A multicenter retrospective study of calcineurin inhibitors in nephrotic syndrome secondary to podocyte gene variants
A multicenter retrospective study of calcineurin inhibitors in nephrotic syndrome secondary to podocyte gene variants
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DOI：
10.1016/j.kint.2023.02.022
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发表时间：
2023-04-19
影响因子：
19.6
通讯作者：
Tullus，Kjell
中科院分区：
文献类型：
--
作者：
Malakasioti，Georgia;Iancu，Daniela;Tullus，Kjell
尽管44%-83%的患有激素抵抗型肾病综合征(SRNS)的儿童没有明确的遗传原因，但对钙调神经磷酸酶抑制剂(CNI)的治疗有反应，目前的指南建议不要在单基因SRNS中使用免疫抑制。尽管现有证据表明CNI治疗缓解是可能的，并且可以改善某些单基因SRNS的预后。在此，我们的回顾性研究评估了接受CNI治疗至少三个月的单基因SRNS儿童的反应频率、反应的预测因素和肾功能结果。资料来自37个儿科肾病中心的203例患儿，年龄0~18岁。遗传学家回顾了变异的致病性，122名A致病基因的患者和19名可能致病基因的患者被纳入分析。经过6个月的治疗和最后一次随访，27.6%和22.5%的患者表现为部分或完全缓解。在最后一次随访中，与无反应相比，在治疗6个月时达到至少部分缓解的肾衰竭风险显著降低(风险比[95%可信区间]0.25，[0.10-0.62])。此外，当只考虑那些随访超过两年的患者时，肾功能衰竭的风险显著降低(风险比0.35，[0.14-0.91])。CNI开始时较高的血清白蛋白水平是与6个月后显著缓解可能性增加相关的唯一因素(优势比[95%可信区间]1.16，[1.08-1.24])。因此，我们的研究结果证明，在患有单基因SRN的儿童中也可以进行CNI治疗试验。
While 44-83% of children with steroid-resistant nephrotic syndrome (SRNS) without a proven genetic cause respond to treatment with a calcineurin inhibitor (CNI), current guidelines recommend against the use of immunosuppression in monogenic SRNS. This is despite existing evidence suggesting that remission with CNI treatment is possible and can improve prognosis in some cases of monogenic SRNS. Herein, our retrospective study assessed response frequency, predictors of response and kidney function outcomes among children with monogenic SRNS treated with a CNI for at least three months. Data from 203 cases (age 0-18 years) were collected from 37 pediatric nephrology centers. Variant pathogenicity was reviewed by a geneticist, and 122 patients with a pathogenic and 19 with a possible pathogenic genotype were included in the analysis. After six months of treatment and at last visit, 27.6% and 22.5% of all patients respectively, demonstrated partial or full response. Achievement of at least partial response at six months of treatment conferred a significant reduction in kidney failure risk at last follow-up compared to no response (hazard ratio [95% confidence interval] 0.25, [0.10-0.62]). Moreover, risk of kidney failure was significantly lower when only those with a follow-up longer than two years were considered (hazard ratio 0.35, [0.14-0.91]). Higher serum albumin level at CNI initiation was the only factor related to increased likelihood of significant remission at six months (odds ratio [95% confidence interval] 1.16, [1.08-1.24]). Thus, our findings justify a treatment trial with a CNI also in children with monogenic SRNS.