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Published on: June 23, 2015
Blood pressure in early autosomal dominant polycystic kidney disease
Robert W Schrier1, Kaleab Z Abebe, Ronald D Perrone
1From 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.).
Insights
Rigorous blood pressure control in autosomal dominant polycystic kidney disease (ADPKD) slowed total kidney volume increase. This approach also reduced left-ventricular mass and urinary albumin excretion without impacting estimated GFR.
Area of Science:
- Nephrology
- Cardiology
- Clinical Trials
Background:
- Hypertension is a common complication of autosomal dominant polycystic kidney disease (ADPKD).
- Elevated blood pressure in ADPKD is linked to increased kidney volume and disease progression.
- Understanding optimal blood pressure management is crucial for ADPKD patients.
Purpose of the Study:
- To evaluate the impact of different blood pressure targets on kidney volume in hypertensive ADPKD patients.
- To assess the effect of dual renin-angiotensin-aldosterone system blockade versus monotherapy on ADPKD progression.
- To investigate the influence of blood pressure control on cardiovascular and renal markers.
Main Methods:
- A double-blind, placebo-controlled trial involving 558 hypertensive ADPKD patients (15-49 years, eGFR >60 ml/min/1.73 m²).
- Participants were randomized to standard (120/70-130/80 mmHg) or low (95/60-110/75 mmHg) blood pressure targets.
- Medication arms included lisinopril plus telmisartan or lisinopril plus placebo, with total kidney volume as the primary outcome.
Main Results:
- The low blood pressure target group showed a significantly lower annual increase in total kidney volume (5.6% vs. 6.6%, P=0.006).
- No significant difference in total kidney volume change was observed between the lisinopril-telmisartan and lisinopril-placebo groups.
- Rigorous blood pressure control led to greater reduction in left-ventricular mass index and urinary albumin excretion, with transient short-term decline in eGFR.
Conclusions:
- In early ADPKD, intensive blood pressure control slows total kidney volume increase compared to standard control.
- The combination of lisinopril and telmisartan did not offer additional benefit in reducing total kidney volume increase.
- Rigorous blood pressure management in ADPKD improves cardiovascular and renal markers without significant long-term impact on GFR.
Background:
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.
Methods:
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.
Results:
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).
Conclusions:
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.).
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