Systematic Review and Meta-Analysis of Plasma and Urine Biomarkers for CKD Outcomes

Background: Sensitive and specific biomarkers are needed to provide better biologic insight into the risk of incident and progressive CKD. However, studies have been limited by sample size and design heterogeneity.

Methods: In this assessment of the prognostic value of preclinical plasma and urine biomarkers for CKD outcomes, we searched Embase (Ovid), MEDLINE ALL (Ovid), and Scopus up to November 30, 2020, for studies exploring the association between baseline kidney biomarkers and CKD outcomes (incident CKD, CKD progression, or incident ESKD). We used random-effects meta-analysis.

Results: After screening 26,456 abstracts and 352 full-text articles, we included 129 studies in the meta-analysis for the most frequently studied plasma biomarkers (TNFR1, FGF23, TNFR2, KIM-1, suPAR, and others) and urine biomarkers (KIM-1, NGAL, and others). For the most frequently studied plasma biomarkers, pooled RRs for CKD outcomes were 2.17 (95% confidence interval [95% CI], 1.91 to 2.47) for TNFR1 (31 studies); 1.21 (95% CI, 1.15 to 1.28) for FGF-23 (30 studies); 2.07 (95% CI, 1.82 to 2.34) for TNFR2 (23 studies); 1.51 (95% CI, 1.38 to 1.66) for KIM-1 (18 studies); and 1.42 (95% CI, 1.30 to 1.55) for suPAR (12 studies). For the most frequently studied urine biomarkers, pooled RRs were 1.10 (95% CI, 1.05 to 1.16) for KIM-1 (19 studies) and 1.12 (95% CI, 1.06 to 1.19) for NGAL (19 studies).

Conclusions: Studies of preclinical biomarkers for CKD outcomes have considerable heterogeneity across study cohorts and designs, limiting comparisons of prognostic performance across studies. Plasma TNFR1, FGF23, TNFR2, KIM-1, and suPAR were among the most frequently investigated in the setting of CKD outcomes.