ASSOCIATION OF MUSCLE MASS WITH INULIN CLEARANCE-BASED GFR AND INTRAGLOMERULAR HEMODYNAMICS IN HEALTHY SUBJECTS, INDEPENDENT OF FASTING PLASMA GLUCOSE AND AGING

The prevalence of chronic kidney disease (CKD) is increasing with aging of the population. Inulin clearance (Cin) is the gold standard for determining GFR, which is required for diagnosis of CKD. Diabetes mellitus and hypertension are causes of CKD, and muscle mass and GFR are also related to each other. Aging, hypertension and plasma glucose have been associated with intra-renal hemodynamics, but the relationship of muscle mass with Cin and intrarenal hemodynamics is unclear. Therefore, the aim of this study is to examine the physiological associations underlying the relationship between Cin and muscle mass in healthy subjects.

Cin and para-aminohippurate clearance (CPAH) were measured and computed tomography (CT) was performed in 164 subjects (55.9±10.8 years, 70 males) who were candidates as kidney donors. Intrarenal hemodynamic parameters were calculated by Gomez's formulae. These formulae only apply for Cin >60 ml/min, and thus, only subjects with this value of Cin were included in the analysis. The psoas muscle mass index (PMI) (cm2/m2) was measured on axial CT images by tracing using image analysis software.

PMI was significantly correlated positively with Cin (r = 0.300, p < 0.0001), CPAH (r = 0.322, p < 0.0001) and glomerular hydrostatic pressure (Pglo) (r = 0.297, p < 0.0001), and negatively with vascular resistance at the afferent arteriole (Ra) (r = -0.235, p = 0.002). The following results were obtained in multiple regression analyses with adjustments for several clinical factors. Higher PMI was independently associated with higher Cin (β = 0.233, p = 0.030), CPAH (β = 0.263, p = 0.014), and Pglo (β = 0.212, p = 0.049), and with lower Ra (β = -0.214, p = 0.044), but not with urinary albumin excretion (UAE) (β = 0.054, p = 0.315). Higher fasting plasma glucose (FPG) was independently associated with higher Cin (β = 0.156, p = 0.037) and Pglo (β = 0.158, p = 0.037), but not with CPAH (β = 0.025, p = 0.733) and Ra (β = -0.029, p = 0.694), and with higher resistance at the efferent arteriole (Re) (β = 0.165, p = 0.032) and UAE (β = 0.334, p < 0.0001). Age was independently associated with lower Cin (β = -0.323, p < 0.0001), CPAH (β = -0.242, p = 0.002) and Pglo (β = -0.322, p < 0.0001) and higher Ra (β = 0.388, p < 0.001), but not with UAE (β = -0.031, p = 0.249). 

These results showing different relationships of GFR and intrarenal hemodynamics with muscle mass, FPG and aging may reflect differences in the impact of these factors on endothelial function. UAE has been suggested to develop only when endothelial dysfunction and hyperfiltration coexist. Myokines secreted from skeletal muscle improve both renal plasma flow and endothelial function via nitric oxide. However, to our knowledge, few reports have linked muscle mass to UAE. Endothelial dysfunction and hyperfiltration have been shown to coexist in patients with higher FPG and may lead to UAE. Aging has been associated with endothelial dysfunction, but GFR is physiologically decreased by aging, which suggests that aging might not be associated with UAE.

Muscle mass is associated with Cin and intraglomerular hemodynamics in healthy subjects, independent of FPG and aging.