Recent studies have suggested that circulating levels of the tumor necrosis factor-α receptor 1 (sTNFαR₁) may be a useful predictor for the risk of end-stage renal disease (ESRD) in patients with diabetes. However, its potential utility as a biomarker has not been formally quantified.

Circulating levels of sTNFαR₁ were assessed in 429 patients with type 1 diabetes and overt nephropathy from the Finnish Diabetic Nephropathy (FinnDiane) cohort study. Predictors of incident ESRD over a median of 9.4 years of follow-up were determined by Cox regression and Fine-Gray competing risk analyses. The added value of sTNFαR₁ was estimated via time-dependent receiver operating characteristic curves, net reclassification index (NRI), and integrated discrimination improvement (IDI) for survival data.

A total of 130 individuals developed ESRD (28%; ESRD incidence rate of 3.4% per year). In cause-specific modeling, after adjusting for baseline renal status, predictors of increased incidence of ESRD in patients with overt nephropathy were an elevated HbA_1c, shorter duration of diabetes, and circulating levels of sTNFαR₁. Notably, sTNFαR₁ outperformed estimated glomerular filtration rate in terms of R². Circulating levels of the sTNFαR₁ also remained associated with ESRD after adjusting for the competing risk of death. A prediction model including sTNFαR₁ (as a −0.5 fractional polynomial) was superior to a model without it, as demonstrated by better global fit, an increment of R², the C index, and area under the curve. Estimates of IDI and NRI(>0) were 0.22 (95% CI 0.16–0.28; P < 0.0001) and 0.98 (0.78–1.23; P < 0.0001), respectively. The median increment in the risk score after including sTNFαR₁ in the prediction model was 0.18 (0.12–0.30; P < 0.0001).

Circulating levels of sTNFαR₁ are independently associated with the cumulative incidence of ESRD. This association is both significant and biologically plausible and appears to provide added value as a biomarker, based on the absolute values of NRI and IDI.