Goumenos D S, Kalliakmani P, Tsakas S, Sotsiou F, Vlachojannis J G
Department of Internal Medicine-Nephrology, University Hospital, Patras, Greece.
Clin Nephrol. 2004 Jan;61(1):17-24. doi: 10.5414/cnp61017.
Idiopathic membranous nephropathy (IMN), a common cause of nephrotic syndrome in adults, is usually treated by combination of corticosteroids with cytotoxic drugs. In cases resistant to this regimen, the use of cyclosporin A (CsA) is followed by frequent remissions of the nephrotic syndrome.
The purpose of this study was to estimate the effectiveness of prednisolone and small doses of CsA as first-line treatment of nephrotic patients with IMN, in relation to the progression of the disease, based on functional and histological changes.
Sixteen patients, with nephrotic syndrome due to IMN and well-preserved renal function, were treated with prednisolone (starting dose: 0.5 mg/kg bw/day) and CsA (starting dose: 3 mg/kg bw/day) for 24 months. A repeat renal biopsy was performed after 18 months of treatment in 10 patients with remission of nephrotic syndrome, to estimate the activity of the disease and to identify any features of CsA toxicity.
Remission of the nephrotic syndrome was observed in 14 out of 16 patients after 5 +/- 2 months of treatment. Complete remission was observed in 8 and partial remission in 6 patients (urinary protein was reduced from 6.9 +/- 3.4-0.2 +/- 0.06 g/24 h and 1.2 +/- 1.0 g/24 h, respectively, p < 0.01). The renal function was well preserved in 13 out of 16 patients over a 24-month period of treatment. Deterioration of renal function was observed in 3 patients (creatinine clearance reduced from 86 +/- 21-37 +/- 17 ml/min, p < 0.05) who had either persistent nephrotic syndrome or frequent relapses. Relapses of the nephrotic syndrome were observed in 5 of 14 patients. Repeat renal biopsies showed that glomerular sclerosis, tubulointerstitial injury, vascular hyalinosis and stage of the disease were deteriorated in most patients. Isometric vacuolization of tubular epithelial cells was observed in 2 of 10 patients.
IMN nephrotic patients treated with prednisolone and low doses of cyclosporin A showed a high remission rate of nephrotic syndrome. However, progression of chronic histological lesions was found in repeat renal biopsies. This suggests that cyclosporin can frequently induce remission of nephrotic syndrome in IMN patients, but even low doses of the drug are not free of potential renal toxicity.
特发性膜性肾病（IMN）是成人肾病综合征的常见病因，通常采用糖皮质激素与细胞毒性药物联合治疗。对于该治疗方案耐药的病例，使用环孢素A（CsA）后肾病综合征常频繁缓解。
本研究的目的是基于功能和组织学变化，评估泼尼松龙和小剂量CsA作为IMN肾病患者一线治疗对疾病进展的有效性。
16例因IMN导致肾病综合征且肾功能良好的患者，接受泼尼松龙（起始剂量：0.5mg/kg体重/天）和CsA（起始剂量：3mg/kg体重/天）治疗24个月。10例肾病综合征缓解的患者在治疗18个月后进行重复肾活检，以评估疾病活动度并确定CsA毒性的任何特征。
16例患者中，14例在治疗5±2个月后肾病综合征缓解。8例完全缓解，6例部分缓解（尿蛋白分别从6.9±3.4降至0.2±0.06g/24小时和从1.2±1.0降至1.2±1.0g/24小时，p<0.01）。16例患者中有13例在24个月的治疗期间肾功能良好。3例患者出现肾功能恶化（肌酐清除率从86±21降至37±17ml/分钟，p<0.05），这些患者要么患有持续性肾病综合征，要么频繁复发。14例患者中有5例肾病综合征复发。重复肾活检显示，大多数患者的肾小球硬化、肾小管间质损伤、血管玻璃样变和疾病分期均恶化。10例患者中有2例观察到肾小管上皮细胞等距空泡化。
接受泼尼松龙和低剂量环孢素A治疗的IMN肾病患者肾病综合征缓解率高。然而，重复肾活检发现慢性组织学病变进展。这表明环孢素可频繁诱导IMN患者肾病综合征缓解，但即使低剂量药物也并非没有潜在肾毒性。
