Fibroblast growth factor 23 and new-onset chronic kidney disease in the general population: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study

Abstract Background Fibroblast growth factor 23 (FGF23), a phosphate-regulating hormone that increases early in the course of chronic kidney disease (CKD), is associated with disease progression in patients with established CKD. Here we aimed to investigate the association between plasma FGF23 and new-onset CKD in the general population. Methods We included 5253 individuals without CKD who participated in the Prevention of Renal and Vascular Endstage Disease study, a prospective, population-based cohort. Multi-variable Cox regression was used to study the association of plasma C-terminal FGF23 with new-onset CKD, defined as a combined endpoint of estimated glomerular filtration rate (eGFR) <60 mL/min/ 1.73 m2, urinary 24-h albumin excretion (UAE) >30 mg/24 h or both, or with all-cause mortality. Results The median baseline FGF23 was 68 [interquartile range (IQR) 56–85] RU/mL, eGFR was 95 ± 13 mL/min/1.73 m2 and UAE was 7.8 (IQR 5.8–11.5) mg/24 h. After follow-up of 7.5 (IQR 7.2–8.0) years, 586 participants developed CKD and 214 participants died. A higher FGF23 level was associated with new-onset CKD, independent of risk factors for kidney disease and parameters of bone and mineral homoeostasis {fully adjusted hazard ratio (HR) 1.25 [95% confidence interval (CI) 1.10–1.44] per doubling of FGF23; P = 0.001}. In secondary analyses, FGF23 was independently associated with new-onset eGFR <60 mL/min/1.73 m2 [adjusted HR 1.28 (95% CI 1.00–1.62); P = 0.048] or with UAE >30 mg/24 h [adjusted HR 1.24 (95% CI 1.06–1.45); P = 0.01] individually. A higher FGF23 level was also associated with an increased risk of all-cause mortality [fully adjusted HR 1.30 (95% CI 1.03–1.63); P = 0.03]. Conclusions High FGF23 levels are associated with an increased risk of new-onset CKD and all-cause mortality in this prospective population-based cohort, independent of established CKD risk factors.

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Obesity, Abdominal Obesity and Chronic Kidney Disease in Young Adults: A Nationwide Population-Based Cohort Study

Journal of Clinical Medicine ◽

10.3390/jcm10051065 ◽

2021 ◽

Vol 10 (5) ◽

pp. 1065

Author(s):

Eun Hui Bae ◽

Sang Yeob Lim ◽

Jin-Hyung Jung ◽

Tae Ryom Oh ◽

Hong Sang Choi ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Young Adults ◽

Kidney Disease ◽

Abdominal Obesity ◽

Population Based ◽

Baseline Body Mass Index ◽

Increased Risk ◽

Baseline Examination ◽

New Onset

Obesity has become a pandemic. It is one of the strongest risk-factors of new-onset chronic kidney disease (CKD). However, the effects of obesity and abdominal obesity on the risk of developing CKD in young adults has not been elucidated. From a nationwide health screening database, we included 3,030,884 young adults aged 20–39 years without CKD during a baseline examination in 2009–2010, who could follow up during 2013–2016. Patients were stratified into five levels based on their baseline body mass index (BMI) and six levels based on their waist circumference (WC; 5-cm increments). The primary outcome was the development of CKD. During the follow up, until 2016, 5853 (0.19%) participants developed CKD. Both BMI and WC showed a U-shaped relationship with CKD risk, identifying the cut-off values as a BMI of 21 and WC of 72 cm in young adults. The obesity group (odd ratio [OR] = 1.320, 95% confidence interval [CI]: 1.247–1.397) and abdominal obesity group (male WC ≥ 90, female WC ≥ 85) (OR = 1.208, 95%CI: 1.332–1.290) showed a higher CKD risk than the non-obesity or non-abdominal obesity groups after adjusting for covariates. In the CKD risk by obesity composite, the obesity displayed by the abdominal obesity group showed the highest CKD risk (OR = 1.502, 95%CI: 1.190–1.895), especially in those under 30 years old. During subgroup analysis, the diabetes mellitus (DM) group with obesity or abdominal obesity paradoxically showed a lower CKD risk compared with the non-obesity or non-abdominal obesity group. Obesity and abdominal obesity are associated with increased risk of developing CKD in young adults but a decreased risk in young adults with diabetes.

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The first consecutive 5000 patients with Coronavirus Disease 2019 from Qatar; a nation-wide cohort study

BMC Infectious Diseases ◽

10.1186/s12879-020-05511-8 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Ali S. Omrani ◽

Muna A. Almaslamani ◽

Joanne Daghfal ◽

Rand A. Alattar ◽

Mohamed Elgara ◽

...

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Cohort Study ◽

Kidney Disease ◽

Older Age ◽

Icu Admission ◽

Increased Risk ◽

All Cause Mortality ◽

Male Sex

Abstract Background There are limited data on Coronavirus Disease 2019 (COVID-19) outcomes at a national level, and none after 60 days of follow up. The aim of this study was to describe national, 60-day all-cause mortality associated with COVID-19, and to identify risk factors associated with admission to an intensive care unit (ICU). Methods This was a retrospective cohort study including the first consecutive 5000 patients with COVID-19 in Qatar who completed 60 days of follow up by June 17, 2020. The primary outcome was all-cause mortality at 60 days after COVID-19 diagnosis. In addition, we explored risk factors for admission to ICU. Results Included patients were diagnosed with COVID-19 between February 28 and April 17, 2020. The majority (4436, 88.7%) were males and the median age was 35 years [interquartile range (IQR) 28–43]. By 60 days after COVID-19 diagnosis, 14 patients (0.28%) had died, 10 (0.2%) were still in hospital, and two (0.04%) were still in ICU. Fatal COVID-19 cases had a median age of 59.5 years (IQR 55.8–68), and were mostly males (13, 92.9%). All included pregnant women (26, 0.5%), children (131, 2.6%), and healthcare workers (135, 2.7%) were alive and not hospitalized at the end of follow up. A total of 1424 patients (28.5%) required hospitalization, out of which 108 (7.6%) were admitted to ICU. Most frequent co-morbidities in hospitalized adults were diabetes (23.2%), and hypertension (20.7%). Multivariable logistic regression showed that older age [adjusted odds ratio (aOR) 1.041, 95% confidence interval (CI) 1.022–1.061 per year increase; P < 0.001], male sex (aOR 4.375, 95% CI 1.964–9.744; P < 0.001), diabetes (aOR 1.698, 95% CI 1.050–2.746; P 0.031), chronic kidney disease (aOR 3.590, 95% CI 1.596–8.079, P 0.002), and higher BMI (aOR 1.067, 95% CI 1.027–1.108 per unit increase; P 0.001), were all independently associated with increased risk of ICU admission. Conclusions In a relatively younger national cohort with a low co-morbidity burden, COVID-19 was associated with low all-cause mortality. Independent risk factors for ICU admission included older age, male sex, higher BMI, and co-existing diabetes or chronic kidney disease.

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Elevated Fibroblast Growth Factor 23 Concentration: Prediction of Mortality among Chronic Kidney Disease Patients

Cardiorenal Medicine ◽

10.1159/000440984 ◽

2015 ◽

Vol 6 (1) ◽

pp. 73-82 ◽

Cited By ~ 9

Author(s):

Shahanas Chathoth ◽

Samir Al-Mueilo ◽

Cyril Cyrus ◽

Chittibabu Vatte ◽

Awatif Al-Nafaie ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Growth Factor ◽

Kidney Disease ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 23 ◽

Control Group ◽

Phosphorus Metabolism ◽

Fibroblast Growth ◽

Saudi Population ◽

Fgf23 Level

Background: The osteocyte-derived hormone, fibroblast growth factor 23 (FGF23), regulates the phosphorus metabolism and suppresses 1,25-dihydroxyvitamin D production, thereby mitigating hyperphosphatemia in patients with renal disorders. An elevated FGF23 level is suggested to be an early biomarker of altered phosphorus metabolism in the initial stages of chronic kidney disease (CKD) and acts as a strong predictor of mortality in dialysis patients. In the Saudi population, there is no report on the FGF23 level in CKD patients to date. This study aims to estimate the plasma FGF23 levels in the Saudi population and to correlate it with its clinical manifestations in order to ascertain its role in the pathogenesis of CKD patients. Methods: The FGF23 level in the plasma samples was determined using ELISA in a diverse cohort of 89 cases with stage 3-5 CKD and 100 healthy subjects. The plasma FGF23 level was correlated with other biochemical parameters. Results: The results revealed that the FGF23 level was markedly elevated among CKD patients compared to the control group, and a significant inverse correlation was observed between the FGF23 level and glomerular filtration rate. FGF23 elevation was approximately 40-fold among stage 5 patients compared to the control, while the elevation of phosphate, parathyroid hormone (PTH) and alkaline phosphatase was 2-, 3- and 8-fold in this stage, respectively. Conclusion: Elevated FGF23 levels may have a strong correlation with the disease pathogenesis. In addition, FGF23 might be a future therapeutic target to intervene against the progression of CKD as well as to increase patient survivability.

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Associations of fibroblast growth factor 23, vitamin D and parathyroid hormone with 5-year outcomes in a prospective primary care cohort of people with chronic kidney disease stage 3

BMJ Open ◽

10.1136/bmjopen-2017-016528 ◽

2017 ◽

Vol 7 (8) ◽

pp. e016528 ◽

Cited By ~ 8

Author(s):

Adam Shardlow ◽

Natasha J McIntyre ◽

Richard J Fluck ◽

Christopher W McIntyre ◽

Maarten W Taal

Keyword(s):

Primary Care ◽

Chronic Kidney Disease ◽

Vitamin D ◽

Kidney Disease ◽

Vitamin D Deficiency ◽

Fibroblast Growth Factor 23 ◽

Fibroblast Growth ◽

Ckd Stage ◽

All Cause Mortality

ObjectivesVitamin D deficiency, elevated fibroblast growth factor 23 (FGF23) and elevated parathyroid hormone (PTH) have each been associated with increased mortality in people with chronic kidney disease (CKD). Previous studies have focused on the effects of FGF23 in relatively advanced CKD. This study aims to assess whether FGF23 is similarly a risk factor in people with early CKD, and how this risk compares to that associated with vitamin D deficiency or elevated PTH.DesignProspective cohort study.SettingThirty-two primary care practices.ParticipantsOne thousand six hundred and sixty-four people who met Kidney Disease: Improving Global Outcomes (KDIGO) definitions for CKD stage 3 (two measurements of estimated glomerular filtration rate (eGFR) between 30 and 60 mL/min/1.73 m2at least 90 days apart) prior to study recruitment.Outcome measuresAll-cause mortality over the period of study follow-up and progression of CKD defined as a 25% fall in eGFR and a drop in GFR category, or an increase in albuminuria category.ResultsTwo hundred and eighty-nine participants died during the follow-up period. Vitamin D deficiency (HR 1.62, 95% CI 1.01 to 2.58) and elevated PTH (HR 1.42, 95% CI 1.09 to 1.84) were independently associated with all-cause mortality. FGF23 was associated with all-cause mortality in univariable but not multivariable analysis. Fully adjusted multivariable models of CKD progression showed no association with FGF23, vitamin D status or PTH.ConclusionsIn this cohort of predominantly older people with CKD stage 3 and low risk of progression, vitamin D deficiency and elevated PTH were independent risk factors for all-cause mortality but elevated FGF23 was not. While FGF23 may have a role as a risk marker in high-risk populations managed in secondary care, our data suggest that it may not be as important in CKD stage 3, managed in primary care.Trial registration numberNational Institute for Health Research Clinical Research Portfolio Study Number 6632.

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The First Consecutive 5000 Patients with Coronavirus Disease 2019 from Qatar; a Nation-wide Cohort Study

10.1101/2020.07.15.20154690 ◽

2020 ◽

Cited By ~ 1

Author(s):

Ali S. Omrani ◽

Muna A. Almaslamani ◽

Joanne Daghfal ◽

Rand A. Alattar ◽

Mohamed Elgara ◽

...

Keyword(s):

Risk Factors ◽

Chronic Kidney Disease ◽

Cohort Study ◽

Kidney Disease ◽

Older Age ◽

Icu Admission ◽

Increased Risk ◽

All Cause Mortality ◽

Male Sex

Background There are limited data on Coronavirus Disease 2019 (COVID-19) outcomes at a national level, and none after 60 days of follow up. The aim of this study was to describe national, 60-day all-cause mortality associated with COVID-19, and to identify risk factors associated with admission to an intensive care unit (ICU). Methods This was a retrospective cohort study including the first consecutive 5000 patients with COVID-19 in Qatar who completed 60 days of follow up by June 17, 2020. Outcomes included all-cause mortality at 60 days after COVID-19 diagnosis, and risk factors for admission to ICU. Results Included patients were diagnosed with COVID-19 between February 28 and April 17, 2020. The majority (4436, 88.7%) were males and the median age was 35 years [interquartile range (IQR) 28-43]. By 60 days after COVID-19 diagnosis, 14 patients (0.28%) had died, 10 (0.2%) were still in hospital, and two (0.04%) were still in ICU. Fatal COVID-19 cases had a median age of 59.5 years (IQR 55.8-68), and were mostly males (13, 92.9%). All included pregnant women (26, 0.5%), children (131, 2.6%), and healthcare workers (135, 2.7%) were alive and not hospitalized at the end of follow up. A total of 1424 patients (28.5%) required hospitalization, out of which 108 (7.6%) were admitted to ICU. Most frequent co-morbidities in hospitalized adults were diabetes (23.2%), and hypertension (20.7%). Multivariable logistic regression showed that older age [adjusted odds ratio (aOR) 1.041, 95% confidence interval (CI) 1.022-1.061 per year increase; P <0.001], male sex (aOR 4.375, 95% CI 1.964-9.744; P <0.001), diabetes (aOR 1.698, 95% CI 1.050-2.746; P 0.031), chronic kidney disease (aOR 3.590, 95% CI 1.596-8.079, P 0.002), and higher BMI (aOR 1.067, 95% CI 1.027-1.108 per unit increase; P 0.001), were all independently associated with increased risk of ICU admission. Conclusions In a relatively younger national cohort with a low co-morbidity burden, COVID-19 was associated with low all-cause mortality. Independent risk factors for ICU admission included older age, male sex, higher BMI, and co-existing diabetes or chronic kidney disease.

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Strength of Fibroblast Growth Factor 23 as a Cardiovascular Risk Predictor in Chronic Kidney Disease Weaken by ProBNP Adjustment

American Journal of Nephrology ◽

10.1159/000497125 ◽

2019 ◽

Vol 49 (3) ◽

pp. 203-211 ◽

Cited By ~ 4

Author(s):

Insa E. Emrich ◽

Vincent Brandenburg ◽

Alexander B. Sellier ◽

Johanna Schauerte ◽

Johanna Wiedenroth ◽

...

Keyword(s):

Risk Factors ◽

Heart Failure ◽

Chronic Kidney Disease ◽

Growth Factor ◽

Kidney Disease ◽

Cardiovascular Events ◽

Fibroblast Growth Factor 23 ◽

Cardiovascular Effects ◽

Fibroblast Growth ◽

Conventional Risk Factors

Background: Various epidemiological studies linked high fibroblast growth factor 23 (FGF23) levels with cardiovascular events in chronic kidney disease (CKD). It remains enigmatic whether high FGF23 exerts adverse cardiovascular effects, or whether it reflects detrimental effects of residual confounders. Earlier studies adjusted for CKD-mineral bone disease (CKD-MBD) regulators of FGF23 rather than for recently discovered non-CKD-MBD regulators, among which iron deficiency and heart failure are of particular importance. Moreover, they used c-terminal FGF23 (cFGF23) assays rather than more specific intact FGF23 (iFGF23) assays. Methods: The CARE FOR HOMe study analyzed plasma ferritin, iFGF23, cFGF23 and N-terminal proBNP (NT-proBNP) along with conventional risk factors, among 575 CKD G2-G4 patients to determine the interaction between FGF23, its non-CKD-MBD regulators, and incident cardiovascular events in CKD patients. The participants were followed up for 5.1 ± 2.1 years for the occurrence of atherosclerotic events and hospitalization for acute decompensated heart failure. Results: cFGF23 correlated strongly with high iFGF23 (r = 0.607), fairly with high NT-proBNP (r = 0.453) and weakly with low ferritin (r = –0.207); correlation coefficients of iFGF23 with NT-proBNP and ferritin were numerically lower. In Kaplan-Meier analyses, both endpoints were predicted by cFGF23 and iFGF23. In Cox regression models, cFGF23 remained an outcome predictor after adjustment for conventional risk factors and ferritin. This prediction was largely eliminated when further adjusting for NT-proBNP. iFGF23 was less consistently associated with adverse outcome in partly adjusted models, and failed to predict outcome in fully adjusted models. Conclusion: In summary, iron deficiency and heart failure affect plasma FGF23. As adjustment for NT-proBNP virtually eliminates the association between plasma FGF23 and predefined outcome, we speculate that high FGF23, rather than exerting detrimental cardiovascular effects, mirrors prevalent heart disease.

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Fibroblast Growth Factor 23 Predicts All-Cause Mortality in a Dose-Response Fashion in Pre-Dialysis Patients with Chronic Kidney Disease

American Journal of Nephrology ◽

10.1159/000454959 ◽

2016 ◽

Vol 45 (2) ◽

pp. 149-159 ◽

Cited By ~ 11

Author(s):

Cheng Xue ◽

Bo Yang ◽

Chenchen Zhou ◽

Bing Dai ◽

Yawei Liu ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Growth Factor ◽

Kidney Disease ◽

Cohort Studies ◽

Dose Response ◽

Fibroblast Growth Factor 23 ◽

Reference Level ◽

Fibroblast Growth ◽

Prospective Cohort Studies ◽

All Cause Mortality

Background: Quantitative dose-response associations between fibroblast growth factor 23 (FGF23) and risks of mortality, cardiovascular disease (CVD), and renal events in chronic kidney disease (CKD) are not known. This study aimed to summarize and quantify the predictive effects of FGF23 among the pre-dialysis CKD stages 1-5 population. Methods: Data sources included PubMed, EMBASE, and Web of Science. Prospective cohort studies assessing the associations between FGF23 and all-cause mortality, CVD, and renal events in CKD patients were selected. Summary risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using the random-effects model. The composite higher or the highest level in FGF23 categories of each study was considered the high level. The reference level was regarded as the low level in the overall analysis. The restricted cubic spline model was used to estimate dose-response associations. Results: Fifteen prospective cohort studies centered around 15,355 subjects were analyzed. A high FGF23 level was associated with increased risks of all-cause mortality (RR 1.46, 95% CI 1.38-1.55, p < 0.001), CVD (RR 1.37, 95% CI 1.15-1.63, p < 0.001), and renal events (RR 1.31, 95% CI 1.07-1.59, p = 0.008), respectively. There was a positive, nonlinear, dose-response relationship between FGF23 and all-cause mortality. The reference level in dose-response analysis was defined as 51 RU/mL of c-terminal FGF23. We then calculated RRs for increments of 20 RU/mL, which was associated with increased risks of mortality (RR 1.04, 95% CI 1.00-1.07, p = 0.038), CVD (RR 1.02, p < 0.001), and renal events (RR 1.01, p < 0.001), respectively. Conclusions: There may be positive dose-response predictive effects of FGF23 on all-cause mortality, CVD, and renal events in patients with CKD.

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