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Reumatismo Jun 2024In this case report, a novel N-acetylgalactosaminyltransferase 3 homozygous mutation (c.782 G>A; p.R261Q) associated with hyperphosphatemic familial tumoral...
In this case report, a novel N-acetylgalactosaminyltransferase 3 homozygous mutation (c.782 G>A; p.R261Q) associated with hyperphosphatemic familial tumoral calcinosis/hyperostosis-hyperphosphatemia syndrome is described. The patient had elbow, pelvis, and lower limb pain and a hard mass in the hip and olecranon regions. Increased levels of inorganic phosphorus (Pi) and C-reactive protein were observed. After treating the patient with conventional drugs, we tested denosumab, which reduced but did not normalize the Pi.
Topics: Humans; Hyperphosphatemia; Denosumab; Calcinosis; N-Acetylgalactosaminyltransferases; Polypeptide N-acetylgalactosaminyltransferase; Bone Density Conservation Agents; Female; Mutation; Male; Hyperostosis, Cortical, Congenital
PubMed: 38916164
DOI: 10.4081/reumatismo.2024.1687 -
Journal of Bone and Mineral Research :... Jun 2024
PubMed: 38905292
DOI: 10.1093/jbmr/zjae098 -
Journal of Renal Care Jun 2024Patients with dialysis-dependent kidney failure and treated for hyperphosphatemia receive a combination of dietary advice, phosphate binders and prolonged dialysis....
BACKGROUND
Patients with dialysis-dependent kidney failure and treated for hyperphosphatemia receive a combination of dietary advice, phosphate binders and prolonged dialysis. However, research focusing on the challenges patients meet in everyday life addressing diet and medication is sparse.
OBJECTIVE
The objective of this study is to explore the everyday challenges patients meet when following treatment for hyperphosphatemia.
DESIGN
Interpretive description was the methodological approach. Semistructured in-depth interviews were employed to study the challenges patients experienced. Data were analysed using Braun and Clarke's reflexive thematic analysis.
PARTICIPANTS
Patients (n = 14) receiving haemodialysis and treated for hyperphosphatemia from two hospitals in Southern Denmark.
FINDINGS
The analysis resulted in one over-arching theme; separation in social gatherings and two subthemes; a new social code, and my food and their food. Participants experienced difficulty integrating diet and medication in daily life, especially at social gatherings. They felt separated from others when special menus were provided for them or struggled when choosing between high and low phosphate-containing food. A new awareness of self and others arose, especially their position among families and friends, and how they presented themselves and their social identity to others. Likewise, a new social code manifested itself, which was difficult to accept. Most participants experienced that diet and medication were accompanied by a moral responsibility of whether to accept prepared food with high phosphorus content or not, which affected commensality.
CONCLUSION
Patients were often nonadherent to hyperphosphatemia treatment at social gatherings. Hyperphosphatemia treatment led to new social identities with new social codes, which patients found difficult to accept.
PubMed: 38899774
DOI: 10.1111/jorc.12506 -
Therapeutic Apheresis and Dialysis :... Jun 2024Chronic kidney disease (CKD) has emerged as one of the leading noncommunicable diseases affecting >10% of the population worldwide. Bone and mineral disorders are a... (Review)
Review
Chronic kidney disease (CKD) has emerged as one of the leading noncommunicable diseases affecting >10% of the population worldwide. Bone and mineral disorders are a common complication among patients with CKD resulting in a poor life quality, high fracture risk, increased morbidity and cardiovascular mortality. According to Kidney Disease: Improving Global Outcomes, renal osteodystrophy refers to changes in bone morphology found in bone biopsy, whereas CKD-mineral and bone disorder (CKD-MBD) defines a complex of disturbances including biochemical and hormonal alterations, disorders of bone and mineral metabolism and extraskeletal calcification. As a result, the management of CKD-MBD should focus on the aforementioned parameters, including the treatment of hyperphosphatemia, hypocalcemia, abnormal PTH and vitamin D levels. Regarding the bone fragility fractures, osteoporosis and renal osteodystrophy, which constitute the bone component of CKD-MBD, anti-osteoporotic agents constitute the mainstay of treatment. However, a thorough elucidation of the CKD-MBD pathogenesis is crucial for the ideal personalized treatment approach. In this paper, we review the pathology and management of CKD-MBD based on the current literature with special attention to recent advances.
PubMed: 38898685
DOI: 10.1111/1744-9987.14177 -
BMC Nephrology Jun 2024Hyperphosphatemia is associated with increased morbidity and mortality in patients with end-stage kidney disease (ESKD). Whereas clinical and observational studies have...
Management of serum phosphorus over a 1-year follow-up in patients on peritoneal dialysis prescribed sucroferric oxyhydroxide as part of routine care: a retrospective analysis.
BACKGROUND
Hyperphosphatemia is associated with increased morbidity and mortality in patients with end-stage kidney disease (ESKD). Whereas clinical and observational studies have demonstrated the effectiveness of sucroferric oxyhydroxide (SO) in controlling serum phosphorus (sP) in ESKD, data on the real-world impact of switching to SO in patients on peritoneal dialysis (PD) are limited. In this retrospective database analysis, we examine the impact of SO on sP management over a 1-year period among PD patients prescribed SO as part of routine clinical care.
METHODS
We analyzed de-identified data from adults on PD in Fresenius Kidney Care clinics who were prescribed SO monotherapy between May 2018 and December 2019 as part of routine clinical management. Changes from baseline in sP levels, phosphate binder (PB) pill burden, and laboratory parameters were evaluated during the four consecutive 91-day intervals of SO treatment.
RESULTS
The mean age of the 402 patients who completed 1 year of SO was 55.2 years at baseline, and they had been on PD for an average of 19.9 months. SO was initiated with no baseline PB recorded in 36.1% of patients, whereas the remaining 257 patients were switched to SO from sevelamer (39.7%), calcium acetate (30.4%), lanthanum (1.2%), ferric citrate (14.0%), or more than one PB (14.8%). Mean sP at baseline was 6.26 mg/dL. After being prescribed SO, the percentage of patients achieving sP ≤ 5.5 mg/dL increased from 32.1% (baseline) to 46.5-54.0% during the 1-year follow-up, whereas the mean number of PB pills taken per day decreased from 7.7 at baseline (among patients on a baseline PB) to 4.6 to 5.4. Serum phosphorus and PB pill burden decreased regardless of changes in residual kidney function over the 12-month period. Similar results were observed for the full cohort (976 patients who either completed or discontinued SO during the 1-year follow-up).
CONCLUSIONS
Patients on PD who were prescribed SO as part of routine care for phosphorus management experienced significant reductions in SP and PB pills per day and improvements in sP target achievement, suggesting the effectiveness of SO on SP management with a concurrent reduction in pill burden.
Topics: Humans; Middle Aged; Male; Retrospective Studies; Female; Ferric Compounds; Phosphorus; Peritoneal Dialysis; Hyperphosphatemia; Kidney Failure, Chronic; Follow-Up Studies; Sucrose; Drug Combinations; Aged; Adult
PubMed: 38886636
DOI: 10.1186/s12882-024-03633-8 -
Pediatric Nephrology (Berlin, Germany) Jun 2024Phosphate is essential for numerous biological processes, and serum levels are tightly regulated to accomplish these functions. The regulation of serum phosphate in a...
Phosphate is essential for numerous biological processes, and serum levels are tightly regulated to accomplish these functions. The regulation of serum phosphate in a narrow physiological range is a well-orchestrated process and involves the gastrointestinal (GI) tract, bone, kidneys, and several hormones, namely, parathyroid hormone, fibroblast growth factor 23 (FGF23), and 1,25-dihydroxyvitamin D (1,25 Vitamin D). Although primarily synthesized in the bone, FGF23, an endocrine FGF, acts on the kidney to regulate phosphate and Vitamin D homeostasis by causing phosphaturia and reduced levels of 1,25 Vitamin D. Recent studies have highlighted the complex regulation of FGF23 including transcriptional and post-translational modification and kidney-bone cross talk. Understanding FGF23 biology has led to the identification of novel therapeutic agents to treat diseases that disrupt phosphate metabolism secondary to FGF23. The focus of this review is to provide an overview of phosphate homeostasis, FGF23 biology, and the role of FGF23 in phosphate balance.
PubMed: 38874635
DOI: 10.1007/s00467-024-06395-5 -
ESMO Open Jun 2024Fibroblast growth factor receptor 2 (FGFR2) fusions and rearrangements are clinically actionable genomic alterations in cholangiocarcinoma (CCA). Pemigatinib is a...
BACKGROUND
Fibroblast growth factor receptor 2 (FGFR2) fusions and rearrangements are clinically actionable genomic alterations in cholangiocarcinoma (CCA). Pemigatinib is a selective, potent, oral inhibitor of FGFR1-3 and demonstrated efficacy in patients with previously treated, advanced/metastatic CCA with FGFR2 alterations in FIGHT-202 (NCT02924376). We report final outcomes from the extended follow-up period.
PATIENTS AND METHODS
The multicenter, open-label, single-arm, phase II FIGHT-202 study enrolled patients ≥18 years old with previously treated advanced/metastatic CCA with FGFR2 fusions or rearrangements (cohort A), other FGF/FGFR alterations (cohort B), or no FGF/FGFR alterations (cohort C). Patients received once-daily oral pemigatinib 13.5 mg in 21-day cycles (2 weeks on, 1 week off) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) in cohort A assessed as per RECIST v1.1 by an independent review committee; secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
RESULTS
FIGHT-202 enrolled 147 patients (cohort A, 108; cohort B, 20; cohort C, 17; unconfirmed FGF/FGFR alterations, 2). By final analysis, 145 (98.6%) had discontinued treatment due to progressive disease (71.4%), withdrawal by patient (8.2%), or adverse events (AEs; 6.8%). Median follow-up was 45.4 months. The ORR in cohort A was 37.0% (95% confidence interval 27.9% to 46.9%); complete and partial responses were observed in 3 and 37 patients, respectively. Median DOR was 9.1 (6.0-14.5) months; median PFS and OS were 7.0 (6.1-10.5) months and 17.5 (14.4-22.9) months, respectively. The most common treatment-emergent AEs (TEAEs) were hyperphosphatemia (58.5%), alopecia (49.7%), and diarrhea (47.6%). Overall, 15 (10.2%) patients experienced TEAEs leading to pemigatinib discontinuation; intestinal obstruction and acute kidney injury (n = 2 each) occurred most frequently.
CONCLUSIONS
Pemigatinib demonstrated durable response and prolonged OS with manageable AEs in patients with previously treated, advanced/metastatic CCA with FGFR2 alterations in the extended follow-up period of FIGHT-202.
Topics: Humans; Cholangiocarcinoma; Male; Female; Middle Aged; Aged; Adult; Bile Duct Neoplasms; Pyrimidines; Receptor, Fibroblast Growth Factor, Type 2; Aged, 80 and over; Morpholines; Pyrroles
PubMed: 38838500
DOI: 10.1016/j.esmoop.2024.103488 -
International Journal of Nephrology and... 2024Hyperphosphataemia represents a significant challenge in the management of chronic kidney disease, exerting a pronounced influence on the pathogenesis of cardiovascular... (Review)
Review
Hyperphosphataemia represents a significant challenge in the management of chronic kidney disease, exerting a pronounced influence on the pathogenesis of cardiovascular complications and mineral bone disorders. Traditional approaches to address hyperphosphataemia involve implementing dietary phosphate restrictions, administering phosphate binders, and, in cases of end-stage renal disease, resorting to dialysis. Unfortunately, these interventions frequently prove inadequate in maintaining phosphate levels within recommended ranges. Additionally, commonly employed pharmacological agents are not immune to eliciting adverse events, thereby limiting their prescription and therapeutic adherence. There is a growing focus on exploring novel therapeutic strategies in this context. The current discussion centres on tenapanor, a pharmacological agent predominantly acting as a selective inhibitor of sodium/hydrogen exchanger isoform 3 (NHE3). Its mechanism of action involves modulating tight junctions, resulting in reduced sodium absorption and intestinal paracellular permeability to phosphate. Furthermore, tenapanor downregulates sodium-dependent phosphate 2b transport protein (NaPi2b) expression, thereby impeding active transcellular phosphate transport. Clinical trials have elucidated the efficacy and safety profile of tenapanor. This evidence hints at a potential paradigm shift in the management of hyperphosphataemia. However, the burgeoning optimism surrounding tenapanor warrants tempered enthusiasm, as further research remains indispensable. The imperative lies in meticulously delineating its efficacy and safety contours within the crucible of clinical practice. In this review, we synthesize the intricate interplay between hyperphosphataemia and Chronic Kidney Disease-Mineral Bone Disorder, and we discuss the existing pharmacological interventions for hyperphosphataemia and explore emerging treatment paradigms that offer novel perspectives in managing elevated phosphate levels in CKD patients.
PubMed: 38831770
DOI: 10.2147/IJNRD.S385826 -
PloS One 2024Hyperphosphatemia and hyperparathyroidism are common in end-stage kidney disease and are associated with poor outcomes. In addition to adequate dialysis, medications are...
The impact of accessibility to non-calcium-based phosphate binders and calcimimetics on mineral outcomes in patients receiving maintenance hemodialysis: A 10-year retrospective analysis of real-world data.
INTRODUCTION
Hyperphosphatemia and hyperparathyroidism are common in end-stage kidney disease and are associated with poor outcomes. In addition to adequate dialysis, medications are usually required for optimum control of serum phosphate and parathyroid hormone (PTH) levels. The use of calcium-based phosphate binders (CBPBs) and active vitamin D is associated with an increase in serum calcium and worsening vascular calcification. To overcome these limitations, non-calcium-based phosphate binders (NCBPBs) and calcimimetics have been developed. However, the coverage for these new medications remains limited in several parts of the world due to the lack of patient-level outcome data and cost. The present study examined the differences in mineral outcomes between two main categories of healthcare programs that provided different coverage for medications used to control mineral and bone disorders (MBD). The Social Security/Universal Coverage (SS/UC) program covered only CBPBs and active vitamin D, whereas the Civil Servant/State Enterprise (CS/SE) program provided coverage of CBPBs, active vitamin D, NCBPBs, and calcimimetics.
METHODS
This 10-year retrospective cohort study examined the differences in mineral outcomes between two healthcare programs in maintenance hemodialysis patients. The differences in serum calcium, phosphate, and PTH levels, as well as the aortic arch calcification score, were analyzed according to dialysis vintage by linear mixed-effects regression analyses. The difference in the composite outcome of severe hyperparathyroidism and parathyroidectomy was analyzed by the Cox-proportional hazard regression model.
RESULTS
714 patients were included in the analyses (full cohort). Of these patients, 563 required at least one type of medication to control MBD (MBD medication subgroup). Serum calcium, phosphate, and the proportions of patients with hypercalcemia and hyperphosphatemia were substantially higher in the SS/UC group compared with the CS/SE group after appropriate adjustments for confounders in both the full cohort and the MBD medication subgroup. These findings were confirmed in propensity-score matched analyses. Higher parathyroid hormone levels and a higher rate of the composite endpoint of severe hyperparathyroidism and parathyroidectomy were also observed in the SS/UC group. A more rapid progression of aortic arch calcification was suggested in the SS/UC group, but between-group changes were not significant.
CONCLUSION
Patients under the healthcare program that did not cover the use of NCBPBs and calcimimetics showed higher serum calcium and phosphate levels and a more rapid progression of hyperparathyroidism. The difference in the progression of vascular calcification could not be confirmed in the present study.
Topics: Humans; Renal Dialysis; Male; Female; Retrospective Studies; Middle Aged; Calcimimetic Agents; Hyperphosphatemia; Calcium; Aged; Phosphates; Kidney Failure, Chronic; Parathyroid Hormone; Vitamin D; Chelating Agents
PubMed: 38820324
DOI: 10.1371/journal.pone.0304649 -
Cureus Apr 2024Rhabdomyolysis, a medical condition caused by the destruction of striated muscle fibers, can have many etiologies, with the most common one being traumatic etiologies,... (Review)
Review
Rhabdomyolysis, a medical condition caused by the destruction of striated muscle fibers, can have many etiologies, with the most common one being traumatic etiologies, that is, crushing injuries, heavy exertion, and being trapped under rubbles, and so forth. Rhabdomyolysis causes many complications, including acute kidney injury and different electrolyte imbalances, which later can cause cardiac dysrhythmia and even death as a result. This systematic review and meta-analysis investigate the incidence of imbalances of four important electrolytes among patients diagnosed with traumatic rhabdomyolysis. PubMed, Scopus, Web of Science, and Embase databases were searched for any article related to traumatic rhabdomyolysis using keywords related to the topic of our study, excluding case studies and case series. Relevant data were extracted from the included articles, and finally, a meta-analysis was performed on them to calculate the pooled incidence of each electrolyte imbalance. Collectively, 32 articles were included in our study (through the database and citation checking). The following were the pooled incidence of each electrolyte imbalance: hyperkalemia, 31% (95%CI 22%-41%); hypokalemia, 10% (95%CI 4%-17%); hypernatremia, 3% (95%CI 0%-8%); hyponatremia, 23% (95%CI 7%-44%); hypercalcemia, 0% (95%CI 0%-1%); hypocalcemia, 57% (95%CI: 22%-88%); hyperphosphatemia, 33% (95%CI 11%-59%); hypophosphatemia, 4% (95%CI 0%-16%). According to the meta-analyses, the rate of hyperkalemia, hyponatremia, hypocalcemia, and hyperphosphatemia is higher than their counterpart in patients diagnosed with traumatic rhabdomyolysis.
PubMed: 38817473
DOI: 10.7759/cureus.59333