Growth Differentiation Factor 15 in Children with Chronic Kidney Disease and after Renal Transplantation

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.