Lean mass modulates glomerular filtration rate in males of normal and extreme body composition J. S.C. Chew-Harris, 1,2 C. M. Florkowski, 1 J. L. Elmslie, 1 J. Livesey, 1 Z. H. Endre 2,3 and P. M. George 1,2 1 Clinical Biochemistry Unit, Canterbury Health Laboratories, 2 Christchurch School of Medicine, University of Otago, Christchurch, New Zealand, and 3 Department of Nephrology, Prince of Wales Hospital and Clinical School, Sydney, Australia Key words glomerular filtration rate, lean mass, chronic kidney disease. Correspondence Janice S. C. Chew-Harris, Clinical Biochemistry Unit, Canterbury Health Laboratories, Corner of Tuam and Hagley Avenue, PO Box 151, Christchurch 8011, New Zealand. Email: janice.harris@cdhb.health.nz Received 18 November 2013; accepted 5 May 2014. doi:10.1111/imj.12479 Abstract Background: Understanding determinants of glomerular filtration rate (GFR) is impor- tant in aiding prediction and interpretation of kidney function. Body composition is known to affect GFR but is not included in current screening of kidney disease. We investigated the association between GFR and body composition in healthy young men with differing body mass but without known diabetes or kidney injury. Methods: Three groups were recruited: normal BMI (n = 22) with a body mass index (BMI) <25 kg/m 2 , muscular (n = 23) with BMI ≥30 kg/m 2 and bioelectrical impedance body fat ≤20% and obese (n = 22) with BMI ≥30 kg/m 2 and bioelectrical impedance body fat ≥30%. Dietary analyses, GFR clearance by 99m Tc-DTPA, urine protein and body composition by dual-energy X-ray absorptiometry were measured in all participants. Linear and nonlinear associations of constituents of body composition with GFR were assessed. Results: Muscular men had a higher GFR (mean 186.4 mL/min; 95% CI 171.7–201.1) than normal BMI and obese groups (P = 0.0007). Urine protein and albumin excretion were not elevated in any participants. On multiple regression analysis (r 2 = 0.60), the variables with strong associations with GFR were age (P = 0.0009) and lean mass (P = 0.0001). Fat mass, protein intake and smoking status were not associated. Skeletal muscle mass correlated significantly with GFR in all subgroups. Conclusion: Age and lean mass were strong determinants of GFR. Estimates of GFR should therefore be indexed to an estimate of lean mass. Introduction Insight into the factors affecting glomerular filtration rate (GFR) in subjects without kidney disease may assist with separating normal from abnormal kidney function and this may help provide strategies for prevention. Although not entirely understood, in subjects with obesity, renal structure and function have been shown to be progressively altered. Several studies showed an asso- ciation between obesity and glomerular hyperfiltration, 1 chronic kidney disease (CKD) 2 and end-stage renal failure. 3 Glomerular hyperfiltration, signified by increases in GFR, often predicts development of nephropathy in patients with type 1 diabetes. 4 Different mechanisms of hyperfiltration are postulated. 5–7 In diabetes, the chain of events includes incremented glomerular intracapillary pressure and glomerulosclerosis with subsequent loss of GFR. Hyperfiltration in obese individuals diminishes after a reduction in bodyweight, 8,9 suggesting body composition may be involved in the regulation of GFR. However, it is not certain whether a reduction in lean or fat mass reduces hyperfiltration to normal levels. Current guide- lines do not address how hyperfiltration should be incor- porated into CKD screening. Two important concepts regarding the effect of body composition on kidney function warrant investigations. First, although not widely documented, several studies have shown that lean mass is correlated with GFR. 10–13 Second, there is growing evidence that normalising GFR to body surface area (BSA) may not be entirely appro- priate as humans have a fixed number of nephrons that must increase filtration in order to meet the demands of body size. 7 Therefore accuracy of prediction equations in estimating GFR is questionable especially for those with Funding: We are extremely grateful to the New Zealand Kidney Foundation and Canterbury Medical Research Foundation for grant support. Conflict of interest: None. © 2014 The Authors Internal Medicine Journal © 2014 Royal Australasian College of Physicians 749