Hypertension is a characteristic complication of X-linked hypophosphatemia

Nakamura, Yukitsugu; Takagi, Masaki; Takeda, Ryojun; Miyai, K; Hasegawa, Yukihiro

doi:10.1507/endocrj.ej16-0199

Cited by 34 publications

(32 citation statements)

References 14 publications

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“…Elevated arterial blood pressure, left ventricular hypertrophy and/or pathological electrocardiograms have been reported in some but not all studies evaluating the cardiovascular status of patients with XLH [104][105][106][107][108][109][110] . Therefore, we suggest at least yearly blood pressure measurements, with a more detailed work-up only in the presence of persistently elevated blood pressure.…”

Section: Radiographic and Imaging Follow-upmentioning

confidence: 99%

Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia

et al. 2019

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X-linked hypophosphataemia (XLH) is an X-linked dominant disorder caused by mutations in PHEX (located at Xp22.1), which encodes a cell-surface-bound protein-cleavage enzyme (phosphate-regulating neutral endopeptidase PHEX), predominantly expressed in osteoblasts, osteocytes and teeth (odontoblasts and cementoblasts). XLH is the most common cause of inherited phosphate wasting, with an incidence of 3.9 per 100,000 live births and a prevalence ranging from 1.7 per 100,000 children to 4.8 per 100,000 persons (children and adults) 1-3. Although the pathogenesis of XLH is not fully understood, animal studies indicate that loss of Phex function results in enhanced secretion of the phosphaturic hormone fibroblast growth factor 23 (FGF23), with osteocytes being the primary source of FGF23 production 4. These effects explain most of the characteristic features of the disease, including renal phosphate wasting with consequent hypophosphataemia, diminished synthesis of active vitamin D (1,25(OH) 2 vitamin D), rickets, osteomalacia, odontomalacia and disproportionate short stature 4-6. Patients usually develop clinical symptoms during the first or second year of life. Early treatment with oral phosphate supplementation and active vitamin D heals rickets, limits dental abscess formation and prevents progressive growth failure, but in a substantial proportion of patients treatment is unsuccessful and/or associated with adverse effects (for example, hyper parathyroidism and nephrocalcinosis) 7,8. Up to two-thirds of children with XLH require lower limb surgery 9-12. Conventional therapy further stimulates FGF23 levels and thereby renal phosphate wasting, resulting in a vicious circle, which might limit its efficacy 6,13-15. Adult patients with XLH are at risk of complications such as early osteoarthritis, enthesopathies, spinal stenosis, pseudofractures and hearing loss, which might limit quality of life 16-18. In 2018, burosumab, a fully human monoclonal IgG1 antibody neutralizing FGF23, was approved by health authorities for the treatment of patients with

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Section: Radiographic and Imaging Follow-upmentioning

confidence: 99%

Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia

et al. 2019

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“…One study reported normal renal function 25 years after acute vitamin D toxicity with nephrocalcinosis in two XLH patients . However, other authors found that 9.1% of adults with XLH had CKD . The authors have also managed XLH patients with CKD stages 3 to 5 as adults.…”

Section: Medical Therapy Of Fgf23‐mediated Skeletal Disordersmentioning

confidence: 99%

“…The authors have also managed XLH patients with CKD stages 3 to 5 as adults. Hypertension is also common in these patients and may relate to lower glomerular filtration rates . In general many of these complications may be the result of failing to adequately balance the risks and the benefits when manipulating therapeutic doses.…”

Section: Medical Therapy Of Fgf23‐mediated Skeletal Disordersmentioning

confidence: 99%

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FGF23, Hypophosphatemia, and Emerging Treatments

2019

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FGF23 is an important hormonal regulator of phosphate homeostasis. Together with its co‐receptor Klotho, it modulates phosphate reabsorption and both 1α‐hydroxylation and 24‐hydroxylation in the renal proximal tubules. The most common FGF23‐mediated hypophosphatemia is X‐linked hypophosphatemia (XLH), caused by mutations in the PHEX gene. FGF23‐mediated forms of hypophosphatemia are characterized by phosphaturia and low or low‐normal calcitriol concentrations, and unlike nutritional rickets, these cannot be cured with nutritional vitamin D supplementation. Autosomal dominant and autosomal recessive forms of FGF23‐mediated hypophosphatemias show a similar pathophysiology, despite a variety of different underlying genetic causes. An excess of FGF23 activity has also been associated with a number of other conditions causing hypophosphatemia, including tumor‐induced osteomalacia, fibrous dysplasia of the bone, and cutaneous skeletal hypophosphatemia syndrome. Historically phosphate supplementation and therapy using analogs of highly active vitamin D (eg, calcitriol, alfacalcidol, paricalcitol, eldecalcitol) have been used to manage conditions involving hypophosphatemia; however, recently a neutralizing antibody for FGF23 (burosumab) has emerged as a promising treatment agent for FGF23‐mediated disorders. This review discusses the progression of clinical trials for burosumab for the treatment of XLH and its recent availability for clinical use. Burosumab may have potential for treating other conditions associated with FGF23 overactivity, but these are not yet supported by trial data. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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“…Most nephrocalcinosis is mild, but occasionally patients develop chronic kidney disease (CKD), the prevalence of which is uncertain, but progression to end‐stage renal disease is rare. Hypertension has been reported in 27% of XLH patients and may relate in part to nephrocalcinosis and CKD .…”

Section: Medical Managementmentioning

confidence: 99%

Pharmacological management of X‐linked hypophosphataemia

Imel

White

2018

Brit J Clinical Pharma

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The most common heritable disorder of renal phosphate wasting, X-linked hypophosphataemia (XLH), was discovered to be caused by inactivating mutations in the phosphate regulating gene with homology to endopeptidases on the X-chromosome (PHEX) gene in 1995. Although the exact molecular mechanisms by which PHEX mutations cause disturbed phosphate handling in XLH remain unknown, focus for novel therapies has more recently been based upon the finding that the bone-produced phosphaturic hormone fibroblast growth factor-23 is elevated in XLH patient plasma. Previous treatment strategies for XLH were based upon phosphate repletion plus active vitamin D analogues, which are difficult to manage, fail to address the primary pathogenesis of the disease, and can have deleterious side effects. A novel therapy for XLH directly targeting fibroblast growth factor-23 via a humanized monoclonal antibody (burosumab-twza/CRYSVITA, henceforth referred to just as burosumab) has emerged as an effective, and recently approved, pharmacological treatment for both children and adults. This review will provide an overview of the clinical manifestations of XLH, the molecular pathophysiology, and summarize its current treatment.

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Hypertension is a characteristic complication of X-linked hypophosphatemia

Cited by 34 publications

References 14 publications

Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia

Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia

FGF23, Hypophosphatemia, and Emerging Treatments

Pharmacological management of X‐linked hypophosphataemia

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