatinine / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007249:Inflammation / Q000473:pathology; D007674:Kidney Diseases / Q000145:classification / Q000601:surgery; D007678:Kidney Glomerulus / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000473:pathology; D008297:Male; D044469:Racial Groups; D012079:Renal Circulation; D014019:Tissue Donors / Q000706:statistics & numerical data; D014184:Transplantation, Homologous / Q000473:pathology
D007166:Immunosuppressive Agents; D003404:Creatinine