Recent studies have revealed a significant relationship between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS), both of which commonly affect middle-aged and older men. These conditions share underlying causes, particularly endothelial dysfunction, atherosclerosis, and chronic pelvic ischemia (CPI). This study investigated the therapeutic potential of LDD175, a large-conductance Ca 2+ -activated K + channel (BKCa channel) opener, in simultaneously treating both conditions using a CPI animal model of male Sprague Dawley rats. Our study investigated the induction of CPI through surgical endothelial damage combined with a high-cholesterol diet. We assessed erectile and voiding functions by measuring intracavernosal pressure (ICP) and intraurethral pressure (IUP), respectively, after nerve stimulation. We performed histological examinations of vascular changes and western blot analyses of cavernous and prostate tissues to understand the underlying mechanisms. This study evaluated the effectiveness of LDD175 compared to standard treatments, such as sildenafil for ED and tamsulosin for LUTS. Therefore, the CPI model successfully demonstrated ED and LUTS symptoms with decreased ICP and increased IUP. Analysis revealed elevated levels of hypoxia-inducible factor-1α, transforming growth factor-β1 and β2 in cavernous tissue, and increased α1A-adrenoceptor expression in prostate tissue. LDD175 administration showed promising results, with dose-dependent improvements in ICP and IUP, and therapeutic effects comparable to those of established treatments. Our findings suggest a novel therapeutic approach that can simultaneously address ED and LUTS, opening new possibilities for clinical application in the treatment of these interconnected conditions.
Male ; Animals ; Erectile Dysfunction/etiology* ; Rats, Sprague-Dawley ; Lower Urinary Tract Symptoms/etiology* ; Ischemia/drug therapy* ; Rats ; Tamsulosin ; Hypoxia-Inducible Factor 1, alpha Subunit/drug effects* ; Sildenafil Citrate/therapeutic use* ; Penis/blood supply* ; Disease Models, Animal ; Transforming Growth Factor beta1/metabolism* ; Pelvis/blood supply* ; Prostate/metabolism* ; Sulfonamides/therapeutic use* ; Large-Conductance Calcium-Activated Potassium Channels/agonists*

BACKGROUND: Given the general unavailability, common adverse effects, and complicated administration of tetracycline, the clinical application of classic bismuth quadruple therapy (BQT) is greatly limited. Whether minocycline can replace tetracycline for Helicobacter pylori ( H . pylori ) eradication is unknown. We aimed to compare the eradication rate, safety, and compliance between minocycline- and tetracycline-containing BQT as first-line regimens. METHODS: This randomized controlled trial was conducted on 434 naïve patients with H . pylori infection. The participants were randomly assigned to 14-day minocycline-containing BQT group (bismuth potassium citrate 110 mg q.i.d., esomeprazole 20 mg b.i.d., metronidazole 400 mg q.i.d., and minocycline 100 mg b.i.d.) and tetracycline-containing BQT group (bismuth potassium citrate/esomeprazole/metronidazole with doses same as above and tetracycline 500 mg q.i.d.). Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed at 4-8 weeks after eradication to evaluate outcome. We used a noninferiority test to compare the eradication rates of the two groups. The intergroup differences were evaluated using Pearson chi-squared or Fisher's exact test for categorical variables and Student's t -test for continuous variables. RESULTS: As for the eradication rates of minocycline- and tetracycline-containing BQT, the results of both intention-to-treat (ITT) and per-protocol (PP) analyses showed that the difference rate of lower limit of 95% confidence interval (CI) was >-10.0% (ITT analysis: 181/217 [83.4%] vs . 180/217 [82.9%], with a rate difference of 0.5% [-6.9% to 7.9%]; PP analysis: 177/193 [91.7%] vs . 176/191 [92.1%], with a rate difference of -0.4% [-5.6% to 6.4%]). Except for dizziness more common (35/215 [16.3%] vs . 13/214 [6.1%], P = 0.001) in minocycline-containing therapy groups, the incidences of adverse events (75/215 [34.9%] vs . 88/214 [41.1%]) and compliance (195/215 [90.7%] vs . 192/214 [89.7%]) were similar between the two groups. CONCLUSION: The eradication efficacy of minocycline-containing BQT was noninferior to tetracycline-containing BQT as first-line regimen for H . pylori eradication with similar safety and compliance. TRIAL REGISTRATION ClinicalTrials.gov, ChiCTR 1900023646.
Humans ; Bismuth/therapeutic use* ; Metronidazole/therapeutic use* ; Esomeprazole/pharmacology* ; Minocycline/pharmacology* ; Helicobacter pylori ; Potassium Citrate/therapeutic use* ; Anti-Bacterial Agents ; Tetracycline/adverse effects* ; Helicobacter Infections/drug therapy* ; Drug Therapy, Combination ; Amoxicillin

Introduction: Urinary citrate is a potent inhibitor of urinary crystallization that is freely filtered in the proximal tubule of the kidney. We aimed to investigate the effect of citrate supplementation with fresh lime juice on the urinary pH and calcium excretion level among healthy individuals compared with that of mist potassium citrate. Methods: In this prospective, cross-over single-centre study, 50 healthy medical student volunteers were randomly allocated to two treatment arms. One arm was prescribed with potassium citrate, while the other arm received citrate supplementation with a home preparation of fresh lime juice. The urinary pH and calcium-to-creatinine ratio (uCa/uCr) were measured at baseline and after 7 days of treatment. This was followed by a washout period of 2 weeks, after which each participant crossed over to the other treatment arm, and the urinary measurements were repeated. Results: Potassium citrate significantly increased the urinary pH among all participants, while fresh lime juice did not. Both fresh lime juice and potassium citrate reduced the uCa/uCr, although this effect was not significant. Conclusion Fresh lime juice is not as effective as potassium citrate in improving the urinary pH and calcium excretion level of healthy individuals. Therefore, it should be used as an adjunct rather than an alternative to potassium citrate.
Potassium Citrate ; Urolithiasis

Urolithiasis is an uncommon complication in renal transplantation. We report a case of hypocitraturia-related ureteral steinstrasse which was spontaneously formed in a renal transplant recipient. The patient who underwent renal transplantation was admitted with acute pyelonephritis. Hydronephrosis in the transplanted kidney and multiple stones (steinstrasse) in the distal ureter were incidentally found on computed tomography scanning. After a failed attempt of ureteroscopic removal of stones, the patient underwent open ureterolithotomy and ureteroureterostomy. On stone analysis, carbonate apatite was confirmed. Urinary citric acid levels were decreased to 127.6 mg/day. Potassium citrate was administered to prevent stone recurrence by increasing urinary citrate excretion. No recurrence of stones was shown six months later. Urolithiasis in renal transplant recipients requires a high index of suspicion. Hypocitraturia can increase the risk for urolithiasis. Rapid recognition by careful surveillance, prompt removal of stones, and precautionary efforts to prevent recurrence are needed.
Carbon ; Citric Acid ; Humans ; Hydronephrosis ; Kidney ; Kidney Transplantation ; Potassium Citrate ; Pyelonephritis ; Recurrence ; Transplantation* ; Ureter* ; Urolithiasis

The prevalence of kidney stone disease is increasing, and newer research is finding that stones are associated with several serious morbidities. These facts suggest that emphasis needs to be placed not only on stone treatment but also stone prevention. However, there is a relative dearth of information on dietary and medical therapies to treat and avoid nephrolithiasis. In addition, studies have shown that there are many misconceptions among both the general community and physicians about how stones should be managed. This article is meant to serve as a review of the current literature on dietary and drug therapies for stone prevention.
Allopurinol/therapeutic use ; Calcium Oxalate/analysis ; Cystine/analysis ; *Diet ; Humans ; Kidney Calculi/chemistry/*prevention & control ; Potassium Citrate/therapeutic use ; Sodium Chloride Symporter Inhibitors/therapeutic use ; Uric Acid/analysis ; Urological Agents/*therapeutic use

PURPOSE: To study the effects of long-term treatment with potassium magnesium citrate and vitamin B-6 prophylaxis (Urikind-KM6; 1,100-mg potassium citrate, 375-mg magnesium citrate, and 20-mg pyridoxine hydrochloride/5 mL) every 8 hours over 3 years. MATERIALS AND METHODS: A total of 247 patients with recurrent idiopathic hypocitraturia with or without hyperuricosuria and randomized controls were studied prospectively for 3 years. The total patients were divided into three groups. Control group 1 consisted of 61 patients (24.7%) who had moderate to severe hypocitraturia with or without hyperuricosuria and were recurrent stone formers but discontinued prophylaxis because of drug intolerance within 1 month of therapy. Control group 2 constituted 53 patients (21.5%) who were first-time stone formers and who had mild hypocitraturia with or without hyperuricosuria and were not put on prophylactic therapy and were followed for 3.16+/-0.08 years. Control group 3 constituted 133 patients (54.8%) who were recurrent stone formers who had moderate to severe hypocitraturia with or without hyperuricosuria and were put on prophylaxis therapy and were followed for 3.16+/-0.08 years. All patients were followed up at 6-month intervals. RESULTS: Potassium magnesium citrate prophylaxis produced a sustained increase in 24-hour urinary citrate excretion from initially low values (221.79+/-13.39 mg/dL) to within normal to high limits (604.04+/-5.00 mg/dL) at the 6-month follow-up. Urinary pH rose significantly from 5.62+/-0.2 to 6.87+/-0.01 and was maintained at 6.87+/-0.01. The stone recurrence rate declined from 3.23+/-1.04 per patient per year to 0.35+/-0.47 per patient per year. CONCLUSIONS: Potassium magnesium citrate prophylaxis was effective in reducing the recurrence of calcium oxalate and phosphate urolithiasis.
Calcium Oxalate* ; Citric Acid* ; Follow-Up Studies ; Humans ; Hydrogen-Ion Concentration ; Magnesium* ; Potassium Citrate ; Potassium* ; Prospective Studies ; Pyridoxine ; Recurrence ; Urolithiasis* ; Vitamins*

OBJECTIVETo analyze the treatment of acute renal failure caused by irrational drug use.

METHODData of 41 cases of acute renal failure seen from July 2008 to June 2012 in our hospital were reviewed. Bilateral renal parenchymas diffuse echo was found enhanced by ultrasound in all cases. Calculus image was not found by X-ray. All children had medical history of using cephalosporins or others. Alkalinization of urine and antispasmodic treatment were given to all children immediately, 17 children were treated with hemodialysis and 4 children accepted intraureteral cannula placement.

RESULTIn 24 children who accepted alkalinization of urine and antispasmodic treatment micturition could be restored within 24 hours, in 11 children micturition recovered after only one hemodialysis treatment and 2 children gradually restored micturition after hemodialysis twice, 4 children who accepted intraureteral cannula immediately restored micturition. In all children micturition recovered gradually after a week of treatment. Ultrasound examination showed that 39 children's calculus disappeared totally and renal parenchymas echo recovered to normal. The residual calculi with diameter less than 5 mm were found in 2 children, but they had no symptoms. The children received potassium sodium hydrogen citrate granules per os and were discharged from hospital. Ultrasound showed calculus disappeared totally one month later.

CONCLUSIONIrrational drug use can cause children urolithiasis combined with acute renal failure, while renal dysfunction can reverse by drug withdrawal and early alkalinization of urine, antispasmodic treatment, intraureteral cannula or hemodialysis when necessary, most calculus can be expelled after micturition recovered to normal.

Acute Kidney Injury ; chemically induced ; diagnosis ; therapy ; Ceftriaxone ; administration & dosage ; adverse effects ; Child ; Child, Preschool ; Diuretics ; therapeutic use ; Female ; Fluid Therapy ; Humans ; Infant ; Kidney ; pathology ; physiopathology ; Male ; Potassium Citrate ; therapeutic use ; Renal Dialysis ; Retrospective Studies ; Treatment Outcome ; Urinary Calculi ; chemically induced ; diagnosis ; therapy

OBJECTIVE: To determine the efficacy and safety of sodium bicarbonate, citric acid, sodium citrate, and tartaric acid (compound drug) in comparison to potassium citrate in the treatment of kidney stones.

METHODS: Prospective randomized controlled trial of patients with kidney stones recruited from February to October 2011 at Out-patient Department was conducted. Ninety subjects, consented and eligible, were enrolled in this study. Random allocation of subjects into two groups was done using computer generated randomization. Subjects assigned to group I were treated with the compound drug(12 grams/day); while group II subjects were given potassium citrate(60mEq/day) for 6 weeks. Urinary pH levels were examined weekly and the effect of medical treatment on stone size changes was evaluated by ultrasonography every two weeks in the six-week treatment period. Intention to treat analysis was done with 95% confidence level(CI). Statistical analysis of results was determined using analysis of variance (ANOVA) with multiple repeated measures for between group urinary pH changes and chi square for between groups difference in stone size changes.

RESULTS: A total of 74 subjects completed the study with a dropout rate of 18%, which was mainly due to geographic and financial reasons. Demographic and baseline stone characteristics of both groups were not significantly different. Treatment outcome between the two groups based on stone size changes (in general and both radiolucent and radioopaque stones subgroups) did not show any significant statistic difference. The pH level changes over six-week treatment period between the two groups showed a total mean pH difference of 0.445, (95% CI: 0.213, 0.677), which was statistically significant (P<0.001) in favor of Group I. Both treatment regimens were well-tolerated with very few non-serious medication adverse effects.

CONCLUSION:  Urinary alkalinization with sodium bicarbonate, citric acid, sodium citrate, and tartaric acid is a well-tolerated and highly effective treatment resulting in dissolution of non-obstructing kidney stones and is comparable to the gold standard potassium citrate.

Human ; Male ; Female ; Aged ; Middle Aged ; Adult ; Young Adult ; Adolescent ; KIDNEY CALCULI ; NEPHROLITHIASIS ; UROLOGIC DISEASES ; KIDNEY DISEASES ; SODIUM BICARBONATE ; CITRIC ACID ; SODIUM CITRATE ; TARTARIC ACID ; POTASSIUM CITRATE ; INORGANIC CHEMICALS ; ORGANIC CHEMICALS ; TREATMENT OUTCOME ; SAFETY

We report the case of a female patient with incomplete distal renal tubular acidosis with nephrocalcinosis. She was admitted to the hospital because of acute pyelonephritis. Imaging studies showed dual medullary nephrocalcinosis. Subsequent evaluations revealed hypokalemia, hypocalcemia, hypercalciuria, and hypocitraturia with normal acid-base status. A modified tubular acidification test with NH4Cl confirmed a defect of urine acidification, which is compatible with incomplete distal tubular acidosis. We treated our patient with potassium citrate, which corrects hypokalemia and prevents further deposition of calcium salts.
Acidosis ; Acidosis, Renal Tubular ; Calcium ; Female ; Humans ; Hypercalciuria ; Hypocalcemia ; Hypokalemia ; Kidney ; Nephrocalcinosis ; Potassium Citrate ; Pyelonephritis ; Salts

A 52-year old woman, who had hypothyroidism associated with autoimmune thyroiditis for 5 years, was hospitalized for tingling sensation and muscle weakness of both lower extremities. Her initial laboratory findings showed severe hypokalemia, metabolic acidosis, and high titer of thyroid autoimmune antibodies. She was diagnosed of distal renal tubular acidosis by bicarbonate loading test (FEHCO(3)(-) <3.0 %) and renal calcifications on pre-enhanced CT scan. Since she had other symptoms of xerostomia and xerophthalmia, primary Sjogren's syndrome was diagnosed by Schirmer test, salivary scan, and serologic findings. She was treated with potassium citrate, potassium chloride, and hydroxychlorquine. Four months later, she has remained well with those treatments. There were only a few case reports about distal renal tubular acidosis associated with Sjogren's syndrome and autoimmune thyroiditis. In Korea, there has not been any report of such cases. Therefore, we report a case of distal renal tubular acidosis and Sjogren's syndrome in a patient with autoimmune thyroiditis.
Acidosis ; Acidosis, Renal Tubular ; Antibodies ; Female ; Humans ; Hypokalemia ; Hypothyroidism ; Korea ; Lower Extremity ; Muscle Weakness ; Potassium Chloride ; Potassium Citrate ; Sensation ; Sjogren's Syndrome ; Thyroid Gland ; Thyroiditis, Autoimmune ; Xerophthalmia ; Xerostomia