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We report a case of severe hypokalaemia and moderate hypophosphataemia from clay ingestion. A 60-year-old woman presented with flaccid paralysis. Investigations revealed a serum potassium level of 1.8 mmol/L, phosphate level of 0.56 mmol/L and creatine kinase level of 30 747 IU/L. She had marked proximal and distal muscle weakness due to severe hypokalaemia and concurrent hypophosphataemia, which likely contributed to the onset of rhabdomyolysis. The patient subsequently admitted to significant pica, most likely secondary to an associated iron deficiency. We conclude that the ingested clay acted as a potassium and phosphate binder. Although we did not investigate the content of the clay in this case, it has been reported that clay can bind potassium in vitro and is rich in minerals such as aluminium that could play a role in the binding of phosphate, although the exact mechanism remains unclear. The patient recovered fully and outpatient follow-up at 6 months and again at 40 months confirmed no electrolyte abnormality, myopathy nor any further geophagia.

High serum phosphate levels have been associated with increased morbidity and mortality in dialysis patients. Nephrologists routinely counteract the positive phosphate balance in dialysis patients through nutritional counselling, stronger phosphate removal by dialysis and prescription of phosphate binders. An individualized choice of phosphate binders is a desirable option to improve the poor adherence with these medications’ prescription that has been associated with hyperphosphataemia.

A series of problems including osteopathy, abnormal serum data, and vascular calcification associated with chronic kidney disease (CKD) are now collectively called CKD-mineral bone disease (CKD-MBD). The pathophysiology of CKD-MBD is becoming clear with the emerging of αKlotho, originally identified as a progeria-causing protein, and bone-derived phosphaturic fibroblast growth factor 23 (FGF23) as associated factors. Meanwhile, compared with calcium and parathyroid hormone, which have long been linked with CKD-MBD, phosphate is now attracting more attention because of its association with complications and outcomes. Incidentally, as the pivotal roles of FGF23 and αKlotho in phosphate metabolism have been unveiled, how phosphate metabolism and hyperphosphatemia are involved in CKD-MBD and how they can be clinically treated have become of great interest. Thus, the aim of this review is reconsider CKD-MBD from the viewpoint of phosphorus, its involvement in the pathophysiology, causing complications, therapeutic approach based on the clinical evidence, and clarifying the importance of phosphorus management.

Background and Aims Hyperphosphatemia is common in end-stage renal disease (ESRD) because of impaired renal phosphate excretion and is treated by dietary measures, dialysis techniques and the use of phosphate binder medication. It is one of the most important cardiovascular risk factors for dialysis patients. Our goal was to involve dialysis patients in the achievement of phosphate targets by self-adjusting the dose of Phosphate Binders (PB) on a meal-to-meal basis, according to the individual dietary P intake Method We conducted an interventional prospective single-arm study with a pre-post design. The inclusion criteria were patients with ESRD who had been receiving dialysis for more than three months, with dialysis schedule for four hours per session, three times per week, and who were older than 18 years of age. The primary endpoints of the study were the number of patients who reached the goal of serum phosphate before and after the training program and the weekly mean serum phosphate levels evaluated after the intervention period and compare them with the pre-intervention baseline levels. The secondary end-point was the burden of PB daily. All patients were trained in a self-administer PB program. A self-adjusted PB dose card was developed based on the phosphate food content list published by the National Technical University of Athens. The aim was to allow patients to immediately calculate the iP content of any food they consume easily. Phosphate Equivalent (PEQ) was defined as the weight of phosphorus having the same phosphate impact as a given weight of food. One PEQ corresponded in 100 mg of inorganic phosphorous and to one tablet of PB (one tablet of 800 mg of sevelamer). After 4 weeks (weeks 1-4) of washout from previous phosphate binders, eligible patients with serum phosphorus concentrations ≥ 6 mg/dl were included in the study. All patients received standard dietary phosphate counseling and a fixed dosing regimen of sevelamer PB was prescribed according to KDIGO and dialysis unit protocols for eight weeks (weeks 5-12 – pre-intervention period) In the 13th week, patients were asked to practice the self-administer PB program for eight more weeks. Results A total of 97 patients were screened for the study. 21 patients were excluded. 74 patients completed the study. The percentage of patients with uncontrolled phosphate levels reduced from 56.76% (42 out of 74) to 36.48 % (27 out of 74) in the post-intervention period. Of 9 patients who initially had a serum phosphorus level ≥9 mg/dl, 8 were reverted to phosphorus levels < 6 mg/dl at the end of the PEQ intervention period. There was a significant reduction of phosphate levels (prePEQ 7.42 ± 1.43 mg/dl vs. postPEQ 5.59 ± 1.82 mg/dL, p=0.036) and Ca × P levels (prePEQ: 67.1 ± 11.5 mg2/dL2; postPEQ: 51.9 ± 13.4 mg2/dL2, p=0.021) after patient education. There was a non-significant increase on serum calcium (pre PEQ: 8.13 ± 1.18 mg/dL; post PEQ: 8.56 ± 0.83mg/dL, p=0.515) and iPTH (prePEQ: 411 ± 376 pg/mL; postPEQ: 381 ± 321 pg/mL,p=0.13) Conclusion Our work shows that providing the patients with a relatively simple tool about the use of phosphate binders as PEQ is, we had a positive effect on the dialysis patients’ knowledge about the use of PB, phosphate content of their meals, and increase their sense of the necessity of the treatment and it was proved more effective than the standard fixed dose method. Using the PEQ education system was rewarding in an additional 20% of the patients with previous uncontrolled hyperphosphatemia. The PEQ education system is an efficient self-adjustment phosphate binder dosage tool in dialysis patients in reducing the serum phosphate level in our hemodialysis patients.

Phosphate is a key uremic toxin associated with adverse outcomes. As chronic kidney disease (CKD) progresses, the kidney capacity to excrete excess dietary phosphate decreases, triggering compensatory endocrine responses that drive CKD-mineral and bone disorder (CKD-MBD). Eventu-ally, hyperphosphatemia develops, and low phosphate diet and phosphate binders are prescribed. Recent data have identified a potential role of the gut microbiota in mineral bone disorders. Thus, parathyroid hormone (PTH) only caused bone loss in mice whose microbiota was enriched in the Th17 cell-inducing taxa segmented filamentous bacteria. Furthermore, the microbiota was required for PTH to stimulate bone formation and increase bone mass, and this was dependent on bacterial production of the short-chain fatty acid butyrate. We review current knowledge on the relationship between phosphate, microbiota and CKD-MBD. Topics include microbial bioactive compounds of special interest in CKD, the impact of dietary phosphate and phosphate binders on the gut microbiota, the modulation of CKD-MBD by the microbiota and the potential therapeutic use of microbiota to treat CKD-MBD through the clinical translation of concepts from other fields of science such as the optimization of phosphorus utilization and the use of phosphate-accumulating organisms., This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 860329, FIS/Fondos FEDER (PI18/01366, PI20/00744, PI19/00815, DTS18/00032, ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009), Sociedad Española de Nefrología, FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM

Introduction: Chronic kidney disease - mineral and bone disorders (CKD-MBD) are common in dialysis patients. Definition of targets for calcium (Ca), phosphorus (P), parathormone (iPTH), and alkaline phosphatase (ALP) and their treatment recommendations, are provided by international guidelines. There are few studies analyzing CKD-MBD in peritoneal dialysis (PD) patients and the impact of guidelines on mineral metabolism control. The aim of our study was to describe the prevalence of biomarkers for CKD-MBD in a large cohort of PD patients in Brazil. Methods: Data from the nation-wide prospective observational cohort BRAZPD II was used. Incident patients were followed between December 2004 and January 2011. According to KDOQI recommendations, reference ranges for total Ca were 8.4 to 9.5 mg/dL, for P, 3.5 to 5.5 mg/dL, for iPTH, 150-300 pg/mL, and for ALP, 120 U/L. Results: Mean age was 59.8 ± 16 years, 48% were male, and 43% had diabetes. In the beginning, Ca was 8.9 ± 0.9 mg/dL, and 48.3% were on the KODQI target. After 1 year, Ca increased to 9.1 ± 0.9 mg/dL and 50.4% were in the KDOQI preferred range. P at baseline was 5.2 ± 1.6 mg/dL, with 52.8% on target, declining to 4.9 ± 1.5 mg/dL after one year, when 54.7% were on target. Median iPTH at baseline was 238 (P25% 110 - P75% 426 pg/mL) and it remained stable throughout the first year; patients within target ranged from 26 to 28.5%. At the end of the study, 80% was in 3.5 meq/L Ca dialysate concentration, 66.9% of patients was taking any phosphate binder, and 25% was taking activated vitamin D. Conclusions: We observed a significant prevalence of biochemical disorders related to CKD-MBD in this dialysis population. Resumo Introdução: Os distúrbios minerais e ósseos da doença renal crônica (DMO-DRC) são comuns em pacientes em diálise. A definição de metas para cálcio (Ca), fósforo (P), paratormônio (PTHi) e fosfatase alcalina (FA) e suas recomendações de tratamento são fornecidas por diretrizes internacionais. Há poucos estudos analisando o DMO-DRC em pacientes em diálise peritoneal (DP) e o impacto das diretrizes no controle do metabolismo mineral. O objetivo do nosso estudo foi descrever a prevalência de alterações nos marcadores para DMO-DRC em uma grande coorte de pacientes em DP no Brasil. Métodos: Foram utilizados dados da coorte observacional prospectiva nacional BRAZPD II. Pacientes incidentes foram acompanhados entre Dezembro de 2004 e Janeiro de 2011. De acordo com as recomendações do KDOQI, os intervalos de referência para Ca total foram de 8,4 a 9,5 mg/dL, para P, 3,5 a 5,5 mg/dL, para PTHi, 150-300 pg/mL, e para FA, 120 U/L. Resultados: A idade média foi de 59,8 ± 16 anos, 48% eram homens e 43% tinham diabetes. No início, o Ca era de 8,9 ± 0,9 mg/dL, e 48,3% estavam na meta do KODQI. Após 1 ano, o Ca aumentou para 9,1 ± 0,9 mg/dL e 50,4% estavam na faixa preferida do KDOQI. P basal era 5,2 ± 1,6 mg/dL, com 52,8% na meta, diminuindo para 4,9 ± 1,5 mg/dL após um ano, quando 54,7% estavam na meta. O PTHi basal mediano foi de 238 (P25% 110 - P75% 426 pg/mL) e permaneceu estável durante o primeiro ano; os pacientes dentro da meta variaram de 26 a 28,5%. No final do estudo, 80% estavam na concentração de 3,5 meq/L de Ca dialisato, 66,9% dos pacientes estavam tomando qualquer quelante de fosfato, e 25% estavam tomando vitamina D ativada. Conclusões: Observamos uma prevalência significativa de distúrbios bioquímicos relacionados ao DMO-DRC nesta população em diálise.

The article describes various methods of synthesizing heat-resistant binders based on large-tonnage wastes of enterprises. The use of pyrite butts and expanded clay dust, respectively, from the Chapayevsky Chemical Plant and the expanded clay plant of the city of Samara in the compositions of heat-resistant concrete on phosphate binders allowed to increase their residual strength in the zone of critical temperatures (1300-1350 °С). The refractoriness of these phosphate binders turned out to be very low (≈1300 °С), which required the use of such a method of its increase as the introduction of fine high-alumina fillers with high melting points into the composition of the binder. It was revealed and justified that the use of an alumina-chromium petrochemical waste IM-2201 allowed to increase the refractoriness of the heat-resistant composition to 1600 °С. On the basis of the developed alumina-iron-phosphate, zirconyliron- phosphate and alumino-silicophosphate binders, the compositions of heavy concrete with chamotte and high-aluminous aggregates of grades 400 and 500 were selected.

Few clinical studies have investigated the value of phosphate (P)-lowering therapies in early chronic kidney disease (CKD) patients in whom hyperphosphataemia has not yet clearly developed and they report conflicting and even unexpected results. In this issue of Clinical Kidney Journal, de Krijger et al. found that sevelamer carbonate (4.8 g/day for 8 weeks) did not induce a significant reduction of pulse wave velocity (PWV) and that fibroblast growth factor 23 (FGF23) did not decrease despite a decline in 24-h urine P excretion. To some extent these findings challenge the concept that ‘preventive’ P binder therapy to lower FGF23 is a useful approach, at least over this short period of time. Interestingly, in a subgroup of patients with absent or limited abdominal vascular calcification, treatment did result in a statistically significant reduction in adjusted PWV, suggesting that PWV is amenable to improvement in this subset. Interpretation of the scarce and heterogeneous observations described in early CKD remains difficult and causality and/or the possibility of ‘preventive’ treatment may not yet be completely disregarded. Moreover, de Krijger et al. contribute to the identification of new sources of bias and methodological issues that may lead to more personalized treatments, always bearing in mind that not all patients and not all P binders are equal.

Background Chronic Kidney Disease - Mineral and Bone Disorder (CKD-MBD) is a significant cause of morbidity among haemodialysis patients and is associated with pathological changes in phosphate, calcium and parathyroid hormone (PTH). In the ACTIVE Dialysis study, extended hours dialysis reduced serum phosphate but did not cause important changes in PTH or serum calcium. This secondary analysis aimed to determine if changes in associated therapies may have influenced these findings and to identify differences between patient subgroups. Methods The ACTIVE Dialysis study randomised 200 participants to extended hours haemodialysis (≥24 h/week) or conventional haemodialysis (≤18 h/week) for 12 months. Mean differences between treatment arms in serum phosphate, calcium and PTH; and among key subgroups (high vs. low baseline phosphate/PTH, region, time on dialysis, dialysis setting and frequency) were examined using mixed linear regression. Results Phosphate binder use was reduced with extended hours (− 0.83 tablets per day [95% CI -1.61, − 0.04; p = 0.04]), but no differences in type of phosphate binder, use of vitamin D, dose of cinacalcet or dialysate calcium were observed. In adjusted analysis, extended hours were associated with lower phosphate (− 0.219 mmol/L [− 0.314, − 0.124; P

Ferric citrate hydrate (FC) is an iron-based phosphate binder approved for hyperphosphataemia in patients with chronic kidney disease. We conducted a randomised controlled trial to evaluate the effects of FC on anaemia management in haemodialysis patients with hyperphosphataemia. We 1:1 randomised 93 patients who were undergoing haemodialysis and being treated with non-iron-based phosphate binders and erythropoiesis-stimulating agents (ESA) to receive 24 weeks of FC or to continue their non-iron-based phosphate binders (control) in a multicentre, open-label, parallel-design. Phosphate level was controlled within target range (3.5–6.0 mg/dL). The primary endpoint was change in ESA dose from baseline to end of treatment. Secondary endpoints were changes in red blood cell, iron and mineral, and bone-related parameters. Compared with control, FC reduced ESA dose [mean change (SD), −1211.8 (3609.5) versus +1195 (6662.8) IU/week; P = 0.03] without significant differences in haemoglobin. FC decreased red blood cell distribution width (RDW) compared with control. While there were no changes in serum phosphate, FC reduced C-terminal fibroblast growth factor (FGF) 23 compared with control. The incidence of adverse events did not differ significantly between groups. Despite unchanged phosphate and haemoglobin levels, FC reduced ESA dose, RDW, and C-terminal FGF23 compared with control.

Objective Hyperphosphatemia is a common complication in patients with end-stage renal disease on hemodialysis. The mainstay of phosphate management involves a low-phosphate diet and use of phosphate binders, yet these are often insufficient. This study was the first to use behavioral change techniques to encourage the use of phosphate binders and dietary modifications through a series of Phosphate Education and Planning (PEP) talks. Design and Methods A total of 46 hemodialysis patients with hyperphosphatemia were enrolled. All patients were eligible to receive a series of 4 talks, each with defined goals of the long-term management of serum phosphate levels. Qualitative data from the talks were gathered during each intervention, whereas serum phosphate was selected as an outcome measure. Results There was a modest improvement (−0.31 mg/dL) in the serum phosphate levels of the patients who received the entire PEP talk series. Furthermore, the most common self-identified barriers for patients were phosphate binder prescriptions not tailored to their eating routines and lack of resources for suitable dietary changes. Conclusions The PEP talk series model is appropriate to manage persistent hyperphosphatemia despite usual management in outpatient dialysis unit by identifying patient-specific barriers and providing resources that can mitigate them. The strength of this model lies in using a multifaceted approach by applying both pharmacotherapy and dietary changes, along with behavioral change, to achieve lasting improvements in serum phosphate levels in hemodialysis patients with persistently elevated serum phosphate levels.

This study is to determine the pharmacological effects of nano-lanthanum hydroxide (nano-LH) in the treatment of hyperphosphatemia, in comparison with other phosphate binders. Rat models of chronic renal failure and hyperphosphatemia were induced by adenine, which were treated with nano-LH (0.15, 0.10, and 0.05 g/Kg/d), lanthanum carbonate (0.30 g/Kg/d), and normal-size lanthanum hydroxide (0.10 g/Kg/d), respectively. To investigate the therapeutic effects, the serum levels of phosphorus, Scr, Ucr, BUN, UUN, PTH, and other hyperphosphatemia-related biochemical indicators were determined. A novel phosphorus-binding agent, nano-LH, was synthesized herein, which was rod-like particle with the length of 30–50 nm, width of 10–20 nm, and diameter of 5–10 nm. In vitro phosphorus binding experiments showed that nano-LH had better binding rate. Pharmacodynamic experiments confirmed that the therapeutic effects of lanthanum-hydroxide (0.10 g/kg/d) were superior to other existing phosphate binders in rat models of hyperphosphatemia, in lowering the blood phosphate level and improving the renal function. In the term of drug safety, our preliminary results showed that the nano-LH at appropriate dose did not cause death cases in mice, and the serum levels of alkaline phosphatase and lactate dehydrogenase were not significantly changed, indicating good oral safety. Nano-LH has high potency compared with several phosphate binders, which might be a promising therapeutic agent for the treatment of hyperphosphatemia in clinic.

Background: Hyperphosphatemia is a major accelerator of complications in chronic kidney disease and dialysis, and phosphate (Pi) binders have been shown to regulate extracellular Pi levels. Research on hyperphosphatemia in mouse models is scarce, and few models display hyperphosphatemia induced by glomerular injury, despite its relevance to human glomerular disease conditions. In this study, we investigated the involvement of hyperphosphatemia in kidney disease progression using a mouse model in which hyperphosphatemia is induced by focal segmental glomerulosclerosis (FSGS). Methods: We established the NEP25 mouse model in which FSGS-hyperphosphatemia is induced by podocyte injury and evaluated the effect of a Pi binder, sevelamer. Results: After disease induction, we confirmed a gradual increase in serum Pi accompanied by reduced renal function and observed increases in serum FGF23 and PTH. Treatment with sevelamer significantly reduced serum Pi and urinary Pi fractional excretion and suppressed increases in serum FGF23 and PTH. A high dose improved serum creatinine and tubular injury markers, and pathological analysis confirmed amelioration of glomerular and tubular damage. Gene expression and marker analysis suggested protective effects on tubular epithelial cells in the diseased kidney. Compared to disease control, NEP25 mice treated with sevelamer retained their mRNA expression of Klotho, a known FGF23 co-receptor and renoprotective factor. Conclusions: Hyperphosphatemia caused by renal function decline was observed in a FSGS-induced NEP25 mouse model. Studies using this model showed that Pi regulation had a positive impact on kidney disease progression, and notably on tubular epithelial cell injury, which indicates the importance of Pi regulation in the treatment of kidney disease progression.

Aim Hyperphosphataemia is associated with increased mortality and morbidity in end stage renal disease. Despite phosphate binder therapy, a large proportion of patients do not reach the treatment target. In five contemporary binders we explored the influence of pH and phosphate concentration on phosphate binding. This interaction could be of relevance in clinical practice. Methods Phosphate binding was quantified in vitro in 25 mL of purified water containing phosphate concentrations of 10, 15 and 20 mM and baseline pH values of 3.0 or 6.0, with a binder over 6 h. Lanthanum carbonate, calcium acetate/magnesium carbonate, sevelamer carbonate, calcium carbonate and sucroferric oxyhydroxide, 67 mg of each, were used. The experiments were performed in duplicate. The primary outcome was the difference in the amount of bound phosphate for each binder after 6 h in solutions at two different pH values. Secondary outcomes were the influence of phosphate concentration on phosphate binding, next to binding patterns and phosphate binder saturation. Results and Conclusion In this specific in vitro setting, lanthanum carbonate, sevelamer carbonate, calcium carbonate and sucroferric oxyhydroxide bound more phosphate in the solution with baseline pH of 3.0. Differences however were small except for lanthanum carbonate. Calcium acetate/magnesium carbonate was most effective in a solution with baseline pH of 6.0. All phosphate binders bound more phosphate in solutions with higher concentrations of phosphate. Sevelamer carbonate, calcium acetate/magnesium carbonate and sucroferric oxyhydroxide bound most phosphate in the first hour and reached maximum binding capacity in less than 6 h.

Introduction: Mineral and bone disorders (MBD) are among the important complications of chronic kidney disease (CKD) including end-stage renal disease. In addition to the higher rate of all-cause and cardiovascular-related mortality, MBD is also a cause of significant morbidity in CKD patients. Materials and Methods: This is a cross-sectional study of all consenting patients on hemodialysis at Aminu Kano Teaching Hospital, between December 2011 and June 2012. With the aid of an interviewer-administered questionnaire, the demographic profile and clinical features of the patients were obtained. After a general physical examination, blood sample was taken for the determination of calcium, phosphate, intact parathyroid hormone, 25 hydroxy (25[OH]) Vitamin D3, packed cell volume, serum creatinine, and potassium. Results: Forty-eight patients on maintenance hemodialysis were recruited for the study, 39 (81.3%) were male and 9 (18.8%) were female. The age range was 40–59 years, with a mean of 45.96 ± 13.7 years. Chronic glomerulonephritis was the predominant cause of CKD (25%). Hyperphosphatemia was noted in 19 (39.5%) of the patients, whereas 22 (46%) had hypocalcemia. In 26 (54.1%) of the patients, the calcium-phosphate product was >4.55 mmol2/L2. We found that 58% of the patients had CKD-MBD, of which 15 (31%) had secondary hyperparathyroidism, whereas 13 (27%) had features suggestive of adynamic bone disease. None of the patient had normal serum 25(OH) Vitamin D3 (mean: 43.79 ± 21 ng/ml). Conclusion: CKD-MBD is common among patients on hemodialysis in our center. Screening for CKD-MBD and appropriate use of phosphate binder and Vitamin D when indicated are highly recommended.

Background Phosphate binders are widely used to achieve serum phosphorus control in patients with end-stage renal disease. However, the large pill burden associated with these medications may decrease adherence to therapy. In clinical trials, sucroferric oxyhydroxide (SO) demonstrated equivalent control of serum phosphorus to sevelamer, with a lower daily pill burden. We examined changes in phosphate binder pill burden, medication possession ratio (MPR), and phosphorus control among in-center hemodialysis (ICHD) patients converting to SO from another phosphate binder as part of routine care. Materials and methods Patients included in this retrospective analysis (N=490) were ≥18 years old, received ICHD at a large dialysis organization (LDO), and were enrolled in the LDO's pharmacy service. Patients converting to SO were those who had supply of another phosphate binder, received a first prescription fill for SO, and subsequently did not refill the non-SO phosphate binder. Patients were followed over the 6 months before and 6 months following the first SO fill and were censored from the analysis upon modality change, loss to follow-up, discontinuation of SO, or fill of a prescription for another phosphate binder after SO initiation (number censored=361). Outcome measures assessed were total phosphate binder pill burden and MPR, serum phosphorus, and percentage of patients with serum phosphorus ≤5.5 mg/dL. Results Among patients converting to SO, mean phosphate binder pill burden was 10.8 pills/day during baseline; this decreased to 5.5 pills/day during follow-up (P

Renal dietitians play a pivotal role in the ongoing management of chronic kidney disease in patients on hemodialysis. Awareness of changes to clinical practice guidelines that may impact laboratory parameters associated with chronic kidney disease-mineral and bone disorder is important for optimal patient care. In this article, the Kidney Disease: Improving Global Outcomes 2017 Clinical Practice Guideline Update recommendations related to the treatment of secondary hyperparathyroidism in adults on hemodialysis are reviewed and treatment implications for renal dietitians discussed. Specific attention is given to the integration of updated recommendations such as the use of calcimimetics as part of a combination approach to the existing treatment paradigm. Renal dietitians can directly apply the updated clinical recommendations in the evaluation of diet composition; food additives; medication adherence challenges with phosphate binder type and use and serial monitoring of phosphorus, calcium, and parathyroid hormone levels to inform clinical decisions on treatment options for patients.

Chronic Kidney Disease (CKD) patient with Mineral and Bone Disorder complication have to chew calcium carbonate tablet as a phosphate binder, but infact, patient swallow it in a whole. Gastrointestinal (GI) disorders can affect the efficacy of medicine. This study aims to analyze the effectiveness comparation of chewed and whole swallowed calcium carbonate tablet in CKD patients with or without gastrointestinal disorders. This prospective quasi experimental study with non-inferiority design was conducted on May 28th to August 22nd 2012, with 22 sample (stage 3-5 CKD), 14 men, 8 women, divided into 4 groups (1st: patients with GI disorder and whole swallowed calcium carbonate, 2nd: with GI disorders and chewed tablet, 3rd: without GI disorders and whole swallowed tablet, 4th group: without GI disorders and chewed tablet, all tablet are used with meal). Before and after the 6th week research period, calcium and phosphate blood levels measurements had been taken, adherence had been measured every two weeks using the Morisky questionnaire and pill count. The results showed that there was no significant difference in the increased of calcium levels, except for group 1 compared to group 3 (p = 0.027), the decreased phosphate levels (p = 0.724; 0.089; 0.089; 0.414; 0.569; 1.000) and the value of the product calcium-phosphate (p = 1.000; 0.308; 0.186; 0.414; 0.425; 0.728). The conclusion is that the way to use the medicine and the states of gastrointestinal disorders did not significantly influence the effectiveness of calcium carbonate tablet.

The article presents various methods of synthesizing heat-resistant binders based on large-tonnage wastes of the ceramic industry. The use of expanded clay dust in the compositions of heat-resistant concrete on portlandcement allowed to increase their residual strength in the zone of critical temperatures (800-1000 ° C). It was revealed and justifi ed that the use of phosphate binders for synthesizing a binder made it possible to increase the refractoriness of the heat-resistant composition based on expanded clay dust to 1300-1350 с. As the experiments show, claydite dust in its composition contains a clay component, which ensures the plasticity of the ramming mass. It was established that samples of ramming mass on orthophosphoric acid did not require heat treatment and can be immediately removed.

Background and objectives Patients with progressive chronic kidney disease (CKD) develop positive phosphate balance that is associated with increased cardiovascular risk and mortality. Modification of dietary phosphate is a commonly used strategy to improve outcomes but is complicated by the need for adequate dietary protein. Surprisingly, the evidence for patient-level benefits from phosphate restriction is tenuous, and the justification for using any phosphate binder for pre-dialysis patients is questionable. Design, setting, participants, and measurements We review the evidence for dietary phosphate modification and the possible role of a smart phone application (app.) that provides information on phosphate, sodium, potassium and nutrients in over 50,000 Australian foods. We performed a pilot study of healthy participants assigned to dietetic advice and standard diet sheets, or dietetic advice, diet sheets and use of the smart phone app. Results Following baseline studies, 25 participants commenced the sodium and phosphate restricted diet. After two weeks, both groups showed non-significant trends to reduction in urinary phosphate and sodium. App. users referred to information on the app. more frequently than the control group participants referred to written instructions, found referring to the app. more convenient, felt they learned more new information, were more motivated to maintain the diet and were more likely to recommend their information source to family or friends (all p

Calcification is one of the major postoperative problems after aortic allograft implantation. We hypothesized that phosphate binders, lanthanum carbonate and calcium carbonate inhibit calcification of implanted aortic allografts and verified this hypothesis using a rat model. Aortas were harvested from 4-week-old Brown Norway rats and implanted into the subdermal space of 4-week-old Lewis rats. Twenty-seven recipient Lewis rats were divided into Group N, Group L, and Group C (9 rats per group), which were fed a normal diet, a normal diet containing 3% lanthanum carbonate, and a normal diet containing 3% calcium carbonate, respectively. Implanted aortic allografts were explanted 2 weeks later. Calcification of aortic allografts was evaluated using von Kossa staining and calcium content assay. Calcification score was defined in von Kossa staining as 0 (none), 1 (mild), 2 (moderate), and 3 (severe). Serum calcium and phosphorus levels at euthanasia were measured. Calcification scores were 2.6, 1.2, and 0.8, and calcium content was 48.9, 15.8, and 8.9 mg/dry·g, in Groups N, L, and C, respectively. Calcification was significantly reduced in Groups L and C. Serum calcium level was 11.5, 12.2, and 13.5 mg/dl, and serum phosphorus level was 15.4, 12.5, and 11.7 mg/dl, in Groups N, L, and C, respectively. Serum calcium level in Group C was significantly higher than in the other two groups. Lanthanum carbonate and calcium carbonate significantly reduced calcification of implanted aortic allografts in young rats. Although calcium carbonate induced hypercalcemia, lanthanum carbonate has significant potential to inhibit calcification of implanted aortic allografts.

AIM To examine possible alterations in acid-base parameters in patients switching from lanthanum carbonate (LanC) to sucroferric oxyhydroxide (SFOH). METHODS Fifteen stable hemodialysis patients were switched from LanC to SFOH. Only nine continued on SFOH, three returned to LanC and the other three switched to sevelamer carbonate. The later six patients served as a control group to the SFOH group of nine patients. Blood was sampled on the 3-d and the last 2-d interval of the week prior to switching and six weeks after. Bicarbonate levels (HCO3-), pH, pO2, pCO2 were measured, and the mean of the two measurements (3-d and 2-d interval) was calculated. RESULTS Comparing pre-switching to post-switching measurements in the SFOH group, no statistically significant differences were found in any of the parameters studied. The mean pre-switching HCO3- was 22.41 ± 1.66 mmol/L and the mean post-switching was 22.62 ± 2.25 mmol/L (P = 0.889). Respectively, the mean pH= 7.38 ± 0.03 vs 7.39 ± 0.03 (P = 0.635), mean pCO2= 38.41 ± 3.29 vs 38.37 ± 3.62 mmHg (P = 0.767), and Phosphate = 1.57 ± 0.27 vs 1.36 ± 0.38mmol/L (P = 0.214). There were not any significant differences when we performed the same analyses in the control group or between the SFOH group and control group. No correlations were found, either between pre-switching LanC daily dose or between post-switching daily dose of the new binder and the measured parameters. CONCLUSION In our small study, switching from LanC to SFOH did not have any significant effect on blood bicarbonate levels and gas analysis, indicating that there is no need to change hemodialysis prescription regarding these parameters.

Background Recently, gadolinium from linear GBCAs has been reported to deposit in various regions of the body. Besides gadolinium, other lanthanides are used in medical care. In the current study, we investigated deposition of lanthanum in two patients who received lanthanum carbonate as a phosphate binder due to chronic kidney injury and compared it to additionally found Gd deposition. Methods Tissue specimens of two patients with long-term application of lanthanum carbonate as well as possible GBCA application were investigated. Spatial distribution of gadolinium and lanthanum was determined by quantitative laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging of tissue sections. The deposition of gadolinium and lanthanum in different organs was compared, and the ratio of Gd concentration to La concentration (Gd-to-La-ratio) was investigated on an individual pixel base within the images. Results Deposition of Gd and La was found in all investigated tissues of both patients. Gd and La exhibited high spatial correlation for all samples, with the main deposition being located in the middle coat (tunica media) of blood vessels. The Gd-to-La-ratio was similar in the tissues investigated (between 8 ± 4 (mean ± standard deviation) and 10 ± 2), except for the thyroid vasculature and surrounding tissue (90 ± 17) as well as the cerebellum (270 ± 18). Here, the ratio was significantly increased towards higher Gd concentration. Conclusion The results of this study demonstrate long-term deposition of La and comparable localization of additionally found Gd in various tissues of the body. La deposition was relatively low, considering the total administered amount of lanthanum carbonate of up to 11.5 kg, indicating a low absorption and/or high excretion of lanthanum. However, the total amount of deposited La is significant and raises questions about possible adverse side effects. The ratio-approach allows for the usage of the additionally generated Gd data, without detailed knowledge about possible GBCA applications. The significantly decreased Gd-to-La-ratio in the brain might be explained by the lanthanum being released and taken up as free La3+ ion in the stomach that impedes a crossing of the blood-brain-barrier while the intravenously injected GBCAs might dechelate first when they have already crossed the blood-brain-barrier.

Anemia affects millions of patients with chronic kidney disease (CKD) and prompt iron supplementation can lead to reductions in the required dose of erythropoiesis-stimulating agents, thereby reducing medical costs. Oral and intravenous (IV) traditional iron preparations are considered far from ideal, primarily due to gastrointestinal intolerability and the potential risk of infusion reactions, respectively. Fortunately, the emergence of novel iron replacement therapies has engendered a paradigm shift in the treatment of iron deficiency anemia in patients with CKD. For example, oral ferric citrate is an efficacious and safe phosphate binder that increases iron stores to maintain hemoglobin levels. Additional benefits include reductions in fibroblast growth factor 23 levels and the activation of 1,25 dihydroxyvitamin D. The new-generation IV iron preparations ferumoxytol, iron isomaltoside 1000, and ferric carboxymaltose are characterized by a reduced risk of infusion reactions and are clinically well tolerated as a rapid high-dose infusion. In patients undergoing hemodialysis (HD), ferric pyrophosphate citrate (FPC) administered through dialysate enables the replacement of ongoing uremic and HD-related iron loss. FPC transports iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration. Moreover, this paper summarizes recent advancements of hypoxia-inducible factor prolyl hydroxylase inhibitors and future perspectives in renal anemia management.

Chronic kidney disease–mineral bone disorder (CKD-MBD) is the most common complication in CKD patients. Although there is a consensus on treatment guidelines for CKD-MBD, it remains uncertain whether these treatment recommendations reflect actual practice. Therefore, the aim of this study was to investigate the CKD-MBD medication trend in real-world practice. This was a retrospective and observational study using a 12-year period database transformed into a common data model from three tertiary university hospitals. Study populations were subjects initially diagnosed as CKD. The date of diagnosis was designated as the index date. New patients were categorized year to year from 2008 to 2019 with a fixed observation period of 365 days to check the prescription of CKD-MBD medications including calcium-containing phosphate binder, noncalcium-containing phosphate binder, aluminium hydroxide, vitamin D receptor activator (VDRA), and cinacalcet. The numbers of CKD patients in the three hospitals were 7555, 2424, and 5351, respectively. The proportion for patients with CKD-MBD medication prescription decreased yearly regardless of hospital and CKD stage ( p for trend < 0.05). The use of aluminium hydroxide disappeared steadily while the use of VDRA increased annually in all settings. Despite these changes in prescription patterns, the mean value for CKD-MBD-related serologic markers was almost within target range. The proportion of the population within the target value was not significantly changed. Irrespective of hospital and CKD stage, similar trends of prescription for CKD-MBD medications were observed in real-world practice. Further research with a distributed network study may be helpful to understand medication trends in CKD-MBD treatment.

Background: It is estimated that chronic kidney disease (CKD) accounts globally for 5 to 10 million deaths annually, mainly due to cardiovascular (CV) diseases. Traditional as well as non-traditional CV risk factors such as vascular calcification are believed to drive this disproportionate risk burden. We aimed to investigate the association of coronary artery calcification (CAC) progression with all-cause mortality in patients new to hemodialysis (HD). Methods: Post hoc analysis of the Independent study (NCT00710788). At study inception and after 12 months of follow-up, 414 patients underwent computed tomography imaging for quantification of CAC via the Agatston methods. The square root method was used to assess CAC progression (CACP), and survival analyses were used to test its association with mortality. Results: Over a median follow-up of 36 months, 106 patients died from all causes. Expired patients were older, more likely to be diabetic or to have experienced an atherosclerotic CV event, and exhibited a significantly greater CAC burden (p = 0.002). Survival analyses confirmed an independent association of CAC burden (hazard ratio: 1.29, 95% confidence interval: 1.17–1.44) and CACP (HR: 5.16, 2.61–10.21) with all-cause mortality. CACP mitigated the risk associated with CAC burden (p = 0.002), and adjustment for calcium-free phosphate binder attenuated the strength of the link between CACP and mortality. Conclusions: CAC burden and CACP predict mortality in incident to dialysis patients. However, CACP reduced the risk associated with baseline CAC, and calcium-free phosphate binders attenuated the association of CACP and outcomes, suggesting that CACP modulation may improve survival in this population. Future endeavors are needed to confirm whether drugs or kidney transplantation may attenuate CACP and improve survival in HD patients.

Phosphate binders such as sevelamer are widely used in patients with chronic kidney disease to lower serum phosphate levels. We present a case of a 67-year-old woman with lower gastrointestinal bleeding after 9 days of using sevelamer carbonate (Renvela®). Sigmoidoscopy revealed multiple deep ulcers (diameter 10–15 mm) and mucosal oedema. Histologic examination showed deposition of sevelamer crystals in these rectal ulcers. We hypothesized that the lower gastrointestinal bleeding was caused by deposition of sevelamer crystals. After cessation of sevelamer, gastrointestinal bleeding stopped. Deposition of sevelamer crystals in the gastrointestinal tract is a rare complication of sevelamer therapy. There are only 17 other recorded cases of gastrointestinal deposition of sevelamer crystals. This adverse effect should be considered in all patients taking sevelamer who present with gastrointestinal symptoms, such as gastrointestinal bleeding and abdominal pain. When sevelamer is discontinued, symptoms and mucosal damage appear to revert.

Magnesium phosphate cements (MPC) are formed by reacting dead burned magnesia with soluble phosphates at room temperature, which are found to be quick setting with significant strength. The reaction is a highly exothermic process with fast hardening process. It is an acid–base reaction to form insoluble phosphate binder. It acts as an alternate binding material to normal Portland cement concrete. MPC is mostly prepared with a retarder, such as borax, to slow down the quick setting of the binder. Dead burned magnesia reacts with phosphate in the hydration of MPC produces struvite which attach onto the MgO particles which have not reacted, leading to the formation of solid particles. The strength and durability of MPC depend on the quantity and characteristics of the ingredients, water to binder ratio and admixtures. In most case of MPC, the phosphates used are dihydrogen phosphates of ammonium and potassium. This study used phosphate of sodium dihydrogen phosphate instead of phosphates of ammonium and potassium. Novel magnesium phosphate cement using dead burnt MgO and sodium dihydrogen phosphate (NaH2PO4) has been developed. Chemically inactive dead burnt MgO used was produced by sintering raw MgO at a controlled temperature of 1750 °C in rotary kiln. The MgO to NaH2PO4 ratio adopted was from 4:1 to 1:4. The study involved the mechanical properties including compressive and split tensile strength, durability and microstructure properties including scanning electron microscope and EDAX, for various proportions. The optimum mix for magnesium sodium dihydrogen phosphate cement (MNPC) was arrived as 70% dead MgO and 30% sodium dihydrogen phosphate which gave the better result in terms of strength and durability.

Background There are often specific endoscopic findings caused by deposition of lanthanum (La) in the gastric mucosa of patients taking lanthanum carbonate (LaC), a novel phosphate binder for patients on hemodialysis. We conducted a retrospective study to investigate the clinical significance of La deposition in the gastric mucosa, and the association between endoscopic features and histologic findings in the same population. Methods We compared background factors in patients taking LaC with and without La deposition in their gastroscopic biopsy specimen. We also investigated the relationship between gastric endoscopic biopsy specimens with La deposition and the concurrent endoscopic images. Results There was a significant difference in the total dose of LaC between the La-positive and La-negative groups (990 g [180–3150 g] vs. 480 g [225–1328 g]; p = 0.013). In 27 biopsy specimens with specific whitish mucosa, 10 showed mild histiocytic infiltration and 17 showed severe infiltration. In contrast, among 24 specimens with non-whitish mucosa, 5 showed no histiocytic infiltration, 10 showed mild infiltration, and 9 showed severe infiltration. There was a significant relationship between endoscopic features and the degree of histiocytic infiltration (p = 0.026). Conclusions We demonstrated that La deposition in the gastric mucosa depended on the total dose of LaC and was not affected by background factors. The specific endoscopic features of La deposition are associated with the infiltration of histiocytes, which represents the body’s normal response to foreign bodies. Trial registry The protocol was registered in the University Hospital Medical Information Network Clinical Trial Registry (UMIN000038929, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000044393).