Growth Differentiation Factor 15 in Children with Chronic Kidney Disease and after Renal Transplantation
Hjørdis Thorsteinsdottir, Cathrin Lytomt Salvador, Geir Mjøen, Anine Lie, Meryam Sugulle, Camilla Tøndel, Atle Brun, Runar Almaas, Anna Bjerre
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 (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>p</mml:mi><mml:mo><</mml:mo><mml:mn>0.001</mml:mn></mml:math>). Univariate associations between GDF-15 and hyperuricemia (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi>p</mml:mi><mml:mo><</mml:mo><mml:mn>0.001</mml:mn></mml:math>), elevated triglycerides (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.028</mml:mn></mml:math>), low HDL (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.038</mml:mn></mml:math>), and obesity (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.028</mml:mn></mml:math>) were found. However, mGFR (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M6"><mml:mi>p</mml:mi><mml:mo><</mml:mo><mml:mn>0.001</mml:mn></mml:math>) and hemoglobin (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M7"><mml:mi>p</mml:mi><mml:mo><</mml:mo><mml:mn>0.001</mml:mn></mml:math>) 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 (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M8"><mml:mi>r</mml:mi><mml:mrow><mml:mo>=</mml:mo></mml:mrow><mml:mrow><mml:mo>−</mml:mo></mml:mrow><mml:mn>0.343</mml:mn></mml:math>, <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M9"><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.002</mml:mn></mml:math>). 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.