Cattran D C, Appel G B, Hebert L A, Hunsicker L G, Pohl M A, Hoy W E, Maxwell D R, Kunis C L
Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Kidney Int. 2001 Apr;59(4):1484-90. doi: 10.1046/j.1523-1755.2001.0590041484.x.
A clinical trial of cyclosporine in patients with steroid-resistant membranous nephropathy (MGN) was conducted. Although MGN remains the most common cause of adult-onset nephrotic syndrome, its management is still controversial. Cyclosporine has been shown to be effective in cases of progressive MGN, but it has not been used in controlled studies at an early stage of the disease.
We conducted a randomized trial in 51 biopsy-proven idiopathic MGN patients with nephrotic-range proteinuria comparing 26 weeks of cyclosporine treatment plus low-dose prednisone to placebo plus prednisone. All patients were followed for an average of 78 weeks, and the short- and long-term effects on renal function were assessed.
Seventy-five percent of the treatment group versus 22% of the control group (P < 0.001) had a partial or complete remission of their proteinuria by 26 weeks. Relapse occurred in 43% (N = 9) of the cyclosporine remission group and 40% (N = 2) of the placebo group by week 52. The fraction of the total population in remission then remained almost unchanged and significant different between the groups until the end of the study (cyclosporine 39%, placebo 13%, P = 0.007). Renal function was unchanged and equal in the two groups over the test medication period. In the subsequent follow-up, renal insufficiency, defined as doubling of baseline creatinine, was seen in two patients in each group, but remained equal and stable in all of the other patients.
This study suggests that cyclosporine is an effective therapeutic agent in the treatment of steroid-resistant cases of MGN. Although a high relapse does occur, 39% of the treated patients remained in remission and were subnephrotic for at least one-year post-treatment, with no adverse effect on filtration function.
开展了一项环孢素治疗激素抵抗型膜性肾病（MGN）患者的临床试验。尽管MGN仍是成人肾病综合征最常见的病因，但其治疗仍存在争议。环孢素已被证明在进行性MGN病例中有效，但尚未在疾病早期的对照研究中使用。
我们对51例经活检证实为特发性MGN且有肾病范围蛋白尿的患者进行了一项随机试验，比较26周的环孢素治疗加小剂量泼尼松与安慰剂加泼尼松的疗效。所有患者平均随访78周，并评估对肾功能的短期和长期影响。
到26周时，治疗组75%的患者蛋白尿部分或完全缓解，而对照组为22%（P<0.001）。到第52周时，环孢素缓解组43%（N=9）的患者复发，安慰剂组40%（N=2）的患者复发。然后，缓解的总人群比例在两组之间几乎保持不变且有显著差异，直至研究结束（环孢素组39%，安慰剂组13%，P=0.007）。在试验用药期间，两组的肾功能均未改变且相当。在随后的随访中，每组有两名患者出现肾功能不全，定义为基线肌酐翻倍，但其他所有患者的肾功能仍相当且稳定。
本研究表明，环孢素是治疗激素抵抗型MGN的有效治疗药物。尽管确实有较高的复发率，但39%的接受治疗患者在治疗后至少一年内保持缓解且蛋白尿低于肾病水平，对滤过功能无不良影响。
