Yang Y, Ohta K, Shimizu M, Nakai A, Kasahara Y, Yachie A, Koizumi S
Department of Pediatrics, Graduate School of Medical Science, Faculty of Medicine, Kanazawa University, Kanazawa, Ishikawa, Japan.
Clin Nephrol. 2005 Jul;64(1):35-40. doi: 10.5414/cnp64035.
IgA nephropathy associated with heavy proteinuria is considered a more progressive form of this disease. In this report, we describe the favorable clinical effect of combination therapy with low doses of an angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) in the chronic stage of pediatric IgA nephropathy associated with heavy proteinuria.
We initially used ACEI for seven children with IgA nephropathy and heavy proteinuria who did not achieve remission with the routine treatment including steroids.
With ACEI therapy alone, only three patients showed an antiproteinuric response. In one of the three patients, the proteinuria decreased by half, but was still over 1 g/day. In the other four patients, the proteinuria did not decrease. In these five patients, of whom one partial was a responder and four were non-responders for ACEI, ARB was added, and in marked contrast to ACEI therapy alone, the antiproteinuric effect was significantly augmented (p < 0.01). The antiproteinuric response induced by combination therapy was not accompanied by blood pressure changes. Urinary low-molecular protein and N-acetyl-beta-D-glucosaminidase (NAG) levels tended to decrease after both ACEI alone and combination therapy.
These data indicate that inhibition therapy of the angiotensin system not only decreases proteinuria levels but also protects renal tubular cells. Moreover, there were no obvious side effects associated with this therapy during the follow-up period of our clinical trial. In conclusion, this report shows that the combination of low doses of ACEI and ARB might provide marked antiproteinuric and long-term renoprotective effects in pediatric IgA nephropathy, with this approach appearing to be both well-tolerated and safe.
与大量蛋白尿相关的IgA肾病被认为是该疾病中一种进展性更强的形式。在本报告中，我们描述了低剂量血管紧张素转换酶抑制剂（ACEI）和血管紧张素II受体阻滞剂（ARB）联合治疗小儿IgA肾病合并大量蛋白尿慢性期的良好临床效果。
我们最初对7例IgA肾病合并大量蛋白尿且采用包括类固醇在内的常规治疗未缓解的患儿使用了ACEI。
仅使用ACEI治疗时，只有3例患者出现降蛋白尿反应。在这3例患者中，有1例蛋白尿减少了一半，但仍超过1g/天。在另外4例患者中，蛋白尿没有减少。在这5例患者中，1例对ACEI部分有反应，4例无反应，随后加用了ARB，与单独使用ACEI治疗形成显著对比的是，联合治疗的降蛋白尿效果显著增强（p<0.01）。联合治疗诱导的降蛋白尿反应未伴随血压变化。单独使用ACEI及联合治疗后，尿低分子蛋白和N-乙酰-β-D-氨基葡萄糖苷酶（NAG）水平均有下降趋势。
这些数据表明，血管紧张素系统抑制治疗不仅能降低蛋白尿水平，还能保护肾小管细胞。此外，在我们的临床试验随访期间，该治疗未出现明显副作用。总之，本报告表明，低剂量ACEI和ARB联合使用可能对小儿IgA肾病具有显著的降蛋白尿和长期肾脏保护作用，且这种方法耐受性良好且安全。
