Indirect Regulation of PTH by Estrogens May Require FGF23

Carrillo-López, Natalia; Román-García, Pablo; Rodríguez-Rebollar, A.; Fernández-Martín, José Luis; Naves-Díaz, Manuel; Cannata-Andía, Jorge B.

doi:10.1681/asn.2008121258

Cited by 93 publications

(65 citation statements)

References 54 publications

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“…Various mechanisms may explain this association, including increased undernutrition with age, decreased renal phosphate reabsorption, and hormonal factors. The association between hyperphosphatemia and female sex has also been reported in many previous studies [19,21,[23][24][25][26][27][28]. Reasons for this association are as yet poorly understood, but some experimental studies have demonstrated that estrogens reduce PTH transcription and vitamin D activation as well as increase FGF-23 circulating levels [29].…”

Section: Discussionmentioning

confidence: 54%

Hyperphosphatemia in Chronic Kidney Disease: Patient Characteristics and Dialysis Mortality during the First Year of Dialysis

Laurain¹

2012

J Nephrol Therapeutic

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Aims: To describe the characteristics of chronic kidney disease patients with hyperphosphatemia before dialysis. To assess the impact of pre-dialysis hyperphosphatemia on dialysis mortality.Methods: All patients beginning a dialysis treatment in [2005][2006] in all the nephrology units operating in the Lorraine region of northeastern France were considered. Among them, those who were referred to a nephrologist more than 1 month before dialysis and had atleast one pre-dialysis phosphatemia measurement were included. All-cause mortality during the first year of dialysis was the outcome of interest and phosphatemia level the parameter of interest.Results: Of 406 patients included (mean age, 68.2 ± 14.8 years), 53% had pre-dialysis hyperphosphatemia, defined by a mean serum phosphate > 1.45 mmol/L during an average pre-dialysis nephrology follow-up period of 10 months. Patients with hyperphosphatemia were younger than those with normophosphatemia, and more often women. They were more likely to have diabetic nephropathy, less likely to have hypertensive nephropathy and cardiovascular comorbidity, and had fewer comorbidities. We found no association between hyperphosphatemia and mortality.Conclusions: This study shows that patients with pre-dialysis hyperphosphatemia differ from those with normophosphatemia. Larger studies are warranted to confirm or refute the absence of a relationship between predialysis hyperphosphatemia and dialysis mortality.

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Section: Discussionmentioning

confidence: 54%

Hyperphosphatemia in Chronic Kidney Disease: Patient Characteristics and Dialysis Mortality during the First Year of Dialysis

Laurain¹

2012

J Nephrol Therapeutic

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“…All of these factors contribute to regulating the renal tubular phosphate reabsorption capacity and might explain the lower phosphorous excretion observed in women than in men reported by Cirillo and co-workers (27). Furthermore, estrogen circulating levels also modulate bone turnover and calcium and phosphorous bone removal (26). Thus, renal tubular reabsorption and bone removal might account for the difference in serum phosphorous levels and for the paradoxical finding of a lower phosphorous toxicity in women as compared with that in men.…”

Section: Discussionmentioning

confidence: 96%

“…The reasons for such a discrepancy might be explained by the lower basal hazard in women as compared with that in men or, possibly, by the complex interplay between sex hormones and phosphorous homeostasis. Although the mechanisms are not completely understood, experimental studies have demonstrated that estrogens reduce PTH transcription and vitamin D activation as well as increase FGF-23 circulating levels (26). All of these factors contribute to regulating the renal tubular phosphate reabsorption capacity and might explain the lower phosphorous excretion observed in women than in men reported by Cirillo and co-workers (27).…”

Section: Discussionmentioning

confidence: 98%

Chronic Kidney Disease Progression and Outcome According to Serum Phosphorus in Mild-to-Moderate Kidney Dysfunction

Bellasi

Mandreoli

Baldrati

et al. 2011

Clinical Journal of the American Society of Nephrology

140

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SummaryBackground and objectives Several factors might alter serum phosphate homeostasis and induce hyperhosphatemia in patients with chronic kidney disease (CKD) not requiring dialysis. However, whether and to what extent hyperphosphatemia is associated with a poor prognosis in different CKD patient groups remain to be elucidated.Design, setting, participants & measurements We utilized the "Prevenzione Insufficienza Renale Progressiva" (PIRP) database, a large project sponsored by the Emilia-Romagna Health Institute. PIRP is a collaborative network of nephrologists and general practitioners located in the Emilia-Romagna region, Italy, aimed at increasing awareness of CKD complications and optimizing CKD patient care. We identified 1716 patients who underwent a GFR and serum phosphorous assessment between 2004 and 2007. We tested whether phosphate levels Ն4.3 mg/dl are associated with the risk of CKD progression or all causes of death.Results Older age and male sex were associated with lower phosphate levels. Instead, higher phosphate levels were noted in patients with diabetes. Patients with phosphate levels Ն4.3 mg/dl were at an increased risk of starting dialysis or dying (hazard ratio 2.04; 95% confidence interval [1.44, 2.90]). Notably, subgroup analyses revealed that the magnitude of the risk associated with hyperphosphatemia varied depending on age, sex, diabetes, and different stages of CKD.Conclusions These analyses lend support to the hypothesis that phosphorous abnormalities might have a negative effect on the residual renal function and prognosis in different groups of CKD patients. However, the risk associated with hyperphosphatemia might vary in specific CKD patient subgroups.

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“…Most studies have found no association between FGF23 and age, but pediatric studies involving very young participants are needed given the differences in phosphorus physiology in infants and toddlers, who manifest markedly higher serum phosphate levels and growth rates than adults. Finally, estradiol stimulates FGF23, 72 and one study reported higher levels in healthy women, 7 but this, too, requires systematic study. Deficiency of klotho, the co-receptor for FGF23, associates with hyperphosphatemia and markedly elevated levels of FGF23.…”

Section: How Do Fgf23 Levels Differ In Specific Ckd Subpopulations?mentioning

confidence: 99%

Forging Forward with 10 Burning Questions on FGF23 in Kidney Disease

Wolf

2010

Journal of the American Society of Nephrology

279

222

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In only a few years, the discovery and characterization of fibroblast growth factor 23 (FGF23) is drastically changing our understanding of disordered mineral metabolism in chronic kidney disease (CKD). The journey of FGF23 from anonymity to center stage began with studies of a family of rare diseases that share a common phenotype, including hypophosphatemia, isolated urinary phosphate wasting, rickets or osteomalacia, and insufficient calcitriol production for the degree of hypophosphatemia. The main diseases in the group are X-linked hypophosphatemia (the most common), autosomal dominant hypophosphatemic rickets, autosomal recessive hypophosphatemic rickets, fibrous dysplasia, and tumor-induced osteomalacia (TIO; a sporadic form). 1,2 With no known cause for the diseases, overexpression of one or more circulating phosphaturic factors, termed "phosphatonins" was hypothesized.Genetic studies provided the breakthrough. Positional cloning revealed missense mutations in the gene encoding FGF23 on chromosome 12 in each of four families with autosomal dominant hypophosphatemic rickets, encompassing 26 affected individuals. 3 These mutations were later shown to protect FGF23 from proteolytic cleavage. 4,5 Confirmation of the causal role of FGF23 in the hypophosphatemic disorders came in 2001, when high expression of FGF23 was isolated from tumor cells from patients with TIO. 6 The development of high-precision assays for measuring FGF23 confirmed elevated circulating levels in patients with TIO, X-linked hypophosphatemia, and ESRD compared with healthy individuals (Figure 1) 7,8 and opened the door to a new era of human physiologic research on FGF23. NORMAL FGF23 PHYSIOLOGYFGF23 is primarily secreted by osteocytes 9 and has several endocrine effects on mineral metabolism (Figure 2): FGF23 induces phosphaturia by decreasing phosphate reabsorption in the proximal tubule through downregulation of luminal sodium-phosphate co-transporters 10,11 ; FGF23 reduces circulating levels of calcitriol by inhibiting renal 1-␣ hydroxylase 10,11 and stimulating 24-hydroxylase, 11 which catalyzes the initial step in vitamin D degradation; and FGF23 inhibits secretion of parathyroid hormone (PTH). 12 These effects are dependent on the presence of klotho, which is highly expressed in the kidney and the parathyroid glands and acts as a co-receptor for FGF23 by markedly increasing the affinity of FGF23 for ubiquitous FGF receptors. 13,14 These aspects of FGF23 physiology were demonstrated in studies of animals that were administered FGF23, 4,10,12,15 transgenic mice that overexpress FGF23, 16 -19 and klotho 20 and FGF23 null mice. 21 Physiologic studies of normal humans were confirmatory, 22-24 as were observations from patients with ABSTRACTThe discovery of fibroblast growth factor 23 (FGF23) as the causal factor in the pathogenesis of rare forms of hypophosphatemic rickets is rapidly reshaping our understanding of disordered mineral metabolism in chronic kidney disease (CKD). Excessive production of FGF23 by osteocytes is an appropriat...

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Indirect Regulation of PTH by Estrogens May Require FGF23

Cited by 93 publications

References 54 publications

Hyperphosphatemia in Chronic Kidney Disease: Patient Characteristics and Dialysis Mortality during the First Year of Dialysis

Hyperphosphatemia in Chronic Kidney Disease: Patient Characteristics and Dialysis Mortality during the First Year of Dialysis

Chronic Kidney Disease Progression and Outcome According to Serum Phosphorus in Mild-to-Moderate Kidney Dysfunction

Forging Forward with 10 Burning Questions on FGF23 in Kidney Disease

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