Rasche Franz Maximilian, Joel Claudia, Ebert Thomas, Frese Thomas, Barinka Filip, Busch Volker, Rasche Wilma Gertrud, Lindner Tom H, Schneider Jochen, Schiekofer Stephan
Department of Internal Medicine, Neurology, Dermatology, Clinic for Endocrinology, Diabetology and Nephrology, University Leipzig, Leipzig, Germany.
Institute of General Practice and Family Medicine, Martin-Luther-University Halle/Wittenberg, Germany.
Exp Clin Endocrinol Diabetes. 2018 Jan;126(1):39-52. doi: 10.1055/s-0043-106440. Epub 2017 Apr 27.
Dual renin-angiotensin-aldosterone blockade (dRAASb) is purposed in the prevention of the cardiorenal syndrome (CRS). However, all attempts with dRAASb even in patients with moderate impaired chronic kidney disease (CKD) were terminated due to the typical severe adverse events (SAE), e. g., hyperkalemia and rise of serum creatinine. The aim of our study with the direct renin inhibitor aliskiren was to evaluate the effect of dRAASb with a washout phase in patients with severely advanced CKD. We have studied 45 patients (G3b to 4, A2 and >A3; median glomerular filtration rate (GFR) CKD-EPI 31 (23-40) ml/min per 1.73 m² BSA (body surface area), albumin-creatinine-ratio in urine (UACR) (0.413 (0.164 to 1.39) g/g) and proteinuria (0.5 (0.2 to 0.9) g/l) before, with and without aliskiren (150 respectively 300 mg per day) added to an angiotensin-converting enzyme inhibitor (ACEi) or an AT1-receptor blocker (ARB) over 4 ½ years. The dRAASb with aliskiren showed a significant decrease of proteinuria (0.5 to 0.38 g/l), especially in patients with an UACR≥350 mg/g and in the subgroup analysis e. g., in patients with diabetes, but proteinuria increased in the washout phase again. The blood pressure (130/80 mm Hg), serum potassium (4.9 to 5.0 mmol/l) and GFR remained nearly constant (31 to 29.5 ml/min per 1.73 m BSA). A more than 30% increase in serum creatinine was associated with an UACR>300 mg/g. The dRAASb has beneficial effects on proteinuria and is safe in patients with severely advanced CKD. However, in patients with high UACR (>300 mg/g) raise of creatinine and potassium have to be controlled.
双重肾素-血管紧张素-醛固酮系统阻断（dRAASb）旨在预防心肾综合征（CRS）。然而，即便在中度慢性肾脏病（CKD）患者中进行的所有dRAASb尝试，均因典型的严重不良事件（SAE），如高钾血症和血清肌酐升高而终止。我们使用直接肾素抑制剂阿利吉仑开展研究的目的，是评估在重度晚期CKD患者中进行有洗脱期的dRAASb的效果。我们研究了45例患者（G3b至4期、A2期及>A3期；CKD-EPI估算肾小球滤过率（GFR）中位数为每1.73m²体表面积（BSA）31（23 - 40）ml/min，尿白蛋白肌酐比值（UACR）为0.413（0.164至1.39）g/g，蛋白尿为0.5（0.2至0.9）g/l），在4年半的时间里，在使用血管紧张素转换酶抑制剂（ACEi）或AT1受体阻滞剂（ARB）的基础上，分别加用阿利吉仑（每天150或300mg），观察加用前后的情况。加用阿利吉仑的dRAASb使蛋白尿显著降低（从0.5降至0.38g/l），尤其是UACR≥350mg/g的患者，在亚组分析中，如糖尿病患者中也是如此，但在洗脱期蛋白尿又再次升高。血压（130/80mmHg）、血清钾（4.9至5.0mmol/l）和GFR基本保持稳定（每1.73m² BSA从31降至29.5ml/min）。血清肌酐升高超过30%与UACR>300mg/g相关。dRAASb对蛋白尿有有益作用，在重度晚期CKD患者中是安全的。然而，对于UACR高（>300mg/g）的患者，必须控制肌酐和钾的升高。
