Acute kidney injury in children after hematopoietic cell transplantation is associated with elevated urine CXCL10 and CXCL9.

TitleAcute kidney injury in children after hematopoietic cell transplantation is associated with elevated urine CXCL10 and CXCL9.
Publication TypeJournal Article
Year of Publication2020
AuthorsErez DLevy, Denburg MR, Afolayan S, Jodele S, Wallace G, Davies SM, Seif AE, Bunin N, Laskin BL, Sullivan KE
JournalBiol Blood Marrow Transplant
Date Published2020 Mar 09
ISSN1523-6536
Abstract

BACKGROUND AND OBJECTIVES: Acute kidney injury (AKI) is nearly universally associated with worse outcomes, especially among children after hematopoietic stem cell transplant (HCT). Our objective was to examine urinary immune biomarkers of AKI after HCT to provide insights into novel mechanisms of kidney injury in this population. Studying patients undergoing allogeneic (HCT) provides a unique opportunity to examine immune markers of AKI because the risk of AKI is high and the immune system newly develops after transplant.

DESIGN, SETTING, PARTICIPANTS: Children (>2 years old) and young adults undergoing their first allogeneic HCT and enrolled in a prospective, observational cohort study at two large children's hospitals had urine collected pre-HCT and monthly for the first 4 months after HCT. Urine samples at each monthly time point were assayed for 8 immune-related biomarkers. AKI was defined as a 1.5-fold increase in the monthly serum creatinine value which was recorded ±1 day from when the research urine sample was obtained, as compared to the pre-HCT baseline. Generalized estimating equation regression analysis evaluated the association between the monthly repeated measures (urinary biomarkers and AKI).

RESULTS: A total of 176 patients were included from two pediatric centers. Thirty-six subjects from one center were analyzed as a discovery cohort and the remaining 140 subjects from the second center were analyzed as a validation cohort. AKI rates were 18-35% depending on the monthly time point after HCT. Urine CXCL10 and CXCL9 concentrations were significantly higher among children who developed AKI compared with children who did not (p<0.01) in both cohorts. In order to gain a better understanding of the cellular source for these biomarkers in the urine, we also analyzed in vitro expression of CXCL10 and CXCL9 in kidney cell lines after stimulation with interferon-gamma and interferon-alpha. HEK293-epithelial kidney cells demonstrated interferon-induced expression of CXCL10 and CXCL9, suggesting a potential mechanism driving the key finding.

CONCLUSIONS: CXCL10 and CXCL9 are associated with AKI after HCT and are therefore promising biomarkers to guide improved diagnostic and treatment strategies for AKI in this high-risk population.

DOI10.1016/j.bbmt.2020.02.024
Alternate JournalBiol. Blood Marrow Transplant.
PubMed ID32165324
Grant ListK23 DK101600 / DK / NIDDK NIH HHS / United States