The online version of this article (doi:10.1186/s12882-017-0509-6) contains supplementary material, which is available to authorized users.
TGF-β is induced in the vasculature with aging suggesting that high plasma TGF-β levels may be a risk factor for chronic kidney disease (CKD) in older adults.
We conducted a cross-sectional analysis of the association between plasma TGF-β levels and CKD including data for 1722 older adults who had participated in the 1996/97 visit of the Cardiovascular Health Study (CHS). Prevalent CKD was defined as eGFR < 60 mL/min/1.73 m2 or urinary albumin/creatinine ratio (ACR) ≥30 mg/g. We also evaluated whether baseline TGF-β levels predicted change in eGFR, cardiovascular (CV) events, or mortality in longitudinal analysis.
Plasma TGF-β levels were significantly and independently associated with lower eGFR in cross-sectional analysis. Doubling of TGF-β was significantly associated with lower eGFR (β estimate after adjusting for CV risk factors = −1.18, 95% CI −2.03, −0.32). We observed no association with albuminuria. There was no association between baseline TGF-β and change in eGFR, but each doubling of TGF-β at baseline was associated with increased risk of a composite outcome of CV events and mortality, adjusted HR 1.10 (95% C.I. 1.02– 1.20, p = 0.006).
In this large cohort of community-dwelling older individuals, high plasma TGF-β levels are modestly, but independently associated with lower eGFR but not with albuminuria in cross-sectional analysis. In addition, TGF-β levels are associated with increased risk of CV events and mortality. Further research is needed to determine the direction of association between plasma TGF-β and the risk of CKD and CKD-associated morbidities in older adults.
Additional file 1: Table S1. Clinical characteristics by availability of TGF-β levels. (DOCX 13 kb)12882_2017_509_MOESM1_ESM.docx
Ziyadeh FN, Hoffman BB, Han DC, Iglesias-De La Cruz MC, Hong SW, Isono M, Chen S, McGowan TA, Sharma K. Long-term prevention of renal insufficiency, excess matrix gene expression, and glomerular mesangial matrix expansion by treatment with monoclonal antitransforming growth factor-beta antibody in db/db diabetic mice. Proc Natl Acad Sci U S A. 2000;97(14):8015–20. CrossRefPubMedPubMedCentral
Wong MG, Perkovic V, Woodward M, Chalmers J, Li Q, Hillis GS, Yaghobian Azari D, Jun M, Poulter N, Hamet P, et al. Circulating bone morphogenetic protein-7 and transforming growth factor-beta1 are better predictors of renal end points in patients with type 2 diabetes mellitus. Kidney Int. 2013;83(2):278–84. CrossRefPubMed
McCullough PA, Li S, Jurkovitz CT, Stevens LA, Wang C, Collins AJ, Chen SC, Norris KC, McFarlane SI, Johnson B, et al. CKD and cardiovascular disease in screened high-risk volunteer and general populations: the Kidney Early Evaluation Program (KEEP) and National Health and Nutrition Examination Survey (NHANES) 1999–2004. Am J Kidney Dis. 2008;51(4 Suppl 2):S38–45. CrossRefPubMed
Sedaghat S, Mattace-Raso FU, Hoorn EJ, Uitterlinden AG, Hofman A, Ikram MA, Franco OH, Dehghan A: Arterial Stiffness and Decline in Kidney Function. Clin J Am Soc Nephrol. 2015;10(12):2190–7.
Wang M, Zhao D, Spinetti G, Zhang J, Jiang LQ, Pintus G, Monticone R, Lakatta EG. Matrix metalloproteinase 2 activation of transforming growth factor-beta1 (TGF-beta1) and TGF-beta1-type II receptor signaling within the aged arterial wall. Arterioscler Thromb Vasc Biol. 2006;26(7):1503–9. CrossRefPubMed
About CHS, CHS Overview [ https://chs-nhlbi.org/CHSOverview].
Stevens LA, Coresh J, Schmid CH, Feldman HI, Froissart M, Kusek J, Rossert J, Van Lente F, Bruce III RD, Zhang YL, et al. Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD. Am J Kidney Dis. 2008;51(3):395–406. CrossRefPubMedPubMedCentral
Agarwal I, Glazer NL, Barasch E, Biggs ML, Djousse L, Fitzpatrick AL, Gottdiener JS, Ix JH, Kizer JR, Rimm EB, et al. Fibrosis-related biomarkers and incident cardiovascular disease in older adults: the cardiovascular health study. Circ Arrhythm Electrophysiol. 2014;7(4):583–9. CrossRefPubMedPubMedCentral
Ives DG, Fitzpatrick AL, Bild DE, Psaty BM, Kuller LH, Crowley PM, Cruise RG, Theroux S. Surveillance and ascertainment of cardiovascular events. Cardiovasc Health Study Ann Epidemiol. 1995;5(4):278–85.
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18(6):499–502. PubMed
R: A language and environment for statistical computing. [ http://www.R-project.org].
Yoshioka K, Takemura T, Murakami K, Okada M, Hino S, Miyamoto H, Maki S. Transforming growth factor-beta protein and mRNA in glomeruli in normal and diseased human kidneys. Lab Invest. 1993;68(2):154–63. PubMed
Wakefield LM, Smith DM, Flanders KC, Sporn MB. Latent transforming growth factor-beta from human platelets. A high molecular weight complex containing precursor sequences. J Biol Chem. 1988;263(16):7646–54. PubMed
Miyazono K, Hellman U, Wernstedt C, Heldin CH. Latent high molecular weight complex of transforming growth factor beta 1. Purification from human platelets and structural characterization. J Biol Chem. 1988;263(13):6407–15. PubMed
- Higher plasma transforming growth factor (TGF)-β is associated with kidney disease in older community dwelling adults
Jorge R. Kizer
Kenneth J. Mukamal
Joachim H. Ix
- BioMed Central
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