Retrospective analysis of predictive factors for AVF dysfunction in patients undergoing MHD.

To construct an early clinical prediction model for AVF dysfunction in patients undergoing Maintenance Hemodialysis (MHD) and perform internal and external verifications. We retrospectively examined clinical data from 150 patients diagnosed with MHD at Hefei Third People's Hospital from January 2014 to June 2023. Depending on arteriovenous fistula (AVF) functionality, patients were categorized into dysfunctional (n = 62) and functional (n = 88) cohorts. Using the least absolute shrinkage and selection operator(LASSO) regression model, variables potentially influencing AVF functionality were filtered using selected variables that underwent multifactorial logistic regression analysis. The Nomogram model was constructed using the R software, and the Area Under Curve(AUC) value was calculated. The model's accuracy was appraised through the calibration curve and Hosmer-Lemeshow test, with the model undergoing internal validation using the bootstrap method. There were 11 factors exhibiting differences between the group of patients with AVF dysfunction and the group with normal AVF function, including age, sex, course of renal failure, diabetes, hyperlipidemia, Platelet count (PLT), Calcium (Ca), Phosphorus, D-dimer (D-D), Fibrinogen (Fib), and Anastomotic width. These identified factors are included as candidate predictive variables in the LASSO regression analysis. LASSO regression identified age, sex, diabetes, hyperlipidemia, anastomotic diameter, blood phosphorus, and serum D-D levels as 7 predictive factors. Unconditional binary logistic regression analysis revealed that advanced age (OR = 4.358, 95% CI: 1.454-13.062), diabetes (OR = 4.158, 95% CI: 1.243-13.907), hyperlipidemia (OR = 3.651, 95% CI: 1.066-12.499), D-D (OR = 1.311, 95% CI: 1.063-1.616), and hyperphosphatemia (OR = 4.986, 95% CI: 2.513-9.892) emerged as independent risk factors for AVF dysfunction in MHD patients. The AUC of the predictive model was 0.934 (95% CI: 0.897-0.971). The Hosmer-Lemeshow test showed high consistency between the model's predictive results and actual clinical observations (χ2 = 1.553, P = .092). Internal validation revealed an AUC of 0.911 (95% CI: 0.866-0.956), with the Calibration calibration curve nearing the ideal curve. Advanced age, coexisting diabetes, hyperlipidemia, blood D-D levels, and hyperphosphatemia are independent risk factors for AVF dysfunction in patients undergoing MHD.

Spurious Hyperphosphatemia in a Patient with Chronic Kidney Disease - a Rare Case of Alteplase Contamination.

Spurious hyperphosphatemia, a rare occurrence, typically arises from substances in a patient's blood interfering with the colorimetric method for serum phosphate measurement. We present a case of factitious hyperphosphatemia caused by alteplase-contaminated blood samples in an 88-year-old CKD patient on hemodialysis, leading to misleadingly high phosphorus levels. Thorough investigations ruled out other etiologies, highlighting the necessity of stringent adherence to blood collection protocols to prevent sample contamination and avert erroneous laboratory results. This unique cause of hyperphosphatemia should be considered in the differential diagnosis when encountering unexplained elevations in phosphorus levels, particularly in the context of normal blood calcium levels.

Phosphonoformic acid reduces hyperphosphatemia-induced vascular calcification via Pit-1.

OBJECTIVE: This study aimed to examine the mechanism of hyperphosphatemia-induced vascular calcification (HPVC). METHODS: Primary human aortic smooth muscle cells and rat aortic rings were cultured in Dulbecco's modified Eagle's medium supplemented with 0.9 mM or 2.5 mM phosphorus concentrations. Type III sodium-dependent phosphate cotransporter-1 (Pit-1) small interfering RNA and phosphonoformic acid (PFA), a Pit-1 inhibitor, were used to investigate the effects and mechanisms of Pit-1 on HPVC. Calcium content shown by Alizarin red staining, expression levels of Pit-1, and characteristic molecules for phenotypic transition of vascular smooth muscle cells were examined. RESULTS: Hyperphosphatemia induced the upregulation of Pit-1 expression, facilitated phenotypic transition of vascular smooth muscle cells, and led to HPVC in cellular and organ models. Treatment with Pit-1 small interfering RNA or PFA significantly inhibited Pit-1 expression, suppressed phenotypic transition, and attenuated HPVC. CONCLUSIONS: Our findings suggest that Pit-1 plays a pivotal role in the development of HPVC. The use of PFA as a Pit-1 inhibitor has the potential for therapeutic intervention in patients with HPVC. However, further rigorous clinical investigations are required to ensure the safety and efficacy of PFA before it can be considered for widespread implementation in clinical practice.

Biochemical markers of iron status and iron accumulation in peritoneal dialysis patients treated with ferric citrate.

BACKGROUND: Hyperphosphataemia is a common complication of kidney disease. Current dialysis techniques do not provide enough phosphorus clearance, hence the need to use phosphorus binders. Treatment options include calcium carbonate, calcium acetate, lanthanum carbonate, sevelamer hydrochloride and iron-based binders. Patients receiving peritoneal dialysis (PD) with sustained elevated ferritin levels exceeding 800 ng/mL are at a higher risk of death. We identify PD patients treated with iron-based binders and compare ferritin and risk of iron accumulation to patients treated with non-iron-based binders. METHODS: All records of patients receiving PD at Emory dialysis centres until 30 October 2021 were reviewed for phosphorus binders. Basic demographics and laboratory data were time-referenced to the days on treatment with a particular binder. Patients were followed until discontinuation of the phosphorus binder, death, transplant, transfer to another dialysis provider or censoring at 36 months after medication was started. RESULTS: Compared to calcium acetate and sevelamer, ferric citrate utilisation in PD patients resulted in a sustained increase in ferritin. The proportion of patients with a ferritin equal to or greater than 800 ng/dL and transferrin saturation greater than 40% increased over time in patients treated with ferric citrate and was higher during the second and third year of follow-up compared to baseline values and to patients treated with calcium acetate or sevelamer. Two patients (7%) treated with ferric citrate developed clinically significant haemosiderosis. CONCLUSIONS: Use of ferric citrated in PD resulted in significant iron accumulation as judged by ferritin levels.

The basics of phosphate metabolism.

Phosphorus is an essential mineral that is, in the form of inorganic phosphate (Pi), required for building cell membranes, DNA and RNA molecules, energy metabolism, signal transduction and pH buffering. In bone, Pi is essential for bone stability in the form of apatite. Intestinal absorption of dietary Pi depends on its bioavailability and has two distinct modes of active transcellular and passive paracellular absorption. Active transport is transporter mediated and partly regulated, while passive absorption depends mostly on bioavailability. Renal excretion controls systemic Pi levels, depends on transporters in the proximal tubule and is highly regulated. Deposition and release of Pi into and from soft tissues and bone has to be tightly controlled. The endocrine network coordinating intestinal absorption, renal excretion and bone turnover integrates dietary intake and metabolic requirements with renal excretion and is critical for bone stability and cardiovascular health during states of hypophosphataemia or hyperphosphataemia as evident from inborn or acquired diseases. This review provides an integrated overview of the biology of phosphate and Pi in mammals.

Efficacy and Safety of Sucroferric Oxyhydroxide Compared with Sevelamer Carbonate in Chinese Dialysis Patients with Hyperphosphataemia: A Randomised, Open-Label, Multicentre, 12-Week Phase III Study.

INTRODUCTION: This study aimed to investigate the efficacy and safety of sucroferric oxyhydroxide (SFOH) versus sevelamer carbonate in controlling serum phosphorus (sP) in adult Chinese dialysis patients with hyperphosphataemia (sP >1.78 mmol/L). METHODS: Open-label, randomised (1:1), active-controlled, parallel group, multicentre, phase III study of SFOH and sevelamer at starting doses corresponding to 1,500 mg iron/day and 2.4 g/day, respectively, with 8-week dose titration and 4-week maintenance (NCT03644264). Primary endpoint was non-inferiority analysis of change in sP from baseline to week 12. Secondary endpoints included sP over time and safety. RESULTS: 415 patients were screened; 286 were enrolled and randomised (142 and 144 to SFOH and sevelamer, respectively). Mean (SD) baseline sP: 2.38 (0.57) and 2.38 (0.52) mmol/L, respectively. Mean (SD) change in sP from baseline to week 12: - 0.71 (0.60) versus -0.63 (0.52) mmol/L, respectively; difference (sevelamer minus SFOH) in least squares means (95% CI): 0.08 mmol/L (-0.02, 0.18) with the lower limit of 95% CI above the non-inferiority margin of -0.34 mmol/L. The SFOH group achieved target sP (1.13-1.78 mmol/L) earlier than the sevelamer group (56.5% vs. 32.8% at week 4) and with a lower pill burden (mean 3.7 vs. 9.1 tablets/day over 4 weeks of maintenance, respectively). Safety and tolerability of SFOH was consistent with previous studies, and no new safety signals were observed. CONCLUSION: SFOH effectively reduced sP from baseline and was non-inferior to sevelamer after 12 weeks of treatment but had a lower pill burden in Chinese dialysis patients with hyperphosphataemia; SFOH benefit-risk profile is favourable in Chinese patients.

Tenapanor for peritoneal dialysis patients with hyperphosphatemia: a phase 3 trial.

BACKGROUND: Tenapanor is a novel selective inhibitor of intestinal sodium/hydrogen exchanger 3 transporter. This is the first trial to assess the efficacy and safety of tenapanor in Japanese patients with hyperphosphatemia who are undergoing peritoneal dialysis. METHODS: This phase 3, open-label, multicenter, single-arm clinical trial targeted patients whose serum phosphorus was within 3.5-7.0 mg/dL with phosphate binders at screening. After phosphate binder washout, tenapanor was orally administered twice-daily, stepwise from 5 to 30 mg/dose for 16 weeks. The primary endpoint, mean change in serum phosphorus level, was evaluated at week 8. The 16-week treatment period was completed with tenapanor alone, and only one phosphate binder type was allowed for combined use after the primary endpoint. RESULTS: Of the 54 patients enrolled, 34 completed the study. At week 8, the primary endpoint, mean change in serum phosphorus level (last observation carried forward), was - 1.18 mg/dL (95% confidence interval: - 1.54, - 0.81 mg/dL) with tenapanor. From a baseline value of 7.65 mg/dL, serum phosphorus decreased to 6.14 and 5.44 mg/dL at weeks 8 and 16, respectively, and 46.3% and 76.5% of patients achieved serum phosphorus within 3.5-6.0 mg/dL at week 8 and week 16, respectively. The most common adverse event, diarrhea, occurred in 74.1% of patients; the severity of diarrhea was mild or moderate. Thus, the discontinuation percentage due to diarrhea was low at 5.6%. CONCLUSIONS: Administration of tenapanor resulted in a sufficient reduction in serum phosphorus level at week 8 and was considered safe and tolerable. TRIAL REGISTRATION: NCT04766385.

Hypocalcemia in combination with hyperphosphatemia impairs muscle cell differentiation in vitro.

PURPOSE: Hypoparathyroidism is a rare endocrine disorder characterized by low or absent secretion of parathyroid hormone (PTH), which leads to decreased calcium and increased phosphorus levels in the serum. The diagnosis of hypoparathyroidism is based on the identification of the aforementioned biochemical abnormalities, which may be accompanied by clinical manifestations. Symptoms of hypoparathyroidism, primarily attributed to hypocalcemia, include muscle cramps or spasms, facial, leg, and foot pain, seizures, and tingling in the lips or fingers. The treatment of hypoparathyroidism depends on the severity of symptoms and the underlying pathology. Over the long term, calcium supplements, active vitamin D analogs, and thiazide diuretics may be needed. In fact, in patient cohorts in which optimal disease control still remains elusive, replacement therapy with recombinant parathyroid hormone analogs may be contemplated. Despite the predominantly neuromuscular symptoms of hypoparathyroidism, further effects of parathyroid hormone deficiency at the muscle cell level remain poorly understood. Thus, the aim of our study was to evaluate the effects of hypocalcemia in combination with hyperphosphatemia on muscle cells differentiation in vitro. METHODS: C2C12 cells, an in vitro model of muscle cells, were differentiated for 2 or 6 days in the presence of hypocalcemia (CaCl2 0.9 mmol/l) and moderate (PO4 1.4 mmol/l) or severe (PO4 2.9 mmol/l) hyperphosphatemia, or combinations of both conditions. Cell differentiation and expression of genes linked to muscle differentiation were evaluated. RESULTS: The combination of hypocalcemia with hyperphosphatemia induced a significant reduction (50%) in differentiation marker levels, such as MyoD (protein 1 for myoblast determination) and myogenin on the 1st day of differentiation, and MHC (myosin heavy chains) after 6 days of differentiation compared to control. Furthermore, this condition induced a statistically significant reduction of insulin-like growth factor-1 (IGF-1) mRNA expression and inhibition of IGF signaling and decrease in ERK phosphorylation compared to control cells. CONCLUSIONS: Our results showed that a condition of hypocalcemia with hyperphosphatemia induced an alteration of muscle cell differentiation in vitro. In particular, we observed the reduction of myogenic differentiation markers, IGF-1 signaling pathway, and ERK phosphorylation in differentiated skeletal myoblasts. These data suggest that this altered extracellular condition might contribute to the mechanisms causing persistence of symptoms in patients affected by hypoparathyroidism.

Predictions of Serum Phosphate Concentration during Continuous Renal Replacement Therapy Using a Steady-State Mass Balance Model.

INTRODUCTION: Hypophosphatemia is common during continuous renal replacement therapy (CRRT), but serum phosphate levels can potentially be maintained during treatment by either intravenous phosphate supplementation or addition of phosphate to renal replacement therapy (RRT) solutions. METHODS: We developed a steady-state phosphate mass balance model to assess the effects of CRRT dose on serum phosphate concentration when using both phosphate-free and phosphate-containing RRT solutions, with emphasis on low CRRT doses. RESULTS: The model predicted that measurements of serum phosphate concentration prior to (initial) and during CRRT (final) together with clinical data on CRRT dose, treatment duration, and phosphate supplementation can determine model patient parameters, that is, both the initial generation rate and clearance of phosphate prior to CRRT. Model parameters were then calculated from average patient data reported in several previous publications with a standard or high CRRT dose. Using representative model parameters for typical patients, predictions were then made of the effect of low CRRT dose on the change in serum phosphate levels after implementation of CRRT. The model predicted that CRRT at a low dose using phosphate-free RRT solutions will limit, but not eliminate, the incidence of hypophosphatemia. Further, the model predicted that CRRT at a low dose will have virtually no influence on the incidence of hyperphosphatemia when using phosphate-containing RRT solutions. CONCLUSIONS: This report identifies the clinical measurements to be used with the proposed model for individualizing the CRRT dose and RRT phosphate concentration to maintain serum phosphate concentrations in a desired range.

Long-term safety and decrease of pill burden by tenapanor therapy: a phase 3 open-label study in hemodialysis patients with hyperphosphatemia.

Phosphate binders (PBs) generally have a high pill burden. Tenapanor selectively inhibits sodium/hydrogen exchanger isoform 3, reducing intestinal phosphate absorption. Tenapanor is a novel drug administered as a small tablet, twice daily. This multicenter, open-label, single-arm, phase 3 study aimed to evaluate the long-term safety of tenapanor and its efficacy in decreasing PB pill burden. Tenapanor 5 mg twice daily was administered to hemodialysis patients with serum phosphorus level 3.5-7.0 mg/dl at baseline; the dose could be increased up to 30 mg twice daily. Patients could also switch from PBs. The primary endpoint was safety during 52-week administration. The key secondary endpoint was a ≥ 30% reduction in the total pill number of daily PBs and tenapanor from baseline. Of 212 patients starting treatment, 154 completed the study. Diarrhea was the most frequent adverse event, occurring in 135 patients (63.7%); most events were classified as mild (74.8%). No clinically significant changes occurred other than serum phosphorus level. At Week 52/discontinuation, 158/204 patients (77.5%) achieved the key secondary endpoint. Complete switching from PBs to tenapanor was achieved in 50-76 patients (26.7%-41.5%), and 80 patients (51.9%) at Week 8-12 and Week 50, respectively. Serum phosphorus remained generally stable within the target range (3.5-6.0 mg/dl). These findings suggest the long-term safety and tolerability of tenapanor. Tenapanor could reduce or eliminate PB pill burden while controlling serum phosphorus levels.Trial registration: NCT04771780.

A 47-Year-Old Man with Hyperphosphatemia Due to Chronic Renal Failure Treated with Lanthanum Carbonate Tablets Presenting Acutely with Partial Large Bowel Obstruction.

BACKGROUND Hyperphosphatemia is a complication of chronic renal failure (CRF) due to reduction in the glomerular filtration rate. Lanthanum carbonate is a commonly used phosphate binder for patients with CRF and hyperphosphatemia, but has adverse effects if patients are not monitored. This report is of a 47-year-old man with hyperphosphatemia due to CRF treated with lanthanum carbonate tablets who presented acutely with partial large bowel obstruction. The incidence of lanthanum carbonate causing intestinal obstruction is rare, and few cases in the literature have described the course of the disease in detail. CASE REPORT A 47-year-old man diagnosed with diabetic nephropathy underwent hemodialysis treatment and was prescribed 0.5 g/day of chewable lanthanum carbonate tablets. After taking lanthanum carbonate for 5 months, the patient experienced symptoms of decreased bowel movements and exhaustion, which progressively worsened. Abdominal computed tomography (CT) revealed multiple hyperdensities in the large bowel, indicating the presence of lanthanum deposition. Lanthanum carbonate was promptly discontinued. After undergoing enema and catharsis treatment, the large bowel obstruction was relieved, and the hyperdensities in the abdominal CT disappeared. The colonoscopy and histologic examination revealed ulcerations and inflammatory changes in the large bowel mucosa. CONCLUSIONS This report highlights the rare association between the use of lanthanum carbonate tablets and intestinal obstruction. Healthcare providers should enhance their vigilance regarding lanthanum carbonate-induced serious gastrointestinal adverse reactions and actively seek to detect lanthanum deposition by abdominal CT or radiography (X-ray). After the occurrence of lanthanum deposition, drug withdrawal and promotion of defecation are primary treatment methods.

Efficacy and Safety of Ferric Citrate on Hyperphosphatemia among Chinese Patients with Chronic Kidney Disease Undergoing Hemodialysis: A Phase III Multicenter Randomized Open-Label Active-Drug-Controlled Study.

INTRODUCTION: Hyperphosphatemia in chronic kidney disease (CKD) patients is positively associated with mortality. Ferric citrate is a potent phosphorus binder that lowers serum phosphorus level and improves iron metabolism. We compared its efficacy and safety with active drugs in Chinese CKD patients with hemodialysis. METHODS: Chinese patients undergoing hemodialysis were randomized into two treatment groups in a 1:1 ratio, receiving either ferric citrate or sevelamer carbonate, respectively, for 12 weeks. Serum phosphorus levels, calcium concentration, and iron metabolism parameters were evaluated every 2 weeks. Frequency and severity of adverse events were recorded. RESULTS: 217 (90.4%) patients completed the study with balanced demographic and baseline characteristics between two groups. Ferric citrate decreased the serum phosphorus level to 0.59 ± 0.54 mmol/L, comparable to 0.56 ± 0.62 mmol/L by sevelamer carbonate. There was no significant difference between two groups (p > 0.05) in the proportion of patients with serum phosphorus levels reaching the target range, the response rate to the study drug, and the changes of corrected serum calcium concentrations, and intact-PTH levels at the end of treatment. The change of iron metabolism indicators in the ferric citrate group was significantly higher than those in the sevelamer carbonate group. There are 47 (40.5%) patients in the ferric citrate group, and 26 (21.3%) patients in the sevelamer carbonate group experienced drug-related treatment emergent adverse events (TEAEs); most were mild and tolerable. Common drug-related TEAEs were gastrointestinal disorders, including diarrhea (12.9 vs. 2.5%), fecal discoloration (14.7 vs. 0%), and constipation (1.7 vs. 7.4%) in ferric citrate and sevelamer carbonate group. CONCLUSION: Ferric citrate capsules have good efficacy and safety in the control of hyperphosphatemia in adult patients with CKD undergoing hemodialysis. Efficacy is not inferior to sevelamer carbonate. The TEAEs were mostly mild and tolerated by the patients.

Family-centered empowerment approach to optimize phosphate management among hemodialysis patients: an experimental study.

BACKGROUND: This study aimed to investigate the effect of a family-centered empowerment program on hyperphosphatemia management. METHOD: This experimental study was performed on 80 randomly selected eligible patients with hyperphosphatemia undergoing hemodialysis. Patients were assigned randomly to two groups of family-centered empowerment program (FCEPG) and control group (CG) by coin toss (40 people per group). Data collection tools were the researcher-made Phosphate Control Knowledge Scale, the researcher-made Adherence to Dietary Restriction of Phosphorus Intake Scale, the eight-item Morisky Medication Adherence Scale, and serum phosphorus measurements. Data were collected before the intervention, one month, and three months after the intervention. Patients in FCEPG participated in a family-centered empowerment program. The statistical significance level was considered to be 0.05. RESULTS: Inter-group comparisons showed no significant difference between FCEPG and CG in terms of the mean score of knowledge of phosphate control, adherence to dietary restriction of phosphorus intake, adherence to medication, and the mean serum phosphorus level before the empowerment program, but showed significant differences between them in these respects at one month after the program and three months after the program (p < 0.05). Intra-group comparisons showed a significant difference in FCEPG between the mean and standard deviation of all four variables before the empowerment program and the corresponding values one month and three months after the program (P < 0.05). CONCLUSION: The findings of this study can be used in various fields of healthcare in the hospital and community.

Educación alimentaria en pacientes en dialisis / Nutritional education in dialysis patients

La enfermedad renal crónica terminal aumenta el riesgo cardiovascular y puede ocasionar defectos en la mineralización ósea. Para prevenir esto, se debe mantener el fósforo plasmático normal, que depende de la diálisis, los quelantes y la ingesta de fósforo, principalmente de origen inorgánico, incorporado mediante aditivos alimentarios. Las intervenciones nutricionales son pilares en el tratamiento de estos pacientes. El objetivo es facilitar estrategias alimentarias a un grupo de pacientes pediátricos en diálisis, mediante educación alimentaria nutricional, para aumentar el consumo de alimentos naturales, disminuyendo la ingesta de fósforo inorgánico especialmente de los productos cárnicos procesados. Materiales y métodos: se estudió una población pediátrica en diálisis. Se preparó un programa educativo con atención personalizada, instrucción alimentaria y seguimiento mensual, seguido de un taller. Resultados: n: 17 pacientes, edad decimal media de 12,3, 53% sexo masculino, 88% en hemodiálisis. Previo a la intervención el 64,7% consumía productos cárnicos procesados. Luego del taller el 58,8% disminuyó su consumo, el 41,2% aumentó la ingesta de preparaciones caseras, el 53% incorporó nuevos condimentos, de los cuales el 89% presentó al incorporarlos, mejor aceptación a las preparaciones. Conclusiones: la hiperfosfatemia está presente en alrededor del 50% de los pacientes en diálisis asociándose a un incremento entre 20% al 40% del riesgo de mortalidad. La presencia de fósforo oculto en los alimentos y la falta de adherencia hacen prioritario trabajar en programas educativos que favorezcan el aprendizaje colaborativo, centralizados en prácticas culinarias, para brindar herramientas que faciliten una alimentación natural, disminuyendo el consumo de ultraprocesados (AU)

Chronic end-stage renal disease increases the risk of cardiovascular disease and may lead to defects in bone mineralization. In order to prevent these risks, normal plasma phosphorus levels should be maintained. Achieving this goal depends on dialysis, chelators, and phosphorus intake, mainly of inorganic origin, incorporated through food supplements. Nutritional interventions are crucial in the treatment of these patients. The objective is to facilitate nutritional strategies to a group of pediatric dialysis patients, through food education, to increase the consumption of natural foods, decreasing the intake of inorganic phosphorus, especially from processed meat products. Materials and methods: a pediatric population undergoing dialysis was studied. An educational program was prepared with personalized care, nutritional instruction, and monthly follow-up visits, followed by a workshop. Results: n: 17 patients, mean age 12.3 years, 53% male, 88% on hemodialysis. Prior to the intervention, 64.7% consumed processed meat products. After the workshop, 58.8% decreased their consumption, 41.2% increased the intake of homemade food, 53% incorporated new seasonings, of whom 89% reported better acceptance of the preparations when they were incorporated. Conclusions: hyperphosphatemia is observed in around 50% of patients undergoing dialysis and is associated with a 20% to 40% increased risk of mortality. The presence of hidden phosphorus in food and the lack of adherence point to the need for the development of educational programs that promote collaborative learning, focusing on food-preparation practices. These programs should provide tools that facilitate a natural diet, reducing the consumption of ultra-processed food (AU)

'Phos'tering a Clear Message: The Evolution of Dietary Phosphorus Management in Chronic Kidney Disease.

Phosphorus is a vital nutrient, but disturbances in phosphorus homeostasis are central to chronic kidney disease-mineral and bone disorder. To minimize disturbances, traditional dietary guidance focused on a numerical phosphorus target leading to the exclusion of many healthy foods and implementation challenges. Contemporary phosphorus guidance focuses on dietary source, avoiding additives, and emphasizing low-phosphorus bioaccessibility foods, leading to a more liberal approach. Additional work is needed to demonstrate the efficacy of these contemporary approaches and understand the influence of specific foods, processing, and cooking methods. Unfortunately, patient education using traditional and contemporary strategies may give mixed messages, particularly related to plant-based foods. Thus, greater clarity on the effects of specific foods and dietary patterns may improve phosphorus education. This review aims to discuss the evolution of dietary phosphorus management while highlighting areas for future research that can help move the field toward stronger evidence-based guidance to prevent and treat hyperphosphatemia.

Efficacy and safety of tenapanor in hemodialysis patients with hyperphosphatemia: A systematic review and meta-analysis of randomized placebo-controlled trials.

BACKGROUND: The effects of tenapanor in reducing serum phosphorus in hemodialysis patients with hyperphosphatemia are uncertain and no relevant meta-analysis has been conducted. We performed a meta-analysis of randomized placebo-controlled trials to evaluate the efficacy and safety of tenapanor. METHODS: All randomized controlled trials of tenapanor were searched up to 1 August 2022. The primary endpoint was the change in serum phosphorus level from baseline with tenapanor and placebo. Data on drug-related adverse events (AEs), gastrointestinal AEs and diarrhea were collected to determine the safety of tenapanor. RESULTS: There were 533 patients throughout five trials that were eligible. Tenapanor significantly lowered blood phosphorus level by 1.79 mg/dl in the mean difference than the placebo. Diarrhea, gastrointestinal AEs, and drug-related AEs were more severe than placebo. CONCLUSIONS: This meta-analysis showed that although drug side effects were common, tenapanor significantly reduced serum phosphorus level in hemodialysis patients.

Effects of EOS789, a novel pan-phosphate transporter inhibitor, on phosphate metabolism : Comparison with a conventional phosphate binder.

BACKGROUND: Inorganic phosphate (Pi) binders are the only pharmacologic treatment approved for hyperphosphatemia. However, Pi binders induce the expression of intestinal Pi transporters and have limited effects on the inhibition of Pi transport. EOS789, a novel pan-Pi transporter inhibitor, reportedly has potent efficacy in treating hyperphosphatemia. We investigated the properties of EOS789 with comparison to a conventional Pi binder. METHODS: Protein and mRNA expression levels of Pi transporters were measured in intestinal and kidney tissues from male Wistar rats fed diets supplemented with EOS789 or lanthanum carbonate (LC). 32Pi permeability was measured in intestinal tissues from normal rats using a chamber. RESULTS: Increased protein levels of NaPi-2b, an intestinal Pi transporter, and luminal Pi removal were observed in rats treated with LC but not in rats treated with EOS789. EOS789 but not LC suppressed intestinal protein levels of the Pi transporter Pit-1 and sodium/hydrogen exchanger isoform 3. 32Pi flux experiments using small intestine tissues from rats demonstrated that EOS789 may affect transcellular Pi transport in addition to paracellular Pi transport. CONCLUSION: EOS789 has differing regulatory effects on Pi metabolism compared to LC. The properties of EOS789 may compensate for the limitations of LC therapy. The combined or selective use of EOS789 and conventional Pi binders may allow tighter control of hyperphosphatemia. J. Med. Invest. 70 : 260-270, February, 2023.

Dentoalveolar Alterations in an Adenine-Induced Chronic Kidney Disease Mouse Model.

Chronic kidney disease (CKD) is characterized by kidney damage and loss of renal function. CKD mineral and bone disorder (CKD-MBD) describes the dysregulation of mineral homeostasis, including hyperphosphatemia and elevated parathyroid hormone (PTH) secretion, skeletal abnormalities, and vascular calcification. CKD-MBD impacts the oral cavity, with effects including salivary gland dysfunction, enamel hypoplasia and damage, increased dentin formation, decreased pulp volume, pulp calcifications, and altered jaw bones, contributing to clinical manifestations of periodontal disease and tooth loss. Underlying mechanisms are not fully understood, and CKD mouse models commonly require invasive procedures with high rates of infection and mortality. We aimed to characterize the dentoalveolar effects of an adenine diet (AD)-induced CKD (AD-CKD) mouse model. Eight-week-old C57BL/6J mice were provided either a normal phosphorus diet control (CTR) or adenine and high-phosphorus diet CKD to induce kidney failure. Mice were euthanized at 15 weeks old, and mandibles were collected for micro-computed tomography and histology. CKD mice exhibited kidney failure, hyperphosphatemia, and hyperparathyroidism in association with porous cortical bone in femurs. CKD mice showed a 30% decrease in molar enamel volume compared to CTR mice. Enamel wear was associated with reduced ductal components, ectopic calcifications, and altered osteopontin (OPN) deposition in submandibular salivary glands of CKD mice. Molar cusps in CKD mice were flattened, exposing dentin. Molar dentin/cementum volume increased 7% in CKD mice and pulp volume decreased. Histology revealed excessive reactionary dentin and altered pulp-dentin extracellular matrix proteins, including increased OPN. Mandibular bone volume fraction decreased 12% and bone mineral density decreased 9% in CKD versus CTR mice. Alveolar bone in CKD mice exhibited increased tissue-nonspecific alkaline phosphatase localization, OPN deposition, and greater osteoclast numbers. AD-CKD recapitulated key aspects reported in CKD patients and revealed new insights into CKD-associated oral defects. This model has potential for studying mechanisms of dentoalveolar defects or therapeutic interventions. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The Impact of Medical Nutrition Intervention on the Management of Hyperphosphatemia in Hemodialysis Patients with Stage 5 Chronic Kidney Disease: A Case Series.

The treatment and interdisciplinary management of patients with chronic kidney disease (CKD) continue to improve long-term outcomes. The medical nutrition intervention's role is to establish a healthy diet plan for kidney protection, reach blood pressure and blood glucose goals, and prevent or delay health problems caused by kidney disease. Our study aims to report the effects of medical nutrition therapy-substituting foods rich in phosphorus-containing additives with ones low in phosphates content on phosphatemia and phosphate binders drug prescription in stage 5 CKD patients with hemodialysis. Thus, 18 adults with high phosphatemia levels (over 5.5 mg/dL) were monitored at a single center. Everyone received standard personalized diets to replace processed foods with phosphorus additives according to their comorbidities and treatment with prosphate binder drugs. Clinical laboratory data, including dialysis protocol, calcemia, and phosphatemia, were evaluated at the beginning of the study, after 30 and 60 days. A food survey was assessed at baseline and after 60 days. The results did not show significant differences between serum phosphate levels between the first and second measurements; thus, the phosphate binders' initial doses did not change. After 2 months, phosphate levels decreased considerably (from 7.322 mg/dL to 5.368 mg/dL); therefore, phosphate binder doses were diminished. In conclusion, medical nutrition intervention in patients with hemodialysis significantly reduced serum phosphate concentrations after 60 days. Restricting the intake of processed foods containing phosphorus additives-in particularized diets adapted to each patient's comorbidities-and receiving phosphate binders represented substantial steps to decrease phosphatemia levels. The best results were significantly associated with life expectancy; at the same time, they showed a negative correlation with the dialysis period and participants' age.

Patiromer Treatment in Patients With CKD, Hyperkalemia, and Hyperphosphatemia: A Post Hoc Analysis of 3 Clinical Trials.

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 sK+at baseline, the mean±SD reduction in sP and sK+after 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 sMg2+in these patients was -0.25±0.23mg/dL while sCa2+remained unchanged. Both sMg2+and sCa2+remained 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 sK+to 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 sK+and sP in hyperkalemic patients with CKD and hyperphosphatemia.