Division of Nephrology, Department of Medicine, Oregon Health Science University, Portland, Oregon.
Division of Nephrology, Department of Medicine, Columbia University Medical Center, New York, New York; and.
Clin J Am Soc Nephrol. 2018 Mar 7;13(3):406-413. doi: 10.2215/CJN.09080817. Epub 2018 Jan 11.
C3 glomerulopathy is a form of complement-mediated GN. Immunosuppressive therapy may be beneficial in the treatment of C3 glomerulopathy. Mycophenolate mofetil is an attractive treatment option given its role in the treatment of other complement-mediated diseases and the results of the Spanish Group for the Study of Glomerular Diseases C3 Study. Here, we study the outcomes of patients with C3 glomerulopathy treated with steroids and mycophenolate mofetil.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective chart review of patients in the C3 glomerulopathy registry at Columbia University and identified patients treated with mycophenolate mofetil for at least 3 months and follow-up for at least 1 year. We studied clinical, histologic, and genetic data for the whole group and compared data for those who achieved complete or partial remission (responders) with those who did not achieve remission (nonresponders). We compared remission with mycophenolate mofetil with remission with other immunosuppressive regimens.
We identified 30 patients who met inclusion criteria. Median age was 25 years old (interquartile range, 18-36), median creatinine was 1.07 mg/dl (interquartile range, 0.79-1.69), and median proteinuria was 3200 mg/g creatinine (interquartile range, 1720-6759). The median follow-up time was 32 months (interquartile range, 21-68). Twenty (67%) patients were classified as responders. There were no significant differences in baseline characteristics between responders and nonresponders, although initial proteinuria was lower (median 2468 mg/g creatinine) in responders compared with nonresponders (median 5000 mg/g creatinine) and soluble membrane attack complex levels were higher in responders compared with nonresponders. For those tapered off mycophenolate mofetil, relapse rate was 50%. Genome-wide analysis on complement genes was done, and in 12 patients, we found 18 variants predicted to be damaging. None of these variants were previously reported to be pathogenic. Mycophenolate mofetil with steroids outperformed other immunosuppressive regimens.
Among patients who tolerated mycophenolate mofetil, combination therapy with steroids induced remission in 67% of this cohort. Heavier proteinuria at the start of therapy and lower soluble membrane attack complex levels were associated with treatment resistance.
C3 肾小球病是一种补体介导的肾小球肾炎。免疫抑制治疗可能对 C3 肾小球病的治疗有益。霉酚酸酯具有治疗其他补体介导疾病的作用，且西班牙肾小球疾病研究组 C3 研究结果表明其是一种有吸引力的治疗选择。在此，我们研究了接受霉酚酸酯和类固醇治疗的 C3 肾小球病患者的结局。
设计、地点、参与者和测量方法：我们对哥伦比亚大学 C3 肾小球病登记处的患者进行了回顾性图表审查，并确定了接受霉酚酸酯治疗至少 3 个月且随访至少 1 年的患者。我们研究了整个组的临床、组织学和遗传数据，并比较了完全或部分缓解（应答者）与未缓解（非应答者）患者的数据。我们比较了霉酚酸酯联合类固醇与其他免疫抑制方案的缓解情况。
我们确定了 30 名符合纳入标准的患者。中位年龄为 25 岁（四分位距 18-36），中位肌酐为 1.07mg/dl（四分位距 0.79-1.69），中位蛋白尿为 3200mg/g 肌酐（四分位距 1720-6759）。中位随访时间为 32 个月（四分位距 21-68）。20 名（67%）患者被归类为应答者。应答者和非应答者之间的基线特征无显著差异，尽管应答者的初始蛋白尿较低（中位数 2468mg/g 肌酐），而非应答者的蛋白尿较高（中位数 5000mg/g 肌酐），且应答者的可溶性膜攻击复合物水平高于非应答者。对于那些停用霉酚酸酯的患者，复发率为 50%。对补体基因进行了全基因组分析，在 12 名患者中发现了 18 个预测为致病性的变异。这些变异均未被报道为致病性。霉酚酸酯联合类固醇优于其他免疫抑制方案。
在耐受霉酚酸酯的患者中，联合类固醇治疗诱导了该队列中 67%的缓解。治疗开始时蛋白尿较重和可溶性膜攻击复合物水平较低与治疗抵抗相关。
