Association between Plasma Levels of Growth Differentiation Factor-15 and Renal Function in the Elderly: Korean Frailty and Aging Cohort Study

Abstract

Background/Aims: Growth differentiation factor-15 (GDF-15) expression has been reported to increase in response to tissue damage and has recently emerged as a useful biomarker for various diseases. Although emerging evidence supports the clinicopathological value of GDF-15 in renal impairment, few studies have analyzed it in the elderly. Thus, we conducted a cross-sectional study to investigate the association of plasma GDF-15 with renal function and the presence of chronic kidney disease (CKD) in community-dwelling elderly. Materials: The present study was based on the baseline data of the Korean Frailty and Aging Cohort Study (KFACS), a nationwide cohort study that began in 2016. Of the 1,559 participants assessed in the first year, 443 with available plasma GDF-15 data were enrolled in this study. We investigated the association of plasma GDF-15 levels with clinical and biochemical parameters. The study population was divided into two groups according to renal function (CKD and non-CKD groups) to investigate whether GDF-15 can determine the presence of renal dysfunction in the elderly. Plasma GDF-15 was measured by enzyme-linked immunosorbent assay (ELISA) kit. Results: In a simple regression analysis, the levels of plasma GDF-15 were negatively correlated with estimated glomerular filtration rate (eGFR; r = –0.383, p < 0.001). In multiple linear regression analysis, GDF-15 levels were still significantly correlated with eGFR, even after adjusting for other parameters (r = –0.259, p < 0.001). Plasma GDF-15 levels were significantly higher in the elderly with CKD than in those without CKD (2,364.025 ± 1,052.23 ng/L and 1,451.23 ± 835.79 ng/L, respectively; p < 0.001). The optimal cut-off value of plasma GDF-15 for detecting the presence of CKD was 1,699.4 ng/L (76.5% sensitivity and 76.0% specificity), as determined by the receiver operating characteristic curve. The area under the curve was 0.793 ± 0.033 (95% CI 0.729–0.857, p < 0.001). Conclusion: Plasma GDF-15 levels were negatively associated with eGFR and were significantly increased in the elderly with CKD. Our results suggested that plasma GDF-15 might be a useful marker for discriminating renal impairment in the elderly. Further large and prospective outcome studies of extended duration are needed.

Prognostic Value of Growth Differentiation Factor 15 in Kidney Donors and Recipients

“…Compared to healthy LD, we observed noticeably increased GDF15 levels in patients with ESRD. This is consistent with observations by others who found that CKD in all age cohorts leads to a significant increase of GDF15 [12,13,15,21]. In addition, GDF15 can also increase in response to acute kidney injuries [10,11].…”

Association of serum growth differentiation factor-15 with eGFR and hemoglobin in healthy older females

“…Here we showed that serum GDF-15 levels were negatively correlated with eGFR in healthy older females. These findings are in agreement with consistent reports of association between GDF-15 and numerous risk factors and biomarkers for cardiovascular diseases [16] , [15] , [19] . Nakajima et al [16] showed that eGFR and anterior thigh muscle thickness were independent determinants of GDF-15 after adjusting for age, sex and BMI in patients with cardiovascular disease.…”

“…Nakajima et al [16] showed that eGFR and anterior thigh muscle thickness were independent determinants of GDF-15 after adjusting for age, sex and BMI in patients with cardiovascular disease. Other studies revealed that eGFR, diabetes mellitus and Hb were predictors for GDF-15 in community-dwelling older subjects [15] .…”

“…Cardiomyocytes [12] and vascular smooth muscle cells [13] produce and secrete GDF-15 in response to oxidative stress or proinflammatory cytokines. A limited number of studies have investigated the association between serum GDF-15 and renal function in older subjects [14] , [15] . In these studies, multiple regression analysis showed that eGFR is an independent variable to predict GDF-15 [14] , [15] , and that hemoglobin (Hb) is an independent determinant of GDF-15 [15] .…”

“…A limited number of studies have investigated the association between serum GDF-15 and renal function in older subjects [14] , [15] . In these studies, multiple regression analysis showed that eGFR is an independent variable to predict GDF-15 [14] , [15] , and that hemoglobin (Hb) is an independent determinant of GDF-15 [15] . In addition, anterior thigh muscle thickness measured by echography as well as eGFR levels is independent determinants of GDF-15 levels in patients with cardiovascular disease [16] .…”