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Meta-Analysis
. 2022 Sep;33(9):1657-1672.
doi: 10.1681/ASN.2022010098. Epub 2022 Jul 20.

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

Caroline Liu  1 , Neha Debnath  2 , Gohar Mosoyan  3 , Kinsuk Chauhan  3 , George Vasquez-Rios  3 , Celine Soudant  4 , Steve Menez  5 , Chirag R Parikh  5 , Steven G Coca  3
Affiliations
Meta-Analysis

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

Caroline Liu et al. J Am Soc Nephrol. 2022 Sep.

Abstract

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.

Keywords: chronic allograft failure; chronic kidney disease.

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Figures

Figure 1.
Figure 1.
Preferred Reporting Items for Systematic Reviews and Meta-analyses flow chart of study selection for systematic review and meta-analysis.
Figure 2.
Figure 2.
Number of studies and pooled relative risks for 12 most frequently studied biomarkers for CKD outcomes. (A) plasma; (B) urine.
Figure 3.
Figure 3.
Forest plots of plasma for CKD outcomes. (A) TNFR1, (B) FGF23, (C) TNFR2, (D) KIM-1, (E) suPAR, and (F) GDF-15.
Figure 3.
Figure 3.
Forest plots of plasma for CKD outcomes. (A) TNFR1, (B) FGF23, (C) TNFR2, (D) KIM-1, (E) suPAR, and (F) GDF-15.
Figure 4.
Figure 4.
Forest plots of urine for CKD outcomes. (A) KIM-1; (B) NGAL.
See this image and copyright information in PMC

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