Kaito Hiroshi, Nozu Kandai, Iijima Kazumoto, Nakanishi Koichi, Yoshiya Kunihiko, Kanda Kyoko, Przybyslaw Krol Rafal, Yoshikawa Norishige, Matsuo Masafumi
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo 6500017, Japan.
Pediatr Nephrol. 2006 Dec;21(12):1824-9. doi: 10.1007/s00467-006-0270-8. Epub 2006 Oct 13.
Recent studies indicate that adding the mineralocorticoid receptor antagonist spironolactone (SP) to angiotensin converting enzyme inhibitors (ACEI) or ACEI and angiotensin receptor blocker (ARB), which is known as a triple blockade, enhances the more beneficial effects on urinary protein excretion of patients with chronic kidney diseases. In this study, we explored the effects of SP on urinary protein excretion in patients with Alport syndrome featuring persistent proteinuria in spite of the long-term use of ACEI (lisinopril) or both ACEI and ARB (candesartan). Five patients with Alport syndrome were enrolled and SP treatment (25 mg/day) was started. At the start of SP administration, all patients showed good renal function and none of them suffered from hypertension. We decided to assess the effect of SP by determining the morning urinary protein/creatinine ratio (U-P/C) and estimated glomerular filtration rate (EGFR). After SP treatment was started, U-P/C was significantly reduced at 3, 6, 12 and 18 months, while EGFR did not change. The drop in systolic and diastolic blood pressure was statistically significant and serum potassium level was slightly elevated. None of the patients showed signs of severe hyperkalemia (>5.0 mEq/l). These results suggest that aldosterone receptor blockade combined with ACEI and ARB therapy offers a valuable adjuvant treatment for the reduction of proteinuria in patients with Alport syndrome as in those with other chronic kidney diseases. SP can thus be expected to constitute a good renoprotective agent for Alport syndrome. These preliminary data indicate that large-scale trials of this therapy should be done.
近期研究表明，在血管紧张素转换酶抑制剂（ACEI）或ACEI与血管紧张素受体阻滞剂（ARB）联合使用的基础上添加盐皮质激素受体拮抗剂螺内酯（SP），即所谓的三联阻断疗法，对慢性肾脏病患者的尿蛋白排泄具有更有益的影响。在本研究中，我们探讨了SP对Alport综合征患者尿蛋白排泄的影响，这些患者尽管长期使用ACEI（赖诺普利）或同时使用ACEI和ARB（坎地沙坦），仍存在持续性蛋白尿。纳入了5例Alport综合征患者并开始SP治疗（25mg/天）。在开始使用SP时，所有患者肾功能良好，且均未患高血压。我们决定通过测定晨尿蛋白/肌酐比值（U-P/C）和估算肾小球滤过率（EGFR）来评估SP的效果。开始SP治疗后，U-P/C在3、6、12和18个月时显著降低，而EGFR未发生变化。收缩压和舒张压的下降具有统计学意义，血清钾水平略有升高。所有患者均未出现严重高钾血症（>5.0 mEq/l）的迹象。这些结果表明，与其他慢性肾脏病患者一样，醛固酮受体阻断联合ACEI和ARB治疗为Alport综合征患者减少蛋白尿提供了一种有价值的辅助治疗方法。因此，SP有望成为Alport综合征的一种良好肾脏保护剂。这些初步数据表明应开展该疗法的大规模试验。
