The Change of Serum FGF-23 Levels Predicts the Progression of Renal Function in Chronic Kidney Disease Patients

2020 ◽  
Vol 103 (11) ◽  
pp. 1155-1162
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Renal Function ◽  
Kidney Disease ◽  
Fibroblast Growth Factor 23 ◽  
Positive Association ◽  
Ckd Progression ◽  
Fgf 23

Background: The role of elevated baseline fibroblast growth factor 23 (FGF-23) levels on the progression of renal function in long term (years) follow-up studies is not yet established. Objective: To circumvent the confounding factors occurring during the study duration, the authors examined the roles of the changing values of FGF-23 and other risk factors on progression of renal function after a shorter term (months) follow-up. Materials and Methods: The present study was a 12-week prospective cohort study to determine the association between traditional and non-traditional risk factors on the progression of renal function. Results: Sixty-five chronic kidney disease (CKD) patients were included. After a 12-week follow-up, significant increases of serum creatinine, cystatin C, vitamin D level, and FGF-23 levels were observed. The delta FGF-23 values increased progressively according to the staging of the CKD. The baseline parathyroid hormone level, which was in the recommended range following the KDIGO guideline, and the delta FGF-23 values were the significant parameters that had association with the decline of the estimated glomerular filtration. There was a positive association between delta FGF-23 and delta 25-OH vitamin D values. Conclusion: The increasing change in serum FGF-23 level is significantly correlated with declining renal function. Thus, delta FGF-23 value could be utilized as a suitable biomarker for following and detecting CKD progression. Keywords: FGF-23, Vitamin D, CKD progression, Biomarker

scholarly journals Fibroblast Growth factor 23 and α-Klotho protein are associated with adverse clinical outcomes in non dialysis chronic kidney disease stage 1-5 patients

2019 ◽  
Author(s):  
Eleni Manou ◽  
Elias Thodis ◽  
George Arsos ◽  
Ploumis Pasadakis ◽  
Stylianos Panagoutsos ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Regression Analysis ◽  
Growth Factor ◽  
Kidney Disease ◽  
Fibroblast Growth Factor 23 ◽  
Serum Phosphate ◽  
Fibroblast Growth ◽  
Fgf 23 ◽  
Stage 1

Abstract Background: Fibroblast Growth Factor 23 (FGF-23) and α-Klotho contribute to the patho-genesis of chronic kidney disease - mineral and bone disorders (CKD-MBD). The aim of our study was to evaluate the association of FGF-23 and α-Klotho levels with CKD-MBD parameters, as well as with renal prognosis and mortality, in CKD patients stage 1-5, not in renal replacement therapy (RRT). Methods: 128 patients were included. At enrollment GFR was measured (mGFR) and plasma levels of carboxyl terminal FGF-23 (cFGF-23) and soluble α-Klotho (sKlotho) were determined by ELISA. Abdominal aorta calcification (AAC) score was assessed in lateral abdominal X ray. The composite end point (event) was initiation of RRT or death. Follow-up was five years (median 36, range 2-60 months). Results: mGFR significantly correlated with cFGF-23 and sKlotho negatively and posi-tievely respectively (p<0.0001 for both). Multiple regression analysis showed an inde-pendent correlation of cFGF-23 with mGFR, 25-OH vitamin D, presence of diabetes melli-tus and AAC score, of sKlotho with mGFR and phosphate and of AAC score with sKlotho and cFGF-23. Multivariate regression tree analysis, led to the formation of three regression groups (A, B, C) based on two “cut off” values: mGFR levels of 60.85 ml/min/1.73m2 and serum phosphate levels of 3.7 mg/dl. These groups significantly correlated with the five CKD stages and additionally cFGF-23 and sKlotho plasma levels (p<0.0001 for both). During follow-up, 40 out of the 128 patients, (31.2%) either initiated RRT or died (31 and 9 respectively). Kaplan Meier survival analysis showed that groups of patients with cFGF-23 levels less than median and those with sKlotho more than median value showing a more favorable course, regarding outcome (p=0.0003 for cFGF-23, p=0.004 for s-Klotho). In Cox regression analysis the association of cFGF-23 (p=0.04), sKlotho (p=0.008) and AAC score (p=0.01) with the presence of “event” remained significant after adjustment for traditional and CKD- related covariates. Conclusions: In CKD patients stage 1-5, cFGF-23 and sKlotho levels are associated with adverse clinical outcomes. mGFR and serum phosphate, in association with sKlotho lev-els, may provide a “new classification” of CKD patients, which appears to be predictive of outcome.

The effect of interactions between proteinuria, activity of fibroblast growth factor 23 and serum phosphate on renal progression in patients with chronic kidney disease: a result from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease study

2019 ◽  
Vol 35 (3) ◽  
pp. 438-446 ◽  
Author(s):  
Hyoungnae Kim ◽  
Jimin Park ◽  
Ki Heon Nam ◽  
Jong Hyun Jhee ◽  
Hae-Ryong Yun ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Significant Interaction ◽  
Independent Risk Factor ◽  
Fibroblast Growth Factor 23 ◽  
Serum Phosphate ◽  
Ckd Progression ◽  
Biologic Activity ◽  
Renal Progression ◽  
Fgf 23

Abstract Background Recent experimental study reported that proteinuria increases serum phosphate by decreasing biologic activity of fibroblast growth factor 23 (FGF-23). We examined this relationship in a large chronic kidney disease (CKD) cohort and evaluated the combined effect of proteinuria, FGF-23 activity and serum phosphate on CKD progression. Methods The activity of FGF-23, measured by the fractional excretion of phosphate (FEP)/FGF-23 ratio, was compared according to the degree of proteinuria in 1909 patients with CKD. Primary outcome was CKD progression defined as ≥50% decline of estimated glomerular filtration rate, doubling of serum creatinine and start of dialysis. Results There was a negative relationship between 24-h urine protein (24-h UP) and FEP/FGF-23 ratio (γ −0.07; P = 0.005). In addition, after matching variables associated with serum phosphate, patients with more proteinuria had higher serum phosphate (P &lt; 0.001) and FGF-23 (P = 0.012), and lower FEP/FGF-23 ratio (P = 0.007) compared with those with less proteinuria. In the matched cohort, low FEP/FGF-23 ratio was an independent risk factor for CKD progression (hazard ratio 0.87 per 1 log increase; 95% confidence interval 0.79–0.95; P = 0.002), and there was significant interaction between 24-h UP and FEP/FGF-23 ratio (P = 0.039). Furthermore, 24-h UP and serum phosphate also had a significant interaction on CKD progression (P &lt; 0.001). Conclusions Proteinuria is associated with decreased biologic activity of FGF-23 and increased serum phosphate. Furthermore, diminished activity of FGF23 is an independent risk factor for renal progression in proteinuric CKD patients.

scholarly journals Correlation between Soluble α-Klotho and Renal Function in Patients with Chronic Kidney Disease: A Review and Meta-Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Qinglian Wang ◽  
Wenyan Su ◽  
Zhenwei Shen ◽  
Rong Wang
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Correlation Coefficient ◽  
Publication Bias ◽  
Meta Analysis ◽  
Significant Negative Correlation ◽  
Significant Heterogeneity ◽  
Fgf 23

Objective. Over decades, numerous inconsistent studies are reported on the relationship between soluble α-Klotho and renal function in patients with chronic kidney disease (CKD). This study aims to perform a meta-analysis to figure out the correlations between soluble α-Klotho and renal function in patients with CKD. Materials and Methods. We searched medical and scientific literature databases, PubMed and EMBASE (from the inception to October 2017), for publications that reported studies on associations between soluble α-Klotho and renal function in patients with CKD. Only publications in English were extracted. Summary correlation coefficient (r) values were extracted from each study, and 95% confidence intervals (CIs) were calculated. Publication bias was tested, and sensitivity and subgroup analyses were performed to investigate potential heterogeneity. Results. Of 611 studies, 9 publications with 1457 patients were included into the analysis. The following data were extracted from the literature: first author, year of publication, research region, research index, sample size, average age and Pearson or Spearman correlation coefficient, study design, the αKlotho/FGF23 assays utilized, full length, or the C-terminal fragment of FGF23. The pooled r between α-Klotho and estimated glomerular filtration rate (eGFR), FGF-23 were 0.35 (95%CI, 0.23~0.46, and P<0.05), -0.10 (95%CI, -0.19~-0.01, and P<0.05) with remarkable significance, indicating moderate heterogeneity. There was no significant heterogeneity between subgroups in analyses of α-Klotho and eGFR stratified by research region, mean age, and eGFR, but heterogeneity exists in analyses of α-Klotho and FGF-23 stratified by research region. There was no significant correlation between a-klotho and Ca and PTH and PHOS. There was no evidence of publication bias with Egger’s test (p=0.360) or with Begg’s test (p=0.902) and the distribution of funnel plots was symmetrical in all of our analysis. Conclusions. There exists a significant positive correlation between soluble α-Klotho and eGFR in patients with CKD. Also, a significant negative correlation between α-Klotho and FGF23 levels is proven. This raises hope to employ αKlotho and FGF23 as early biomarkers of CKD. However, further large prospective follow-up researches are needed to validate this hypothesis and to explore whether maintaining or elevating the Klotho level could improve renal function and complications in CKD patients.

scholarly journals The Urinary Phosphate to Serum Fibroblast Growth Factor 23 Ratio, Deemed the Nephron Index, Is a Useful Clinical Index for Early Stage Chronic Kidney Disease in Patients with Type 2 Diabetes: An Observational Pilot Study

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Hodaka Yamada ◽  
Makoto Kuro-o ◽  
Shunsuke Funazaki ◽  
San-e Ishikawa ◽  
Masafumi Kakei ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Growth Factor ◽  
Kidney Disease ◽  
Early Stage ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth

Renal function decline is associated with progressive type 2 diabetes mellitus, which causes mineral and bone disorders. In the present study, we defined the ratio of urinary phosphate excretion (mg/day) to serum fibroblast growth factor 23 as the nephron index. We examined changes in the nephron index in type 2 diabetes patients with early stage chronic kidney disease (stages 1–3), enrolling 15 patients and retrospectively analysing the follow-up data. After follow-up at 5.4 years, we observed no significant changes in the estimated glomerular filtration rate; the nephron index, however, was significantly reduced between the baseline and the follow-up. We propose that the nephron index may be potentially useful as a biomarker for monitoring the decline of renal function in the early stages of diabetic chronic kidney disease patients.

scholarly journals 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 ◽  
2017 ◽  
Vol 7 (8) ◽  
pp. e016528 ◽  
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.

scholarly journals MO527REFERRAL CRITERIA TO NEPHROLOGY AND MATCHING DEGREE WITH THE CONSENSUS DOCUMENT FOR CHRONIC KIDNEY DISEASE DETECTION AND MANAGEMENT

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Guillermo Ferrer García ◽  
Lorena Herráez García ◽  
Maria Paz Castro Fernández ◽  
Esperanza Moral Berrio ◽  
Eliana Olazo Gutierrez ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Statistical Significance ◽  
Categorical Variables ◽  
Ckd Progression ◽  
Spanish Society ◽  
Consensus Document

Abstract Background and Aims Consensus document of the Spanish Society of Nephrology and many Primary Care (PC) related societies for chronic kidney disease (CKD) detection and management provides to the PC doctor referral criteria (RC) to nephrology clinic. The aim of the study is to describe the referrals to our center nephrology clinic and evaluate the influencing factors for RC adequacy. Method Retrospective observational study. We included the referred patients to our nephrology clinic from October 2019 to May 2020. We recollected demographic variables, as well as comorbidity, renal function, RC adequacy and follow-up. Categorical variables are expressed as percentages and compared using Chi2 test. Quantitative variables are expressed as mean ± standard deviation and compared using t-student test. Cox regression was performed to determine independent predictors for RC adequacy. Statistical significance for a value of p&lt; 0,05 or CI 95%. Statistical analysis was performed with SPSS 25.0. Results 238 patients, 55.5% male. Average age 63 ± 17 years, being 34% older than 75 years. 67.6% had at least 3 cardiovascular risk factors. 85.3% were referred from PC with 57.1% of them from a rural center. There was adequation to the RC on 55%. The most frequent RC was CKD progression (37.4%). Mean serum creatinine at the time of referring was 1.91 ± 0.59 mg/dl with a glomerular filtration rate 34 ± 11 ml/min/1.73m2 and 329.43 ± 992.01 mg/g or mg/24h of albuminuria. From the 45% of those who did not had RC adequacy 51.4% had CKD III stage and 21.5% had false refractory hypertension (controlled or under-treated). Mean time of follow-up was 5 ± 1.7 months. RC adequacy was related with being referred from PC (59.6% vs 28.6% p=0.001), smoking (65.9% vs 49% p=0.012), time of referring creatinine (1.54 ± 0.86 vs 1.18 ± 0.39 p=0.001) and albuminuria (43406 ± 1009.7 vs 136.13 ± 637.16 p=0.019) and end of follow-up albuminuria (265.84 ± 516.82 vs 81.67 ± 250.7 p=0.007). RC adequacy was associated with receiving follow-up on nephrology clinic (80.2% vs 19.8% p=0.001). Logistic regression showed that being referred from PC (OR 3.64 IC 95% 1.03-12.8 p=0.044) and a worse renal function at the referring (OR 2.49 IC 95% 1.19-5.24 p=0.015) were associated with RC adequacy. Conclusion The experience in our center shows that there is not an adequacy on the current RC from the Spanish Society of Nephrology in almost half of the patients. That proportion decreases when patients are referred from PC close to 40%. CKD progression is the main reason for referral with most of patients being elderly and with a high cardiovascular risk. The need for greater dissemination of RC can be inferred from the significant number of inappropriate referrals, encouraging us to propose their review.

scholarly journals Sex modulates the association of radial artery augmentation index with renal function decline in individuals without chronic kidney disease

2021 ◽  
Author(s):  
Qiao Qin ◽  
Fangfang Fan ◽  
Jia Jia ◽  
Yan Zhang ◽  
Bo Zheng
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Arterial Stiffness ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Adjusted Odds Ratio ◽  
Augmentation Index ◽  
Renal Function Decline

Abstract Purpose An increase in arterial stiffness is associated with rapid renal function decline (RFD) in patients with chronic kidney disease (CKD). The aim of this study was to investigate whether the radial augmentation index (rAI), a surrogate marker of arterial stiffness, affects RFD in individuals without CKD. Methods A total of 3165 Chinese participants from an atherosclerosis cohort with estimated glomerular filtration rates (eGFR) of ≥ 60 mL/min/1.73 m2 were included in this study. The baseline rAI normalized to a heart rate of 75 beats/min (rAIp75) was obtained using an arterial applanation tonometry probe. The eGFRs at both baseline and follow-up were calculated using the equation derived from the Chronic Kidney Disease Epidemiology Collaboration. The association of the rAIp75 with RFD (defined as a drop in the eGFR category accompanied by a ≥ 25% drop in eGFR from baseline or a sustained decline in eGFR of > 5 mL/min/1.73 m2/year) was evaluated using the multivariate regression model. Results During the 2.35-year follow-up, the incidence of RFD was 7.30%. The rAIp75 had no statistically independent association with RFD after adjustment for possible confounders (adjusted odds ratio = 1.12, 95% confidence interval: 0.99–1.27, p = 0.074). When stratified according to sex, the rAIp75 was significantly associated with RFD in women, but not in men (adjusted odds ratio and 95% confidence interval: 1.23[1.06–1.43], p = 0.007 for women, 0.94[0.76–1.16], p = 0.542 for men; p for interaction = 0.038). Conclusion The rAI might help screen for those at high risk of early rapid RFD in women without CKD.

scholarly journals FGF-23 and Phosphate in Children with Chronic Kidney Disease: A Cross-Sectional Study in Kazakhstan

Medicina ◽  
2020 ◽  
Vol 57 (1) ◽  
pp. 15
Author(s):  
Altynay Balmukhanova ◽  
Kairat Kabulbayev ◽  
Harika Alpay ◽  
Assiya Kanatbayeva ◽  
Aigul Balmukhanova
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Fibroblast Growth Factor 23 ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
Ckd Stage ◽  
Advanced Stages ◽  
Fgf 23 ◽  
Stage 1

Background and objectives: Chronic kidney disease (CKD) in children is a complex medical and social issue around the world. One of the serious complications is mineral-bone disorder (CKD-MBD) which might determine the prognosis of patients and their quality of life. Fibroblast growth factor 23 (FGF-23) is a phosphaturic hormone which is involved in the pathogenesis of CKD-MBD. The purpose of the study was to determine what comes first in children with CKD: FGF-23 or phosphate. Materials and Methods: This cross-sectional study included 73 children aged 2–18 years with CKD stages 1–5. We measured FGF-23 and other bone markers in blood samples and studied their associations. Results: Early elevations of FGF-23 were identified in children with CKD stage 2 compared with stage 1 (1.6 (1.5–1.8) pmol/L versus 0.65 (0.22–1.08), p = 0.029). There were significant differences between the advanced stages of the disease. FGF-23 correlated with PTH (r = 0.807, p = 0.000) and phosphate (r = 0.473, p = 0.000). Our study revealed that the elevated level of FGF-23 went ahead hyperphosphatemia and elevated PTH. Thus, more than 50% of children with CKD stage 2 had the elevating level of serum FGF-23, and that index became increasing with the disease progression and it achieved 100% at the dialysis stage. The serum phosphate increased more slowly and only 70.6% of children with CKD stage 5 had the increased values. The PTH increase was more dynamic. Conclusions: FGF-23 is an essential biomarker, elevates long before other markers of bone metabolism (phosphate), and might represent a clinical course of disease.

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