Urine pH Research Articles

Urinary Response to Consuming Plant-Based Meat Alternatives in Persons with Normal Kidney Function: The SWAP-MEAT Pilot Trial.

Consuming excess animal meat may exacerbate kidney disorders such as urinary stone disease and chronic kidney disease. Plant-based meat alternatives imitate animal meat, and replace animal with vegetable protein, but it is unclear whether eating plant-meat confers similar health benefits as eating whole vegetables. We hypothesized that eating plant-meat when compared with animal meat decreases dietary acid load but increases dietary phosphorus and nitrogen. SWAP-MEAT was a randomized eight-week, crossover trial (NCT03718988) of participants consuming >2 servings/day of either plant-meat or animal meat for each eight-week phase. We measured urine sulfate, ammonium, pH, phosphorus, urea nitrogen, citrate, and creatinine concentrations, and serum creatinine and bicarbonate concentrations from stored participant samples from each phase. At a single site, we enrolled 36 generally healthy participants (mean±SD age 50.2 ± 13.8 years, 67% women, and 69% White). Eating the plant-meat diet vs. eating the animal meat diet was associated with lower mean concentration of urine sulfate (-6.7 mEq/L; 95% CI -11.0, -2.4), urine ammonium (-4.2 mmol/L; 95% CI -8.2, -0.1), urine phosphorus (-9.0 mg/dL; 95% CI -17.5, -0.5), and urine urea nitrogen (-124.8 mg/dL; 95% CI -226.9, -22.6). Eating plant-meat compared with eating animal meat was associated with higher mean urine pH (+0.3 units; 95% CI 0.2, 0.5) and mean urine citrate/creatinine ratio (+111.65; 95% CI 52.69-170.60). After participants consumed a plant-meat diet compared with when they consumed an animal meat diet, mean serum creatinine concentration was lower (-0.07 mg/dL, 95% CI -0.10, -0.04), whereas mean serum bicarbonate concentration was not different. Eating plant-based meat products, compared with eating animal meat, was associated with lower urinary excretion of sulfate, ammonium, phosphorus, and urea nitrogen and higher urinary excretion of citrate. Our findings provide rationale for examining whether plant-based meat will benefit patients with kidney disease.

Effects of benzoic acid in pig diets on nitrogen utilization, urinary pH, slurry pH, and odorous compounds.

The objective was to investigate the effects of dietary benzoic acid (BA) on nitrogen (N) balance, urinary pH, slurry pH, and odorous compounds in feces and slurry of pigs. Twelve barrows with an initial body weight of 56.2±2.6 kg were individually housed in metabolism crates. The animals were allocated to a replicated 6×4 incomplete Latin square design with 12 animals, 6 experimental diets, and 4 periods, resulting in 8 observations per treatment. The basal diet consisted mainly of corn, soybean meal, and rapeseed meal. Benzoic acid was supplemented to the basal diet at 0.5%, 1.0%, 1.5%, 2.0%, or 2.5% BA at the expense of corn starch. Each period consisted of a 4-day adaptation period and a 24-hour collection period for slurry, followed by a 4-day collection period for feces and urine. On day 5, feces and urine were collected for 24 hours and mixed to obtain slurry samples. The daily digested N linearly increased (p<0.05) with increasing BA supplementation. Supplemental BA lowered urinary pH (p<0.001) and slurry pH (p<0.05) in a linear and quadratic manner. In the fecal samples, the concentrations of acetate, propionate, butyrate, and skatole linearly decreased (p<0.05) with supplemental BA. In the slurry samples, the concentrations of butyrate, isovalerate, and skatole linearly decreased (p<0.05) by supplemental BA. In conclusion, supplemental benzoic acid has the potential to improve nitrogen digestion in a dose-dependent manner for pigs. Additionally, dietary benzoic acid lowers urinary pH, slurry pH, and concentrations of odorous compounds in pig feces and slurry.

Dietary Intervention of Benzoic Acid for Intestinal Health and Growth of Nursery Pigs.

The objectives of this review are to investigate how benzoic acid can mitigate the negative effects of weaning stress, improve the intestinal microbiota, intestinal health, and growth of nursery pigs, determine the optimal dose level of benzoic acid for the growth rate in nursery pigs, and compare the efficacy of benzoic acid and other acids in pig feeds. After weaning, pigs are exposed to less lactose and solid feed with high acid-binding capacity at infrequent intervals, causing an increase in digesta pH, reducing protein digestion, and increasing ammonia-producing bacteria in the stomach. Benzoic acid supplementation has improved the intestinal health and growth of nursery pigs through its antimicrobial properties and pH reduction in the digesta. The positive modulation of luminal microbiota in the small intestine of pigs by benzoic acid improves intestinal morphology and enhances nutrient utilization, especially nitrogen, of nursery pigs. Benzoic acid supplementation of up to 1% in feeds also increases hippuric acid contents in the urine of nursery pigs, decreasing urinary pH, which is related to ammonia emission and barn conditions in intensive pig production. Supported by the beneficial impacts of benzoic acid, the growth performance of nursery pigs was also improved. However, excessive benzoic acid (over 2.5% up to 5%) in feeds reduces the growth performance of nursery pigs. Thus, this review conducted a meta-analysis of the results from 16 papers to determine the optimal dose level of benzoic acid for body weight gain of nursery pigs, which was found to be 0.60%. The efficacy of benzoic acid was similar to that of other organic acids, including citric acid, fumaric acid, formic acid, and formate salts. Collectively, benzoic acid supplementation can positively modulate the luminal and mucosal microbiota in the small intestine, increase nutrient utilization and intestinal health, decrease urinary pH, and improve the growth performance of nursery pigs.

Simultaneous Detection of Biomarkers in Urine Using a Multicalibration Potentiometric Sensing Array Combined with a Portable Analyzer.

Domestic monitoring devices make real-time and long-term health monitoring possible, allowing people to track their health status regularly. Uric acid (UA), creatinine, and urea in urine are three important biomarkers for various diseases, especially kidney diseases. This work proposed a 10-channel potentiometric sensing array containing a UA electrode group, a creatinine electrode group, a urea electrode group, a pH electrode group, and one pair of reference channels, which could be connected with a portable potentiometric analyzer, realizing the simultaneous detection of UA, creatinine, urea, and pH in urine. The prepared Pt/carbon nanotubes (CNTs)-uricase, creatinine deiminase, Au@urease, and polyaniline were employed as the sensing materials, showing responses to four targets with high sensitivity and selectivity. To improve the accuracy of domestic monitoring, a calibration channel was integrated into each electrode group to calibrate the basic potential of the sensing channels, and the influences of pH and temperature on the responses were investigated through the pH electrode group and an external temperature probe to calibrate the slope and intercept. With the preset of the deduced calibration parameters and computational formula for the four targets in the analyzer in Lab Mode, the concentrations of UA, creatinine, and urea and the pH of the human urine samples were directly displayed on the screen of the analyzer in Practical Mode. The agreement of these results with those obtained from commercial kits and pH meters reveals the high potential of these methods for developing domestic devices to facilitate health monitoring.

Protein Intake and High Uric Acid Stone Risk

Rationale & ObjectiveWe evaluated the metabolic differences between pure and impure uric acid stone formers in this retrospective study of uric acid kidney stone formers diagnosed between 1996 and 2021. Study DesignDemographics and medical history were compared by chi-squared tests. 24-hour urine chemistries were compared using logistic regressions while controlling for demographics and comorbidities. Setting & ParticipantsPatients from Yale Urology and Nephrology Clinics with a documented kidney stone analysis containing uric acid were included. 4294 kidney stone formers had a stone analysis and 722 (16.8%) contained uric acid. Patients with all stone analyses ≥50% uric acid were allocated to the pure group, while patients with at least one stone analysis <50% uric acid were allocated to the impure group. ResultsAmong kidney stone formers, the prevalence of uric acid nephrolithiasis was 16.8%. Pure uric acid stone formers were more likely to be older, heavier, and were 1.5 times more likely to have chronic kidney disease. When controlling for age, sex, race, ethnicity, and body mass index, pure uric acid stone formers had lower urine pH and lower urine citrate normalized for creatinine. Additionally, they had a higher protein catabolic rate, urine urea nitrogen, and urine sulfur normalized for creatinine, all markers of dietary protein intake. These findings persisted after controlling for chronic kidney disease. LimitationsThis is a retrospective study from a single center. ConclusionsPure uric acid stone formation is more common with diminished kidney function; however, after controlling for kidney function, pure uric acid stone formation is associated with protein intake, suggesting that modifying protein intake may reduce risk.

Effects of pH on the Pathogenicity of Escherichia coli and Klebsiella pneumoniae on the Kidney: In Vitro and In Vivo Studies.

Urine pH reflects the functional integrity of the body and may influence the virulence of uropathogenic Escherichia coli and Klebsiella pneumoniae, the main causes of urinary tract infections (UTIs). This study evaluated the effects of acidic pH on the pathogenicity of uropathogenic E. coli and K. pneumoniae strains, in vitro and in vivo. Four uropathogenic E. coli and four K. pneumoniae strains were used. Biofilm formation, growth competition indices, motility, and adhesion and invasion of human renal cells were analyzed in media with acidic, neutral, and alkaline pH. A murine lower UTI model was used, with urine adjusted to acidic, neutral, or alkaline pH. At acidic pH, E. coli and K. pneumoniae exhibited higher bacterial concentrations in the kidneys and systemic symptoms, including bacteremia. Alkaline urine pH did not affect bacterial concentrations of any strain. In mice with UTIs caused by E. coli Nu14 and K. pneumoniae HUVR42 and acidic urine pH, histopathological studies of the kidneys showed acute inflammation affecting the urothelium and renal parenchyma, which are traits of acute pyelonephritis. These results indicate that acidic pH could increase the pathogenicity of E. coli and K. pneumoniae in murine models of lower UTI, promoting renal infection and acute inflammation.

A Urine pH-Ammonium Acid/Base Score and CKD Progression.

Acidosis is associated with exacerbated loss of kidney function in chronic kidney disease (CKD). Currently, acid/base status is assessed by plasma measures, although organ-damaging covert acidosis, subclinical acidosis, may be present before reflected in plasma. Low urine NH4+ excretion associates with poor kidney outcomes in CKD and is proposed as a marker for subclinical acidosis. However, low NH4+ excretion could result from either a low capacity or a low demand for acid excretion. We hypothesized that a urine acid/base-score reflecting both the demand and capacity for acid excretion would better predict CKD progression. 24-hour urine collections were included from three clinical studies of patients with CKD stage 3 and 4: A development cohort (n=82), a variation cohort (n=58), and a validation cohort (n=73). A urine acid/base-score was derived and calculated from urinary pH and [NH4+]. Subclinical acidosis was defined as an acid/base-score below the lower limit of the 95% prediction interval of healthy controls. Main outcomes were change in measured GFR after 18 months and CKD progression (defined as ≥50% decline in eGFR, initiation of long-term dialysis or kidney transplantation) during up to 10 years of follow-up. Subclinical acidosis was prevalent in all cohorts (n=54/82, 48/73, and 40/58, ∼67%). Subclinical acidosis was associated with an 18% (95% CI: 2-32) larger decrease of measured GFR after 18 months. During a median follow-up of 6 years, subclinical acidosis was associated with a markedly higher risk for CKD progression. Adjusted hazard ratios were 9.88 (95% CI 1.27-76.7) in the development cohort and 11.1 in the validation cohort (95% CI: 2.88-42.5). The acid/base-score had a higher predictive value for CKD progression than NH4+ excretion alone. Subclinical acidosis, defined by a new urine acid/base-score, was associated with a higher risk of CKD progression in patients with CKD stage 3 and 4.

Association of proteinuria at time of diagnosis with survival times in dogs with lymphoma.

Lymphoma has been implicated as a possible cause of proteinuria in dogs. However, information about the potential importance of proteinuria in dogs with lymphoma is limited. To determine if the presence of proteinuria at diagnosis was associated with median survival times in dogs with lymphoma and if lymphoma stage (I-V) or type (B vs T) were associated with the presence of proteinuria. Eighty-six client-owned dogs with a new diagnosis of lymphoma between 2008 and 2020. This was a retrospective cross-sectional study with dogs divided into proteinuric or nonproteinuric groups based on dipstick urine protein (protein ≥30 mg/dL classified as proteinuric) or a ratio of dipstick protein to urine specific gravity (ratio ≥1.5 classified as proteinuric). Dogs were excluded for: (1) treatment within 2 months with glucocorticoid, anti-neoplastic, or anti-proteinuric therapies, (2) diagnosed hypercortisolism or renal lymphoma, (3) active urine sediment, or (4) urine pH >8. Survival analysis utilized a Kaplan-Meier estimator and log-rank testing. There was a significant difference in median survival between proteinuric and nonproteinuric dogs classified by urine dipstick (245 days [91, 399] vs 335 days [214, 456]; P = .03) or UP : USG (237 days [158, 306] vs 304 days [173, 434]; P = .03). No difference in prevalence of proteinuria was identified between stages (I-V) or types (B and T). Proteinuria appears to be negatively associated with survival time in dogs newly diagnosed with lymphoma.

Time Series AI Model for Acute Kidney Injury Detection Based on a Multicenter Distributed Research Network: Development and Verification Study.

Acute kidney injury (AKI) is a marker of clinical deterioration and renal toxicity. While there are many studies offering prediction models for the early detection of AKI, those predicting AKI occurrence using distributed research network (DRN)-based time series data are rare. In this study, we aimed to detect the early occurrence of AKI by applying an interpretable long short-term memory (LSTM)-based model to hospital electronic health record (EHR)-based time series data in patients who took nephrotoxic drugs using a DRN. We conducted a multi-institutional retrospective cohort study of data from 6 hospitals using a DRN. For each institution, a patient-based data set was constructed using 5 drugs for AKI, and an interpretable multivariable LSTM (IMV-LSTM) model was used for training. This study used propensity score matching to mitigate differences in demographics and clinical characteristics. Additionally, the temporal attention values of the AKI prediction model's contribution variables were demonstrated for each institution and drug, with differences in highly important feature distributions between the case and control data confirmed using 1-way ANOVA. This study analyzed 8643 and 31,012 patients with and without AKI, respectively, across 6 hospitals. When analyzing the distribution of AKI onset, vancomycin showed an earlier onset (median 12, IQR 5-25 days), and acyclovir was the slowest compared to the other drugs (median 23, IQR 10-41 days). Our temporal deep learning model for AKI prediction performed well for most drugs. Acyclovir had the highest average area under the receiver operating characteristic curve score per drug (0.94), followed by acetaminophen (0.93), vancomycin (0.92), naproxen (0.90), and celecoxib (0.89). Based on the temporal attention values of the variables in the AKI prediction model, verified lymphocytes and calcvancomycin ium had the highest attention, whereas lymphocytes, albumin, and hemoglobin tended to decrease over time, and urine pH and prothrombin time tended to increase. Early surveillance of AKI outbreaks can be achieved by applying an IMV-LSTM based on time series data through an EHR-based DRN. This approach can help identify risk factors and enable early detection of adverse drug reactions when prescribing drugs that cause renal toxicity before AKI occurs.

Racial differences in serological markers across the first year of injury in spinal cord injury: a retrospective analysis of a multi-center interventional study

Study designSecondary analysis of a randomized, multi-center, placebo-controlled study(Sygen®).ObjectivesTo evaluate racial differences in serological markers in individuals with spinal cord injury(SCI) across the first year of injury.SettingHospitals in North America.MethodsSerological markers (e.g.,cell count, liver, kidney, and pancreatic function, metabolism, and muscle damage) were assessed among 316 participants (247 White, 69 Black) at admission, weeks 1, 2, 4, 8, and 52 post-injury. Linear mixed models were employed to explore the main effects of time, race (Black vs. White), and their interaction, with adjustment of covariates such as study center, polytrauma, injury (level, completeness), treatment group, and sex.ResultsA main effect of race was observed where White individuals had higher alanine transaminase, blood urea nitrogen(BUN), BUN/Creatinine ratio, sodium, and chloride, while Black individuals had higher calcium, total serum protein, and platelets. For markers with interaction effects, post-hoc comparisons showed that at week 52, White individuals had higher mature neutrophils, hematocrit, hemoglobin, mean corpuscular hemoglobin, albumin, and triglycerides, and Black individuals had higher amylase. Eosinophils, monocytes, red blood cells, aspartate aminotransferase, bilirubin, cholesterol, partial thromboplastin time, urine specific gravity, urine pH, CO2, and inorganic phosphorus did not differ between races.ConclusionsOur results revealed racial differences in serological markers and underscores the importance of considering race as a determinant of physiological responses. Future studies are warranted to explore the causes and implications of these racial disparities to facilitate tailored clinical management and social policy changes that can improve health equity.

Unlocking New Approaches to Urolithiasis Management Via Nutraceuticals.

Urolithiasis, commonly known as kidney stones, is characterized by the formation of hard deposits in the urinary tract. These stones can cause severe pain and discomfort, and their management typically involves a combination of medical interventions and lifestyle modifications. According to the literature, 30% and 50% of urolithiasis cases recur. Between 9 and 12% of persons in industrialised countries are predicted to have urolithiasis at some time. Due to the high frequency of stone formation, recurrent nature, and prevalence in adults, it has a significant impact on society, the person, and the health care system. Adopting the best prophylactic measures is crucial in light of these developments to decrease the impact of urolithiasis on individuals and society. In recent years, there has been growing interest in the potential role of nutraceuticals in the management of urolithiasis. Nutraceuticals, such as herbal extracts, vitamins, minerals, and probiotics, have gained recognition for their potential in promoting urinary health and reducing the risk of urolithiasis. These compounds can aid in various ways, including inhibiting crystal formation, enhancing urine pH balance, reducing urinary calcium excretion, and supporting kidney function. Additionally, nutraceuticals can help alleviate symptoms associated with urolithiasis, such as pain and inflammation. While medical interventions remain crucial, incorporating nutraceuticals into a comprehensive management plan can offer a holistic approach to urolithiasis, improving patient outcomes and quality of life. Therefore, nutraceuticals may be a desirable choice for treating and avoiding recurring urolithiasis for patients and medical professionals. Therefore, the present study has focused on nutraceuticals' role in preventing urolithiasis.

Urine pH as predictor of blood acid-base status in dairy cattle fed acidogenic diets

We determined the association between urine pH and blood acid-base indicators and assessed a urine pH cut-off value to predict severe metabolic acidosis under field conditions in cows fed acidogenic diets. Eighty-six cows were sampled for urine and blood. Urine pH was evaluated immediately after collection, and blood acid-base status was evaluated within 2 hours of collection using a portable blood analyzer. Twenty-five cows were classified as having severe metabolic acidosis (blood pH ≤ 7.4; bicarbonate < 24 mmol/L, base excess ≤ −0.5; PCO2 low to normal concentrations and urine pH between 4.88 and 5.71. There was a positive linear association between urine pH and blood pH (r = 0.46), and between urine pH and base excess (r = 0.74). The area under the ROC curve was 0.91 (CI 95 %= 0.84–0.96; good-excellent test). The optimal cut-off value for urine pH to categorize a cow with severe metabolic acidosis was 5.5 (94 % specificity and 72 % sensitivity). For each 0.1 unit of decrease in urine pH below 5.5, cows were 1.6 times (95 % CI= 1.3–2.1) more likely to exhibit a severe metabolic acidosis. We conclude that a urine pH of 5.5 or less is indicative of more life-threatening metabolic acidosis in dairy cows.

Комплексные средства для коррекции уровня рН мочи при метафилактике мочекаменной болезни.

Introduction. Urolithiasis is a serious medical, social and economic problem. Over the past decades the world has seen a progressive, approximately 3% per year, increase in its incidence. Urolithiasis occupies a leading position in the structure of urological diseases and has a high recurrence rate in the absence of metaphylaxis. In turn, the effectiveness of properly selected anti-relapse therapy has been proven by many studies and is about 50- 80%. The development of “tools” for rational metaphylaxis represents a potential “growth area” for improving the effectiveness of treatment for patients with urolithiasis. One of these tools is the correction of urine pH levels, since its violations are the most common. However, drugs used to correct pH levels have a number of limitations, which greatly complicates their use. One of the possible solutions to these shortcomings may be the creation of combined drugs that can comprehensively influence the factors that provoke the recurrence of stone formation such as the line of Litcontrol® Litura® products from Devicare (Spain). The purpose of this publication is the scientific rationale of the clinical effects of Litura® Up and Litura® Down in the metaphylaxis of urolithiasis. Materials and methods. A literature search and analysis of foreign and domestic literature was carried out from 1990 to 2024 with the selection of relevant publications in the еLibrary, PubMed databases and Google including keywords – the active components of Lit-Control® pH Up – potassium-magnesium citrate, theobromine, zinc, vitamin A, and Lit-Control® pH Down – phytates, L-methionine, zinc, vitamin A. References in included sources were reviewed to identify additional potentially relevant studies. 189 sources were found, based on the relevance of which 60 articles were selected. Results. The use of Litura® Up and Litura® Down has a scientific basis, and the included substances and their combination potentiate the clinical effect in the metaphylaxis of urolithiasis. However, controlled clinical studies are necessary to assess the prospects for using these complex agents. Conclusions. Based on foreign data from experimental and clinical studies, we can conclude that the Lit-Control® Litura® line of products used to correct urine pH levels and inhibit crystallization in various types of stone formation can be considered as a new promising approach to the metaphylaxis of urolithiasis.

Метаболические факторы риска и формирование мочевых камней. Исследование IX: Особенности литогенеза камней мономинерального и смешанного состава у мужчин и женщин.

Introduction. The study of lithogenic substances excretion in stone formers with pure monomineral stones allows us to identify characteristic metabolic changes, the long-term effect of which determines the originality of the pathogenetic mechanism features of the formation of urinary stones consisting of pure minerals. The problem of studying lithogenesis of «pure» (monomineral) stones in stone formers is of great clinical importance, since it assumes the existence of various approaches to prevention and metaphylaxis of urolithiasis in patients with «pure» stones and mixed stones. Materials and methods. We examined 982 patients with urolithiasis (439 men and 543 women aged from 18 to 79 years. Of these, 837 patients (384 men and 453 women) had «pure» urinary stones of various types, represented by one mineral. Metabolic parameters of excretion in patients were studied men and women with monomineral urinary stones of various chemical types. Results. In oxalate stones, the most active accumulation of the calcium oxalate mineral component and an increase in the number of «pure» oxalate stones by 1.25 times was observed in men than in women (p=0.046). Increased calcium excretion activates oxalate lithogenesis in men, as opposed to women, contributing to the accumulation of veddelite in pure oxalate stones. In contrast to women, the accumulation of calcium oxalate in stones in men is associated with increased excretion of uric acid, phosphates, and partly magnesium (p&lt;0.01). In uric acid stones consisting of pure uric acid and uric acid dihydrate, pure uric acid stones were 1.52 times more common in women than in men (p&lt;0.01), and did not depend on the level of uricosuria. Patients with pure uric acid stones had lower urine pH than patients with pure calcium-oxalate stones. The accumulation of uric acid in stones to the level of pure uric acid stones was accompanied in the groups of men by an increase in phosphaturia (p=0.021), and in the groups of women – with an increase in body mass index (p=0.028). Men with 100% uric acid stones had higher levels of excretion of calcium, uric acid and phosphates compared to female patients by 1.21 times, 1.3 times and 1.26 times, respectively (p&lt;0.05). Urinary stones from pure carbonate apatite were rare in men and women. In women, stones of mixed composition with 80-90% carbonatapatite were more often detected, and in men with 60-70% of this mineral. In men, compared with women, with the accumulation of carbonatapatite in stones, an increase in the excretion of calcium, uric acid, phosphates and magnesium was observed (p&lt;0.05). About 80% of mixed stones in stone formers men and women are pure calcium oxalate-phosphate bimineral stones consisting only of carbonate apatite and calcium oxalate. In men, in contrast to women, there was a predominance of calcium oxalate (1.24 times), the accumulation of which in these stones was higher. It is associated with increased excretion of calcium, uric acid, phosphates, and magnesium (1.41-fold, 1.32-fold, 1.35-fold, and 1.33-fold, respectively (p&lt;0.05). Men with calcium oxalate-phosphate stones had higher calcium excretion than those with pure calcium oxalate or carbonate apatite stones and lower urine pH values than those with carbonate apatite stones (p&lt;0.01). In women, level of calciuria did not play a big role in the genesis of pure calcium oxalate-phosphate, calcium oxalate and carbonate apatite stones. A more important factor in their lithogenesis was the alkaline reaction of urine, which led to the activation of carbonate apatite stone formation. Conclusion. The formation of urinary stone and the distribution of its mineral components depend on the interaction of various metabolic factors. The study of groups of patients with pure (100%) monomineral stones and patients with stones of mixed composition, in which main mineral is only the predominant part, allows us to identify characteristic complexes of lithogenic metabolic factors that distinguish these groups of patients from each other. This approach is important both for understanding the pathogenetic mechanisms of stone formation, and for choosing the directions of empirical therapy for urolithiasis and developing further metaphylactic measures that also take into account the gender of patients.

Fisetin Protects the Wistar Rats from the Oxidative and Inflammatory Damage Caused by Ethelene Glycol Induced Urolithiasis

Urolithiasis, commonly referred to as urinary stones, is the third most prevalent condition affecting the urinary system and affects 12% of people worldwide. In this investigation, we assessed the prospective flavonoid fisetin's anti-urolithiasis activity. Fisetin reduced the nucleation, aggregation, and crystallization of kidney stones in in vitro tests at dosages of 62.5, 125, 250, 500, and 1,000 ug/mL in a dose-dependent manner. Twenty-four male Wistar rats (n = 6) were induced with urolithiasis using ethylene glycol (0.75% v/v) with ammonium chloride (1% w/v) in drinking water for seven days. Except for the animals in the vehicle control and disease control groups, the remaining animals were supplemented with either Fisetin 15 mg/kg or 30 mg/kg body weight from days 7 to 21. On day 22, a urine evaluation showed that fisetin significantly increased the glycosaminoglycan (GAG) content, corrected urine pH, increased creatinine clearance, and increased urine volume. Additionally, fisetin decreased the levels of calcium, creatinine, uric acid, and N-acetyl glucouronidase (NAG) activity. Serum biochemical analysis revealed that fisetin reduced the excretion of creatinine, uric acid, and blood urea nitrogen (BUN). Further, fisetin reduced the content of total protein, calcium, oxalate, protein carbonyl content (PCC), malondialdehyde (MDA), tumor necrosis factor (TNF-α), interlukin-6 (IL-6), and increased the content of reduced glutathione (GSH), the activities of superoxide dismutase (SOD), and catalase (CAT). Histological findings also support our findings. Based on the above observations, fisetin can be a potential candidate for the treatment of urolithiasis.

Exploring the Influence of Acid-Base Status on Athletic Performance during Simulated Three-Day 400 m Race.

This study aimed to investigate the ability of highly trained athletes to consistently perform at their highest level during a simulated three-day 400 m race and to examine the impact of an alkaline diet associated with chronic consumption of bicarbonate-rich water or placebo on their blood metabolic responses before and after the three races. Twenty-two highly trained athletes, divided into two groups-one with an alkalizing diet and placebo water (PLA) and the other with an alkalizing diet and bicarbonate-rich water (BIC)-performed a 400 m race for three consecutive days. Performance metrics, urine and blood samples assessing acid-base balance, and indirect markers of neuro-muscular fatigue were measured before and after each 400 m race. The evolution of the Potential Renal Acid Load (PRAL) index and urinary pH highlights the combination of an alkalizing diet and bicarbonate-rich hydration, modifying the acid-base state (p < 0.05). Athletes in the PLA group replicated the same level of performance during three consecutive daily races without an increase in fatigue-associated markers. Athletes experienced similar levels of metabolic perturbations during the three 400 m races, with improved lactate clearance 20 min after the third race compared to the first two (p < 0.05). This optimization of the buffering capacity through ecological alkaline nutrition and hydration allowed athletes in the BIC group to improve their performance during the third 400 m race (p < 0.01). This study highlights athletes' ability to replicate high-level performances over three consecutive days with the same extreme level of metabolic disturbances, and an alkaline diet combined with bicarbonate-rich water consumption appears to enhance performance in a 400 m race.

Identification of novel genetic susceptibility loci for calcium-containing kidney stone disease by genome-wide association study and polygenic risk score in a Taiwanese population.

Approximately 80% of kidney stone diseases contain calcium. Inherited genetic factors are among the variables that influence the development of calcium-containing kidney stone diseases (CKSD). Previous genome-wide association studies (GWAS) on stone diseases have been reported worldwide; however, these are not focused on calcium-containing stones. We conducted a GWAS to identify germline genetic polymorphisms associated with CKSD in a Medical Center in Taiwan; hence, this study was based primarily on a hospital-based database. CKSD was diagnosed using the chart records. Patients infected with urea-splitting-microorganisms and those with at least two urinary pH value below 5.5 were excluded. None of the patients had cystic stones based on stone analysis. Those over 40 years of age with no history of CKSD and no microscopic hematuria on urinalysis were considered as controls. The DNA isolated from the blood of 14,934 patients (63.7% male and 36.3% female) with CKSD and 29,868 controls (10,830 men and 19,038 women) at a medical center was genotyped for approximately 714,457 single nucleotide polymorphisms (SNPs) with minor allele frequency of ≥ 0.05. We used PLINK 1.9 to calculate the polygenic risk score (PRS) to investigate the association between CKSD and controls. The accuracy of the PRS was verified by dividing it into the training and testing groups. The statistical analyses were calculated with the area under the curve (AUC) using IBM SPSS version 22. We identified 432 susceptibility loci that reached a genome-wide threshold of P < 1.0 × 10- 5. A total of 132 SNPs reached a threshold of P < 5 × 10- 8 using a stricter definition of significance on chromosomes 4, 13, 16, 17, and 18. At the top locus of our study, SNPs in DGKH, PDILT, BCAS3, and ABCG2 have been previously reported. RN7SKP27, HDAC4, PCDH15, AP003068.2, and NFATC1 were novel findings in this study. PRS was adjusted for sex and age, resulting in an AUC of 0.65. The number of patients in the top quartile of PRS was 1.39 folds in the risk of CKSD than patients in the bottom quartile. Our data identified the significance of GWAS for patients with CKSD in a hospital-based study. The PRS also had a high AUC for discriminating patients with CKSD from controls. A total of 132 SNP loci of SNPs significantly associated with the development of CKSD. This first survey, which focused on patients with CKSD, will provide novel insights specific to CKSD and its potential clinical biomarkers.

Medical treatment of uric acid kidney stones.

The prevalence of uric acid stones increases regularly due to its high correlation with obesity, hypertension, metabolic syndrome, type 2 diabetes, and aging. Uric acid stone formation is mainly due to an acidic urinary pH secondary to an impaired urinary ammonium availability responsible for uric acid rather than soluble urate excretion. Alkalization of urine is therefore advocated to prevent uric acid crystallization and considered effective therapy. We report a large series of 120 patients with uric acid kidney stones who were successfully treated with potassium citrate (K-citrate) for stone dissolution without any urologic intervention to prevent stone recurrence, with a median 3.14 years followup. The K-citrate was diluted in 1.5 L of water, avoiding gastrointestinal disorders. Among 75 patients having stones in their kidney at initiation of therapy, a complete chemolysis was obtained in 88% of cases. Stone risk factors decreased under treatment, mainly due to increased diuresis, urinary pH, and citrate excretion. Treatment was stopped in only 2% of patients due to side effects, with no hyperkalemia onset despite a median urinary potassium increase of 44 mmol/day. Contrary to other reports, our data show that medical treatment of uric acid kidney stones is well-tolerated and efficient if regular monitoring of urinary pH is performed.

Oral alkalinizing supplementation suppressed intrarenal reactive oxidative stress in mild-stage chronic kidney disease: a randomized cohort study.

The beneficial effects of oral supplements with alkalinizing agents in patients with chronic kidney disease (CKD) have been limited to the severe stages. We investigated whether two types of supplements, sodium bicarbonate (SB) and potassium citrate/sodium citrate (PCSC), could maintain renal function in patients with mild-stage CKD. This was a single-center, open-labeled, randomized cohort trial. Study participants with CKD stages G2, G3a, and G3b were enrolled between March 2013 and January 2019 and randomly assigned by stratification according to age, sex, estimated glomerular filtration rate (eGFR), and diabetes. They were followed up for 6months (short-term study) for the primary endpoints and extended to 2years (long-term study) for the secondary endpoints. Supplementary doses were adjusted to achieve an early morning urinary pH of 6.8-7.2. We observed renal dysfunction or new-onset cerebrovascular disease and evaluated urinary surrogate markers for renal injury. Overall, 101 participants were registered and allocated to three groups: standard (n = 32), SB (n = 34), and PCSC (n = 35). Two patients in the standard group attained the primary endpoints (renal stones and overt proteinuria) but were not statistically significant. There was one patient in the standard reduced eGFR during the long-term study (p = 0.042 by ANOVA). SB increased proteinuria (p = 0.0139, baseline vs. 6months), whereas PCSC significantly reduced proteinuria (p = 0.0061, baseline vs. 1year, or p = 0.0186, vs. 2years) and urinary excretion of 8-hydroxy-2'-deoxyguanosine (p = 0.0481, baseline vs. 6months). This study is the first to report supplementation of PCSC reduced intrarenal oxidative stress in patients with mild-stage CKD.

Machine learning models predicts risk of proliferative lupus nephritis.

This study aims to develop and validate machine learning models to predict proliferative lupus nephritis (PLN) occurrence, offering a reliable diagnostic alternative when renal biopsy is not feasible or safe. This study retrospectively analyzed clinical and laboratory data from patients diagnosed with SLE and renal involvement who underwent renal biopsy at West China Hospital of Sichuan University between 2011 and 2021. We randomly assigned 70% of the patients to a training cohort and the remaining 30% to a test cohort. Various machine learning models were constructed on the training cohort, including generalized linear models (e.g., logistic regression, least absolute shrinkage and selection operator, ridge regression, and elastic net), support vector machines (linear and radial basis kernel functions), and decision tree models (e.g., classical decision tree, conditional inference tree, and random forest). Diagnostic performance was evaluated using ROC curves, calibration curves, and DCA for both cohorts. Furthermore, different machine learning models were compared to identify key and shared features, aiming to screen for potential PLN diagnostic markers. Involving 1312 LN patients, with 780 PLN/NPLN cases analyzed. They were randomly divided into a training group (547 cases) and a testing group (233 cases). we developed nine machine learning models in the training group. Seven models demonstrated excellent discriminatory abilities in the testing cohort, random forest model showed the highest discriminatory ability (AUC: 0.880, 95% confidence interval(CI): 0.835-0.926). Logistic regression had the best calibration, while random forest exhibited the greatest clinical net benefit. By comparing features across various models, we confirmed the efficacy of traditional indicators like anti-dsDNA antibodies, complement levels, serum creatinine, and urinary red and white blood cells in predicting and distinguishing PLN. Additionally, we uncovered the potential value of previously controversial or underutilized indicators such as serum chloride, neutrophil percentage, serum cystatin C, hematocrit, urinary pH, blood routine red blood cells, and immunoglobulin M in predicting PLN. This study provides a comprehensive perspective on incorporating a broader range of biomarkers for diagnosing and predicting PLN. Additionally, it offers an ideal non-invasive diagnostic tool for SLE patients unable to undergo renal biopsy.