Changes in Microbiome in Patients with Kidney Injury after Allogeneic Hematopoietic Stem Cell Transplantation.

Abstract

Acute kidney injury (AKI) is a common complication of allogeneic hematopoietic cell transplantation (allo-HCT) that increases the risk of mortality. In contrast, higher diversity of intestinal microbiota at the time of neutrophil engraftment has been associated with lower mortality. We aimed to better understand kidney outcomes in relation to changes in gut diversity in this patient population, hypothesizing that patients with lower microbiome diversity at baseline and at engraftment were at higher risk of developing kidney complications. We performed a single-center retrospective study of 419 hematopoietic cell transplant recipients from 2014-2017 at our institution whose gut microbiota were analyzed. We defined AKI and CKD based on KDIGO criteria and estimated glomerular filtration rate (GFR) using the CKD Epidemiology Collaboration equation. We defined gut microbiome diversity using Shannon and Simpson reciprocal diversity indices, with higher levels indicating more diverse microbiota. Simpson reciprocal DI and Shannon DI were 21.8 (IQR: 13.7, 35.2; range: 1.6, 102.5) and 3.7 (IQR: 3.2, 4.2; range: 0.7,5.2) in our cohort at baseline and 6.3 (IQR: 3.7, 10.4) and 2.3 (IQR: 1.7, 2.8) at peri-engraftment. Of the 419, 263 patients (63%) developed any grade AKI in 100 days post-HCT, and 114 (27%) developed Grade 2+ AKI. There were no significant differences in microbiome diversity at baseline or peri-engraftment in patients who developed post-transplant AKI or CKD, respectively, in comparison to those who did not develop kidney complications. Our findings do not support the existence of a link between baseline or peri-engraftment gut diversity and the risk for development of AKI or CKD in patients undergoing allo-HCT. This study highlights the complex and multifactorial etiology of AKI in allo-HCT recipients and the need for additional prospective and mechanistic studies.