Uric Acid Stone Formation Research Articles

Self-control study of multi-omics in identification of microenvironment characteristics in urine of uric acid stone

AbstractThe aim of this study is to perform proteomic and metabolomic analyses in bilateral renal pelvis urine of patients with unilateral uric acid kidney stones to identify the specific urinary environment associated with uric acid stone formation. Using cystoscopy-guided insertion of ureteral catheters, bilateral renal pelvis urine samples are collected. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is employed to identify differentially expressed proteins and metabolites in the urine environment. Differentially expressed proteins and metabolites are further analyzed for their biological functions and potential metabolic pathways through Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In the urine from the stone-affected side, eight differential proteins were significantly upregulated, and six metabolites were dysregulated. The uric acid stone urinary environment showed an excess of α-ketoisovaleric acid and 3-methyl-2-oxovaleric acid, which may contribute to the acidification of the urine. Functional and pathway analyses indicate that the dysregulated metabolites are mainly associated with insulin resistance and branched chain amino acid metabolism.

SGLT2 Inhibitors and Their Effect on Urolithiasis: Current Evidence and Future Directions.

Urolithiasis (UL) is increasingly prevalent due to rising cardiorenometabolic diseases, posing significant management challenges despite advances in urological techniques. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, primarily used for type 2 diabetes mellitus, chronic kidney disease, and heart failure, have emerged as a potential novel approach for UL treatment. These inhibitors may help reduce the risk of urolithiasis, particularly in patients with diabetes, by improving glycemic control and altering urinary chemistry, which are crucial factors in stone formation. However, the changes in urinary composition induced by SGLT2 inhibitors might also increase the risk of uric acid stone formation. This review evaluates the potential of SGLT2 inhibitors in managing UL, highlighting both the benefits and the risks. While these inhibitors show promise in reducing new and recurrent urinary stones in patients with diabetes, data on their effects in patients without diabetes who form stones are limited. Current human evidence largely comes from post hoc analyses of randomized controlled trials (RCTs) and large-scale database studies, with only one study providing detailed stone composition data. Experimental studies in animal models and cell lines have focused on calcium oxalate (CaOx) stones, showing that SGLT2 inhibitors specifically target CaOx stone formation and related renal inflammation. Although primarily studied for CaOx stones, their potential impact on other calcium-containing stones, such as calcium phosphate, remains promising. Further research is needed to explore their therapeutic potential and optimize treatment strategies.

Fat Distribution and Urolithiasis Risk Parameters in Uric Acid Stone Formers and Patients with Type 2 Diabetes Mellitus

Background: Uric acid (UA) nephrolithiasis affects approximately 10% of kidney stones, with a greater preponderance among patients with obesity and diabetes mellitus. UA lithogenicity is driven by abnormally acidic urine pH. Distinguishing the contribution of intrinsic (e.g., body adiposity) versus external (e.g., dietary) factors to UA stone propensity is challenging due to uncontrolled diets in outpatients in previously published studies. Methods: This compilation of metabolic studies with body composition examined by dual-energy X-ray absorptiometry (DXA) scan, and blood and urine biochemistry collected under a controlled metabolic diet was conducted across three distinct populations: 74 UA stone formers (UASF group), 13 patients with type 2 diabetes mellitus without kidney stones (DM group), and 51 healthy volunteers (HV group). Results: Compared to HV, both UASF and DM exhibited higher levels of net acid excretion (NAE), and significantly lower urine pH and lower proportion of NAE excreted as ammonium (NH4 +/NAE), all under controlled diets. UASF exhibited significantly lower NH4 +/NAE compared with DM. UASFs also showed higher total body and truncal fat compared to controls. Among the HV, lower NH4 +/NAE ratio correlated with higher truncal and total fat. However, this association was abolished in the UASF and DM groups who exhibit a fixed low NH4 +/NAE ratio across a range of body and truncal fat. Conclusion: The findings suggest a dual defect of diet-independent increase in acid production and impaired kidney NH4 + excretion as major contributors to the risk for uric acid stone formation. There is an inverse physiologic association between body fat content and NH4 +/NAE in HV while NH4 +/NAE is persistently low in UASF and DM regardless of body fat representing pathophysiology.

Acute Effect of High Fat Intake on Urinary Acidification Parameters in Uric Acid Stone Formers and Non-stone Forming Controls

Acute Effect of High Fat Intake on Urinary Acidification Parameters in Uric Acid Stone Formers and Non-stone Forming Controls

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.

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.

Assessment of Hounsfield Units and Factors Associated with Fragmentation of Renal Stones by Extracorporeal Shock Wave Lithotripsy: A Computerized Tomography Study.

This retrospective single-center study was conducted in the King Fahad Hospital. Sixty-seven adult patients with renal and ureteric stones were selected randomly and enrolled in the study. Their ages ranged from 20 to 69 years. The patients were examined with non-contrast enhancement (NCCT) to assess the HU of their stones and were consequently treated with ESWL. Of the 67 patients, 37.3% had stones that were completely fragmented, while 62.7% had stones that were partially fragmented. The HU, location of the stone, multiplicity of the stone, and patient age were found to be significant factors contributing to stone fragility (p-values < 0.05). The HU data were found to have a positive significant linear correlation with serum calcium (r = 0.28, p-value = 0.036), while serum acid had a negative correlation (r = -0.55, p-value < 0.001). Thus, the probability of calcium-containing stone formation increases with increased HU. In contrast, uric acid stone formation likely develops with decreasing HU with serum uric acid. Renal stones in patients with diabetes mellitus and hypertension were not completely fragmented compared to those without clinical history. Mean HU, location of the stone, laterality, stone status, and the number of ESWL sessions are the most significant factors affecting stone fragility. CT attenuation values can predict the composition of stones from serum calcium and uric acid examinations. Hypertension and diabetes mellitus are risk factors for renal stone fragmentation.

Acute renal failure after kidney transplantation due to mizoribine-induced ureteral stones

IntroductionMizoribine (MZR) is used to prevent rejection reactions after kidney transplantation and increase the risk of hyperuricemia. There is a lack of reports of MZR-induced ureteral stones after kidney transplantation. The surgery treatment of ureteral stones in transplanted kidney is a challenging clinical issue that should only be performed by experienced urologists at professional centers. It is very important to have a thorough understanding of the patient's medical history, analyze the causes of stone formation, and choose a reasonable treatment plan based on the characteristics of the stones. The case report is aim to emphasize the recognition of the possibility of mizoribine-induced ureteral uric acid stones in transplanted kidney and to avoid unnecessary surgery.Case presentationA patient after kidney transplantation was diagnosed with acute renal failure caused by ureteral stones. The medical history, CT images of the renal graft, the results of laboratory test and stone composition analysis were provided. Based on medical history and laboratory test results, it was determined that the ureteral stones of renal graft was induced by MZR. To our best knowledge, this is the first report of MZR-induced stones in transplanted kidney and ureters. It was completely cured by urinary alkalinization, avoiding surgery treatment. We summarize the characteristics, treatment and methods for preventing the formation of uric acid stones of patients with MZR.ConclusionBy analyze our case report, it shows that acute renal failure with ureteral stones after kidney transplantation can caused by MZR. Urinary alkalinization for MZR induced uric acid stones is simple and effective.

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 &lt;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 &lt;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&lt;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&lt;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.

Distinguishing Uric Acid Stone Formers from Type 2 Diabetics with Low Urine pH: The Role of Impaired Buffering

Distinguishing Uric Acid Stone Formers from Type 2 Diabetics with Low Urine pH: The Role of Impaired Buffering

Increased risk of chronic kidney disease in uric acid stone formers with high neutrophil-to-lymphocyte ratio

Urolithiasis is associated with an increased risk of chronic kidney disease (CKD), irrespective of stone compositions. Chronic inflammation is an important factor for CKD progression. Neutrophil-to-lymphocyte ratio (NLR) has been recognized as a reliable biomarker of inflammation, yet its use in predicting renal deterioration in patients with urolithiasis remains limited. We aimed to explore whether the combination of stone composition and NLR could be useful as a predictor for CKD risk. A total of 336 stone formers with at least one stone submission for analysis were enrolled in the retrospective study. Stones were classified into uric acid and calcium groups. Renal functions were assessed at least one month after stone treatment. Uric acid stone formers had significantly lower estimated glomerular filtration rate (eGFR) compared with calcium stone formers (p < 0.001). NLR was significantly higher in uric acid stone formers (p = 0.005), and a significantly negative correlation (p < 0.001) between NLR and eGFR had been observed only in uric acid stone group. Univariate and multivariate logistic regression analyses showed that higher proportion of uric acid stone composition and higher NLR were both significantly associated with CKD risks. A nomogram integrating independent predictors was generated for CKD prediction, yielding an AUC of 0.811 (0.764–0.858). In conclusion, our study demonstrated that stone formers with higher proportion of uric acid composition and higher NLR levels were associated with higher CKD risk.

Метаболические факторы риска и формирование мочевых камней. Исследование VII: Литогенные свойства урикозурии у мужчин и женщин.

Introduction. Hyperuricosuria usually considered as the main metabolic factor in the formation of uric acid stones, but this issue remains unclear. Gender differences in the prevalence of urolithiasis (UL) indicate the need for a more detailed study of the lithogenic properties of uricosuria and its role in the development of various metabolic types of UL. In this study, was investigated the effect of varying degrees of uricosuria in men and women with UL on metabolic parameters and the frequency of detection of urinary stones of different chemical composition. Materials and methods. A total of 982 patientsа with UL (439 men and 543 women aged 18 to 79 years)were examined. To assess the lithogenic activity of uricosuria in men and women with UL, the values of uric acid excretion (in mmol/day) were ranked in ascending order and divided into 10 equal parts (ten 10%-х percentilesей). In each of the ranges, the percentage distribution of types of urinary stones and biochemical parameters of urine and blood were determined. Results. As the degree of uricosuria increased from minimum to maximum values in men and women, there were no differences in the percentage distribution of uric acid stones. The different orientation of the processes of urate lithogenesis is noted, which was manifested in uricosuria above 3.48 mM/day by the accumulation of anhydrous uric acid in the stones in women 1.47 times greater than in men, in whom the proportion of uric acid in the stones, on the contrary, decreased by 1.36 times. It was found that uricosuria above 3.48 mM/day was accompanied by activation of oxalate lithogenesis rather than uric acid: the incidence of oxalate stones in men increased by 1.55 times (p=0.0025), and in women by 2.16 times (p=0.0013). At the same time, the proportions of the oxalate component in the stones of male and female patients, respectively, increased, mainly due to the wevellite component. An increase in uric acid excretion over 3.48 mM/day led to a relative decrease in the frequency of detection of carbonatapatite stones in men by 1.85 times (p=0.0104), and in women by 2.0 times (p=0.0153). With increasing uricosuria, both men and women experienced an almost linear increase in the levels of calcium, phosphate, and magnesium excretion (p&lt;0.0001). The blood phosphate content in women was on average 7-11. 6% higher than in men, and uric acid was lower by 8.5-16.0% for almost all values of uricosuria. Calcemia levels in men and women did not have statistically significant differences. for all values of uricosuria. Men in the age groups from 30-39yr to 60-79yr have a higher uric acid excretion than women, which also corresponds to a higher incidence of oxalate stones in men, exceeding this indicator in women in all age groups by 2.5 -1.8 times (p&lt;0.05). The formation of uric acid stones is observed in men of an earlier age than in women, namely from the age of 18-29yr, while in women the formation of stones of this type is detected only from the age group of 40-49yr and older. Conclusion. Characteristic property of uricosuria of various degrees is its different ability to influence the dynamics of metabolic parameters of excretion and lithogenesis of calcium stones (oxalate and phosphate stones) in men and women in the absence of a noticeable effect on the lithogenesis of uric acid stones, which should be taken into account when conducting personalized metaphylaxis of urolithiasis.

Anaerobic purinolytic enzymes enable dietary purine clearance by engineered gut bacteria

Uric acid, the end product of purine degradation, causes hyperuricemia and gout, afflicting hundreds of millions of people. The debilitating effects of gout are exacerbated by dietary purine intake, and thus a potential therapeutic strategy is to enhance purine degradation in the gut microbiome. Aerobic purine degradation involves oxidative dearomatization of uric acid catalyzed by the O2-dependent uricase. The enzymes involved in purine degradation in strictly anaerobic bacteria remain unknown. Here we report the identification and characterization of these enzymes, which include four hydrolases belonging to different enzyme families, and a prenyl-flavin mononucleotide-dependent decarboxylase. Introduction of the first two hydrolases to Escherichia coli Nissle 1917 enabled its anaerobic growth on xanthine as the sole nitrogen source. Oral supplementation of these engineered probiotics ameliorated hyperuricemia in a Drosophila melanogaster model, including the formation of renal uric acid stones and a shortened lifespan, providing a route toward the development of purinolytic probiotics.

Investigations on melamine-based uric acid kidney stone formation and its prevention by inhibitors.

Melamine (Mel) as a milk powder adulterant came to light in September 2008, when a kidney stone disease (KSD) outbreak struck China. The mechanism of the formation of Mel-associated uric acid (UA) stones is relatively unknown. Therefore, in the present study, Mel's influence was explored at comparatively higher and lower concentrations in artificial urine. The parameter optimization performed when the Mel concentration in artificial urine was low, which revealed that higher pH values and lower UA concentration considerably delayed the induction of UA crystallization. When Mel concentration was increased relative to UA concentration, the induction time of UA crystallization decreased dramatically. At the highest concentration of Mel investigated (at UA-Mel molar ratio 1:1), PXRD analysis and SEM revealed a change in crystalline structure of the samples. Based on FTIR analysis, it was determined that UA-Mel interactions are essentially physical, because no new characteristic bands developed. Two inhibitors, namely tri-potassium citrate (TPC) and 3, 7-dimethylxanthine (DMX), were investigated for their inhibitory action on UA crystallization in the presence of Mel. DMX was observed to be more promising than TPC in delaying the induction of crystallisation and hence inhibiting crystal formation.

MP10-05 LITHOPROTECTIVE EFFECT OF GLP-1 AGONISTS IN DIABETIC STONE FORMERS

You have accessJournal of UrologyCME1 Apr 2023MP10-05 LITHOPROTECTIVE EFFECT OF GLP-1 AGONISTS IN DIABETIC STONE FORMERS Kelley Zhao, Brian Shkolnik, Jennifer Lu, Joshua Miller, and David Schulsinger Kelley ZhaoKelley Zhao More articles by this author , Brian ShkolnikBrian Shkolnik More articles by this author , Jennifer LuJennifer Lu More articles by this author , Joshua MillerJoshua Miller More articles by this author , and David SchulsingerDavid Schulsinger More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003225.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Type 2 Diabetes mellitus (T2DM) is associated with increased risk of calcium oxalate and uric acid (UA) stones. The most commonly prescribed medication for T2DM, Metformin, worsens this risk by increasing urinary oxalate, increasing urinary calcium and decreasing urine pH. With the increasing popularity of next-generation hypoglycemic agents, it is important to study the risk of stone formation with these newer medications. This study aims to assess the effects of various hypoglycemic agents on 24-hour urine studies in diabetic stone formers. METHODS: A retrospective review was conducted for all patients with a history of nephrolithiasis and a 24-hour urine study seen between July 2017-December 2019 for an outpatient visit. Patients with T2DM were assessed for use of hypoglycemic agents (metformin, sulfonylurea, GLP-1 agonist, DPP-4 inhibitors, SGLT-2 inhibitors, insulin), stone analysis, BMI, HbA1c, and 24-hour urine study. Two-tailed t-tests were used for mean comparison and chi square tests for stone rate comparison. RESULTS: Among the included 510 patients, 86 had T2DM (45 males, 41 females, mean age 63.6 years). Compared to the non-T2DM cohort, T2DM patients had lower urine pH (5.62 vs 6.14, p<0.00001), higher urine oxalate (41.7 vs 36.14, p=0.013) and higher UA supersaturation (1.45 vs 0.94, p<0.00001). Patients on GLP-1 agonists had greater urinary citrate than both the T2DM cohort (927.94 vs 544.59, p=0.007) and the non-T2DM cohort (566.55, p<0.0001). Between diabetic GLP-1 agonist users and non-users, there was no significant difference in BMI (non-GLP 33.1 vs GLP 35.4, p=0.34) or HbA1c (non-GLP 7.0 vs GLP 7.2, p=0.74). Though T2DM patients had higher rates of UA stones (31.7% vs 12.1%, p<0.0001), GLP-1 agonists users did not have a higher rate of UA stones compared to non-T2DM patients (18.2% vs 12.1%, p=0.54). There were no significant differences found with Metformin, sulfonylurea, DPP-4 inhibitors, SGLT-2 inhibitors, or insulin. CONCLUSIONS: T2DM is a known risk factor for nephrolithiasis, however, treatment with GLP-1 agonists may be litho-protective. The significant increase in urine citrate and reduction in UA stone formation suggests a lithoprotective effect of GLP-1 agonists independent of weight or diabetes control. Consideration should be made to recommend GLP-1 agonists to T2DM patients with nephrolithiasis. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e115 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kelley Zhao More articles by this author Brian Shkolnik More articles by this author Jennifer Lu More articles by this author Joshua Miller More articles by this author David Schulsinger More articles by this author Expand All Advertisement PDF downloadLoading ...

Stone Formation Features in the Kidney of Residents in the South Region of Kyrgyzstan

Kidney stone disease (KSD), otherwise urolithiasis, is one of the most common and frequent diseases and occurs most often in patients of working age. With “urolithiasis” there is a metabolic disorder characterized by the presence of stones in the kidneys and urinary tract. Formation of kidney stones in residents of southern region in Kyrgyzstan has not been studied. Research objectives: determination of stone formation features in the kidney of patients in the southern region of Kyrgyzstan. Research materials and methods: a literary review of urolithiasis (KSD) of the kidneys and identification of stone formation features. Research results: kidney stone formation is a complex physical and chemical process, accompanied by growth, aggregation and retention of urinary stone in parts of tubular cells. Conclusions: formation of calcium oxalate and uric acid stones is associated with various metabolic processes in the body. Urinary calculi are formed as a result of a series of sequence of stages.

Urinary Risk Profile, Impact of Diet, and Risk of Calcium Oxalate Urolithiasis in Idiopathic Uric Acid Stone Disease.

The role of diet in the pathogenesis of uric acid (UA) nephrolithiasis is incompletely understood. This study investigated the effect of dietary intervention on the risk of UA stone formation under standardized conditions. Twenty patients with idiopathic UA stone disease were included in the study. Dietary intake and 24 h urinary parameters were collected on the usual diet of the patients and a standardized balanced mixed diet. Although urinary UA excretion did not change, the relative supersaturation of UA decreased significantly by 47% under the balanced diet primarily due to the significant increase in urine volume and pH. Urinary pH was below 5.8 in 85% of patients under the usual diet, and in 60% of patients under the balanced diet. The supersaturation of calcium oxalate declined significantly under the balanced diet due to the significant decrease in urinary calcium and oxalate excretion and the increase in urine volume. Dietary intervention is a key component in the management of UA nephrolithiasis. Urinary calcium and oxalate excretion should also be monitored in patients with pure UA calculi to reduce the risk of mixed stone formation with calcium oxalate. Lower urinary pH in UA stone patients can only be partially explained by diet.

Differences of Uric Acid Transporters Carrying Extracellular Vesicles in the Urine from Uric Acid and Calcium Stone Formers and Non-Stone Formers.

Background: Low urine pH and volume are established risk factors for uric acid (UA) stone disease (UASD). Renal tubular epithelial cells exposed to an acidic pH and/or UA crystals can shed extracellular vesicles (EVs) into the tubular fluid, and these EVs may be a pathogenic biomarker of UASD. Methods: Urinary EVs bearing UA transporters (SLC2A9, SLC17A3, SLC22A12, SLC5A8, ABCG2, and ZNF365) were quantified in urine from UA stone formers (UASFs), calcium stone formers (CSFs), and age-/sex-matched non-stone formers (NSFs) using a standardized and published method of digital flow cytometry. Results: Urinary pH was lower (p < 0.05) and serum and urinary UA were greater (p < 0.05) in UASFs compared with NSFs. Urinary EVs carrying SLC17A3 and SLC5A8 were lower (p < 0.05) in UASFs compared with NSFs. Urinary EVs bearing SLC2A9, SLC22A12, SLC5A8, ABCG2, and ZNF365 were lower (p < 0.05) in CSFs than UASFs, while excretion of SLC17A3-bearing EVs did not differ between groups. Conclusion: EVs bearing specific UA transporters might contribute to the pathogenesis of UASD and represent non-invasive pathogenic biomarkers for calcium and UA stone risk.

The effect of metabolic risk factors on urinary stone composition: An observational study.

To investigate how the risk factors of metabolic diseases affect urinary stone composition, particularly uric acid (UA) stones. Overall, 583 patients with data on urinary stone composition were retrospectively analyzed and classified into UA and nonUA stone formers according to the presence of the UA component. Various factors were compared between both groups. Participants were categorized according to age, glucose level, HbA1c level, and estimated glomerular filtration rate (eGFR) into subgroups, and the incidence of UA stone was compared. Overall, 137 UA stone formers (23.5%) and 446 nonUA stone formers (76.5%) were included. Mean age and male-to-female ratio were higher in the UA group than in the nonUA group. The rates of diabetes mellitus (DM), hypertension, chronic kidney disease, and coronary artery disease, all of which were associated with differences in urinary stone composition, were higher in the UA group than in the nonUA group. The UA group exhibited lower mean eGFR and higher glucose and HbA1c levels. Similarly, the UA group had higher mean UA levels and predictably lower urinary pH. In subgroup analysis, higher age, glucose level, HbA1c level, and lower eGFR were associated with an increased risk of UA stone formation. In the multivariate logistic regression analysis, the UA group showed a significantly higher age (P < .001), DM frequency (P = .049), and HbA1c level (P = .032), but significantly lower eGFR than the nonUA group (P < .001). Age and DM were independent risk factors for UA urolithiasis, implying a relationship between urinary stone composition and metabolic diseases. Additionally, renal function and HbA1c level were risk factors for UA stones.

Are there seasonal variations in renal colic in uric acid stone formers in Germany?

Seasonal variations in renal colic have been described by many authors for different countries worldwide. In most studies, there was no differentiation with regard to stone composition. Recently, we demonstrated that there was no seasonal variation in renal colic and urine chemistry for calcium oxalate stone formers in Germany. As we have many uric acid stone formers (UASFs) in our region, we were interested in learning the situation of this type of stone. We studied 286 consecutive UASFs with symptoms of renal colic. We divided them into four groups according to the quarters of the year. For stone analysis, X-ray diffraction/polarizing microscopy was used. Additionally, the following general parameters were examined in all patients: age, BMI, blood pressure, stone frequency, diabetes mellitus; blood: creatinine, glucose, uric acid, calcium, sodium and potassium; urine: pH, volume, calcium, uric acid, citrate, ammonia, and urea. Using the statistical program Prism 5 (GraphPad Software, San Diego, USA), significant differences between the four groups were calculated by the Kruskal-Wallis test. We observed significantly more UASFs with renal colic in the third and fourth quarters of the year. This is in contrast to our findings in calcium oxalate patients. However, there was no variation in metabolic parameters. The reasons are unclear; different temperatures are not a sufficient explanation, as one quarter is in the warm season and the other one is in the cold season. Unfortunately, no data have been reported in the literature thus far. Further studies are required to better understand these findings.