J Am Soc Nephrol. 2009 Sep;20(9):1888-93. Epub 2009 Aug 20.
Renal volume, renin-angiotensin-aldosterone system, hypertension, and left ventricular hypertrophy in patients with autosomal dominant polycystic kidney disease.
Schrier RW.
Department of Medicine, University of Colorado Denver, Denver, Colorado, USA. robert.schrier@ucdenver.edu
Abstract
The relationship between renal volume and hypertension in autosomal dominant polycystic kidney disease (ADPKD) occurs in childhood. Hypertension is associated not only with increased kidney volume but also with significantly increased left ventricular mass index. Moreover, this increase in left ventricular mass index occurs in children who have ADPKD with borderline hypertension (75th to 95th percentile) and is prevented with angiotensin-converting enzyme inhibitor (ACEI) monotherapy. Progression from borderline to overt hypertension (> or =95th percentile) occurs during a 5-yr follow-up in approximately 50% of children with ADPKD and borderline hypertension. Renal cyst enlargement in ADPKD in adults is associated with stimulation of both the circulating and intrarenal renin-angiotensin-aldosterone system. In addition to hypertension, the resultant angiotensin in ADPKD is a pivotal factor in cyst proliferation and expansion, increased sympathetic and endothelin activity, oxidant injury, and fibrosis. There is a close correlation between the level of hypertension, left ventricular hypertrophy, deterioration of GFR, and the progressive enlargement of the cystic kidneys in adult ADPKD. Randomized clinical investigation indicates that ACEI and a BP goal of 120/80 mmHg are associated in a 7-yr study to reverse left ventricular hypertrophy. The effect of renin-angiotensin-aldosterone system inhibition with dual blockade, ACEI and angiotensin receptor antagonists, on renal volume and kidney function is under study in the Halt Progression of Polycystic Kidney Disease (HALT PKD) trial.
PMID: 19696226 [PubMed - indexed for MEDLINE]

Clin J Am Soc Nephrol. 2010 Jan;5(1):102-9.
The HALT polycystic kidney disease trials: design and implementation.
Chapman AB, Torres VE, Perrone RD, Steinman TI, Bae KT, Miller JP, Miskulin DC, Rahbari Oskoui F, Masoumi A, Hogan MC, Winklhofer FT, Braun W, Thompson PA, Meyers CM, Kelleher C, Schrier RW.
Emory University School of Medicine, Atlanta, GA 30322, USA. Arlene_chapman@emory.org
Abstract
BACKGROUND AND OBJECTIVES: Two HALT PKD trials will investigate interventions that potentially slow kidney disease progression in hypertensive autosomal dominant polycystic kidney disease (ADPKD) patients. Studies were designed in early and later stages of ADPKD to assess the impact of intensive blockade of the renin-angiotensin-aldosterone system and level of BP control on progressive renal disease. Design, settings, participants, and measurements: PKD-HALT trials are multicenter, randomized, double-blind, placebo-controlled trials studying 1018 hypertensive ADPKD patients enrolled over 3 yr with 4 to 8 yr of follow-up. In study A, 548 participants, estimated GFR (eGFR) of >60 ml/min per 1.73 m(2) were randomized to one of four arms in a 2-by-2 design: combination angiotensin converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) therapy versus ACEi monotherapy at two levels of BP control. In study B, 470 participants, eGFR of 25 to 60 ml/min per 1.73 m2 compared ACEi/ARB therapy versus ACEi monotherapy, with BP control of 120 to 130/70 to 80 mmHg. Primary outcomes of studies A and B are MR-based percent change kidney volume and a composite endpoint of time to 50% reduction of baseline estimated eGFR, ESRD, or death, respectively. RESULTS: This report describes design issues related to (1) novel endpoints such as kidney volume, (2) home versus office BP measures, and (3) the impact of RAAS inhibition on kidney and patient outcomes, safety, and quality of life. CONCLUSIONS: HALT PKD will evaluate potential benefits of rigorous BP control and inhibition of the renin-angiotensin-aldosterone system on kidney disease progression in ADPKD.
PMID: 20089507 [PubMed - indexed for MEDLINE]PMCID: PMC2801653 [Available on 2011/1/1]