Evidence of impaired glomerular charge selectivity in nondiabetic subjects with microalbuminuria: relevance to cardiovascular disease.

Microalbuminuria is associated with excess cardiovascular morbidity and mortality in diabetic and nondiabetic subjects. Loss of glomerular charge selectivity may explain the development of microalbuminuria in diabetic subjects. The primary population in this cross-sectional study was 124 subjects aged 40 to 75 years without glucose intolerance and with a previous (3 years before the present study) urinary albumin excretion rate (UAE) in the normal (<20 microgram/min) or microalbuminuric (>20 microgram/min) range. The secondary population consisted of 39 offspring aged 15 to 40 years. The main outcome measures included UAE, urinary IgG/IgG4 selectivity index (SI), and the presence of ischemic heart disease as determined by questionnaire or ECG. Among the primary population, a significant inverse correlation was found between SI and UAE (r=-.40, P<.001). Reduction in SI could be demonstrated in subjects with UAE >10 microgram/min. In multiple regression analysis reduction in SI was found with increasing age, independent of UAE. In 20 subjects with clinical cardiovascular disease a reduction in SI was found (1.9+/-0.6 versus 2.6+/-1.3, P=.001) without concomitant elevation in UAE (P=.99). Offspring from parents with microalbuminuria had an SI comparable to offspring from parents with normal UAE (2.7+/-0.7 versus 3.3+/-1.6, P=.17). In nondiabetic subjects the development of microalbuminuria is associated with reduced SI, suggesting impairment of glomerular charge selectivity. SI may offer a more sensitive monitoring of abnormalities in glomerular permselectivity than does measurements of UAE, but the ability of SI to predict development of cardiovascular disease needs to be evaluated prospectively.