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Body Mass Index Is Associated with Increased Creatinine Clearance by a Mechanism Independent of Body Fat Distribution

Division of Metabolism, Endocrinology, and Nutrition (F.G., J.T., K.M.U., S.Z., J.U., W.Y.F., S.E.K.), Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, Washington 98108; Division of General Internal Medicine, Department of Medicine (M.J.M., E.J.B.), Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology (D.B.C.), and Department of Anthropology (D.L.L.), University of Washington, Seattle, Washington 98195; Epidemiologic Research and Information Center (B.A.Y., E.J.B.), VA Puget Sound Health Care System, Seattle, Washington 98108; and Division of Nephrology (B.A.Y., I.H.d.B.), Department of Medicine, University of Washington, Seattle, Washington 98195

Address all correspondence and requests for reprints to: Steven E. Kahn, M.B., Ch.B., VA Puget Sound Health Care System (151), 1660 South Columbian Way, Seattle, Washington 98108. E-mail: skahn{at}u.washington.edu.

Context: Although obesity has been, in general, associated with glomerular hyperfiltration, visceral adiposity has been suggested to be associated with reduced glomerular filtration.

Objective: The aim of the study was to evaluate the differential effects of obesity and body fat distribution on glomerular filtration.

Design and Setting: We conducted a cross-sectional study of the Japanese-American community in Seattle, Washington.

Participants: We studied a representative sample of second-generation Japanese-American men and women with normal glucose tolerance (n = 124) and impaired glucose metabolism (impaired fasting glucose and/or impaired glucose tolerance) (n = 144) residing in King County, Washington.

Main Outcome Measures: Glomerular filtration rate was estimated by 24-h urinary creatinine clearance, body size by body mass index (BMI), and intra-abdominal fat (IAF), sc fat (SCF), and lean thigh areas by CT scan.

Results: Creatinine clearance was positively correlated with BMI (r = 0.429; P < 0.001), fasting glucose (r = 0.198; P = 0.001), and insulin levels (r = 0.125; P = 0.042), as well as IAF (r = 0.239; P < 0.001), SCF (r = 0.281; P < 0.001), and lean thigh (r = 0.353; P < 0.001) areas. The association between creatinine clearance and BMI remained significant after adjustments for IAF, SCF areas, and fasting insulin levels (r = 0.337; P < 0.001); whereas IAF and SCF areas were not independently associated with creatinine clearance after adjusting for BMI. Creatinine clearance increased with increasing BMI after adjusting for fasting insulin, fasting glucose, IAF and SCF areas in subjects with normal glucose tolerance (r = 0.432; P < 0.001) and impaired glucose metabolism (r = 0.471; P < 0.001).

Conclusions: BMI rather than body fat distribution is an independent determinant of creatinine clearance in nondiabetic subjects. Lean body mass, rather than adiposity, may explain this association.