van den Meiracker Anton H, Baggen Rini Ga, Pauli Sacha, Lindemans Anouk, Vulto Arnold G, Poldermans Don, Boomsma Frans
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
J Hypertens. 2006 Nov;24(11):2285-92. doi: 10.1097/01.hjh.0000249708.44016.5c.
To study the effects of addition of spironolactone to angiotensin-converting enzyme (ACE) inhibition or angiotensin II (AngII) receptor antagonism on proteinuria, blood pressure (BP) and renal function in overt type 2 diabetic nephropathy.
A placebo-controlled, double-blind, parallel-group trial in patients from two outpatient clinics with a follow-up of 1 year.
Type 2 diabetic patients with macroalbuminuria, despite long-term use of an ACE inhibitor or AngII receptor blocker were allocated to spironolactone, 25-50 mg once daily (n = 29) or placebo (n = 30). Urinary albumin to creatinine ratio, BP and biochemical parameters were measured at regular intervals.
Five patients of the spironolactone and one of the placebo group developed hyperkalemia and had to be excluded. Compared to other patients their baseline serum creatinine [161 (123-248) versus 88 (72-170) micromol/l] and potassium concentrations (4.7 +/- 0.3 versus 4.2 +/- 0.2 mmol/l) were elevated (P < 0.001). Albuminuria decreased by 40.6% [95% confidence interval (CI) 23.4-57.8%] and BP by 7 mmHg (2-12 mmHg)/3 mmHg (1-6 mmHg) with spironolactone, but did not change with placebo. Estimated glomerular filtration rate (eGFR) during the 1-year follow-up declined on average by 12.9 ml/min per 1.73 m (9.5-16.5 ml/min per 1.73 m) in the spironolactone and by 4.9 ml/min per 1.73 m (0.8-8.9 ml/min per 1.73 m) in the placebo group (P = 0.004). This decline was progressive in the placebo but leveled off in the spironolactone group. In the spironolactone group changes in albuminuria and GFR were correlated (r = 0.48, P = 0.007).
Addition of spironolactone to an ACE inhibitor or AngII receptor blocker is associated with a marked and sustained antiproteinuric effect, which in part relates to the more pronounced reduction in GFR.
研究在显性2型糖尿病肾病中，在血管紧张素转换酶（ACE）抑制或血管紧张素II（AngII）受体拮抗基础上加用螺内酯对蛋白尿、血压（BP）和肾功能的影响。
一项来自两家门诊诊所患者的安慰剂对照、双盲、平行组试验，随访1年。
尽管长期使用ACE抑制剂或AngII受体阻滞剂，但仍有大量蛋白尿的2型糖尿病患者被分配至螺内酯组，每日一次25 - 50 mg（n = 29）或安慰剂组（n = 30）。定期测量尿白蛋白肌酐比值、血压和生化参数。
螺内酯组有5例患者和安慰剂组有1例患者发生高钾血症，不得不被排除。与其他患者相比，他们的基线血清肌酐[161（123 - 248）对88（72 - 170）μmol/l]和钾浓度（4.7±0.3对4.2±0.2 mmol/l）升高（P < 0.001）。使用螺内酯后蛋白尿减少40.6%[95%置信区间（CI）23.4 - 57.8%]，血压降低7 mmHg（2 - 12 mmHg）/3 mmHg（1 - 6 mmHg），而安慰剂组无变化。在1年随访期间，螺内酯组的估计肾小球滤过率（eGFR）平均每1.73 m²下降12.9 ml/min（9.5 - 16.5 ml/min每1.73 m²），安慰剂组为每1.73 m²下降4.9 ml/min（0.8 - 8.9 ml/min每1.73 m²）（P = 0.004）。安慰剂组这种下降是渐进性的，而螺内酯组趋于平稳。在螺内酯组，蛋白尿变化与GFR变化相关（r = 0.48，P = 0.007）。
在ACE抑制剂或AngII受体阻滞剂基础上加用螺内酯与显著且持续的抗蛋白尿作用相关，这部分与GFR更明显的降低有关。
