Ecder T, Chapman A B, Brosnahan G M, Edelstein C L, Johnson A M, Schrier R W
Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado School of Medicine, Denver, CO 80262, USA.
Am J Kidney Dis. 2000 Mar;35(3):427-32. doi: 10.1016/s0272-6386(00)70195-8.
Hypertensive patients with autosomal dominant polycystic kidney disease (ADPKD) have a faster progression to end-stage renal disease (ESRD) than their normotensive counterparts. The aim of this prospective, randomized study is to compare the effects of the calcium channel blocker amlodipine and the angiotensin-converting enzyme inhibitor enalapril as first-line therapy on blood pressure, renal function, and urinary albumin excretion in hypertensive patients with ADPKD. Twenty-four patients with ADPKD with hypertension with creatinine clearances (Ccrs) greater than 50 mL/min/1.73 m(2) were included in the study. Twelve patients received amlodipine (mean dose, 9 mg/d), and 12 patients received enalapril (mean dose, 17 mg/d). The patients were followed up for 5 years. Baseline mean arterial pressures, which were 109 +/- 3 mm Hg in the amlodipine group and 108 +/- 3 mm Hg in the enalapril group, decreased significantly after 1 year of follow-up (amlodipine, 96 +/- 3 mm Hg; P < 0.005; enalapril, 89 +/- 2 mm Hg; P < 0.0005) and remained stable at year 5 (amlodipine, 97 +/- 3 mm Hg; P < 0.0005 versus baseline; enalapril, 94 +/- 3 mm Hg; P < 0.005 versus baseline). Ccrs, which were 83 +/- 5 mL/min/1.73 m(2) in the amlodipine group and 77 +/- 6 mL/min/1.73 m(2) in the enalapril group, remained stable after 1 year of follow-up and decreased significantly at year 3 in both groups (amlodipine, 67 +/- 5 mL/min/1.73 m(2); P < 0.01 versus year 1 and baseline; enalapril, 58 +/- 4 mL/min/1.73 m(2); P < 0.05 versus year 1 and P < 0.0005 versus baseline) with no significant change thereafter. No change was observed in urinary albumin-creatinine ratio in the amlodipine group (baseline, 68 +/- 21 mg/g; year 1, 52 +/- 21 mg/g; year 5, 148 +/- 74 mg/g), whereas it decreased significantly in the enalapril group at year 1 (baseline, 23 +/- 4 mg/g; year 1, 13 +/- 3 mg/g; P < 0.05) and remained stable until the end of the study at year 5 (14 +/- 6 mg/g). The investigators concluded that blood pressure was similar in both groups but only enalapril had a significant effect to sustain decreased urinary albumin excretion for a 5-year follow-up. Although proteinuria has been considered a surrogate of renal disease progression, further studies will be necessary to confirm this hypothesis in ADPKD, because after 5 years, no differences in renal function were observed between the enalapril and amlodipine groups. In comparison with patients with ADPKD with uncontrolled hypertension, effective control of blood pressure, as undertaken in the present study, should delay the onset of ESRD by approximately 15 years.
与血压正常的常染色体显性多囊肾病(ADPKD)患者相比,高血压ADPKD患者向终末期肾病(ESRD)进展得更快。这项前瞻性随机研究的目的是比较钙通道阻滞剂氨氯地平和血管紧张素转换酶抑制剂依那普利作为一线治疗对高血压ADPKD患者的血压、肾功能及尿白蛋白排泄的影响。24例肌酐清除率(Ccrs)大于50 mL/min/1.73 m²的高血压ADPKD患者纳入本研究。12例患者接受氨氯地平治疗(平均剂量9 mg/d),12例患者接受依那普利治疗(平均剂量17 mg/d)。对患者进行了5年的随访。基线平均动脉压在氨氯地平组为109±3 mmHg,依那普利组为108±3 mmHg,随访1年后显著下降(氨氯地平组为96±3 mmHg;P<0.005;依那普利组为89±2 mmHg;P<0.0005),并在第5年保持稳定(氨氯地平组为97±3 mmHg;与基线相比P<0.0005;依那普利组为94±3 mmHg;与基线相比P<0.005)。氨氯地平组的Ccrs为83±5 mL/min/1.73 m²,依那普利组为77±6 mL/min/1.73 m²,随访1年后保持稳定,两组在第3年显著下降(氨氯地平组为67±5 mL/min/1.73 m²;与第1年和基线相比P<0.01;依那普利组为58±4 mL/min/1.73 m²;与第1年相比P<0.05,与基线相比P<0.0005),此后无显著变化。氨氯地平组尿白蛋白肌酐比值无变化(基线为68±21 mg/g;第1年为52±21 mg/g;第5年为148±74 mg/g),而依那普利组在第1年显著下降(基线为23±4 mg/g;第1年为13±3 mg/g;P<0.05),并在研究结束时的第5年保持稳定(14±6 mg/g)。研究者得出结论,两组血压相似,但仅依那普利在5年随访中对维持尿白蛋白排泄减少有显著作用。尽管蛋白尿一直被视为肾病进展的替代指标,但在ADPKD中还需要进一步研究来证实这一假设,因为5年后,依那普利组和氨氯地平组在肾功能方面未观察到差异。与未控制高血压的ADPKD患者相比,本研究中进行的有效血压控制应能将ESRD的发病推迟约15年。