Abstract
Growth differentiation factor 15 (GDF-15) is strongly associated with cardiovascular disease (CVD). The aim of our study was to evaluate plasma and urinary levels of GDF-15 after pediatric renal transplantation (Rtx) and in children with chronic kidney disease (CKD) and its associations to cardiovascular risk factors. In this cross-sectional study, GDF-15 was measured in plasma and urine from 53 children with a renal transplant and 83 children with CKD and related to cardiovascular risk factors (hypertension, obesity, and cholesterol) and kidney function. Forty healthy children served as a control group. Plasma levels of GDF-15 (median and range) for a Tx (transplantation) cohort, CKD cohort, and healthy controls were, respectively, 865 ng/L (463-3039 ng/L), 508 ng/L (183-3279 ng/L), and 390 ng/L (306-657 ng/L). The CKD and Tx cohorts both had significantly higher GDF-15 levels than the control group (p < 0.001). Univariate associations between GDF-15 and hyperuricemia (p < 0.001), elevated triglycerides (p = 0.028), low HDL (p = 0.038), and obesity (p = 0.028) were found. However, mGFR (p < 0.001) and hemoglobin (p < 0.001) were the only significant predictors of GDF-15 in an adjusted analysis. Urinary GDF-15/creatinine ratios were 448 ng/mmol (74–5013 ng/mmol) and 540 ng/mmol (5–14960 ng/mmol) in the Tx cohort and CKD cohort, respectively. In the CKD cohort, it was weakly correlated to mGFR (r = −0.343, p = 0.002). Plasma levels of GDF-15 are elevated in children with CKD and after Rtx. The levels were not associated with traditional cardiovascular risk factors but strongly associated with renal function.
Highlights
Growth differentiation factor 15 (GDF-15), known as macrophage inhibitory cytokine-1 (MIC-1), is a distant member of the transforming growth factor-β (TGF-β) superfamily
We found that plasma levels of GDF-15 are significantly elevated in children with a renal transplant and in children with chronic kidney diseases compared to healthy children and that plasma GDF-15 levels are strongly associated with kidney function
This is the first time GDF-15 has been related to kidney function in a pediatric cohort an association between renal function and plasma GDF-15 has been found in adults [7, 19]
Summary
Growth differentiation factor 15 (GDF-15), known as macrophage inhibitory cytokine-1 (MIC-1), is a distant member of the transforming growth factor-β (TGF-β) superfamily. It was originally identified by Bootcov et al in 1997 as one of the macrophages’ regulating factors [1]. Urinary GDF-15 levels have been shown to be elevated and negatively correlated with eGFR in adults with diabetes [8]. Increasing data exists on GDF-15 in children, but only one study on children with kidney disease is published and demonstrates elevated GDF-15 levels in patients on hemodialysis and peritoneal dialysis [9]
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