Burosumab Therapy for X-Linked Hypophosphatemia and Therapeutic Implications for CKD

Perwad, Farzana; Portale, Anthony A.

doi:10.2215/cjn.15201218

Cited by 15 publications

(10 citation statements)

References 10 publications

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“…When tumors are unresectable or with multiple recurrences, calcitriol and oral phosphate supplementation is recommended [17]. Human monoclonal antibody therapy against FGF-23, burosumab, initially approved for the treatment of X-linked hypophosphatemia [18], is currently been evaluated among patients with Onc-Ost. However, in our patient due to complicated clinical presentation, the diagnosis of NK T-cell lymphoma could not be made early enough and the patient expired within 4 days of chemotherapy initiation.…”

Section: Discussionmentioning

confidence: 99%

A Case of Hypophosphatemia due to Oncogenic Osteomalacia in a Patient with Natural Killer T-Cell Lymphoma

Zheng

Kanduri

Canterbury

et al. 2021

Kidney Blood Press Res

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Introduction: Oncogenic osteomalacia (Onc-Ost) is a paraneoplastic phenomenon characterized by hypophosphatemia due to elevated fibroblast growth factor-23 (FGF-23). Onc-Ost has been previously reported in patients with germ line mesenchymal tumors and solid organ malignancies. This is the first report of aggressive natural killer (NK) T-cell lymphoma presenting as Onc-Ost. Case Description: A 33-year-old Vietnamese female with active hepatitis B and Mycobacterium avium complex, on ongoing therapy with tenofovir disoproxil, azithromycin, and ethambutol, presented with persistent fevers and developed refractory hypophosphatemia. Workup confirmed severe renal phosphate wasting. Tenofovir disoproxil was initially suspected; however, presence of isolated phosphaturia without Fanconi syndrome and persistence of hypophosphatemia despite discontinuation of medication led to clinical suspicion of Onc-Ost. Elevated FGF-23 warranted further workup, leading to a definitive diagnosis of clinically subtle NK T-cell lymphoma. Chemotherapy was initiated; however, patient continued to deteriorate clinically and expired. Conclusion: Along with commonly reported germ line mesenchymal tumors and solid malignancies, NK T-cell lymphoma can also present as Onc-Ost. Timely detection of associated tumors and subsequent antitumor therapy would likely reverse hypophosphatemia and improve clinical outcomes.

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Section: Discussionmentioning

confidence: 99%

A Case of Hypophosphatemia due to Oncogenic Osteomalacia in a Patient with Natural Killer T-Cell Lymphoma

Zheng

Kanduri

Canterbury

et al. 2021

Kidney Blood Press Res

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“…While burosumab therapy is costly, it is the only drug on the market to directly mitigate XLH's clinical manifestations. Pending the results of ongoing clinical trials, future uses of burosumab may include other diseases that manifest due to elevated levels of intact FGF23 [24].…”

Section: Discussionmentioning

confidence: 99%

The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology

Vincze

Skinner

Tucker

et al. 2021

Life

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The authors present a stereotypical case presentation of X-linked hypophosphatemia (XLH) and provide a review of the pathophysiology and related pharmacology of this condition, primarily focusing on the FDA-approved medication burosumab. XLH is a renal phosphate wasting disorder caused by loss of function mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). Typical biochemical findings include elevated serum levels of bioactive/intact fibroblast growth factor 23 (FGF23) which lead to (i) low serum phosphate levels, (ii) increased fractional excretion of phosphate, and (iii) inappropriately low or normal 1,25-dihydroxyvitamin D (1,25-vitD). XLH is the most common form of heritable rickets and short stature in patients with XLH is due to chronic hypophosphatemia. Additionally, patients with XLH experience joint pain and osteoarthritis from skeletal deformities, fractures, enthesopathy, spinal stenosis, and hearing loss. Historically, treatment for XLH was limited to oral phosphate supplementation, active vitamin D supplementation, and surgical intervention for cases of severe bowed legs. In 2018, the United States Food and Drug Administration (FDA) approved burosumab for the treatment of XLH and this medication has demonstrated substantial benefit compared with conventional therapy. Burosumab binds circulating intact FGF23 and blocks its biological effects in target tissues, resulting in increased serum inorganic phosphate (Pi) concentrations and increased conversion of inactive vitamin D to active 1,25-vitD.

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“…Anti-FGF23 Antibodies In early CKD stages, FGF23 oversecretion is a compensatory mechanism to maintain mineral homeostasis. However, FGF23 downregulates vitamin D and is associated with various adverse events in advanced CKD patients [120,121]. Burosumab is a monoclonal antibody against FGF23 approved by the FDA for treatment of children [122] and adults [123] with X-linked hypophosphatemia.…”

Section: New Therapiesmentioning

confidence: 99%

“…However, it might pose a lower risk in ESRD patients, as different modalities regulate phosphorus homeostasis. Further studies are needed before using burosumab in CKD patients [ 120 , 121 ].…”

Section: Pharmacological Approachmentioning

confidence: 99%

Bone Quality in Chronic Kidney Disease Patients: Current Concepts and Future Directions – Part II

et al. 2021

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Background: Patients with chronic kidney disease (CKD) have an increased risk of osteoporotic fractures, which is due not only to low bone volume and mass but also poor microarchitecture and tissue quality. The pharmacological and nonpharmacological interventions detailed, herein, are potential approaches to improve bone health in CKD patients. Various medications build up bone mass but also affect bone tissue quality. Antiresorptive therapies strikingly reduce bone turnover; however, they can impair bone mineralization and negatively affect the ability to repair bone microdamage and cause an increase in bone brittleness. On the other hand, some osteoporosis therapies may cause a redistribution of bone structure that may improve bone strength without noticeable effect on BMD. This may explain why some drugs can affect fracture risk disproportionately to changes in BMD. Summary: An accurate detection of the underlying bone abnormalities in CKD patients, including bone quantity and quality abnormalities, helps in institution of appropriate management strategies. Here in this part II, we are focusing on advancements in bone therapeutics that are anticipated to improve bone health and decrease mortality in CKD patients. Key Messages: Therapeutic interventions to improve bone health can potentially advance life span. Emphasis should be given to the impact of various therapeutic interventions on bone quality.

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Burosumab Therapy for X-Linked Hypophosphatemia and Therapeutic Implications for CKD

Cited by 15 publications

References 10 publications

A Case of Hypophosphatemia due to Oncogenic Osteomalacia in a Patient with Natural Killer T-Cell Lymphoma

A Case of Hypophosphatemia due to Oncogenic Osteomalacia in a Patient with Natural Killer T-Cell Lymphoma

The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology

Bone Quality in Chronic Kidney Disease Patients: Current Concepts and Future Directions – Part II

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