Washington University School of Medicine and St. Louis Children's Hospital, Room NWT 10-119, CB 8116, 660 South Euclid Avenue, St. Louis, MO, 63110, USA.
Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Pediatr Nephrol. 2024 Nov;39(11):3317-3331. doi: 10.1007/s00467-024-06452-z. Epub 2024 Jul 13.
Recurrence of focal segmental glomerulosclerosis (FSGS) or steroid-resistant nephrotic syndrome (SRNS) after kidney transplant leads to significant morbidity and potentially earlier allograft loss. To date however, reported rates, risk factors and treatment outcomes have varied widely.
We applied computational phenotypes to a multicenter aggregation of electronic health records data from 7 large pediatric health systems in the USA, to identify recurrence rates, risk factors, and treatment outcomes. We refined the data collection by chart review.
From > 7 million patients, we compared children with primary FSGS/SRNS who received a kidney transplant between 2009 and 2020 and who either developed recurrence (n = 67/165; 40.6%) or did not (n = 98/165). Serum albumin level at time of transplant was significantly lower and recipient HLA DR7 presence was significantly higher in the recurrence group. By 36 months post-transplant, complete remission occurred in 58.2% and partial remission in 17.9%. Through 6 years post-transplant, no remission after recurrence was associated with an increased risk of allograft loss over time (p < 0.0001), but any remission showed similar allograft survival and function decline to those with no recurrence. Since treatments were used in non-random fashion, using spline curves and multivariable non-linear analyses, complete + partial remission chance was significantly higher with greater plasmapheresis sessions, CTLA4-Ig doses or LDL-apheresis sessions. Only treatment with anti-CD20, CTLA4-Ig agents, or LDL-apheresis sessions were associated with complete remission. Excluding 25 patients with mutations did not significantly change our results.
Our contemporary high-risk cohort had higher favorable response rates than most prior reports, from combinations of agents.
肾移植后局灶节段性肾小球硬化症（FSGS）或激素耐药性肾病综合征（SRNS）的复发会导致严重的发病率，并可能导致早期移植物丢失。然而，迄今为止，报告的复发率、危险因素和治疗结果差异很大。
我们应用计算表型学方法对来自美国 7 个大型儿科医疗系统的电子病历数据进行了多中心聚集分析，以确定复发率、危险因素和治疗结果。我们通过病历回顾对数据收集进行了细化。
在超过 700 万患者中，我们比较了 2009 年至 2020 年期间接受肾移植且发生或未发生复发的原发性 FSGS/SRNS 儿童（复发组 n=67/165；40.6%，无复发组 n=98/165）。移植时血清白蛋白水平显著较低，受体 HLA DR7 存在显著较高。移植后 36 个月时，完全缓解率为 58.2%，部分缓解率为 17.9%。移植后 6 年，复发后无缓解与移植物丢失风险随时间增加相关（p<0.0001），但任何缓解与无复发者的移植物存活率和功能下降相似。由于治疗是非随机使用的，因此通过样条曲线和多变量非线性分析，血浆置换次数、CTLA4-Ig 剂量或 LDL 吸附次数越多，完全+部分缓解的机会越高。只有抗 CD20、CTLA4-Ig 药物或 LDL 吸附治疗与完全缓解相关。排除 25 名有突变的患者并没有显著改变我们的结果。
我们当代的高危队列的治疗效果比大多数先前的报告要好，这是由于多种药物联合使用的结果。
