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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.

We describe a case of severe symptomatic tumoral calcinosis in a young man with end stage kidney disease secondary to antineutrophil cytoplasmic antibodies‐associated vasculitis with longstanding hyperphosphatemia and secondary hyperparathyroidism while on several years of peritoneal dialysis. The use of intravenous sodium thiosulfate, optimization of clearance with five times weekly hemodialysis, and intradialytic nutrition were used to treat his inoperable tumoral calcinosis. Over 3 months, he had a remarkable reduction in the size of his calcified masses and associated improvement in pain. He subsequently received a living donor kidney transplant. [ABSTRACT FROM AUTHOR]

Background VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part Phase 2 study evaluated the tolerability, safety and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD). Methods In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50 and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50 or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus. Results The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during Weeks 1–2 of treatment). Most gastrointestinal disorders resolved without intervention, and none was serious. In Part 1, serum phosphorus significantly improved (mean change −2.0 mg/dL; 95% confidence interval −2.7, −1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day [mean change −1.6 (−2.2, −1.0), −1.8 (−2.4, −1.2) and −1.4 (−2.2, −0.5) mg/dL, respectively]. In both parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation. Conclusion VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. Clinical Trial registration number NCT04551300 [ABSTRACT FROM AUTHOR]

Simple Summary: The present study evaluated the literature investigating the potential differences in the quantitative calcium (Ca), phosphorus (P) and magnesium (Mg) metabolism in horses and ponies and between "organic" (plant origin) and "inorganic" mineral sources (mineral salts). For P sources, the "inorganic" P salts were also differentiated according to water solubility. The present study found unequivocal differences in apparent Mg digestibility between horses and ponies, whereby horses require a greater amount of this nutrient. "Organic" Ca was shown to have a higher bioavailability than "inorganic" Ca. When considering P sources, the distinction was made between water-soluble "inorganic" sources and all other sources. The water-soluble sources were highly available, and they increased serum P levels and renal P excretion, which presents a potential health risk. The aims of the present meta-analysis were (i) to re-evaluate the factorially calculated Ca, P and Mg requirements to replace endogenous faecal losses, taking new data into account, (ii) to identify potential differences between horses and ponies regarding requirements, apparent digestibility, serum levels and renal excretion of Ca, P and Mg and (iii) to investigate the influence of mineral sources, i.e., "inorganic" sources from added mineral salts and "organic" sources from feed plants. For P, the water solubility of "inorganic" sources was taken into consideration. Data on the aforementioned parameters from 42 studies were plotted against intake, similar to the Lucas test for true digestibility and faecal endogenous losses. Within specific intake ranges, data were compared using t-tests and an ANOVA, followed by Holm–Sidak post hoc tests. Ponies had lower endogenous faecal Mg losses than horses. Consequently, apparent Mg digestibility was higher in ponies. Factorial calculations of Mg requirements to replace faecal losses showed that ponies needed approximately half of the current recommended amount, while horses required 1.9 times the amount currently recommended by Kienzle and Burger. The overall mean matched previous recommendations. For Ca, there was no discernible difference between ponies and horses. True Ca digestibility calculated by the Lucas test was higher and endogenous losses were lower when "organic" Ca was fed as opposed to when "inorganic" sources were used. The resulting factorial calculations of the requirements to replace faecal losses were close to current recommendations for "organic" Ca. For "inorganic" sources, however, the new calculations were below the recommended level. For P, there were no discernible differences between horses and ponies. There were also no clear effects of "inorganic" or "organic" P sources. The water solubility of "inorganic" sources was the key factor determining P metabolism. Water-soluble P sources exhibited higher true and apparent digestibility. The intake of these P sources led to hyperphosphatemia and hyperphosphaturia, even at low intakes. In other species, this has been shown to pose a health risk. Therefore, it is recommended to avoid the use of highly water-soluble "inorganic" P sources in horses and ponies. Given the lower digestibility of insoluble P sources, the factorially calculated P requirements for such sources are higher than the current recommendations. [ABSTRACT FROM AUTHOR]

Aim: This research aimed to explore the serum levels of solute carrier family 7 member 11 (SLC7A11) in patients with maintenance peritoneal dialysis (MPD) and its correlation with vascular calcification (VC) and clinical results. Methods: This present prospective observational cohort study enrolled 189 patients with MPD who were undergoing regular peritoneal dialysis for over 3 months in our hospital from February 2020 to July 2022. The abdominal aortic calcification score was used to assess the VC condition of MPD patients. The serum SLC7A11, interleukin (IL)‐6, IL‐1β and C‐reactive protein levels were measured by enzyme‐linked immunosorbent assay (ELISA). Demographic and clinical statistics were collected. All patients were followed up for 1 year and the overall survival time (OS) of all patients were recorded. All data used SPSS 18.0 for statistical analyses. Results: Patients with moderate/severe calcification in MPD had a longer duration of dialysis, higher serum levels of phosphate (P) and calcium (Ca) and lower serum levels of SLC7A11. Spearman's analysis revealed a negative correlation between serum SLC7A11 levels and the levels of P, Ca and IL‐1β. Additionally, we observed an association between serum SLC7A11 levels and clinical prognosis as well as the extent of VC in MPD patients. Multivariate logistic regression analysis indicated that dialysis duration, SLC7A11, and P were risk factors for VC in MPD patients. Conclusion: The serum SLC7A11 levels decreased remarkably in MPD patients with moderate/severe calcification. This study may provide new targets and comprehensive approach to cardiovascular protection in patients with chronic kidney disease. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review is a critical analysis of treatment results obtained in clinical trials conducted in patients with chronic kidney disease (CKD) and secondary hyperparathyroidism (SHPT), hyperphosphatemia, or both. Recent Findings: Patients with CKD have a high mortality rate. The disorder of mineral and bone metabolism (CKD-MBD), which is commonly present in these patients, is associated with adverse outcomes, including cardiovascular events and mortality. Clinical trials aimed at improving these outcomes by modifying CKD-MBD associated factors have most often resulted in disappointing results. The complexity of CKD-MBD, where many players are closely interconnected, might explain these negative findings. Summary: We first present an historical perspective of current knowledge in the field of CKD-MBD and then examine potential flaws of past and ongoing clinical trials targeting SHPT and hyperphosphatemia respectively in patients with CKD. [ABSTRACT FROM AUTHOR]

Background: Hyperphosphatemia has been emphasized to be a significant risk factor for vascular calcification in CKD patients. This study aims to investigate the effect of magnesium supplementation on the reduction of phosphate levels and carotid intima media thickness in children as predictor on vascular calcification with CKD and hyperphosphatemia, compared to a placebo. Methods: A randomized, double-blind, placebo-controlled trial was conducted at Pediatric Ward and Outpatient Clinic of Pediatric Nephrology in our setting during October-March 2023. We compared oral magnesium supplementation (6 mg/kg body weight/day for two months) with a placebo in children with CKD and hyperphosphatemia (ages 1-18 years old). Patients who were on dialysis and had serum magnesium levels of <1.6 mg/dL and >2.4 mg/dL, and were allergic to magnesium supplementation were excluded. A paired T-test and the Wilcoxon signed-rank test were used for statistical analysis. Results: We collected 25 children in the experimental group and 25 children in the placebo group. Phosphate levels were decreased in both the magnesium supplementation and placebo groups (6.1 ± 0.79 to 6.0 ± 0.63 mg/dL; p-value = 0.852 and 6.01 ± 0.55 to 5.8 ± 0.64 mg/dL; p-value=0.365). However, when compared between groups, the reductions were not significantly different (0.1 vs 0.21; p-value=0.935). A significant improvement was found in carotid intima media thickness in both groups (0.05±0.01 to 0.05±0.01; p-value=0.000 and 0.05±0.01 to 0.05±0.01; p-value=0.000), and the reductions were significantly different (0.01 vs 0.01; p-value=0.000). Conclusion: Magnesium supplements have considerably lower phosphate levels and significantly reduced the thickness on carotid intima media in children with CKD and hyperphosphatemia. [ABSTRACT FROM AUTHOR]

Chronic kidney disease mineral bone disorder (CKD-MBD) is a complex clinical syndrome responsible for the accelerated cardiovascular mortality seen in individuals afflicted with CKD. Current approaches to therapy have failed to improve clinical outcomes adequately, likely due to targeting surrogate biochemical parameters as articulated by the guideline developer, Kidney Disease: Improving Global Outcomes (KDIGO). We hypothesized that using a Systems Biology Approach combining machine learning with mathematical modeling, we could test a novel approach to therapy targeting the abnormal movement of mineral out of bone and into soft tissue that is characteristic of CKD-MBD. The mathematical model describes the movement of calcium and phosphate between body compartments in response to standard therapeutic agents. The machine-learning technique we applied is reinforcement learning (RL). We compared calcium, phosphate, parathyroid hormone (PTH), and mineral movement out of bone and into soft tissue under four scenarios: standard approach (KDIGO), achievement of KDIGO guidelines using RL (RLKDIGO), targeting abnormal mineral flux (RLFLUX), and combining achievement of KDIGO guidelines with minimization of abnormal mineral flux (RLKDIGOFLUX). We demonstrate through simulations that explicitly targeting abnormal mineral flux significantly decreases abnormal mineral movement compared with standard approach while achieving acceptable biochemical outcomes. These investigations highlight the limitations of current therapeutic targets, primarily secondary hyperparathyroidism, and emphasize the central role of deranged phosphate homeostasis in the genesis of the CKD-MBD syndrome. NEW & NOTEWORTHY: Artificial intelligence is a powerful tool for exploration of complex processes but application to clinical syndromes is challenging. Using a mathematical model describing the movement of calcium and phosphate between body compartments combined with machine learning, we show the feasibility of testing alternative goals of therapy for Chronic Kidney Disease Mineral Bone Disorder while maintaining acceptable biochemical outcomes. These simulations demonstrate the potential for using this platform to generate and test hypotheses in silico rapidly, inexpensively, and safely. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is associated with various pathologic changes, including elevations in serum phosphate levels (hyperphosphatemia), vascular calcification, and skeletal muscle atrophy. Elevated phosphate can damage vascular smooth muscle cells and cause vascular calcification. Here, we determined whether high phosphate can also affect skeletal muscle cells and whether hyperphosphatemia, in the context of CKD or by itself, is associated with skeletal muscle atrophy. As models of hyperphosphatemia with CKD, we studied mice receiving an adenine-rich diet for 14 weeks and mice with deletion of Collagen 4a3 (Col4a3−/−). As models of hyperphosphatemia without CKD, we analyzed mice receiving a high-phosphate diet for three and six months as well as a genetic model for klotho deficiency (kl/kl). We found that adenine, Col4a3−/−, and kl/kl mice have reduced skeletal muscle mass and function and develop atrophy. Mice on a high-phosphate diet for six months also had lower skeletal muscle mass and function but no significant signs of atrophy, indicating less severe damage compared with the other three models. To determine the potential direct actions of phosphate on skeletal muscle, we cultured primary mouse myotubes in high phosphate concentrations, and we detected the induction of atrophy. We conclude that in experimental mouse models, hyperphosphatemia is sufficient to induce skeletal muscle atrophy and that, among various other factors, elevated phosphate levels might contribute to skeletal muscle injury in CKD. [ABSTRACT FROM AUTHOR]

Vascular calcification is quite common in patients with end-stage chronic kidney disease and is a major trigger for cardiovascular complications in these patients. These complications significantly impact the survival rate and long-term prognosis of individuals with chronic kidney disease. Numerous studies have demonstrated that the development of vascular calcification involves various pathophysiological mechanisms, with the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) being of utmost importance. High phosphate levels, bone morphogenetic protein 2 (BMP2), and runt-related transcription factor 2 (RUNX2) play crucial roles in the osteogenic transdifferentiation process of VSMCs. This article primarily reviews the molecular mechanisms by which high phosphate, BMP2, and RUNX2 regulate vascular calcification secondary to chronic kidney disease, and discusses the complex interactions among these factors and their impact on the progression of vascular calcification. The insights provided here aim to offer new perspectives for future research on the phenotypic switching and osteogenic transdifferentiation of VSMCs, as well as to aid in optimizing clinical treatment strategies for this condition, bearing significant clinical and scientific implications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: There was limited research on the epidemiology of hyperphosphatemia in early-stage chronic kidney disease (CKD) patients. We aimed to explore the clinical characteristics and prognostic value of hyperphosphatemia in patients with CKD stages 1–2. Methods: We enrolled adult patients with CKD stages 1–2 from 24 regional central hospitals across China. Hyperphosphatemia was defined as a serum phosphate level exceeding 1.45 mmol/L. The study outcomes included all-cause and cardiovascular (CV) mortality. Cox proportional hazard models were used to investigate the association of hyperphosphatemia with all-cause and CV mortality. Results: Among 99,266 patients with CKD stages 1–2 across China, the prevalence of hyperphosphatemia was 8.3%. The prevalence of hyperphosphatemia was increased with the level of urinary protein and was higher in younger and female patients. Among 63,121 patients with survival information, during a median of 5.2 years follow-up period, there were 436 (8.0%) and 4,695 (8.1%) deaths in those with and without hyperphosphatemia, respectively. After adjusting for potential confounders, compared with patients without hyperphosphatemia, patients with hyperphosphatemia were associated with a higher risk of all-cause mortality (hazard ratio: 1.28, 95% CI: 1.16–1.41). Although nearly 60.3% of hyperphosphatemia could be relieved without phosphate-lowering drug therapy among patients with CKD stages 1–2, transient hyperphosphatemia was also associated with an increased risk of all-cause mortality (p = 0.048). Conclusions: Hyperphosphatemia was not rare in patients with CKD stages 1–2 and was associated with an increased risk of mortality. Clinicians should closely monitor serum phosphorus levels in patients with CKD, even in those with normal kidney function.

Abstract Background Data is limited on the prevalence of hypophosphatemia in general hospitalized patients, and its association with length of hospital stay (LOS) and mortality remained unclear. We aimed to investigate the prevalence of admission phosphate abnormality and the association between serum phosphate level and length of hospital stay and all-cause mortality in adult patients. Methods This was a multi-center retrospective study based on real-world data. Participants were classified into five groups according to serum phosphate level (inorganic phosphorus, iP) within 48 h after admission: G1, iP

Abstract 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.

Background: Clinical evidence suggests an association between phosphate concentrations in aqueous humor and the risk of intraocular lens (IOL) calcification. To test this hypothesis the influence of different phosphate concentrations on IOL calcification was evaluated in an in vitro electrophoresis model. Methods: 20 IOLs of two hydrophilic IOL models (CT Spheris 204, Zeiss; Lentis L-313, Oculentis) and one hydrophobic control IOL model (Clareon CNA0T0, Alcon) were exposed to physiologic and elevated phosphate concentrations, similar to diabetic aqueous humor. IOL calcification was analyzed by alizarin red staining, von Kossa staining, scanning electron microscopy, energy dispersive x-ray spectroscopy and transmission electron microscopy with electron diffraction. Results: Higher phosphate concentrations were associated with IOL calcification. Analyses of IOL surfaces and cross-sections documented calcification in no CT Spheris and 4 Lentis IOLs following exposure to 10 mM Na2HPO4, compared with 7 and 11 positive analyses following exposure to 14 mM Na2HPO4, respectively. Furthermore, a clear association between IOL calcification and the duration of electrophoresis was demonstrated, confirming increased phosphate concentrations and duration of exposure as risk factors of IOL calcification. Conclusions: Findings suggest that higher phosphate concentrations in aqueous humor, as seen in diabetic patients, contribute to an increased IOL calcification risk, potentially explaining clinical observations showing an increased risk of IOL calcification in patients with diabetes. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion With age, lungs undergo typical changes that lead to a deterioration of respiratory function. Our aim was to assess the role of age‐associated hyperphosphatemia in these changes.We used C57BL6 mice to study an ageing model in vivo and human lung fibroblasts were treated with a phosphate donor, beta‐glycerophosphate (BGP), to explore mechanisms involved. Respiratory function was registered with a double chamber plethysmograph. Lung structure was analysed by different staining, phosphate and cytokines levels by colorimeric kits, expression of fibrosis, inflammation and ET‐1 system by western blot or RT‐PCR.Old mice showed hyperphosphatemia, along with lung fibrosis, loss of elastin, increased expression of pro‐inflammatory cytokines and impaired respiratory function. BGP induced inflammation and fibrosis in fibroblasts through the activation and binding of NFkB to the MCP‐1 or FN promoters. BGP increased ECE‐1 expression by inducing NFkB binding to the ECE‐1 promoter. QNZ, an NFkB inhibitor, blocked these effects. When ECE‐1 was inhibited with phosphoramidon, BGP‐induced inflammation and fibrosis were significantly reduced, suggesting a role for ET‐1 in BGP‐mediated effects.ET‐1 produced effects similar to those of BGP, which were also dependent on NFkB. To study the pathophysiological relevance of hyperphosphatemia in vivo, a low‐P diet was administered to a group of old animals, showing an improvement in fibrosis, inflammation and respiratory function compared to old mice on a standard diet.These results suggest that age‐related hyperphosphatemia induces inflammation, fibrosis, and impaired respiratory function in old mice; these effects appear to be mediated by ET‐1 and NFkB activation. [ABSTRACT FROM AUTHOR]

What is this summary about? This is a summary of an article that was published in the medical journal Kidney360 describing results from the NORMALIZE study. The NORMALIZE study looked at how well tenapanor tablets reduced higher-than-normal levels of phosphate in the blood of persons with kidney disease who are on maintenance dialysis. These persons are unable to keep their blood phosphate levels in a normal range, and high levels of phosphate can contribute to several serious health consequences. Tenapanor is approved as an add-on treatment for high levels of phosphate in the blood of adults with chronic kidney disease who are on maintenance dialysis and whose disease does not respond adequately to treatment with phosphate binders or who are not able to take phosphate binders. In earlier clinical studies, tenapanor was studied alone or studied together with phosphate binders. In a 1-year clinical study called PHREEDOM, researchers learned that when tenapanor was used alone, it lowered blood phosphate levels, and treated patients experienced acceptable safety and tolerability as determined by the doctors running the study. In the NORMALIZE study, adult patients took a 30-mg tenapanor tablet twice a day, either alone or with sevelamer, for up to 18 months after they completed the PHREEDOM study. What were the main conclusions reported by the researchers? The researchers found that one-third of patients taking tenapanor, either alone or with sevelamer, achieved normal blood phosphate levels. This is an improvement from the current standard of care with sevelamer alone to reduce blood phosphate levels. As seen in the earlier studies of tenapanor, the most common adverse event experienced by patients was softer or loose stools. No new safety concerns were reported in the NORMALIZE study. What are the key takeaways? The researchers concluded that tenapanor, used alone or combined with sevelamer, can be used long-term by adult patients receiving maintenance dialysis to reduce the phosphate levels in their blood to within the normal range. Patients who take tenapanor may experience softer or loose stools. This summary was developed by the authors to help adult patients with chronic kidney disease receiving dialysis, and their family members and/or caregivers, better understand the effects of taking tenapanor. This is an abstract of the Plain Language Summary of Publication article. of this article to read the full-text Link to original article [ABSTRACT FROM AUTHOR]

In the article by AlHabobi and colleagues ([1]), a reader identified a typographical error in the section "What is the main message for physicians who are not nephrology specialists?" under "The potassium binder patiromer also reduces serum phosphorus levels." The article stated that among 86 participants with baseline hyperphosphatemia, the mean reduction in serum phosphorus levels after 4 weeks of treatment was 0.7 mEq/L; this should instead be 0.62 mg/dL. The text has been corrected. [Extracted from the article]

Introduction: Several calcimimetics, other than cinacalcet, are commercially available; however, their effects on calcium and phosphate levels have not yet been fully studied. We conducted a systematic review and meta‐analysis of randomized controlled trials to evaluate the impact of calcimimetics on the management of serum calcium and phosphate levels in patients with secondary hyperparathyroidism undergoing dialysis. Methods: A systematic literature search through October 2023 and a meta‐analysis were conducted on the effects of upacicalcet, etelcalcetide, evocalcet, and cinacalcet on serum calcium and phosphate levels in patients with secondary hyperparathyroidism undergoing dialysis; we searched PubMed, Ovid MEDLINE, and the Cochrane Central Register of Controlled Trials, and 21 studies comprising 6371 patients undergoing dialysis were included. Results: Participants treated with calcimimetics had lower serum calcium and phosphate levels than placebo. Conclusion: Calcimimetics significantly reduced serum calcium and phosphate levels compared to placebo in patients with secondary hyperparathyroidism undergoing dialysis, independent of therapeutic strategy or concomitant vitamin D treatment. [ABSTRACT FROM AUTHOR]

Introduction: The clinical benefits of aspirin in patients undergoing hemodialysis remain unclear. Methods: The secondary analysis of the LANDMARK trial investigated whether aspirin use was associated with cardiovascular events (CVEs) and all‐cause mortality was performed. A total of 2135 patients at risk for vascular calcification were analyzed using a Cox proportional hazards model with propensity score matching. Results: The risk of CVEs was comparable between participants with aspirin use at baseline and those without at baseline, between participants with aspirin use during the study period and those without during the study period, and between participants with new aspirin prescription and those without aspirin use during the study period. Conclusion: Aspirin use was not significantly associated with a lower risk of CVEs in participants undergoing hemodialysis patients at risk of vascular calcification. [ABSTRACT FROM AUTHOR]

Background: Data is limited on the prevalence of hypophosphatemia in general hospitalized patients, and its association with length of hospital stay (LOS) and mortality remained unclear. We aimed to investigate the prevalence of admission phosphate abnormality and the association between serum phosphate level and length of hospital stay and all-cause mortality in adult patients. Methods: This was a multi-center retrospective study based on real-world data. Participants were classified into five groups according to serum phosphate level (inorganic phosphorus, iP) within 48 h after admission: G1, iP < 0.64 mmol/L; G2, iP 0.64–0.8 mmol/L; G3, iP 0.8–1.16 mmol/L; G4, iP 1.16–1.45 mmol/L; and G5, iP ≥ 1.45 mmol/L, respectively. Both LOS and in-hospital mortality were considered as outcomes. Clinical information, including age, sex, primary diagnosis, co-morbidity, and phosphate-metabolism related parameters, were also abstracted from medical records. Results: A total number of 23,479 adult patients (14,073 males and 9,406 females, aged 57.7 ± 16.8 y) were included in the study. The prevalence of hypophosphatemia was 4.74%. An "L-shaped" non-linear association was determined between serum phosphate level and LOS and the inflection point was 1.16 mmol/L in serum phosphate level. Compared with patients in G4, patients in G1, G2 or G3 were significantly associated with longer LOS after full adjustment of covariates. Each 0.1 mmol/L decrease in serum phosphate level to the left side of the inflection point led to 0.64 days increase in LOS [95% confidence interval (CI): 0.46, 0.81; p for trend < 0.001]. But there was no association between serum phosphate and LOS where serum levels of phosphate ≥ 1.16 mmol/L. Multivariable logistic regression analysis showed that adjusted all-cause in-hospital mortality was 3.08-fold greater in patients in G1 than those in G4 (95% CI: 1.52, 6.25; p for trend = 0.001). Similarly, no significant association with either LOS or mortality were found in patients in G5, comparing with G4. Conclusions: Hypophosphatemia, but not hyperphosphatemia, was associated with LOS and all-cause mortality in adult inpatients. It is meaningful to monitor serum levels of phosphate to facilitate early diagnosis and intervention. [ABSTRACT FROM AUTHOR]

Objective: To explore the risk factors for severe infection and the influencing factors of adverse cardiovascular events in patients with chronic renal failure in the uremic stage undergoing hemodialysis maintenance therapy. Methods: Sixty patients with chronic renal failure and uremia admitted to our hospital from October 2021 to October 2023 were selected as the study subjects, and all patients received maintenance hemodialysis treatment. Group patients according to the number of severe infections and adverse cardiovascular events. The infection group (n=20), non infection group (n=40), and adverse cardiovascular event group (n=22), non adverse cardiovascular event group (n=38). Analyze the general clinical situation of all patients, with severe infection and adverse cardiovascular events as dependent variables, and incorporate them into a logistic regression model to analyze the independent influencing factors of severe infection and adverse cardiovascular events. Results: There were significant differences in age, diabetes, dialysis time, heart failure, indwelling venous catheter, hemoglobin, Hs CRP, albumin and fasting blood glucose between the infected group and the non infected group (P<0.05); Age, diabetes, indwelling venous catheter, Hs CRP and fasting blood glucose were independent risk factors for severe infection in patients with chronic renal failure in uremic stage undergoing hemodialysis maintenance treatment (P<0.05); There were significant differences in primary disease, hypertension, diabetes, hyperlipidemia, smoking history, hyperphosphatemia, dialysis time, Hs-CRP, LDL-C between the adverse cardiovascular event group and the non adverse cardiovascular event group(P<0.05); Hypertension, hyperlipidemia, hyperphosphatemia, Hs CRP, and dialysis time are independent risk factors for adverse cardiovascular events in patients with chronic renal failure in the uremic stage undergoing hemodialysis maintenance therapy(P<0.05). Conclusion: Age, diabetes, indwelling venous catheter, Hs CRP, and fasting blood glucose are independent risk factors for severe infection in patients with chronic renal failure in uremic stage undergoing hemodialysis maintenance treatment. Hypertension, hyperlipidemia, hyperphosphatemia, Hs CRP, and dialysis time are independent risk factors for adverse cardiovascular events. [ABSTRACT FROM AUTHOR]

Background Lack of evaluations of the dietary phosphorus and dialysis phosphorus removal in daily clinical practice are common obstacles to assessing phosphorus balance and controlling phosphorus in hemodialysis patients. We aimed to investigate whether individualized therapy using a phosphorus balance calculator improves phosphorus control. Methods A randomized, open-label, multicenter, 4-week clinical trial was conducted. A total of 119 maintenance hemodialysis patients aged 18–85 years old and with serum phosphorus level >1.45 mmol/L from three university teaching hospitals in Shanghai were enrolled. Patients were randomized in a 1:1 ratio to individualized therapy (n  = 60) or conventional therapy (n  = 59). The primary outcome was the serum phosphorus concentration after 4-week treatment. Secondary outcomes included the serum calcium and parathyroid hormone (PTH) concentrations, changes in serum phosphorus, calcium and PTH concentrations, and the proportion of patients achieving target ranges of serum phosphorus, calcium and PTH after 4-week treatment. Results Among 119 randomized participants [mean age 62 years; 68 male (57%)], 116 completed the trial. Using the phosphorus balance calculator, the individualized group achieved a better phosphorus balance state and significantly reduced serum phosphorus (1.62 ± 0.45 mmol/L versus 1.85 ± 0.45 mmol/L, P  = .006), increased the proportions of patients achieving target serum phosphorus range (41% versus 18%, P  = .006) and had greater adjusted mean difference in change in serum phosphorus over the 4 weeks (−0.47 versus −0.23 mmol/L, P  = .010) when compared with conventional therapy. No significant changes were observed in serum calcium and PTH levels, the proportion of patients achieving target serum calcium or PTH levels, or the adjusted mean difference of serum calcium and PTH levels over the treatment period. Conclusion Phosphorus balance calculator was proved to improve serum phosphorus control in patients undergoing maintenance hemodialysis, offering a new tool for managing hyperphosphatemia. [ABSTRACT FROM AUTHOR]

Objective: To explore the influencing factors of concurrent skin pruritus in maintenance hemodialysis patients and its correlation with serum inflammatory factors in β2-MG. Methods: 100 maintenance hemodialysis patients from our hospital from January 2019 to December 2023, compared with general data and laboratory indicators of patients with and without pruritus, and statistically significant indicators for Logistic-analysis. The scores of pruritus patients were evaluated according to the 5D-IS scale, and the pruritus patients were divided into mild, moderate and severe groups according to the scores, and the serum inflammatory factors and β2-MG levels of the three groups were compared. The therapeutic effect of pregabalin was analyzed, and the serum levels of β2-MG, CRP, TNF-α and IL-6 in the effective and ineffective groups were compared before and after treatment. Results: In the itching group, age, blood creatinine level, dialysis age, calcium and phosphorus product, blood phosphorus level, parathyroid hormone level, dry skin disease, serum β2-MG, CRP, TNF-α, and IL-6 levels were significantly higher than in the no itching group, while SF level and Kt / V 1.2 proportion were significantly lower than in the no itching group(P<0.05). Binary Logistic regression analysis found that The risk factors of maintenance hemodialysis complicated with itching were age≥60 years, dialysis duration≥1 year, calcium-phosphorus product ≥65 (mg²/dl²), Kt/V<1.2, parathyroid hormone level ≥300 pg/mL, dry skin disease, serum β2-MG≥4.06 mg/L, serum CRP≥10 mg/L, and serum TNF-α≥1.54 ng/mL, serum IL-6≥0.46 ng/L (P<0.05). Among 45 patients with maintenance hemodialysis complicated with pruritus, 28 cases were mild, 10 cases were moderate, and 7 cases were severe. Serum levels of β2-MG, CRP, TNF-α and IL-6 in severe group were higher than those in mild and moderate groups, and the above indexes in moderate group were higher than those in mild group (all P<0.05). Among 45 patients with pruritus caused by maintenance hemodialysis, 15 cases had complete remission, 10 cases had obvious effect, 10 cases were effective, and 10 cases were ineffective. After treatment, the levels of serum β2-MG, CRP, TNF-α and IL-6 in the effective group were lower than those before treatment(P<0.05). There was no significance in the ineffective group before and after treatment (P>0.05). After treatment, the above indexes in effective group were lower than those in ineffective group (P<0.05). Conclusion: The risk factors for pruritosis in maintenance hemodialysis patients included age≥60 years, dialysis duration≥1 year, calcium-phosphorus product≥65 (mg²/dl²), Kt/V<1.2, parathyroid hormone level ≥300 pg/mL, dry skin disease, serum β2-MG≥4.06 mg/L, serum CRP≥10 mg/L Serum TNF-α≥1.54 ng/mL, serum IL-6≥0.46 ng/L, serum CRP, TNF-α, IL-6 and β2-MG were correlated with the severity and prognosis of skin itching complicated by maintenance hemodialysis patients. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a significant challenge for pediatric endocrinologists, as children with CKD may present a variety of endocrine complications. Growth failure is common in CKD, and its severity is correlated with the degree of renal insufficiency. Management strategies include addressing reversible comorbidities, optimizing nutrition, and ensuring metabolic control. Kidney replacement therapy, including transplantation, determines a significant improvement in growth. According to a recent Consensus Statement, children with CKD stage 3—or on dialysis older >6 months—are eligible for treatment with recombinant growth hormone (rGH) in the case of persistent growth failure. Treatment with rGH may be considered for those with height between the 3rd and 10th percentile and persistent growth deceleration. In children who received kidney transplantation but continue to experience growth failure, initiation of GH therapy is recommended one year post-transplantation if spontaneous catch-up growth does not occur and steroid-free immunosuppression is not an option. In children with CKD, due to nephropathic cystinosis and persistent growth failure, GH therapy should be considered at all stages of CKD. Potential adverse effects and benefits must be regularly assessed during therapy. Treatment with GH is safe in children with CKD. However, its general efficacy is still controversial. All possible problems with a negative impact on growth should be timely addressed and resolved, whenever possible with a personalized approach to the patient. GH therapy may be useful in promoting catch-up growth in children with residual growth potential. Future research should focus on refining effective therapeutic strategies and establishing consensus guidelines to optimize growth outcomes in this population. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular (CVS) conditions remain the main etiology of death in individuals with chronic kidney disease (CKD) even after control of classic risk factors of cardiovascular disease (CVD). Aim: This study is to detect the sequalae of serum phosphorus and calcium level abnormalities in individuals with CKD and their relation to occurrence of acute coronary syndrome (ACS) in those cases. Methods: A cross-sectional work involved 100 individuals with CKD managed with or without dialysis. They were admitted to Internal Medicine Department, Coronary Care Unit of Sohag University Hospital. Each participant had been subjected to full history taking, clinical assessment, and investigations including serum calcium, phosphorus, creatinine, blood urea, parathyroid hormone level, lipid profile, troponin, CK-MB, electrocardiogram, and echocardiography. Results: A substantial elevation in serum calcium and phosphorus levels was existed in individuals with CKD with ACS group compared to patients with CKD without ACS group (p = 0.026 and 0.001 respectively). The mean calcium/phosphorus ratio was 3.04 ± 2.14 in patients with CKD with ACS group, while it was 2.31 ± 1.17 in patients with CKD without ACS group. A substantial raise in calcium/phosphorus ratio was existed in CKD with ACS group as compared to patients with CKD without ACS group (p = 0.047). ROC curve analysis shows that calcium/phosphorus ratio can predict acute coronary syndrome at cutoff 1.94 with area under the curve 0.652 with sensitivity and specificity that were 77.8% and 52.1% correspondingly (p = 0.007). Conclusion: A substantial raise in calcium and phosphorus levels was existed in individuals with CKD with ACS group contrasted to individuals with CKD without ACS group. Calcium/phosphorus ratio can predict acute coronary syndrome at cutoff 1.94. Clinical trial registration number: NCT05134220. [ABSTRACT FROM AUTHOR]

The global derangement of mineral metabolism that accompanies chronic kidney disease (CKD-MBD) is a major driver of the accelerated mortality for individuals with kidney disease. Advances in the delivery of dialysis, in the composition of phosphate binders, and in the therapies directed towards secondary hyperparathyroidism have failed to improve the cardiovascular event profile in this population. Many obstacles have prevented progress in this field including the incomplete understanding of pathophysiology, the lack of clinical targets for early stages of chronic kidney disease, and the remarkably wide diversity in clinical manifestations. We describe in this review a novel approach to CKD-MBD combining mathematical modelling of biologic processes with machine learning artificial intelligence techniques as a tool for the generation of new hypotheses and for the development of innovative therapeutic approaches to this syndrome. Clinicians need alternative targets of therapy, tools for risk profile assessment, and new therapies to address complications early in the course of disease and to personalize therapy to each individual. The complexity of CKD-MBD suggests that incorporating artificial intelligence techniques into the diagnostic, therapeutic, and research armamentarium could accelerate the achievement of these goals. [ABSTRACT FROM AUTHOR]

Vignette: Hypophosphatasia (HPP) is the dento-osseous disorder caused by deactivating mutation(s) of ALPL, the gene that encodes the "tissue-nonspecific" isoenzyme of alkaline phosphatase (TNSALP). In HPP, 3 natural substrates of cell-surface TNSALP accumulate extracellularly; phosphoethanolamine (PEA), inorganic pyrophosphate (PPi), and pyridoxal 5′-phosphate (PLP). Hypophosphatasemia together with elevated plasma levels of PEA, PPi, and PLP comprise its biochemical signature. PPi can inhibit mineralization and in extracellular excess can impair bone and tooth hardening and perhaps explain weak muscle. Autosomal dominant or autosomal recessive inheritance from among more than 400 mutations of ALPL largely accounts for HPP's broad-ranging severity, greatest among all skeletal diseases. Pediatric HPP spans life-threatening perinatal and infantile forms, childhood forms, and odonto-HPP selectively featuring premature loss of deciduous teeth. ALPL gene testing and TNSALP supplementation therapy have bolstered familiarity with HPP, but there are new considerations for diagnosis. Herein, diagnosis of a boy's mild childhood HPP was delayed by missteps involving his medical and dental history, physical examination, radiographic findings, and clinical laboratory studies. We review how pediatric HPP is now identified. Prompt diagnosis while appreciating the broad-ranging severity of HPP underlies the safe and effective management of this inborn-error-of-metabolism. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate novel strategies for reducing adverse reactions caused by erdafitinib through a drug combination based on its pharmacokinetic characteristics. The spectrum and characterizations of drugs that can inhibit the metabolism of erdafitinib are examined both in vitro and in vivo. The efficacy of combination regimens are then evaluated using subcutaneous xenograft tumor models. The results demonstrated that sertraline and duloxetine, out of more than 100 screened drugs, inhibited the metabolism of erdafitinib through mixed and non-competitive inhibition, respectively. This inhibition primarily occurred via the CYP2C9 and CYP2D6 pathways. The primary alleles of CYP2C9 and CYP2D6 not only determine the metabolic characteristics of erdafitinib but also influence the strength of drug-drug interactions. Co-administration of sertraline or duloxetine with erdafitinib in rats and mice resulted in nearly a three-fold increase in the blood exposure of erdafitinib and its major metabolite M6. When sertraline or duloxetine was combined with 1/3 of the erdafitinib dosage, the anti-proliferative and pro-apoptotic effects on SNU-16 xenografts were comparable to those of the original full dose of erdafitinib. However, the combination regimen significantly mitigated hyperphosphatemia, retinal damage, intestinal villus damage, and gut microbiome dysbiosis. This study utilized pharmacokinetic methods to propose a new formulation of erdafitinib combined with sertraline or duloxetine. The findings suggest that this combination has potential for clinical co-administration based on a database analysis, thereby providing a novel strategy for anti-tumor treatment with fibroblast growth factor receptor (FGFR) inhibitors.

Vascular calcification is quite common in patients with end-stage chronic kidney disease and is a major trigger for cardiovascular complications in these patients. These complications significantly impact the survival rate and long-term prognosis of individuals with chronic kidney disease. Numerous studies have demonstrated that the development of vascular calcification involves various pathophysiological mechanisms, with the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) being of utmost importance. High phosphate levels, bone morphogenetic protein 2 (BMP2), and runt-related transcription factor 2 (RUNX2) play crucial roles in the osteogenic transdifferentiation process of VSMCs. This article primarily reviews the molecular mechanisms by which high phosphate, BMP2, and RUNX2 regulate vascular calcification secondary to chronic kidney disease, and discusses the complex interactions among these factors and their impact on the progression of vascular calcification. The insights provided here aim to offer new perspectives for future research on the phenotypic switching and osteogenic transdifferentiation of VSMCs, as well as to aid in optimizing clinical treatment strategies for this condition, bearing significant clinical and scientific implications.