scholarly journals Gender-Related Differences in Chronic Kidney Disease-Associated Vascular Calcification Risk and Potential Risk Mediators: A Scoping Review

Healthcare ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 979
Author(s):  
Patrick Yihong Wu ◽  
Szu-Ying Lee ◽  
Ke-Vin Chang ◽  
Chia-Ter Chao ◽  
Jenq-Wen Huang
Keyword(s):  
Chronic Kidney Disease ◽  
At Risk ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Large Scale ◽  
Fibroblast Growth Factor 23 ◽  
Vascular Wall ◽  
Matrix Gla Protein ◽  
Phenotypic Change ◽  
Fgf 23

Vascular calcification (VC) involves the deposition of calcium apatite in vascular intima or media. Individuals of advanced age, having diabetes mellitus or chronic kidney disease (CKD) are particularly at risk. The pathogenesis of CKD-associated VC evolves considerably. The core driver is the phenotypic change involving vascular wall constituent cells toward manifestations similar to that undergone by osteoblasts. Gender-related differences are observed regarding the expressions of osteogenesis-regulating effectors, and presumably the prevalence/risk of CKD-associated VC exhibits gender-related differences as well. Despite the wealth of data focusing on gender-related differences in the risk of atherosclerosis, few report whether gender modifies the risk of VC, especially CKD-associated cases. We systematically identified studies of CKD-associated VC or its regulators/modifiers reporting data about gender distributions, and extracted results from 167 articles. A significantly higher risk of CKD-associated VC was observed in males among the majority of original investigations. However, substantial heterogeneity exists, since multiple large-scale studies yielded neutral findings. Differences in gender-related VC risk may result from variations in VC assessment methods, the anatomical segments of interest, study sample size, and even the ethnic origins of participants. From a biological perspective, plausible mediators of gender-related VC differences include body composition discrepancies, alterations involving lipid profiles, inflammatory severity, diversities in matrix Gla protein (MGP), soluble Klotho, vitamin D, sclerostin, parathyroid hormone (PTH), fibroblast growth factor-23 (FGF-23), and osteoprotegerin levels. Based on our findings, it may be inappropriate to monotonously assume that male patients with CKD are at risk of VC compared to females, and we should consider more background in context before result interpretation.

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.

scholarly journals Emerging Role of Vitamins D and K in Modulating Uremic Vascular Calcification: The Aspect of Passive Calcification

Nutrients ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 152 ◽  
Author(s):  
Yi-Chou Hou ◽  
Chien-Lin Lu ◽  
Cai-Mei Zheng ◽  
Ruei-Ming Chen ◽  
Yuh-Feng Lin ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Vitamin K ◽  
Matrix Vesicles ◽  
Vital Role ◽  
Matrix Gla Protein ◽  
Protein Receptor ◽  
Calciprotein Particles

Vascular calcification is a critical complication in patients with chronic kidney disease (CKD) because it is predictive of cardiovascular events and mortality. In addition to the traditional mechanisms associated with endothelial dysfunction and the osteoblastic transformation of vascular smooth muscle cells (VSMCs), the regulation of calcification inhibitors, such as calciprotein particles (CPPs) and matrix vesicles plays a vital role in uremic vascular calcification in CKD patients because of the high prevalence of vitamin K deficiency. Vitamin K governs the gamma-carboxylation of matrix Gla protein (MGP) for inhibiting vascular calcification, and the vitamin D binding protein receptor is related to vitamin K gene expression. For patients with chronic kidney disease, adequate use of vitamin D supplements may play a role in vascular calcification through modulation of the calciprotein particles and matrix vesicles (MVs).

An Overview of the Pathophysiology of Vascular Calcification in Chronic Kidney Disease

2007 ◽  
Vol 27 (2_suppl) ◽  
pp. 215-222 ◽  
Author(s):  
Tomasz Stompór
Keyword(s):  
Chronic Kidney Disease ◽  
Calcium Phosphate ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Vessel Wall ◽  
Matrix Gla Protein ◽  
Soft Tissue Calcification ◽  
Poor Control ◽  
Bone Morphogenetic Protein 7 ◽  
Morphogenetic Protein

Abnormalities of calcium–phosphate balance, with subsequent bone metabolism disorders, are among the key and earliest features of chronic kidney disease (CKD). Recently, another consequence of these abnormalities was brought to light—namely, vascular calcification. Most studies performed in patients on dialysis suggest that their vascular calcification is more advanced than that seen in the general population. Furthermore, the progression of vessel wall mineralization is much more dynamic in patients with CKD. Apart from the commonly assessed factors that promote vascular calcification, such as age, duration of dialysis, or poor control of calcium–phosphate status, several other factors have recently been identified. In the spectrum of substances involved in the regulation of the process of soft-tissue calcification, the most extensively studied in the nephrology literature are bone morphogenetic protein 7, osteoprotegerin, matrix Gla protein, fetuin-A, and the phosphatonins. Better understanding of the mechanisms underlying excess vascular mineralization have led to the development of promising new therapies.

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.

scholarly journals Histology and Immunohistochemistry of Radial Arteries Are Suggestive of an Interaction between Calcification and Early Atherosclerotic Lesions in Chronic Kidney Disease

Medicina ◽  
2021 ◽  
Vol 57 (11) ◽  
pp. 1156
Author(s):  
Aikaterini Lysitska ◽  
Nikiforos Galanis ◽  
Ioannis Skandalos ◽  
Christina Nikolaidou ◽  
Sophia Briza ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Morphometric Analysis ◽  
Intima Media Thickness ◽  
Inflammatory Cells ◽  
Vascular Wall ◽  
Control Group ◽  
Group A ◽  
Group B

Background and Objectives: recent studies suggest an implication of immune mechanisms in atherosclerotic disease. In this paper, the interaction between inflammation, calcification, and atherosclerosis on the vessel walls of patients with chronic kidney disease (CKD) is described and evaluated. Materials and Methods: patients with stage V CKD, either on pre-dialysis (group A) or on hemodialysis (HD) for at least 2 years (group B), in whom a radiocephalic arteriovenous fistula (RCAVF) was created, were included in the study. The control group included healthy volunteers who received radial artery surgery after an accident. The expressions of inflammatory cells, myofibroblasts, and vascular calcification regulators on the vascular wall were estimated, and, moreover, morphometric analysis was performed. Results: the expressions of CD68(+) cells, matrix carboxyglutamic acid proteins (MGPs), the receptor activator of nuclear factor-kB (RANK) and RANK ligand (RANKL), and osteoprotegerin (OPG), were significantly increased in CKD patients compared to the controls p = 0.02; p = 0.006; p = 0.01; and p = 0.006, respectively. In morphometric analysis, the I/M and L/I ratios had significant differences between CKD patients and the controls 0.3534 ± 0.20 vs. 0.1520 ± 0.865, p = 0.003, and 2.1709 ± 1.568 vs. 4.9958 ± 3.2975, p = 0.03, respectively. The independent variables correlated with the degree of vascular calcification were the intensity of CD34(+), aSMA(+) cells, and OPG, R2 = 0.76, p < 0.0001, and, with intima-media thickness (IMT), the severity of RANKL expression R2 = 0.3, p < 0.0001. Conclusion: atherosclerosis and vascular calcification in CKD seem to be strongly regulated by an immunological and inflammatory activation on the vascular wall.

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.

THE ROLE OF FBROBLAST GROWTH FACTOR 23 (FGF 23) IN THE MINERAL AND BONE DISORDER (MBD) OF THE PATENTS WITH CHRONIC KIDNEY DISEASE

2016 ◽  
pp. 9-14
Author(s):  
Huu Vu Quang Nguyen ◽  
Tam Vo
Keyword(s):  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Kidney Function ◽  
Mineral Metabolism ◽  
Fibroblast Growth Factor 23 ◽  
Normal Kidney ◽  
Mineral And Bone Disorder ◽  
Normal Kidney Function ◽  
Fgf 23

Fibroblast growth factor 23 (FGF23) is a key regulator of phosphorus metabolism whose effects in patients with chronic kidney disease (CKD) have only recently begun to be appreciated. Recent study of this phosphaturic hormone has revealed new path-ways of mineral regulation in both individuals with normal kidney function and in patients with CKD. While the effects of FGF23 on mineral metabolism in CKD appears to be similar to its effects in individuals with normal kidney function, elevated levels of the protein in the CKD population have also been linked to kidney disease progression, altered skeletal histology, and increased mortality rates, relationships that have not been examined in the general population.Thus, potential differences in FGF23 metabolism accompany the elevated levels found in CKD patients and, although the exact pathophysiological consequences remain mostly unknown, elevated FGF23 levels appear to contribute to major complications of CKD that plague both adults and children. Key words: FGF23, chronic kidney

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