Growth Differentiation Factor-15 and Risk of CKD Progression.

Nair V, Robinson-Cohen C, Smith MR, Bellovich KA, Bhat ZY, Bobadilla M, Brosius F, de Boer IH, Essioux L, Formentini I, Gadegbeku CA, Gipson D, Hawkins J, Himmelfarb J, Kestenbaum B, Kretzler M, Magnone MC, Perumal K, Steigerwalt S, Ju W, Bansal N
J Am Soc Nephrol. 2017 28 (7): 2233-2240

PMID: 28159780 · PMCID: PMC5491285 · DOI:10.1681/ASN.2016080919

Growth differentiation factor-15 (GDF-15) is a member of the TGF- 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 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 transcript levels (=0.54, =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; =0.003) and 65% higher (95% confidence interval, 1.08 to 2.50; =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 and significantly associated with increased risk of CKD progression in two independent cohorts. Circulating GDF-15 may be a marker for intrarenal -related signaling pathways associated with CKD and CKD progression.

Copyright © 2017 by the American Society of Nephrology.

MeSH Terms (9)

Disease Progression Female Growth Differentiation Factor 15 Humans Kidney Failure, Chronic Male Middle Aged Renal Insufficiency, Chronic Risk Assessment

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