Growth Differentiation Factor-15 and Risk of CKD Progression.
Growth differentiation factor-15 (GDF-15) is a member of the TGF-βcytokine 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 ofGDF15mRNA 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 intrarenalGDF15transcript 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 ofGDF15and significantly associated with increased risk of CKD progression in two independent cohorts. Circulating GDF-15 may be a marker for intrarenalGDF15-related signaling pathways associated with CKD and CKD progression.
Department of Internal Medicine, Division of Nephrology.
Viji
V
Nair
Kidney Research Institute, Division of Nephrology, University of Washington, Seattle, Washington.
Cassianne
C
Robinson-Cohen
Department of Internal Medicine, Division of Nephrology.
Michelle R
MR
Smith
Division of Nephrology, St. Clair Nephrology Research, Detroit, Michigan.
Keith A
KA
Bellovich
Department of Internal Medicine, Division of Nephrology, Wayne State University, Detroit, Michigan.
Zeenat Yousuf
ZY
Bhat
F. Hoffmann-La Roche, Roche Partnering, Basel, Switzerland.
Maria
M
Bobadilla
Department of Internal Medicine, Division of Nephrology.
Frank
F
Brosius
Kidney Research Institute, Division of Nephrology, University of Washington, Seattle, Washington.
Ian H
IH
de Boer
Roche Pharmaceutical Research and Early Development, Discovery Biology-Pharmaceutical Sciences, Roche Innovation Center Basel, Basel, Switzerland.
Laurent
L
Essioux
Roche Pharmaceutical Research and Early Development, Discovery Biology-Pharmaceutical Sciences, Roche Innovation Center Basel, Basel, Switzerland.
Ivan
I
Formentini
Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania; and.
Crystal A
CA
Gadegbeku
Department of Internal Medicine, Division of Pediatrics, and.
Debbie
D
Gipson
Department of Internal Medicine, Division of Nephrology.
Jennifer
J
Hawkins
Kidney Research Institute, Division of Nephrology, University of Washington, Seattle, Washington.
Jonathan
J
Himmelfarb
Kidney Research Institute, Division of Nephrology, University of Washington, Seattle, Washington.
Bryan
B
Kestenbaum
Department of Internal Medicine, Division of Nephrology.|Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan.
Matthias
M
Kretzler
Roche Pharmaceutical Research and Early Development, Discovery Biology-Pharmaceutical Sciences, Roche Innovation Center Basel, Basel, Switzerland.
Maria Chiara
MC
Magnone
John H. Stroger, Jr. Hospital of Cook County, Chicago, Illinois.
Kalyani
K
Perumal
Department of Internal Medicine, Division of Pediatrics, and.
Susan
S
Steigerwalt
Department of Internal Medicine, Division of Nephrology, nbansal@nephrology.washington.edu wenjunj@med.umich.edu.|Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan.
Wenjun
W
Ju
Kidney Research Institute, Division of Nephrology, University of Washington, Seattle, Washington; nbansal@nephrology.washington.edu wenjunj@med.umich.edu.
Nisha
N
Bansal
D018450:Disease Progression; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood* / Q000502:physiology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000209:etiology; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications; D018570:Risk Assessment
C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15
chronic kidney disease; end-stage renal disease; gene expression; glomerular filtration rate; kidney biopsy