Circulating Tnf Receptors 1 And 2 Predict Progression Of Diabetic Kidney Disease

Background: We conducted a meta-analysis to investigate the association of circulating tumor necrosis factor-1(TNFR-1)and TNFR-2 with diabetic kidney disease(DKD)progression,which is the first-ever quantitative analysis of these associations thus far.Whether TNFRs were better than albumin-creatinine ratio(ACR)in predicting DKD progression was also explored.Methods: A systematic search of the PubMed,EMBASE,and Cochrane Library databases up to 1 February 2018,was conducted.The main outcome was DKD progression,which was defined as eGFR decline,macroalbuminuria,or incidence of DKD-related events.Eligible studies were included for pooled analysis using either fixed-effects or random-effects models to incorporate between-study variation by different measurement standards.Publication bias was evaluated using Egger’s test.Results: The meta-analysis included 6526 participants from 11 cohorts with circulating TNFR-1 measurements and 5385 participantsfrom 10 prospective studies with circulating TNFR-2 measurements.Compared with the lowest level category,diabetic patients with the highest TNFR-1 or TNFR-2 level category exhibited a higher risk of DKD progression(RR 2.51,95% CI [1.92-3.27] for TNFR-1;3.23[1.99-5.26] for TNFR-2).The risk of DKD progression was also increased with the per unit increment of TNFR-1 or TNFR-2(1.68[1.43-1.97] for TNFR-1;1.69 [1.31-2.17] for TNFR-2).Although existing studies did not support a direct comparison between ACR and TNFRs,it was undeniable that TNFRs could improve the predictive value in DKD progression.Conclusions: Circulating TNFR-1 and TNFR-2 are reliable predictors of DKD progression.Whether TNFRs are better than ACR at predicting DKD progression needs to be further investigated.