Potassium (Citrate)

This meta-analysis summarizes the available evidence on the effectiveness of citrate supplement for preventing the recurrence of nephrolithiasis in patients undergoing extracorporeal shock wave lithotripsy (SWL). Electronic searches were conducted using Medline-PubMed, Web of Science, Embase, BVS (Scielo, Lilacs), and Google Scholar literature databases. The authors worked in pairs to select studies that met the following criteria: randomized controlled trials that were conducted in adults and assessed the effect of potassium citrate supplement before or after SWL therapy for urolithiasis. Our primary aim was to asses the stone-free rate among the groups included in the studies. Fixed effect was used in the meta-analysis with 95% confidence interval (95% CI). Heterogeneity was analyzed by the I 2 value. A total of 2505 references were initially selected. Of those, four were subjected to meta-analysis contributing five samples. These four studies included 374 participants who were followed for a period of 12 months after SWL. Mean potassium citrate dosage was approximately 55 mEq/day (18 mmol). The results showed that citrate supplement significantly protected against the recurrence of nephrolithiasis during 1 year after SWL [RR; 95% CI 0.21 (0.13, 0.31)]. The heterogeneity was not significant across the analyzed studies (p = 0.224). The quality of the analyzed studies was generally low. The available evidence shows that citrate supplement effectively reduces the recurrence of nephrolithiasis in patients undergoing SWL. However, statistical analysis of a larger trial conducted with methodological rigor is warranted.

The role of acid-base metabolism in bone health is controversial. In this meta-analysis, potassium bicarbonate and potassium citrate lowered urinary calcium and acid excretion and reduced the excretion of the bone resorption marker NTX. These salts may thus be beneficial to bone health by conserving bone mineral. INTRODUCTION: The role of acid-base homeostasis as a determinant of bone health and the contribution of supplemental alkali in promoting skeletal integrity remain a subject of debate. The objective of this study was, therefore, to conduct a meta-analysis to assess the effects of supplemental potassium bicarbonate (KHCO3) and potassium citrate (KCitr) on urinary calcium and acid excretion, markers of bone turnover and bone mineral density (BMD) and to compare their effects with that of potassium chloride (KCl). METHODS: A total of 14 studies of the effect of alkaline potassium salts on calcium metabolism and bone health, identified by a systematic literature search, were analysed with Review Manager (Version 5; The Cochrane Collaboration) using a random-effects model. Authors were contacted to provide missing data as required. Results are presented as the standardised (SMD) or unstandardized mean difference (MD) (95 % confidence intervals). RESULTS: Urinary calcium excretion was lowered by intervention with both KHCO3 (P = 0.04) and KCitr (P = 0.01), as was net acid excretion (NAE) (P = 0.002 for KHCO3 and P = 0.0008 for KCitr). Both salts significantly lowered the bone resorption marker NTX (P < 0.00001). There was no effect on bone formation markers or BMD. KHCO3 and KCitr lowered calcium excretion to a greater extent than did KCl. CONCLUSIONS: This meta-analysis confirms that supplementation with alkaline potassium salts leads to significant reduction in renal calcium excretion and acid excretion, compatible with the concept of increased buffering of hydrogen ions by raised circulating bicarbonate. The observed reduction in bone resorption indicates a potential benefit to bone health.

OBJECTIVES: The efficacy of keverprazan-amoxicillin dual therapy (KA) in the treatment of Helicobacter pylori (H. pylori) has not yet been demonstrated. Here, we aimed to compare the eradication rate of the KA regimen with esomeprazole-based bismuth quadruple therapy (EBQT) containing amoxicillin and clarithromycin for H. pylori initial eradication in the Chinese population. METHODS: Patients aged between 18-75 years were randomly assigned into KA group or the EBQT group. The KA group patients received keverprazan 20 mg (b.i.d.) and amoxicillin 1.0 g (t.i.d.) for 14 days. The EBQT group patients took esomeprazole 20 mg (b.i.d.), amoxicillin 1.0 g (b.i.d.), clarithromycin 0.5 g (b.i.d.), and bismuth potassium citrate 220 mg (b.i.d.) for 14 days. The primary outcome was the H. pylori eradication rate 28 days after therapy. Secondary outcomes included compliance and adverse events. RESULTS: A total of 394 patients were enrolled in this study. Eradication rates in the KA group and the EBQT group were 87.88% and 84.18% in intention-to-treat analysis (ITT) (rate difference: 3.70%, 95% CI: -3.14% to 10.53%), 92.55% and 88.24% in modified ITT analysis (rate difference: 4.32%, 95% CI: -1.63% to 10.27%), and 93.99% and 90.56% in per-protocol analysis (PP) (rate difference: 3.43%, 95% CI: -2.05% to 8.92%), respectively. The eradication rates for the KA group were not inferior to those of the EBQT group in ITT, modified ITT, and PP analysis. The incidences of nausea and overall adverse effects in the KA group were significantly lower than those of the EBQT group. CONCLUSIONS: Keverprazan 20 mg twice daily with high-dose amoxicillin demonstrates a noninferior efficacy to bismuth quadruple therapy for initial H. pylori eradication. TRIAL REGISTRATION: Chinese Clinical Trial Registry, registration No: ChiCTR2400092511. © 2026 John Wiley & Sons Ltd.

BACKGROUND: Bismuth quadruple therapy (BQT) is a recommended first-line regimen for Helicobacter pylori (H. pylori) eradication., but its use is limited by side effects and restricted bismuth availability. Probiotic represents an investigational alternative strategy. This study compared the efficacy and safety of triple therapy plus probiotics (TTP)with BQT. METHODS: Patients with H. pylori infection were randomised to receive either TTP (probiotics, amoxicillin, clarithromycin and esomeprazole) or BQT (bismuth potassium citrate, amoxicillin, clarithromycin and esomeprazole) for 14 d. The primary endpoint was the eradication rate by 13C-urea breath test ≥28 d after treatment completion. Secondary endpoints included adverse events and adherence. RESULTS: The eradication rates for TTP vs. BQT were 76.4% (126/165) and 86.6% (142/164) in the intention-to-treat (ITT) analysis (difference, -10.2%; 95% CI: -18.5% to -1.9%; P = 0.521) and 84.0% (126/150) and 94.7% (142/150) in the protocol (PP) analysis (difference, -10.7%; 95% CI: -17.5% to -3.8%, P = 0.576). Among patients aged ≥40 y, eradication rates were comparable between TTP and BQT in both the ITT and PP analysis (91.9% vs. 84.9% and 97.1% vs. 93.8%, P = 0.015 and P = 0.019 for noninferiority, respectively). The incidence of adverse event was lower in the TTP group (17.8% vs. 28.7%; P = 0.029). Furthermore, TTP preserved gut microbiota stability, whereas BQT induced dysbiosis. CONCLUSION: While TTP was inferior to BQT in eradication efficacy, it demonstrated better tolerability and protective effects against gut microbiota dysbiosis. In patients aged ≥40 y, TTP achieved non-inferior eradication rates, suggesting this subgroup may warrant further investigation. TRIAL REGISTRATION NUMBER: ChiCTR2200058491.

BACKGROUND: Recurrent urolithiasis is a major clinical challenge, with more than 50% of patients experiencing recurrence within 5 years. While potassium citrate effectively reduces recurrence, poor adherence due to cost and gastrointestinal side effects limits its long-term use. Citrus-based interventions, such as lime juice, have shown potential in enhancing urinary citrate and alkalinity but require further validation. This study evaluated the efficacy of a lime-based phytochemical-rich regimen (LPR) in preventing stone recurrence and reducing urinary inflammation in post-operative urolithiasis patients. OBJECTIVE: This multicenter, double-blind, randomized controlled trial aimed to evaluate the efficacy and safety of a novel lime-based preparation called LPR in preventing kidney stone recurrence over 24 months. METHODS: In a double-blind, randomized, placebo-controlled, multicenter trial, 173 patients with calcium oxalate urolithiasis who had undergone successful stone removal were enrolled from six hospitals in Thailand. Participants were randomized to receive either LPR or placebo for 24 months. The primary outcome was the incidence of stone recurrence confirmed by computerized topography (CT). Secondary outcomes included changes in urinary protein excretion and urinary interleukin-8 (IL-8) level, a pro-inflammatory cytokine implicated in renal inflammation and stone formation. Kaplan-Meier survival analysis and multivariate Cox regression were used to assess recurrence risk. RESULTS: Of 173 enrolled participants, 151 completed the study. The recurrence rate at 2 years was significantly lower in the LPR group (14%) compared to placebo (45%) (p < 0.001). Kaplan-Meier analysis demonstrated a hazard ratio (HR) of 0.24 (95% CI: 0.13-0.44; log-rank p < 0.0001) favoring LPR. Among completers, LPR significantly reduced urinary IL-8 level (p = 0.017) and 24-hour urinary protein excretion (p = 0.032) compared to baseline and placebo. No serious adverse events were reported, and adherence was high in both groups. CONCLUSION: LPR, a lime-based supplement rich in citrate and flavonoids, significantly reduced the 2-year recurrence rate of calcium oxalate stones by appro

BACKGROUND: The health benefits of dietary potassium have been linked to potassium-induced natriuresis. However, it is unknown whether potassium loading in patients with chronic kidney disease (CKD) induces natriuresis and to what degree it increases plasma potassium. We hypothesize that potassium-induced natriuresis remains intact and that potassium loading is safe in patients with CKD. METHODS: In this placebo-controlled crossover study, 18 healthy individuals and 9 patients with non-diabetic CKD stage G3b-G4 received an acute oral load of potassium chloride (KCl), potassium citrate (K-cit) (40 mmol each) or placebo, either with or without 6 weeks of lisinopril (10 mg/day) pretreatment. Differences in placebo-subtracted plasma potassium and natriuresis between groups during 4-h follow-up were analysed using linear mixed models. RESULTS: In healthy individuals, but not in patients with CKD, urinary sodium excretion increased 2 h after potassium supplementation, independent of lisinopril pretreatment. Compared with patients with CKD, mean urinary sodium excretion in healthy individuals was 13 mmol [95% confidence interval (CI) 4-22; P = .005] and 13 mmol (95% CI 4-22; P = .006) higher 2 h after KCl and K-cit, respectively. Estimated glomerular filtration rate positively correlated with urinary sodium excretion 2 h after KCl and K-cit, both with and without lisinopril pretreatment. Plasma potassium after potassium supplementation was higher in patients with CKD than in healthy individuals independent of lisinopril pretreatment. CONCLUSIONS: These findings indicate that in CKD, potassium-induced natriuresis does not occur and oral potassium loading is accompanied by an increased risk of hyperkalaemia. © The Author(s) 2025. Published by Oxford University Press on behalf of the ERA. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact [email protected].

To compare the efficacy of low PRAL dietary intervention against potassium citrate (PCi) extended-release medication in modifying key urinary lithogenic parameters for oxalate calcium calculi formation over a four-week duration. We conducted a three-arm, parallel-group study with 46 participants randomized into a Diet group (n = 14), a Medicine group (n = 16), and a Control group (n = 16). Twenty-four-hour urine samples were collected at baseline, two weeks, and four weeks. Nine primary urinary outcomes were analyzed: Citrate (Cit), Potassium (UK), pH, Oxalate (OX), Calcium (UCa), Sodium (UNa), Chloride (UCl), Urine Volume, and estimated Potential Renal Acid Load (PRAL). Longitudinal changes were assessed using Linear Mixed-Effects Models (LMMs). Baseline characteristics were well-balanced across the three groups (p > 0.05 for most of indicators) except citrate. The LMM analysis revealed that the Medicine group showed statistically significant improvements compared to the Control group in urine potassium and PRAL at two weeks and continued to four weeks (p < 0.001). Urine laboratory tests changes in diet intervention were not significant over time, however, the Diet group showed slight modification of the urine protective factors, such as urine potassium and pH, to alkalinization. Diet intervention no significant changes were observed in urine stone formation potential lithogenic factors including calcium, sodium, chloride, or oxalate. The low-potential renal acid load (PRAL) diet, characterized by higher consumption of vegetables, fruits, and less animal-based proteins, produced gradual but modest improvements in urinary parameters linked to calcium oxalate stone prevention. While prolonged dietary compliance was associated with correcting urine acidification, the dietary intervention exerted only a limited impact on other major lithogenic factors. © 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

BACKGROUND: Current Helicobacter pylori (H. pylori) eradication regimens-standard triple, bismuth-containing quadruple, and non-bismuth quadruple therapies-still face issues such as adverse effects and poor compliance. High-dose dual therapy, with its simplicity, lower pill burden, and comparable efficacy, has recently gained attention. However, existing studies are largely single-center with small sample sizes and lack sufficient evidence-based support. This study aims to further evaluate the efficacy and safety of ilaprazole-based dual and quadruple therapies for H. pylori eradication. METHODS: This was a prospective, multicenter, randomized controlled, non-inferiority clinical trial conducted at five hospitals from January to November 2023. A total of 480 patients were randomly assigned to one of three treatment groups for 14 days: Group A (ilaprazole 5 mg, amoxicillin 1 g, clarithromycin 500 mg, and bismuth potassium citrate 220 mg, all administered twice daily), Group B (ilaprazole 5 mg twice daily and amoxicillin 1 g three times daily), and Group C (ilaprazole 10 mg twice daily and amoxicillin 1 g three times daily). The eradication rates, adverse events, and patient compliance were recorded. RESULTS: The eradication rates of H. pylori in Groups A, B, and C were 76.9%, 88.1%, and 88.7% (p = 0.004) by intention-to-treat analysis, respectively, and 78.3%, 90.4%, and 91.0% (p = 0.001) using modified intention-to-treat analysis, and 81.8%, 92.1%, 92.2% (p = 0.005) by per-protocol analysis. The adverse event rates were 28.0%, 10.2%, 10.8% in Groups A, B, and C, respectively (p < 0.001), while patient compliance rates were 91.1%, 98.1%, 98.7%, respectively (p = 0.001). Sex, smoking history, alcohol intake, and sharing tableware or cups did not affect the efficacy of the three treatment regimens. CONCLUSIONS: The standard- or high-dose dual therapy with ilaprazole demonstrated superior efficacy, safety, and patient compliance compared to quadruple therapy. No significant differences were observed between these dual therapies, which are expected to become promising alternatives for the primary treatment of H. pylori infection. TRIAL REGISTRATION: Chinese Clinical

BACKGROUND: Tailored therapy based on genetic testing of fecal samples is a promising method for Helicobacter pylori eradication, but relevant research is still lacking, and the effectiveness remains unclear. OBJECTIVE: This study conducted a randomized controlled trial to evaluate the efficacy, safety, and compliance of triple plus bismuth therapy (TBT) guided by clarithromycin and levofloxacin genotypic resistances and CYP2C19 polymorphisms from stool samples. A preliminary health economics analysis was also conducted. DESIGN: Six hundred and sixteen treatment-naïve patients were randomly divided into tailored (individualized drug selection based on genetic testing for 7 or 14 days) and empiric (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg, all twice daily for 14 days) TBT groups. Safety and compliance were assessed within 1-3 days after eradication. 13C-urea breath test was performed within 4-8 weeks after eradication to evaluate the therapeutic outcome. RESULTS: The eradication rates of the tailored TBT group were non-inferior to those of the empiric TBT group [intention-to-treat analysis 87.7% vs. 80.8%, rate difference 6.8% (95% confidence interval 0.8%-12.9%); modified intention-to-treat analysis 93.4% vs. 86.8%, rate difference 6.7% (95% confidence interval 1.5%-11.9%); per-protocol analysis 95.7% vs. 88.7%, rate difference 7.0% (95% confidence interval 2.2%-11.8%)]. The tailored TBT group achieved satisfactory efficacies (acceptable in intention-to-treat and excellent in per-protocol analyses). Safety and compliance were similar between the two groups. The average cost of each successful eradication case in the tailored TBT group is lower than that in the empiric TBT group. CONCLUSION: The tailored TBT guided by antibiotic genotypic resistances and CYP2C19 polymorphisms detected from fecal specimens achieved satisfactory efficacy, safety, and compliance in the first-line Helicobacter pylori eradication with less expenses (ChiCTR2300068620). TRIAL REGISTRATION: Chinese Clinical Trials Registration: ChiCTR2300068620. © 2025 John Wiley & Sons Ltd.

BACKGROUND: Rifasutenizol (TNP-2198) is a new molecular entity with a synergistic dual mechanism of action under clinical development for the treatment of Helicobacter pylori infection. We aimed to evaluate the efficacy and safety of a rifasutenizol-based triple therapy (RTT) versus bismuth plus clarithromycin-based triple therapy (BCTT) for the treatment of H pylori infection in treatment-naive patients. METHODS: EVEREST-HP was a phase 3, randomised, triple-dummy, double-blind, active-controlled, non-inferiority trial with adaptive design for sample size re-estimation conducted at 40 research hospitals in China. Treatment-naive patients aged 18-65 years, with a positive [13C]urea breath test ([13C]UBT), further confirmed by gastric biopsy and histological examination, were randomly assigned (1:1) to receive RTT (rifasutenizol 400 mg oral capsules, amoxicillin 1 g oral capsules, and rabeprazole 20 mg enteric-coated tables) or BCTT (bismuth potassium citrate 240 mg oral tablets, clarithromycin 500 mg oral tablets, amoxicillin 1 g oral capsules, and rabeprazole 20 mg enteric-coated tablets), all twice a day for 14 days. Randomisation was done centrally by a secure interactive web response system using block sizes of two or four and stratified by study site. RTT was compared against BCTT using a triple-dummy approach to ensure masking. The primary endpoint was H pylori eradication rate based on [13C]UBT 4-6 weeks after the end of treatment in the modified intention-to-treat population, which included all participants who received at least one dose of the study drugs. The eradication rates of RTT and BCTT were compared using a one-sided α value of 0·025 and a non-inferiority margin of -10%. Safety endpoints included investigator assessed treatment-emergent adverse events, the severity and relationship with study drugs, findings from physical examinations, vital signs, laboratory tests, and electrocardiogram. An interim analysis was conducted by an independent data monitoring committee after 50% (350) of patients completed the last [13C]UBT. The trial is registered with ClinicalTrials.gov, NCT05857163. FINDINGS: Between May 18, 2023, and Nov 10, 2023, 1267 patients w

Erratum in Sci Rep. 2025 Jun 13;15(1):20064. doi: 10.1038/s41598-025-04526-y. This study evaluated the efficacy, safety, and cost of minocycline, ornidazole, esomeprazole, and bismuth (MOEB) therapy versus classical therapy (amoxicillin, clarithromycin, esomeprazole, and bismuth potassium citrate, ACEB) for Helicobacter pylori eradication. In a randomized trial of 390 patients, MOEB demonstrated superior eradication rates (93.2% per-protocol, 78.5% intention-to-treat) compared to ACEB (82.5% per-protocol, 72.8% intention-to-treat). Adverse events were significantly lower with MOEB (19.3% vs. 33.8%, p = 0.0019). MOEB was also more cost-effective, with a direct cost of 675.7 CNY versus 970.1 CNY for ACEB, yielding an incremental cost-effectiveness ratio of -27.5 CNY per eradication rate. MOEB is a safe, effective, and cost-efficient first-line regimen for H. pylori eradication. © 2025. The Author(s).

BACKGROUND AND AIMS: Tegoprazan, a new class of drugs, is a potassium-competitive acid blocker (P-CAB) that inhibits gastric H+/K+-ATPase through a different mechanism than proton pump inhibitor. Tetracycline also has anti-Helicobacter pylori properties. However, only a few randomized controlled trials (RCTs) have investigated the efficacy of tegoprazan and tetracycline-containing quadruple therapy (TTQT) for treating H. pylori infections, which this RCT explored. METHODS: This multicenter RCT included treatment-naïve adults with H. pylori infection who received 7 or 14 days of TTQT (50-mg tegoprazan, 220-mg bismuth potassium citrate, and 1000-mg amoxicillin twice daily with 500-mg tetracycline four times daily). The primary outcome was the eradication rate; secondary endpoints included the incidence of adverse events, treatment compliance, and regimen costs. RESULTS: The study included 258 patients. The eradication rates in the 7- and 14-day groups were 90.70% (117/129, 95% confidence interval [CI]: 83.98%-94.89%) and 91.47% (118/129, 95% CI: 84.90%-95.45%), respectively, in the intention-to-treat analysis (difference: -0.78%; -7.01%-8.58%; noninferiority p < 0.001); 92.86% (117/126, 95% CI: 86.50%-96.48%) and 93.65% (118/126, 95% CI: 87.47%-97.02%), respectively, in the modified intention-to-treat analysis (difference: 0.79%; 95% CI: -6.36%-7.99%; noninferiority p < 0.001); and 94.35% (117/124, 95% CI: 88.29%-97.50%) and 95.12% (117/123, 95% CI: 89.24%-98.00%), respectively, in the per-protocol analysis (difference: -0.77%; 95% CI: -5.91%-7.48%; noninferiority p < 0.001). Significantly fewer adverse events occurred in the 7-day group than in the 14-day group (22.48% vs. 35.67%, p = 0.020). Treatment compliance did not differ between the two groups. CONCLUSIONS: The 7- and 14-day TTQT efficacies for the first-line treatment of H. pylori infection were comparable, and fewer adverse effects occurred in the 7-day group. This trial has been registered at Clinical Trials.gov (NCT05997433). © 2025 John Wiley & Sons Ltd.

Ilaprazole, a proton pump inhibitor, has been approved and marketed in Korea and China for the treatment of gastric ulcer, duodenal ulcer, gastroesophageal reflux disease, and erosive esophagitis. This study evaluated the in vitro antibacterial activity of ilaprazole against Helicobacter pylori (H. pylori), both as a single agent and in combination with other components used in the standard quadruple therapy. The antibacterial activity of ilaprazole was tested on 25 H. pylori strains, including the clinical isolates resistant to clarithromycin (CLA), amoxicillin (AMX), levofloxacin, and/or metronidazole. Antibacterial activities and killing kinetics were evaluated by the minimal inhibitory concentration (MIC) and time-kill curve determination, respectively. Synergistic effects were assessed in checkerboard and time-kill assays. Resistance development was assessed through serial passage over 12 cycles. Ilaprazole exhibited potent in vitro antibacterial activity against H. pylori, with MIC50 and MIC90 values of 8 µg/mL, demonstrating activity against drug-resistant strains. When combined with CLA, ilaprazole showed synergistic effects against 36% of the tested strains. Notably, the quadruple combination of ilaprazole + AMX + CLA + bismuth potassium citrate exhibited an obvious synergistic effect. Importantly, repeated exposure to ilaprazole over 12 passages did not induce resistance. These findings highlight the promising in vitro antibacterial activity of ilaprazole against H. pylori, including drug-resistant strains, and its potential to enhance the efficacy of quadruple therapy. The study supports the inclusion of ilaprazole in treatment regimens for H. pylori infections, offering a compelling rationale for its clinical use. IMPORTANCE H. pylori infection remains a major global health issue, contributing to a wide range of gastric diseases. Despite current treatment regimens, rising antibiotic resistance limits their effectiveness, emphasizing the need for novel therapeutic approaches. This study highlights the promising in vitro antibacterial activity of ilaprazole against H. pylori, including drug-resistant strains. Ilaprazole not only exhibits direct antimic

BACKGROUND: Tegoprazan is a potassium-competitive acid blocker that inhibits gastric acid and which may be used for eradicating Helicobacter pylori. This study focuses on the pharmacokinetic interaction and safety between tegoprazan and the combination of clarithromycin, amoxicillin and bismuth in healthy Chinese subjects. METHODS: An open-label, three-period, single-center, multiple-dosage, single-sequence, phase I trial was conducted in 22 healthy subjects. In period 1, the subjects took tegoprazan 50 mg twice daily for 7 days, and in period 2 they were administered clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 600 mg twice daily for 7 days (days 14-20). Tegoprazan, clarithromycin, amoxicillin and bismuth potassium citrate were then administered in combination for 7 days (days 21-27) in period 3. Blood samples were collected up to 12 h after the last dose of each period. Safety assessments were performed in each period. RESULTS: The geometric mean ratios (GMRs) [90% confidence interval (CI)] of maximum plasma concentration at steady state (Cmax,ss) and area under the plasma concentration-time curve over the dosing interval (AUCτ) at steady state were 195.93% (175.52-218.71%) and 287.54% (263.28-314.04%) for tegoprazan and 423.23% (382.57-468.22%) and 385.61% (354.62-419.30%) for tegoprazan metabolite M1, respectively. The GMRs (90% CI) of Cmax,ss and AUCτ were 83.69% (77.44-90.45%) and 110.30% (102.74-118.41%) for clarithromycin, 126.25% (114.73-138.93%) and 146.94% (135.33-159.55%) for 14-hydroxyclarithromycin, 75.89% (69.73-82.60%) and 94.34% (87.94-101.20%) for amoxicillin, and 158.43% (125.43-200.11%) and 183.63% (156.42-215.58%) for bismuth, respectively. All reported adverse events were mild. The frequency of adverse events during the coadministration stage was not higher than that during the single- or triple-drug administration stages. CONCLUSION: The plasma exposure of tegoprazan, M1, 14-hydroxyclarithromycin and bismuth was increased after the coadministration of tegoprazan, clarithromycin, amoxicillin and bismuth. The coadministration exhibited favorable safety and tolerability. CLINICAL TRIALS REGISTRATION: CTR20230643.

Extracellular pH (pHe) of tumor cells is characteristic of tumor microenvironment (TME). Acidic TME impairs the responses of tumors to some anti-cancer chemotherapies. In this study, we showed that daily oral dosing of sodium potassium citrate (K/Na citrate) increased blood HCO3- concentrations, corresponding to increase of HCO3- concentrations and pHs in urine, and neutralized the tumor pHe. Neutralization of acidic TME by alkaline substance like HCO3-, an active metabolite of K/Na citrate, well potentiated the therapeutic effect of anticancer agent TS-1®, an orally active 5-fuluoro-uracil derivative, in Panc-1 pancreatic cancer-xenograft murine model. Neutralization of acidic TME by using an alkaline K/Na citrate is a smart approach for enhancement of the therapeutic effects of anticancer agents for pancreatic cancer in the end stage.

OBJECTIVE: We investigated and compared the effects of taraxasterol, aqueous extract of T. officinale (AET) aerial part, and potassium citrate (PC) on calcium oxalate (CaOx) crystallization in vitro. MATERIALS AND METHODS: CaOx crystallization was induced by adding sodium oxalate to synthetic urine. Taraxasterol (2.5, 5, 7.5 and 12.5 μg/mL), extract (1, 2, 4 and 8 mg/mL), and PC (100, 150, 200 and 350 mg/mL) were subjected to anti-crystallization activities. The absorbance and %inhibition of nucleation of CaOx crystals were evaluated by spectrophotometer at 2, 4, 6, 8, 10, 20, 30, 40, 50 and 60 min and the number and morphology of crystals were studied by light microscopy after 60 min. RESULTS: Presence of taraxasterol, extract and PC decreased absorbance in experimental samples compared to control, significantly. The nucleation of crystals is inhibited by taraxasterol, extract, and PC (26-64, 55-63 and 60-70%, respectively). The number of CaOx crystals were decreased in presence of taraxasterol (p < .01), extract (p < .001), and PC (p < .001) in a dose-dependent manner. Presence of taraxasterol, extract, and PC decreased the number of CaC2O4 monohydrate, while increased CaC2O4 dihydrate crystals, significantly. Also, the diameter of CaC2O4 dihydrate crystals was decreased in presence of taraxasterol, extract and PC, significantly. CONCLUSIONS: This research indicated that taraxasterol and extract have anti-crystallization activities and effectiveness of the extract is more potent than taraxasterol. It could be because of another constituent in the extract with the synergistic effect.

Comment in Eur Urol. 2007 May;51(5):1445. doi: 10.1016/j.eururo.2007.02.023. Calcium oxalate monohydrate (COM), which represents a major component of kidney stones, is an end metabolite of ethylene glycol. COM accumulation has been linked with acute renal toxicity in ethylene glycol poisoning. COM injures the kidney either by directly producing cytotoxicity to the kidney cells or by aggregating in the kidney lumen leading to the blockage of urine flow. The present studies were designed to examine whether aluminum citrate could reduce the toxicity of COM. Toxicity was determined in human proximal tubule cells by leakage of lactate dehydrogenase or uptake of ethidium homodimer and in erythrocytes by degree of hemolysis. Aluminum citrate significantly inhibited the leakage of lactate dehydrogenase from human proximal tubule cells and protected against cell death from COM. The inhibitory effect of aluminum citrate was greater than that of other citrate or aluminum salts such as sodium citrate, aluminum chloride, calcium citrate, ammonium citrate or potassium citrate. Aluminum citrate significantly inhibited the aggregation of COM crystals in vitro and decreased red cell membrane damage from COM. Aluminum citrate appeared to directly interact with COM, but not with the cell membrane. As such, aluminum citrate reduced the cytotoxicity by a physico-chemical interaction with the COM surface, and not by dissolving the COM crystals. These studies suggest that aluminum citrate may protect against tissue damage that occurs with high levels of oxalate accumulation, especially in ethylene glycol poisoning and possibly in hyperoxaluric states.

OBJECTIVES: To examine urinary parameters among normal individuals and patients with calcium oxalate (CaOx) stones after oral administration of potassium-sodium citrate (KNa-Cit) and magnesium oxide (MgO). Urinary citrate and magnesium have been known as the inhibitors of CaOx stone formation. Supplementation with potassium-magnesium citrate prevents the recurrence of CaOx stones. METHODS: Twenty-five male volunteers aged 21 to 42 years without a history of urinary stones were given either KNa-Cit or MgO, or both. Fourteen patients with recurrent CaOx stones were also given both supplements, and 24-hour urine samples were collected to determine the urinary parameters. RESULTS: The administration of both KNa-Cit and MgO to the normal individuals increased the excretion of citrate, magnesium, and potassium by 70.0%, 44.2%, and 50.0%, respectively. These parameters increased less when KNa-Cit or MgO was administered individually. After administration of both supplements to the patients with stones, the citrate, magnesium, and potassium levels increased by 62.1%, 63.3%, and 25.3%, respectively, and oxalate decreased by 66.5%. In both normal individuals and patients, the ion activity product index of CaOx decreased significantly more after administration of the combination than with either compound alone or before administration. CONCLUSION: The combination of KNa-Cit and MgO is more effective than either supplement alone in inhibiting the crystallization of CaOx stones. The combination may improve the urinary parameters of patients with stones accompanied by hypocitraturia and/or hypomagnesuria.

Following recent concern over probable interactions between the 4-quinolones and metal ions, the effect of co-administered drugs--sodium bicarbonate, potassium citrate, ferrous sulphate, magnesium trisilicate, calcium carbonate and aluminium hydroxide--on the saliva and urine pharmacokinetics of ofloxacin in healthy human volunteers has been investigated. The Cmax and AUC0-9 in saliva were generally in the range 1.05-1.40 mg/L and 4.89-6.16 mg.h/L, respectively, and were unaffected (P less than 0.05) by the metallic drugs, except aluminium hydroxide which lowered these values. Again, only aluminium hydroxide modified the Ka of ofloxacin, resulting in a slower absorption rate. However, none of the metallic drugs altered the T1/2 beta of the 4-quinolone in saliva. In-vitro studies using simulated gastric fluid showed that ferrous sulphate, aluminium hydroxide and calcium carbonate reduced ofloxacin availability to 67.4%, 69.3% and 73.8%, respectively. This effect was ascribed to the formation of complexes between ofloxacin and the metal ions concerned. Substantial correlation between in-vitro and in-vivo availability data was demonstrated in all cases except for ofloxacin combinations with ferrous sulphate and calcium carbonate. In general, there was also good correlation between the saliva and urine data.

The minimum inhibitory concentrations of three bismuth subcarbonate preparations: 1. bismuth subcarbonate, 2. a mixture of 50% bismuth subcarbonate and 50% citric acid, 3. a mixture of 50% bismuth subcarbonate and 50% potassium citrate were assayed against 30 strains of Campylobacter pylori employing the agar dilution method. Bismuth subcarbonate alone exhibited an MIC50 of 2 mg/l and was more effective than the two combinations (MIC50 4 mg/l). It is concluded that the addition of citrate ions does not improve antibacterial activity.

109. Clin Nephrol. 1986 Oct;26(4):169-73. Triamterene-induced crystalluria and cylinduria: clinical and experimental studies. Fairley KF, Woo KT, Birch DF, Leaker BR, Ratnaike S. We examined the occurrence of crystals and casts in the urine of healthy subjects after administration of triamterene and the site of crystal formation in experimental animals. Twenty out of twenty healthy subjects had abundant triamterene crystals and casts in acid urine after receiving a single 100 mg dose. Casts were present in the urine from 2-11 hours after administration of the diuretic. Cast formation occurred in acidic urine and was prevented by alkalinization of the urine with potassium citrate. Animal studies showed that crystallization and cast formation occurred in the medullary and papillary collecting ducts of the rat kidney. These findings provide a possible explanation for the reported nephrotoxicity of triamterene, particularly when given to patients who are receiving non-steroidal anti-inflammatory agents.

110. J Gen Virol. 1975 Aug;28(2):185-91. doi: 10.1099/0022-1317-28-2-185. Inhibition of multiplication of tobacco mosaic virus in protoplasts by antibiotics and its prevention by divalent metals. Kassanis B, White RF, Woods RD. At concentrations that inhibit bacterial growth, some antibiotics including gentamicin completely inhibited virus multiplication in protoplasts, and other antibiotics partially inhibited virus multiplication. The inhibition caused by each antibiotic was largely prevented by adding a divalent metal; MnC1(2) was more effective than CaC1(2) and other salts of divalent metals when added at 10 mM to the incubation medium. When added immediately after infection, 1 mug/ml of gentamicin halved the final virus concentration and 3 mug/ml completely inhibited virus multiplication, although 10 mug/ml was required to stop bacterial growth. Gentamicin inhibited virus multiplication even when added 24 h after virus inoculation. Also, when protoplasts were exposed to gentamicin for only 1 or 2 h, either immediately after inoculation or 2 h later, the virus concentration was considerably decreased. Gentamicin seemed not to affect virus multiplication in whole plants. Sap from Dianthus barbatus also strongly inhibited virus multiplication in protoplasts but, unlike gentamicin, it acted in the presence of MnC1(2). By contrast, chelating agents such as 1 mM-EDTA or 5 mM-potassium citrate was strong inhibitors of virus multiplication that were inactive in the presence of MnC1(2). It is suggested that gentamicin and other antibiotics may chelate metals from the protoplast membranes, thus disorganizing their function and affecting virus multiplication.

The study was performed to compare the efficacy of a herbal plant, Orthosiphon grandiflorus (OG), and the drug sodium potassium citrate (SPC) in treatment of renal calculi. Forty-eight rural stone formers identified by ultrasonography were recruited and randomly assigned to two treatment groups (G1 and G2). For a period up to 18 months, subjects in G1 received 2 cups of OG tea daily, each tea cup made from an OG tea bag (contained 2.5 g dry wt), and G2 received 5-10 g of granular SPC in solution divided into three times a day. Once every 5 to 7 weeks, subjects were interviewed, given an additional drug supply, administered a kidney ultrasound and had spot urine samples collected for relevant biochemical analysis. From the recorded ultrasound images, rates of stone size reduction per year (ROSRPY) were calculated. The mean ROSRPY was 28.6+/-16.0% and 33.8+/-23.6% for G1 and G2, respectively. These two means were not significantly different. ROSRPY values of G1 and G2 were combined and divided into three levels: Level A (ROSRPY > mean + 0.5 SD), Level M (ROSRPY = mean +/- 0.5 SD) and Level B (ROSRPY < mean - 0.5 SD). Dissolution of stones was least in Level B which was related to higher excretions of Ca and uric acid in the urine. After treatment, 90% of the initial clinical symptoms (ie back pain, headaches and joint pain) were relieved. Fatigue and loss of appetite were observed in 26.3% of G2 subjects. Our study indicates that treatment of renal calculi with OG tea is an alternative means of management. Further investigation is needed to improve dissolution of stones with a low ROSRPY.

BACKGROUND: Primary hyperparathyroidism (pHPT) is infrequently associated with calcium-containing kidney stones, despite hypercalciuria. Parathyroidectomy (PTX) is the only curative treatment of the metabolic disorder and is indirectly regarded as prophylaxis of recurrence of stone formation. The aim of the systematic review was to evaluate the impact of PTX on stone recurrence and to identify possible predictors of recurrent stone formation. METHODS: Following PRISMA guidelines, a systematic PubMed search was conducted through April 2025. Eligible studies including adults with successfully surgically treated pHPT, documented nephrolithiasis and a follow-up of at least 12 months were analyzed. RESULTS: A total of 13 studies (2 prospective cohorts, 10 retrospective cohorts, 1 randomized controlled trial, RCT) comprising more than 8000 patients met the inclusion criteria. After PTX, recurrence rates in prospective studies ranged from 0-30% among stone formers, while retrospective series showed a wider range (between 0% and 58%). Registry data indicated that in patients with a history of nephrolithiasis, the recurrence risk seems higher shortly after PTX compared with conservative management of pHPT but decreases substantially with each subsequent year. In patients without a stone history, de novo stone formation was rare; in the RCT, recurrence occurred in 0% after PTX versus 4% under observation. Consistent predictors of recurrence included persistent hypercalciuria, multiple preoperative stone episodes, hypocitraturia, elevated body mass index, and male sex. CONCLUSION: The use of PTX significantly reduces the long-term risk of stone recurrence but does not eliminate it entirely. In patients with a history of nephrolithiasis, short-term risk may be elevated after PTX but declines markedly over time. Individualized follow-up including regular assessment of serum calcium, parathyroid hormone, renal function, and 24‑h urinary parameters, together with preventive measures where indicated, such as adequate fluid intake, dietary counselling, potassium citrate or thiazide therapy, is recommended, particularly in patients with persistent risk factors. Decisions regardin

INTRODUCTION: Kidney stones represent a significant health burden due to their high prevalence, recurrence, and associated healthcare costs. Medical interventions are crucial for preventing and treating kidney stones, especially for patients at high risk or those undergoing extracorporeal shock wave lithotripsy (SWL). This umbrella review aims to synthesize evidence from systematic reviews and meta-analyses of randomized controlled trials (RCTs) evaluating the efficacy of non-surgical medical treatments in preventing and managing kidney stones. EVIDENCE ACQUISITION: A comprehensive search was conducted across Medline, Embase, and Web of Science until February 2024. Systematic reviews with meta-analyses of RCTs focusing on non-surgical medical interventions for kidney stone prevention and treatment were included. The GRADE framework evaluated the certainty of evidence. EVIDENCE SYNTHESIS: Among 2481 records initially considered, nine systematic reviews comprising 88 RCTs and 27,286 participants were included. Supported by a high level of evidence according to the GRADE, tamsulosin, compared to placebo, demonstrated improved stone clearance post-SWL, while vitamin D and calcium supplementation were ineffective for primary prevention. In 571 patients affected by recurrent kidney calculi, the use of thiazides, compared to placebo, was associated with a statistically significant decrease in renal stones of 66% (GRADE: high level of evidence). The use of potassium citrate was able to prevent the risk of nephrolithiasis recurrence of 79%, supported by a high level of evidence. CONCLUSIONS: Several medical interventions for kidney stone management are supported by high-certainty evidence, particularly post-SWL α-blocker therapy and potassium citrate for recurrence prevention.

BACKGROUND: In the eradication of Helicobacter pylori, the efficacy of bismuth remains inconclusive. We aimed to compare the efficacy of bismuth on various H. pylori eradication regimens. METHODS: Randomized controlled trials were collected to compare the efficacy of bismuth to nonbismuth regimens in H. pylori eradication. We pooled information to study eradication, adverse events, and drug compliance. In addition, subgroup analyses for eradication efficacy were performed according to high or low clarithromycin-resistance area, bismuth drug form, and amount of bismuth element. RESULTS: Records for a total of 2506 patients in 15 trials from 13 randomized controlled studies were included. The eradication of H. pylori was superior when bismuth compared to nonbismuth regimen (odds ratio [OR] = 1.63, 95% confidence interval [CI], 1.33-2.00 in intention-to-treat [ITT]; OR = 2.05, 95% CI, 1.58-2.68 in per-protocol [PP] analyses), without significant difference in drug compliance or adverse events. Bismuth regimens in the high clarithromycin resistance area tend to enhance the eradication rate (OR = 1.66, 95% CI, 1.34-2.05 in ITT; OR = 2.22, 95% CI, 1.67-2.95 in PP analyses). Bismuth potassium citrate and bismuth subcitrate were more effective drug forms in regard to eradication rate. Bismuth at a dosage of < 500 mg/day was significantly higher for the eradication rate. CONCLUSIONS: Bismuth to the H. pylori eradication regimens achieve a higher eradication rate, especially in the high clarithromycin resistance area. It could be an eradication option achieving sufficient resistance rates without increasing antibiotic resistance, side effects, or poor compliance. © 2024 The Author(s). Helicobacter published by John Wiley & Sons Ltd.

PURPOSE OF REVIEW: We wanted to analyse the outcomes of surgical (SWL, URS, PCNL) and medical management of cystine stones in the paediatric population in terms of stone-free status and complication rates, based on all the available literature evidence. RECENT FINDINGS: A systematic review of literature was performed for all studies with paediatric cystine stone management. Twelve studies met the eligibility criteria, of which 4 analysed outcomes of SWL, 2 of URS and 3 of PCNL and 3 focused on the effect of either alkalising agents (potassium citrate, citric acid) or cysteine-binding thiol (CBT) agents (tiopronin, penicillamine). The reported SFR in studies ranged from 50 to 83%, 59 to 100% and 63 to 80.6%, with a complication rate of 2.8-51%, 14-27% and 12.9-15.4% with SWL, URS and PCNL, respectively. Paediatric cystine stones treatment should aim at complete stone clearance, preservation of renal function and prevention of further recurrences. SWL achieves inferior results in case of cystine stones. URS and PCNL are safe and effective procedures in the paediatric population, with a low rate of major complications. Adherence to medical prevention therapies may prolong recurrence-free periods. © 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

PURPOSE: Hypocitraturia is a low urinary excretion of citrate and a well-known risk factor for kidney stone development in children. This systematic review aimed to evaluate the dietary management of hypocitraturia in children with urolithiasis. METHODS: Literature search was performed on 30th September 2022 using Embase, PubMed, and Cochrane Central Controlled Register of Trials. Studies were included if children with stones and hypocitraturia were managed with diet supplements. RESULTS: Six papers were included. Four studies evaluated the role of oral potassium citrate associated with high fluid intake on stone resolution and recurrence. Two studies assessed the impact of oral potassium citrate on long-term stone recurrence after percutaneous nephrolithotomy and shock wave lithotripsy. All studies demonstrated that the association of potassium citrate and high fluid intake was well tolerated with no side effects and restored normal urine citrate excretion, allowed a reduction in stone size, and, following definitive treatments, was associated with a lower rate of stone regrowth and recurrence compared with controls. These effects were demonstrated across all pediatric ages. CONCLUSIONS: Our review infers that oral potassium citrate and high fluid assumption are safe and effective in restoring urine citrate excretion, treating and preventing stone recurrence with no serious adverse events, and should probably be the first-line treatment of pediatric patients with asymptomatic stones and hypocitraturia. © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Comment in J Urol. 2021 Feb;205(2):623-626. doi: 10.1097/JU.0000000000001485. Cystinuria (OMIM 220100) is an autosomal recessive hereditary disorder in which high urinary cystine excretion leads to the formation of cystine stones because of the low solubility of cystine at normal urinary pH. We developed clinical practice recommendation for diagnosis, surgical and medical treatment, and follow-up of patients with cystinuria. Elaboration of these clinical practice recommendations spanned from June 2018 to December 2019 with a consensus conference in January 2019. Selected topic areas were chosen by the co-chairs of the conference. Working groups focusing on specific topics were formed. Group members performed systematic literature review using MEDLINE, drafted the statements, and discussed them. They included geneticists, medical biochemists, pediatric and adult nephrologists, pediatric and adult urologists experts in cystinuria, and the Metabolic Nephropathy Joint Working Group of the European Reference Network for Rare Kidney Diseases (ERKNet) and eUROGEN members. Overall 20 statements were produced to provide guidance on diagnosis, genetic analysis, imaging techniques, surgical treatment (indication and modalities), conservative treatment (hydration, dietetic, alkalinization, and cystine-binding drugs), follow-up, self-monitoring, complications (renal failure and hypertension), and impact on quality of life. Because of the rarity of the disease and the poor level of evidence in the literature, these statements could not be graded. This clinical practice recommendation provides guidance on all aspects of the management of both adults and children with cystinuria, including diagnosis, surgery, and medical treatment.

BACKGROUND: Nephrolithiasis, or urinary stone disease, in children causes significant morbidity, and is increasing in prevalence in the North American population. Therefore, medical and dietary interventions (MDI) for recurrent urinary stones in children are poised to gain increasing importance in the clinical armamentarium. OBJECTIVES: To assess the effects of medical and dietary interventions (MDI) for the prevention of idiopathic urinary stones in children aged from one to 18 years. SEARCH METHODS: We searched multiple databases using search terms relevant to this review, including studies identified from the Cochrane Central Register of Controlled Trials (CENTRAL, 2017, Issue 1), MEDLINE OvidSP (1946 to 14 February 2017), Embase OvidSP (1980 to 14 February 2017), International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Additionally, we handsearched renal-related journals and the proceedings of major renal conferences, and reviewed weekly current awareness alerts for selected renal journals. The date of the last search was 14 February 2017. There were no language restrictions. SELECTION CRITERIA: Randomized controlled trials of at least one year of MDI versus control for prevention of recurrent idiopathic (non-syndromic) nephrolithiasis in children. DATA COLLECTION AND ANALYSIS: We used standard methodologic procedures expected by Cochrane. Titles and abstracts were identified by search criteria and then screened for relevance, and then data extraction and risk of bias assessment were carried out. We assessed the quality of evidence using GRADE. MAIN RESULTS: The search identified one study of 125 children (72 boys and 53 girls) with calcium-containing idiopathic nephrolithiasis and normal renal morphology following initial treatment with shockwave lithotripsy (SWL). Patients were randomized to oral potassium citrate 1 mEq/kg per day for 12 months versus no specific medication or preventive measure with results reported for a total of 96 patients (48 per group). This included children who were stone-free (n = 52) or had residual stone fragments (n = 44) following SWL. Primary outcomes:Medical therapy may lower rates of stone recurr