Saint Louis University Transplant Center, SSM-Saint Louis University Hospital, 1201 S. Grand Blvd., St. Louis, MO, 63104, USA.
Division of Nephrology, Istanbul University Istanbul School of Medicine, Istanbul, Turkey.
J Nephrol. 2023 May;36(4):979-986. doi: 10.1007/s40620-023-01588-x. Epub 2023 Feb 20.
Atypical hemolytic syndrome (aHUS) and C3 glomerulopathy (C3G) are complement-mediated rare diseases with excessive activation of the alternative pathway. Data to guide the evaluation of living-donor candidates for aHUS and C3G are very limited. The outcomes of living donors to recipients with aHUS and C3G (Complement disease-living donor group) were compared with a control group to improve our understanding of the clinical course and outcomes of living donation in this context.
Complement disease-living donor group [n = 28; aHUS(53.6%), C3G(46.4%)] and propensity score-matched control-living donor group (n = 28) were retrospectively identified from 4 centers (2003-2021) and followed for major cardiac events (MACE), de novo hypertension, thrombotic microangiopathy (TMA), cancer, death, estimated glomerular filtration rate (eGFR) and proteinuria after donation.
None of the donors for recipients with complement-related kidney diseases experienced MACE or TMA whereas two donors in the control group developed MACE (7.1%) after 8 (IQR, 2.6-12.8) years (p = 0.15). New-onset hypertension was similar between complement disease and control donor groups (21.4% vs 25%, respectively, p = 0.75). There were no differences between study groups regarding last eGFR and proteinuria levels (p = 0.11 and p = 0.70, respectively). One related donor for a recipient with complement-related kidney disease developed gastric cancer and another related donor developed a brain tumor and died in the 4th year after donation (2, 7.1% vs none, p = 0.15). No recipient had donor-specific human leukocyte antigen antibodies at the time of transplantation. Median follow-up period of transplant recipients was 5 years (IQR, 3-7). Eleven (39.3%) recipients [aHUS (n = 3) and C3G (n = 8)] lost their allografts during the follow-up period. Causes of allograft loss were chronic antibody-mediated rejection in 6 recipients and recurrence of C3G in 5. Last serum creatinine and last eGFR of the remaining patients on follow up were 1.03 ± 038 mg/dL and 73.2 ± 19.9 m/min/1.73 m2 for aHUS patients and 1.30 ± 0.23 mg/dL and 56.4 ± 5.5 m/min/1.73 m2 for C3G patients.
The present study highlights the importance and complexity of living related-donor kidney transplant for patients with complement-related kidney disorders and motivates the need for further research to determine the optimal risk-assessment for living donor candidates to recipients with aHUS and C3G.
非典型溶血性尿毒综合征（aHUS）和 C3 肾小球病（C3G）是补体介导的罕见疾病，其替代途径过度激活。指导 aHUS 和 C3G 活体供者评估的数据非常有限。因此，本研究比较了 aHUS 和 C3G（补体疾病-活体供者组）受者的活体供者与对照组的结局，以更好地了解在此背景下活体捐献的临床过程和结局。
从 4 个中心（2003-2021 年）回顾性确定补体疾病-活体供者组（n=28；aHUS[53.6%]，C3G[46.4%]）和倾向评分匹配的对照组-活体供者组（n=28），并随访主要心脏事件（MACE）、新发高血压、血栓性微血管病（TMA）、癌症、死亡、供体捐献后的估计肾小球滤过率（eGFR）和蛋白尿。
无补体相关肾脏疾病受者的供者发生 MACE 或 TMA，而对照组的 2 名供者在 8 年后（IQR，2.6-12.8）发生 MACE（7.1%，p=0.15）。补体疾病和对照组活体供者组新发高血压的发生率相似（分别为 21.4%和 25%，p=0.75）。两组之间最后 eGFR 和蛋白尿水平无差异（p=0.11 和 p=0.70，分别）。1 名补体相关肾脏疾病受者的相关供者发生胃癌，另 1 名相关供者发生脑瘤并在捐献后第 4 年死亡（2 例，7.1%；均无，p=0.15）。移植时受者均未出现供者特异性人类白细胞抗原抗体。移植受者的中位随访时间为 5 年（IQR，3-7）。11 名（39.3%）受者[aHUS（n=3）和 C3G（n=8）]在随访期间失去了同种异体移植物。6 名受者因慢性抗体介导的排斥反应，5 名受者因 C3G 复发而导致同种异体移植物丢失。最后一次血清肌酐和 eGFR 随访时 aHUS 患者分别为 1.03±0.38mg/dL 和 73.2±19.9m/min/1.73m2，C3G 患者分别为 1.30±0.23mg/dL 和 56.4±5.5m/min/1.73m2。
本研究强调了补体相关肾脏疾病患者进行活体相关供者肾移植的重要性和复杂性，并促使人们需要进一步研究以确定 aHUS 和 C3G 受者活体供者候选者的最佳风险评估。
