Increased Urine pH Research Articles

Метаболические факторы риска и формирование мочевых камней. Исследование VIII: Литогенные свойства кислотности мочи у мужчин и женщин.

Introduction. Urine acidity is an important factor that can actively modulate the process of stone formation in the kidneys, which allows using this indicator to use this indicator to assess the risk urinary stone formation and control the result of anti-relapse treatment in patients with urolithiasis (UL). There are gender differences in the prevalence of UL, which may be related to differences in urine acidity. In this study, the effect of varying degrees of pH urine on metabolic parameters and the frequency of detection of urinary stones of various chemical compositions was studied in men and women with UL. Materials and methods. We examined 982 patients with ICD (439 men and 543 women aged 18 to 79 years). To assess the lithogenic activity of uricosuria in men and women with UL, the pH values of morning urine were distributed in ascending order and divided into several groups. In each of the ranges, the percentage distribution of types of urinary stones and biochemical parameters of urine and blood were determined. Results. At urine pH of 5.1-6.5, men have higher calciuria and are more prone to oxalate stone formation, which is 1.5-2.2 times more active in them than in women (p <0.05). In contrast to men, the urinary pH level of women had a greater effect on the frequency of detection of oxalate stones, which decreased by 75.9% with a urine pH of 5.5-5.9 and higher, and was accompanied by a 33.3% decrease in calciuria (p <0.05). Uric acid lithogenesis was more dependent on changes in the pH of urine than on the activity of urocosuria. The frequency of formation of uric acid stones was inversely correlated with the pH of urine in men (r=-0.833, p=0.0102) and women (r=-0.929, p=0.0009). With a decrease in the pH of urine below 6.0, the incidence of uric acid stones in women increased by 5.76 times (p<0.0001), and in men by 1.91 times (p=0.0087). Active phosphate lithogenesis in women did not depend on the level of phosphate excretion, which was 25.5-39.7% lower than in men and progressively decreased with increasing urine pH values (p<0.00029). When the urine pH is higher than 5.9, women have a significantly increased risk of developing calculi from carbonatapatite compared to men (p=0.0005). Struvite lithogenesis increased with urine alkalinization and was more pronounced in women than in men (p=0.043). Comparison of age groups did not reveal any differences in the acidity of morning urine between men and women, however, in contrast to men, a noticeable predominance of the proportion of women with carbonatapatite stones was observed in the groups of patients older than 49 years. Conclusion. Shifts in the pH of urine can change the nature and direction of lithogenesis in men and women in different ways and are not always associated with the excretion of certain metabolic factors involved in stone formation. Gender features of the lithogenesis of various types of stones in conditions of different acidity of urine should be taken into account when conducting personalized metaphylaxis of urolithiasis.

Risk Profile of Patients with Brushite Stone Disease and the Impact of Diet.

This study examined the profile of patients and the impact of diet on the risk of brushite stone formation under controlled, standardized conditions. Sixty-five patients with brushite nephrolithiasis were enrolled in the study. Metabolic, dietary, and 24 h urinary parameters were collected under the habitual, self-selected diet of the patients and the balanced mixed, standardized diet. The [13C2]oxalate absorption, ammonium chloride, and calcium loading tests were conducted. All patients had at least one abnormality on the usual diet, with hypercalciuria (84.6%), increased urine pH (61.5%), and hyperphosphaturia (43.1%) being the most common. Absorptive hypercalciuria was present in 32.1% and hyperabsorption of oxalate in 41.2%, while distal renal tubular acidosis (dRTA) was noted in 50% of brushite stone formers. The relative supersaturation of brushite did not differ between patients with and without dRTA. Among all recent brushite-containing calculi, 61.5% were mixed with calcium oxalate and/or carbonate apatite. The relative supersaturation of brushite, apatite, and calcium oxalate decreased significantly under the balanced diet, mainly due to the significant decline in urinary calcium, phosphate, and oxalate excretion. Dietary intervention was shown to be effective and should be an integral part of the treatment of brushite stone disease. Further research on the role of dRTA in brushite stone formation is needed.

Relative supersaturation values distinguish between feline urinary and non-urinary foods and align with expected urine analytes contributions to uroliths.

Uroliths are concretions formed in the urinary tract. These can be problematic in humans and companion animals such as cats. Magnesium ammonium phosphate (struvite) and calcium oxalate (CaOx) are the most common forms of uroliths. The relative supersaturation (RSS) is a relative risk index of crystal formation. Here, an updated program for calculating RSS, EQUIL-HL21, was used to detect differences in RSS values when cats were fed foods formulated for urinary and non-urinary conditions. In addition, the contributions of urinary analytes to RSS values were examined via regression analyses. Historical data from feeding trials including foods indicated for use in urinary or non-urinary conditions were analyzed for nutrient composition and urinary parameters. RSS was calculated by EQUIL-HL21. The relationship between RSS values calculated by EQUIL-HL21 and urinary analytes was examined by regression models, which were selected by R2 and stepwise methods. Cats that consumed urinary foods had significantly greater levels of urinary sodium and chloride compared with those that consumed non-urinary foods, consistent with the greater amounts of sodium and chloride in the urinary foods. Those that consumed non-urinary foods had higher urine pH, ammonium, potassium, phosphorus, magnesium, oxalate, citrate, and sulfate. Struvite RSS value and number of urinary crystals were significantly lower in cats fed the urinary foods. Mean CaOx RSS values were similar in both foods, though the number of CaOx crystals were significantly higher in cats that consumed non-urinary foods. A model predicting the natural log of struvite RSS values indicated that these values would increase with increasing urine pH, ammonium, chloride, calcium, phosphorus, and magnesium, and would decrease with increasing urine citrate and sulfate. CaOx RSS was predicted to increase as urinary chloride, calcium, and oxalates increased, and would decrease as urine pH, sodium, phosphorus, citrate, and sulfate increased. These analyses demonstrate that the EQUIL-HL21 program can accurately detect expected differences between foods formulated for urinary and non-urinary indications. Regression models showed the eight urinary analytes that, respectively, contribute to the predicted RSS values for struvite and CaOx.

Effect of a high-citrate beverage on urine chemistry in patients with calcium kidney stones.

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 500ml of water, contains 24.5meq 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.

Loss of the Secretin Receptor Impairs Renal Bicarbonate Excretion and Aggravates Metabolic Alkalosis in Mice during Acute Base-Loading.

During acute base excess, the renal collecting duct β -intercalated cells ( β -ICs) become activated to increase urine base excretion. This process is dependent on pendrin and cystic fibrosis transmembrane regulator (CFTR) expressed in the apical membrane of β -ICs. The signal that leads to activation of this process was unknown. Plasma secretin levels increase during acute alkalosis, and the secretin receptor (SCTR) is functionally expressed in β -ICs. We find that mice with global knockout for the SCTR lose their ability to acutely increase renal base excretion. This forces the mice to lower their ventilation to cope with this challenge. Our findings suggest that secretin is a systemic bicarbonate-regulating hormone, likely being released from the small intestine during alkalosis. The secretin receptor (SCTR) is functionally expressed in the basolateral membrane of the β -intercalated cells of the kidney cortical collecting duct and stimulates urine alkalization by activating the β -intercalated cells. Interestingly, the plasma secretin level increases during acute metabolic alkalosis, but its role in systemic acid-base homeostasis was unclear. We hypothesized that the SCTR system is essential for renal base excretion during acute metabolic alkalosis. We conducted bladder catheterization experiments, metabolic cage studies, blood gas analysis, barometric respirometry, perfusion of isolated cortical collecting ducts, immunoblotting, and immunohistochemistry in SCTR wild-type and knockout (KO) mice. We also perfused isolated rat small intestines to study secretin release. In wild-type mice, secretin acutely increased urine pH and pendrin function in isolated perfused cortical collecting ducts. These effects were absent in KO mice, which also did not sufficiently increase renal base excretion during acute base loading. In line with these findings, KO mice developed prolonged metabolic alkalosis when exposed to acute oral or intraperitoneal base loading. Furthermore, KO mice exhibited transient but marked hypoventilation after acute base loading. In rats, increased blood alkalinity of the perfused upper small intestine increased venous secretin release. Our results suggest that loss of SCTR impairs the appropriate increase of renal base excretion during acute base loading and that SCTR is necessary for acute correction of metabolic alkalosis. In addition, our findings suggest that blood alkalinity increases secretin release from the small intestine and that secretin action is critical for bicarbonate homeostasis.

Urine pH and Citrate as Predictors of Calcium Phosphate Stone Formation.

Urinary parameters including urine pH and citrate are recognized as critical in the pathophysiology of calcium-based stones. The factors contributing to variation in these parameters between calcium oxalate and calcium phosphate stone formers are however not well understood. In this study using readily available laboratory data, we explore these differences to delineate the odds of forming calcium phosphate (CaP) versus calcium oxalate (CaOx) stones. In this single-center retrospective study, we compared serum and urinary parameters between adult CaP stone formers (SF), CaOx SF, and non-stone formers (NSF). Urine pH was higher and urine citrate lower in CaP SF compared to same-sex CaOx SF and NSF. In CaP SF, higher urine pH and lower citrate were independent of markers of dietary acid intake and gastrointestinal alkali absorption, suggesting abnormal renal citrate handling and urinary alkali excretion. In a multivariable model, urine pH and urine citrate were most discriminatory between CaP SF and CaOx SF (Receiver Operating Characteristic Area Under the Curve of 0.73 and 0.65 respectively). An increase in urine pH by 0.35, a decrease in urine citrate by 220 mg/day, a doubling of urine calcium, and female sex all independently doubled the risk of CaP compared to CaOx. High urine pH and hypocitraturia are two clinical parameters that distinguish the urine phenotype of CaP SF from CaOx SF. The alkalinuria is due to intrinsic differences in the kidney independent of intestinal alkali absorption and is accentuated in the female sex.

Effects of alkalization therapy on hepatocellular carcinoma: a retrospective study.

In hepatocellular carcinoma (HCC) patients, is difficult to prevent recurrence even when remission is achieved. In addition, even with the advent of drugs that are effective for the treatment of HCC, a satisfactory extension of patient survival has not been achieved. To overcome this situation, we hypothesized that the combination of alkalization therapy with standard treatments will improve the prognosis of HCC. We here report the clinical results of HCC patients treated with alkalization therapy at our clinic. Patients with HCC treated at Karasuma Wada Clinic (in Kyoto, Japan), from January 1, 2013, to December 31, 2020 were analyzed. Overall survival (OS) from both the time of diagnosis and the start of alkalization therapy for each patient was compared. The mean urine pH was also calculated as a surrogate marker of tumor microenvironment pH, and OS from the start of alkalization therapy was compared between patients with a mean urine pH of ≥ 7.0 and those with a mean urine pH of < 7.0. Twenty-three men and six women were included in the analysis, with a mean age at diagnosis of 64.1 years (range: 37-87 years). Seven of the 29 patients had extrahepatic metastases. Patients were divided into two groups according to their mean urine pH after the initiation of alkalization therapy: 12 of the 29 patients had a mean urine pH of ≥ 7.0, and 17 had a mean urine pH of < 7.0. The median OS from diagnosis was 95.6 months (95% confidence interval [CI] = 24.7-not reached), and from the start of alkalization therapy was 42.3 months (95% CI = 8.93-not reached). The median OS from the start of alkalization therapy in patients with a urine pH of ≥ 7.0 was not reached (n = 12, 95% CI = 3.0-not reached), which was significantly longer than that in patients with a pH of < 7.0 (15.4 months, n = 17, 95% CI = 5.8-not reached, p < 0.05). The addition of alkalization therapy to standard therapies may be associated with more favorable outcomes in HCC patients with increased urine pH after alkalization therapy.

Clinical review of alkalization therapy in cancer treatment.

One of the most unique characteristics of cancer metabolism is activated aerobic glycolysis, which is called the “Warburg effect”, and is a hallmark of cancer. An acidic tumor microenvironment (TME) resulting from activated anaerobic glycolysis is associated with cancer progression, multi-drug resistance, and immune escape. Several in vitro and in vivo studies reported that neutralization of the acidic TME by alkalizing agents, such as bicarbonate, resulted in the suppression of cancer progression and a potential benefit for anti-cancer drug responses. In clinical settings, alkalizing effects were achieved not only by alkalizing agents, but also by a following a particular diet. An epidemiological study demonstrated that more fruits and vegetables and less meat and dairy products are associated with an increase in urine pH, which may reflect the alkalizing effect on the body. However, it remains unclear whether alkaline dietary intervention improves the effects of cancer treatment. Moreover, there are few clinical reports to date regarding cancer treatments being performed on patients together with alkalization therapy. In this review, we investigated whether alkalization therapy, which includes an alkaline diet and/or alkalizing agents, improves cancer treatment.

What treatments reduce kidney stone risk in patients with bowel disease?

We examined how physicians made therapeutic choices to decrease stone risk in patients with bowel disease without colon resection, many of whom have enteric hyperoxaluria (EH), at a single clinic. We analyzed clinic records and 24-h urine collections before and after the first clinic visit, among 100 stone formers with bowel disease. We used multivariate linear regression and t tests to compare effects of fluid intake, alkali supplementation, and oxalate-focused interventions on urine characteristics. Patients advised to increase fluid intake had lower initial urine volumes (L/day; 1.3 ± 0.5 vs. 1.7 ± 0.7) and increased volume more than those not so advised (0.7 ± 0.6 vs. 0.3 ± 0.6 p = 0.03; intervention vs. non-intervention). Calcium oxalate supersaturation (CaOx SS) fell (95% CI -4.3 to -0.8). Alkali supplementation increased urine pH (0.34 ± 0.53 vs. 0.22 ± 0.55, p = 0.26) and urine citrate (mg/d; 83 ± 256 vs. 98 ± 166, p = 0.74). Patients advised to reduce oxalate (mg/day) absorption had higher urine oxalate at baseline (88 ± 44 vs. 50 ± 26) which was unchanged on follow-up (88 (baseline) vs. 91 (follow-up), p = 0.90). Neither alkali (95% CI -1.4 to 2.1) nor oxalate-focused advice (95% CI -1.2 to 2.3) lowered CaOx SS. Physicians chose treatments based on baseline urine characteristics. Advice to increase fluid intake increased urine volume and decreased CaOx SS. Alkali and oxalate interventions were ineffective.

Over-the-Counter Alkali Agents to Raise Urine pH and Citrate Excretion: A Prospective Crossover Study in Healthy Adults

ObjectiveTo assess the effect of 2 over-the-counter alkalizing agents on 24 hour urinary parameters. Materials and MethodsTen healthy volunteers without a history of kidney stones were recruited to complete a baseline 24 hour urinalysis with a 4 day diet inventory. Participants then maintained the same diet on either LithoLyte (20 mEq 2 times per day) or KSPtabs (1 tablet 2 times per day) and submitted another 24 hour urinalysis. The process was repeated with the other supplement. Urinary alkali parameters were compared to baseline, and side effects were elicited with a questionnaire. ResultsLithoLyte intake resulted in a non-significant increase in citrate (597-758 mg/day, P =.058, an increase in urine pH (6.46-6.66, P =.028), and a decrease in urine ammonium (41-36 mmol/day, P =.005) compared to baseline. KSPtabs resulted in an increase in citrate (597-797 mg/day, P =.037) and urine pH (6.46-6.86, P =.037), with a non-significant decrease in ammonium (41-34 mmol/day, P =.059). No significant differences were seen comparing urinary analytes between LithoLyte and KSPtabs. With Litholyte, no side effects, mild, moderate, and severe side effects were seen in 50%, 40%, 10%, and 0%, respectively. With KSPtabs, rates were 60%, 20%, 10%, and 10%, respectively. ConclusionIn healthy participants without a history of kidney stones, LithoLyte and KSPtabs are effective over-the-counter alkali supplements, with a similar side effect profile to prescription potassium citrate.

MO557: Lanthanum Dioxycarbonate is Safe in Rats

Abstract BACKGROUND AND AIMS Over 7 million patients suffer from end-stage kidney disease (ESKD) worldwide.[1] Due to low kidney function, patients often become hyperphosphatemic, which leads to negative outcomes[2] including increased risk of death.[3] Patients usually rely on dietary restriction and phosphate(P) binders to address hyperphosphatemia. However, current P binders often do not achieve desired P levels[4] and have a high pill burden due to high quantity of large pills.[5,6] Having a therapeutic option using the same quantity of elemental lanthanum as existing therapies (and therefore similar efficacy) but with a potentially smaller and easy-to-administer pills would enhance patient quality of life (QoL). Lanthanum dioxycarbonate, RENAZORB(LDC), is a novel nanotechnology product that combines lanthanum, which has the highest binding capacity versus other P binders,[7] with a potentially smaller pill size that is swallowed rather than chewed to treat hyperphosphatemia in ESRD patients. However, its safety results have not yet been published. We present the results from a toxicity study evaluating safety of lanthanum dioxycarbonate in rats. METHOD A repeat-dose toxicology study was conducted to evaluate the potential toxicological profile of LDC. Rats were administered oral doses of LDC at 200, 600 or 2000 mg/kg/day by gavage for approximately 6 weeks. Blood samples for TK analysis were obtained from cohorts of 3 rats/sex/group/time pre-dose and at 1, 2, 4, 8, 12, 24 and 48 h after Day 1 and 38 dosing. RESULTS LDC was well tolerated at all test doses. The only test article-related effects noted at the high dose of 2000 mg/kg in both sexes were decreased mean cell hemoglobin (MCH) and mean cell hemoglobin concentration (MCHC), and increased urine pH, and at 600 mg/kg increased urine pH in female rats. The increased urinary pH was considered not of toxicologic relevance, and the decreases in MCH and MCHC were considered to be small enough to not adversely affect the animals’ health. The no-observed-adverse-effect level was 2000 mg/kg. CONCLUSION All doses of lanthanum dioxycarbonate were well tolerated and found safe in rats. These results suggest lanthanum dioxycarbonate may be a suitable candidate for further development. Potential benefits of LDC may include reduced pill burden and ease of dose administration (smaller easy-to-swallow versus chewable), which collectively has potential to enhance patient adherence, improve treatment outcomes and enhance QoL.

MP26-04 24-HOUR URINE COLLECTIONS PERFORMED IN THE IMMEDIATE POST-OPERATIVE PERIOD ARE ACCURATE FOR METABOLIC STONE EVALUATION

You have accessJournal of UrologyCME1 May 2022MP26-04 24-HOUR URINE COLLECTIONS PERFORMED IN THE IMMEDIATE POST-OPERATIVE PERIOD ARE ACCURATE FOR METABOLIC STONE EVALUATION Emily Serrell, Margaret Knoedler, Shuang Li, Sean Hedican, Sara Best, Kristina Penniston, and Stephen Nakada Emily SerrellEmily Serrell More articles by this author , Margaret KnoedlerMargaret Knoedler More articles by this author , Shuang LiShuang Li More articles by this author , Sean HedicanSean Hedican More articles by this author , Sara BestSara Best More articles by this author , Kristina PennistonKristina Penniston More articles by this author , and Stephen NakadaStephen Nakada More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002569.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Many experts advocate collecting an initial 24-hour (24h) urine study at least one month after stone surgery. We believe performing 24h urines earlier improves compliance without compromising results. We hypothesize that in the absence of medical or metabolic intervention, 24h urine studies collected within a month of stone treatment will not differ significantly from those collected later. METHODS: An IRB approved retrospective database of adult patients who underwent surgical treatment for urolithiasis (1/1/2009-8/31/2021) was analyzed. Information was collected for those with a first 24h urine study within a month of surgery and a second within 24 months of the first. Patients were divided into four groups based on treatment between collections: no new treatment; seen in metabolic stone clinic without new medication; seen in metabolic stone clinic with new medication; not seen in metabolic stone clinic but with new medication prescribed by a urologist. Direct differences between two urine studies were compared by multivariate analysis. 24h urine analytes included: calcium, oxalate, uric acid, citrate, pH, volume, sodium, phosphate, magnesium, potassium, creatinine, and sulfate. RESULTS: Of 172 patients with 24h urine studies within a month of surgery, a second study was collected an average of 8.4±4 months later. In 26 patients with no new treatment between first and second study, there were no significant differences in urine analytes (Figure 1A). The 46 patients seen at metabolic stone clinic with new medication had increased urine pH (6±0.7 vs 6.2 ±0.7, p=0.01) and potassium (54±24.4 vs 62.5±28.4, p=0.02). The 89 patients seen at metabolic stone clinic with no new medication had increased volume (2.1±0.8 vs 2.4±0.9, 0.004). The 12 patients with new medication prescribed by urologist had increased potassium (48.9±17.4 vs 65.7±16.8, 0.016) and volume (1.9±0.6 vs 2.5± 0.9, p=0.014; Figure 1B). CONCLUSIONS: Twenty-four hour urine studies performed within a month of stone surgery did not differ significantly from studies collected later. Our report suggests that collections performed in the immediate post-operative period are valid, which should improve compliance in metabolic evaluation. Source of Funding: na © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e439 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Emily Serrell More articles by this author Margaret Knoedler More articles by this author Shuang Li More articles by this author Sean Hedican More articles by this author Sara Best More articles by this author Kristina Penniston More articles by this author Stephen Nakada More articles by this author Expand All Advertisement PDF DownloadLoading ...

Randomized Clinical Study, Comparative of Parallel Groups, to Evaluate the Effectiveness of Three Preparations of Potassium Citrate in Producing an Increase in Urinary pH in Patients with a History of Kidney Stones

Background: A very strict control of urinary pH is recommended to maintain it between 5.5 and 6.2, preventing formation or recurrence of crystals. Kidney stones are a common problem, with a high rate of recurrence, not altered by the success of surgery. Medical treatment prevents recurrence. Potassium Citrate inhibits crystallization of calcium salts. It influences calculogenesis by increasing urinary citrates and alkalinizing the urine. Purpose: to evaluate the similarity in the effect of three K citrate products, K citrate reference product Urocit® 10 mEq, and K citrate from Laboratorios LETI S.A.V., 10 mEq and 15 mEq, on urinary pH. Materials and Methods: We carried out a prospective, randomized study of three parallel groups. We admitted female and male patients with history of kidney stones or evidence of lithiasis (grit, microlithiasis) in the renal echosonogram. Laboratory assessments: urine, 24-hour urine, urinary pH, Calcium, uric acid, Phosphorus, Sodium, protein and urinary creatinine at times: start, day 7, day 21, 30 of treatment. Results: all three products produced a slight increase in urinary pH in the simple urine test and 24-hour urine, with no differences between groups or their logarithmically transformed means and their CI95, which did not exceed the range between 80% and 125%. Conclusions: K Citrate, 10 mEq and 7.5 mEq, from Laboratorios LETI, S.A.V., at a dose of 30 mEq daily in patients with history of kidney stones are equivalent to the reference product Urocit®, in its effects on urinary pH in 24-hour urine, and in the simple urine test.

Effects of sodium bicarbonate ingestion on prolonged running performance and recovery in trained runners

Background: While the effects of sodium bicarbonate on buffering capacity have been repeatedly examined on short-term and high-intensity exercise performance, studies on prolonged endurance performances such as running are scarce. Thus, the purpose of this study was to investigate the effect of NaHCO? (0.3 g/kgBW) ingestion 60-minutes prior to the prolonged running testing and recovery in trained runners.Methods: A total of 10 trained male runners (age: 20.70±1.10 years; weight: 61.30±6.20 kg; height: 166.10±3.70 cm; VO2max 58.43±5.62 mL/kg/min) were recruited in this study. Subjects undertook 1 preliminary testing and 2 experimental trials: Sodium Bicarbonate (SB) and Placebo (PLA) trials, which consisted of: (i) a 60-minutes Prolonged Exercise Testing (PET) (30-minutes of constant speed run at 65 % of VO2max followed by a self-selected speed of 30-minutes maximum distance run) and (ii) 30-minutes of the recovery period in randomized order. Data were analyzed using SPSS version 23 for Windows.Results: Subjects ran further during the SB trial than the PLA trial (5,233.60±524.70 m vs. 5,021.40±440.10 m; p=0.012) associated with a greater blood lactate level (5.66±1.09 mmol/L vs. 3.68±0.71 mmol/L). Ingestion of SB drinks significantly increased urine pH during PET and recovery period (p&lt;0.01). During post-recovery, a greater decrease in blood lactate level was found in the SB trial (2.53±0.91 mmol/L; 55%) as compared to the PLA trial (2.17±0.50 mmol/L; 41%) (p&lt;0.01).Conclusion: The ingestion of NaHCO?(0.30 g/kgBW) 60-minutes prior to the PET improved prolonged running performance associated with a faster lactate removal rate during the 30-minutes recovery period.

Optimisation of a lozenge-based sensor for detecting impending blockage of urinary catheters

Catheter-associated urinary tract infections resulting from urease-positive microorganisms are more likely to cause a urinary catheter blockage owing to the urease activity of the microbes. Catheter blockage can be dangerous and increases the risk of severe infections, such as sepsis. Ureases, a virulence factor in Proteus mirabilis, cause an increase in urine pH - leading to blockage. An optimised biosensor “lozenge” is presented here, which is able to detect impending catheter blockage. This lozenge has been optimised to allow easy manufacture and commercialisation. It functions as a sensor in a physiologically representative model of a catheterised urinary tract, providing 6.7 h warning prior to catheter blockage. The lozenge is stable in healthy human urine and can be sterilized for clinical use by ethylene oxide. Clinically, the lozenge will provide a visible indication of impending catheter blockage, enabling quicker clinical intervention and thus reducing the morbidity and mortality associated with blockage.

PD21-08 OVER-THE-COUNTER ALKALI AGENTS TO RAISE URINE PH AND CITRATE EXCRETION: A PROSPECTIVE CROSSOVER STUDY IN HEALTHY ADULTS

You have accessJournal of UrologyStone Disease: Medical & Dietary Therapy (PD21)1 Sep 2021PD21-08 OVER-THE-COUNTER ALKALI AGENTS TO RAISE URINE PH AND CITRATE EXCRETION: A PROSPECTIVE CROSSOVER STUDY IN HEALTHY ADULTS Noah Canvasser, Marcelino Rivera, Seth Bechis, Johann Ingimarsson, John Knoedler, Karen Stern, Christa Stoughton, Daniel Wollin, Michael Borofsky, Naeem Bhojani, Marawan El Tayeb, Guido Kamphuis, David Leavitt, Ryan Hsi, and Kymora Scotland Noah CanvasserNoah Canvasser More articles by this author , Marcelino RiveraMarcelino Rivera More articles by this author , Seth BechisSeth Bechis More articles by this author , Johann IngimarssonJohann Ingimarsson More articles by this author , John KnoedlerJohn Knoedler More articles by this author , Karen SternKaren Stern More articles by this author , Christa StoughtonChrista Stoughton More articles by this author , Daniel WollinDaniel Wollin More articles by this author , Michael BorofskyMichael Borofsky More articles by this author , Naeem BhojaniNaeem Bhojani More articles by this author , Marawan El TayebMarawan El Tayeb More articles by this author , Guido KamphuisGuido Kamphuis More articles by this author , David LeavittDavid Leavitt More articles by this author , Ryan HsiRyan Hsi More articles by this author , and Kymora ScotlandKymora Scotland More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002010.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urinary citrate is a potent inhibitor of kidney stones; hypocitraturia is a common abnormality in the recurrent stone former. The American Urological Association guidelines specifically recommend potassium citrate for urinary alkalization based on the significant improvement in urinary parameters, and the reduced risk of recurrent stone disease. However, there is poor adherence to prescribed potassium citrate therapy. More recently, patients have had increased access to alternative over-the-counter alkali preparations. Our goal was to assess the effect of two over-the-counter alkalizing agents on 24-hour urinary parameters in healthy adults without a history of kidney stones. METHODS: Ten healthy volunteers without a history of kidney stones were recruited to complete a baseline 24-hour urinalysis with a four-day diet inventory. Participants were randomized 1:1 to take LithoLyte® (20 mEq two times per day) or KSPtabsTM (1 tablet two times per day) while maintaining the same diet and submit another 24-hour urinalysis. The process was repeated with the other supplement. Urinary parameters including citrate, pH and ammonium were compared to baseline. Side effects of each supplement were elicited with a questionnaire after each urine collection. RESULTS: LithoLyte® intake resulted in a non-significant increase in citrate (597 to 758 mg/day, p=0.058, an increase in urine pH (6.46 to 6.66, p=0.028), and a decrease in urine ammonium (41 to 36 mmol/day, p=0.005) compared to baseline (table 1). KSPtabsTM resulted in an increase in citrate (597 to 797 mg/day, p=0.037) and urine pH (6.46 to 6.86, p=0.037), with a non-significant decrease in ammonium (41 to 34 mmol/day, p=0.059). No significant differences were seen comparing urinary analytes between LithoLyte® and KSPtabsTM supplements. With Litholyte®, no side effects, mild, moderate, and severe side effects were seen in 50%, 40%, 10%, and 0%, respectively. With KSPtabsTM, rates were 60%, 20%, 10%, and 10%, respectively. CONCLUSIONS: In healthy participants without a history of kidney stones, LithoLyte® and KSPtabsTM are effective over-the-counter alkali supplements. Their side effect profiles appear similar to prescription potassium citrate. Source of Funding: This was an investigator-initiated project where the protocol, data collection, statistical analysis and drafting of the manuscript was performed by the authors. The study supplements, Litholyte® and KSPtabsTM, and 24-hour urine testing were funded by the manufacturers © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e377-e377 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Noah Canvasser More articles by this author Marcelino Rivera More articles by this author Seth Bechis More articles by this author Johann Ingimarsson More articles by this author John Knoedler More articles by this author Karen Stern More articles by this author Christa Stoughton More articles by this author Daniel Wollin More articles by this author Michael Borofsky More articles by this author Naeem Bhojani More articles by this author Marawan El Tayeb More articles by this author Guido Kamphuis More articles by this author David Leavitt More articles by this author Ryan Hsi More articles by this author Kymora Scotland More articles by this author Expand All Advertisement Loading ...

Intravesical mitomycin C (MMC) and MMC + cytosine arabinoside for non-muscle-invasive bladder cancer: a randomised clinical trial.

ObjectivesTo compare the urinary pH, recurrence‐free survival (RFS), and safety of adjuvant intravesical therapy in patients with non‐muscle‐invasive bladder cancer (NMIBC) receiving mitomycin C (MMC) therapy and MMC + cytosine arabinoside (Ara‐C) therapy.Patients and MethodsA total of 165 patients with NMIBC from six hospitals were randomly allocated to two groups: weekly instillation of MMC + Ara‐C (30 mg/30 mL + 200 mg/10 mL) for 6 weeks and the same instillation schedule of MMC (30 mg/40 mL). The primary outcome was RFS, and secondary outcomes were urinary pH and toxicity in the two groups.ResultsA total of 81 and 87 patients were randomised into the MMC and MMC + Ara‐C groups, respectively. Overall, the RFS in the MMC + Ara‐C group was significantly longer (P = 0.018) than that in the MMC group. A similar significant difference was detected in patients with intermediate‐risk NMIBC, but not in those with high‐risk NMIBC. The mean (SD) urinary pH was significantly higher in the MMC + Ara‐C group than in the MMC group, at 6.56 (0.61) vs 5.78 (0.64) (P < 0.001), and the frequency of a urinary pH of >7.0 in the MMC and MMC + Ara‐C groups was 6.3% and 26.7%, respectively (P < 0.001). Multivariate analysis models including clinicopathological features and second transurethral resection demonstrated that increased urinary pH was associated with better outcomes (hazard ratio 0.18, 95% confidential interval 0.18–0.038; P < 0.001). In all, there were 14 and 10 adverse events in the MMC and MMC + Ara‐C groups, respectively, without a significant difference (P = 0.113).ConclusionsOur randomised clinical trial suggested that intravesical therapy with MMC and Ara‐C is useful and safe for patients with intermediate‐risk NMIBC. Increase in urinary pH with Ara‐C is speculated as a mechanism for increased anti‐cancer effects.

When Baking Soda Goes on Shortage

▪Background: High dose methotrexate (HDMTX), defined as doses > 500-1000 mg/m2, is used to treat a variety of adult and pediatric malignancies. HDMTX can cause significant nephrotoxicity. Volume depletion and acidic urine are major risk factors for acute kidney injury. Precipitation of MTX crystals is most likely to occur in acidic urine when pH drops below 5.5. Increasing urine pH from 6.0 to 7.0 has been demonstrated to increase the solubility of MTX and its metabolites by five to eight-fold. Continuous intravenous (IV) sodium bicarbonate has been a simple long term solution for urinary alkalization allowing for rapid titration to accommodate fluctuations in urinary pH.1-2A recent breakdown in the supply chain of IV sodium bicarbonate has become a healthcare crisis compromising patient care. Sodium bicarbonate (8.4% and 7.5%) 50mL syringes are estimated to remain on back order until at least August 2017. Alternative sources, such as sodium acetate, are in limited supply as well.3-4 In a small case series, acetazolamide 500 mg IV q6H was reported to achieve adequate urinary alkalization, however efficacy of such a regimen has not been examined in a large population.5 Our lack of IV sodium bicarbonate created an urgent need to establish a practical alternative for urinary alkalization in patients receiving HDMTX.Methods: We designed a pilot algorithm for urinary alkalization in patients undergoing HDMTX (table 1). The algorithm relies on administration of IV acetazolamide to induce urinary alkalosis in combination with oral sodium bicarbonate to mitigate the metabolic acidosis induced by acetazolamide.5 MTX is not administered until urinary alkalization (urine pH > 7) is achieved, and the algorithm is continued until serum MTX levels are confirmed to be < 0.1 micromol/L. Additional supportive measures including hydration and leucovorin rescue are routinely provided per our institutional practice. Parameters for additional supportive measures are not defined by the algorithm and dose adjustment of leucovorin was left to the discretion of the treating physician in collaboration with the hematology/oncology clinical pharmacist.Results: Our algorithm was utilized in a patient on three separate encounters, all of which involved administration of HDMTX (8 gm/m2 IV) for primary central nervous system lymphoma. Time to urine pH > 7 using acetazolamide was < 2.5 hours allowing prompt initiation of therapy on admission. Urine pH < 7 was seen once while on IV sodium bicarbonate compared with a total of five times on our pilot algorithm; however the urine pH never dropped below 6.5 on our algorithm (table 1). Average length of stay was similar between both groups (five days with IV sodium bicarbonate and 4.67 days with our algorithm). No cycles resulted in elevations of serum creatinine, liver function tests, or mucositis. Utilizing a maximum dose of IV acetazolamide and oral sodium bicarbonate required for these patients, wholesale acquisition drug cost comparison for 24 hours of therapy is similar for both strategies.Conclusions: In summary, our pilot algorithm for urine alkalization demonstrated that using IV acetazolamide with oral sodium bicarbonate is a tolerable and effective alternative to the use of continuous sodium bicarbonate infusion when treating patients with HDMTX. The algorithm allowed safe treatment of patients with HDMTX at our institution during a period of no access to intravenous sodium bicarbonate. Our observations include prompt urine alkalinization, effective control of urine pH > 7, ease of administration and tolerability, and rapid reductions in plasma MTX concentrations. Limitation to the widespread use of acetazolamide includes metabolic acidosis though not seen in this limited experience. Notwithstanding this limitation, our algorithm demonstrates a viable alternative to sodium bicarbonate infusion and clearly merits further investigation. With the ongoing lack of access to IV sodium bicarbonate, we continue to utilize the algorithm for additional patients undergoing treatment with HDMTX. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Urinary tract infections in culled sows from Greek herds: prevalence and associations between findings of histopathology, bacteriology and urinalysis

BackgroundUrinary tract infections (UTI) of sows characterized by cystitis, which may progress to ureteritis and pyelonephritis, can affect their productivity, longevity and welfare. In this study, we determined the prevalence of UTI by histopathology and bacteriology. Furthermore, we investigated possible associations between histologically confirmed cystitis and the results of urinalysis and urine cultures in culled sows from three farrow-to-finish herds in Greece.Materials and methodsOne hundred eighty-five routinely culled sows were included in the study. Their urinary bladder was collected from abattoirs and subjected to histopathology. Furthermore, urinalysis and urine cultures were performed on urine samples aseptically collected from the bladders.ResultsHistologically confirmed cystitis was evident in 85/185 (45.94%) culled sows. Among those, 44 (51.76%) suffered from acute and 41 (48.24%) from chronic inflammation. The majority of positive urine cultures were due to colonization of the urinary tract with E.coli, which accounted for 55.81% of the total cases, followed by Staphylococcus spp. which accounted for 18.60% of detected infections. Evidence of cystitis was associated with bacteriuria and sows with bacteriuria were 2.30 (P = 0.03, 95% CI: 1.10–4.83) times more likely to have histologically confirmed cystitis compared to sows with negative urine cultures. Bacteriuria was associated with proteinuria (P < 0.01, OR = 9.72, 2.63–35.88), increased urine pH (P < 0.01, 3.40, 1.10–10.56) and presence of sediment (P < 0.01, 6.00, 1.50–23.76) in urine. Sows with proteinuria had 9.72 (P < 0.01, 2.63–35.88) times higher odds of bacteriuria than those without. Histologically defined cystitis was associated with proteinuria (P < 0.01, 2.03–13.20) and decreased urine pH (P < 0.01, 0.13–0.72). Sows with proteinuria were 5.18 (P < 0.01, 2.03–13.2) times more likely to have histological lesions consistent with cystitis, than those without. For one unit increase in pH, it was 3.20 (P = 0.006, 1.39–7.69) times less likely for a sow to have chronic or acute cystitis compared to absence of cystitis.ConclusionIn the studied population, UTI affected almost one out of two culled sows. Bacteriuria, which was more common among sows with UTI than those without, was mainly ascribed to members of the intestinal and environmental bacteria. Proteinuria and the existence of urine sediment which were associated with UTI, could be used as proxy traits for UTI in live sows.

Effect of Bicarbonate on Net Acid Excretion, Blood Pressure, and Metabolism in Patients With and Without CKD: The Acid Base Compensation in CKD Study

Patients with CKD are at elevated risk of metabolic acidosis due to impaired net acid excretion (NAE). Identifying early markers of acidosis may guide prevention in chronic kidney disease (CKD). This study compared NAE in participants with and without CKD, as well as the NAE, blood pressure (BP), and metabolomic response to bicarbonate supplementation. Randomized order, cross-over study with controlled feeding. Participants consisted of 8 patients with CKD (estimated glomerular filtration rate 30-59mL/min/1.73m2 or 60-70mL/min/1.73m2 with albuminuria) and 6 patients without CKD. All participants had baseline serum bicarbonate concentrations between 20 and 28 mEq/L; they did not have diabetes mellitus and did not use alkali supplements at baseline. Participants were fed a fixed-acid-load diet with bicarbonate supplementation (7 days) and with sodium chloride control (7 days) in a randomized order, cross-over fashion. Urine NAE, 24-hour ambulatory BP, and 24-hour urine and plasma metabolomic profiles were measured after each period. During the control period, mean NAE was 28.3±10.2 mEq/d overall without differences across groups (P=0.5). Urine pH, ammonium, and citrate were significantly lower in CKD than in non-CKD (P<0.05 for each). Bicarbonate supplementation reduced NAE and urine ammonium in the CKD group, increased urine pH in both groups (but more in patients with CKD than in those without), and increased; urine citrate in the CKD group (P< 0.2 for interaction for each). Metabolomic analysis revealed several urine organic anions were increased with bicarbonate in CKD, including 3-indoleacetate, citrate/isocitrate, and glutarate. BP was not significantly changed. Small sample size and short feeding duration. Compared to patients without CKD, those with CKD had lower acid excretion in the form of ammonium but also lower base excretion such as citrate and other organic anions, a potential compensation to preserve acid-base homeostasis. In CKD, acid excretion decreased further, but base excretion (eg, citrate) increased in response to alkali. Urine citrate should be evaluated as an early and responsive marker of impaired acid-base homeostasis. National Institute of Diabetes and Digestive and Kidney Diseases and the Duke O'Brien Center for Kidney Research. Registered atClinicalTrials.gov with study number NCT02427594.