Hyperhomocysteinemia is independently associated with albuminuria in the population-based CoLaus study

Franziska Marti,Fred Paccaud,Vincent Mooser,Peter Vollenweider,Gérard Waeber,Murielle Bochud,Pedro-Manuel Marques-Vidal

doi:10.1186/1471-2458-11-733

Abstract

BackgroundIncreased serum levels of homocysteine and uric acid have each been associated with cardiovascular risk. We analyzed whether homocysteine and uric acid were associated with glomerular filtration rate (GFR) and albuminuria independently of each other. We also investigated the association of MTHFR polymorphisms related to homocysteine with albuminuria to get further insight into causality.MethodsThis was a cross-sectional population-based study in Caucasians (n = 5913). Hyperhomocysteinemia was defined as total serum homocysteine ≥ 15 μmol/L. Albuminuria was defined as urinary albumin-to-creatinine ratio > 30 mg/g.ResultsUric acid was associated positively with homocysteine (r = 0.246 in men and r = 0.287 in women, P < 0.001). The prevalence of albuminuria increased across increasing homocysteine categories (from 6.4% to 17.3% in subjects with normal GFR and from 3.5% to 14.5% in those with reduced GFR, P for trend < 0.005). Hyperhomocysteinemia (OR = 2.22, 95% confidence interval: 1.60-3.08, P < 0.001) and elevated serum uric acid (OR = 1.27, 1.08-1.50, per 100 μmol/L, P = 0.004) were significantly associated with albuminuria, independently of hypertension and type 2 diabetes. The 2-fold higher risk of albuminuria associated with hyperhomocysteinemia was similar to the risk associated with hypertension or diabetes. MTHFR alleles related to higher homocysteine were associated with increased risk of albuminuria.ConclusionsIn the general adult population, elevated serum homocysteine and uric acid were associated with albuminuria independently of each other and of renal function.

Highlights

Increased serum levels of homocysteine and uric acid have each been associated with cardiovascular risk
In order to evaluate whether the association between total homocysteine (tHcy) and albuminuria could be causal, we looked at the association between albuminuria and the methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms strongly correlated with tHcy
In conclusion, hyperhomocysteinemia was associated with higher prevalence of albuminuria in men and in women, independently of renal function

Summary

Introduction

Increased serum levels of homocysteine and uric acid have each been associated with cardiovascular risk. The population-based Hoorn study, which included subjects aged 50 to 75 years, found that baseline tHcy was associated with microalbuminuria at baseline [10], and after a mean follow-up of 6.1 years, independently of renal function [11]. In the National Health and Nutrition Examination Survey 19911994, the largest population-based study available so far (3387 subjects aged ≥ 40 years), elevated tHcy was associated with albuminuria independently of vitamin B status [1]. It remains unclear whether tHcy causes albuminuria or is merely the consequence of reduced renal function, which is itself reflected by albuminuria [14]. As albuminuria is an established marker of kidney damage in diabetic and nondiabetic individuals and a strong predictor of cardiovascular morbidity and mortality [15,16], a better understanding of the determinants of albuminuria is of great interest

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