Circulating TNF receptors and risk of renal disease progression, cardiovascular disease events and mortality in patients with diabetes: a systematic review and meta-analysis

Purpose Inflammation plays an important role in the pathogenesis of diabetes complications. This study aims to assess the association between circulating inflammatory biomarkers TNF receptors (TNFRs) and the risk of renal disease progression, cardiovascular disease (CVD) events, and mortality in patients with diabetes. Methods PubMed and Embase databases were comprehensively searched up to March 2019. Data were extracted independently by two reviewers. A random effects model was performed for the pooled analyses. Results Five studies in 3316 subjects assessed TNFRs with renal disease in patients with type 1 diabetes and showed both TNFR-1 and TNFR-2 were consistently associated with the renal outcomes. Fourteen studies in 7696 subjects evaluated TNFRs in patients with type 2 diabetes. The pooled risk ratio per doubling increase in TNFR-1 and TNFR-2 for renal disease progression was more than two (2.64 [1.98, 3.52] and 2.23 [1.69, 2.94]). The subgroup analyses and sensitivity analyses further illustrated these results of renal outcome and its robustness. Moreover, higher TNFR-1 and TNFR-2 was also significantly associated with CVD events and mortality in patients with type 2 diabetes. Conclusions Circulating TNFR-1 and TNFR-2 are independently associated with higher risk of renal disease progression, CVD events, and mortality in patients with diabetes and might contribute to the clinical risk assessment in the future.