Lee, Jung EunGohda, TomohitoWalker, William H.Skupien, JanSmiles, Adam M.Holak, Rita R.Jeong, JacksonMcDonnell, Kevin P.Krolewski, AndrzejNiewczas, Monika2013-05-132013Lee, Jung Eun, Tomohito Gohda, William H. Walker, Jan Skupien, Adam M. Smiles, Rita R. Holak, Jackson Jeong, Kevin P. McDonnell, Andrzej Stefan Krolewski, and Monika Anna Niewczas. 2013. Risk of ESRD and all cause mortality in Type 2 diabetes according to circulating levels of FGF-23 and TNFR1. PLoS ONE 8(3): e58007.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:10622952Introduction: Recent studies demonstrated that circulating fibroblast growth factor (FGF)-23 was associated with risk of end stage renal disease (ESRD) and mortality. This study aims to examine whether the predictive effect of FGF-23 is independent from circulating levels of tumor necrosis factor receptor 1 (TNFR1), a strong predictor of ESRD in Type 2 diabetes (T2D). Methods: We studied 380 patients with T2D who were followed for 8–12 years and were used previously to examine the effect of TNFR1. Baseline plasma FGF-23 was measured by immunoassay. Results: During follow-up, 48 patients (13%) developed ESRD and 83 patients (22%) died without ESRD. In a univariate analysis, baseline circulating levels of FGF-23 and TNFR1 were significantly higher in subjects who subsequently developed ESRD or died without ESRD than in those who remained alive. In a Cox proportional hazard model, baseline concentration of FGF-23 was associated with increased risk of ESRD, however its effect was no longer significant after controlling for TNFR1 and other clinical characteristics (HR 1.3, p = 0.15). The strong effect of circulating level of TNFR1 on risk of ESRD was not changed by including circulating levels of FGF-23 (HR 8.7, p<0.001). In the Cox multivariate model, circulating levels of FGF-23 remained a significant independent predictor of all-cause mortality unrelated to ESRD (HR 1.5, p<0.001). Conclusions: We demonstrated that the effect of circulating levels of FGF-23 on the risk of ESRD is accounted for by circulating levels of TNFR1. We confirmed that circulating levels of FGF-23 have an independent effect on all-cause mortality in T2D.en-USBiologyImmunologyImmune SystemCytokinesMedicineClinical Research DesignCohort StudiesEpidemiologyProspective StudiesDiagnostic MedicinePathologyClinical PathologyEndocrinologyDiabetic EndocrinologyDiabetes Mellitus Type 2Cardiovascular Disease EpidemiologyClinical EpidemiologyNephrologyChronic Kidney DiseaseJournal Article2013-05-1310.1371/journal.pone.0058007