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 #
5U01DK062408-11
Application #
8242884
Study Section
Special Emphasis Panel (ZDK1-GRB-N (O1))
Program Officer
Flessner, Michael Francis
Project Start
2002-08-15
Project End
2014-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
11
Fiscal Year
2012
Total Cost
$585,579
Indirect Cost
$207,068
Name
Emory University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Nowak, Kristen L; You, Zhiying; Gitomer, Berenice et al. (2018) Overweight and Obesity Are Predictors of Progression in Early Autosomal Dominant Polycystic Kidney Disease. J Am Soc Nephrol 29:571-578
Cornec-Le Gall, Emilie; Chebib, Fouad T; Madsen, Charles D et al. (2018) The Value of Genetic Testing in Polycystic Kidney Diseases Illustrated by a Family With PKD2 and COL4A1 Mutations. Am J Kidney Dis 72:302-308
Dad, Taimur; Abebe, Kaleab Z; Bae, K Ty et al. (2018) Longitudinal Assessment of Left Ventricular Mass in Autosomal Dominant Polycystic Kidney Disease. Kidney Int Rep 3:619-624
Cornec-Le Gall, Emilie; Olson, Rory J; Besse, Whitney et al. (2018) Monoallelic Mutations to DNAJB11 Cause Atypical Autosomal-Dominant Polycystic Kidney Disease. Am J Hum Genet 102:832-844
Brosnahan, Godela M; Abebe, Kaleab Z; Rahbari-Oskoui, Frederic F et al. (2017) Effect of Statin Therapy on the Progression of Autosomal Dominant Polycystic Kidney Disease. A Secondary Analysis of the HALT PKD Trials. Curr Hypertens Rev 13:109-120
Reddy, Bharathi V; Chapman, Arlene B (2017) A Patient with a Novel Gene Mutation Leading to Autosomal Dominant Polycystic Kidney Disease. Clin J Am Soc Nephrol 12:1695-1698
Torres, Vicente E; Abebe, Kaleab Z; Schrier, Robert W et al. (2017) Dietary salt restriction is beneficial to the management of autosomal dominant polycystic kidney disease. Kidney Int 91:493-500
Irazabal, María V; Abebe, Kaleab Z; Bae, Kyongtae Ty et al. (2017) Prognostic enrichment design in clinical trials for autosomal dominant polycystic kidney disease: the HALT-PKD clinical trial. Nephrol Dial Transplant 32:1857-1865
Porath, Binu; Gainullin, Vladimir G; Cornec-Le Gall, Emilie et al. (2016) Mutations in GANAB, Encoding the Glucosidase II? Subunit, Cause Autosomal-Dominant Polycystic Kidney and Liver Disease. Am J Hum Genet 98:1193-1207
Heyer, Christina M; Sundsbak, Jamie L; Abebe, Kaleab Z et al. (2016) Predicted Mutation Strength of Nontruncating PKD1 Mutations Aids Genotype-Phenotype Correlations in Autosomal Dominant Polycystic Kidney Disease. J Am Soc Nephrol 27:2872-84

Showing the most recent 10 out of 23 publications