Increase Urinary Biomarkers of Kidney Injury in Patients After Allogenic Hematopoietic Stem Cell Transplant Reflect Kidney Damage Even in Normal Kidney Function

Abstract

Kidney function in patients undergoing hematopoietic stem cell transplant (HSCT) is frequently worsened by previous chemotherapy and exposure to a variety of nephrotoxic drugs. The aim of the study was to assess biomarkers of kidney injury in patients at least 3 months after HSCT under ambulatory care of the Hematology, Oncology and Internal Medicine Department. We studied 80 prevalent patients after allogeneic HSCT and 32 healthy volunteers to obtain normal ranges for biomarkers. In this cross-sectional study, the following biomarkers of kidney injury in urine were evaluated using commercially available assays: IGFBP7 and TIMP2, netrin-1, and semaphorin A2. All of the biomarkers studied were significantly higher in patients after HSCT compared with the healthy volunteers. When we divided patients according to kidney function (below and over 60 mL/min/1.73m2), we found that only concentration of IGFBP7 was significantly higher in 23 patients with chronic kidney disease (CKD) stage 3 relative to patients with an estimated glomerular filtration rate (eGFR) over 60 mL/min/1.73m2. All biomarkers in both subgroups of patients with eGFRs below and over 60 mL/min/1.73m2 were significantly higher relative to healthy volunteers. In univariate correlations, semaphorin A2 was related to netrin-1 (r = 0.47, P < .001), IGFBP7 (r = 0.35, P < .01), and TIMP2 (r = 0.32, P < .01), whereas IGFBP7 was positively related to serum creatinine (r = 0.38, P < .001) and inversely to eGFR (r = -0.36, P < .001). Patients after allogeneic HSCT, despite normal or near normal kidney function, show evidence of kidney injury.