FGF‐23 and Osteoprotegerin but not Fetuin‐A are associated with death and enhance risk prediction in non‐dialysis chronic kidney disease stages 3–5.

Alderson, Helen; Ritchie, James; Middleton, Rachel; Larsson, Anders; Larsson, Tobias E.; Kalra, Philip A.

doi:10.1111/nep.12664

Cited by 27 publications

(35 citation statements)

References 35 publications

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“…[27][28][29] Eight studies reported associations that could not be extracted or reliably expressed as RRs comparing the top versus bottom third of baseline FGF-23 concentration (see Supplemental Table 4 for results from these and the other excluded studies). [30][31][32][33][34][35][36][37] Of 34 studies included in primary analyses, 17 were in predominantly general population cohorts, 22,[38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] nine were in patients with CKD not on dialysis, 23,[54][55][56][57][58][59][60][61] and eight in patients on dialysis 24,[62][63][64][65][66][67][68] ( Figure 1). For patients on dialysis, a single large trial (EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular ...…”

Section: Resultsmentioning

confidence: 99%

“…Twenty-three studies reported associations between FGF-23 and all-cause mortality: seven in a general population, 39,40,44,47,49,51,53 eight in a nondialyzed CKD population, 23,44,54,56,57,[59][60][61] and eight in a dialysis population. 24,[62][63][64][65][66][67][68] Overall, comparing participants in the top versus bottom third of baseline FGF-23 concentration, there was an increased risk of death from all causes (RR, 1.70; 95% CI, 1.52 to 1.91).…”

Section: Association Between Fgf-23 and Mortalitymentioning

confidence: 99%

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Fibroblast Growth Factor-23 and Risks of Cardiovascular and Noncardiovascular Diseases: A Meta-Analysis

Marthi¹,

Donovan²,

Haynes

et al. 2018

JASN

150

120

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Fibroblast growth factor-23 (FGF-23) has been hypothesized to play a role in the increased risk of cardiovascular disease in patients with CKD. We identified prospective studies reporting associations between FGF-23 concentration and risk of cardiovascular events. Maximally adjusted risk ratios (RRs) were extracted for each outcome and scaled to a comparison of the top versus bottom third of the baseline FGF-23 concentration, and the results aggregated. Depending on the assay used, median FGF-23 concentrations were 43-74 RU/ml and 38-47 pg/ml in 17 general population cohorts; 102-392 RU/ml in nine cohorts of patients with CKD not requiring dialysis; and 79-4212 RU/ml and 2526-5555 pg/ml in eight cohorts of patients on dialysis. Overall, comparing participants in the top and bottom FGF-23 concentration thirds, the summary RRs (95% confidence intervals [95% CIs]) were 1.33 (1.12 to 1.58) for myocardial infarction, 1.26 (1.13 to 1.41) for stroke, 1.48 (1.29 to 1.69) for heart failure, 1.42 (1.27 to 1.60) for cardiovascular mortality, and 1.70 (1.52 to 1.91) for all-cause mortality. The summary RR for noncardiovascular mortality, calculated indirectly, was 1.52 (95% CI, 1.28 to 1.79). When studies were ordered by average differences in FGF-23 concentration between the top and bottom thirds, there was no trend in RRs across the studies. The similarly-sized associations between increased FGF-23 concentration and cardiovascular (atherosclerotic and nonatherosclerotic) and noncardiovascular outcomes, together with the absence of any exposure-response relationship, suggest that the relationship between FGF-23 and cardiovascular disease risk may be noncausal.

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Section: Resultsmentioning

confidence: 99%

Section: Association Between Fgf-23 and Mortalitymentioning

confidence: 99%

Fibroblast Growth Factor-23 and Risks of Cardiovascular and Noncardiovascular Diseases: A Meta-Analysis

Marthi¹,

Donovan²,

Haynes

et al. 2018

JASN

150

120

View full text Add to dashboard Cite

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“…This was a sub-study of the Salford Kidney Study, a single-centre, longitudinal, observational study of patients with stage 3 to 5 CKD referred to an adult secondary care nephrology outpatient clinic [25,26] .…”

Section: Methodsmentioning

confidence: 99%

The Association of Baseline and Longitudinal Change in Endothelial Microparticle Count with Mortality in Chronic Kidney Disease

Green¹,

Skeoch

Alexander

et al. 2017

Nephron

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Background: Chronic kidney disease (CKD) is associated with a unique milieu of vascular pathology, and effective biomarkers of active vascular damage are lacking. A candidate biomarker is the quantification of circulating endothelial microparticles (EMPs). This study observed baseline and longitudinal EMP change (δEMP) and established the association of these with all-cause mortality and cardiovascular events in CKD. Method: An observational study in adults with CKD (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m²). EMPs were quantified by flow cytometry of platelet poor plasma in 2 samples 12 months apart and categorised as EMP if AnnexinV+/CD31+/CD42b- EMPs were compared between primary renal diagnoses, and correlations between EMP/δEMP and other parameters made. Adjusted hazard ratios (HRs) for time to all-cause mortality and cardiovascular events were calculated for log-transformed EMP and δEMP using a Cox proportional hazard model. Results: There were 123 patients (age 63 ± 11 years, systolic blood pressure 135 ± 18 mm Hg, eGFR 32 ± 16 mL/min/1.73 m²). The median baseline EMP count was 144/μL (range 10-714/μL). EMPs were numerically the highest in autosomal dominant polycystic kidney disease (253 [41-610]). An increase in urine protein:creatinine ratio was associated with an increase in EMP (co-efficient 0.21, p = 0.02). The adjusted HR for all-cause mortality for EMP was 8.20 (1.67-40.2, p = 0.01) and for δEMP was 2.69 (0.04-165, p = 0.64). There was no association between EMP or δEMP and cardiovascular events. Conclusion: Although EMP count was a significant marker of mortality risk, longitudinal change was not. This may reflect disease-specific EMP behaviour and the limitation of EMP as a generalised biomarker in CKD.

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“…When reviewing the full text of the remaining 283 articles, we excluded a further 264 additional articles, leaving 19 prospective studies17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 eligible for inclusion in the meta‐analysis. Patients were recruited on the basis of having diabetes mellitus in 2 studies, kidney disease in 7 studies, preexisting heart disease in 5 studies, and recent acute coronary syndromes in 5 studies.…”

Section: Resultsmentioning

confidence: 99%

Osteoprotegerin and Cardiovascular Events in High‐Risk Populations: Meta‐Analysis of 19 Prospective Studies Involving 27 450 Participants

Tschiderer

Klingenschmid

Nagrani

et al. 2018

JAHA

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BackgroundOsteoprotegerin is a cytokine involved in bone metabolism as well as vascular calcification and atherogenesis. Although circulating osteoprotegerin levels are robustly associated with incident cardiovascular disease (CVD) in the general population, its relevance as a biomarker among populations at high CVD risk is less clear.Methods and ResultsThree independent reviewers systematically searched PubMed, EMBASE, and Web of Science to identify prospective studies that had recruited participants on the basis of having conditions related to high CVD risk. A total of 19 studies were eligible for inclusion, reporting on 27 450 patients with diabetes mellitus (2 studies), kidney disease (7 studies), preexisting heart disease (5 studies), or recent acute coronary syndromes (5 studies) at baseline. Over a mean follow‐up of 4.2 years, 4066 CVD events were recorded. In a random‐effects meta‐analysis, the pooled risk ratio for CVD events comparing people in the top versus the bottom tertile of osteoprotegerin concentration was 1.30 (95% confidence interval, 1.12–1.50; P<0.001; I2=68.3%). There was evidence for presence of publication bias (P value from Egger's test=0.013). Correction for publication bias using the trim‐and‐fill method reduced the risk ratio to 1.21 (95% confidence interval, 1.03–1.42; P<0.001). The risk ratios did not vary significantly by population type, geographical region, statistical adjustment, sample or assay type, age, sex, or length of follow‐up.ConclusionsIn populations at high CVD risk, elevated circulating osteoprotegerin levels are associated with a higher risk for future CVD events. The magnitude of association appears weaker than in the general population.

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FGF‐23 and Osteoprotegerin but not Fetuin‐A are associated with death and enhance risk prediction in non‐dialysis chronic kidney disease stages 3–5.

Cited by 27 publications

References 35 publications

Fibroblast Growth Factor-23 and Risks of Cardiovascular and Noncardiovascular Diseases: A Meta-Analysis

Fibroblast Growth Factor-23 and Risks of Cardiovascular and Noncardiovascular Diseases: A Meta-Analysis

The Association of Baseline and Longitudinal Change in Endothelial Microparticle Count with Mortality in Chronic Kidney Disease

Osteoprotegerin and Cardiovascular Events in High‐Risk Populations: Meta‐Analysis of 19 Prospective Studies Involving 27 450 Participants

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