Association between high-sensitivity C-reactive protein and diabetic nephropathy: a systematic review and meta-analysis

Abstract

Background Diabetic nephropathy (DN) is a major complication of diabetes, driven by inflammation and progressive kidney damage. High-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation, has been linked to DN progression, but study findings are inconsistent. This systematic review and meta-analysis aimed to evaluate the association between hs-CRP levels and DN risk. MethodsWe searched PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, and Embase from inception to July 22, 2024, for observational studies examining hs-CRP and DN. Although IL-6 and ESR were initially considered for analysis, they were excluded from the meta-analysis due to insufficient data for pooling. Fifteen studies involving 16,324 participants were included. A random-effects model pooled effect sizes, with heterogeneity assessed using the I-2 statistic and Cochran Q test. Subgroup analyses explored variations by study design and sample size. Results From 8312 citations, 15 studies met the inclusion criteria, comprising 16,324 participants from diverse geographic locations. Meta-analysis of the 15 studies showed that elevated hs-CRP levels (above vs. below a clinical threshold of 2.5 mg/L) were associated with 65 increased odds of DN (OR = 1.65, 95 CI: 1.36-1.99, P = 0.002), with substantial heterogeneity (I-2 = 79.4, P < 0.001). Conclusion Elevated hs-CRP levels are significantly associated with increased DN risk, supporting its clinical utility for risk stratification in diabetic patients and its relevance for guiding future research into anti-inflammatory therapies. However, high heterogeneity, likely due to differences in study design, population characteristics, and measurement methods, limits the generalizability of these findings. Future research should clarify causal mechanisms and validate hs-CRP's role in clinical decision-making for DN prevention. Clinical trial numberIt is not applicable.