Urinary Citrate Research Articles

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.

Plasma CoQ10 Status in Patients with Propionic Acidaemia and Possible Benefit of Treatment with Ubiquinol.

Propionic acidaemia (PA) is an innate error of metabolism involving a deficiency in the enzyme propionyl-CoA carboxylase. Better control of acute decompensation episodes together with better treatment and monitoring have improved the prognosis of patients with this problem. However, long-term complications can arise in those in whom good metabolic control is achieved, the result of mitochondrial dysfunction caused by deficient anaplerosis, increased oxidative stress, and reduced antioxidative capacity. Coenzyme Q10 (CoQ10) is a nutritional supplement that has a notable antioxidative effect and has been shown to improve mitochondrial function. The present prospective, interventional study examines the plasma concentration of CoQ10 in patients with PA, their tolerance of such supplementation with ubiquinol, and its benefits. Seven patients with PA (aged 2.5 to 20 years, 4 males) received supplements of CoQ10 in the form of ubiquinol (10 mg/kg/day for 6 months). A total of 6/7 patients showed reduced plasma CoQ10 concentrations that normalized after supplementation with ubiquinol (p-value < 0.001), which was well tolerated. Urinary citrate levels markedly increased during the study (p-value: 0.001), together with elevation of citrate/methlycitrate ratio (p-value: 0.03). No other significant changes were seen in plasma or urine biomarkers of PA. PA patients showed a deficiency of plasma CoQ10, which supplementation with ubiquinol corrected. The urinary excretion of Krebs cycle intermediate citrate and the citrate/methylcitrate ratio significantly increased compared to the baseline, suggesting improvement in anaplerosis. This treatment was well tolerated and should be further investigated as a means of preventing the chronic complications associated with likely multifactorial mitochondrial dysfunction in PA.

Simultaneous determination of oxalate and citrate in urine and serum of calcium oxalate kidney stone rats by IP-RP LC-MS/MS

Oxalate and citrate in 24 h urine and serum are considered to be associated with the incidence and recurrence risk of calcium oxalate kidney stones. The quantification of oxalate and citrate contributes to understand the pathological metabolism of kidney stones and guide the early diagnosis and recurrence monitoring. Although simultaneous quantification of oxalate and citrate in urine using liquid chromatography tandem mass spectrometry (LC-MS/MS) have been reported, the optimization of chromatographic column, mobile phase and mass spectrometry (MS) parameters has not been performed. In addition, these is a lack of suitable method for simultaneous detection of oxalate and citrate both in serum and urine. Therefore, we developed a method for the simultaneous determination of oxalate and citrate in urine and serum based on ion-pairing reversed-phase (IP-RP) LC-MS/MS. Herein, five ion-pair reagents, namely, triethanolamine, dimethylbutyl amine, diisopropenyl amine, N,N-dimethylcyclohexylamine and tripropylamine, and three ion-pairing reagent (IPR) buffers, namely, acetic acid, hexafluoro-2-isopropanol, and hexafluoro-2-methyl-2-propanol, were compared in regard to their chromatographic peak abundance and separation of oxalate and citrate. Moreover, MS parameters and the multiple reaction monitoring (MRM) conditions were also evaluated and optimized to obtain the maximum peak abundance. After that, the method was validated in the linear range of 0.25–1000 µM, and the correlation coefficient was ≥ 0.99. The precision and accuracy were < 14.70% and < 19.73%, respectively. The extraction recovery was 80.53–108.79%, and the matrix effect was < 8.79%. The quality control samples were stable at room temperature for 4 h, 4 °C for 24 h, and for 3 freeze–thaw cycles. Finally, this method was applied to the determination of oxalate and citrate in the serum and urine of rats with calcium oxalate kidney stones. The establishment of a stable and effective oxalate and citrate detection method is conducive to the diagnosis and monitoring of kidney stones.

Proteomic analysis of inhibitory protein profiles in the urine of children with nephrolithiasis: implication for disease prevention.

In this study we aimed to screen for the presence of biomarkers that are downregulated in children with nephrolithiasis (RS) compared to healthy controls (HC) using a proteomic approach. We hypothesized that RS and HC would display unique inhibitory protein profiles that could be used for comparative pathway analysis. This is a prospective, controlled, pilot study of pooled urine from RS (N = 30, 24 females, mean age 12.95 ± 4.03years) versus age- and gender-matched HC, using liquid chromatography-mass spectrometry. The criteria for protein selection were: (1) patient/control abundance ratio of < 0.5; and (2) ≤ 0.05 p-value for the Fisher's Exact Test. Results were confirmed by ELISA testing in individual samples. 67 proteins were downregulated in RS group, and 17 of those were significantly different compared to controls. Of those seventeen proteins, five (two actins, annexin A5, keratin 6B, and serpin B4) were completely absent in the urine of stone patients but were found in controls. The remaining twelve proteins were significantly less abundant in the patient's urine compared to healthy controls. Protein-protein interaction modeling of significant proteins identified syndecan-1 as the key node, a protein associated with adhesion pathways. ELISA analysis by subgroups showed statistically significant difference in the urinary excretion of osteopontin (5.1 ± 3.22ng/mg creatinine vs 14.1 ± 9.5ng/mg creatinine, p = 0.046) between stone patients with hypocitraturia and controls. Urinary osteopontin concentration was positively correlated with urinary citrate excretion (r = 0.417, p = 0.03). Children with RS have a different urinary inhibitory polypeptide profile compared to HC. Decreased urinary excretion of these proteins indicates their potential inhibitory role in renal stone formation, especially of the adhesion phase. Lower concentration of urinary osteopontin in children with nephrolithiasis and hypocitraturia suggests its potential involvement in the pathogenesis of this disease. Further characterization of these proteins in a larger sample is imperative.

Machine Learning Models to Predict 24 Hour Urinary Abnormalities for Kidney Stone Disease

OBJECTIVETo help guide empiric therapy for kidney stone disease, we sought to demonstrate the feasibility of predicting 24-hour urine abnormalities using machine learning methods. METHODSWe trained a machine learning model (XGBoost [XG]) to predict 24-hour urine abnormalities from electronic health record-derived data (n = 1314). The machine learning model was compared to a logistic regression model [LR]. Additionally, an ensemble (EN) model combining both XG and LR models was evaluated as well. Models predicted binary 24-hour urine values for volume, sodium, oxalate, calcium, uric acid, and citrate; as well as a multiclass prediction of pH. We evaluated performance using area under the receiver operating curve (AUC-ROC) and identified predictors for each model. RESULTSThe XG model was able to discriminate 24-hour urine abnormalities with fair performance, comparable to LR. The XG model most accurately predicted abnormalities of urine volume (accuracy = 98%, AUC-ROC = 0.59), uric acid (69%, 0.73) and elevated urine sodium (71%, 0.79). The LR model outperformed the XG model alone in prediction of abnormalities of urinary pH (AUC-ROC of 0.66 vs 0.57) and citrate (0.69 vs 0.64). The EN model most accurately predicted abnormalities of oxalate (accuracy = 65%, ROC-AUC = 0.70) and citrate (65%, 0.69) with overall similar predictive performance to either XG or LR alone. Body mass index, age, and gender were the three most important features for training the models for all outcomes. CONCLUSIONUrine chemistry prediction for kidney stone disease appears to be feasible with machine learning methods. Further optimization of the performance could facilitate dietary or pharmacologic prevention.

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.

The effects of drinking bicarbonate-rich mineral water in calcium oxalate stone formers: an open label prospective randomized controlled study in an Asian cohort.

To examine the effects of drinking bicarbonate-rich mineral water in patients with calcium oxalate stones. This was an open label prospective randomized controlled study comparing the effects of a bicarbonate-rich mineral water versus plain water on urine biochemistry in patients with calcium oxalate stones. The mineral water group were instructed to consume 1.25L of mineral water per day at meal times, and supplemented by plain water. Their total intake was up to 3L/day. Control group consumed only plain water up to 3L/day. 24h urine analyses were performed at baseline, 1, 4, 8 and 12weeks after starting protocol. 58 patients were recruited for the study. 51 patients were included in the final analysis. Baseline data were comparable between the two groups. Over the course of 12weeks, compared to patients drinking plain water, those drinking mineral water had higher overall urinary volume (difference = 644.0ml/24h, 95% CI = (206.7, 1081.3)), higher overall urinary magnesium (difference = 1.894mmol/24h, 95% CI = (1.006, 2.782)), and pH (difference = 0.477, 95% CI = (0.149, 0.804)). However, there was no difference in urinary oxalate and Tiselius index. Mineral water group had net increase of urinary citrate (at each study point compared to baseline) which was sustained until week 12, whereas plain water group showed no significant change. Drinking bicarbonate-rich mineral water in calcium oxalate stone formers increased stone inhibitors such as magnesium, citrate and moderate degree of urinary alkalinization compared to patients drinking plain water, but it did not alter Tiselius index or urinary oxalate after 12weeks.

Regulation of Acid-Base Balance in Patients With Chronic Kidney Disease.

Normallly the kidneys handle the daily acid load arising from net endogenous acid production from the metabolism of ingested animal protein (acid) and vegetables (base). With chronic kidney disease, reduced acid excretion by the kidneys is primarily due to reduced ammonium excretion such that when acid excertion falls below acid porduction, acid accumulation occurs. With even mild reductions in glomerular filtration rate (60 to 90 ml/min), net acid excretion may fall below net acid production resulting in acid retention which may be initially sequestered in interstitial compartments in the kidneys, bones, and muscles resulting in no fall in measured systemic bicarbonate levels (eubicarbonatemic metabolic acidosis). With greater reductions in kidney function, the greater quantities of acid retained spillover systemically resulting in low pH (overt metabolic acidosis). The evaluation of acid-base balance in patients with CKD is complicated by the heterogeneity of clinical acid-base disorders and by the eubicarbonatemic nature of the early phase of acid retention. If supported by more extensive studies, blood gas analyses to confirm the acid-base disorder and newer ways for assessing the presence of acidosis such as urinary citrate measurements may become routine tools to evaluate and treat acid-base disorders in individuals with CKD.

Primary Contributors to Dietary Acid Load in Patients With Urolithiasis

In susceptible individuals, high dietary acid load may contribute to the formation of certain types of kidney stones via lowering urine pH and citrate excretion. The objective of this study is to determine the contribution of dietary acid from food groups in people with urolithiasis. Patients with calcium urolithiasis (n=83) who completed food records were used for this retrospective analysis. Descriptive statistics were calculated for nutrients, potential renal acid load (PRAL), and estimated net endogenous acid production (NEAPest). Pearson's correlations were calculated between PRAL and NEAPest with each nutrient. Data from a total of 83 patients were used. Average PRAL was positively correlated with energy (r=0.260, P=.02), total protein (r=0.463, P<.001), animal protein (r=0.555, P<.001), total fat (P=.399, P<.001), sodium (r=0.385, P<.001), and phosphorus (r=0.345, P<.001) intake. PRAL was negatively correlated with fiber (r=-0.246, P=.03) intake. NEAPest was positively correlated with total protein (r=0.269, P=.01), animal protein (r=0.377, P<.001), fat (r=0.222, P=.04), and sodium (r=0.250, P=.02) intake. NEAPest was negatively correlated with fiber (r=-0.399, P<.001), potassium (r=-0.360, P<.001), and magnesium (r=-0.233, P=.03) intake. For PRAL, meat contributed the highest acid load (52.7%), followed by grains (19.6%) and combination foods (19.6%). Beverages contributed the greatest alkali load (35.1%), followed by vegetables (30.6%) and fruits (28.6%). For NEAPest, cheese contributed the highest acid load (21.8%), followed by grains (19.3%) and meat (18.1%). For individuals with urolithiasis promoted by acidic urine and/or low urine citrate, dietary patterns with a high dietary acid load may contribute to recurrence risk. Meat and grains were the major contributors to dietary acid load in this cohort of patients with a history of kidney stones, whereas beverages, fruits, and vegetables contributed netalkali.

Management of Renal Calculi: A Review

Renal calculi are a common cause of blood in the urine (hematuria) and pain in the abdomen, flank, or groin. They occur in one in 11 people at some time in their lifetimes with men affected 2 to 1 over women. Development of the stones is related to decreased urine volume or increased excretion of stone-forming components such as calcium, oxalate, uric acid, cystine, xanthine, and phosphate. Calculi may also be caused by low urinary citrate levels or excessive urinary acidity. Renal calculi present with excruciating pain and most patients present to the emergency department in agony. A single event does not cause kidney failure but recurrent renal calculi can damage the tubular epithelial cells, which can lead to functional loss of the renal parenchyma.

Enteral nutrition and the risk of nephrolithiasis in complex pediatric patients

Medically complex, non-ambulatory children can often suffer from nephrolithiasis. The purpose of this study is to determine risk factors which are predictive for recurrent stone formation in this patient population. A retrospective cohort study was performed on non-ambulatory patients with cerebral palsy and/or severe developmental delay presenting to a high-volume Pediatric Stone Center from 2015 to 2019. Two 24-hour urine collections were performed as a baseline prior to pharmacotherapeutic and/or dietary intervention. Healthy stone-forming children served as a control group. 28 non-ambulatory subjects and 38 healthy controls were evaluated. The study group had a higher rate of bilateral nephrolithiasis but a similar history of previous surgical procedures. 89% of the non-ambulatory children were fed via a gastrostomy. The median calcium excretion was the same in both groups (3.0mg/kg/day). The median 24-hour excretion of oxalate was significantly increased in the study group (54 vs 31mg/1.73m2/day, p=0.0001). Urinary citrate and phosphorus excretions, and the supersaturations of calcium oxalate and calcium phosphate were similar between study subjects and controls. Calcium oxalate stones were noted in 57% of those with known stone composition in the study group. Enteral feeding formulas were primarily based on soy protein, a known high oxalate food. Urinary oxalate excretion is significantly increased in a cohort of medically complex, non-ambulatory stone-forming children. Urinary calcium excretion was not elevated between study subjects and healthy controls. Further analysis is needed to assess if dietary intervention to limit oxalate excretion results in decreased stone formation.

Sensitive Ion-Chromatographic Determination of Citric Acid in Urine

Urine citrate analysis is relevant in the screening and monitoring of patients with calcium nephrolithiasis. A sensitive, fast, easy, and low-maintenance ion chromatographic (IC) method with conductivity detection for the analysis of urine citrate is developed and validated. Its application on true samples is also reported. Sample urine is diluted with a water solution containing internal standard (IS) before the chromatographic assay. The isocratic chromatographic run time is twenty-five minutes, using sodium hydroxide aqueous solution as the mobile phase. The method is fully validated as a quantitative method to objectively demonstrate its applicability for the intended use. The analytical response is linear in the 0.08–10.4 mmol/L concentration range. Precision and accuracy studies carried out on spiked urine and internal quality control samples reveal an imprecision CV% lower than 11% and an accuracy between 85 and 103%. The stability of citrate in urine samples is also evaluated. An easy, rapid, and low-maintenance, cost-effective IC method for urinary citrate determination is developed and validated. Internal standardization improves reliability and precision. The method has been currently used in our laboratory over recent years to analyze more than 1000 samples per year.

MO437: Decreased Urinary Citrate Levels as a Marker of Progressive Deterioration of Glomerular Filtration in Patients With Autosomic Dominant Polycystic Kidney Disease (ADPKD)

Abstract BACKGROUND AND AIMS In a previous work we have found that there is a reduction in urinary citrate levels in autosomic dominant polycystic kidney disease (ADPKD) patients. Their levels are related to GFR but not serum bicarbonate levels. Our aim was to analyse whether there is any relationship between rate of GFR deterioration and citraturia in ADPKD patients. METHOD We collected routinary determinations of urine citrate in 24-h urine samples and analysed its predictive role for GFR deterioration with general linear modelling. RESULTS We included 94 patients, 42 ± 14 years old, 59.6% men and 40.4% women. Follow-up from citrate determination 55 ± 28 months (range 16–119). Baseline data: urea 40.2 ± 12.3, Cr 1.15 ± 0.38 mg/dL, GFR 78 ± 26 mL/min/1.73 m2. Bicarbonate 25.1 ± 2.5 (18.2–29.2) mEq/L. Final GFR: 69 ± 32 mL/min/1.73 m2. GFR variation: −2.23 ± 4.14 mL/min/year (range −13.7 to 10). We classified patients according to urinary citrate tertiles (≤117, 117 to ≤ 303, &amp;gt;303 mg/gCr). GFR was different at baseline (67.5 ± 27.9, 74.3 ± 24.3, 92.4 ± 19.7, respectively, P &amp;lt; 0.001) and at final observation (51.1 ± 31.8; 71.4 ± 30.1; 85.3 ± 24.9, respectively P &amp;lt; 0.001). There were no differences in albuminuria or proteinuria at baseline, but there were differences in uric acid serum levels and urine output. There were no differences in follow-up time. We observed that GFR rate was different according to tertiles: −4.62 ± 3.66, −0.58 ± 2.78 and −1.53 ​​± 4.74 mL/min/year, respectively (P &amp;lt; 0.001). When comparing CKD by stages, we found that patients with citrate ≤ 117 mg/gCr showed higher GFR rates than when they had higher levels: CKD1 −7.74 ± 3.37, CKD2 −4.5 ± 4.4, CKD3 −3.04 ± 1.79 versus citrate patients &amp;gt; 117 mg/gCr with deterioration &amp;lt; 2 mL/min/year (P &amp;lt; 0.05). With multivariate analysis, we found that final GFR was positively associated with baseline GFR and negatively with age, follow-up time and citrate levels ˂ 117 mg/gCr. CONCLUSION Urinary citrate levels decrease as GFR reduction is observed in ADPKD. The reduction of urinary citrate to values ≤ 117 mg/gCr is associated with faster deterioration of renal function in patients with ADPKD.

MO128: Predisposing Metabolic Factors to Urinary System Stone Formation in Patients with Autosomal Dominant Polycystic Kidney Disease

Abstract BACKGROUND AND AIMS The risk of urinary tract stone formation in patients with autosomal dominant polycystic kidney disease (ADPKD) is 20%, twice as high as in the normal population. The most important reason for this increased tendency to stone disease is thought to be anatomic changes in the kidney. To investigate metabolic factors that predispose to urinary system stone formation in individuals with ADPKD. METHOD A total of 180 volunteers who applied to our outpatient clinic between December 2019 and May 2021 were included in the study. Four groups were formed: patients with ADPKD and urinary system stones (ADPKD + STONE) (n = 42), patients with ADPKD but no stones (ADPKD + STONE FREE) (n = 43), stone patients without ADPKD (STONE) (n = 47) and healthy controls (HEALTHY) (n = 48) groups. Spot urine pH, 24-h urine volume, calcium, uric acid, oxalate, citrate, sodium and magnesium parameters were measured. STONE group data were obtained retrospectively. Along with these parameters, serum electrolyte, parathormone (PTH), ferritin, albumin, creatinine, urea and uric acid values were also compared. A P value of &amp;lt;.05 was considered significant for statistical analysis. RESULTS There was no statistically significant difference between the four groups in terms of age and gender (P &amp;gt; .05). The citrate value in 24-h urine was significantly lower in the ADPKD + STONE and ADPKD + STONE-FREE groups than the STONE and HEALTHY groups (P &amp;lt; .05). The citrate value in the 24-h urine was significantly lower in the STONE group than in the HEALTHY group (P &amp;lt; .05). The citrate value in 24-h urine did not differ significantly between the ADPKD + STONE and ADPKD + STONE FREE groups (P &amp;gt; .05). In the ADPKD + STONE and ADPKD + STONE-FREE groups, the 24-h urinary calcium value was significantly lower than the STONE and HEALTHY groups (P &amp;lt; .05). In the STONE group, the 24-h urinary calcium value was significantly higher than the HEALTHY group (P &amp;lt; .05). There was no significant difference in the 24-h urinary calcium value between the ADPKD + STONE and ADPKD + STONE FREE groups (P &amp;gt; .05). The uric acid level in 24-h urine was significantly lower in the ADPKD + STONE and ADPKD + STONE-FREE groups than in the HEALTHY group (P &amp;lt; .05). The uric acid value in the 24-h urine did not differ significantly between the ODPBH + STONE, ADPKD + STONE-FREE and STONE groups (P &amp;gt; .05). The uric acid value in 24-h urine did not differ significantly between the STONE and HEALTHY groups (P &amp;gt; .05). Oxalate, sodium and magnesium values in 24-h urine and 24-h urine volume did not differ significantly between the groups (P &amp;gt; .05). Urine pH value was significantly lower in the ADPKD + STONE, ADPKD + STONE-FREE and STONE groups than in the HEALTHY group (P &amp;lt; .05). The pH value did not differ significantly between ADPKD + STONE, ADPKD + STONE-FREE and STONE groups (P &amp;gt; .05). Serum PTH values were significantly higher in the ADPKD + STONE and ADPKD + STONE-FREE groups than in the HEALTHY group (P &amp;lt; .05). The PTH values did not differ significantly between the STONE and HEALTHY groups (P &amp;gt; .05). PTH values did not differ significantly between ODPBH + STONE, ADPKD + STONE-FREE and STONE groups (P &amp;gt; .05). There was no significant difference between the groups in terms of serum ferritin, sodium, potassium, calcium, phosphorus, magnesium and uric acid values (P &amp;gt; .05). CONCLUSION In our study, 24-h urine citrate level was found to be significantly lower in both ADPKD + STONE and ADPKD + STONE-FREE patients compared to the volunteers in the STONE and HEALTHY groups (P &amp;lt; .05). In conclusion, patients with ADPKD should also be evaluated for hypocitraturia in the outpatient clinic.

Proton pump inhibitors use and risk of incident nephrolithiasis.

Proton pump inhibitors (PPIs) are widely prescribed medications that have effects on both enteric and urinary solute handling with an unknown effect on risk of nephrolithiasis. Our objectives were to examine the association between PPI exposure and incident nephrolithiasis and to determine its effect on 24H urine chemistry. We performed a single-center retrospective study on patients diagnosed with gastroesophageal reflux disease (GERD) without a history of kidney stones. Exposure to PPIs was abstracted, and then subsequent kidney stone diagnoses were identified. Multivariable Cox models with time-varying covariates were used to estimate the hazard of PPI use on incident nephrolithiasis. We used multivariable linear regression to analyze a subset of patients who went through 24-h urine analysis. We identified n = 55,765 PPI-naïve GERD patients without prior kidney stone diagnoses of whom 40,866 (73.2%) were exposed to PPI over a median of 3year follow up. On multivariable analysis, PPI use was associated with higher risk of incident kidney stone diagnoses (HR 1.19, 95% CI 1.06-1.34). Among 593 patients with GERD with 24-H urine data, the PPI-exposed group (n = 307) had significantly lower mean urinary citrate (mean 3.0 vs 3.4mmol, p = 0.029) and urinary magnesium (mean 3.6 vs 4.3mmol, p < 0.001) on multivariable analyses. Exposure to PPIs is associated with an increased risk of kidney stones among patients with GERD. Hypomagnesemia and hypocitraturia associated with PPI exposure may contribute to kidney stone risk.

MP26-01 COMPLETENESS OF 24-HOUR URINE TESTING AMONG US VETERANS WITH URINARY STONE DISEASE

You have accessJournal of UrologyCME1 May 2022MP26-01 COMPLETENESS OF 24-HOUR URINE TESTING AMONG US VETERANS WITH URINARY STONE DISEASE Ryan Hsi, Autumn Valicevic, Sanjeevkumar Patel, John Hollingsworth, and Vahakn Shahinian Ryan HsiRyan Hsi More articles by this author , Autumn ValicevicAutumn Valicevic More articles by this author , Sanjeevkumar PatelSanjeevkumar Patel More articles by this author , John HollingsworthJohn Hollingsworth More articles by this author , and Vahakn ShahinianVahakn Shahinian More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002569.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Contemporary guidelines for the prevention of urinary stone disease (USD) recommend that a 24-hour urine collection be analyzed with a minimum set of urinary analytes. However, unlike a comprehensive metabolic panel, there is no approved set of measurements that a provider can easily order, potentially leading to incomplete testing. To examine this possibility, we analyzed data from the Veterans Health Administration (VHA). METHODS: Using files from the VHA Corporate Data Warehouse (2012 to 2019), we identified a cohort of patients, who primarily use the VHA for their healthcare needs, with at least two outpatient or one surgical encounter for USD. Next, we determined the subset who performed a 24-hour urine collection within 12 months of their index USD encounter. Through Logical Observation Identifiers Names and Codes, we evaluated each collection’s completeness, defined as including all of urine volume, calcium, oxalate, citrate, uric acid, and creatinine. We then fit a multilevel logistic regression model with random effects for facility to evaluate factors associated with testing completeness. RESULTS: In total, 15,660 patients performed a 24-hour urine collection, but nearly half of tests (46.1%) were incomplete. The percentage of complete collections increased over time (43.1% in 2012 to 63.2% in 2019). The facility where a patient was seen mattered. The Figure shows wide variation in unadjusted rates of 24-urine completeness among facilities, ranging from as low as 0% to as high as 98.1%. In the adjusted analysis, there was considerable between-facility variation in 24-hour urine completeness (Median Odds Ratio, 4.98; 95% CI, 3.50-5.50). Collectively, individual facilities contributed almost 46% (ICC, 0.46; 95% CI, 0.35-0.49) to the observed variation in 24-hour urine completeness. Older age, Hispanic ethnicity, and presence of conditions associated with high risk of USD recurrence were significantly associated with a lower odds, whereas female sex and more recent calendar year were associated with a higher odds, of complete testing. CONCLUSIONS: Nearly half of 24-hour urine tests obtained for prevention of USD do not have the minimum set of urinary analytes. These data suggest that addressing the facility level variation in testing completeness may improve the quality of USD care within VHA facilities. Source of Funding: NIDDK R01 DK121709 © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e438 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ryan Hsi More articles by this author Autumn Valicevic More articles by this author Sanjeevkumar Patel More articles by this author John Hollingsworth More articles by this author Vahakn Shahinian More articles by this author Expand All Advertisement PDF DownloadLoading ...

HydroZitLa inhibits calcium oxalate stone formation in nephrolithic rats and promotes longevity in nematode Caenorhabditis elegans

Low fluid intake, low urinary citrate excretion, and high oxidative stress are main causative factors of calcium oxalate (CaOx) nephrolithiasis. HydroZitLa contains citrate and natural antioxidants and is developed to correct these three factors simultaneously. Antioxidants theoretically can prolong the lifespan of organisms. In this study, we preclinically investigated the antilithogenic, lifespan-extending and anti-aging effects of HydroZitLa in HK-2 cells, male Wistar rats, and Caenorhabditis elegans. HydroZitLa significantly inhibited CaOx crystal aggregation in vitro and reduced oxidative stress in HK-2 cells challenged with lithogenic factors. For experimental nephrolithiasis, rats were divided into four groups: ethylene glycol (EG), EG + HydroZitLa, EG + Uralyt-U, and untreated control. CaOx deposits in kidneys of EG + HydroZitLa and EG + Uralyt-U rats were significantly lower than those of EG rats. Intrarenal expression of 4-hydroxynonenal in EG + HydroZitLa rats was significantly lower than that of EG rats. The urinary oxalate levels of EG + HydroZitLa and EG + Uralyt-U rats were significantly lower than those of EG rats. The urinary citrate levels of EG + HydroZitLa and EG + Uralyt-U rats were restored to the level in normal control rats. In C. elegans, HydroZitLa supplementation significantly extended the median lifespan of nematodes up to 34% without altering feeding ability. Lipofuscin accumulation in HydroZitLa-supplemented nematodes was significantly lower than that of non-supplemented control. Additionally, HydroZitLa inhibited telomere shortening, p16 upregulation, and premature senescence in HK-2 cells exposed to lithogenic stressors. Conclusions, HydroZitLa inhibited oxidative stress and CaOx formation both in vitro and in vivo. HydroZitLa extended the lifespan and delayed the onset of aging in C. elegans and human kidney cells. This preclinical evidence suggests that HydroZitLa is beneficial for inhibiting CaOx stone formation, promoting longevity, and slowing down aging.

Urinary Metabolic Disturbances During Topiramate Use and their Reversibility Following Drug Cessation

ObjectiveTo understand the metabolic disturbances of stone formers currently taking topiramate and to examine the reversibility of these disturbances with cessation of the medication. Materials and MethodsAll progress notes written by 5 endourologists from a single academic center were retrospectively reviewed from January 2010 to July 2020 containing the words “topiramate” or “topamax.” Inclusion criteria were age >18 and presence of either a 24-hour urine sample or stone analysis while on topiramate. In addition, a subgroup of 18 patients with 24-hour urine samples before and after stopping topiramate were identified. ResultsA total of 93 patients were identified and included for final analysis. Twenty-four hour urine samples were available in 67 patients and showed mean citrate excretion of 331 ± 322 mg/d, mean pH of 6.6 ± 0.5, and mean calcium phosphate supersaturation of 1.9 ± 1.1. In the subgroup analysis urinary citrate excretion increased from 225 mg/d to 614 mg/d (P <.01) and pH decreased from 6.59 ± 0.54 to 6.33 ± 0.47 (P = .06) after stopping topiramate. In addition, 114 stone events occurred in 73 distinct patients, with 50% of stones either pure or majority (≥50%) calcium phosphate by composition. ConclusionHypocitraturia and elevated pH is seen during topiramate use with resultant higher rate of calcium phosphate stone formation compared to the general population. Stopping topiramate leads to significant increase in citrate excretion and normalization of pH. These metabolic disturbances appear to be reversible with medication cessation.

Comparison of the effects of potassium citrate and hydrochlorothiazide on the ureteral stent encrustation in patients with long stent survival; a single-blinded clinical trial

Introduction: The probability of encrustation after embedding ureteral stent is 9.6% in six weeks, 47.5% in 6 to 12 weeks and 76.3% in more than 12 weeks. Objectives: This study was designed to evaluate the effect of potassium citrate and hydrochlorothiazide on ureteral stent encrustation as a single-blinded clinical trial. Patients and Methods: After embedding ureteral stent in 130 patients, the individuals were randomly divided into two groups using random allocation software. Convenience sampling method was used in this study. One group was given hydrochlorothiazide and potassium citrate, and the other group did not receive any medication. All stents were the same brand and the maximum time of stents being in situ was six weeks. Four to six weeks after stent implantation, patients were referred for stent removal. Then, ureteral stent encrustation was recorded in the two groups according to the visual appearance and the difficulty in stent removing due to stent encrustation. Results: The mean age of the patients was 42.62±14.86 years. Regarding gender, 78 patients (67.8%) were male and 37 patients (32.2%) were female. In this study, 15 patients (13%) had ureteral stent encrustation, of which 13 patients (20%) were in the group without medication and two patients (4%) were in the group who received hydrochlorothiazide and potassium citrate (P = 0.012). Conclusion: The rate of ureteral stent encrustation in the patients who received hydrochlorothiazide and potassium citrate was significantly lower than the patients in the control group. This can be justified by the diuretic properties of hydrochlorothiazide and the reduction of urinary calcium levels. Additionally, high urinary citrate level and induction of urinary alkalization after the administration of potassium citrate. Are the ameliorating factors. Trial Registration: Registration of trial protocol has been approved by Iranian Registry of Clinical Trials (identifier: IRCT20180625040232N3, https://en.irct.ir/trial/46227, ethical code# IR.UMSU. REC.1396.130).

Simultaneous Determination of Oxalate and Citrate in Urine and Serum of Calcium Oxalate Kidney Stone Rats by Ip-Rp Lc-Ms

Simultaneous Determination of Oxalate and Citrate in Urine and Serum of Calcium Oxalate Kidney Stone Rats by Ip-Rp Lc-Ms