Urinary Citrate Excretion Research Articles

Citrate in autosomal dominant polycystic kidney disease: biomarker or therapeutic agent?

Purpose of review This review highlights the latest findings regarding hypocitraturia in autosomal dominant polycystic kidney disease (ADPKD), from both experimental and clinical studies, exploring the underlying pathophysiology and potential therapeutic approach. Recent findings Experimental studies have shown that the lodging of microcrystals in the tubules can trigger cyst formation and growth in polycystic kidney disease (PKD). ADPKD patients are prone to developing hypocitraturia in early stages, which could predispose to calcium microcrystal formation. Low urinary citrate excretion has been associated with a more rapid decline in eGFR and poorer renal survival in ADPKD patients. Animal studies employing citrate supplementation have shown promising effects on preserving the decline in estimated glomerular filtration rate (eGFR) and cyst growth. Summary Current knowledge suggests that urinary citrate could be incorporated into existing prognostic markers for disease progression and potential adjuvant therapy in ADPKD, but further clinical studies to support such hypothesis must be undertaken.

A Metabolome-Wide Association Study of fruit and vegetable consumption and associations with cardiovascular risk factors: the INTERMAP study

BackgroundEpidemiological evidence linking blood pressure (BP) and body weight-lowering effects with fruit and vegetable consumption mostly relies on self-reported dietary assessment prone to misreport and under- or overestimation of relationships. We characterized objective 24-hr urinary metabolites and a derived metabolite score associated with fruit and vegetable intake and assessed their associations with BP and body mass index (BMI), with validation across cohorts. MethodsWe used untargeted proton nuclear magnetic resonance spectroscopy (1H NMR) of two timed repeated 24-hr urine collections from free-living participants from the US (n=2,032) and the UK (n=449) of the cross-sectional International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP). We evaluated correlations between fruit and vegetable intake assessed by 24-hr dietary recalls with 7,100 1H NMR features, adjusted for confounders and multiple testing. We related identified metabolites and a metabolite score with BP and BMI using extensively adjusted multiple linear regression models. ResultsWe characterized eleven 1H NMR-derived 24-hr urinary metabolites related to fruit and vegetable intake, reproducible across multiple 24-hr urine collections of both cohorts. Proline betaine, citrate, N-methylproline, scyllo-inositol, 2-hydroxy-2-(4-methyl cyclohex-3-en-1-yl) propoxyglucuronide, and proline were associated with fruit intake, specifically with Rutaceae intake, while S-methyl-L-cysteine sulfoxide and S-methyl-L-cysteine sulfoxide metabolite were associated with Brassicacea intake. The metabolite score, explaining 39.8% of fruit and vegetable intake, was inversely associated with systolic BP (-1.65 mmHg; 95% confidence interval (CI): -2.68,-0.62, P<0.002) and BMI (-1.21 kg/m2; 95% CI: -1.62,-0.78, P<0.0001). These associations were to a large extent explained by urinary citrate excretion. ConclusionWe identified 1H NMR-derived urinary metabolites associated with fruit and vegetable consumption, consistent and reproducible between urine collections and across populations. A higher fruit and vegetable-related metabolite score showed associations with lower systolic BP and BMI, mainly mediated by citrate, but would need confirmation in further studies. Study registrationThis study was registered at the clinicaltrials.gov registration (https://clinicaltrials.gov/study/NCT00005271?term=NCT00005271&rank=1) as NCT00005271.

AN IN VITRO EVALUATION OF ANTI-UROLITHIASIS POTENTIAL OF SIDDHA FORMULATION SAGALANOI CHOORANAM USING STRUVITE CRYSTAL GROWTH INHIBITION ASSAY

Renal calculus is a rising concern, with a prevalence of 12% across the world and 12% in India, which is around 2 million people affected by Urolithiasis. The rise in the ratio has been correlated to genetic predisposition, working in high temperatures, high caffeine intake, lack of physical activity, and groundwater consumption. Yet the major risk factor is a diet that consists of excess animal proteins, which reduces urinary PH and citrate excretion, leading to the formation of Renal calculi. The main aim of this article is to evaluate the anti-urolithiatic potential of a polyherbal Siddha formulation Sagalanoi chooranam obtained from the classical Siddha text Brahmamuni Karukidai Soothiram 380. From the results, it was concluded that the drug has a high potential as an alternative for the management of renal calculus in Siddha. The ingredients efficiently manage renal calculus due to their potent anti-urolithiasis activity, diuretic and anti-inflammatory activity as cited in modern research articles and by mitigating azhal and Vata humour as mentioned in classical Siddha texts. The effect of Sagalanoi chooranam on struvite crystal growth inhibition assay through a significant reduction in the crystal size further validates the drug's efficiency in managing Renal calculus. In such a scenario, the Siddha drug Sagalanoi chooranam can be used as an individual drug or alongside Biomedicine in the management of Renal calculi.

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.

MAGNESIUM SUPPLEMENTATION INCREASES URINE MAGNESIUM AND CITRATE IN STONE FORMERS WITH HYPOMAGNESURIA

To compare the effects of magnesium repletion by a foods-alone approach or by magnesium supplementation on urinary magnesium and citrate excretion in patients with urine magnesium <70 mg/day. We reviewed medical records of patients in our stone prevention practice who were advised to start a magnesium supplement (Sup), 250-500 mg/d, or increase dietary magnesium consumption. We included adults with 24h UMg <70 mg, those who received magnesium recommendations (corroborated by the dietitian's clinical notes), and those with a follow-up 24h urine collection ≤18 months. Urine results were assessed by group. Groups [No Sup (n=74) and Sup (n=56)] were not different for age, gender, stone history, malabsorption, or other clinical indices. All patients raised UMg (53 to 69 and 47 to 87 mg/d for No Sup and Sup, respectively); however, the increase was significantly higher in the Sup group. Moreover, while 88% of Sup patients achieved UMg ≥70 mg/d, only 58% in the No Sup group did so. Within-group increases in urine citrate were significant only in the Sup group. Among patients with low UMg, both higher consumption from foods and magnesium supplementation significantly increased UMg. However, those who supplemented were significantly more likely to reach or exceed UMg 70 mg/d and achieved higher mean UMg. The change in urine citrate was significant only among those in the Sup group.

#2827 Beyond the scale: unveiling the kidney stone risk after bariatric surgery

Abstract Background and Aims Nephrolithiasis is a prevalent condition, with calcium oxalate being the primary component found in kidney stones. Both obesity and gastric bypass surgery pose as risk factors for nephrolithiasis. Malabsorptive bariatric procedures alter 24-hour urine profiles, leading to increased urinary oxalate and reduced urinary citrate levels. This study aims to evaluate the risk factors for calcium oxalate lithiasis in a population after gastric bypass surgery at our center. Method We performed a monocentric retrospective study to evaluate hyperoxaluria and urinary lithiasis in patients who underwent gastric bypass surgery between 2020 and 2021. We assessed urinary oxalate excretion, urinary citrate excretion, and urinary sodium excretion between 4 and 28 months after surgery. To confirm the adequacy of the collection, a comparison was made with the expected urinary creatinine value (20 to 25 mg/kg ideal weight for men and 15 to 20 mg/kg ideal weight for women). We developed a risk score: citraturia &amp;lt; 288 mg/24 h (1 point); oxaluria &amp;gt; 45 mg/L (1 point) and natriuresis &amp;gt; 97.75 mmol/24 h (1 point). Patients were classified as without risk (0 points), at low risk (1 point), at high risk (2 points), and at very high risk (3 points). Additionally, the patients’ historical incidence of lithiasis was examined, both preoperatively and postoperatively, using clinical records. Post-surgery assessments included imaging evidence of lithiasis (when available) or clinical episodes of renal colic. Results Fifty-six patients underwent a 24-hour urine collection. Twenty-two were excluded due to incomplete urine collection, determined by the expected urinary creatinine value and a time lapse exceeding 28 months between surgery and analytical assessment. The median time elapsed between surgery and analytical evaluation was 9.5 months [IQR 6.3 - 12] months. A total of 34 patients were included in the study, 8.8% were male and the median age of the patients was 51.5 [IQR 42.3–57.8] years. The median body mass index decreased from 43.1 [IQR 39.7–46.3] kg/m2 before to 31.8 [IQR 28.6–35.7] kg/m2 six months after surgery. The low risk for calcium oxalate lithiasis in the examined patient sample was 52.9% (n = 18); high risk 20.6% (n = 7), no risk 26.5% (n = 9) and very high risk 0%. We detected 3 (8.8%) patients with concentration hyperoxaluria, 20 (58.8%) patients with natriuresis &amp;gt; 97.75 mmol/24 h and 8 (23.5%) patients with reduced urinary citrate levels. All patients exhibited normal kidney function. The median follow-up duration was 27 months. Out of the total number of patients, only 3 reported renal colic episodes, and imaging evidence of lithiasis was found in just 2 of them before surgery. Among those with a risk score &amp;gt; 0, only 1 had a history of lithiasis. Throughout the follow-up period, none of the patients experienced new lithiasis post-surgery. Regarding the limitations of our study, we highlight the relatively brief duration of follow-up, which may pose challenges in comprehensively evaluating outcomes such as lithiasis. Additionally, the absence of imaging screening represents a notable constraint, impeding the comprehensive assessment of patients with asymptomatic lithiasis. Conclusion This study concludes that within the bariatric surgery population, a specific subgroup is at an elevated risk for renal lithiasis. Recognizing this subgroup promptly and instituting heightened preventive measures may prove advantageous within this demographic.

Increased risk of nephrolithiasis: an emerging issue in children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

PurposeTo investigate the incidence of nephrolithiasis in a cohort of children with congenital adrenal hyperplasia (CAH), and to study if there is an association with the metabolic control of the disease.MethodsThis study was designed as a multicenter 1 year-prospective study involving 52 subjects (35 males) with confirmed molecular diagnosis of CAH due to 21-hydroxylase deficiency (21-OHD). Each patient was evaluated at three different time-points: T0, T1 (+6 months of follow-up), T2 (+12 months of follow up). At each follow up visit, auxological data were collected, and adrenocorticotrophic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), Δ4-androstenedione, dehydroepiandrosterone sulfate (DHEAS) serum levels, and urinary excretion of creatinine, calcium, oxalate and citrate were assayed. Moreover, a renal ultrasound was performed.ResultsThe incidence of nephrolithiasis, assessed by ultrasound was 17.3% at T0, 13.5% at T1 and 11.5% at T2. At T0, one subject showed nephrocalcinosis. In the study population, a statistically significant difference was found for 17-OHP [T0: 11.1 (3.0–25.1) ng/mL; T1: 7.1 (1.8–19.9) ng/mL; T2: 5.9 (2.0–20.0) ng/mL, p < 0.005], and Δ4-androstenedione [T0: 0.9 (0.3–2.5) ng/mL; T1: 0.3 (0.3–1.1) ng/mL; T2: 0.5 (0.3–1.5) ng/mL, p < 0.005] which both decreased over the follow up time. No statistically significant difference among metabolic markers was found in the group of the subjects with nephrolithiasis, even if 17-OHP, DHEAS and Δ4-androstenedione levels showed a tendency towards a reduction from T0 to T2. Principal component analysis (PCA) was performed to study possible hidden patterns of associations/correlations between variables, and to assess the trend of them during the time. PCA revealed a decrease in the amount of the variables 17-OHP, Δ4-androstenedione, and ACTH that occurred during follow-up, which was also observed in subjects showing nephrolithiasis.Conclusionsour data demonstrated that children affected with 21-OHD can be at risk of developing nephrolithiasis. Additional studies are needed to clarify the pathogenesis and other possible risk factors for this condition, and to establish if regular screening of kidney ultrasound in these patients can be indicated.

The Association Between &lt;i&gt;Sodium Citrate Cotransporter (NaDC-1)&lt;/i&gt; Gene Polymorphism and Urinary Citrate Excretion in Patients with Calcium-containing Kidney Stones

The Association Between &lt;i&gt;Sodium Citrate Cotransporter (NaDC-1)&lt;/i&gt; Gene Polymorphism and Urinary Citrate Excretion in Patients with Calcium-containing Kidney Stones

Abstract 11900: Potassium Magnesium Citrate is Superior to Potassium Chloride in Reversing Metabolic Side Effects of Chlorthalidone

Thiazide-type diuretics (TD) are the first-line treatment of hypertension in many guidelines because of its consistent benefit in lowering BP and cardiovascular risk. TD is also known to cause excess risk of diabetes mellitus (DM), which may limit its long-term use. Although hypokalemia was thought to be the main mechanism of TD-induced dysglycemia, potassium (K) supplementation alone does not consistently prevent TD-induced elevation in fasting plasma glucose (FPG). In addition to reducing serum K, TD triggers magnesium (Mg) depletion. However, it is unknown if Mg supplementation attenuates metabolic side effects of TD. Accordingly, we conducted a randomized double-blinded clinical trial in 60 hypertensive patients without DM to compare effects of KCl (40 meq daily) vs. KMgCitrate (Cit) powder containing identical amount of K, 20 meq of Mg, and 74 meq of Cit daily during chlorthalidone (CTD) treatment. Each patient received CTD alone (25 mg/day) for 3 weeks prior to randomization. The primary endpoint was the change in FPG after 4-month of treatment from baseline (CTD alone) after adjusting for baseline FPG as a covariate. The mean age of subjects was 59±11 years (45% Female, 30% Black participants). We found that CTD induced a significant rise in FPG, insulin, and a significant fall in serum K and 24-h urinary citrate excretion (all p &lt; 0.05). We found that KMgCit significantly increased serum K, 24-hour urinary Mg, and 24-hour urinary Cit excretion; and attenuated the rise in FPG which was not observed with KCl (Figure 1 A-C). There were no significant differences in liver fat by MRI or fasting plasma insulin between the 2 groups. In conclusion, our study showed beneficial effects of magnesium supplementation in maintaining serum K and reversing effects CTD on plasma glucose, which may improve safety profile and optimize long-term cardiovascular outcomes in hypertensive patients.

Potassium Magnesium Citrate Is Superior to Potassium Chloride in Reversing Metabolic Side Effects of Chlorthalidone.

Thiazide diuretics (TD) are the first-line treatment of hypertension because of its consistent benefit in lowering blood pressure and cardiovascular risk. TD is also known to cause an excess risk of diabetes, which may limit long-term use. Although potassium (K) depletion was thought to be the main mechanism of TD-induced hyperglycemia, TD also triggers magnesium (Mg) depletion. However, the role of Mg supplementation in modulating metabolic side effects of TD has not been investigated. Therefore, we aim to determine the effect of potassium magnesium citrate (KMgCit) on fasting plasma glucose and liver fat by magnetic resonance imaging during TD therapy. Accordingly, we conducted a double-blinded RCT in 60 nondiabetic hypertension patients to compare the effects of KCl versus KMgCit during chlorthalidone treatment. Each patient received chlorthalidone alone for 3 weeks before randomization. Primary end point was the change in fasting plasma glucose after 16 weeks of KCl or KMgCit supplementation from chlorthalidone alone. The mean age of subjects was 59±11 years (30% Black participants). Chlorthalidone alone induced a significant rise in fasting plasma glucose, and a significant fall in serum K, serum Mg, and 24-hour urinary citrate excretion (all P<0.05). KMgCit attenuated the rise in fasting plasma glucose by 7.9 mg/dL versus KCl (P<0.05), which was not observed with KCl. There were no significant differences in liver fat between the 2 groups. KMgCit is superior to KCl, the common form of K supplement used in clinical practice, in preventing TD-induced hyperglycemia. This action may improve tolerability and cardiovascular safety in patients with hypertension treated with this drug class.

Hypocitraturia and Risk of Bone Disease in Patients With Kidney Stone Disease.

Patients with kidney stone disease are at higher risk for bone disease. Hypocitraturia is common in patients with kidney stone disease and a key risk factor for stone recurrence. In this retrospective cohort study, we sought to determine whether hypocitraturia is also a risk factor for incident bone disease in patients with kidney stone disease. We used nationwide data from the Veterans Health Administration and identified 9025 patients with kidney stone disease who had a 24-hour urine citrate measurement between 2007 and 2015. We examined clinical characteristics of patients by level of 24-hour urine citrate excretion (<200, 200-400, and >400 mg/d) and the time to osteoporosis or fracture according to 24-hour urine citrate excretion level. Almost one in five veterans with kidney stone disease and a 24-hour urine citrate measurement had severe hypocitraturia, defined as <200 mg/d. Patients with severe hypocitraturia were at risk for osteoporosis or fracture (hazard ratio [HR] = 1.23; confidence interval [CI] 1.03-1.48), but after adjustment for demographic factors, comorbid conditions, and laboratory abnormalities associated with hypocitraturia, the association was no longer statistically significant (HR = 1.18; CI 0.98-1.43). Our results in a predominantly male cohort suggest a modest association between hypocitraturia and osteoporosis or fracture; there are likely to be other explanations for the potent association between kidney stone disease and diminished bone health. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Effect of preoperative metabolic profiling to reduce the risk of kidneystones after bariatric surgery in patients with a historyofstoneformation.

Roux-en-Y gastric bypass (RYGB) is associated with an increased risk of kidney stone formation. This is not observed after sleeve gastrectomy (SG). Aim of this study was to assess whether preoperative metabolic profiling is helpful in selecting the most optimal bariatric procedure for patients with a kidney stone history. General hospital, the Netherlands. Patients with a kidney stone history and in the run up to bariatric surgery were screened with non-contrast abdominal computed tomography (CT), serum profiling, and 24-hour urine analysis. Those with stones on radiologic imaging and/or high preoperative urinary oxalate were advised to undergo SG instead of RYGB. Pre- and postoperative urine and serum profile differences between both groups were evaluated retrospectively. Postoperatively, RYGB (N = 28, M:F = 8:20) was associated with a 23.5% reduction in urinary volume, a 85% increase in urinary oxalate excretion with a 230% increase in calcium oxalate (CaOx) supersaturation and a 62% decrease in urinary citrate. Although SG (N = 30, M:F = 12:18) was also associated with a reduction in urinary volume, it had no adverse effects on urinary oxalate and citrate excretion, nor on calcium oxalate supersaturation (CaOx-SS). Both RYGB and SG showed favorable effects on postoperative sodium, calcium, uric acid, and phosphate excretion. This study indicates that preoperative metabolic profiling is important to select the optimal bariatric procedure in patients with an a priori increased risk of kidney stone development. These patients should be strongly encouraged to undergo SG instead of RYGB to prevent progressive or recurrent kidney stone disease.

MP10-02 DIETARY INTERVENTION IN ENTERIC HYPEROXALURIA

You have accessJournal of UrologyCME1 Apr 2023MP10-02 DIETARY INTERVENTION IN ENTERIC HYPEROXALURIA William DeFoor, Joonsue Lee, Nehus Edward, Marion Schulte, Sydney Huesman, Ashleigh Libs, and Prasad Devarajan William DeFoorWilliam DeFoor More articles by this author , Joonsue LeeJoonsue Lee More articles by this author , Nehus EdwardNehus Edward More articles by this author , Marion SchulteMarion Schulte More articles by this author , Sydney HuesmanSydney Huesman More articles by this author , Ashleigh LibsAshleigh Libs More articles by this author , and Prasad DevarajanPrasad Devarajan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003225.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Medically complex, gastrostomy-fed children are particularly vulnerable to forming kidney stones. We have previously shown that there are elevated urinary oxalate levels in patients using enteral feeding formulas primarily based on soy protein, a known high oxalate food. Enteric hyperoxaluria may predispose patients to calcium oxalate stones. The objective of this study is assess if targeted dietary intervention decreases urinary oxalate excretion. METHODS: A retrospective cohort study was performed on medically complex children with cerebral palsy and severe developmental delay presenting to a high-volume Pediatric Stone Center with nephrolithiasis from 2015 to 2020. Inclusion criteria included those who underwent a dietary and urinary metabolic evaluation before and after the index visit. Diets were analyzed by a registered dietitian. Urinary metabolites including calcium, oxalate, and citrate as well as the supersaturations of calcium oxalate and calcium phosphate were analyzed via two 24-hour urine collections. Dietary oxalate load was determined by evaluating individual recipes for known high oxalate ingredients or soy-based formulas. Patients were stratified into those on a low versus high oxalate diet. Statistical analysis was performed using paired t-tests. RESULTS: A total of 13 medically complex stone-forming children met inclusion criteria. All patients were non-ambulatory. 11 of 13 (85%) were primarily fed via gastrostomy. Of the 13 patients, 4 were on a low oxalate diet and 9 were found to have a diet of high oxalate foods. The baseline urinary oxalate excretion (26 vs. 71 mg/m2/day, P = 0.001) and supersaturation of calcium oxalate (6.1 vs. 14.3, P=0.01) were lower in those with a low oxalate diet. Four patients on high oxalate diets were targeted for lowering the enteral oxalate load. A follow-up urinary metabolic evaluation was performed a mean of 6.5 months after the dietary intervention. The urinary oxalate level decreased from 71 to 33 mg/m2/day (P=0.049). Urinary excretion of calcium and citrate as well as the supersaturation of calcium phosphate were similar following dietary modifications. CONCLUSIONS: Urinary oxalate excretion and supersaturation of calcium oxalate were elevated in medically complex stone-forming children with high dietary oxalate content. Targeted dietary intervention to reduce the oxalate load in enteral formulas can lead to a substantial decrease in urinary oxalate excretion. Further investigation is required to determine if this leads to lower stone recurrence, hospitalizations, and the need for surgical interventions. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e114 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information William DeFoor More articles by this author Joonsue Lee More articles by this author Nehus Edward More articles by this author Marion Schulte More articles by this author Sydney Huesman More articles by this author Ashleigh Libs More articles by this author Prasad Devarajan More articles by this author Expand All Advertisement PDF downloadLoading ...

Troublesome Teeth, Search for Stones – Enamel-Renal Syndrome

Background: Enamel-renal syndrome (ERS), is a rare autosomal recessive disorder involving family with sequence similarity 20 member A (FAM20A) gene. This unique syndrome is characterized by severe enamel hypoplasia, intrapulpal calcification, nephrocalcinosis, or nephrolithiasis. This case report highlights the early presentation and incidental detection of chronic kidney disease (CKD) in a young child with enamel defects. Clinical Description: A 10-year-old girl, with no significant past or family history, presented with delayed tooth eruption and abnormal shaped teeth. She was detected to have generalized gingival hyperplasia and multiple unerupted teeth. Suspecting amelogenesis imperfecta, she was screened for coexisting systemic conditions. On evaluation, abdominal ultrasound demonstrated bilateral nonobstructive nephrolithiasis. Further renal workup done showed an abnormal creatinine (stage 2 CKD) and mild metabolic acidosis. Reduced urinary citrate excretion with no evidence of hypercalciuria was noted on extensive urine assessment. Genetic testing revealed a novel pathogenic variant in FAM20A, confirming the diagnosis of ERS. Management: The child was initiated on citrate supplements, salt restriction, and adequate hydration. She was advised of dental interventions, including pulp therapy and full-coverage restoration of decayed teeth. The family was counseled about the need for close monitoring of growth, renal function, and progression of nephrolithiasis. Conclusion: Prompt screening for renal associations in oro-dental and systemic disease must be undertaken to ensure early detection of kidney disease and timely institution of appropriate treatment. In children diagnosed to have kidney involvement, the importance of regular follow-up with clinical, biochemical, and imaging modalities, even during adulthood, must be emphasized.

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.

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.

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.

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.

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.