Coronary heart disease nearly 50% more likely to develop in individuals with proteinuria.

Two new studies have linked early signs of kidney disease to higher risks for cardiovascular disease and diabetes.

One study, a meta-analysis, confirms “a strong and continuous association between urinary proteinuria and subsequent risk of coronary heart disease (CHD).”

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The data are so robust that “urinary proteinuria should be incorporated into the assessment of an individual’s cardiovascular risk,” the Australian researchers wrote in PLoS Med. (2008;5:e207).

Led by Vlado Perkovic, MBBS, PhD, of the George Institute for International Health in Sydney, Australia, the investigators looked at 26 cohort studies involving 169,949 individuals and 7,117 coronary events, 27% of which were fatal. This was followed by an analysis of the risk of coronary disease with respect to three factors: proteinuria (total urinary protein excretion greater than 300 mg/day), microalbuminuria (urinary albumin excretion [UAE] of 30-300 mg/day), and macroalbuminuria (UAE greater than 300 mg/day).

Proteinuria was associated with about a 50% increase in the likelihood of developing CHD. Albuminuria appeared to have a dose-dependent relationship. While subjects with microalbuminuria were at about 50% greater risk, those with macroalbuminuria were more than twice as likely to develop CHD as those with normal urinary albumin.

In the second study, Jean-Michel Halimi, MD, PhD, of François Rabelais University in Tours, France, and colleagues identified an association between elevated UAE and a significantly higher risk of diabetes in men, but not women. Measuring UAE may provide a simple new test to assess diabetes risk, they concluded in the Journal of Hypertension (2008;26:2198-2206).

The association between UAE and diabetes risk showed a dose-response relationship. The risk rose steadily with UAE until risk more than quadrupled for those with UAE greater than 200 mg/L compared with subjects with a UAE less than 9 mg/L.

UAE was not a significant risk factor among women for reasons that are not clear, the researchers reported. In men, the association between UAE and diabetes risk was independent of BMI, activity, diet, smoking, family history, and other established variables.

The analysis was based on data from an ongoing study of risk factors for insulin resistance syndrome. The 3,851 men and women were 30-64 years old and were not diabetic at baseline. During nine years of follow-up, the disease developed in 171 participants. Microalbuminuria was defined as UAE of 20-200 mg/L and macroalbuminuria as UAE greater than 200 mg/L, a level that indicates established kidney disease.

The next step, the researchers suggested, is to determine whether lowering UAE can help reduce diabetes risk.