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Nephrology, Dialysis, Transplantation :... Jan 2024Phosphorus is an essential mineral that is, in the form of inorganic phosphate (Pi), required for building cell membranes, DNA and RNA molecules, energy metabolism,... (Review)
Review
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.
Topics: Animals; Humans; Phosphates; Phosphorus; Intestinal Absorption; Hyperphosphatemia; Minerals; Mammals
PubMed: 37660247
DOI: 10.1093/ndt/gfad188 -
Journal of Neurogastroenterology and... Oct 2023Constipation is a frequent symptom in patients with chronic kidney disease (CKD). This review outlines the mechanisms and management of constipation in patients with CKD... (Review)
Review
Constipation is a frequent symptom in patients with chronic kidney disease (CKD). This review outlines the mechanisms and management of constipation in patients with CKD from a physician's perspective. Common causes of constipation in patients with CKD include concomitant medications, low dietary fiber intake, water-restricted diet, lack of physical activity, altered gut microbiota, and reduced gastrointestinal motility. Constipation has a negative impact on overall health, and, in particular, the presence of constipation has been associated with worsening kidney function and increased risk of developing advanced stages of CKD. Although lifestyle and dietary modifications may not always be practical for patients with CKD, they are recommended because they are beneficial as they lower mortality in patients with CKD. The use of laxatives containing magnesium salts, bulking agents, and osmotic laxatives may have insufficient efficacy and may be associated with adverse effects. In contrast, lactulose and lubiprostone have been shown to exhibit reno-protective effects. Linaclotide and plecanatide have very limited systemic absorption and appear safe in patients with CKD. Tenapanor reduces paracellular intestinal phosphate absorption in addition to blocking sodium uptake by enterocytes, and provides additional benefit in patients patients with CKD who have hyperphosphatemia and constipation. Prucalopride leads to improvements in bowel function and constipation-related symptoms in cases in which response to conventional laxatives are inadequate. However, the dose of prucalopride should be reduced to 1 mg once daily for patients with CKD. In conclusion, there are important advances on the impact and treatment of constipation in patients with CKD.
PubMed: 37814433
DOI: 10.5056/jnm23133 -
Scientific Reports Nov 2023Phosphate binders (PBs) generally have a high pill burden. Tenapanor selectively inhibits sodium/hydrogen exchanger isoform 3, reducing intestinal phosphate absorption....
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.
Topics: Humans; Hyperphosphatemia; Phosphates; Phosphorus; Renal Dialysis; Sodium-Hydrogen Exchanger 3
PubMed: 37925471
DOI: 10.1038/s41598-023-45080-9 -
Biomedicines Oct 2023Chronic kidney disease (CKD) is a progressive and incurable disease that impairs kidney function. Its prevalence is estimated to affect up to 800 million individuals... (Review)
Review
Chronic kidney disease (CKD) is a progressive and incurable disease that impairs kidney function. Its prevalence is estimated to affect up to 800 million individuals within the general population, and patients with diabetes and hypertension are particularly at risk. This disorder disrupts the physiological mechanisms of the body, including water and electrolyte balance, blood pressure regulation, the excretion of toxins, and vitamin D metabolism. Consequently, patients are exposed to risks such as hyperkalemia, hyperphosphatemia, metabolic acidosis, and blood pressure abnormalities. These risks can be reduced by implementing appropriate diagnostic methods, followed by non-pharmacological (such as physical activity, dietary, and lifestyle adjustment) and pharmacological strategies after diagnosis. Selecting the appropriate diet and suitable pharmacological treatment is imperative in maintaining kidney function as long as possible. Drugs such as finerenone, canakinumab, and pentoxifylline hold promise for improved outcomes among CKD patients. When these interventions prove insufficient, renal replacement therapy becomes essential. This is particularly critical in preserving residual renal function while awaiting renal transplantation or for patients deemed ineligible for such a procedure. The aim of this study is to present the current state of knowledge and recent advances, providing novel insights into the treatment of chronic kidney disease.
PubMed: 37893119
DOI: 10.3390/biomedicines11102746 -
Cell Reports. Medicine Oct 2023Approved fibroblast growth factor receptor (FGFR) inhibitors include erdafitinib, pemigatinib, and futibatinib. We review the most common toxicities associated with FGFR... (Review)
Review
Approved fibroblast growth factor receptor (FGFR) inhibitors include erdafitinib, pemigatinib, and futibatinib. We review the most common toxicities associated with FGFR inhibitors and provide practical advice regarding their management. Hyperphosphatemia can be managed with careful monitoring, dose reduction or interruption, a prophylactic low-phosphate diet, and phosphate-lowering therapy. Ocular adverse events (AEs) are managed by withholding or adjusting the dose of the FGFR inhibitor. Dermatologic AEs include alopecia, which can be managed with minoxidil, and dry skin, which can be treated with moisturizers. Hand-foot syndrome can be prevented by lifestyle changes and managed with moisturizing creams, urea, or salicylic acid. Among gastrointestinal AEs, diarrhea may be managed with loperamide; stomatitis can be managed with baking soda rinses, mucosa-coating agents, and topical anesthetics; and dry mouth may be alleviated with salivary stimulants. Most FGFR inhibitor-associated toxicities are manageable with prophylactic measures and treatments; proactive monitoring is key to ensuring optimal clinical benefits.
Topics: Receptor, Fibroblast Growth Factor, Type 2; Phosphates
PubMed: 37757826
DOI: 10.1016/j.xcrm.2023.101204 -
Clinical Kidney Journal Nov 2023High energy intake combined with low physical activity generates positive energy balance, which, when maintained, favours obesity, a highly prevalent morbidity linked to... (Review)
Review
High energy intake combined with low physical activity generates positive energy balance, which, when maintained, favours obesity, a highly prevalent morbidity linked to development of non-communicable chronic diseases, including chronic kidney disease (CKD). Among many factors contributing to disproportionately high energy intakes, and thereby to the obesity epidemic, the type and degree of food processing play an important role. Ultraprocessed foods (UPFs) are industrialized and quite often high-energy-dense products with added sugar, salt, unhealthy fats and food additives formulated to be palatable or hyperpalatable. UPFs can trigger an addictive eating behaviour and is typically characterized by an increase in energy intake. Furthermore, high consumption of UPFs, a hallmark of a Western diet, results in diets with poor quality. A high UPF intake is associated with higher risk for CKD. In addition, UPF consumption by patients with CKD is likely to predispose and/or to exacerbate uraemic metabolic derangements, such as insulin resistance, metabolic acidosis, hypertension, dysbiosis, hyperkalaemia and hyperphosphatemia. Global sales of UPFs per capita increased in all continents in recent decades. This is an important factor responsible for the nutrition transition, with home-made meals being replaced by ready-to-eat products. In this review we discuss the potential risk of UPFs in activating hedonic eating and their main implications for health, especially for kidney health and metabolic complications of CKD. We also present various aspects of consequences of UPFs on planetary health and discuss future directions for research to bring awareness of the harms of UPFs within the CKD scenario.
PubMed: 37915903
DOI: 10.1093/ckj/sfad103 -
Renal Failure Dec 2023This study was designed to examine the relative safety and efficacy of sevelamer in the treatment of chronic kidney disease (CKD) patients in comparison to placebo,... (Meta-Analysis)
Meta-Analysis Review
This study was designed to examine the relative safety and efficacy of sevelamer in the treatment of chronic kidney disease (CKD) patients in comparison to placebo, calcium carbonate (CC), or lanthanum carbonate (LC). The PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases were searched for articles published through 18 June 2022. The quality of relevant studies was independently analyzed by two investigators who also extracted data from these manuscripts as per Cochrane Collaboration Handbook 5.3. The safety and efficacy of sevelamer as a treatment for hyperphosphatemia in CKD patients were then examined through a meta-analysis, with the primary patient-level outcomes of interest in this analysis being all-cause mortality and the incidence of gastrointestinal adverse effects. Vascular calcification score was also examined as an intermediate outcome, while serum biochemical parameters including levels of phosphate (P), calcium (Ca), intact parathyroid hormone (iPTH), lipids, C-reactive protein (CRP), or fibroblast growth factor-23 (FGF-23) were additionally assessed. In total, this meta-analysis incorporated data from 34 randomized controlled trials (RCTs) enrolling 2802 patients. Sevelamer was associated with reduced all-cause mortality (RR 0.28, CI 0.19 - 0.41, ) and Vessel calcification score (RR -0.58, CI -1.11 to -0.04, ) and induced less hypercalcemia (MD -0.28, CI 0.40 to -0.16, ) and hyperphosphatemia (MD -0.22, CI -0.32 to -0.13, ) when compared with Ca-based binders in CKD5D individuals. No significant differences in gastrointestinal adverse events (GAEs) incidence were observed. These data suggest that sevelamer may represent a beneficial means of protecting CKD patients against death and vessel calcification when used to treat hyperphosphatemia, while we found no clinically important benefits in decreasing gastrointestinal adverse effects.
Topics: Humans; Sevelamer; Hyperphosphatemia; Chelating Agents; Phosphates; Renal Insufficiency, Chronic; Renal Dialysis
PubMed: 37272189
DOI: 10.1080/0886022X.2023.2210230 -
Journal of Bone and Mineral Research :... Aug 2023Chronic 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...
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).
Topics: Mice; Animals; Chronic Kidney Disease-Mineral and Bone Disorder; Adenine; X-Ray Microtomography; Hyperphosphatemia; Mice, Inbred C57BL; Renal Insufficiency, Chronic; Phosphorus
PubMed: 37191192
DOI: 10.1002/jbmr.4829 -
Jornal Brasileiro de Nefrologia 2024The Brazilian Dialysis Survey (BDS) is an annual national survey about patients on chronic dialysis that contributes to health policies.
INTRODUCTION
The Brazilian Dialysis Survey (BDS) is an annual national survey about patients on chronic dialysis that contributes to health policies.
OBJECTIVE
To report the 2022 epidemiological data from the BDS of the Brazilian Society of Nephrology (BSN).
METHODS
A survey was carried out in Brazilian chronic dialysis centers using an online questionnaire that included clinical and epidemiological aspects of patients on chronic dialysis, dialysis therapy data, and dialysis center characteristics.
RESULTS
Overall, 28% (n = 243) of the centers answered the questionnaire. In July 2022, the estimated total number of patients on dialysis was 153,831. The estimated prevalence and incidence rates of patients per million population (pmp) were 758 and 214, respectively. Of the prevalent patients, 95.3% were on hemodialysis (HD, 4.6% of these on hemodiafiltration) and 4.7% on peritoneal dialysis (PD). Only 1.3% of patients were not vaccinated against COVID-19. The prevalence of anemia (Hb < 10g/dL) was 27% and hyperphosphatemia (P > 5.5mg/dL) reached 30%. The estimated overall crude annual mortality rate was 17.1%.
CONCLUSIONS
The absolute number and prevalence rate of patients on chronic dialysis continue to increase. A growing number of patients were receiving hemodiafiltration. The mortality rate decreased, probably due to the end of COVID-19 pandemic. The conclusions were drawn in the context of relatively low voluntary participation, which imposed methodological limitations on our estimates.
Topics: Humans; Renal Dialysis; Brazil; Pandemics; Surveys and Questionnaires; Peritoneal Dialysis; Kidney Failure, Chronic
PubMed: 38078834
DOI: 10.1590/2175-8239-JBN-2023-0062en