Patterns of Renal Dysfunction and Profile of Kidney Biopsies in Hematopoietic Stem Cell Transplant Recipients

Abstract

Introduction: Post hematopoietic stem cell transplant (HSCT), kidney can be subjected to injury by various causes. Of these, Graft versus Host Disease (GvHD) affecting the kidney is an under-recognized entity with no clear guidelines on its diagnosis, clinicopathological manifestations and outcomes. Material and Methods: Out of 2930 patients who underwent HSCT at our centre between 2005 and 2020, kidney biopsy was performed in 19 allogenic and 5 autologous recipients. Results: The mean age of the cohort at transplant was 33.2 ± 7 years and 15 (62%) were males. Median time to kidney biopsy from HSCT was 14 (IQR, 9-30) months. Aplastic anemia was the most common underlying hematological disease (54.2%). All 19 allogenic recipients were classified based on clinicopathological manifestations into either thrombotic microangiopathy [TMA, 12/19 (63%)] or nephrotic syndrome [NS, 7/19 (37%)] pattern. Glomerular tuft ‘mesangiolysis’ was the dominant pattern of injury noted in 9/12 cases of TMA pattern. There was a predominance of acute microangiopathic changes restricted primarily to the glomerular compartment. Of the seven patients with NS pattern, membranous nephropathy (MN) was seen in 4 (57%) and minimal change disease (MCD) in 3 (43%) patients. Thirty nine percent (7/18) stained positive for C4d which was predominantly glomerular. Allogenic recipients who did not receive immunosuppression (IS) for renal disease had a lower eGFR at biopsy, a longer latency between withdrawal of GvHD prophylaxis and biopsy and were significantly at higher risk of kidney failure (IS: 2/11, 18.1% vs. No IS: 2/6, 33.3%, p=0.04). ‘Associated extra-renal GvHD’ occurred in 11/19 (57.9%) allogenic recipients. Patients with ‘associated extra-renal GvHD’ had significantly more death (6/11, 60% vs. 0, p=0.02) but comparable renal outcomes. Conclusion: Renal GvHD can present with or without ‘associated extra-renal GvHD’ after a prolonged period of withdrawal of GvHD prophylaxis, requiring careful diagnostic vigilance and consideration of immunosuppression.