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Cureus Mar 2024Hyperphosphatemia familial tumoral calcinosis (HFTC) and hyperphosphatemia hyperostosis syndrome (HHS) are rare autosomal recessive disorders caused by mutations in the...
Hyperphosphatemia familial tumoral calcinosis (HFTC) and hyperphosphatemia hyperostosis syndrome (HHS) are rare autosomal recessive disorders caused by mutations in the polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3), fibroblast growth factor 23 (FGF23), or klotho (KL) genes. They are characterized by hyperphosphatemia and recurrent episodes of bone lesions with hyperostosis and/or soft tissue calcinosis. Management options include phosphate-lowering therapies, anti-inflammatory medications, and surgical excision of the calcified masses in significantly disabled cases. We describe three cases from a consanguineous family who were found to have the same genetic mutation caused by a homozygous mutation in intron eight of GALNT3 c.1524+1 G>A (IVS8+1). The first case had a presentation similar to chronic osteomyelitis, while the second one presented with a calcified mass in her gluteal area. The third case presented with left leg pain. Being a rare disease, the findings of tumoral calcinosis/ bony abnormalities, along with elevated phosphate levels, should raise the possibility of this entity. Family history and biochemical findings can help reach the diagnosis.
PubMed: 38576700
DOI: 10.7759/cureus.55575 -
Cureus Feb 2024Albright's hereditary osteodystrophy is a rare hereditary disease due to a mutation of the complex guanine nucleotide-binding protein, alpha-stimulating activity...
Albright's hereditary osteodystrophy is a rare hereditary disease due to a mutation of the complex guanine nucleotide-binding protein, alpha-stimulating activity polypeptide. This condition is commonly associated with type 1A and 1C pseudohypoparathyroidism and pseudo-pseudohypoparathyroidism due to resistance of parathyroid hormone. Patients present with specific characteristics such as brachydactyly, short stature, round facies, subcutaneous ossifications, developmental delay, and obesity, associated with hypocalcemia and hyperphosphatemia. This case presents a 55-year-old woman with short stature and neurocognitive impairment, who was admitted to the emergency department with acute decompensated heart and respiratory failure. On admission, hypocalcemia and hyperphosphatemia were noted, which in combination with the patient's clinical history led to an etiological investigation. This case stresses the importance of not only treating the acute disease but also looking at the patient and their clinical and analytical features to diagnose this disease and prevent its complications.
PubMed: 38558694
DOI: 10.7759/cureus.55200 -
Endocrine Journal Apr 2024Bone secrets the hormone, fibroblast growth factor 23 (FGF23), as an endocrine organ to regulate blood phosphate level. Phosphate is an essential mineral for the human... (Review)
Review
Bone secrets the hormone, fibroblast growth factor 23 (FGF23), as an endocrine organ to regulate blood phosphate level. Phosphate is an essential mineral for the human body, and around 85% of phosphate is present in bone as a constituent of hydroxyapatite, Ca(PO)(OH). Because hypophosphatemia induces rickets/osteomalacia, and hyperphosphatemia results in ectopic calcification, blood phosphate (inorganic form) level must be regulated in a narrow range (2.5 mg/dL to 4.5 me/dL in adults). However, as yet it is unknown how bone senses changes in blood phosphate level, and how bone regulates the production of FGF23. Our previous data indicated that high extracellular phosphate phosphorylates FGF receptor 1 (FGFR1) in an unliganded manner, and its downstream intracellular signaling pathway regulates the expression of GALNT3. Furthermore, the post-translational modification of FGF23 protein via a gene product of GALNT3 is the main regulatory mechanism of enhanced FGF23 production due to high dietary phosphate. Therefore, our research group proposes that FGFR1 works as a phosphate-sensing receptor at least in the regulation of FGF23 production and blood phosphate level, and phosphate behaves as a first messenger. Phosphate is involved in various effects, such as stimulation of parathyroid hormone (PTH) synthesis, vascular calcification, and renal dysfunction. Several of these responses to phosphate are considered as phosphate toxicity. However, it is not clear whether FGFR1 is involved in these responses to phosphate. The elucidation of phosphate-sensing mechanisms may lead to the identification of treatment strategies for patients with abnormal phosphate metabolism.
Topics: Fibroblast Growth Factor-23; Humans; Phosphates; Fibroblast Growth Factors; Animals; Receptor, Fibroblast Growth Factor, Type 1; Signal Transduction; Bone and Bones; N-Acetylgalactosaminyltransferases; Hyperphosphatemia; Polypeptide N-acetylgalactosaminyltransferase
PubMed: 38556320
DOI: 10.1507/endocrj.EJ24-0082 -
Lanthanum hydroxide protects kidney through gut microbiota in a rat model of chronic kidney disease.Pharmacology Research & Perspectives Apr 2024The progression of chronic kidney diseases (CKD) is complex, influenced by a myriad of factors including gut microbiota. While emerging evidence suggests that gut...
The progression of chronic kidney diseases (CKD) is complex, influenced by a myriad of factors including gut microbiota. While emerging evidence suggests that gut microbiota can have beneficial effects in managing CKD, it is also recognized that dysbiosis may contribute to the progression of CKD and associated uremic complications. Our previous research has demonstrated the efficacy of lanthanum hydroxide in delaying kidney failure and preserving renal function. However, the role of lanthanum hydroxide in modulating gut microbiota in this context remains unclear. In our study, we induced CKD in rats using adenine, leading to gut microbial dysbiosis, kidney pathology, and disturbances in amino acid metabolism. In this adenine-induced CKD model with hyperphosphatemia, treatment with lanthanum hydroxide improved renal function. This improvement was associated with the restoration of gut microbial balance and an increase in urine ammonium metabolism. These results suggest that the therapeutic potential of lanthanum hydroxide in CKD may be partly due to its ability to reshape gut microbiota composition. This study underscores the significance of lanthanum hydroxide in kidney protection, attributing its benefits to the modulation of gut microbiota in a rat model of CKD.
Topics: Rats; Animals; Gastrointestinal Microbiome; Dysbiosis; Kidney; Renal Insufficiency, Chronic; Adenine; Lanthanum
PubMed: 38546116
DOI: 10.1002/prp2.1187 -
Biomedicines Mar 2024The amount of evidence indicates that hyperphosphataemia (HP) can induce endothelial damage and significantly impair endothelial nitric oxide synthase (eNOS) expression....
The amount of evidence indicates that hyperphosphataemia (HP) can induce endothelial damage and significantly impair endothelial nitric oxide synthase (eNOS) expression. There are no clinical studies that have assessed HP and its correlation with circulating eNOS concentration in patients with end-stage renal disease (ESRD). Our preliminary study aimed to evaluate the relationship between plasma inorganic phosphorus (P) levels and circulating plasma eNOS concentration in patients on haemodialysis (HD). A total of 50 patients on HD were enrolled to the study. They were divided into groups according to the tertiles of P. The examined HD group was also analysed and compared with controls as a whole group; then, the group was divided into patients with and without dyslipidaemia (D) as well as into those with and without type 2 diabetes mellitus (type 2 DM). A total of 26 age-matched healthy volunteers were included in the study as the control group. The plasma levels of eNOS in HD patients are reduced in comparison to those in healthy subjects. There was no difference in plasma eNOS concentrations between HD patients with type 2 DM and those without DM as well as between those with D and without D. In the entire group of HD patients, there were positive correlations between circulating levels of eNOS and plasma P concentrations. In HD patients with D, higher systolic and diastolic blood pressure were accompanied by decreased plasma eNOS concentrations. In conclusion, HP and high blood pressure appear to decrease the circulating eNOS levels. These findings demonstrate an additional negative impact of HP on eNOS activity.
PubMed: 38540300
DOI: 10.3390/biomedicines12030687 -
Cureus Feb 2024Wilson's disease (WD) encompasses diverse clinical symptoms involving the liver, nervous system, and kidneys. The fundamental cause of this condition is the build-up of...
Wilson's disease (WD) encompasses diverse clinical symptoms involving the liver, nervous system, and kidneys. The fundamental cause of this condition is the build-up of copper in organs, mainly the hepatic and brain parenchyma. Here, we are reporting the hospital presentation of a male patient in his 20s who had been experiencing severe irritability, abdominal pain, distension, and yellowish discoloration of the skin for the previous 75 days. Upon examination of blood pressure, a refractory carpopedal spasm was found in him. In addition to Kayser-Fleischer (KF) rings in his cornea, he exhibited elevated 24-hour urine copper and serum ceruloplasmin (CP). He was diagnosed as a case of WD with a rare association of hypoparathyroidism.
PubMed: 38516426
DOI: 10.7759/cureus.54516 -
Frontiers in Pharmacology 2024The application of ferric citrate therapy has yielded unexpected benefits in recent years for Chronic kidney disease patients suffering from hyperphosphatemia and iron... (Review)
Review
The application of ferric citrate therapy has yielded unexpected benefits in recent years for Chronic kidney disease patients suffering from hyperphosphatemia and iron deficiency -anaemia. Despite this, earlier research on the impact of ferric citrate on NDD-CKD has been contentious. The goal of the meta-analysis is to evaluate the evidence regarding the advantages and dangers of ferric citrate for the treatment of hyperphosphatemia and iron deficiency anaemia in NDD-CKD patients. Between the start of the study and June 2022, we searched PubMed, Embase, Cochrane, EBSCO, Scopus, Web of Science, Wan Fang Data, CNKI, and VIP databases for randomised controlled trials of iron citrate for hyperphosphatemia and anaemia in patients with NDD-CKD. For binary categorical data, risk ratios (OR) were employed, and for continuous variables, weighted mean differences The effect sizes for both count and measurement data were expressed using 95% confidence intervals The meta-analysis includes eight trials with a total of 1281 NDD-CKD patients. The phosphorus-lowering effect of ferric citrate was greater compared to the control group (WMD, -0.55, 95% CI, -0.81 to -0.28; I = 86%, < 0.001). Calcium (WMD, 0.092; 95% CI, -0.051 to 0.234; > 0.05; I = 61.9%), PTH (WMD, -0.10; 95% CI, -0.44 to 0.23; I = 75%, > 0.05) and iFGF23 (WMD, -7.62; 95% CI, -21.18 to 5.94; I = 20%, > 0.05) levels were not statistically different after ferric citrate treatment compared to control treatment. Furthermore, ferric citrate increased iron reserves and haemoglobin. The ferric citrate group had considerably greater levels than the controls. Ferric citrate, on the other hand, may raise the risk of constipation, diarrhoea, and nausea. This meta-analysis found that ferric citrate had a beneficial effect in the treatment of NDD-CKD, particularly in reducing blood phosphorus levels when compared to a control intervention. It also shown that ferric citrate has a favourable effect on iron intake and anaemia management. In terms of safety, ferric citrate may increase the likelihood of gastrointestinal side effects.
PubMed: 38515853
DOI: 10.3389/fphar.2024.1285012 -
Asian Biomedicine : Research, Reviews... Feb 2024Dietary protein restriction has been considered to be a nutritional-related strategy to reduce risk for end-stage kidney disease among patients with... (Review)
Review
Dietary protein restriction has been considered to be a nutritional-related strategy to reduce risk for end-stage kidney disease among patients with non-dialysis-dependent chronic kidney disease (CKD). However, there is insufficient evidence to recommend a particular type of protein to slow down the CKD progression. Recently, various plant-based diets could demonstrate some additional benefits such as a blood pressure-lowering effect, a reduction of metabolic acidosis as well as hyperphosphatemia, and gut-derived uremic toxins. Furthermore, the former concerns about the risk of undernutrition and hyperkalemia observed with plant-based diets may be inconsistent in real clinical practice. In this review, we summarize the current evidence of the proposed pleiotropic effects of plant-based diets and their associations with clinical outcomes among pre-dialysis CKD patients.
PubMed: 38515633
DOI: 10.2478/abm-2024-0002 -
American Journal of Physiology. Renal... May 2024
Topics: Hyperphosphatemia; Humans; Zinc; Renal Insufficiency, Chronic; Animals; Nutritional Status; Phosphates
PubMed: 38511220
DOI: 10.1152/ajprenal.00052.2024 -
Seminars in Dialysis 2024Dialytic phosphate removal is a cornerstone of the management of hyperphosphatemia in peritoneal dialysis (PD) patients, but the influencing factors on peritoneal... (Observational Study)
Observational Study
BACKGROUND
Dialytic phosphate removal is a cornerstone of the management of hyperphosphatemia in peritoneal dialysis (PD) patients, but the influencing factors on peritoneal phosphate clearance (PPC) are incompletely understood. Our objective was to explore clinically relevant factors associated with PPC in patients with different PD modality and peritoneal transport status and the association of PPC with mortality.
METHODS
This is a cross-sectional and prospective observational study. Four hundred eighty-five PD patients were enrolled and divided into 2 groups according to PPC. All-cause mortality was evaluated after followed-up for at least 3 months.
RESULTS
High PPC group showed lower mortality compared with Low PPC group by Kaplan-Meier analysis and log-rank test. Both multivariate linear regression and multivariate logistic regression revealed that high transport status, total effluent dialysate volume per day, continuous ambulatory PD (CAPD), and protein in total effluent dialysate volume appeared to be positively correlated with PPC; body mass index (BMI) and the normalized protein equivalent of total nitrogen appearance (nPNA) were negatively correlated with PPC. Besides PD modality and membrane transport status, total effluent dialysate volume showed a strong relationship with PPC, but the correlation differed among PD modalities.
CONCLUSIONS
Higher PPC was associated with lower all-cause mortality risk in PD patients. Higher PPC correlated with CAPD modality, fast transport status, higher effluent dialysate volume and protein content, and with lower BMI and nPNA.
Topics: Humans; Male; Female; Middle Aged; Prospective Studies; Peritoneal Dialysis; Cross-Sectional Studies; Phosphates; Hyperphosphatemia; Kidney Failure, Chronic; Aged; Peritoneal Dialysis, Continuous Ambulatory; Dialysis Solutions; Adult
PubMed: 38506151
DOI: 10.1111/sdi.13205