Growth differentiation factor-15 and Risk of CKD progression

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.