Enfermedad óseo mineral relacionada con la enfermedad renal crónica: Klotho y FGF23; implicaciones cardiovasculares

Villanueva, Laura Salanova; González, Carmen Sánchez; Tomero, José Antonio Sánchez; Aguilera, Abelardo; Junco, Esther Ortega

doi:10.1016/j.nefro.2016.01.011

Cited by 12 publications

(4 citation statements)

References 86 publications

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“…CKD-MBD is one of the striking features associated with the high morbidity and mortality of cardiovascular events in CKD and ESRD [ 51 , 139 ]. Abnormal mineral metabolism includes high serum phosphate, FGF23, and PTH levels, which are closely associated with or even induced by klotho deficiency [ 14 , 140 – 142 ]. Clinical studies in patients with CKD have shown that soluble klotho is lower than normal (519 ± 183 versus 845 ± 330 pg/mL, P < .0001) in renal patients, and soluble klotho is positively correlated with serum calcium and negatively correlated with serum phosphate, PTH, and FGF23, suggesting that soluble klotho might reflect the ensuing tubular resistance to FGF23, which could be an early marker of CKD-MBD [ 143 , 144 ].…”

Section: Main Textmentioning

confidence: 99%

The role of klotho in chronic kidney disease

et al. 2018

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Chronic kidney disease (CKD) is an inherently systemic disease that refers to a long-term loss of kidney function. The progression of CKD has repercussions for other organs, leading to many kinds of extrarenal complications. Intensive studies are now being undertaken to reveal the risk factors and pathophysiological mechanism of this disease. During the past 20 years, increasing evidence from clinical and basic studies has indicated that klotho, which was initially known as an anti-aging gene and is mainly expressed in the kidney, is significantly correlated with the development and progression of CKD and its complications. Here, we discuss in detail the role and pathophysiological implications of klotho in ion disorders, the inflammation response, vascular calcification, mineral bone disorders, and renal fibrosis in CKD. Based on the pathogenic mechanism of klotho deficiency and klotho decline in urine early in CKD stage 2 and even earlier in CKD stage 1, it is not difficult to understand that soluble klotho can serve as an early and sensitive marker of CKD. Moreover, the prevention of klotho decline by several mechanisms can attenuate renal injuries, retard CKD progression, ameliorate extrarenal complications, and improve renal function. In this review, we focus on the functions and pathophysiological implications of klotho in CKD and its extrarenal complications as well as its potential applications as a diagnostic and/or prognostic biomarker for CKD and as a novel treatment strategy to improve and decrease the burden of comorbidity in CKD.

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Section: Main Textmentioning

confidence: 99%

The role of klotho in chronic kidney disease

et al. 2018

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“…Alterations of bone and mineral metabolism and anemia are common and occur early in the course of CKD and when left untreated carry an increased risk for adverse outcomes [ 4 , 5 ]. Approximately 36% of hemodialysis patients in the USA have hyperphosphatemia (when defined as a phosphate concentration > 5.5 mg/dL) [ 6 ], although older surveys cite higher percentages [ 7 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…An increasing number of studies support the idea that fibroblast growth factor 23 (FGF23), a key phosphate-regulating hormone, is associated with adverse outcomes in CKD [ 12 ]. Along with parathyroid hormone (PTH), FGF23 is an important factor involved in the disordered bone and mineral metabolism that contributes to CKD morbidity and mortality [ 5 , 12 ]. Normally, FGF23 regulates phosphate and vitamin D metabolism through a negative endocrine feedback loop it shares with PTH; however, production of 1,25-dihydroxyvitamin D 3 is inhibited by FGF23 but stimulated by PTH, whereas both FGF23 and PTH share the phosphaturic effect [ 12 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

Mechanism of Action and Clinical Attributes of Auryxia® (Ferric Citrate)

Ganz

Bino

Salusky

2019

Drugs

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Chronic kidney disease (CKD) is a major cause of morbidity and premature mortality and represents a significant global public health issue. Underlying this burden are the many complications of CKD, including mineral and bone disorders, anemia, and accelerated cardiovascular disease. Hyperphosphatemia and elevated levels of fibroblast growth factor 23 (FGF23) have been identified as key independent risk factors for the adverse cardiovascular outcomes that frequently occur in patients with CKD. Auryxia ® (ferric citrate; Keryx Biopharmaceuticals, Inc., Boston, MA, USA) is an iron-based compound with distinctive chemical characteristics and a mechanism of action that render it dually effective as a therapy in patients with CKD; it has been approved as a phosphate binder for the control of serum phosphate levels in adult CKD patients treated with dialysis and as an iron replacement product for the treatment of iron deficiency anemia in adult CKD patients not treated with dialysis. This review focuses on Auryxia, its mechanism of action, and the clinical attributes that differentiate it from other, non-pharmaceutical-grade, commercially available forms of ferric citrate and from other commonly used phosphate binder and iron supplement therapies for patients with CKD. Consistent with the chemistry and mechanism of action of Auryxia, multiple clinical studies have demonstrated its efficacy in both lowering serum phosphate levels and improving iron parameters in patients with CKD. Levels of FGF23 decrease significantly with Auryxia treatment, but the effects associated with the cardiovascular system remain to be evaluated in longer-term studies.

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“…Several biomarkers relevant to bone and mineral metabolism in chronic kidney disease (CKD)—for which type 2 diabetes mellitus (T2DM) is an important risk—are associated with cardiovascular complications. Among them, serum levels of fibroblast growth factor 23 (FGF23) have been identified, from as early as stage 2 CKD, as one of the earliest biomarkers that start increasing, and correlate with cardiac hypertrophy, heart failure, and all-cause mortality [ 1 , 2 ].…”

Section: Introductionmentioning

confidence: 99%

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

Yamada

Kuro‐o

Funazaki

et al. 2018

International Journal of Nephrology

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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.

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Enfermedad óseo mineral relacionada con la enfermedad renal crónica: Klotho y FGF23; implicaciones cardiovasculares

Cited by 12 publications

References 86 publications

The role of klotho in chronic kidney disease

The role of klotho in chronic kidney disease

Mechanism of Action and Clinical Attributes of Auryxia® (Ferric Citrate)

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

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