-
International Journal of Nephrology and... 2024Hyperphosphataemia represents a significant challenge in the management of chronic kidney disease, exerting a pronounced influence on the pathogenesis of cardiovascular... (Review)
Review
Hyperphosphataemia represents a significant challenge in the management of chronic kidney disease, exerting a pronounced influence on the pathogenesis of cardiovascular complications and mineral bone disorders. Traditional approaches to address hyperphosphataemia involve implementing dietary phosphate restrictions, administering phosphate binders, and, in cases of end-stage renal disease, resorting to dialysis. Unfortunately, these interventions frequently prove inadequate in maintaining phosphate levels within recommended ranges. Additionally, commonly employed pharmacological agents are not immune to eliciting adverse events, thereby limiting their prescription and therapeutic adherence. There is a growing focus on exploring novel therapeutic strategies in this context. The current discussion centres on tenapanor, a pharmacological agent predominantly acting as a selective inhibitor of sodium/hydrogen exchanger isoform 3 (NHE3). Its mechanism of action involves modulating tight junctions, resulting in reduced sodium absorption and intestinal paracellular permeability to phosphate. Furthermore, tenapanor downregulates sodium-dependent phosphate 2b transport protein (NaPi2b) expression, thereby impeding active transcellular phosphate transport. Clinical trials have elucidated the efficacy and safety profile of tenapanor. This evidence hints at a potential paradigm shift in the management of hyperphosphataemia. However, the burgeoning optimism surrounding tenapanor warrants tempered enthusiasm, as further research remains indispensable. The imperative lies in meticulously delineating its efficacy and safety contours within the crucible of clinical practice. In this review, we synthesize the intricate interplay between hyperphosphataemia and Chronic Kidney Disease-Mineral Bone Disorder, and we discuss the existing pharmacological interventions for hyperphosphataemia and explore emerging treatment paradigms that offer novel perspectives in managing elevated phosphate levels in CKD patients.
PubMed: 38831770
DOI: 10.2147/IJNRD.S385826 -
ACS Omega Nov 2023Polyphosphate polymers are chains of phosphate monomers chemically bonded together via phosphoanhydride bonds. They are found in all prokaryotic and eukaryotic organisms...
Polyphosphate polymers are chains of phosphate monomers chemically bonded together via phosphoanhydride bonds. They are found in all prokaryotic and eukaryotic organisms and are among the earliest, most anionic, and most mysterious molecules known. They are everywhere, from small cellular components to additives in our food. There is a strong association between hyperphosphatemia and mortality. That is why it is crucial to assess how polyphosphates, as food additives, affect the quality of edible proteins. This study investigated the effect of inexpensive and widely used food additives (hexametaphosphate labeled as E452) on bakery items, meat products, fish, and soft drinks. Using various spectroscopic and microscopic techniques, we examined how hexametaphosphate affected the aggregation propensity, structure, and stability of a commonly used food protein: hen egg white lysozyme (HEWL). The solubility of HEWL is affected in a bimodal fashion by the concentration of hexametaphosphate. The bimodal concentration-dependent effect was also observed in the tertiary and secondary structural changes. Hexametaphosphate-induced HEWL aggregates were amorphous, as evidenced by ThT fluorescence, far-UV CD, and TEM imaging. This study showed that the food additive (hexametaphosphate) may denature and aggregate proteins and may lead to undesirable health issues.
PubMed: 38027328
DOI: 10.1021/acsomega.3c06210 -
Frontiers in Veterinary Science 2023Cardiovascular and renal diseases are known to affect each other in the cardiovascular renal axis disorder (CvRD). Although CvRD, which includes myxomatous mitral valve...
INTRODUCTION
Cardiovascular and renal diseases are known to affect each other in the cardiovascular renal axis disorder (CvRD). Although CvRD, which includes myxomatous mitral valve disease (MMVD) and chronic kidney disease (CKD), has been described in dogs, there are only a few reports on the progression of CKD in accordance with the severity of MMVD. The aim of this study was to evaluate whether the presence of MMVD is associated with the rate of progression of CKD in dogs. The time from the initial diagnosis to the worsening of the International Renal Interest Society (IRIS) stage and the time for the occurrence of hyperphosphatemia and isosthenuria were evaluated.
MATERIALS AND METHODS
In this retrospective study, CKD progression was determined as an increase in the IRIS stage by at least one level and the development of hyperphosphatemia or isosthenuria. The CKD progression was compared in dogs with and without comorbid MMVD.
RESULTS
Dogs with CKD were divided into two groups: dogs with and without MMVD ( = 63, concurrent group; = 52, CKD group, respectively). The concurrent group was further divided into two subgroups based on the American College of Veterinary Internal Medicine guidelines (B1 group, = 24; B2 group, = 39). The time for progression of CKD from IRIS stage 1 to IRIS stage 2 was significantly shorter in the concurrent group than in the CKD group (log-rank test, < 0.001). MMVD was associated with an increased risk of progression from stage 1 to stage 2 (hazard ratio, 6.442; 95% confidence interval (CI), 2.354 to 18.850; < 0.001). The timing of the onset of hyperphosphatemia or isosthenuria in the concurrent group and the CKD group was not significantly different.
CONCLUSION
The results of this study suggest that MMVD could be a risk factor for the progression of CKD. Our findings may help predict the prognosis of dogs with both CKD and MMVD compared to CKD only.
PubMed: 37691634
DOI: 10.3389/fvets.2023.1200653 -
Journal of Clinical Biochemistry and... Nov 2023Disorder of phosphate metabolism is a common pathological condition in chronic kidney disease patients. Excessive intake of dietary phosphate deteriorates chronic kidney...
Disorder of phosphate metabolism is a common pathological condition in chronic kidney disease patients. Excessive intake of dietary phosphate deteriorates chronic kidney disease and various complications including cardiovascular and infectious diseases. Recent reports have demonstrated that gut microbiome disturbance is associated with both the etiology and progression of chronic kidney disease. However, the relationship between dietary phosphate and gut microbiome remains unknown. Here, we examined the effects of excessive intake of phosphate on gut microbiome. Five-week-old male C57BL/6J mice were fed either control diet or high phosphate diet for eight weeks. Analysis of the gut microbiota was carried out using MiSeq next generation sequencer, and short-chain fatty acids were determined with GC-MS. In analysis of gut microbiota, significantly increased in and decreased in were observed in high phosphate diet group. Furthermore, high phosphate diet induced reduction of microbial diversity and decreased mRNA levels of colonic tight junction markers. These results suggest that the excessive intake of dietary phosphate disturbs gut microbiota and affects intestinal barrier function.
PubMed: 37970557
DOI: 10.3164/jcbn.23-9 -
Journal of Epidemiology Nov 2023Pseudohypoparathyroidism (PHP) and nonsurgical hypoparathyroidism (NS-HypoPT) are rare diseases with hypocalcemia, hyperphosphatemia, and high and low parathyroid...
BACKGROUND
Pseudohypoparathyroidism (PHP) and nonsurgical hypoparathyroidism (NS-HypoPT) are rare diseases with hypocalcemia, hyperphosphatemia, and high and low parathyroid hormone levels, respectively. In Japan, over 20 years have passed since the last survey on these diseases. We carried out a nationwide cross-sectional survey to estimate the prevalence of these diseases in 2018.
METHODS
We conducted a nationwide mail-based survey targeting hospitals in 2018. From a total of 13,156 departments throughout Japan, including internal medicine, pediatrics, neurology, and psychiatry, 3,501 (27%) departments were selected using a stratified random sampling method. We asked each included department to report the number of patients with PHP and NS-HypoPT in 2017.
RESULTS
The overall survey response rate was 52.0% (1,807 departments). The estimated number of patients with PHP and NS-HypoPT was 1,484 (95% confidence interval [CI], 1,143-1,825) and 2,304 (95% CI, 1,189-3,419), respectively; the prevalence per 100,000 population was 1.2 and 1.8, respectively.
CONCLUSION
In this study, we generated estimates of the national prevalence of PHP and NS-HypoPT in Japan during 2017, which were found to be higher than those previously reported.
Topics: Humans; Child; Prevalence; Japan; Cross-Sectional Studies; Pseudohypoparathyroidism; Hypoparathyroidism
PubMed: 36123043
DOI: 10.2188/jea.JE20220152 -
Kidney International Reports Nov 2023
PubMed: 38025212
DOI: 10.1016/j.ekir.2023.10.001 -
Frontiers in Medicine 2024We aimed to investigate the association between serum phosphate levels and the risk for developing sepsis associated acute kidney injury (SAKI).
OBJECTIVE
We aimed to investigate the association between serum phosphate levels and the risk for developing sepsis associated acute kidney injury (SAKI).
METHODS
Septic patients from the Medical Information Mart for Intensive Care IV (MIMIC IV) and the eICU Collaborative Research Database (eICU-CRD) were enrolled. Restricted cubic spline (RCS) was used to visualize the relationship between phosphate levels and the risk of SAKI. Patients were divided into four categories based on their serum phosphate levels. Logistic regression analysis, receiver operating characteristic (ROC) curve and subgroup analysis were performed to evaluate the predictive value of serum phosphate for SAKI.
RESULTS
A total of 9,244 and 2,124 patients from the MIMIC IV and eICU-CRD database were included in the final analysis. RCS curve revealed a non-linear correlation between phosphate levels and the risk of SAKI ( for non-linearity <0.05). Each 1 mg/dL increase in phosphate levels was associated with a 1.51 to 1.64-fold increased risk of SAKI (OR 2.51-2.64, < 0.001) in the MIMIC IV cohort and a 0.29 to 0.38-fold increased risk (OR 1.29-1.38, < 0.001) in the eICU-CRD cohort. Compared to the normal-low category, hyperphosphatemia and normal-high category were independently associated with an increased risk of SAKI, while hypophosphatemia was independently associated with a decreased risk in the MIMIC IV cohort. A similar trend was observed in the eICU-CRD cohort, but statistical significance disappeared in the hypophosphatemia category and the adjusted model of normal high category. These finding was consistent in subgroup analysis.
CONCLUSION
Elevated serum phosphate, even within the normal range, is an independent risk factor for developing SAKI in septic patients. Abnormal change in serum phosphate levels may be a novel biomarker for early prediction of SAKI occurrence.
PubMed: 38585149
DOI: 10.3389/fmed.2024.1367064 -
Clinical and Experimental Nephrology Feb 2024Tenapanor 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...
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.
Topics: Humans; Diarrhea; Hyperphosphatemia; Isoquinolines; Peritoneal Dialysis; Phosphates; Phosphorus; Sulfonamides
PubMed: 37910313
DOI: 10.1007/s10157-023-02406-1 -
Kidney International Reports Nov 2023Serum phosphorus management is important for patients with chronic kidney disease on dialysis to reduce the risk of hyperparathyroidism and ectopic vascular...
INTRODUCTION
Serum phosphorus management is important for patients with chronic kidney disease on dialysis to reduce the risk of hyperparathyroidism and ectopic vascular calcification. Phosphate binders (PBs) control serum phosphorus levels; however, some patients do not achieve adequate control with existing PBs. The similar mechanisms of action of each PB may limit their ability to lower serum phosphorus levels. Therefore, drugs with novel mechanisms of action that can be added to existing PBs to further lower serum phosphorus levels are desired. Tenapanor, a novel selective inhibitor of intestinal sodium/hydrogen exchanger 3 transporters, decreases passive phosphate absorption in the intestine, thereby decreasing serum phosphorus levels.
METHODS
This study evaluated the efficacy and safety of tenapanor treatment with up-titration when added to PBs among Japanese hemodialysis patients with hyperphosphatemia poorly controlled by PBs alone. In total, 169 patients taking PBs whose serum phosphorus level was ≥6.1 and <10.0 mg/dl initiated the 8-week treatment (placebo + PB, = 85; tenapanor + PB, = 84).
RESULTS
The least squares mean change from baseline to week 8 in serum phosphorus level was -0.24 and -2.00 mg/dl in the placebo and tenapanor groups, respectively, with a statistically significant difference between groups (-1.76 mg/dl; < 0.0001). Diarrhea as a treatment-emergent adverse event (TEAE) occurred in 14.1% and 63.1% of patients in the placebo and tenapanor groups, respectively. All diarrhea events were mild or moderate.
CONCLUSION
Tenapanor added to PBs improved serum phosphorus levels that could not previously be controlled by PBs alone, and no new safety concerns were raised.
PubMed: 38025211
DOI: 10.1016/j.ekir.2023.08.003 -
Cureus Apr 2024Rhabdomyolysis, a medical condition caused by the destruction of striated muscle fibers, can have many etiologies, with the most common one being traumatic etiologies,... (Review)
Review
Rhabdomyolysis, a medical condition caused by the destruction of striated muscle fibers, can have many etiologies, with the most common one being traumatic etiologies, that is, crushing injuries, heavy exertion, and being trapped under rubbles, and so forth. Rhabdomyolysis causes many complications, including acute kidney injury and different electrolyte imbalances, which later can cause cardiac dysrhythmia and even death as a result. This systematic review and meta-analysis investigate the incidence of imbalances of four important electrolytes among patients diagnosed with traumatic rhabdomyolysis. PubMed, Scopus, Web of Science, and Embase databases were searched for any article related to traumatic rhabdomyolysis using keywords related to the topic of our study, excluding case studies and case series. Relevant data were extracted from the included articles, and finally, a meta-analysis was performed on them to calculate the pooled incidence of each electrolyte imbalance. Collectively, 32 articles were included in our study (through the database and citation checking). The following were the pooled incidence of each electrolyte imbalance: hyperkalemia, 31% (95%CI 22%-41%); hypokalemia, 10% (95%CI 4%-17%); hypernatremia, 3% (95%CI 0%-8%); hyponatremia, 23% (95%CI 7%-44%); hypercalcemia, 0% (95%CI 0%-1%); hypocalcemia, 57% (95%CI: 22%-88%); hyperphosphatemia, 33% (95%CI 11%-59%); hypophosphatemia, 4% (95%CI 0%-16%). According to the meta-analyses, the rate of hyperkalemia, hyponatremia, hypocalcemia, and hyperphosphatemia is higher than their counterpart in patients diagnosed with traumatic rhabdomyolysis.
PubMed: 38817473
DOI: 10.7759/cureus.59333