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Urolithiasis Jul 2023A well-accepted strategy to prevent kidney stones is to increase urine volume by increasing oral intake of fluids, especially water, to lower supersaturation of the...
A well-accepted strategy to prevent kidney stones is to increase urine volume by increasing oral intake of fluids, especially water, to lower supersaturation of the relevant, relatively insoluble salts, and thereby lower the risk of precipitation. Randomized controlled trials have shown that this strategy works. It is inexpensive, safe, and intuitively attractive to patients. However, although any beverage can increase urine volume, and citrus juices can increase urine citrate content and pH, no beverage other than water has been clearly shown by randomized controlled trial to prevent kidney stones. We designed an innovative, palatable, low-calorie, high alkali citrate beverage to prevent kidney stones, called Moonstone. One packet of Moonstone powder, mixed in 500 ml of water, contains 24.5 meq of alkali citrate. We administered one packet twice a day to ten calcium stone formers. Moonstone resulted in an increase in mean 24-h urine citrate and urine pH, and a decrease in supersaturation of calcium oxalate in calcium stone formers compared to an equal volume of water. These changes, comparable to those seen in a prior study of a similar amount of (potassium-magnesium) citrate, will likely be associated with a clinically meaningful reduction in kidney stone burden in patients with calcium stones. The effect to increase urine pH would also be expected to benefit patients with uric acid and cystine stones, groups that we hope to study in a subsequent study. The study preparation was well tolerated and was selected as a preferred preventative strategy by about half the participants. Moonstone is an alternative, over-the-counter therapy for kidney stone prevention.
Topics: Humans; Citric Acid; Calcium; Kidney Calculi; Citrates; Water
PubMed: 37479949
DOI: 10.1007/s00240-023-01468-w -
Geochimica Et Cosmochimica Acta Jun 2023Green rusts (GR) are important drivers for trace metal and nutrient cycling in suboxic environments. We investigated whether green rusts would incorporate aluminum (Al)...
Green rusts (GR) are important drivers for trace metal and nutrient cycling in suboxic environments. We investigated whether green rusts would incorporate aluminum (Al) or other elements from naturally-formed clay minerals containing easily-weatherable clay minerals (e.g. mica, interlayered clays). We isolated the clay minerals from a Matapeake silt loam soil by removal of silt and sand, organic matter, and reducible oxides to study mechanisms of interaction between Fe(II) and soil-sourced clay minerals. We conducted batch Fe(II) sorption experiments at multiple near-neutral pHs (6.5-7.5) and reaction times (2 h-365 days). Mineral transformations were characterized by selective extractions, X-ray diffraction (XRD), and Fe X-ray absorption spectroscopy (XAS) analyzed by shell-fitting and linear combination fitting (LCF) with natural and synthetic standards. Clay mineral fraction contained a mixture of quartz, kaolinite, interlayered vermiculite, mica, and chlorite with significant structural Fe (2.6% wt). Uptake of Fe(II) increased with pH and kinetics were rapid until 5 days, followed by slow continuous Fe(II) uptake. Citrate-bicarbonate desorption kinetics from Fe(II) sorbed clay released more Al and silicon (Si) compared with unreacted soil clay fraction whereas magnesium (Mg) and potassium (K) were unaffected. Citrate-bicarbonate extracted Fe contained more Fe(II) than an ideal GR with an Fe(II)/Fe(III) molar ratio of 5.50. Analysis of the Fe EXAFS by both LCF and shell fitting was best modeled as a combination of Fe(III)-clay reduction to Fe(II) and precipitation of GR and Fe(II)-Al LDH. After 7 days of Fe(II) sorption, LCF identified 55.2% total Fe in clay, 33.4% GR(Cl) and 11.4% Fe(II)-Al LDH. These results provide novel evidence of Fe(II)-Al LDHs precipitating on naturally-formed soil clay minerals as a minor phase to GR. The geochemical implications are that GRs formed in soils and sediments should be considered to have Al and Si as well as Mg substitutions affecting their structure and reactivity.
PubMed: 37469621
DOI: 10.1016/j.gca.2023.04.001 -
Experimental and Therapeutic Medicine Aug 2023Distal renal tubular acidosis (RTA) is a rare adverse reaction to immune checkpoint inhibitors, which only occurs in a small number of cases. To the best of our...
Distal renal tubular acidosis (RTA) is a rare adverse reaction to immune checkpoint inhibitors, which only occurs in a small number of cases. To the best of our knowledge, distal RTA caused by sintilimab, a programmed cell death protein 1 (PD-1) inhibitor, has not been previously reported. In the present study, the case of a 62-year-old man with metastatic cardiac carcinoma treated with sintilimab anti-PD-1 therapy was reported. After the fourth administration of sintilimab, the treatment course was interrupted by metabolic hyperchloraemic acidosis with hypokalaemia. Following urine and blood tests, immunotherapy-induced distal RTA was suspected. Treatment with sintilimab and chemotherapy was stopped, and treatment with sodium bicarbonate and potassium citrate was started, which resulted in an adequate response. The present study provides the first case of distal RTA secondary to sintilimab treatment.
PubMed: 37456171
DOI: 10.3892/etm.2023.12084 -
Clinical Pharmacology in Drug... Oct 2023Quadruple therapy comprising 2 antibiotics, a proton pump inhibitor, and bismuth, is recommended for Helicobacter pylori eradication in China. This Phase 1,... (Randomized Controlled Trial)
Randomized Controlled Trial
Pharmacokinetics, Safety, and Tolerability of Vonoprazan- or Esomeprazole-Based Bismuth-Containing Quadruple Therapy: A Phase 1, Double-Blind, Parallel-Group Study in Adults with Helicobacter pylori Infection in China.
Quadruple therapy comprising 2 antibiotics, a proton pump inhibitor, and bismuth, is recommended for Helicobacter pylori eradication in China. This Phase 1, double-blind, parallel-group study aimed to evaluate the pharmacokinetics, safety, and tolerability of bismuth-containing vonoprazan- or esomeprazole-based quadruple therapy in H. pylori-positive healthy subjects at a single site in China. Quadruple therapy comprising vonoprazan 20 mg or esomeprazole 20 mg with bismuth potassium citrate 600 mg (equivalent to bismuth 220 mg), clarithromycin 500 mg, and amoxicillin 1000 mg was administered twice daily for 2 weeks. Forty-four subjects were enrolled, 22 each in the vonoprazan (mean age, 34.5 years; men, 63.6%) and esomeprazole (mean age, 31.6 years; men, 59.1%) groups. Day 14 bismuth plasma pharmacokinetic parameters area under the plasma concentration-time curve during a dosing interval (geometric mean ratio, 1.07 [90% confidence interval, 0.82-1.40]) and maximum observed plasma concentration (geometric mean ratio, 1.30 [90% confidence interval, 0.94-1.81]) were similar between the treatment groups. At Day 42 follow-up, 100% and 94.4% of subjects were H. pylori negative in the vonoprazan and esomeprazole groups, respectively. The incidence of treatment-emergent adverse events was similar between the groups, with no serious adverse events. No new safety concerns were identified. In conclusion, vonoprazan had no significant effect on plasma bismuth exposure compared with esomeprazole.
Topics: Adult; Humans; Male; Bismuth; Drug Therapy, Combination; Esomeprazole; Helicobacter Infections; Helicobacter pylori; Female
PubMed: 37443412
DOI: 10.1002/cpdd.1276 -
American Journal of Translational... 2023Potassium voltage-gated channel subfamily Q member 1 (KCNQ1), is implicated in the onset and progression of gastric carcinoma (GC), one of the most common types of...
BACKGROUND
Potassium voltage-gated channel subfamily Q member 1 (KCNQ1), is implicated in the onset and progression of gastric carcinoma (GC), one of the most common types of stomach malignancies. This research aims to investigate the potential prognostic implications of KCNQ1 mRNA in GC using various databases such as The Cancer Genome Atlas (TCGA), The Human Protein Atlas (HPA), LinkedOmics, TISIDB, ESTIMATE, and TIMER.
METHODS
We searched the HPA database to obtain information on KCNQ1 levels in human normal tissues, organs, and cell lines as well as in pan-cancer tissues. Then, we used TIMER and UALCAN to comparatively analyze the KCNQ1 mRNA levels in different types of cancers relative to their adjacent normal counterparts. Based on TCGA and Gene Expression Omnibus, the correlation of clinical information with KCNQ1 expression was analyzed using logistic regression model. Univariable and Multivariate Cox analyses were then carried out to compare differences in survival among patients with different clinical characteristics. The multivariate methods, such as Kaplan-Meier plotter and GEPIA survival curves, were further employed to identify the correlation of KCNQ1 expression with overall survival (OS). Besides, LinkedOmics was used to identify differentially expressed genes for functional enrichment analysis.
RESULTS
KCNQ1 exhibited tissue-specific imprinting and expression in human normal tissues, organs and cell lines, while it was aberrantly expressed in pan-cancer tissues. Lower KCNQ1 mRNA expression was determined in GC tissue samples versus normal counterparts. In GC cases, elevated KCNQ1 levels were strongly linked to a longer OS and strongly correlated with invasion depth (χ=12.631, P=0.006), TNM stage (χ=8.750, P=0.033), differentiation grade (χ=7.426, P=0.024), and vital status (χ=5.676, P=0.017). Furthermore, KCNQ1 was identified by univariable and multivariate Cox analyses as an independent risk factor for GC. Based on Gene Ontology analysis, digestion as well as tricarboxylic acid metabolic, carbohydrate catabolic, and small molecule catabolic processes were differentially enriched in the up-regulated KCNQ1 phenotypic pathway. While carbon metabolism, fatty acid degradation, peroxisome, and citrate cycle (TCA cycle) were identified by the Kyoto Encyclopedia of Genes and Genomes-based analysis as pathways with differential enrichment.
CONCLUSION
Being a prognostic biomarker, KCNQ1 may play an inhibitory role and involve in the metabolic process of GC.
PubMed: 37434821
DOI: No ID Found -
CEN Case Reports Apr 2024A 11-year-old girl was referred to the pediatric nephrology services of our hospital for evaluation of vitamin-D-refractory rickets. She was born to second-degree...
A 11-year-old girl was referred to the pediatric nephrology services of our hospital for evaluation of vitamin-D-refractory rickets. She was born to second-degree consanguineous parents. On examination, she had wrist widening and bilateral genu varum. She had normal anion gap metabolic acidosis, hypokalemia, and hyperchloremia. The fractional excretion of bicarbonate was 3% and the urine anion gap was positive. She also had hypercalciuria, but no phosphaturia, glucosuria or aminoaciduria. In view of a family history of an elder sister having rigidity with cognitive and speech impairment, an ophthalmic evaluation by slit lamp examination was performed in the index case that revealed bilateral Kayser-Fleischer rings. Serum ceruloplasmin was low and 24-h urine copper was elevated in the index case. Whole exome sequencing unveiled a novel pathogenic variant in exon 2 of the ATP7B gene (chr13: c.470del; Depth: 142x) (homozygous) that resulted in a frameshift and premature truncation of the protein, 15 amino acids downstream to codon 157 (p. Cys157LeufsTer15; NM_000053.4) confirming Wilson disease. There were no mutations in the ATP6V0A4, ATP6V1B1, SLC4A1, FOXI1, WDR72 genes or other genes that are known to cause distal RTA. Therapy with D-penicillamine and zinc supplements was initiated. A low dose of 2.5 mEq/kg/day of potassium citrate supplementation normalized the serum bicarbonate levels. This case was notable for the absence of hepatic or neurological involvement at admission. Wilson disease is well known to cause proximal renal tubular acidosis and Fanconi syndrome, with relatively lesser involvement of the distal renal tubules in the literature. However, isolated distal renal tubular involvement as presenting manifestation of Wilson disease (without hepatic or neurological involvement) is rare and can lead to diagnostic confusion.
Topics: Aged; Child; Female; Humans; Acidosis, Renal Tubular; Bicarbonates; Forkhead Transcription Factors; Hepatolenticular Degeneration; Mutation; Potassium Citrate; Vacuolar Proton-Translocating ATPases
PubMed: 37415038
DOI: 10.1007/s13730-023-00806-6 -
Clinical Journal of the American... Oct 2023A potassium replete diet is associated with lower cardiovascular risk but may increase the risk of hyperkalemia, particularly in people using... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
A potassium replete diet is associated with lower cardiovascular risk but may increase the risk of hyperkalemia, particularly in people using renin-angiotensin-aldosterone system inhibitors. We investigated whether intracellular uptake and potassium excretion after an acute oral potassium load depend on the accompanying anion and/or aldosterone and whether this results in altered plasma potassium change.
METHODS
In this placebo-controlled interventional cross-over trial including 18 healthy individuals, we studied the acute effects of one oral load of potassium citrate (40 mmol), potassium chloride (40 mmol), and placebo in random order after overnight fasting. Supplements were administered after a 6-week period with and without lisinopril pretreatment. Linear mixed effect models were used to compare blood and urine values before and after supplementation and between the interventions. Univariable linear regression was used to determine the association between baseline variables and change in blood and urine values after supplementation.
RESULTS
During the 4-hour follow-up, the rise in plasma potassium was similar for all interventions. After potassium citrate, both red blood cell potassium-as measure of the intracellular potassium-and transtubular potassium gradient (TTKG)-reflecting potassium secretory capacity-were higher than after potassium chloride or potassium citrate with lisinopril pretreatment. Baseline aldosterone was significantly associated with TTKG after potassium citrate, but not after potassium chloride or potassium citrate with lisinopril pretreatment. The observed TTKG change after potassium citrate was significantly associated with urine pH change during this intervention ( R =0.60, P < 0.001).
CONCLUSIONS
With similar plasma potassium increase, red blood cell potassium uptake and kaliuresis were higher after an acute load of potassium citrate as compared with potassium chloride alone or pretreatment with lisinopril.
CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER
Potassium supplementation in patients with chronic kidney disease and healthy subjects: effects on potassium and sodium balance, NL7618.
Topics: Humans; Potassium; Potassium Citrate; Potassium Chloride; Chlorides; Lisinopril; Aldosterone
PubMed: 37382933
DOI: 10.2215/CJN.0000000000000228 -
Pharmaceuticals (Basel, Switzerland) May 2023Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive disorder affecting <1/1,000,000 people. It is caused by mutations...
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive disorder affecting <1/1,000,000 people. It is caused by mutations in the CLDN16 (FHHNC Type 1) or CLDN19 (FHHNC Type 2) genes, which are located on Chromosomes 3q27 and 1p34.2, respectively. There are no drug therapies for this condition. Although magnesium salts represent an important class of compounds and exhibit various therapeutic actions as a supplement for magnesium deficiency in FHHNC, various formulations on the market have different bioavailability. We report the case of a patient with FHNNC first treated, in our Pediatric Institute, with high doses of magnesium pidolate and magnesium and potassium citrate. The patient began to neglect this therapy after experiencing frequent daily episodes of diarrhoea. Our pharmacy received a request for an alternative magnesium supplement that would better comply by ensuring a good magnesium intake which will result in adequate blood magnesium levels. In response, we developed a galenic compound in the form of effervescent magnesium. Here, we report on the promise of this formulation not only for better compliance than pidolate, but also for better bioavailability.
PubMed: 37375733
DOI: 10.3390/ph16060785 -
Food Research International (Ottawa,... Sep 2023The off-odors associated with spoilage of acidic beverages are linked to the germination and growth of Alicyclobacillus acidoterrestris (AAT) spores. As a consequence,...
The off-odors associated with spoilage of acidic beverages are linked to the germination and growth of Alicyclobacillus acidoterrestris (AAT) spores. As a consequence, we determined the influence of nutrients, non-nutrient germinants, dual-frequency thermosonication (DFTS), and food matrix on spore germination. AAT spores in orange juice (OJ), supplemented by L-alanine (L-ala), had the highest germination rate and lowest DPA content at 10 h of incubation. The formation of microscopic pores in cell membranes during DFTS caused irreversible damage in AAT spores in citrate buffer solution (CBS); however, it stimulated AAT spore germination in CBS containing L-ala. Hence, the germination potential was established in the order: L-ala > Calcium dipicolinate > asparagine, glucose, fructose, and potassium ion mixture (AGFK) > L-valine. The conductivity analysis indicated that membrane damage could be a key factor contributing to the artificial germination in CBS. AFM images revealed that after 2 h of adding L-ala, the protein content increased with increased germinated cells. TEM showed that membrane poration and coat detachment were the main pre-germination morphological changes detected after DFTS treatment. This study provides evidence that germination stimulated with DFTS might be an effective strategy for reducing A. acidoterrestris spores in fruit juices.
Topics: Spores, Bacterial; Alicyclobacillus; Beverages; Fruit and Vegetable Juices
PubMed: 37330854
DOI: 10.1016/j.foodres.2023.113054