Management of Hyperphosphatemia in End-Stage Renal Disease: A New Paradigm

Rastogi, Anjay; Bhatt, Nisha; Rossetti, Sandro; Beto, Judith A.

doi:10.1053/j.jrn.2020.02.003

Cited by 58 publications

(56 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Hyperphosphatemia is a common complication observed among patients receiving maintenance dialysis, and is associated with dystrophic calcification (affecting vasculature and heart valves), fractures, cardiovascular mortality and all-cause mortality (1)(2)(3). Current approaches to hyperphosphatemia managementincreasing hemodialysis session length or frequency, dietary phosphate restriction and phosphate binder therapyare difficult to implement (4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of Tenapanor for Long-term Serum Phosphate Control in Maintenance Dialysis: A 52-Week Randomized Phase 3 Trial (PHREEDOM)

Block¹,

Bleyer

Silva

et al. 2021

Kidney360

View full text Add to dashboard Cite

Background: Treating hyperphosphatemia is a tenet of dialysis care. This trial assessed the safety and efficacy of tenapanor for the management of hyperphosphatemia. Methods: In this 52-week phase 3 study (NCT03427125), participants receiving maintenance dialysis with both hyperphosphatemia (serum phosphorus 6.0-10.0 mg/dl) and a 1.5 mg/dl increase following phosphate binder washout were randomized (3:1) to tenapanor 30 mg twice daily for 26 weeks (randomized treatment period) or sevelamer carbonate (52-week safety control). Participants completing 26 weeks' treatment with tenapanor were re-randomized (1:1) to tenapanor or placebo for 12 weeks (randomized withdrawal period) and were eligible to enter the 14-week safety extension period. With input from the US Food and Drug Administration, the primary efficacy endpoint was the difference in the change in serum phosphorus from the end of the randomized treatment period to the end of the randomized withdrawal period among participants who achieved ≥1.2 mg/dl decrease in serum phosphorus during the randomized treatment period (efficacy analysis set). Efficacy was also evaluated in the intention-to-treat (ITT) analysis set. Results: Of 564 eligible participants randomized to receive tenapanor (n=423) or sevelamer carbonate (n=141) during the randomized treatment period, 255 (60%) in the tenapanor group subsequently were re-randomized to tenapanor (n=128) or placebo (n=127) during the randomized withdrawal period. In the efficacy analysis set (n=131), the difference in estimated mean change in serum phosphorus level between tenapanor and placebo from the beginning to the end of the randomized withdrawal period was −1.4 mg/dl (P<0.0001); in the ITT analysis set (n=243), the estimated mean difference was −0.7 mg/dl (P=0.002). Loosened stools were the most frequently reported adverse event (53% during the randomized treatment period). Serious adverse events were reported more frequently for participants treated with sevelamer carbonate (16-23% across the three study periods) compared with tenapanor (11-17%). Conclusions: Tenapanor reduced serum phosphorus concentrations and maintained control of serum phosphorus in participants receiving maintenance dialysis, with an acceptable safety and tolerability profile.

show abstract

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of Tenapanor for Long-term Serum Phosphate Control in Maintenance Dialysis: A 52-Week Randomized Phase 3 Trial (PHREEDOM)

Block¹,

Bleyer

Silva

et al. 2021

Kidney360

View full text Add to dashboard Cite

show abstract

“…Kadar PTH yang berlebihan selanjutnya menyebabkan mobilisasi kalsium dari tulang dan osteitis fibrosa. 6,9,18 Progresivitas penurunan fungsi ginjal juga menyebabkan penurunan responsivitas reseptor vitamin D (VDR) pada kelenjar paratiroid yang berakibat peningkatan produksi PTH lebih lanjut. Kondisi ini juga menurunkan ekspresi reseptor peka kalsium pada kelenjar paratiroid yang menginduksi terjadinya hiperplasia kelenjar.…”

Section: Abnormalitas Parameter Biokimiaunclassified

Pengelolaan Gangguan Mineral Tulang pada Penyakit Ginjal Kronik

Nugroho¹

2022

JPDI

View full text Add to dashboard Cite

Penyakit ginjal kronik (PGK) sampai dengan saat ini masih menjadi beban kesehatan dunia, yang mana penderitanya mencapai 11-13% dari seluruh populasi. Gangguan mineral dan tulang (GMT-PGK) merupakan komplikasi yang umum ditemukan pada pasien PGK. Komplikasi ini terjadi pada stadium awal penyakit dan mengalami progresivitas seiring dengan penurunan fungsi ginjal. Komplikasi ini umumnya ditandai dengan perubahan pada berbagai parameter laboratorium termasuk di antaranya kalsium, fosfat, dan hormon paratiroid. Perubahan homeostasis parameter ini dikaitkan dengan adanya gangguan tulang dan abnormalitas vaskular, dimana akan meningkatkan risiko terhadap morbiditas dan mortalitas penyakit kardiovaskular maupun mortalitas secara keseluruhan. Sampai dengan saat ini, tata laksana GMT-PGK fokus pada koreksi abnormalitas biokimiawi dan hormonal untuk membatasi kemungkinan efek yang dapat terjadi. Pilihan terapi pada GMT-PGK dan komplikasinya saat ini dilakukan berdasarkan kadar kalsium, fosfat, dan hormon paratiroid secara bersamaan, tidak hanya pada salah satu parameter. Terapi ini juga bersifat individual dikarenakan manfaatnya yang berbeda-beda pada masing-masing pasien.

show abstract

“…Data suggest that nocturnal hemodialysis more effectively lowers serum phosphate than conventional hemodialysis (from 1.78 to 1.44 mmol/L [5.5 to 4.5 mg/dL]). 34 , 35 In the Nocturnal trials, patients receiving 6x-weekly sessions experienced a relative decrease of 0.40 mmol/L (1.2 mg/dL) in mean serum phosphate compared with patients receiving 3x-weekly sessions. Similarly, the Daily trial demonstrated that patients receiving 6x weekly sessions experienced a relative decrease of 0.15 mmol/L (0.5 mg/dL) in mean serum phosphate levels compared with patients receiving 3x weekly sessions.…”

Section: Strategies To Manage Hyperphosphatemiamentioning

confidence: 99%

“…Aluminum-hydroxide has a high ionic binding affinity, low pill burden, and is relatively inexpensive. 34 However, in the 1970s an increasing number of dialysis patients experienced severe aluminum intoxication. While dialysis fluid contamination by aluminum was identified as the culprit, intoxication with aluminum-containing phosphate binders was later reported in non-dialyzed patients.…”

Section: Strategies To Manage Hyperphosphatemiamentioning

confidence: 99%

Multidisciplinary Perspectives of Current Approaches and Clinical Gaps in the Management of Hyperphosphatemia

Vallée¹,

Weinstein²,

Battistella³

et al. 2021

IJNRD

View full text Add to dashboard Cite

Population-based studies have shown that most patients with advanced chronic kidney disease (CKD) do not have optimal phosphate levels. Meta-analyses suggest that there is a morbidity and mortality benefit associated with the lowering of serum phosphate levels. However, to date there is no conclusive evidence from randomized controlled trials (RCTs) that lowering serum phosphate levels reduces the risk of morbidity and mortality. However, hyperphosphatemia may pose a risk to patients and treatment should be considered. We therefore sought to conduct a multidisciplinary review to help guide clinical decision-making pending results of ongoing RCTs. Restricting dietary phosphate intake is frequently the first step in the management of hyperphosphatemia. Important considerations when proposing dietary restriction include the patient’s socioeconomic status, lifestyle, dietary preferences, comorbidities, and nutritional status. While dietary phosphate restriction may be a valid strategy in certain patients, serum phosphate reductions achieved solely by limiting dietary intake are modest and should be considered in conjunction with other interventions. Conventional dialysis is also typically insufficient; however phosphate removal may be augmented by increased frequency or duration of dialysis, or through enhanced methods such as hemodiafiltration. Phosphate binders have been shown to reduce absorption of dietary phosphate and lower serum phosphate levels. There are several phosphate binders available, and while they all lower phosphate levels to variable degrees, they differ with respect to their pill burden, potential to induce or exacerbate vascular calcification or ectopic calcification, tissue accumulation, safety, and tolerability. The widespread treatment of hyperphosphatemia requires convincing data from RCTs to ascertain whether lowering serum phosphate levels improves patient-important outcomes, as well as the optimal method and degree of phosphate control. In the interim, the decision and approach used to treat hyperphosphatemia should be based on the best available data, as well as patient needs and clinical judgment.

show abstract

Management of Hyperphosphatemia in End-Stage Renal Disease: A New Paradigm

Cited by 58 publications

References 99 publications

Safety and Efficacy of Tenapanor for Long-term Serum Phosphate Control in Maintenance Dialysis: A 52-Week Randomized Phase 3 Trial (PHREEDOM)

Safety and Efficacy of Tenapanor for Long-term Serum Phosphate Control in Maintenance Dialysis: A 52-Week Randomized Phase 3 Trial (PHREEDOM)

Pengelolaan Gangguan Mineral Tulang pada Penyakit Ginjal Kronik

Multidisciplinary Perspectives of Current Approaches and Clinical Gaps in the Management of Hyperphosphatemia

Contact Info

Product

Resources

About