Growth Differentiation Factor–15 and Risk of CKD Progression

• DOI: 10.1681/asn.2016080919
• Publication Date: 2017-02-04T01:40:26Z
• Authors: Viji Nair; Cassianne Robinso...; Michelle R. Smith; Keith A. Bellovich; Zeenat Yousuf Bhat; Maria Bobadilla; Frank Brosius; Ian H. de Boer; Laurent Essioux; Ivan Formentini; Crystal A. Gadegbeku; Debbie Gipson; Jennifer Hawkins; Jonathan Himmelfarb; Bryan Kestenbaum; Matthias Kretzler; Maria Chiara Magnone; Kalyani Perumal; Susan Steigerwalt; Wenjun Ju; Nisha Bansal
• Keywords: Male; 0301 basic medicine; 03 medical and health sciences; Growth Differentiation Factor 15; 0302 clinical medicine; Disease Progression; Humans; Kidney Failure, Chronic; Female; Middle Aged; Renal Insufficiency, Chronic; 16. Peace & justice; Risk Assessment

Growth differentiation factor–15 (GDF-15) is a member of the TGF-β cytokine superfamily that is widely expressed and may be induced in response to tissue injury. Elevations in GDF-15 may identify a novel pathway involved in loss of kidney function among patients with CKD. Among participants in the Clinical Phenotyping and Resource Biobank (C-PROBE) study and the Seattle Kidney Study (SKS), we tested whether kidney tissue expression of GDF15 mRNA correlates with circulating levels of GDF-15 and whether elevations in circulating GDF-15 are associated with decline in kidney function. In matching samples of 24 patients with CKD from the C-PROBE study, circulating GDF-15 levels significantly correlated with intrarenal GDF15 transcript levels (r=0.54, P=0.01). Among the 224 C-PROBE and 297 SKS participants, 72 (32.1%) and 94 (32.0%) patients, respectively, reached a composite end point of 30% decline in eGFR or progression to ESRD over a median of 1.8 and 2.0 years of follow up, respectively. In multivariable models, after adjusting for potential confounders, every doubling of GDF-15 level associated with a 72% higher (95% confidence interval, 1.21 to 4.45; P=0.003) and 65% higher (95% confidence interval, 1.08 to 2.50; P=0.02) risk of progression of kidney disease in C-PROBE and SKS participants, respectively. These results show that circulating GDF-15 levels strongly correlated with intrarenal expression of GDF15 and significantly associated with increased risk of CKD progression in two independent cohorts. Circulating GDF-15 may be a marker for intrarenal GDF15-related signaling pathways associated with CKD and CKD progression.