常染色体显性遗传性多囊肾病晚期的血管紧张素阻断
Angiotensin blockade in late autosomal dominant polycystic kidney disease.
作者信息
Torres Vicente E, Abebe Kaleab Z, Chapman Arlene B, Schrier Robert W, Braun William E, Steinman Theodore I, Winklhofer Franz T, Brosnahan Godela, Czarnecki Peter G, Hogan Marie C, Miskulin Dana C, Rahbari-Oskoui Frederic F, Grantham Jared J, Harris Peter C, Flessner Michael F, Moore Charity G, Perrone Ronald D
机构信息
From the Mayo Clinic College of Medicine, Rochester, MN (V.E.T., M.C.H., P.C.H.); University of Pittsburgh School of Medicine, Pittsburgh (K.Z.A., C.G.M.); Emory University School of Medicine, Atlanta (A.B.C., F.F.R.-O.); University of Colorado Health Sciences Center, Denver (R.W.S., G.B.); Cleveland Clinic, Cleveland (W.E.B.); Beth Israel Deaconess Medical Center (T.I.S., P.G.C.) and Tufts Medical Center (D.C.M., R.D.P.) - both in Boston; Kansas University Medical Center, Kansas City (F.T.W., J.J.G.) and the National Institutes of Health, Bethesda, MD (M.F.F.).
出版信息
N Engl J Med. 2014 Dec 11;371(24):2267-76. doi: 10.1056/NEJMoa1402686. Epub 2014 Nov 15.
BACKGROUND
Hypertension develops early in patients with autosomal dominant polycystic kidney disease (ADPKD) and is associated with disease progression. The renin-angiotensin-aldosterone system (RAAS) is implicated in the pathogenesis of hypertension in patients with ADPKD. Dual blockade of the RAAS may circumvent compensatory mechanisms that limit the efficacy of monotherapy with an angiotensin-converting-enzyme (ACE) inhibitor or angiotensin II-receptor blocker (ARB).
METHODS
In this double-blind, placebo-controlled trial, we randomly assigned 486 patients, 18 to 64 years of age, with ADPKD (estimated glomerular filtration rate [GFR], 25 to 60 ml per minute per 1.73 m(2) of body-surface area) to receive an ACE inhibitor (lisinopril) and placebo or lisinopril and an ARB (telmisartan), with the doses adjusted to achieve a blood pressure of 110/70 to 130/80 mm Hg. The composite primary outcome was the time to death, end-stage renal disease, or a 50% reduction from the baseline estimated GFR. Secondary outcomes included the rates of change in urinary aldosterone and albumin excretion, frequency of hospitalizations for any cause and for cardiovascular causes, incidence of pain, frequency of ADPKD-related symptoms, quality of life, and adverse study-medication effects. Patients were followed for 5 to 8 years.
RESULTS
There was no significant difference between the study groups in the incidence of the composite primary outcome (hazard ratio with lisinopril-telmisartan, 1.08; 95% confidence interval, 0.82 to 1.42). The two treatments controlled blood pressure and lowered urinary aldosterone excretion similarly. The rates of decline in the estimated GFR, urinary albumin excretion, and other secondary outcomes and adverse events, including hyperkalemia and acute kidney injury, were also similar in the two groups.
CONCLUSIONS
Monotherapy with an ACE inhibitor was associated with blood-pressure control in most patients with ADPKD and stage 3 chronic kidney disease. The addition of an ARB did not alter the decline in the estimated GFR. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; HALT-PKD [Study B] ClinicalTrials.gov number, NCT01885559.).
背景
常染色体显性遗传性多囊肾病（ADPKD）患者早期即会出现高血压，且高血压与疾病进展相关。肾素-血管紧张素-醛固酮系统（RAAS）与ADPKD患者高血压的发病机制有关。对RAAS进行双重阻断可能会规避那些限制血管紧张素转换酶（ACE）抑制剂或血管紧张素II受体阻滞剂（ARB）单药治疗疗效的代偿机制。
方法
在这项双盲、安慰剂对照试验中，我们将486例年龄在18至64岁之间、患有ADPKD（估计肾小球滤过率[GFR]为每分钟每1.73 m²体表面积25至6 ml）的患者随机分组，分别接受ACE抑制剂（赖诺普利）加安慰剂或赖诺普利加ARB（替米沙坦）治疗，并调整剂量以使血压达到110/70至130/80 mmHg。复合主要结局为至死亡、终末期肾病或估计GFR较基线降低50%的时间。次要结局包括尿醛固酮和白蛋白排泄的变化率、因任何原因和心血管原因住院的频率、疼痛发生率、ADPKD相关症状的频率、生活质量以及研究用药的不良影响。对患者随访5至8年。
结果
研究组之间在复合主要结局的发生率上无显著差异（赖诺普利-替米沙坦组的风险比为1.08；95%置信区间为0.82至1.42）。两种治疗在控制血压和降低尿醛固酮排泄方面相似。两组在估计GFR、尿白蛋白排泄率以及其他次要结局和不良事件（包括高钾血症和急性肾损伤）的下降率方面也相似。
结论
对于大多数ADPKD和3期慢性肾病患者，ACE抑制剂单药治疗可控制血压。加用ARB并未改变估计GFR的下降情况。（由美国国立糖尿病、消化和肾脏疾病研究所及其他机构资助；HALT-PKD[研究B]，ClinicalTrials.gov编号，NCT01885559。）
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