Unità Operativa Nefrologia Spedali Riuniti di Livorno, Livorno, Italy.
Am J Kidney Dis. 2010 Apr;55(4):671-81. doi: 10.1053/j.ajkd.2009.11.006. Epub 2010 Jan 25.
Chronic kidney disease (CKD) caused by idiopathic glomerular diseases usually is progressive. Inhibition of the renin-angiotensin system (RAS) retards, but does not abrogate, CKD progression. Statins and spironolactone may decrease the rate of CKD progression independently or in addition to RAS inhibition.
Randomized open-label study.
SETTING & PARTICIPANTS: We recruited 128 patients (82 men and 46 women) with a clinical diagnosis of idiopathic chronic glomerulonephritis and estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m(2) (range, 36-102 mL/min/1.73 m(2)), and urine protein-creatinine ratio ranging from 1.1-5.2 g/g.
Intensive therapy (a combination of RAS inhibitors [angiotensin-converting enzyme [ACE] inhibitors plus angiotensin receptor blockers [ARBs] plus a high-dose statin and spironolactone) versus conventional therapy (a regimen based on ACE inhibitors with a low-dose statin).
Changes in eGFR, proteinuria, and adverse events after 3 years of therapy.
With intensive therapy, urine protein-creatinine ratio decreased from 2.65 (range, 1.1-5.2) to 0.45 (0.14-1.51) g/g (P < 0.001) and eGFR did not significantly change over time (64.6 +/- 2.1 vs 62.9 +/- 2.9 mL/min/1.73 m(2)). With conventional therapy, urine protein-creatinine ratio decreased from 2.60 (range, 1.32-5.4) to 1.23 (0.36-3.42) g/g (P < 0.001) and eGFR decreased from 62.5 +/- 1.7 to 55.8 +/- 1.9 mL/min/1.73 m(2) (P < 0.001). Comparison of the decreases in proteinuria and GFR between intensive versus conventional therapy was significantly different starting in the 1st and 12th months, respectively. Systolic blood pressure was lower with intensive than conventional therapy (113.5 +/- 1.4 vs 122.7 +/- 1.2 mm Hg; P < 0.01). We found an inverse relationship between percentage of decrease in proteinuria and change in eGFR (P < 0.001). Patients on intensive therapy were more likely to develop adverse events, such as hyperkalemia (9 vs 3 patients in the conventional therapy group) and discontinue therapy (15 vs 8 patients in the conventional therapy group).
Open-label design.
A more intensive therapy that includes a combination of ACE inhibitors and ARBs plus high-dose statins and spironolactone may retard CKD progression more effectively than conventional therapy based on ACE inhibitors plus low-dose statin, but may lead to more adverse effects and discontinuation of therapy.
特发性肾小球疾病导致的慢性肾脏病（CKD）通常呈进行性发展。肾素-血管紧张素系统（RAS）的抑制可延缓，但不能消除 CKD 的进展。他汀类药物和螺内酯的单独或联合应用除了抑制 RAS 外，还可能降低 CKD 的进展速度。
随机开放标签研究。
我们招募了 128 名（82 名男性和 46 名女性）临床诊断为特发性慢性肾小球肾炎且估计肾小球滤过率（eGFR）＞30ml/min/1.73m²（范围为 36-102ml/min/1.73m²）、尿蛋白/肌酐比值为 1.1-5.2g/g 的患者。
强化治疗（联合使用 RAS 抑制剂[血管紧张素转换酶抑制剂（ACEI）加血管紧张素受体阻滞剂（ARB）加高剂量他汀类药物和螺内酯]与常规治疗[基于 ACEI 的方案加低剂量他汀类药物]）。
治疗 3 年后 eGFR、蛋白尿和不良事件的变化。
强化治疗组尿蛋白/肌酐比值从 2.65（范围 1.1-5.2）降至 0.45（0.14-1.51）g/g（P＜0.001），eGFR 在整个研究期间无明显变化（64.6±2.1 比 62.9±2.9ml/min/1.73m²）。常规治疗组尿蛋白/肌酐比值从 2.60（范围 1.32-5.4）降至 1.23（0.36-3.42）g/g（P＜0.001），eGFR 从 62.5±1.7 降至 55.8±1.9ml/min/1.73m²（P＜0.001）。从第 1 个月和第 12 个月开始，强化治疗与常规治疗相比，蛋白尿和 GFR 降低的差异有统计学意义。强化治疗组收缩压低于常规治疗组（113.5±1.4 比 122.7±1.2mmHg；P＜0.01）。我们发现蛋白尿减少百分比与 eGFR 变化之间呈负相关（P＜0.001）。强化治疗组患者更易发生不良反应，如高钾血症（强化治疗组 9 例，常规治疗组 3 例）和停药（强化治疗组 15 例，常规治疗组 8 例）。
开放性标签设计。
与基于 ACEI 加低剂量他汀类药物的常规治疗相比，包含 ACEI 和 ARB 联合高剂量他汀类药物和螺内酯的强化治疗可能更有效地延缓 CKD 的进展，但可能导致更多的不良反应和停药。
