Urinary Citrate Levels Research Articles

#2830 Treatment of primary and secondary distal renal tubular acidosis with a prolonged release formulation of potassium citrate and potassium bicarbonate

Abstract Background and Aims Distal renal tubular acidosis (dRTA) is a rare kidney disease. It can be inherited, i.e. primary (PdRTA), or acquired i.e. secondary (SdRTA). Secondary dRTA is more prevalent in the adult population and is usually caused by underlying autoimmune diseases (e.g. Sjogren syndrome). Both forms of dRTA are characterized by alkaline urine, kidney stone formation, nephrocalcinosis, chronic kidney disease, while metabolic acidosis can be variable. The treatment is based on the substitution of alkali substances. Our clinical study aims to describe a cohort of adult dRTA patients (both PdRTA and SdRTA) treated for 18 months by a prolonged-release alkalizing formulation of potassium citrate and potassium bicarbonate, in terms of electrolyte disbalance correction, metabolic control, nephrolithiasis complications and kidney function. Method Data from seven patients with dRTA (3 with PdRTA and 4 with SdRTA, mean age 44 years, women 71%) taking prolonged-release alkalizing formulation of potassium citrate and potassium bicarbonate in our center, were retrospectively collected and analyzed. The patients were previously treated with alkalizing agents (mostly sodium bicarbonate and potassium citrate). Patients were followed up for up to 18 months after inducing prolonged-release alkalizing formulation of potassium citrate and potassium bicarbonate was introduced. Kidney function, metabolic acidosis control (serum bicarbonate), serum electrolytes, urinary calcium excretion, and urinary citrate were measured. Nephrolithiasis complications and patient compliance were also evaluated. The urine and blood samples were analyzed two weeks after introducing the new drug and every 3 months afterward. Data are presented as mean ± standard error of the mean. Student T-test was used to calculate p values. Results The patients were taking on average 48 mEq of the drug (range 32-72 mEq), the dosage remained the same during the follow-up period (p = 0.365). The average follow-up period was 10 months (range 3-18 months). The metabolic acidosis was well controlled (serum bicarbonate was 24 ± 1.71 mmol/l at baseline, 24.4 ± 1.5 mmol/l at the end of follow-up, p = 0.680). Kidney function remained stable (GFR 73.5 ± 22.67 ml/min/1.73 m2 at baseline, 73 ± 22.69 ml/min/1.73 m2 at the end, p = 0.977). Serum potassium was also well controlled (4.07 ± 0.45 mmol/l at baseline, 4.32 ± 0.40 mmol/l at the end, p = 0.344), as well as calcium in 24-hour urine (2.75 ± 0.59 mmol/24-hour urine at baseline, 2.35 ± 0.12 mmol/24-hour urine at the end, p = 0.222). Urinary citrate levels (calculated as citrate/creatinine ratio) remained in the lower part of the reference range during the follow-up period (103.3 ± 68.3 mmol/mol at baseline, 114.6 ± 64.9 mmol/l at the end, p = 0.775). Two patients had acute renal colic caused by nephrolithiasis, without the need for surgical intervention. Safety and adherence to treatment remained good with no gastrointestinal side effects, one patient discontinued the drug due to headaches. Conclusion Our data show that treatment with a prolonged-release alkalizing formulation of potassium citrate and potassium bicarbonate in adult dRTA patients can achieve good control of metabolic acidosis and electrolyte disbalance with stable kidney function without the need to escalate the dose of the drug during the follow-up period. The adherence to the treatment remained good with no gastrointestinal side effects.

#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 < 288 mg/24 h (1 point); oxaluria > 45 mg/L (1 point) and natriuresis > 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 > 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 > 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.

Is the "Pandemic Diet" Nonlithogenic?

Introduction and Objective: The COVID-19 pandemic and worldwide quarantine resulted in major changes in individual lifestyles. In New York State, March 16, 2020, marked the end of in-restaurant dining and a reported shift to more cooking at home. We investigated the 24-hour urine of patients with known history of nephrolithiasis to see if changes during COVID-19 pandemic altered the risk of stone disease. Methods: Retrospectively, patients with history of nephrolithiasis seen for an outpatient visit from April 1, 2020, to December 31, 2020, were studied. All patients had a 24-hour urine study "pre-COVID" defined as before March 16, 2020, "during-COVID" from March 16, 2020, to December 31, 2020; if available, "post-COVID" from January 1, 2021, to October 31, 2022, was also included. Mean study values were compared using paired, two-tailed t-tests. Results: Ninety-three patients (M = 54, F = 39) with a mean age of 60 years were evaluated. Twenty-four-hour urine revealed a significant reduction in urinary sodium (uNa) levels from pre-COVID (166.15 ± 7.51 mEq/L) compared with during-COVID (149.09 ± 7.55 mEq/L) (p = 0.015) and urinary calcium (uCa) levels from pre-COVID (214.18 ± 13.05 mg) compared with during-COVID (191.48 ± 13.03 mg) (p = 0.010). Post-COVID 24-hour urine (N = 73) levels for uNa (138.55 ± 6.83 mEq/L, p = 0.0035) and uCa (185.33 ± 12.61 mg, p = 0.012) remained significantly reduced compared with pre-COVID values, but with no difference compared with during-COVID values. Upon age stratification, this significance was found only in patients younger than 65. There were no significant differences in 24-hour urine total volume, magnesium, or citrate levels. Conclusions: During the COVID-19 lockdown, dietary choices limited to home-cooked meals allowed patients to better identify their food choices. This study demonstrates that home-cooked meals improved urinary parameters minimizing lithogenic risk factors for stone formation, including hypernatriuria and hypercalciuria. That these changes persisted into the post-COVID period may indicate improved dietary practices after the lockdown ended.

Antiurolithiatic effects of Cassia fistula Lin. fruit extracts on ethylene glycol-induced nephrolithiasis in rats.

Urinary stones are a growing disease that results from pathological biomineralization. Cassia fistula Lin. is traditionally used to treat urinary stones. However, no scientific evidence is available to prove its antilithiatic effect. This study evaluates the antilithiatic potential of aqueous and ethanolic extract of Cassia fistula Lin. fruit (Cff) against calcium oxalate kidney stones. Forty-two male Wistar rats were divided into seven groups (n = 6/group): Group I (control), Group II (rats treated with ethylene glycol and ammonium chloride developed nephrolithiasis after 28 days), Group III (lithiatic rats receiving distilled water for 30 days), Group IV and V (lithiatic rats receiving aqueous extract of Cff at doses of 1 and 100 mg/kg body weight for 30 days, respectively) and Group VI and VII (lithiatic rats receiving ethanolic extract of Cff at doses of 1 and 100 mg/kg body weight for 30 days, respectively). Some parameters of urine and serum, and also renal oxidative stress and histopathology were used to determine the antilithiatic effect of aqueous and ethanolic extract of Cff. Therefore, the types of extracts of Cff improved abnormal levels of urine, serum, and renal oxidative stress and histopathology parameters. This antilithiatic effect of aqueous and ethanolic extracts of Cff, can be attributed to the anti-crystallization and antioxidant properties of the extracts and the ability to improve urine and serum biochemistry. RESEARCH HIGHLIGHTS: Ethylene glycol and ammonium chloride-induced urolithiasis, aggregation of calcium oxalate deposits, increase of some urinary and serum parameters, relative kidney weight, kidney size and MDA activity, decrease of some urinary parameters, relative body weight and SOD activity. Aqueous and ethanolic extracts of Cassia fistula Lin. lead to the treatment of urolithic rats by decreasing levels of urinary oxalate, phosphate, urea, serum urea, uric acid, creatinine, calcium, phosphate, MDA, kidney weight and kidney size, increasing levels of urinary calcium, creatinine, magnesium, citrate, body weight and SOD activity in the kidney, eliminating CaOx deposition (esp. ethanolic extract).

A prospective case-control study on the evaluation of oxidative stress in renal stone formers.

Association of increased oxidative stress (OS) with the pathophysiology of renal stone formation has not been explored greatly in the field of urolithiasis. In this prospective case-control study, we measured 24-h urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in patients with urolithiasis and compared them with matched healthy controls. We also measured 24-h urinary uric acid, calcium, oxalate, and citrate levels in patients with renal stone disease and studied their relation with urinary 8-OHdG levels. Seventy-five cases of renal stone disease and 75 well-matched controls were included. Median 24-h urinary 8-OHdG levels were significantly higher in cases compared to controls (7.6 vs. 3.7µg/g of creatinine; p < 0.000). Receiver-operating curve (ROC) analysis for 8-OHdG between cases and controls revealed an area under the curve of 0.90. At 8-OHdG (µg/g of creatinine) value of 5 or more, a sensitivity and a specificity of 84% each were obtained. A positive correlation between 8-OHdG (µg/g of creatinine) and 24-h urinary oxalate level was noted (r = 0.461, p = 0.000). No correlation between 8-OHdG (µg/g of creatinine) and other variables was noted. On multivariate linear regression analysis, we noted 24-h urinary oxalate levels to be an independent predictor of urinary 8-OHdG levels. OS is significantly higher in patients with renal stone diseases compared to healthy controls. Urinary oxalate levels were significantly correlated with urinary 8-OHdG levels.

MP10-12 FOLLOW-UP 24-URINE STUDIES DURING AND POST-COVID-19 PANDEMIC

You have accessJournal of UrologyCME1 Apr 2023MP10-12 FOLLOW-UP 24-URINE STUDIES DURING AND POST-COVID-19 PANDEMIC Jennifer Lu, Brian Shkolnik, Kelley Zhao, Pankti Kothari, Scott Herfel, Hailey Schulsinger, Yefim Sheynkin, and David Schulsinger Jennifer LuJennifer Lu More articles by this author , Brian ShkolnikBrian Shkolnik More articles by this author , Kelley ZhaoKelley Zhao More articles by this author , Pankti KothariPankti Kothari More articles by this author , Scott HerfelScott Herfel More articles by this author , Hailey SchulsingerHailey Schulsinger More articles by this author , Yefim SheynkinYefim Sheynkin More articles by this author , and David SchulsingerDavid Schulsinger More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003225.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In New York State, March 16, 2020 marked the end of any in-restaurant dining due to the COVID-19 pandemic. The general population was forced to do more cooking at home and less dining out. Dietary modifications like this are considered first line therapy for calcium stone formers due to an effort to reduce dietary sodium intake which is known to affect lithogenic risk factors including hypernatriuria and hypercalciuria. This study aims to see if dietary changes made during the pandemic changed the risk of stone disease as evidenced in 24-hour urine studies and if these changes ceased after the end of widespread shutdowns. METHODS: All patients with nephrolithiasis seen for an outpatient visit from April 1, 2020-December 31, 2020 were queried and included if they had a 24-hour urine study pre-COVID (before March 16, 2020) and during-COVID (March 16, 2020-December 31, 2020); a post-COVID study was included if available (January 1, 2021- October 31, 2022). Values were compared using paired, 2-tailed t-tests. RESULTS: 93 patients (54 males, 39 females, mean age 60.1) were studied pre-COVID, during-COVID, and post-COVID time periods with 24-hour urine studies. Stone analysis revealed calcium oxalate (61%), calcium phosphate (15%), uric acid (15%), other (9%). The 24-hour urine revealed a significant reduction in urinary sodium (uNa) and urinary calcium (uCa) in these patients. uNa levels decreased from 166.15±7.5 mEq/L pre-COVID to 149.09±7.6 mEq/L during-COVID (p=0.015) and maintained improved at 138.55±6.83 mEq/L post-COVID era (p=0.0035). uCa levels decreased from 214.18±13.05 mEq/L pre-COVID to 191.48±13.03 mEq/L during-COVID levels (p=0.010) and remained improved at 185.33±12.61 mEq/L post-COVID (p=0.012). There were no significant differences in 24-hour urine total volume, magnesium, or citrate levels. CONCLUSIONS: During the COVID-19 lockdown, dietary choices limited to home cooked meals allowed patients to better identify their food choices. This study demonstrates that known urinary risk factors for lithogenesis, such as urinary sodium and calcium, improved during the lockdown and these improvements were maintained even after restrictions in restaurants were lifted. Moving forward, it will be imperative to monitor patient’s 24-hour urine to ensure these dietary modifications are continued in the post-pandemic era and to see if these improved urinary parameters will impact stone formation in these patients. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e119 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jennifer Lu More articles by this author Brian Shkolnik More articles by this author Kelley Zhao More articles by this author Pankti Kothari More articles by this author Scott Herfel More articles by this author Hailey Schulsinger More articles by this author Yefim Sheynkin More articles by this author David Schulsinger More articles by this author Expand All Advertisement PDF downloadLoading ...

Metabolic stone workup abnormalities are not as important as stone culture in patients with recurrent stones undergoing percutaneous nephrolithotomy

To investigate the association between metabolic urinary abnormalities and urinary tract infection (UTI) and the stone recurrence status in patients undergoing percutaneous nephrolithotomy (PCNL). A prospective evaluation was performed for patients who underwent PCNL between November 2019 and November 2021 and met the inclusion criteria. Patients with previous stone interventions were classified as recurrent stone formers. Before PCNL, a 24 h metabolic stone workup and midstream urine culture (MSU-C) were done. Renal pelvis (RP-C) and stones (S-C) cultures were collected during the procedure. The association between the metabolic workup and UTI results with stone recurrence was evaluated using univariate and multivariate analyses. The study included 210 patients. UTI factors that showed significant association with stone recurrence included positive S-C [51 (60.7%) vs 23 (18.2%), p < 0.001], positive MSU-C [37 (44.1%) vs 30 (23.8%), p = 0.002], and positive RP-C [17 (20.2%) vs 12 (9.5%), p = 0.03]. Other factors were mean ± SD GFR (ml/min) (65 ± 13.1 vs 59.5 ± 13.1, p = 0.003), calcium-containing stones [47 (55.9%) vs 48 (38.1%), p = 0.01], median (IQR) urinary citrate levels (mg/day) [333 (123–512.5) vs 221.5 (120.3–412), p = 0.04], and mean ± SD urinary pH (6.1 ± 1 vs 5.6 ± 0.7, p < 0.001). On multivariate analysis, only positive S-C was the significant predictor of stone recurrence (odds ratio: 9.9, 95% confidence interval [CI] (3.8–28.6), p < 0.001). Positive S-C, and not metabolic abnormalities, was the only independent factor associated with stone recurrence. A focus on preventing UTI might prevent further stone recurrence.

Anti-urolithiatic effect of Cucumis melo L. var inodorous in male rats with kidney stones.

Melon seed extracts have high antioxidant activities and are effective against a variety of diseases, including kidney stones. In kidney stone model rats, the anti-urolithiatic effects of the hydro-ethanolic extract of melon seed and potassium citrate were studied and compared. After urolithiasis induction by ethylene glycol, the extract and potassium citrate were treated orally for 38days concurrent with ethylene glycol. Then, urine and kidney sampling were done, and the urinary parameter levels were measured. The melon and potassium citrate treatments reduced the kidney index, the levels of urinary calcium and oxalate, calcium oxalate deposit numbers, the score of crystal deposits, histo-pathological damages, and the score of inflammation in the kidney sections, while elevating the urinary pH, magnesium, and citrate levels, and also the expression of the UMOD, spp1, and reg1 genes in the kidney of treated animals. The effect of potassium citrate is the same as the effect of melon in treated animals. So, their effects could be by normalizing urinary parameters, reducing crystal deposits, excreting small deposits from the kidney, reducing the chance of them being retained in the urinary tract, and elevating the expression of the UMOD, spp1, and reg1 genes, which are involved in kidney stone formation.

A simple, fast, high-throughput, modified method for the simultaneous determination of citrate and oxalate in a single purified urine sample using two commercially available kits

Background: Urine citrate and oxalate levels are risk markers for renal stone formation. Urine citrate measurements are prone to interferences and linearity issues. This study investigates modification of sample preparation for citric acid assay using the pH adjusted purified urine sample used for oxalate analysis.

The effect of Myrtus communis L. extract on nephrolithiasis model in rats.

Nephrolithiasis is a common urological disease that can lead to renal failure. Oxidative stress has been shown to be a contributing factor for nephrolithiasis and many agents have been studied to prevent and treat oxidative stress-related nephrolithiasis and renal damage. Myrtus communis (MC) extract has been shown to be an important antioxidant in different animal models. In this study, MC extract was administered preventively or therapeutically to rats with kidney stones, and its effectiveness was investigated. Wistar albino rats were divided into four groups (n=8); control (C), ethylene glycol (EG), EG+preventive MC, and EG+curative MC groups. The nephrolithiasis model was created by adding 0.75% EG to drinking water for 8 weeks. Ultimately, 24-hour urine was collected to measure calcium, citrate, and creatinine levels. After decapitation, kidney tissues were harvested for histological analyses, measurement of osteopontin and 8-hydroxydeoxyguanosine (8-OHdG) levels, and N-acetyl-β-glucosaminidase (NAG), myeloperoxidase (MPO) and caspase-3 activities. In 24-hour urine samples, calcium, citrate and creatinine levels were decreased in the EG group, while oxalate levels were increased and in treatment groups these parameters returned to control levels. MPO, 8-OHdG, caspase-3 and NAG activity were significantly increased in tissue and these changes were reversed in both MC groups. Histological findings also supported the biochemical parameters. MC can reduce oxidative stress and histopathological changes in kidney tissues in rat nephrolithiasis model when used as either a preventive or therapeutic agent. If supported with further clinical trials, MC might have clinical implications in preventing oxidative renal cell injury and ultimately kidney stone formation.

Spot Urinary Citrate Normograms in Children

Citrate in the urine inhibits nephrolithiasis, and oral citrate solutions are used to prevent stones forming. The present study aimed to estimate the normograms of the urinary levels of citrate, creatinine, and their ratio in spot urine samples collected from 237 healthy children, aged from 1 month to 14 years. The findings showed the mean, standard deviation, median, and 5th and 95th percentiles of the values and compared them among age groups and between the sexes by using analysis of variance and independent t-tests. Our findings indicate that the ratio of spot urinary citrate to creatinine was higher for children younger than 18 months of age, possibly related to the consumption of dairy protein as their main meal. The 5th percentiles (lower cut off) for spot urinary citrate-to-creatinine ratio, were 915 mg/g for children aged under 18 months, 109 mg/g and 126 mg/g for older boys and girls.

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.

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.

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.

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.

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).

Role of Citrus Fruit Juices in Prevention of Kidney Stone Disease (KSD): A Narrative Review.

To explore the relationship between citrus fruit juices (oranges, grapefruits, and lemonades) and kidney stone disease (KSD). Methods: A systematic review was performed using the Medline, EMBASE, and Scopus databases, in concordance with the PRISMA checklist for all English, French, and Spanish language studies regarding the consumption of citrus fruit juices and the relationship to urinary stone disease. The main outcome of interest was the association of citrus fruit juices with KSD. Results: Thirteen articles met the criteria for inclusion in the final review. Three large epidemiological studies found that grapefruit juice was a risk factor for stone formation, while orange juice did not increase the risk for KSD. Ten small prospective clinical studies found that orange, grapefruit, and lemon juices all increased urinary citrate levels. Only orange and grapefruit juices had an alkalinizing effect and while lemon juice has a protective effect by raising urinary citrate levels, it lacked a significant alkalinizing effect on urine pH. Orange juice and grapefruit juices significantly increased urinary oxalate levels, while orange juice also had a high carbohydrate content. Conclusion: While orange juice seems to play a protective role against stone formation, grapefruit was found to raise the risk of KSD in epidemiological studies but had a protective role in smaller clinical studies. Lemon juice had a smaller protective role than orange juice. Larger amounts of, as well as more accurate, data is needed before recommendations can be made and a high carbohydrate content in these juices needs to be taken into consideration.

Nephroprotective Effect of Functional Beverage of Dolichous Biflorus Seeds on Ethylene Glycol Induced Urolithiasis: A Mechanistic Approach

Calcium oxalate is the most common type of urolithiasis and is suggested due to membrane oxalate transporters dysfunction. This study has used Dolichos biflorus seeds as a functional beverage to explore its bioactive substances’ role on membrane transporters for managing urolithiasis. Urolithiasis model of ethylene glycol induced calcium oxalate crystals in albino Wistar rats was used in this study. Treatment of functional beverage of Dolichos biflorus seeds restored normal blood and urinary oxalate and citrate level and showed anti-urolithiasis activity. Probenecid, a membrane organic anion transporter (Slc26) inhibitor, treatment has abolished anti-urolithiasis activity of functional beverage and suggested Dolichos biflorus produce effect through the restoration of membrane oxalate transporters activity. An oxalate-less diet did not significantly reduce urinary, and plasma oxalate in probenecid treated animals and suggested that dietary oxalate is not primarily involved in calcium oxalate urolithiasis and conditions like hyperoxalemia and hyperoxaluria. Therefore, our findings suggested that endogenous oxalate in conjunction with idiopathic or chronic reduced activity or defective Slc26 transporters due to aging results in calcium oxalate kidney stones. The functional beverage of Dolichos biflorus seeds exhibited anti-urolithiasis activity through improving the activity of Slc26 transporters.

Effect of Hydroalcholic Extract of Allium noeanum Reut. ex Regel on Ethylene Glycol- Induced Kidney Stone in Male Wistar Rats

We want to evaluate the effect of Allium noeanum Reut. ex Regel (Bonsor) known (traditional medicine agent) in calcium oxalate stones in kidney. 36 male rats were divided into 6 groups. I: healthy model + water, II: negative model + 1% ethylene glycol in water, III: 750 mg/kg of total extract +1% of ethylene glycol in water(Prevention), IV: 250 mg/kg flavonoid extract +1% of ethylene glycol in water (Prevention), V: 1500 mg/kg of total extract from 15th day+ 1% of ethylene glycol in water (Treatment), VI: 500 mg/kg of flavonoid extract from 15th of the study + 1% of ethylene glycol in water (Treatment).24-hour urine and blood samples were collected in 30th day for analysis. Pathology of kidneys was checked. Serum urea, uric acid, creatinine and urine calcium and oxalate were significantly increased, urine citrate was decreased in group II Vs I. (P &lt; .05). Extract administration significantly decreased serum creatinine, urea and uric acid. Urine calcium and oxalate significantly decreased in treated groups. Urine calcium levels were significantly decreased in treated rats, but urine citrate levels were increased Vs group II. (P &lt; .05). No crystal accumulation and tubular cast were observed in prevention groups. Hydroalcholic extract of Allium noeanum was able to reduce urine oxalate.

Urinary citrate as a marker of renal function in patients with autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is frequent to find low urinary citrate levels. Recently, it has been suggested that urinary citrate could be a marker of covert metabolic acidosis in chronic kidney disease. Our aim was to analyze relationship between urinary citrate levels, renal function, and serum bicarbonate in ADPKD patients. We determined citrate in 24-h collected urine from ADPKD patients and correlated with glomerular filtration rate (CKD-EPI equation) and serum bicarbonate concentration. We included 120 patients, 60% men, eGFR was 71 ± 32mL/min/1.73 m2. Urinary citrate/creatinine ratio was 195 ± 152mg/gCr (range 1.2-689) with levels significantly higher in females. Urinary citrate lower than 300mg/gCr was present in 75% of patients and when considering chronic kidney stages (CKD), we observed reduced levels in 48.8% in CKD1 stage, in 79.4% in CKD2 stage, in 96.2% in CKD3 stage, and in 94.7% of patients in CKD4 stage. Urinary citrate was correlated with serum creatinine (r = - 0.61, p < 0.001) and eGFR (r = 0.55, p < 0.001) in both gender. We did not find any correlation with serum bicarbonate. Using a general linear modeling analysis, we found as predictors of urinary citrate/creatinine ratio to glomerular filtration rate, gender, and age. Lower levels of urinary citrate were accompanied by a decline in urinary osmolality and in renal excretion of calcium and uric acid. In a subgroup of patients, we measured total kidney volume and we found an inverse correlation with urinary citrate levels that disappeared when it was corrected with glomerular filtration rate. Urinary citrate is very frequently reduced in ADPKD patients being present from very early CKD stages. Their levels in urine are inversely correlated with glomerular filtration rate and it is not related with serum bicarbonate concentration. We think that it would be interesting to study urinary citrate as a marker of chronic kidney disease in ADPKD patients.