Serum hepatocyte growth factor is associated with truncal fat mass and increased mortality in chronic kidney disease stage 5 patients with protein-energy wasting

Abstract

Background: Obese sarcopenia characterized by increased fat mass and protein-energy wasting (PEW) is not uncommon in chronic kidney disease (CKD) stage 5 patients in whom it is associated with worse outcomes. Serum hepatocyte growth factor (HGF) is associated with obesity in the general population and is increased in CKD patients in whom its association with body composition is not known. We studied the associations between HGF, PEW and body composition, and between HGF and mortality, in CKD stage 5 patients starting dialysis.

Methods: In 224 CKD stage 5 patients (139 males, mean age 52 years, mean glomerular filtration rate (GFR) 6.6 mL/min), blood samples were obtained for analyses of HGF, high-sensitivity C-reactive protein (hsCRP), glucose, insulin and lipids. Total fat mass index (FMI), truncal fat mass index (TFMI) and lean body mass index (LBMI) assessed by dual-energy X-ray absorptiometry and PEW assessed by subjective global assessment (SGA) were recorded at baseline. Patients were followed up for 5 years.

Results: Serum HGF levels were higher in patients with high TFMI versus low TFMI [3.1 (IQR: 2.4-4.5) versus 2.7 (IQR: 1.9-3.8) ng/mL; P = 0.01] and in those with PEW versus non-PEW [3.4 (IQR: 2.4-3.6) versus 2.8 (IQR: 2.1-3.8) ng/mL; P = 0.03]. Patients with both high TFMI and presence of PEW had significantly (P < 0.001) higher HGF concentration [4.4 (IQR: 3.3-6.6) ng/mL] than other patient groups (high TFMI and non-PEW, low TFMI and PEW or low TFMI and non-PEW). Multivariate linear regression showed that TFMI was an independent predictor of HGF (R(2) = 0.21, P = 0.048). In Cox analysis, patients with high HGF and presence of PEW had worse all-cause mortality after adjusting for age, gender and hsCRP (HR: 3.59, 95% CI: 1.19-5.35).

Conclusions: Increased TFMI was an independent predictor of HGF in CKD stage 5 patients. Moreover, an elevated HGF level increased the mortality risk in the presence of PEW. These results suggest a central role of HGF in the metabolic and nutritional alterations in CKD stage 5 patients.

Keywords: body composition; dual-energy X-ray absorptiometry; inflammation; protein-energy wasting; sarcopenia.