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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 -
Alcohol (Fayetteville, N.Y.) Nov 2023The diagnosis of alcoholic ketoacidosis (AKA) has traditionally been made based only on clinical history and the presence of severe metabolic acidosis with a high anion...
BACKGROUND
The diagnosis of alcoholic ketoacidosis (AKA) has traditionally been made based only on clinical history and the presence of severe metabolic acidosis with a high anion gap (AG); however, the concentration of beta-hydroxybutyrate (BOHB), a pivotal ketone body in AKA, is not evaluated in most cases. The aim of this study was to clarify the clinical spectrum of AKA in terms of the severity of ketoacidosis by using a point-of-care capillary BOHB measurement device.
METHODS
This retrospective case series was conducted at a Japanese private teaching hospital. Patients with suspected AKA, based on their clinical history, who underwent BOHB measurement using a point-of-care capillary measurement device in the emergency department, were included. Data on their clinical presentations, blood tests, and treatments were collected, described, and compared between patients with a BOHB concentration higher than 3.0 mmol/L (H-BOHB) and those with a concentration less than 3.0 mmol/L (L-BOHB).
RESULTS
A total of 83 patients were included in this study. Sixty-eight patients were categorized as having H-BOHB and 15 as having L-BOHB. Nausea (71%), vomiting (71%), tachycardia (76%), and tachypnea (46%) were commonly observed at presentation. Hyponatremia (46%), hypokalemia (34%), hypomagnesemia (42%), and hyperphosphatemia (41%) were frequent electrolyte abnormalities upon presentation. Rehydration with balanced crystalloids and glucose-containing intravenous fluids, electrolyte supplementation, and thiamine replacement were the major treatments. The mean length of stay in the ICU and hospital were 4.4 and 7.0 days, respectively, with low overall mortality (1%). The H-BOHB and L-BOHB groups did not differ in terms of clinical data. Seventy percent of patients with L-BOHB had severe metabolic acidosis with a high AG due to hyperlactatemia (mean lactate concentration: 8.5 mmol/L).
CONCLUSIONS
We described the clinical features of AKA measured by using a point-of-care capillary BOHB measurement device. Although certain patients diagnosed with AKA based only on their clinical history had predominant lactic acidosis with minor elevations in BOHB concentration, the BOHB concentration had no effect on the clinical spectrum of AKA in this study.
Topics: Humans; 3-Hydroxybutyric Acid; Point-of-Care Systems; Retrospective Studies; Acidosis; Ketosis; Electrolytes
PubMed: 37453462
DOI: 10.1016/j.alcohol.2023.06.005 -
European Journal of Endocrinology Nov 2023Pseudohypoparathyroidism type 1a (PHP1a) is a rare endocrine disease caused by partial defects of the α subunit of the stimulatory Guanosin triphosphate (GTP) binding...
BACKGROUND
Pseudohypoparathyroidism type 1a (PHP1a) is a rare endocrine disease caused by partial defects of the α subunit of the stimulatory Guanosin triphosphate (GTP) binding protein (Gsα) resulting from maternal GNAS gene variation. The clinical manifestations are related to PTH resistance (hypocalcemia, hyperphosphatemia, and elevated serum intact PTH) in the presence or absence of multihormone resistance, and Albright's hereditary osteodystrophy (AHO).
OBJECTIVES
To summarize the molecular genetics results and clinical characteristics as well as to explore the correlations between them.
METHODS
Articles pertaining to PHP1a until May, 31, 2021 were reviewed and 527 patients with genetic diagnosis were included in the data analysis. The clinical characteristics and molecular genetics results of these patients were analyzed and compared to explore the correlations between them.
RESULTS
A total of 258 GNAS rare variants (RVs) were identified in 527 patients. The RVs were most commonly found in exons 1 and 7 (17.6% each), with frameshift (36.8%), and missense (31.3%) being the main types of RVs. The median age of onset was 5.0 years old. The most common clinical manifestations were elevation of PTH (86.7%) and AHO (87.5%). Thyroid stimulating hormone resistance was the most common hormone resistance (75.5%) other than PTH resistance. Patients with missense and in-frame RVs had lower incidence rates of the round face (P = .001) and subcutaneous ossifications (P < .001) than those with loss-of-function (non-sense, frameshift, splicing site variants, and large deletions) variants.
CONCLUSIONS
This study revealed the correlation between loss-of-function RVs with round faces and subcutaneous ossifications in PHP 1a patients. Further exploration of genotype-phenotype correlations through more standardized and prospective studies with long-term follow-up is necessary.
Topics: Humans; Child, Preschool; Prospective Studies; Chromogranins; Pseudohypoparathyroidism; GTP-Binding Protein alpha Subunits, Gs; Genetic Association Studies
PubMed: 37837607
DOI: 10.1093/ejendo/lvad142 -
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 -
Nephrology, Dialysis, Transplantation :... Mar 2024VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part phase 2 study evaluated the tolerability, safety,...
BACKGROUND
VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part phase 2 study evaluated the tolerability, safety, and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD).
METHODS
In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50, and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50, or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus.
RESULTS
The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during weeks 1‒2 of treatment). Most gastrointestinal disorders resolved without intervention, and none were serious. In Part 1, serum phosphorus significantly improved (mean change -2.0 mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day (mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2), and -1.4 (-2.2, -0.5) mg/dL, respectively). In both Parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation.
CONCLUSION
VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. Clinical Trial registration number: NCT04551300.
PubMed: 38453435
DOI: 10.1093/ndt/gfae053 -
Kidney International Reports Nov 2023
PubMed: 38025212
DOI: 10.1016/j.ekir.2023.10.001 -
Clinical Nephrology Aug 2023Calcific uremic arteriolopathy (CUA) represents a rare but severe disease with high morbimortality. The authors present the case of a 58-year-old male patient with... (Review)
Review
Calcific uremic arteriolopathy (CUA) represents a rare but severe disease with high morbimortality. The authors present the case of a 58-year-old male patient with chronic kidney disease due to obstructive uropathy, on hemodialysis (HD). He started HD due to uremic syndrome with a severe renal dysfunction, dysregulation of calcium and phosphate metabolism, and he presented with distal penile ischemia, which was treated with surgical debridement and hyperbaric oxygen therapy. Four months later, painful distal digital necrosis of both hands was observed. Extensive arterial calcification was observed on X-ray. A skin biopsy confirmed the presence of CUA. Sodium thiosulfate was administered for 3 months, HD was intensified, and hyperphosphatemia control was achieved, with progressive improvement of the lesions. This case illustrates an uncommon presentation of CUA in a patient on HD for a few months, non-diabetic and not anticoagulated, but with a severe dysregulation of calcium and phosphate metabolism.
Topics: Male; Humans; Middle Aged; Calciphylaxis; Kidney Failure, Chronic; Calcium; Renal Dialysis; Phosphates
PubMed: 37212158
DOI: 10.5414/CN110990 -
Nephrology, Dialysis, Transplantation :... Apr 2024Chronic kidney disease (CKD) is a growing global health concern. Recent research has indicated sex disparities in CKD-related complications, yet the impact of sex...
BACKGROUND AND HYPOTHESIS
Chronic kidney disease (CKD) is a growing global health concern. Recent research has indicated sex disparities in CKD-related complications, yet the impact of sex differences on critical kidney function levels that trigger these complications and mortality remains inadequately documented.
METHODS
We investigated sex-specific disparities in CKD-related complications and mortality according to eGFR levels. We analyzed NHANES data spanning from 1999 to 2018, including adult participants with an eGFR of 15-150 ml/min per 1.73m². The outcomes were CKD-related complications (hypertension, anaemia, CV diseases, acidosis, hyperphosphatemia, hyperparathyroidism) and all-cause and cause-specific mortality (CV mortality and non-CV mortality). Sex-stratified multivariable logistic and Cox regression models yielded odds ratios (ORs) and hazard ratios (HRs) for the relationship between eGFR categories and outcomes. Sex-stratified natural splines were used to explore the relationship between continuous eGFR and outcomes and identified eGFR thresholds of statistical significance.
RESULTS
The study included 49 558 participants (50.3% women, 49.7% men). Multivariable logistic regression demonstrated a significant eGFR association with all CKD-related complications, exhibiting a linear trend across eGFR categories. Modelling eGFR as a natural spline revealed varied significance thresholds between sexes for anaemia and hyperparathyroidism. Additionally, the eGFR-hyperphosphatemia association was more pronounced in men. We observed substantial but not statistically significant differences between men and women in the thresholds of statistical significance for CV (significance appeared at a higher eGFR in men) and non-CV mortality (significance appeared at a higher eGFR in women).
CONCLUSIONS
Research shows sex disparities in most CKD-related complications. Men develop anaemia and hyperparathyroidism earlier, women show steeper anaemia increase. Men have higher CV mortality risk. As eGFR decreased, men faced a higher risk of CV mortality at a higher eGFR threshold than women.
PubMed: 38632041
DOI: 10.1093/ndt/gfae087 -
Targeted Oncology May 2024Futibatinib (LYTGOBI) is an oral small molecule compound that selectively, irreversibly and potently inhibits the tyrosine kinase activity of fibroblast growth factor... (Review)
Review
Futibatinib (LYTGOBI) is an oral small molecule compound that selectively, irreversibly and potently inhibits the tyrosine kinase activity of fibroblast growth factor receptor (FGFR)1-4. It is approved in the EU, Japan and the USA for the treatment of adults with locally advanced or metastatic cholangiocarcinoma (CCA) harbouring an FGFR2 fusion or rearrangement who have progressed following systemic therapy. In the phase II part (FOENIX-CCA2) of a multinational phase I/II study in this patient population, monotherapy with futibatinib 20 mg once daily was associated with clinically meaningful and durable responses, sustained health-related quality of life (HR-QOL), and a manageable safety profile with supportive care and as-needed dose modifications. Indeed, hyperphosphataemia (the most common all grade and grade 3 treatment-related adverse event) was manageable with phosphate-lowering therapy and dose reductions or interruptions. Although further efficacy and tolerability data are expected, current evidence indicates that futibatinib is a valuable targeted therapy option for adults with locally advanced or metastatic CCA harbouring an FGFR2 fusion or rearrangement who have progressed following systemic therapy, a patient population with limited treatment options and poor life expectancy.
Topics: Humans; Cholangiocarcinoma; Bile Duct Neoplasms; Neoplasm Metastasis; Pyrimidines; Pyrazoles; Pyrroles
PubMed: 38724820
DOI: 10.1007/s11523-024-01059-8 -
Therapeutic Apheresis and Dialysis :... Jun 2024Chronic kidney disease (CKD) has emerged as one of the leading noncommunicable diseases affecting >10% of the population worldwide. Bone and mineral disorders are a... (Review)
Review
Chronic kidney disease (CKD) has emerged as one of the leading noncommunicable diseases affecting >10% of the population worldwide. Bone and mineral disorders are a common complication among patients with CKD resulting in a poor life quality, high fracture risk, increased morbidity and cardiovascular mortality. According to Kidney Disease: Improving Global Outcomes, renal osteodystrophy refers to changes in bone morphology found in bone biopsy, whereas CKD-mineral and bone disorder (CKD-MBD) defines a complex of disturbances including biochemical and hormonal alterations, disorders of bone and mineral metabolism and extraskeletal calcification. As a result, the management of CKD-MBD should focus on the aforementioned parameters, including the treatment of hyperphosphatemia, hypocalcemia, abnormal PTH and vitamin D levels. Regarding the bone fragility fractures, osteoporosis and renal osteodystrophy, which constitute the bone component of CKD-MBD, anti-osteoporotic agents constitute the mainstay of treatment. However, a thorough elucidation of the CKD-MBD pathogenesis is crucial for the ideal personalized treatment approach. In this paper, we review the pathology and management of CKD-MBD based on the current literature with special attention to recent advances.
PubMed: 38898685
DOI: 10.1111/1744-9987.14177