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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 -
Experimental and Clinical... Nov 2023Hypoparathyroidism occurs as a part of a complex autoimmune syndrome or iatrogenically after neck surgery. The disease presents many challenges, such as hypocalcemia,...
OBJECTIVES
Hypoparathyroidism occurs as a part of a complex autoimmune syndrome or iatrogenically after neck surgery. The disease presents many challenges, such as hypocalcemia, hyperphosphatemia, and low/undetectable parathormone levels. Allotransplantation of parathyroid tissue or cells has been reported as a promising option to overcome these effects. Transplantation of microencapsulated parathyroid tissue or cells offers an immune escape, which particularly restores the parathyroid function for autoimmune-related hypoparathyroidism. So far, clinical and in vivo studies have demonstrated limited graft survival and instability for the available biocompatible materials. In addition, the transplant site, proper local isolation, and biocompatibility of materials are directly related to survival rate.
MATERIALS AND METHODS
A microencapsulated parathyroid xenotransplant model by using high guluronic acid-containing ultrapure alginate transplanted into rat omentum was tested in vivo for 1 year.
RESULTS
After stability of empty microcapsules was ensured, parathyroid cells were microencapsulated and transplanted in rats, with results compared versus rats with naked (nonencapsulated) parathyroid cells (both groups followed for 64 weeks). Rats remained normocalcemic, and preinflammatory cytokine levels showed dramatic changes. Despite a delay posttransplant, parathormone levels increased significantly. All retrieved microencapsules elicited pericapsular fibrotic overgrowth; however, the fibrosis area was shown to be well tolerated.
CONCLUSIONS
The possible role of accumulation/cell infiltration of immune response remains to be elucidated. In conjunction with this, the use of nonencapsulated parathyroid cells was also positively correlated with survival rates. A similar evaluation using ultrapure alginate materials and omental transplantation may enable the future determination for the long-term effects of correction of parathormone insufficiency in patients with severe hypocalcemic responses and other endocrine diseases.
Topics: Humans; Rats; Animals; Transplantation, Heterologous; Parathyroid Glands; Hypoparathyroidism; Parathyroid Hormone; Alginates
PubMed: 34387152
DOI: 10.6002/ect.2020.0403 -
Kidney360 May 2024Tenapanor, a first-in-class local inhibitor of sodium/hydrogen exchanger isoform 3, acts as a phosphate absorption inhibitor by decreasing paracellular phosphate... (Randomized Controlled Trial)
Randomized Controlled Trial
KEY POINTS
Tenapanor, a first-in-class local inhibitor of sodium/hydrogen exchanger isoform 3, acts as a phosphate absorption inhibitor by decreasing paracellular phosphate absorption. Tenapanor alone or with phosphate binders achieved ≤ 5.5 mg/dl over 10 weeks in 34%–38% of patients taking phosphate binders at baseline. Tenapanor can help adults with CKD on maintenance dialysis achieve normal serum phosphate concentrations.
BACKGROUND
OPTIMIZE was a randomized, open-label study evaluating different tenapanor initiation methods. OPTIMIZE evaluated tenapanor alone and in combination with phosphate binders (PBs) to achieve target serum phosphate (P) ≤5.5 mg/dl.
METHODS
Patients with inadequately controlled P receiving maintenance dialysis from 42 US locations who were taking PBs with baseline > 5.5 mg/dl and ≤ 10.0 mg/dl, or were PB-naive with baseline > 4.5 mg/dl and ≤ 10.0 mg/dl, were included in OPTIMIZE. Participants taking PBs at baseline were randomized to switch from PBs to tenapanor (; =151) or reduce PB dosage by ≥50% and add tenapanor (; =152); PB-naive patients started tenapanor alone (; =30). Participants received tenapanor 30 mg twice a day for 10 weeks (part A), followed by an elective, 16-week open-label extension (part B). Outcomes included changes from baseline in P, intact fibroblast growth factor 23, parathyroid hormone, serum calcium, and medication burden; patient-reported outcomes; and safety.
RESULTS
By part A end point, 34.4% (), 38.2% (), and 63.3% () of patients achieved ≤ 5.5 mg/dl. Mean P reduction and median pill burden reduction from baseline to part A end point were 0.91±1.7 mg/dl and 4 pills/d for the and 0.99±1.8 mg/dl and 1 pill/d for the group. The mean P reduction for patients was 0.87±1.5 mg/dl. Among and patients who completed patient experience questionnaires, 205 of 243 (84.4%) reported an improved phosphate management routine. Diarrhea was the most common adverse event (133 of 333 [39.9%]).
CONCLUSIONS
Tenapanor as monotherapy or in combination with PBs effectively lowered P toward the target range in patients who were PB-naive or who were not at goal despite PB use.
CLINICAL TRIAL REGISTRATION NUMBER
NCT04549597.
Topics: Humans; Hyperphosphatemia; Renal Dialysis; Isoquinolines; Sulfonamides; Male; Female; Middle Aged; Treatment Outcome
PubMed: 38323855
DOI: 10.34067/KID.0000000000000387 -
Clinics and Practice Sep 2023Patients with chronic kidney disease (CKD) necessitate specialized renal diets to prevent complications such as hyperkalemia and hyperphosphatemia. A comprehensive...
Patients with chronic kidney disease (CKD) necessitate specialized renal diets to prevent complications such as hyperkalemia and hyperphosphatemia. A comprehensive assessment of food components is pivotal, yet burdensome for healthcare providers. With evolving artificial intelligence (AI) technology, models such as ChatGPT, Bard AI, and Bing Chat can be instrumental in educating patients and assisting professionals. To gauge the efficacy of different AI models in discerning potassium and phosphorus content in foods, four AI models-ChatGPT 3.5, ChatGPT 4, Bard AI, and Bing Chat-were evaluated. A total of 240 food items, curated from the for CKD patients, were input into each model. These items were characterized by their potassium (149 items) and phosphorus (91 items) content. Each model was tasked to categorize the items into high or low potassium and high phosphorus content. The results were juxtaposed with the recommendations. The concordance between repeated sessions was also evaluated to assess model consistency. Among the models tested, ChatGPT 4 displayed superior performance in identifying potassium content, correctly classifying 81% of the foods. It accurately discerned 60% of low potassium and 99% of high potassium foods. In comparison, ChatGPT 3.5 exhibited a 66% accuracy rate. Bard AI and Bing Chat models had an accuracy rate of 79% and 81%, respectively. Regarding phosphorus content, Bard AI stood out with a flawless 100% accuracy rate. ChatGPT 3.5 and Bing Chat recognized 85% and 89% of the high phosphorus foods correctly, while ChatGPT 4 registered a 77% accuracy rate. Emerging AI models manifest a diverse range of accuracy in discerning potassium and phosphorus content in foods suitable for CKD patients. ChatGPT 4, in particular, showed a marked improvement over its predecessor, especially in detecting potassium content. The Bard AI model exhibited exceptional precision for phosphorus identification. This study underscores the potential of AI models as efficient tools in renal dietary planning, though refinements are warranted for optimal utility.
PubMed: 37887080
DOI: 10.3390/clinpract13050104 -
JBMR Plus Dec 2023Although the eyes are the main site of metastatic calcification in patients with chronic kidney disease (CKD), corneal and conjunctival calcification (CCC) is poorly...
Although the eyes are the main site of metastatic calcification in patients with chronic kidney disease (CKD), corneal and conjunctival calcification (CCC) is poorly evaluated in this population. Whether CCC correlates with coronary artery calcification remains unknown since studies so far have relied on methods with low sensitivity. Our objective was to test the relationship between CCC and coronary calcification based on tomography. This was a cross-sectional study that included patients on maintenance dialysis. Clinical, demographic, and biochemical data (calcium, phosphorus, parathormone, alkaline phosphatase, and 25(OH)-vitamin D) were recorded. Hyperparathyroidism was defined as parathyroid hormone (PTH) > 300 pg/mL. CCC was evaluated by anterior segment optical coherence tomography (AS-OCT), and coronary calcium scores (Agatston method) were assessed by computed tomography. We compared no/mild with moderate/severe CCC. Twenty-nine patients were included (49.6 ± 15.0 years, 62.1% female, on hemodialysis for 5.7 [2.7-9.4] years, 17.2% with diabetes mellitus, 75.9% with hyperparathyroidism). CCC was found in 82.7% of patients, with median scores of 9 (3, 14.5), ranging from 0 to 16. CCC was classified as absent/mild, moderate, and severe in 27.6%, 20.7%, and 51.7%, respectively. Coronary calcification was found in 44.8% of patients, with median scores of 11 (0, 464), varying from 0 and 6456. We found no significant correlation between coronary calcium scores and CCC ( = 0.203, = 0.282). Hyperphosphatemia was more frequent in patients with moderate/severe CCC than in those with absent/mild CCC. We concluded that CCC was frequent in patients with CKD on dialysis and did not correlate with coronary calcium scores. Hyperphosphatemia appears to contribute to CCC. © 2023 The Authors. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
PubMed: 38130747
DOI: 10.1002/jbm4.10823 -
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 -
BMC Nephrology Mar 2024Hyperphosphatemia is common in chronic kidney disease (CKD), associated with higher mortality in dialysis patients. Its impact in non-dialysis patients, especially those...
BACKGROUND
Hyperphosphatemia is common in chronic kidney disease (CKD), associated with higher mortality in dialysis patients. Its impact in non-dialysis patients, especially those with preserved kidney function, remains uncertain.
METHODS
A prospective cohort study was conducted using data from the National Health and Nutrition Examination Survey (2001-2008). Serum phosphorus was analyzed as a continuous variable, or categorized into three groups: < 3.5 mg/dL, 3.5 to < 4.5 mg/dL, and ≥ 4.5 mg/dL. Cox proportional hazards models were used to analyze the association between phosphorus with all-cause and cardiovascular disease (CVD) mortality, with or without adjustment for age, sex, race, hemoglobin, estimated glomerular filtration rate (eGFR), serum albumin, serum calcium, 25(OH)D, obesity, hypertension, diabetes, and CVD.
RESULTS
A total of 7694 participants were included in the analysis, representing 28 million CKD patients in the United States. During mean 92 months of follow up, 2708 all-cause deaths (including 969 CVD deaths) were observed. Per 1 mg/dL increase in phosphorus was associated with a 13% and 24% increased risk of all-cause mortality (hazard ratio [HR], 1.13; 95%CI, 1.02-1.24) and CVD mortality (HR, 1.24; 95%CI, 1.07-1.45), respectively. Compared with the < 3.5 mg/dL, phosphorus ≥ 4.5 mg/dL was associated with a 28% and 57% increased risk of all-cause mortality (HR, 1.28; 95%CI, 1.05-1.55) and CVD mortality (HR, 1.57; 95CI, 1.19-2.08), respectively. In participants with eGFR < 60 ml/min/1.73m, elevated phosphorus (≥ 4.5 mg/ dL) were significantly associated with increased risk of all-cause mortality (HR, 1.36; 95%CI, 1.07-1.72). No significant association was observed in eGFR ≥ 60 ml/min/1.73m group (HR, 1.31; 95%CI, 0.86-1.99). This correlation does not differ significantly between subgroups defined by eGFR level (P for interaction = 0.889).
CONCLUSION
Serum phosphorus above 4.5 mg/dL is significantly associated with a 28% and 57% increased risk of all-cause and CVD death in non-dialysis CKD patients, respectively. This relationship still demonstrated in patients with eGFR < 60 ml/min/1.73m. However, for population with eGFR ≥ 60 ml/min/1.73m, further verification is needed.
Topics: Humans; Renal Dialysis; Nutrition Surveys; Prospective Studies; Cardiovascular Diseases; Phosphorus; Renal Insufficiency, Chronic
PubMed: 38448815
DOI: 10.1186/s12882-024-03525-x -
Nephron 2024This study aimed to investigate the efficacy and safety of sucroferric oxyhydroxide (SFOH) versus sevelamer carbonate in controlling serum phosphorus (sP) in adult... (Randomized Controlled Trial)
Randomized Controlled Trial
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.
Topics: Adult; Humans; Sevelamer; Hyperphosphatemia; Renal Dialysis; Ferric Compounds; Phosphorus; China; Chelating Agents; Drug Combinations; Sucrose
PubMed: 37473746
DOI: 10.1159/000531869 -
Medicine Apr 2024To construct an early clinical prediction model for AVF dysfunction in patients undergoing Maintenance Hemodialysis (MHD) and perform internal and external...
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.
Topics: Humans; Hyperphosphatemia; Models, Statistical; Prognosis; Retrospective Studies; Arteriovenous Fistula; Nomograms; Phosphorus; Diabetes Mellitus; Hyperlipidemias
PubMed: 38640314
DOI: 10.1097/MD.0000000000037737 -
International Journal of Molecular... Feb 2024Runx2 (runt related transcription factor 2) is an essential transcription factor for osteoblast proliferation and differentiation. Uridine diphosphate...
Runx2 (runt related transcription factor 2) is an essential transcription factor for osteoblast proliferation and differentiation. Uridine diphosphate (UDP)-N-acetylgalactosamine (GalNAc): polypeptide GalNAc-transferase 3 (Galnt3) prevents proteolytic processing of fibroblast growth factor 23 (Fgf23), which is a hormone that regulates the serum level of phosphorus. and were expressed in osteoblasts and osteocytes, and expression was restricted to osteocytes in bone. Overexpression and knock-down of upregulated and downregulated, respectively, the expressions of and , and Runx2 directly regulated the transcriptional activity of in reporter assays. The expressions of and in osteoblast-specific knockout () mice were about half those in mice. However, the serum levels of phosphorus and intact Fgf23 in mice were similar to those in mice. The trabecular bone volume was increased during aging in both male and female mice, but the osteoid was reduced. The markers for bone formation and resorption in mice were similar to the control in both sexes. mice exhibited hyperphosphatemia and hypercalcemia, and the intact Fgf23 was about 40% that of wild-type mice. These findings indicated that Runx2 regulates the expressions of and and that Galnt3 decelerates the mineralization of osteoid by stabilizing Fgf23.
Topics: Animals; Female; Male; Mice; Calcinosis; Core Binding Factor Alpha 1 Subunit; Fibroblast Growth Factors; N-Acetylgalactosaminyltransferases; Osteoblasts; Phosphorus; Polypeptide N-acetylgalactosaminyltransferase; Calcification, Physiologic
PubMed: 38396954
DOI: 10.3390/ijms25042275