Uric acid and the state of the intrarenal renin-angiotensin system in humans.
BACKGROUND
Experimental hyperuricemia is marked by an activated intrarenal renin-angiotensin system (RAS). The renal vascular response to exogenous angiotensin II (Ang II) provides an indirect measure of intrarenal RAS activity. We tested the hypothesis that the serum uric acid concentration predicts the renal vascular response to Ang II.


METHODS
A total of 249 subjects in high sodium balance had the renal plasma flow (RPF) response to Ang II measured. Para-aminohippuric acid (PAH) clearance was used to estimate RPF. Multivariable regression analysis determined if the serum uric acid concentration independently predicts the RPF response to Ang II. Variables considered included age, gender, race, body mass index (BMI), hypertension status, blood pressure, basal RPF, creatinine clearance, serum insulin, serum glucose, serum high-density lipoprotein (HDL), serum triglycerides, and plasma renin activity (PRA).


RESULTS
Uric acid concentration negatively correlated with the RPF response to Ang II (r=-0.37, P < 0.001). In univariate analysis, age, BMI, hypertension, triglycerides, and blood pressure were negatively associated, and basal RPF, HDL, and female gender were positively associated with the RPF response to Ang II. In multivariable analysis, serum uric acid concentration independently predicted the RPF response to Ang II (beta=-5.3, P < 0.001).


CONCLUSIONS
Serum uric acid independently predicted blunted renal vascular responsiveness to Ang II, consistent with results from experimental hyperuricemia showing an activated intrarenal RAS. This could be due to a direct effect of uric acid or reflect a more fundamental renal process. These data may have relevance to the association of uric acid with risk for hypertension and nephropathy.
Endocrinology, Diabetes and Hypertension Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. tperlstein@partners.org
Todd S
TS
Perlstein
Olga
O
Gumieniak
Paul N
PN
Hopkins
Laine J
LJ
Murphey
Nancy J
NJ
Brown
Gordon H
GH
Williams
Norman K
NK
Hollenberg
Naomi D L
ND
Fisher
D000328:Adult; D000804:Angiotensin II / Q000378:metabolism; D001794:Blood Pressure; D005260:Female; D006801:Humans; D006977:Hypertension, Renal / Q000378:metabolism*; D033461:Hyperuricemia / Q000453:epidemiology / Q000378:metabolism*; D007668:Kidney / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012079:Renal Circulation; D012084:Renin-Angiotensin System / Q000502:physiology*; D012307:Risk Factors; D014527:Uric Acid / Q000097:blood*
D000804:Angiotensin II; D014527:Uric Acid