Introduction: In patients with diabetes, albuminuria lacks the predictive accuracy for the development of progressive diabetic kidney disease (DKD). Baseline serum sTNFR1 levels have been shown to be a useful predictor of progressive DKD, however the relationship between sTNFR1 levels and eGFR decline remains to be defined¹.  The aim of this study was to examine the relationship between longitudinal changes in sTNFR1 levels and eGFR in patients with diabetes.

Methods:  From a clinic database, we identified a group of patients with stable eGFR (n=10) and those who had an early rapid decline in eGFR (>3.5 ml/min/1.73m² per year, n=17). Both groups were matched for initial eGFR, albumin excretion rate (AER), duration of diabetes, HbA1c, blood pressure control and treatment, gender and type of diabetes. Patients were only included in the study if they had a minimum follow up of 4 years that also included at least 4 GFR estimations.  A pooled ordinary least squares (pooled OLS) regression model was used to examine the relationship between changes in sTNFR1 levels and eGFR.

Results: In patients with an early rapid decline in renal function, sTNFR1 values increased (2407 ± 144 vs 3568 ± 293 pg/ml, p< 0.01) as eGFR decreased (84±2 vs 44±2 ml/min/1.73m², p<001). This decline in eGFR was not accompanied by a significant increase in AER. There were no significant changes in sTNFR1 levels or AER in the stable eGFR group. In a pooled-OLS regression model that included other established clinical and biochemical risk markers, changes in sTNFR1 levels were independently associated with eGFR decline (F= 69.8, p < 0.001). The addition of sTNFR1 levels to the pooled OLS model improved the explained variable of eGFR decline (R² increased from 31% to 50%).

Conclusions:  Circulating sTNFR1 levels increase as eGFR declines independently of AER. Measurement of sTNFR1 levels improves prediction of eGFR decline on top of established risk markers for progression of DKD.

¹Gohda T. Curr Diab Rep 2013, 14, 560