Schrier Robert W, Abebe Kaleab Z, Perrone Ronald D, Torres Vicente E, 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, Bae Kyongtae T, Moore Charity G, Chapman Arlene B
From the University of Colorado, Denver (R.W.S., G.B.); University of Pittsburgh School of Medicine, Pittsburgh (K.Z.A., K.T.B., C.G.M.); Tufts Medical Center (R.D.P., D.C.M.) and Beth Israel Deaconess Medical Center (T.I.S., P.G.C.) - both in Boston; Mayo Clinic College of Medicine, Rochester, MN (V.E.T., M.C.H., P.C.H.); Cleveland Clinic, Cleveland (W.E.B.); Kansas University Medical Center, Kansas City (F.T.W., J.J.G.); Emory University School of Medicine, Atlanta (F.F.R.-O., A.B.C.); and the National Institutes of Health, Bethesda, MD (M.F.F.).
N Engl J Med. 2014 Dec 11;371(24):2255-66. doi: 10.1056/NEJMoa1402685. Epub 2014 Nov 15.
Hypertension is common in autosomal dominant polycystic kidney disease (ADPKD) and is associated with increased total kidney volume, activation of the renin-angiotensin-aldosterone system, and progression of kidney disease.
In this double-blind, placebo-controlled trial, we randomly assigned 558 hypertensive participants with ADPKD (15 to 49 years of age, with an estimated glomerular filtration rate [GFR] >60 ml per minute per 1.73 m(2) of body-surface area) to either a standard blood-pressure target (120/70 to 130/80 mm Hg) or a low blood-pressure target (95/60 to 110/75 mm Hg) and to either an angiotensin-converting-enzyme inhibitor (lisinopril) plus an angiotensin-receptor blocker (telmisartan) or lisinopril plus placebo. The primary outcome was the annual percentage change in the total kidney volume.
The annual percentage increase in total kidney volume was significantly lower in the low-blood-pressure group than in the standard-blood-pressure group (5.6% vs. 6.6%, P=0.006), without significant differences between the lisinopril-telmisartan group and the lisinopril-placebo group. The rate of change in estimated GFR was similar in the two medication groups, with a negative slope difference in the short term in the low-blood-pressure group as compared with the standard-blood-pressure group (P<0.001) and a marginally positive slope difference in the long term (P=0.05). The left-ventricular-mass index decreased more in the low-blood-pressure group than in the standard-blood-pressure group (-1.17 vs. -0.57 g per square meter per year, P<0.001); urinary albumin excretion was reduced by 3.77% with the low-pressure target and increased by 2.43% with the standard target (P<0.001). Dizziness and light-headedness were more common in the low-blood-pressure group than in the standard-blood-pressure group (80.7% vs. 69.4%, P=0.002).
In early ADPKD, the combination of lisinopril and telmisartan did not significantly alter the rate of increase in total kidney volume. As compared with standard blood-pressure control, rigorous blood-pressure control was associated with a slower increase in total kidney volume, no overall change in the estimated GFR, a greater decline in the left-ventricular-mass index, and greater reduction in urinary albumin excretion. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; HALT-PKD [Study A] ClinicalTrials.gov number, NCT00283686.).
高血压在常染色体显性遗传性多囊肾病（ADPKD）中很常见，并且与肾脏总体积增加、肾素 - 血管紧张素 - 醛固酮系统激活以及肾脏疾病进展相关。
在这项双盲、安慰剂对照试验中，我们将558名患有ADPKD的高血压参与者（年龄15至49岁，估计肾小球滤过率[GFR]>60 ml/分钟/1.73 m²体表面积）随机分为标准血压目标组（120/70至130/80 mmHg）或低血压目标组（95/60至110/75 mmHg），并分为血管紧张素转换酶抑制剂（赖诺普利）加血管紧张素受体阻滞剂（替米沙坦）组或赖诺普利加安慰剂组。主要结局是肾脏总体积的年度百分比变化。
低血压组肾脏总体积的年度百分比增加显著低于标准血压组（5.6%对6.6%，P = 0.006），赖诺普利 - 替米沙坦组与赖诺普利 - 安慰剂组之间无显著差异。两个药物组的估计GFR变化率相似，与标准血压组相比，低血压组短期内斜率差异为负（P<0.001），长期内斜率差异为边缘性正值（P = 0.05）。低血压组的左心室质量指数下降幅度大于标准血压组（-1.17对-0.57 g/平方米/年，P<0.001）；低血压目标使尿白蛋白排泄减少3.77%，标准目标使尿白蛋白排泄增加2.43%（P<0.001）。低血压组头晕和头轻脚重比标准血压组更常见（80.7%对69.4%，P = 0.002）。
在早期ADPKD中，赖诺普利和替米沙坦联合使用并未显著改变肾脏总体积的增加速率。与标准血压控制相比，严格的血压控制与肾脏总体积增加较慢、估计GFR无总体变化、左心室质量指数下降幅度更大以及尿白蛋白排泄减少幅度更大相关。（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A]，ClinicalTrials.gov编号，NCT00283686。）
