Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) As a Biomarker of Acute Kidney Injury Requiring Dialysis (AKI-D) in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation (HCT): Results from the Blood and Marrow Transplant Clinical Trials Network 1202 Study

Background AKI is a frequent complication following HCT. suPAR is a biomarker of AKI in the non-HCT population. We evaluated suPAR levels and association with AKI-D in patients undergoing allogeneic HCT. Performance of suPAR was compared with traditional biomarkers- serum creatinine (sCr) and neutrophil gelatinase-associated lipocalin (NGAL). Methods Data were obtained from BMT CTN 1202 cohort (NCT01879072). Patients 18 years or older with AKI post-HCT were included in the study. Subjects who did not develop AKI were included as controls and matched 1:1. Serum samples at 7,14, 21, 28, 56 & 90 days were analyzed for NGAL and suPAR (measured by ELISA) and sCr (measured by kinetic absorbance). The association between suPAR levels and AKI-D was analyzed using conditional logistic regression while Cox regression was used for overall survival (OS) with matching status stratified. P-value of < 0.01 was considered statistically significant. Results 62 pairs were included in the study. The two groups were balanced in demographic variables, except for graft vs. host disease (GVHD) prophylaxis- 80% of cases received tacrolimus-based prophylaxis as compared to controls (72%). The median time from transplant to AKI-D was 2.6 months in cases. The median day 7 suPAR was higher in cases (2.7 ng/mL) as compared to controls (2.1 ng/mL), P=0.002. In multivariable analysis, only day 7 suPAR was associated with development of AKI-D (odds ratio (OR) 1.83; P=0.009) (Table 1). The ROC curve for day 7 suPAR levels yielded AUC of 0.75. Neither NGAL nor sCr were associated with AKI-D at any time point. In multivariable analysis, day 7 suPAR was significantly associated with OS in both groups (Figure 1). Conclusion suPAR levels at day 7 post HCT may be an independent, early prognostic factor for occurrence of AKI-D. Early suPAR elevation post-HCT may be an early marker of inflammatory events leading to AKI-D. Also, day 7 suPAR may be prognostic of OS independent of AKI-D. These findings need to be validated in future studies.