Kidney biopsy analysis of 14 cases of renal disease after unrelated cord blood transplantation

Objective To evaluate kidney biopsy findings to clarify renal disease in patients after hematopoietic stem cell transplantation (HSCT) using unrelated umbilical cord blood transplantation (UCBT). Methods We retrospectively examined 14 patients who underwent UCBT at Toranomon Hospital, Tokyo, Japan, from 2015 to 2023 and subsequently developed kidney injury requiring biopsy. Results At biopsy, median urinary protein was 0.57 g/day (IQR, 0.27–1.67), median serum creatinine was 1.97 mg/dL (IQR, 1.81–2.6), and median eGFR was 25.3 mL/min/1.73 m 2 (IQR, 18.1–34.2). In 13 of 14 patients, mesangiolysis, glomerular basement membrane (GBM) duplication, and subendothelial widening without thrombi were observed—lesions defined as glomerular microangiopathy (GMA). Immunofluorescence and electron microscopy revealed no immune deposits typical of membranous nephropathy. Eleven patients showed distinctive arterial and arteriolar changes termed vascular microangiopathy. Nine exhibited severe interstitial fibrosis and tubular basement membrane duplication involving > 50% of the cortex. Human leukocyte antigen (HLA) incompatibility was found in 13 patients (92.9%) and ABO incompatibility in nine (64.2%). C4d positivity in glomeruli or peritubular capillaries was detected in 12 patients (85.7%). Conclusion: The coexistence of glomerular, vascular, and tubulointerstitial microangiopathic lesions was associated with mild proteinuria and renal dysfunction after UCBT. These findings suggest a chronic endothelial injury process distinct from classical thrombotic microangiopathy.