The Prognostic Role of Klotho in Patients with Chronic Kidney Disease: A Systematic Review and Meta-analysis

Abstract

Objective. The prognostic role of Klotho in patients with chronic kidney disease is still controversial. Therefore, we performed this meta-analysis to assess the relationship between the low sKlotho level and the risk of adverse kidney outcomes. Materials and Methods. We systematically searched medical databases, such as PubMed, Embase, and the Cochrane Library, for eligible publications regarding the relationship between the low sKlotho level and risk of adverse kidney outcomes. The quality of included studies was assessed by using the Newcastle–Ottawa Scale. Combined hazard ratios (HRs) and its 95% confidence intervals (CIs) were calculated using a random- or fixed-effect model. Subgroup analysis was conducted with stratification by age, estimated glomerular filtration rate (eGFR), follow-up interval, region, and study quality. All data was analyzed by RevMan 5.3 analysis software. Results. Eight cohort studies with 3586 participants from 3818 studies were included in our final analysis. Levels of sKlotho were significantly correlated with the eGFR, with a summary correlation coefficient r and 95% CI of 0.469 (0.226, 0.658). Additionally, low sKlotho levels were strongly associated with increased adverse kidney outcomes, and the pooled HR and its 95% CI were 1.64 (1.19, 2.26; P=0.002), despite publication bias and statistical heterogeneity (I2=52%, P=0.07). Furthermore, this positive correlation was still observed in all of the subgroup analyses. However, heterogeneity was present in subgroup analyses stratified by the eGFR and follow-up interval. Conclusion. Levels of sKlotho are positively correlated with the eGFR, and low sKlotho levels are significantly associated with an increased risk of poor kidney outcomes. Therefore, sKlotho could be used as a novel biomarker for early diagnosis and prognostic assessment for patients with chronic kidney disease. Studies with a larger sample size and longer follow-up period are warranted to validate our results.