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

Liu, Qifeng; Liu, Yu; Jiang, Feng; Sun, Qiang; Li, Shasha; Ye, Jian-Ming

doi:10.1155/2019/6468729

Cited by 27 publications

(29 citation statements)

References 53 publications

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“…More importantly, in longitudinal human studies, downregulated sKlotho levels were shown to correlate strongly with rapid decline of estimated glomerular filtration rate or increase in mortality in CKD patients not undergoing dialysis [ 13 , 24 ]. All of the above studies support the notion that sKlotho may represent a novel potential prognostic biomarker for CKD patients [ 24 – 26 ]. This notion was also confirmed in our previous study [ 13 ].…”

Section: Discussionsupporting

confidence: 61%

Association of Soluble Klotho Level with Adverse Outcomes in Patients on Maintenance Hemodialysis

Liu

Jiang

et al. 2020

Disease Markers

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Background. The predictive value of soluble Klotho (sKlotho) for adverse outcomes in patients on maintenance hemodialysis (MHD) is controversial. In this study, we aimed to clarify the potential association of sKlotho levels with adverse outcomes in this patient population. Materials. A total of 211 patients on MHD were identified and stratified according to the median sKlotho level. Patients were followed up for adverse outcomes including cardiovascular (CV) morbidity and all-cause mortality. Results. During the 36-month follow-up, 75 patients [51 CV events (including 16 CV deaths) and 40 deaths] experienced adverse outcomes. After stratification according to median sKlotho level, patients with a lower sKlotho level had a greater risk of CV events (38.2% vs. 19.5%, p = 0.006 ), all-cause mortality (28.4% vs. 11.6%, p = 0.003 ), and combined adverse outcomes (51.0% vs. 24.2%, p < 0.001 ). Similar observations were made from analyses using Kaplan-Meier survival curves. Cox regression analysis showed that a low sKlotho level was strongly correlated with CV morbidity [1.942 (1.030–3.661), p = 0.040 )], all-cause mortality [2.073 (1.023–4.203), p = 0.043 ], and combined adverse outcomes [1.818 (1.092–3.026), p = 0.021 ] in fully adjusted models. Conclusions. The sKlotho level was an independent predictive factor of adverse outcomes including CV morbidity and mortality in patients on MHD.

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Section: Discussionsupporting

confidence: 61%

Association of Soluble Klotho Level with Adverse Outcomes in Patients on Maintenance Hemodialysis

Liu

Jiang

et al. 2020

Disease Markers

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“…On the other hand, data on the relationship between klotho and kidney function are divergent. Some studies have shown that a decrease in serum klotho correlates with a reduction in renal function; nevertheless, in other studies, such a relationship has not been confirmed [237,238]. Similar controversies concern the link between klotho and both PTH and FGF-23 [187].…”

Section: Klotho Proteinmentioning

confidence: 99%

Chronic Kidney Disease as Oxidative Stress- and Inflammatory-Mediated Cardiovascular Disease

Podkowińska¹,

2020

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Generating reactive oxygen species (ROS) is necessary for both physiology and pathology. An imbalance between endogenous oxidants and antioxidants causes oxidative stress, contributing to vascular dysfunction. The ROS-induced activation of transcription factors and proinflammatory genes increases inflammation. This phenomenon is of crucial importance in patients with chronic kidney disease (CKD), because atherosclerosis is one of the critical factors of their cardiovascular disease (CVD) and increased mortality. The effect of ROS disrupts the excretory function of each section of the nephron. It prevents the maintenance of intra-systemic homeostasis and leads to the accumulation of metabolic products. Renal regulatory mechanisms, such as tubular glomerular feedback, myogenic reflex in the supplying arteriole, and the renin–angiotensin–aldosterone system, are also affected. It makes it impossible for the kidney to compensate for water–electrolyte and acid–base disturbances, which progress further in the mechanism of positive feedback, leading to a further intensification of oxidative stress. As a result, the progression of CKD is observed, with a spectrum of complications such as malnutrition, calcium phosphate abnormalities, atherosclerosis, and anemia. This review aimed to show the role of oxidative stress and inflammation in renal impairment, with a particular emphasis on its influence on the most common disturbances that accompany CKD.

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“…The association of FGF-23 with CKD progression has been previously reported; however, the number of studies investigating the prognostic value of sKlotho is very limited and their results are contradictory [19,20]. In a recent meta-analysis of 8 cohort studies, the relationship between sKlotho and risk of adverse renal outcomes in CKD patients was examined, finding out that low sKlotho is significantly associated with an increased risk of poor renal outcomes [31]. However, there are many conflicting results about Klotho that require further studies.…”

Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor 23 and α-Klotho Protein Are Associated with Adverse Clinical Outcomes in Non-Dialysis CKD Patients

Manou

Thodis

Arsos

et al. 2020

Kidney Blood Press Res

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Background: Fibroblast growth factor 23 (FGF-23) and α-Klotho protein appear to have an important role in the pathogenesis of CKD-mineral and bone disorders. The aim of this study was to investigate the association of FGF-23 and α-Klotho levels with adverse clinical outcomes in patients with non-dialysis CKD. Materials and Methods: We conducted a prospective cohort study, enrolling participants with non-dialysis CKD from a single center in Greece. At enrollment, glomerular filtration rate (GFR) was measured (mGFR) and plasma levels of carboxyl terminal FGF-23 (cFGF-23) and soluble α-Klotho (sKlotho) were determined by enzyme-linked immunoassay. Participants were followed for up to 5 years or until the occurrence of the primary endpoint of initiation of renal replacement therapy or death. Multivariate regression tree analysis was used to identify informative baseline parameters in order to categorize participants. Also, using median values of cFGF-23 and sKlotho, participants were categorized into 4 groups, in whom survival was compared using Kaplan-Meier and Cox regression analysis. Results: 128 participants were enrolled with a median mGFR of 41.5 mL/min/1.73 m2 (IQR = 28.2). Baseline mGFR correlated with cFGF-23 and sKlotho (r = −0.54 and r = 0.49, respectively; p < 0.0001 for both). cFGF-23 and sKlotho levels correlated negatively (r = −0.24, p = 0.006). Multivariate regression tree analysis resulted in 3 groups defined by cutoff values of mGFR (60.9 mL/min/1.73 m2) and phosphate (3.7 mg/dL). These groups correlated with CKD stage, cFGF-23, and sKlotho (p < 0.0001 for all). During a median follow-up of 36 months (IQR = 22), 40 (31.2%) participants reached the primary endpoint (31 initiated renal replacement therapy, 9 died). Survival to primary endpoint differed among the 4 groups formed using median values of both biomarkers, with the low FGF-23/high Klotho and high FGF-23/low Klotho having the longest and shortest survival, respectively. High FGF-23/low Klotho group, compared to the opposite one, had a significantly elevated risk of the primary outcome (HR, 6.8; 95% CI, 2.3–19.6; p = 0.0004). Conclusions: In patients with CKD stages 1–5, the combination of higher cFGF-23 and lower sKlotho levels along with mGFR and serum phosphate was associated with adverse clinical outcomes. The utility of combinations of traditional and novel biomarkers to predict outcomes warrants further study.

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

Cited by 27 publications

References 53 publications

Association of Soluble Klotho Level with Adverse Outcomes in Patients on Maintenance Hemodialysis

Association of Soluble Klotho Level with Adverse Outcomes in Patients on Maintenance Hemodialysis

Chronic Kidney Disease as Oxidative Stress- and Inflammatory-Mediated Cardiovascular Disease

Fibroblast Growth Factor 23 and α-Klotho Protein Are Associated with Adverse Clinical Outcomes in Non-Dialysis CKD Patients

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