Urinary elafin and kidney injury in hematopoietic cell transplant recipients

Abstract

Background and objectives Graft-versus-host disease (GVHD) is associated with kidney injury after hematopoietic cell transplantation (HCT). Because plasma elafin levels correlate with skin GVHD, this study examined urinary elafin as a potential marker of renal inflammation and injury. Design, setting, participants,&measurementsUrinewas collected prospectively on 205 patients undergoing their first HCT from 2003 to 2010. Collections were done at baseline, weekly through day 100, and monthly through year 1 to measure elafin and urine albumin-to-creatinine ratio (ACR). Associations between urinary elafin levels andmicroalbuminuria,macroalbuminuria, AKI and CKD, and mortalitywere examined using Cox proportional hazards or linear regressionmodels.Available kidney biopsy specimenswere processed for immunohistochemistry. Results Mean urinary elafin levels to day 100were higher in patients withmicro- ormacroalbuminuria (adjusted mean difference, 529 pg/ml; P=0.03) at day 100 than in thosewith a normal ACR (adjustedmean difference, 1295 pg/ml; P˂0.001). Mean urinary elafin levels were higher in patients with AKI compared with patients without AKI (adjusted mean difference, 558 pg/ml; P˂0.01). The average urinary elafin levels within the first 100 days after HCT were higher in patients who developed CKD at 1 year than in patients without CKD (adjusted mean difference, 894 pg/ml; P=0.002). Among allogeneic recipients, a higher proportion of patients with micro- or macroalbuminuria at day 100 also had grade II-IV acute GVHD (80% and 86%, respectively) compared with patients with a normal ACR (58%; global P˂0.01). Each increase in elafin of 500 pg/ml resulted in a 10%increase in risk of persistent macroalbuminuria (hazard ratio, 1.10; 95%confidence interval [95%CI], 1.06 to 1.13; P˂0.001) and a 7% increase in the risk of overall mortality (95% CI, 1.02 to 1.13, P˂0.01). Renal biopsy specimens from a separate cohort of HCT survivors demonstrated elafin staining in distal and collecting duct tubules. Conclusion Higher urinary elafin levels are associated with an increased risk of micro- and macroalbuminuria, AKI and CKD, and death after HCT.