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American Journal of Kidney Diseases :... Jul 2023Patients with chronic kidney disease (CKD), hyperkalemia (serum potassium [sK]>5.0 mEq/L), and hyperphosphatemia experience poor clinical outcomes. Patiromer, a...
RATIONALE & OBJECTIVE
Patients with chronic kidney disease (CKD), hyperkalemia (serum potassium [sK]>5.0 mEq/L), and hyperphosphatemia experience poor clinical outcomes. Patiromer, a potassium binder that uses calcium as the exchange ion, may also reduce serum phosphorus (sP). We characterized the effect of patiromer on sP in patients with CKD, hyperkalemia, and hyperphosphatemia.
STUDY DESIGN
A post hoc pooled analysis of individual-level data from the AMETHYST-DN, OPAL-HK, and TOURMALINE trials of patiromer.
SETTING & PARTICIPANTS
Patients with CKD and hyperkalemia.
EXPOSURE
Patients treated with patiromer (8.4-33.6 g/day).
OUTCOME
Mean changes from baseline in sP, sK, serum calcium (sCa2), and serum magnesium (sMg2) after 2 and 4 weeks of treatment.
ANALYTICAL APPROACH
Descriptive statistics to summarize pooled data on the study outcomes from the 3 studies.
RESULTS
We included 578 patients in the analysis. Of these participants, 86 patients (14.9%) had baseline hyperphosphatemia of whom 75.6% (65 of 86) had CKD stage 4/5 and 31.1% (153 of 492) with sP≤4.5mg/dL had CKD stage 4/5. Among the patients with elevated sP and sKat baseline, the mean±SD reduction in sP and sKafter 4 weeks of patiromer treatment was-0.62±1.09mg/dL and-0.71± 0.51 mEq/L, respectively. Additionally, the mean±SD reduction in sMgin these patients was -0.25±0.23mg/dL while sCaremained unchanged. Both sMgand sCaremained within the normal range. Patiromer was generally well tolerated, and no serious adverse events were considered related to patiromer.
LIMITATIONS
These were post hoc analyses, no placebo comparison was performed due to the design of the original studies, and the follow-up period was limited to 4 weeks.
CONCLUSIONS
Reductions in sP and sKto the normal range were observed after 2 weeks of patiromer treatment, and the reduction was sustained during 4 weeks of treatment among patients with non-dialysis-dependent CKD, hyperkalemia, and hyperphosphatemia. Future controlled trials are needed to establish if patiromer is useful to reduce both sKand sP in hyperkalemic patients with CKD and hyperphosphatemia.
Topics: Humans; Hyperkalemia; Hyperphosphatemia; Calcium; Potassium; Renal Insufficiency, Chronic; Phosphorus
PubMed: 36965827
DOI: 10.1053/j.ajkd.2023.01.444 -
Saudi Medical Journal Jan 2015Hyperphosphatemia is a major cause of morbidity and mortality in patients with chronic kidney disease. The association between hyperphosphatemia and increased risk of... (Review)
Review
Hyperphosphatemia is a major cause of morbidity and mortality in patients with chronic kidney disease. The association between hyperphosphatemia and increased risk of death from cardiovascular disease/vascular calcification has been well established for a long time. This review explores the new aspects of pathogenesis of vascular calcification, as demonstrated by recent advances showing a recognized regulating role of phosphorus in vascular smooth muscle cell calcification. This novel mechanism may help in finding a new pharmacological therapy to reduce, or prevent blood vessel calcification. Furthermore, recent experimental and clinical studies involved in the treatment of hyperphosphatemia are reviewed in this article.
Topics: Cardiovascular Diseases; Humans; Hyperphosphatemia; Parathyroid Hormone; Renal Insufficiency, Chronic; Risk Factors; Vascular Calcification
PubMed: 25629999
DOI: 10.15537/smj.2015.1.9843 -
ELife Mar 2022Elevations in plasma phosphate concentrations (hyperphosphatemia) occur in chronic kidney disease (CKD), in certain genetic disorders, and following the intake of a...
Elevations in plasma phosphate concentrations (hyperphosphatemia) occur in chronic kidney disease (CKD), in certain genetic disorders, and following the intake of a phosphate-rich diet. Whether hyperphosphatemia and/or associated changes in metabolic regulators, including elevations of fibroblast growth factor 23 (FGF23) directly contribute to specific complications of CKD is uncertain. Here, we report that similar to patients with CKD, mice with adenine-induced CKD develop inflammation, anemia, and skeletal muscle wasting. These complications are also observed in mice fed high phosphate diet even without CKD. Ablation of pathologic FGF23-FGFR4 signaling did not protect mice on an increased phosphate diet or mice with adenine-induced CKD from these sequelae. However, low phosphate diet ameliorated anemia and skeletal muscle wasting in a genetic mouse model of CKD. Our mechanistic in vitro studies indicate that phosphate elevations induce inflammatory signaling and increase hepcidin expression in hepatocytes, a potential causative link between hyperphosphatemia, anemia, and skeletal muscle dysfunction. Our study suggests that high phosphate intake, as caused by the consumption of processed food, may have harmful effects irrespective of pre-existing kidney injury, supporting not only the clinical utility of treating hyperphosphatemia in CKD patients but also arguing for limiting phosphate intake in healthy individuals.
Topics: Anemia; Animals; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Hyperphosphatemia; Inflammation; Mice; Muscle, Skeletal; Receptor, Fibroblast Growth Factor, Type 4
PubMed: 35302487
DOI: 10.7554/eLife.74782 -
Journal of Nephrology Apr 2022Hyperphosphatemia is a common complication in dialysis-dependent patients with chronic kidney disease. Most dialysis-dependent patients need oral phosphate binder... (Review)
Review
Hyperphosphatemia is a common complication in dialysis-dependent patients with chronic kidney disease. Most dialysis-dependent patients need oral phosphate binder therapy to control serum phosphorus concentrations. Most phosphate binders have a high daily pill burden, which may reduce treatment adherence and impair phosphorus control. Sucroferric oxyhydroxide is a potent iron-based phosphate binder approved for use in dialysis-dependent patients in 2013. A randomized controlled trial of sucroferric oxyhydroxide demonstrated its efficacy for reduction of serum phosphorus with a lower pill burden than sevelamer carbonate. Clinical trials carefully select patients, monitor adherence, and routinely titrate medications to a protocol-defined goal. Consequently, trials may not reflect real-world use of medications. Since its approval, we and others have performed retrospective and prospective analyses of sucroferric oxyhydroxide in real-world clinical practice in > 6400 hemodialysis and approximately 500 peritoneal dialysis patients in the USA and Europe. Consistent with the clinical trial data, real-world observational studies have demonstrated that sucroferric oxyhydroxide can effectively reduce serum phosphorus with a lower daily pill burden than most other phosphate binders. These studies have also shown sucroferric oxyhydroxide provides effective serum phosphorus control in different treatment settings, including as monotherapy in phosphate binder-naïve patients, in patients switching from other phosphate binders, or when used in combination with other phosphate binders. These observational studies indicate a favorable safety and tolerability profile, and minimal, if any, systemic iron absorption. This article reviews the key results from these observational studies of sucroferric oxyhydroxide and evaluates its role in the management of hyperphosphatemia in clinical practice.
Topics: Drug Combinations; Ferric Compounds; Humans; Hyperphosphatemia; Iron; Phosphates; Phosphorus; Prospective Studies; Randomized Controlled Trials as Topic; Renal Dialysis; Retrospective Studies; Sucrose
PubMed: 35138627
DOI: 10.1007/s40620-021-01241-5 -
Nephrology, Dialysis, Transplantation :... Feb 2016Phosphate binders are prescribed to chronic kidney disease (CKD) patients based on associations of serum phosphate concentrations with mortality and calcification,... (Review)
Review
Phosphate binders are prescribed to chronic kidney disease (CKD) patients based on associations of serum phosphate concentrations with mortality and calcification, experimental evidence for direct calcifying effects of phosphate on vascular smooth muscle tissue and the central importance of phosphate retention in CKD-mineral and bone disorder (CKD-MBD). Current knowledge regarding phosphate metabolism in CKD provides important insight into disease mechanisms and supports future clinical trials of phosphate binders in CKD patients to determine the impact of these medications on clinically relevant outcomes. The risks and benefits of phosphate binders cannot be inferred from association studies of serum phosphate concentrations, which are inconsistent and subject to confounding, animal-experimental data, which are based on conditions that differ from human disease, or physiological arguments, which are limited to known regulatory factors. Many interventions that targeted biochemical pathways suggested by association studies and suspected biological importance have yielded null or harmful results. Clinical trials of phosphate binders are of high clinical and scientific importance to nephrology. Demonstration of reduced rates of clinical disease in such trials could lead to important health benefits for CKD patients, whereas negative results would refocus efforts to understand and treat CKD-MBD. Clinical trials that employ highly practical or 'pragmatic' designs represent an optimal approach for determining the safety and effectiveness of phosphate binders in real-world settings. Absent clinical trial data, observational studies of phosphate binders in large CKD populations could provide important information regarding the benefits, risks and/or unintended side effects of these medications.
Topics: Humans; Hyperphosphatemia; Phosphates; Renal Insufficiency, Chronic
PubMed: 26681747
DOI: 10.1093/ndt/gfv406 -
Jornal Brasileiro de Nefrologia 2021
Topics: Humans; Hypercalcemia; Hyperphosphatemia; Phosphates; Renal Insufficiency, Chronic
PubMed: 34910797
DOI: 10.1590/2175-8239-JBN-2021-S105 -
Drugs Jun 2019Chronic kidney disease (CKD) is a major cause of morbidity and premature mortality and represents a significant global public health issue. Underlying this burden are... (Review)
Review
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.
Topics: Administration, Intravenous; Anemia, Iron-Deficiency; Cardiovascular Diseases; Chelating Agents; Clinical Trials as Topic; Ferric Compounds; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Hyperphosphatemia; Iron; Iron Overload; Phosphates; Renal Insufficiency, Chronic; Risk Factors; Treatment Outcome
PubMed: 31134521
DOI: 10.1007/s40265-019-01125-w -
Primary Care Jun 2008Disorders of mineral metabolism are common in both the office and hospital setting. The diagnosis can be simplified by remembering the target organs involved--intestine,... (Review)
Review
Disorders of mineral metabolism are common in both the office and hospital setting. The diagnosis can be simplified by remembering the target organs involved--intestine, kidney, and bone--and by assessing the presence of kidney disease, levels of parathyroid hormone, and vitamin D status. Although the list of possible causes for these derangements is long, most patients who have hypercalcemia have hyperparathyroidism or malignancy; those who have hypocalcemia, hypophosphatemia, and hypomagnesemia have reduced gastrointestinal absorption, and those who have hyperphosphatemia and hypermagnesemia have increased intake in the setting of kidney disease.
Topics: Calcium; Humans; Hypercalcemia; Hyperphosphatemia; Hypocalcemia; Hypophosphatemia; Magnesium; Metabolic Diseases; Phosphorus
PubMed: 18486714
DOI: 10.1016/j.pop.2008.01.007 -
Medicina (Kaunas, Lithuania) May 2023Hyperphosphatemia is a secondary disorder of chronic kidney disease that causes vascular calcifications and bone-mineral disorders. As per the US Centers for Disease... (Review)
Review
Hyperphosphatemia is a secondary disorder of chronic kidney disease that causes vascular calcifications and bone-mineral disorders. As per the US Centers for Disease Control and Prevention, renal damage requires first-priority medical attention for patients with COVID-19; according to a Johns Hopkins Medicine report, SARS-CoV-2 can cause renal damage. Therefore, addressing the research inputs required to manage hyperphosphatemia is currently in great demand. This review highlights research inputs, such as defects in the diagnosis of hyperphosphatemia, flaws in understanding the mechanisms associated with understudied tertiary toxicities, less cited adverse effects of phosphate binders that question their use in the market, socioeconomic challenges of renal treatment and public awareness regarding the management of a phosphate-controlled diet, novel biological approaches (synbiotics) to prevent hyperphosphatemia as safer strategies with potential additional health benefits, and future functional food formulations to enhance the quality of life. We have not only introduced our contributions to emphasise the hidden aspects and research gaps in comprehending hyperphosphatemia but also suggested new research areas to strengthen approaches to prevent hyperphosphatemia in the near future.
Topics: Humans; Hyperphosphatemia; Quality of Life; Renal Dialysis; COVID-19; SARS-CoV-2; Renal Insufficiency, Chronic; Phosphates
PubMed: 37241191
DOI: 10.3390/medicina59050959 -
Frontiers in Endocrinology 2020Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare and disabling disorder of fibroblast growth factor 23 (FGF23) deficiency or resistance. The disorder is... (Review)
Review
Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare and disabling disorder of fibroblast growth factor 23 (FGF23) deficiency or resistance. The disorder is manifest by hyperphosphatemia, inappropriately increased tubular reabsorption of phosphate and 1,25-dihydroxy-Vitamin D, and ectopic calcifications. HFTC has been associated with autosomal recessive pathogenic variants in: (1) the gene encoding FGF23; (2) , which encodes a protein responsible for FGF23 glycosylation; and (3) , the gene encoding KLOTHO, a critical co-receptor for FGF23 signaling. An acquired autoimmune form of hyperphosphatemic tumoral calcinosis has also been reported. Periarticular tumoral calcinosis is the primary cause of disability in HFTC, leading to pain, reduced range-of-motion, and impaired physical function. Inflammatory disease is also prominent, including diaphysitis with cortical hyperostosis. Multiple treatment strategies have attempted to manage blood phosphate, reduce pain and inflammation, and address calcifications and their complications. Unfortunately, efficacy data are limited to case reports and small cohorts, and no clearly effective therapies have been identified. The purpose of this review is to provide a background on pathogenesis and clinical presentation in HFTC, discuss current approaches to clinical management, and outline critical areas of need for future research.
Topics: Calcinosis; Disease Management; Fibroblast Growth Factor-23; Humans; Hyperostosis, Cortical, Congenital; Hyperphosphatemia
PubMed: 32457699
DOI: 10.3389/fendo.2020.00293