Laurin Louis-Philippe, Gasim Adil M, Poulton Caroline J, Hogan Susan L, Jennette J Charles, Falk Ronald J, Foster Bethany J, Nachman Patrick H
Division of Nephrology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada; Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec, Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada; Division of Nephrology and Hypertension, University of North Carolina Kidney Center and
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina;
Clin J Am Soc Nephrol. 2016 Mar 7;11(3):386-94. doi: 10.2215/CJN.07110615. Epub 2016 Feb 16.
In primary FSGS, calcineurin inhibitors have primarily been studied in patients deemed resistant to glucocorticoid therapy. Few data are available about their use early in the treatment of FSGS. We sought to estimate the association between choice of therapy and ESRD in primary FSGS.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used an inception cohort of patients diagnosed with primary FSGS by kidney biopsy between 1980 and 2012. Factors associated with initiation of therapy were identified using logistic regression. Time-dependent Cox models were performed to compare time to ESRD between different therapies.
In total, 458 patients were studied (173 treated with glucocorticoids alone, 90 treated with calcineurin inhibitors with or without glucocorticoids, 12 treated with other agents, and 183 not treated with immunosuppressives). Tip lesion variant, absence of severe renal dysfunction (eGFR≥30 ml/min per 1.73 m(2)), and hypoalbuminemia were associated with a higher likelihood of exposure to any immunosuppressive therapy. Only tip lesion was associated with initiation of glucocorticoids alone over calcineurin inhibitors. With adjusted Cox regression, immunosuppressive therapy with glucocorticoids and/or calcineurin inhibitors was associated with better renal survival than no immunosuppression (hazard ratio, 0.49; 95% confidence interval, 0.28 to 0.86). Calcineurin inhibitors with or without glucocorticoids were not significantly associated with a lower likelihood of ESRD compared with glucocorticoids alone (hazard ratio, 0.42; 95% confidence interval, 0.15 to 1.18).
The use of immunosuppressive therapy with calcineurin inhibitors and/or glucocorticoids as part of the early immunosuppressive regimen in primary FSGS was associated with improved renal outcome, but the superiority of calcineurin inhibitors over glucocorticoids alone remained unproven.
在原发性局灶节段性肾小球硬化(FSGS)中,钙调神经磷酸酶抑制剂主要在被认为对糖皮质激素治疗耐药的患者中进行研究。关于其在FSGS治疗早期的使用数据很少。我们试图评估原发性FSGS治疗选择与终末期肾病(ESRD)之间的关联。
设计、地点、参与者及测量:我们使用了一个起始队列,该队列中的患者在1980年至2012年间通过肾活检被诊断为原发性FSGS。使用逻辑回归确定与开始治疗相关的因素。采用时间依赖性Cox模型比较不同治疗方法至ESRD的时间。
总共研究了458例患者(173例仅接受糖皮质激素治疗,90例接受钙调神经磷酸酶抑制剂治疗,联合或不联合糖皮质激素,12例接受其他药物治疗,183例未接受免疫抑制剂治疗)。顶端病变变异型、无严重肾功能不全(估算肾小球滤过率[eGFR]≥30 ml/min/1.73 m²)和低白蛋白血症与接受任何免疫抑制治疗的可能性较高相关。只有顶端病变与仅开始使用糖皮质激素而非钙调神经磷酸酶抑制剂相关。经校正的Cox回归分析显示,与不进行免疫抑制相比,使用糖皮质激素和/或钙调神经磷酸酶抑制剂进行免疫抑制治疗与更好的肾脏存活率相关(风险比,0.49;95%置信区间,0.28至0.86)。与仅使用糖皮质激素相比,联合或不联合糖皮质激素使用钙调神经磷酸酶抑制剂与ESRD发生可能性较低无显著关联(风险比,0.42;95%置信区间,0.15至1.18)。
在原发性FSGS的早期免疫抑制方案中,使用钙调神经磷酸酶抑制剂和/或糖皮质激素进行免疫抑制治疗与改善肾脏结局相关,但钙调神经磷酸酶抑制剂相对于单独使用糖皮质激素的优越性仍未得到证实。