文献速递 | 治疗微小病变肾病，他克莫司与糖皮质激素谁优谁劣？

微小病变肾病（MCD）又称微小病变性肾小球疾病，是引起原发性肾病综合征（NS）的常见病理类型，占成人原发性NS的10%～15%^[1]。大剂量糖皮质激素被推荐用于MCD的初始治疗，儿童MCD对糖皮质激素治疗敏感，而成人MCD对糖皮质激素反应则较差^[2]，复发率超过50%，且有三分之一的患者为频繁复发或糖皮质激素依赖^[3]，导致患者需要反复或长期使用糖皮质激素。由此产生的糖皮质激素相关不良反应给患者造成了严重影响，包括外貌改变、体重增加、糖耐量受损、骨质疏松、感染和胃肠道出血^[4,5]。因此临床一直在积极探索糖皮质激素替代治疗方案。

他克莫司（tacrolimus，TAC）作为第二代钙调磷酸酶抑制剂，可以抑制IL-2转录，抑制T细胞的生长和分化，从而最终减少足细胞的免疫损伤，此外还能通过稳定足细胞骨架起到足细胞保护作用^[6,7]。多项研究显示TAC可成功治疗频繁复发、激素依赖和激素抵抗MCD^[8,9]。但TAC单药作为成人MCD一线初始药物的疗效有待进一步确证。

2022年发表的一项Meta分析^[10]比较TAC单药与糖皮质激素作为初始治疗在成人MCD患者中的疗效和安全性，该项Meta分析共纳入4项随机对照试验（RCT），196例成人MCD患者。

疗效分析

结果显示，TAC单药治疗与糖皮质激素具有相似的完全缓解率（OR1.06，95%CI0.47-2.41，P=0.89）、总缓解率（OR1.30，95%CI 0.39-4.35，P=0.67）、复发率（OR0.63，95%CI0.28-1.42，P=0.26）。

安全性分析

结果显示，初期TAC组患者的感染发生率（OR0.54，95%CI0.23-1.27，P=0.15）和葡萄糖不耐受发生率（OR0.55，95%CI0.16-1.84，P=0.33）低于糖皮质激素组，但无统计学差异；两组急性肾衰竭发生率相当（OR1.37，95%CI0.36-7.31，P=0.71）。

结论：TAC单药治疗MCD的初期疗效与糖皮质激素单药相当，该结论需要更多大型多中心RCT证实。

参考文献：

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[2]Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021;100(4S):S1-S276.

[3]Tse KC, Lam MF, Yip PS, et al. Idiopathic minimal change nephrotic syndrome in older adults: steroid responsiveness and pattern of relapses. Nephrol Dial Transplant. 2003;18(7):1316-1320.

[4]Shinzawa M, Yamamoto R, Nagasawa Y, et al. Comparison of methylprednisolone plus prednisolone with prednisolone alone as initial treatment in adult-onset minimal change disease: a retrospective cohort study. Clin J Am Soc Nephrol. 2014;9(6):1040-1048.

[5]Eguchi A, Takei T, Yoshida T, Tsuchiya K, Nitta K. Combined cyclosporine and prednisolone therapy in adult patients with the first relapse of minimal-change nephrotic syndrome. Nephrol Dial Transplant. 2010;25(1):124-129.

[6]Rauch MC, San Martín A, Ojeda D, et al. Tacrolimus causes a blockage of protein secretion which reinforces its immunosuppressive activity and also explains some of its toxic side-effects. Transpl Immunol. 2009;22(1-2):72-81.

[7]Faul C, Donnelly M, Merscher-Gomez S, et al. The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A[J]. Nat Med, 2008, 14(9): 931-8.

[8]Li H, Shi X, Shen H, et al. Tacrolimus versus intravenous pulse cyclophosphamide therapy in Chinese adults with steroid-resistant idiopathic minimal change nephropathy: a multicenter, open-label, nonrandomized cohort trial. Clin Ther. 2012;34(5):1112-1120.

[9]Li X, Li H, Chen J, et al. Tacrolimus as a steroid-sparing agent for adults with steroid-dependent minimal change nephrotic syndrome. Nephrol Dial Transplant. 2008;23(6):1919-1925.

[10]Lu J, Xu Z, Xu W, et al. Efficacy and safety of tacrolimus versus corticosteroid as initial monotherapy in adult-onset minimal change disease: a meta-analysis. Int Urol Nephrol. 2022;54(9):2205-2213.