Growth differentiation factor-15 and Risk of CKD progression

Viji Nair, Cassianne Robinson-Cohen, 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 JuNisha Bansal

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

Growth differentiation factor-15 (GDF-15) is a member of the TGF-b cytokine superfamily that is widely expressed andmay be induced in response to tissue injury. Elevations inGDF-15may 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 ofGDF15mRNA correlates with circulating levels ofGDF-15 and whether elevations in circulating GDF-15 are associated with decline in kidney function. Inmatching samples of 24 patients with CKD fromthe 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 ESRDover a median of 1.8 and 2.0 years of follow up, respectively. Inmultivariablemodels, after adjusting for potential confounders, every doubling ofGDF-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-15may be amarker for intrarenalGDF15-related signaling pathways associated with CKD and CKD progression.

Original languageEnglish (US)
Pages (from-to)2233-2240
Number of pages8
JournalJournal of the American Society of Nephrology
Volume28
Issue number7
DOIs
StatePublished - Jul 2017
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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