Supplementary Material for: Patterns of Renal Dysfunction and Profile of Kidney Biopsies in Hematopoietic Stem Cell Transplant Recipients

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.

引言：造血干细胞移植（hematopoietic stem cell transplant, HSCT）后，肾脏可受多种因素损伤。其中，累及肾脏的移植物抗宿主病（graft versus host disease, GvHD）是一种未被充分认识的疾病，目前尚无关于其诊断、临床病理表现及预后的明确指南。
材料与方法：2005年至2020年间，本中心共完成2930例造血干细胞移植术，其中19例异体移植受体与5例自体移植受体接受了肾脏活检。
结果：本队列患者移植时的平均年龄为33.2±7岁，其中15例（62%）为男性。从造血干细胞移植至肾脏活检的中位时间为14个月（四分位间距，9~30个月）。再生障碍性贫血是最常见的基础血液系统疾病（54.2%）。所有19例异体移植受体均根据临床病理表现分为血栓性微血管病（thrombotic microangiopathy, TMA）组[12/19例（63%）]或肾病综合征（nephrotic syndrome, NS）组[7/19例（37%）]。在TMA组的12例患者中，9例可见肾小球簇“系膜溶解”为主要损伤模式，且以主要累及肾小球的急性微血管病变为主。在7例NS组患者中，4例（57%）为膜性肾病（membranous nephropathy, MN），3例（43%）为微小病变肾病（minimal change disease, MCD）。18例患者中7例（39%）的C4d染色呈阳性，且阳性信号主要分布于肾小球。未接受肾脏疾病免疫抑制治疗（immunosuppression, IS）的异体移植受体在活检时的估算肾小球滤过率（eGFR）更低，从停用移植物抗宿主病预防治疗至活检的潜伏期更长，且发生肾衰竭的风险显著更高（免疫抑制组：2/11例，18.1% vs 未免疫抑制组：2/6例，33.3%，p=0.04）。11例（57.9%）异体移植受体出现“伴发肾外GvHD”。伴发肾外GvHD的患者死亡率显著更高（6/11例，60% vs 0，p=0.02），但肾脏预后无显著差异。
结论：肾移植物抗宿主病可在停用移植物抗宿主病预防治疗较长一段时间后出现，伴或不伴肾外GvHD，临床需保持审慎的诊断警惕性，并考虑给予免疫抑制治疗。