Soluble Tumor Necrosis Factor Receptors (sTNFRs) as biomarkers for Diabetic Kidney Disease

Multiple biomarkers have been associated with Diabetic Kidney Disease (DKD) progression and its associated exaggerated risk for cardiovascular events and mortality. Chronic inflammation plays an important role in the progression of DKD. Tumor Necrosis Factor alpha (TNF-α) is a central proinflammatory cytokine that binds to its soluble receptor (sTNFR) and has been implicated in the pathogenesis of DKD. sTNFRs are a family of membrane proteins that regulate gene expression and activate cell death pathways. They are involved in the immune system and can bind to cytokines related to TNF. Higher levels of the type 1 (sTNFR1) and type 2 (sTNFR2) receptor have consistently been associated with progressive DKD, notably rapid GFR decline and progression to kidney failure. They offer enhanced risk prediction for progressive DKD over and above established risk markers. Higher levels of sTNFR1 and sTNFR2 also predict incident cardiovascular disease and mortality in people with diabetes. Further studies are required to define the temporal relationship between changes in circulating sTNFR levels and progression of kidney function loss. The influence of medications with kidney protective effects on sTNFR levels also requires further investigation.