Association of uric acid with kidney function and albuminuria: the Uric Acid Right for heArt Health (URRAH) Project
Authors: Russo Elisa , Viazzi Francesca , Pontremoli Roberto , Barbagallo Carlo Maria , Bombelli Michele , Casiglia Edoardo , Cicero Arrigo Francesco Giuseppe , Cirillo Massimo , Cirillo Pietro , Desideri Giovambattista , D’Elia Lanfranco , Ferri Claudio , Galletti Ferruccio , Gesualdo Loreto , Giannattasio Cristina , Iaccarino Guido , Leoncini Giovanna , Mallamaci Francesca , Maloberti Alessandro , Masi Stefano , Mengozzi Alessandro , Mazza Alberto , Muiesan Maria Lorenza , Nazzaro Pietro , Palatini Paolo , Parati Gianfranco , Rattazzi Marcello , Rivasi Giulia , Salvetti Massimo , Tikhonoff Valérie , Tocci Giuliano , Ungar Andrea , Verdecchia Paolo , Virdis Agostino , Volpe Massimo , Grassi Guido , Borghi Claudio ,   on behalf of the Working Group on UricAcid and Cardiovascular Risk of the Italian Society of Hypertension
Published: March 2021

Abstract
Background
Hyperuricemia is commonly observed in patients with chronic kidney disease (CKD). However, a better understanding of the relationship among uric acid (UA) values, glomerular filtration rate (GFR) and albuminuria may shed light on the mechanisms underlying the excess of cardiovascular mortality associated with both chronic kidney disease and hyperuricemia and lead to better risk stratification. Our main goal was to study the relationships between serum uric acid and kidney disease measures (namely estimated GFR [eGFR] and albuminuria) in a large cohort of individuals at cardiovascular risk from the URic acid Right for heArt Health (URRAH) Project database.

Methods
Clinical data of 26,971 individuals were analyzed. Factors associated with the presence of hyperuricemia defined on the basis of previously determined URRAH cutoffs for cardiovascular and all-cause mortality were evaluated through multivariate analysis. Chronic kidney disease was defined as eGFR < 60 ml/min per 1.73 m2 and/or abnormal urinary albumin excretion diagnosed as: (i) microalbuminuria if urinary albumin concentration was > 30 and ≤ 300 mg/L, or if urinary albumin-to-creatinine ratio (ACR) was > 3.4 mg/mmol and ≤ 34 mg/mmol; (ii) macroalbuminuria if urinary albumin concentration was > 300 mg/L, or if ACR was > 34 mg/mmol.

Results
Mean age was 58 ± 15 years (51% males, 62% with hypertension and 12% with diabetes), mean eGFR was 81 ml/min per 1.73m22with a prevalence of eGFR < 60 and micro- or macroalbuminuria of 16, 15 and 4%, respectively. Serum uric acid showed a trend towards higher values along with decreasing renal function. Both the prevalence of gout and the frequency of allopurinol use increased significantly with the reduction of eGFR and the increase in albuminuria. Hyperuricemia was independently related to male gender, eGFR strata, and signs of insulin resistance such as body mass index (BMI) and triglycerides.

Conclusions
The lower the eGFR the higher the prevalence of hyperuricemia and gout. In subjects with eGFR < 60 ml/min the occurrence of hyperuricemia is about 10 times higher than in those with eGFR > 90 ml/min. The percentage of individuals treated with allopurinol was below 2% when GFR was above 60 ml/min, it increased to 20% in the presence of CKD 3b and rose further to 35% in individuals with macroalbuminuria.

Graphic abstract