Progression of Chronic Kidney Disease: Adrenergic Genetic Influence on Glomerular Filtration Rate Decline in Hypertensive Nephrosclerosis

Overview

Journal Am J Nephrol

Publisher Karger

Specialty Nephrology

Date 2010 May 21

PMID 20484896

Citations 10

Authors

Yuqing Chen

Michael S Lipkowitz

Rany M Salem

Maple M Fung

Vibha Bhatnagar

Manjula Mahata

Caroline M Nievergelt

Fangwen Rao

Sushil K Mahata

Nicholas J Schork

Pamela J Hicks

Donald W Bowden

Barry I Freedman

Victoria H Brophy

Daniel T OConnor

Affiliations

Soon will be listed here.

Abstract

Background: African-Americans are likely to develop hypertension and hypertensive nephrosclerosis. This grave prognosis, coupled with familial aggregation of end-stage renal disease (ESRD) in Blacks, prompts a search for genetic risk factors for ESRD. Recent evidence implicates a crucial role for the sympathetic nervous system in progressive renal disease.

Methods: We used the African-American Study of Kidney Disease to probe whether beta2-adrenergic receptor (ADRB2) predicts glomerular filtration rate (GFR) decline rate. A total of 580 participants were included. Baseline GFR was 51.2 +/- 0.5 ml/min/1.73 m2. Subjects were randomized in a 2 x 3 block design: to intensively lowered (MAP < or = 92 mm Hg) versus 'usual' (MAP = 102-107 mm Hg) blood pressure goal groups, and also divided by three randomized antihypertensive drugs (ramipril, metoprolol, or amlodipine). We scored 4 SNPs at the ADRB2 locus.

Results: Haplotypes at ADRB2 predicted chronic GFR decline rate, GFR declined more slowly in individuals with haplotype-1 (-804G-->173T-->16Gly-->27GIn), and faster in those who carried haplotype-3 (-804G-->173T-->16Arg-->27Gln). ADRB2 genotype interacted with antihypertensive drug class to influence GFR slope (p = 0.001-0.037). We extended our findings to an independent case/control sample of Black hypertensive ESRD, in which we found that variant Gly16Arg that tagged the GFR slope-determining ADRB2 haplotype also conferred risk for the ESRD trait in Blacks.

Conclusions: The GFR decline/progression rate in hypertensive renal disease is controlled in part by genetic variation within the adrenergic pathway.

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