Rapid decline of kidney function in diabetic kidney disease is associated with high soluble Klotho levels

Bob, Flaviu; Schiller, Adalbert; Timar, Romulus; Lighezan, Daniel; Schiller, Oana; Timar, Bogdan; Bujor, Cristiana Georgeta; Munteanu, Mircea; Gădălean, Florica; Mihaescu, Adelina; Grosu, Iulia; Hategan, Andreea; Chisavu, Lazar; Pusztai, Agneta Maria; Covic, Adrian

doi:10.1016/j.nefro.2018.08.004

Cited by 15 publications

(33 citation statements)

References 39 publications

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“…Eight cohort studies were included in our final analysis of 3586 participants [13, 16, 18, 21–25]. Three studies provided information on the sKlotho level and the eGFR (Pearson correlation coefficients or Spearman correlation coefficients) [13, 16, 25], and two studies reported data on sKlotho and an annual decline in eGFR (Pearson correlation coefficients) [21, 24]. Four studies reported data on the sKlotho level and kidney outcomes (HR and its 95% CI) [13, 18, 24, 25].…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, OR was estimated on the basis of data that were provided in another study [22] because its HR could not be obtained directly or calculated indirectly. Three studies reported correlation coefficients for FGF23 and eGFR [13, 21, 25]. Two studies reported HRs and 95% CIs for FGF23 levels and kidney outcomes [18, 25].…”

Section: Resultsmentioning

confidence: 99%

“…Three studies reported data on FGF23 levels and the eGFR, and all of the three studies showed a negative association between FGF23 levels and the eGFR [13, 21, 25]. Our combined Fisher's Z value with its 95% CI was −0.61 (−0.86, −0.36), despite significant heterogeneity ( I 2 = 82%, P = 0.004, Figure 3), and the calculated summary r and its 95% CI were −0.544 (−0.696, −0.345).…”

Section: Resultsmentioning

confidence: 99%

“…Only two studies reported data on sKlotho levels and an annual decline in the eGFR [21, 24]. In Kim et al's study, sKlotho levels were negatively correlated with an annual decline in the eGFR ( r = −0.217, P = 0.009) after adjustment for clinical parameters including baseline eGFR [24].…”

Section: Resultsmentioning

confidence: 99%

“…In Kim et al's study, sKlotho levels were negatively correlated with an annual decline in the eGFR ( r = −0.217, P = 0.009) after adjustment for clinical parameters including baseline eGFR [24]. However, in Bob et al's study, sKlotho was positively associated with an annual decline in the eGFR ( r = 0.714, P = 0.0004) and one increase with a standard deviation in the sKlotho level followed by an augmentation with 0.623 standard deviation in the decline of eGFR adjusting for confounding factors [21]. However, high heterogeneity was observed in these two studies ( I 2 = 98%, P < 0.001) when the data were combined.…”

Section: Resultsmentioning

confidence: 99%

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

Liu

Jiang

et al. 2019

Disease Markers

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

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

Liu

Jiang

et al. 2019

Disease Markers

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Associations of Plasma Biomarkers of Inflammation, Fibrosis, and Kidney Tubular Injury With Progression of Diabetic Kidney Disease: A Cohort Study

Gutiérrez

Shlipak

Katz

et al. 2022

American Journal of Kidney Diseases

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Potential application of Klotho as a prognostic biomarker for patients with diabetic kidney disease: a meta-analysis of clinical studies

Yu,

Sha,

Chen

et al. 2023

Therapeutic Advances in Chronic Disease

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Background: Diabetic kidney disease (DKD) is a serious diabetic complication and the performance of serum Klotho in DKD’s prognostic evaluation is controversial. Objective: To assess the association of serum Klotho with adverse kidney and non-kidney clinical outcomes in patients with DKD. Design: Clinical studies regarding the relationship of serum Klotho with DKD were included. Study quality was assessed using the Newcastle–Ottawa scale. Subgroup and sensitive analyses were performed to search for the source of heterogeneity. Data sources and methods: We comprehensively searched PubMed, Embase, Web of Science, and Cochrane library databases up to 27 September 2022. The associations of Klotho with albuminuria, such as the urinary albumin creatinine ratio (UACR), kidney outcomes such as persistent albuminuria, estimated glomerular filtration rate decline, and non-kidney outcomes such as diabetic retinopathy, cardiovascular morbidity, and mortality, were evaluated. The indicators, such as the correlation coefficient ( r), odds ratio (OR), relative risk, and hazard ratio, were retrieved or calculated from the eligible studies. Results: In all, 17 studies involving 5682 participants fulfilled the inclusion criteria and were included in this meta-analysis. There was no significant association of serum Klotho with UACR in DKD patients [summary r, −0.28 (−0.55, 0.04)] with high heterogeneity. By contrast, a strong association was observed regarding serum Klotho with kidney outcomes [pooled OR, 1.60 (1.15, 2.23)], non-kidney outcomes [pooled OR, 2.78 (2.11, 3.66)], or combined kidney and non-kidney outcomes [pooled OR, 1.96 (1.45, 2.65)] with moderate heterogeneity. Subgroup analysis indicated that age, study design, and the estimated glomerular filtration rate may be the sources of heterogeneity. Conclusion: A decreased serum Klotho level is possibly associated with an increased risk of developing kidney and non-kidney clinical outcomes in DKD patients; thus, Klotho may be a possible biomarker to predict DKD clinical outcomes. Additional studies are needed to clarify and validate Klotho’s prognostic value.

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Rapid decline of kidney function in diabetic kidney disease is associated with high soluble Klotho levels

Cited by 15 publications

References 39 publications

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

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

Associations of Plasma Biomarkers of Inflammation, Fibrosis, and Kidney Tubular Injury With Progression of Diabetic Kidney Disease: A Cohort Study

Potential application of Klotho as a prognostic biomarker for patients with diabetic kidney disease: a meta-analysis of clinical studies

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