Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common genetic renal disease and is the third most common cause of renal failure in this country. In ADPKD cysts grow in the kidneys over time due to cyst development and expansion. Early ADPKD patients develop hypertension which is associated with a faster rate of progression to renal failure. To date no effective therapy has been developed for patients with hypertension and ADPKD that slow progression of disease. Activation of the reninangeotensin- aldosterone system is associated with hypertension in ADPKD. There are now two classes of antihypertensive medications which inhibit the activation of this system. These include Angiotensin Converting Enzyme Inhibitors (ACEI) and Angiotensin Receptor Blocking Agents (ARB). It is not known whether combining these agents together will be effective in slowing progression of renal failure in ADPKD and if levels of blood pressure control are important in slowing progression of renal failure. HALT is a prospective longitudinal randomized double blinded study will be performed in 1018 subjects at 7 clinical sites over a period of four years. There will be 254 subjects studied at Emory University involving two patient populations. Study A will involve subjects'age 17-45 years with normal renal function (estimated GFR >60 ml/min) and the rate of change in renal size measured by magnetic resonance imaging (MRI) will be determined. Subjects will also be separated into two levels of blood pressure control, <110/75 (rigorous control) or <130/80 mm Hg (standard control). In study Group B, subjects'age 18-64 years with less than normal renal function (estimated GFR 25-60 ml/min) will be treated to the same level of blood pressure level (<130/80 mm Hg). The composite primary end point for Study B includes time to doubling of serum creatinine concentration, renal replacement therapy or death. All eligible subjects will undergo washout from their antihypertensive medications, undergo a baseline evaluation, followed by a dose titration phase and a maintenance phase for the duration of the study. This study will determine the efficacy of dual inhibition of the RAAS as well as rigorous blood pressure control in preventing progression of renal disease in ADPKD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK062408-12
Application #
8477024
Study Section
Special Emphasis Panel (ZDK1-GRB-N (O1))
Program Officer
Flessner, Michael Francis
Project Start
2002-08-15
Project End
2015-01-31
Budget Start
2013-02-01
Budget End
2015-01-31
Support Year
12
Fiscal Year
2013
Total Cost
$535,578
Indirect Cost
$258,360
Name
Emory University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Hogan, Marie C; Abebe, Kaleab; Torres, Vicente E et al. (2015) Liver involvement in early autosomal-dominant polycystic kidney disease. Clin Gastroenterol Hepatol 13:155-64.e6
Chapman, Arlene B (2014) The importance of quantifying genetic heterogeneity in ADPKD. Kidney Int 85:236-7
Torres, Vicente E; Abebe, Kaleab Z; Chapman, Arlene B et al. (2014) Angiotensin blockade in late autosomal dominant polycystic kidney disease. N Engl J Med 371:2267-76
Miskulin, Dana C; Abebe, Kaleab Z; Chapman, Arlene B et al. (2014) Health-related quality of life in patients with autosomal dominant polycystic kidney disease and CKD stages 1-4: a cross-sectional study. Am J Kidney Dis 63:214-26
Schrier, Robert W; Abebe, Kaleab Z; Perrone, Ronald D et al. (2014) Blood pressure in early autosomal dominant polycystic kidney disease. N Engl J Med 371:2255-66
Tkachenko, Oleksandra; Helal, Imed; Shchekochikhin, Dmitry et al. (2013) Renin-Angiotensin-aldosterone system in autosomal dominant polycystic kidney disease. Curr Hypertens Rev 9:12-20
Torres, Vicente E; Chapman, Arlene B; Perrone, Ronald D et al. (2012) Analysis of baseline parameters in the HALT polycystic kidney disease trials. Kidney Int 81:577-85
Rahbari-Oskoui, Frederic F; Miskulin, Dana C; Hogan, Marie C et al. (2011) Short-term reproducibility of ambulatory blood pressure monitoring in autosomal dominant polycystic kidney disease. Blood Press Monit 16:47-54
Perrone, Ronald D; Abebe, Kaleab Z; Schrier, Robert W et al. (2011) Cardiac magnetic resonance assessment of left ventricular mass in autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol 6:2508-15
Chapman, Arlene B; Stepniakowski, Konrad; Rahbari-Oskoui, Frederic (2010) Hypertension in autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis 17:153-63

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