Glomerular monocytes predict worse outcomes after acute renal allograft rejection independent of C4d status.
BACKGROUND
Both peritubular capillary (PTC) C4d deposition and macrophage/monocyte (MO) infiltration in acute rejection (AR) have separately been shown to be associated with reduced graft survival and recently were demonstrated to be closely correlated in AR. Whether MO infiltration is an independent predictor of graft outcome is uncertain.


METHODS
All patients with biopsy-proven AR (over a 3-year period) were included (N= 96). All biopsies (N= 121) were graded according to the Banff 97 criteria and immunohistochemically stained for C4d and MO (CD68). The primary outcome was glomerular filtration rate (GFR) <30 mL/min 1-year posttransplant as estimated by the Modified Diet in Renal Disease (MDRD) Formula. Secondary outcomes at 2 and 4 years' posttransplant were also explored. A variety of clinical and biopsy variables were statistically analyzed to establish univariate predictors of graft outcome. Stepwise multivariate logistic regression modeling was applied to determine independent predictors of outcomes.


RESULTS
There was a close correlation between PTC C4d and glomerular MO infiltration (P < 0.001). Univariate predictors of primary outcome (GFR <30 mL/min 1-year posttransplant) included mean glomerular MO count > or =1.0 MO/glomerulus (P= 0.014), female sex (P= 0.02), higher peak (P= 0.005), and pretransplant (P= 0.003) panel-reactive antibody levels, cadaveric donor (P= 0.006), transplant glomerulitis (P= 0.004), and longer cold ischemic time (CIT) (P= 0.002). Mean MO/glomerulus > or =1.0 [OR 10.3 (1.23, 87.1)], female sex [OR 5.27(1.31, 21.1)], and CIT [OR 1.14 (1.06, 1.25)] were identified as independent predictors of adverse graft outcome. Furthermore, mean MO/glomerulus > or =1.0 independently predicted poor renal function at 2 years [OR 3.89 (1.19, 12.70)] and 4 years [OR 4.03 (1.22, 13.28)] posttransplant.


CONCLUSIONS
The results demonstrate that glomerular MO infiltration is an independent predictor of worse outcomes posttransplant following acute renal allograft rejection.
Tinckam
Kathryn J
KJ
Division of Nephrology, Department of Medicine, Centre for Health Evaluation and Outcome Sciences, St. Paul's Hospital, Vancouver, British Columbia, Canada.
Djurdjev
Ognjenka
O
Magil
Alex B
AB
D000208:Acute Disease; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D015935:Complement C4b / Q000378:metabolism*; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology*; D010446:Peptide Fragments / Q000378:metabolism*; D011183:Postoperative Complications / Q000276:immunology / Q000473:pathology; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D014184:Transplantation, Homologous
D015415:Biomarkers; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d