TNFR1 is associated with short-term mortality in patients with diabetes and acute dyspnea seeking care at the emergency department

Abstract

Background Circulating levels of TNF alpha receptor 1 (TNFR1) and 2 (TNFR2) are associated with increased long-term mortality and impaired kidney function. Aim To study association between circulating levels of TNFR1 and TNFR2 and short-term mortality in patients with diabetes and dyspnea. Population and methods Patients aged ≥ 18 years seeking at emergency department (ED) during daytime on weekdays between December 2013 and July 2018, with diabetes and acute dyspnea, identified at the triage process, were included. Participants (n = 291) were triaged according to Medical Emergency Triage and Treatment System-Adult score, and blood samples were collected. Association between TNFR1 and TNFR2, respectively, and 90-day mortality were estimated by Cox regression models adjusted for age, sex, BMI, creatinine and CRP. Results Univariate models showed significant associations between TNFR1 and TNFR2, respectively, and CRP, age and creatinine. TNFR1 and TNFR2 tended to be elevated in patients with the highest triage level, compared to patients with lower triage levels (ns). In longitudinal analyses, TNFR1 but not TNFR2 was associated with increased short-term mortality, HR adjusted for age, BMI and creatinine 1.43 (95% CI 1.07–1.91), but not in the model also adjusted for CRP, HR 1.29 (95% CI 0.94–1.77). In secondary analysis for quartile 4 versus quartiles 1–3 of TNFR1, corresponding HRs were 2.46 (95% CI 1.27–5.15) and 2.21 (95% CI 1.07–2.56). Conclusions We found a trend for the association between circulating TNFR1 levels and short-term mortality in patients with diabetes and acute dyspnea at the ED, possibly suggesting an inflammatory pathway for the association.

Tumor Necrosis Factor Receptors: Pleiotropic Signaling Complexes and Their Differential Effects

“…In diabetics presenting to an ER with shortness of breath, elevations associated with short-term mortality, HR, BMI, and renal function; was not significant when adjusting for CRP ( 125 )…”

“…While interventional evidence is lacking, several publications demonstrate disease associations with differential TNFR effects, particularly for serum levels of sTNFR ( 119 – 123 , 125 – 129 , 131 ). Intriguingly, the concentrations of both sTNFR1 and sTNFR2 follow circadian rhythms that run about 1 h ahead of the well-established cortisol fluctuations ( 152 ).…”

“…Overall, the most robust clinical association for sTNFR1 is for predicting future renal disease in diabetics ( 126 – 128 ). Elevated sTNFR1 (but not sTNFR2) was associated with worse outcomes when presenting to an emergency room with shortness of breath, but also lost statistical significance when adjusting for CRP ( 125 ). Associations unique to sTNFR1 were also seen with treatment-responsive lupus ( 122 ), sleep disruption in depression ( 119 ), worse outcomes in GVHD after ablative-conditioned BMT ( 129 ), and mortality and dialysis needs for post-liver transplant patients ( 120 ).…”