Urinary CXCL10 and CXCL9 Are Associated with Acute Kidney Injury in Children after Hematopoietic Stem Cell Transplantation: Results of a Discovery and Validation Cohort

Abstract

Introduction Acute kidney injury (AKI) is a frequent occurrence within the first 100 days post HCT. The incidence varies widely, reports ranging from 27-70%. The development of targeted strategies to reduce this risk is limited by multiple risk features of HCT. Methods We analyzed urine samples and clinical data from children (2-19 yrs) undergoing their first allogeneic HCT and enrolled in a prospective cohort study at the Children's Hospital of Philadelphia (CHOP) and Cincinnati Children's Hospital (CCHMC). Urine was collected at baseline and monthly for the first 4 months, frozen, and later analyzed by ELISA for the chemoattractant cytokines CXCL10 and CXCL9. Data were analyzed as raw concentrations and also adjusted for urine creatinine. AKI was defined as a 1.5x increase of serum creatinine from the day of urine sample collection (±1 day) compared to the pre-HCT baseline. Generalized estimating equations, accounting for repeated measures, tested the association between the urinary biomarkers and AKI. Results 36 subjects received HCT at CHOP and 141 subjects received HCT at CCHMC (Table). Overall, 35% of patients at CHOP and 16% of those at CCHMC developed AKI in the first 4 months after HCT. Acute graft versus host disease occurred in 21/36 (58%) and 50/141 (35%) at CHOP and CCHMC, respectively. Dialysis was required in 1/36 (2.7%) at CHOP and 14/141 (9%) at CCHMC. Raw urine CXCL10 and CXCL9 concentrations were significantly higher among children who developed AKI compared with children who did not develop AKI. CXCL10 adjusted for creatinine was also significantly associated with AKI (p 200 pg/ml was 4.6 (95% CI 1.7-12.6; p 0 pg/ml was 4.7 (95% CI 1.7-12.7; p 200 pg/ml was 2.65 (95% CI 1.2-6.0; p 0 pg/ml was 2.2 (95% CI 1.3-3.9; p Conclusions AKI is common in the first 4 months after HCT, although the risk varied across centers. Higher urine concentrations of CXCL9 and CXCL10 were significantly associated with AKI. This data supports a potential role for inflammation in the pathogenesis of AKI after HCT.