The overall hypothesis of the proposed studies is that an intensified interventional strategy aimed at blocking the renin angiotensin system at multiple levels (angiotensin II-receptor interaction by an angiotensin II AT1-receptor blocker or ARB, angiotensin II generation by an angiotensin I converting-enzyme inhibitor or ACEI, an angiotensin II AT1-receptor density and intracellular signaling by inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase or statin) will slow down the progression of the renal cystic disease in patients with normal or near-normal renal function (GFR > 60ml/min/1.73m2) and the decline of renal function in patients with mild to moderate renal insufficiency (30-60 ml/min/1.73 m2) (Main Study) and that the success of this strategy will be predicted by the extent to which it corrects the intrarenal hemodynamic alterations associated with autosomal dominant polycystic kidney disease (ADPKD) (Pilot Study). The primary end-points for the Main Study will be a 15% increase in kidney volume or a 30% increase in cyst volume measured by MR in patients with normal or near-normal renal function and a 50% reduction in GFR or a doubling in serum creatinine in patients with mild to moderate renal insufficiency. MR determinations of renal blood flow (RBF), renal vascular resistance (RVR) and arterial compliance will be obtained to ascertain the extent to which the hemodynamic changes in response to therapeutic interventions can predict their success in delaying the progression of the renal cystic disease or the decline of renal function. Similar methodology will be used to ascertain the potential value of novel antihypertensive therapies in ADPKD. The protocols for the Main Study will be conducted in 500 patients, 250 recruited at the Mayo Clinic, 150 recruited at KUMC, and 100 at the Cleveland Clinic. Approximately one-half of these patients will have normal or near-normal renal function and one-half have mild to moderate renal insufficiency. The protocols for the Pilot Study will be conducted only at the Mayo Clinic.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01DK062410-01
Application #
6546952
Study Section
Special Emphasis Panel (ZDK1-GRB-3 (M1))
Program Officer
Flessner, Michael Francis
Project Start
2002-08-15
Project End
2009-01-31
Budget Start
2002-08-15
Budget End
2003-01-31
Support Year
1
Fiscal Year
2002
Total Cost
$250,000
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
Brosnahan, Godela; 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 :
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
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
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
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
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
Moore, Charity G; Spillane, Susan; Simon, Gertrude et al. (2015) Closeout of the HALT-PKD trials. Contemp Clin Trials 44:48-55
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
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

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