Potassium Citrate Therapy Research Articles

Effects of lemon-tomato juice consumption on crystal formation in the urine of patients with calcium oxalate stones: A randomized crossover clinical trial.

Dietary supplementation with citrate-containing juices may serve as an effective alternative to potassium citrate therapy for preventing calcium oxalate stone recurrence. This study was performed to evaluate whether consumption of lemon-tomato juice can decrease the tendency for stone formation in the urine of calcium oxalate stone formers. The study was conducted as a prospective interventional randomized crossover clinical trial with a repeated-measures design. Twenty-two patients with calcium oxalate stones and no metabolic abnormalities in the urine treated with lithotripsy at a tertiary care center from August 2017 to July 2018 were recruited. After a 14-hour overnight fasting, urine samples were collected after the patients consumed either milk only or milk and lemon-tomato juice. Their urine was tested for multiple parameters, including urine pH, specific gravity, calcium-creatinine ratio, and supersaturation with sodium oxalate, followed by optical density measurement via spectrophotometry. There were no significant differences in the background characteristics between the 2 groups. The optical density of the urine samples obtained after consumption of milk only was significantly higher than that after consumption of milk and lemon-tomato juice (mean = 0.131 for milk only vs. 0.053 for milk and lemon-tomato juice, p < 0.001). The urine calcium-creatinine ratio was similar between the groups (mean = 0.141 for milk only vs. 0.076 for milk and lemon-tomato juice, p = 0.019). The addition of lemon-tomato juice as a source of citrate in the diet significantly decreases the established risk factors for calcium oxalate stone formation in patients. This study was prospectively registered at CTRI under number CTRI/2017/04/008312 on April 7, 2017.

Çocuklarda üriner taş hastalığı: Türkiye’deki bir üçüncü basamak merkez deneyimi

Purpose: The incidence of pediatric nephrolithiasis/urolithiasis (NL/UL) has increased in the last few decades due to dietary habits and a sedentary lifestyle. This study aimed to determine the etiological factors and six months of follow-up results of patients with NL/UL in pediatric nephrology and urology clinics in our center. &#x0D; Materials and Methods: Children with NL/UL between December 2018 and December 2020 were enrolled in this study. The medical records were reviewed to collect data about admission complaints, consanguinity, metabolic risk factors for NL/UL, medical treatments, surgical interventions, and presence of stones after 6 months of follow-up.&#x0D; Results: A total of 93 patients (46 male and 47 female) were included in the study. Consanguinity and a positive family history for stones was present in 46.2% and 78.5% of patients, respectively. The urinary metabolic risk factors were hyperuricosuria (11/83, 13.3%), hypercalciuria (12/93, 12.9%), hyperoxaluria (6/51, 11.8%), cystinuria (7/90, 7.8%), and hypocitraturia (2/41, 4.9%). Twenty patients (29.9%) with NL/UL and without cystinuria received potassium citrate therapy. After 6 months of follow-up (n = 27) of these patients, stone progression was not observed in any of the patients who received potassium citrate treatment (n=11) or underwent surgical intervention (n=10). &#x0D; Conclusions: Most patients had a family history of stones. Hyperuricosuria was the most common urinary risk factor for NL/UL. Potassium citrate therapy might be useful to prevent stone progression in patients with NL/UL.

PD21-08 OVER-THE-COUNTER ALKALI AGENTS TO RAISE URINE PH AND CITRATE EXCRETION: A PROSPECTIVE CROSSOVER STUDY IN HEALTHY ADULTS

You have accessJournal of UrologyStone Disease: Medical & Dietary Therapy (PD21)1 Sep 2021PD21-08 OVER-THE-COUNTER ALKALI AGENTS TO RAISE URINE PH AND CITRATE EXCRETION: A PROSPECTIVE CROSSOVER STUDY IN HEALTHY ADULTS Noah Canvasser, Marcelino Rivera, Seth Bechis, Johann Ingimarsson, John Knoedler, Karen Stern, Christa Stoughton, Daniel Wollin, Michael Borofsky, Naeem Bhojani, Marawan El Tayeb, Guido Kamphuis, David Leavitt, Ryan Hsi, and Kymora Scotland Noah CanvasserNoah Canvasser More articles by this author , Marcelino RiveraMarcelino Rivera More articles by this author , Seth BechisSeth Bechis More articles by this author , Johann IngimarssonJohann Ingimarsson More articles by this author , John KnoedlerJohn Knoedler More articles by this author , Karen SternKaren Stern More articles by this author , Christa StoughtonChrista Stoughton More articles by this author , Daniel WollinDaniel Wollin More articles by this author , Michael BorofskyMichael Borofsky More articles by this author , Naeem BhojaniNaeem Bhojani More articles by this author , Marawan El TayebMarawan El Tayeb More articles by this author , Guido KamphuisGuido Kamphuis More articles by this author , David LeavittDavid Leavitt More articles by this author , Ryan HsiRyan Hsi More articles by this author , and Kymora ScotlandKymora Scotland More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002010.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urinary citrate is a potent inhibitor of kidney stones; hypocitraturia is a common abnormality in the recurrent stone former. The American Urological Association guidelines specifically recommend potassium citrate for urinary alkalization based on the significant improvement in urinary parameters, and the reduced risk of recurrent stone disease. However, there is poor adherence to prescribed potassium citrate therapy. More recently, patients have had increased access to alternative over-the-counter alkali preparations. Our goal was to assess the effect of two over-the-counter alkalizing agents on 24-hour urinary parameters in healthy adults without a history of kidney stones. METHODS: Ten healthy volunteers without a history of kidney stones were recruited to complete a baseline 24-hour urinalysis with a four-day diet inventory. Participants were randomized 1:1 to take LithoLyte® (20 mEq two times per day) or KSPtabsTM (1 tablet two times per day) while maintaining the same diet and submit another 24-hour urinalysis. The process was repeated with the other supplement. Urinary parameters including citrate, pH and ammonium were compared to baseline. Side effects of each supplement were elicited with a questionnaire after each urine collection. RESULTS: LithoLyte® intake resulted in a non-significant increase in citrate (597 to 758 mg/day, p=0.058, an increase in urine pH (6.46 to 6.66, p=0.028), and a decrease in urine ammonium (41 to 36 mmol/day, p=0.005) compared to baseline (table 1). KSPtabsTM resulted in an increase in citrate (597 to 797 mg/day, p=0.037) and urine pH (6.46 to 6.86, p=0.037), with a non-significant decrease in ammonium (41 to 34 mmol/day, p=0.059). No significant differences were seen comparing urinary analytes between LithoLyte® and KSPtabsTM supplements. With Litholyte®, no side effects, mild, moderate, and severe side effects were seen in 50%, 40%, 10%, and 0%, respectively. With KSPtabsTM, rates were 60%, 20%, 10%, and 10%, respectively. CONCLUSIONS: In healthy participants without a history of kidney stones, LithoLyte® and KSPtabsTM are effective over-the-counter alkali supplements. Their side effect profiles appear similar to prescription potassium citrate. Source of Funding: This was an investigator-initiated project where the protocol, data collection, statistical analysis and drafting of the manuscript was performed by the authors. The study supplements, Litholyte® and KSPtabsTM, and 24-hour urine testing were funded by the manufacturers © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e377-e377 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Noah Canvasser More articles by this author Marcelino Rivera More articles by this author Seth Bechis More articles by this author Johann Ingimarsson More articles by this author John Knoedler More articles by this author Karen Stern More articles by this author Christa Stoughton More articles by this author Daniel Wollin More articles by this author Michael Borofsky More articles by this author Naeem Bhojani More articles by this author Marawan El Tayeb More articles by this author Guido Kamphuis More articles by this author David Leavitt More articles by this author Ryan Hsi More articles by this author Kymora Scotland More articles by this author Expand All Advertisement Loading ...

The Effect of Potassium Citrate on Overactive Bladder Disease: A Cross-sectional Study.

To show the effect of potassium citrate treatment on overactive bladder disease in patients with kidney stone and overactive bladder symptoms. Experimental study. Department of Urology, Alanya Alaaddin Keykubat University and Department of Urology, Süleyman Demirel University, Turkey, from October 2019 to July 2020. Patients with an indication for starting potassium citrate therapy because of kidney stone, and patients with symptoms of overactive bladder disease were included in the study. At the beginning of the treatment, the overactive bladder-version 8 form was filled and potassium citrate 10 meq 2x2 dose was started to the patients. The effect of potassium citrate on the symptoms of overactive bladder disease was demonstrated by filling the overactive bladder-version 8 form after one month of treatment. A total of 82 people, 36 men and 46 women, participated in the study. Potassium citrate treatment caused a significant increase in urine pH levels (p<0.001). After potassium citrate treatment, there was a significant decrease in the score of the overactive bladder-version 8 form. (p<0.001). A positive correlation was found between age and overactive bladder-version 8 score change (p = 0.004). Potassium citrate can be used in the treatment of overactive bladder disease. The effect of potassium citrate treatment on ameliorating overactive bladder symptoms is more distinct in elderly patients. Key Words: Renal stones, Potassium citrate, Overactive bladder.

Spot urinary citrate-to-creatinine ratio is a marker for acid-base status in chronic kidney disease

Due to multiple compensating mechanisms, the serum bicarbonate concentration is a relatively insensitive marker of acid-base status; especially in chronic kidney disease (CKD). This is a major drawback that impairs the ability to diagnose acid excess or monitor alkali therapy. We postulated that it is more logical to measure the compensatory defense mechanism(s) rather than the defended parameter, which remains normal if the compensation is successful. Therefore, a retrospective cross-sectional study was performed in 1733 stone formers along with a prospective cross-sectional study of 22 individuals with normal kidney function and 50 patients in different stages of CKD. While serum bicarbonate was flat and did not fall below the reference range until near CKD stage 5, citrate excretion (24-hour urinary citrate excretion rate; urinary citrate-to-creatinine ratio, in the retrospective analysis, and spot urinary citrate-to-creatinine ratio in the prospective study) progressively and significantly declined starting from CKD stage 2. Following an acute acid load in 25 participants with a wide range of estimated glomerular filtration rates, the urinary citrate-to-creatinine ratio inversely and significantly associated with acid accumulation, whereas serum bicarbonate did not. We compared changes in serum bicarbonate and urinary citrate-to-creatinine ratio in response to alkali therapy in patients with CKD stage 3 or 4 started on potassium citrate in our kidney stone database. With alkali therapy, there was no change in serum bicarbonate, but the urinary citrate-to-creatinine ratio rose consistently in all patients adherent to potassium citrate therapy. Thus, the urinary citrate-to-creatinine ratio (the defense mechanism) is a potential easily implementable, pragmatic, and a superior parameter to serum bicarbonate (the defended entity) to assess acid-base status, and monitor alkali therapy. Additional studies are needed before a clinical test can be devised.

Predictive Factors for Kidney Stone Recurrence in Type 2 Diabetes Mellitus

ObjectiveTo determine the predictive factors for kidney stone recurrence in type 2 diabetic patients. MethodsA retrospective cohort study was conducted from 2013 to 2019 by using the database of diabetic patients diagnosed with kidney stone disease. The patients were divided into 2 groups according to stone disease status: recurrent stone and nonrecurrent stone. Baseline characteristics were compared and logistic regression was done to assess which variables could predict a stone recurrence. ResultsThere were 1617 type 2 diabetic patients with kidney stone disease, 1244 (77%) did not have a stone recurrence and 373 (23%) had a stone recurrence. Of these patients with recurrent stone, 40% had asymptomatic stones, 43% visited emergency department, and 45% required a surgical intervention. Median time to recurrence was 64 months. Multivariable analysis revealed that body mass index (odds ratios [OR] 1.032, 95% confidence interval [CI] 1.016-1.047), urine pH (OR 0.500, CI 0.043-0.581), HbA1c (OR 1.186, CI 1.012-1.277), diabetic neuropathy (OR 1.839, CI 1.413-2.392), diabetic retinopathy (OR 1.690, CI 1.122-2.546), insulin as well as potassium citrate therapy (OR 0.611, CI 0.426-0.87), and stone with calcium oxalate and uric acid composition (OR 1.955, CI 1.420-2.691 and OR 2.221, CI 1.249-3.949, respectively) are significant predictors for stone recurrence. ConclusionThe severity of diabetes and stone composition are strong predictors for stone recurrence in type 2 diabetic patients, while HbA1c and urine pH are important modifiable factors.

Changes in Some Urinary Variables After Potassium Citrate Therapy In Patients With Recurrent Urinary Stone Disease In Tikrit City, Iraq

Objective: to determine the effect of oral potassium citrate (k-citrate) on urinary calcium, magnesium, volume, and pH in patients with recurrent stone disease.Patients & Method: Interventional clinical trial study was implemented from June 2016 to February 2019 in Tikrit city, Iraq. 94 patients with recurrent urinary stone disease were enrolled in this study. Oral k-citrate therapy was given to patients in a dose of 15 meq three times daily for 2 weeks. Patients instructed for 24 hours urinary collection before and after therapy. Urinary calcium, magnesium, volume, and pH were measured before and after therapy to examine the effect of k-citrate.Results: mean age was 38.5 (SD 17.4) years. Male patients were 64% while 36% of patients were females. Mean urinary calcium level decreased significantly after k-citrate therapy, p value < 0.001. Mean urinary volume and pH increased significantly after therapy, p value < 0.01 and < 0.05 respectively. No significant change was identified in mean urinary magnesium level after therapy, p value = 0.14. No adverse effects related to k-citrate therapy were reported by patients during study period.Conclusion: Urinary volume and pH increased significantly in patients after potassium citrate therapy. Also k-citrate therapy significantly produced marked decrease in urinary calcium level. No change was observed in mean urinary magnesium level before and after k-citrate therapy. No adverse effects related to k-citrate therapy were reported by patients during study period.

Re: The Impact of Potassium Citrate Therapy in the Natural Course of Medullary Sponge Kidney with Associated Nephrolithiasis.

Re: The Impact of Potassium Citrate Therapy in the Natural Course of Medullary Sponge Kidney with Associated Nephrolithiasis.

Impact of potassium citrate on urinary risk profile, glucose and lipid metabolism of kidney stone formers in Switzerland.

BackgroundHypocitraturia and hypercalciuria are the most prevalent risk factors in kidney stone formers (KSFs). Citrate supplementation has been introduced for metaphylaxis in KSFs. However, beyond its effects on urinary parameters and stone recurrence, only a few studies have investigated the impact of citrate on other metabolic pathways such as glucose or lipid metabolism.MethodsWe performed an observational study using data from the Swiss Kidney Stone Cohort. Patients were subdivided into two groups based on treatment with potassium citrate or not. The outcomes were changes of urinary risk parameters, haemoglobin A1c (HbA1c), fasting glucose, cholesterol and body mass index (BMI).ResultsHypocitraturia was present in 19.3% of 428 KSFs and potassium citrate was administered to 43 patients (10.0%) at a mean dosage of 3819 ± 1796 mg/day (corresponding to 12.5 ± 5.9 mmol/ day). Treatment with potassium citrate was associated with a significantly higher mean change in urinary citrate (P = 0.010) and urinary magnesium (P = 0.020) compared with no potassium citrate treatment. Exogenous citrate administration had no effect on cholesterol, fasting glucose, HbA1c and BMI. Multiple linear regression analysis demonstrated no significant association of 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3] levels with urinary citrate excretion.ConclusionPotassium citrate supplementation in KSFs in Switzerland resulted in a beneficial change of the urinary risk profile by particularly increasing anti-lithogenic factors. Fasting glucose, HbA1c, cholesterol levels and BMI were unaffected by potassium citrate therapy after 3 months, suggesting that potassium citrate is safe and not associated with unfavourable metabolic side effects. Lastly, 1,25(OH)2 D3 levels were not associated with urinary citrate excretion.

The impact of potassium citrate therapy in the natural course of Medullary Sponge Kidney with associated nephrolithiasis.

The present study was carried out to evaluate the effectiveness of medical therapy with potassium citrate in preventing calculosis complicating Medullary Sponge Kidney (MSK) without renal acidification defects. In a open, uncontrolled, retrospective analysis, 49 MSK patients with nephrolithiasis without renal tubular acidosis, underwent a complete metabolic evaluation and received potassium citrate therapy 4-6 g/day. The course of stone disease before and after citrate therapy was determined in each patient from a combination of clinical history, past records, radiographs and kidney ultrasound. The rate of new stone formation/pt/yr, of endourological and extracorporeal procedures, of urinary tract infection (UTI) and number of hospitalization before and after medical treatment were calculated. Metabolic anomalies (hypercalciuria, hypocitraturia, hyperuricuria and hyperoxaluria) were present in 83% of the patients. Follow-up before and after alkali citrate therapy was comparable (4.7+/-1.4 and 4.9+/-1.7 years respectively). Medical treatment significantly reduced rates of stone formation from 2.0+/-1.0 to 0.2+/-0.5 pt/yr, ureteroscopy (URS) from 0.9+/0.8 to 0.4+/-0.5 pt/yr, extratracoporeal lithotripsy (ESWL) from 1.1+/-0.8 to 0.4+/-0.6 pt/yr, urinary tract infections (UTIs) from 0.8+/-1.2 to 0.3+/-0.5 pt/yr and hospitalization from 1.1+/-0.6 to 0.2+/-0.3 pt/yr, p < 0.001. This effect was observed also in MSK patients without metabolic anomalies. In 35 patients the asymptomatic disappearance of calcium stones was also observed. Our study documents the effectiveness of potassium citrate therapy in preventing neprolithiasis in MSK patients also in the absence of distal tubular acidosis. It suggests that in MSK patients alkali citrate may promote calcium stone dissolution by oral administration.

Metabolic Characteristics and Risks Associated with Stone Recurrence in Korean Young Adult Stone Patients.

The aim of this study was to assess the metabolic characteristics and risks of stone recurrence in young adult stone patients in Korea. The medical records of 1532 patients presenting with renal or ureteric stones at our stone clinic between 1994 and 2015 were retrospectively reviewed. Patients were grouped according to age (young adult, 18-29 years; intermediate onset, 30-59 years; old age, ≥60 years) at first presentation, and measurements of clinicometabolic characteristics and risks of stone recurrence were compared. Overall, excretion of urinary stone-forming substances was highest in the intermediate onset group, followed by the young adult and old age groups. Importantly, excretion of urinary citrate was lowest in the young adult group. Kaplan-Meier analyses identified a significant difference between the three age groups in terms of stone recurrence (log rank test, p < 0.001). Multivariate Cox regression analyses revealed that age at first stone presentation was an independent risk factor for stone recurrence. Urinary citrate excretion was an independent risk factor for stone recurrence in young adult stone patients. Younger age (18-29 years) at first stone presentation was a significant risk factor for stone recurrence, and urinary citrate excretion was an independent risk factor affecting recurrence in this group. Metabolic evaluation and potassium citrate therapy should be considered for young adult stone patients to prevent recurrence.

MP90-07 THE EFFECT OF POTASSIUM CITRATE ON THE HEALTH-RELATED QUALITY OF LIFE OF STONE FORMERS

You have accessJournal of UrologyStone Disease: Medical & Dietary Therapy1 Apr 2017MP90-07 THE EFFECT OF POTASSIUM CITRATE ON THE HEALTH-RELATED QUALITY OF LIFE OF STONE FORMERS Eric Raffin, Kristina Penniston, Stephen Nakada, Jodi Antonelli, Davis Viprakasit, Timothy Averch, Sri Sivalingam, Roger Sur, Ben Chew, Vincent Bird, Lawrence Dagrosa, Rebecca Smith, and Vernon Pais Eric RaffinEric Raffin More articles by this author , Kristina PennistonKristina Penniston More articles by this author , Stephen NakadaStephen Nakada More articles by this author , Jodi AntonelliJodi Antonelli More articles by this author , Davis ViprakasitDavis Viprakasit More articles by this author , Timothy AverchTimothy Averch More articles by this author , Sri SivalingamSri Sivalingam More articles by this author , Roger SurRoger Sur More articles by this author , Ben ChewBen Chew More articles by this author , Vincent BirdVincent Bird More articles by this author , Lawrence DagrosaLawrence Dagrosa More articles by this author , Rebecca SmithRebecca Smith More articles by this author , and Vernon PaisVernon Pais More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2826AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Potassium citrate has an established role in medical management of stone disease but many patients have reported unwanted side effects, notably gastrointestinal (GI). It is not currently well understood how the benefits of potassium citrate affect patients' health-related quality of life (HRQOL). We sought to evaluate the effect of potassium citrate on patients' stone-related HRQOL. METHODS Utilizing the previously validated Wisconsin Stone-QOL questionnaire (WISQOL), a kidney stone-specific instrument, we analyzed cross-sectional data from patients both new to and already established in stone prevention who were enrolled at sites participating in the North American Stone Quality of Life Consortium. We compared HRQOL in the WISQOL domains of social impact, emotional impact, disease impact, and vitality between patients prescribed potassium citrate and those not. In addition to student's t-test, multivariate linear regression controlling for age, gender, BMI, and number of stone events was performed to determine the strength of any differences found. Additionally, univariate and multivariate logistic regression were used to assess the likelihood of complaints of nausea and stomach upset or cramps between those prescribed and not prescribed potassium citrate. RESULTS 1511 stone formers were included (787 male, 724 female), of whom 258 were on potassium citrate at study enrollment. Patients prescribed potassium citrate scored significantly higher (better HRQOL) in each of the domains. With multivariate analysis, these differences maintained their significance (mean domain scores were higher by 2.5, 2.8, 2.8, 1.3 points, respectively, all p<0.0001). In item-level analysis, patients prescribed potassium citrate were less likely than those not prescribed it to report any nausea, stomach upset or cramps (43% vs 55%, p<0.001). Multivariate logistic regression showed a 40% lower likelihood of having GI complaints among patients prescribed potassium citrate, p=0.001, when controlling for the aforementioned factors. CONCLUSIONS Among chronic stone forming patients, the use of potassium citrate is associated with higher HRQOL across all domains of the WISQOL. Those prescribed potassium citrate appear less likely to endorse GI complaints compared to those not. These findings may be useful when encouraging patients to consider initiating potassium citrate therapy. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1212-e1213 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Eric Raffin More articles by this author Kristina Penniston More articles by this author Stephen Nakada More articles by this author Jodi Antonelli More articles by this author Davis Viprakasit More articles by this author Timothy Averch More articles by this author Sri Sivalingam More articles by this author Roger Sur More articles by this author Ben Chew More articles by this author Vincent Bird More articles by this author Lawrence Dagrosa More articles by this author Rebecca Smith More articles by this author Vernon Pais More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Long-Term Therapy With Wu-Ling-San, a Popular Antilithic Chinese Herbal Formula, Did Not Prevent Subsequent Stone Surgery: A Nationwide Population-Based Cohort Study.

Traditional Chinese herbal medicine (CHM), which is widely used to treat pain and urolithiasis, is a promising therapy for urinary stone prevention. This study investigated the clinical efficacy of a popular CHM, Wu-Ling-San (WLS), in Taiwan for the prophylaxis of recurrent nephrolithiasis as assessed by surgical stone treatment via a nationwide population-based cohort study. The National Health Insurance Research Database, 2000–2010, which included one million patient records. All patients diagnosed with stone disease at the beginning of the study. The matched controls (4-fold the number of WLS patients) were stone patients who did not take WLS. Data analysis included the stone surgeries following the first treatment. We enrolled 11 900 patients with stone disease, and the incidence of stone patients in this database was 1.19%. The prevalence of comorbidities such as benign prostate hyperplasia, chronic kidney disease, diabetes mellitus, and urinary tract infection, but not hypertension, was significantly higher in WLS users. Several patients in both groups were prescribed potassium citrate. The stone treatment rate was significantly higher in WLS users (17.85%) than in the non-WLS users (14.47%). WLS users with an associated comorbidity had a higher treatment rate than the non-WLS users: 21.05% versus 16.70%, respectively. The surgery rate for upper urinary tract stones was higher in WLS users than in the non-WLS users (adjusted hazard ratio, 1.28; 95% confidence interval, 1.08-1.52; P < .05). The stone treatment rate (52.79%) was significantly higher in patients who used a very high amount of WLS (adjusted hazard ratio, 3.02; 95% confidence interval, 2.30-3.98). Stone patients using a high amount of WLS use had a high stone surgical rate. Long-term therapy with WLS did not have a preventive effect on stone surgical treatment. Long-term potassium citrate therapy as a preventive measure appeared to be underutilized in this study.

Potassium citrate decreases urine calcium excretion in patients with hypocitraturic calcium oxalate nephrolithiasis.

Two previous studies (<10 patients each) have demonstrated that alkali therapy may reduce urine calcium excretion in patients with calcium oxalate nephrolithiasis. The hypothesized mechanisms are (1) a decrease in bone turnover due to systemic alkalinization by the medications; (2) binding of calcium by citrate in the gastrointestinal tract; (3) direct effects on TRPV5 activity in the distal tubule. We performed a retrospective review of patients on potassium citrate therapy to evaluate the effects of this medication on urinary calcium excretion. A retrospective review was performed of a metabolic stone database at a tertiary care academic hospital. Patients were identified with a history of calcium oxalate nephrolithiasis and hypocitraturia who were on potassium citrate therapy for a minimum of 3 months. 24-h urine composition was assessed prior to the initiation of potassium citrate therapy and after 3 months of therapy. Patients received 30-60 mEq potassium citrate by mouth daily. Inclusion criterion was a change in urine potassium of 20 mEq/day or greater, which suggests compliance with potassium citrate therapy. Paired t test was used to compare therapeutic effect. Twenty-two patients were evaluated. Mean age was 58.8 years (SD 14.0), mean BMI was 29.6 kg/m(2) (SD 5.9), and gender prevalence was 36.4% female:63.6% male. Mean pre-treatment 24-h urine values were as follows: citrate 280.0 mg/day, potassium 58.7 mEq/day, calcium 216.0 mg/day, pH 5.87. Potassium citrate therapy was associated with statistically significant changes in each of these parameters-citrate increased to 548.4 mg/day (p < 0.0001), potassium increased to 94.1 mEq/day (p < 0.0001), calcium decreased to 156.5 mg/day (p = 0.04), pH increased to 6.47 (p = 0.001). Urine sodium excretion was not different pre- and post-therapy (175 mEq/day pre-therapy versus 201 mEq/day post-therapy, p = NS). Urinary calcium excretion decreased by a mean of 60 mg/day on potassium citrate therapy-a nearly 30 % decrease in urine calcium excretion. These data lend support to the hypothesis that alkali therapy reduces urine calcium excretion.

Distinct Metabolic Characteristics and Risk of Stone Recurrence in Patients With Multiple Stones at the First-time Presentation

To characterize the clinical and metabolic abnormalities of patients presenting with multiple stones and determine their risk of new stone formation. This retrospective case-controlled study consisted of 911 patients who had ureter stones for the first time and 107 age- and sex-matched patients without stones. The patients were classified into 2 groups: those with a single ureter stone (n= 690) and those with 1 or more additional stones somewhere in the ureter or kidney (n= 221). All patients underwent 24-hour urinary metabolic evaluation. The 240 patients (26.3%) who were followed for >12months (median follow-up, 35.0months) were included in recurrence analyses. Stone recurrence was defined as "new stone formation," namely, the radiographic appearance of stones that had not been present in previous examinations. The multiple-stone group had significantly lower urinary citrate excretion than the single-stone (P= .011) and control (P= .003) groups. Compared with the single-stone group, it also had a higher incidence of hypocitraturia (P= .011) and stone recurrence (27 of 84 [32.1%] vs 29 of 156 [18.6%] patients; P= .025). Multivariate Cox regression analyses revealed that stone multiplicity (hazard ratio, 2.343; 95% confidence interval, 1.302-4.220; P= .005) was an independent predictor of recurrent stone formation. Kaplan-Meier curves showed identical results. The patients with multiple stones had distinct metabolic characteristics, particularly hypocitraturia and a significantly higher risk of recurrence than patients with 1 stone. Patients with multiple stones, even if it is their first stone episode, should undergo metabolic evaluation and possibly also potassium citrate therapy to prevent future stones.

2244 TOPIRAMATE RESULTS IN A RAPID AND PROGRESSIVE DECLINE IN URINARY CITRATE OVER 60 DAYS: A PROSPECTIVE STUDY

INTRODUCTION AND OBJECTIVES: Topiramate is commonly prescribed for migraine headaches and, recently, weight loss. It exerts a well-known hypocitraturic effect. We characterized the time course to hypocitraturia, a risk factor for calcium lithiasis. METHODS: Under IRB approval, headache clinic providers offered participation to adult patients starting topiramate; a titrated dosage regimen reaching 100-200 mg/d within 1 month was prescribed. Patients withheld initiation until a baseline 24-h urine collection could be done. After starting topiramate, patients provided 24-h urine collections at 30 and 60 d for comparison. RESULTS: Twelve patients (M:F, 0.71; 38 y) were recruited from 9/2011-4/2012 and contributed complete 24-h urine collections, confirmed by 24-h urinary creatinine excretion. At baseline, 83% (n 10) were normocitraturic (urinary citrate 581 274 mg/d); 2 patients were mildly hypocitraturic (250 39 mg/d). At 30 d, mean urinary citrate excretion decreased nearly 300 mg and averaged 279 121 mg/d; it continued to decrease through 60 d (218 82 mg/d), at which time, 83% (6 of 7 patients with 24-h urine analyses) were hypocitraturic (196 64 mg/d for 6 with hypocitraturia). Paired t-tests confirmed differences in urinary citrate between baseline and 30-d and between baseline and 60-d (p 0.01 and 0.002, respectively) but not between 30 and 60 d, though the 22% decline in mean urinary citrate excretion from 30 to 60 d is nonetheless clincally relevant. Urine pH increased from 6.1 at baseline to 6.6 and 6.5 at 30and 60-d, respectively (p 0.04 for each comparison), increasing brushite supersaturation of urine. No patients reported stone events in the 6-12 month evaluation period. Of 8 hypocitraturic patients offered potassium citrate therapy (30 mEq/d), 4 agreed to initiate it. In the 1 patient from this group who has thus far completed a follow-up 24-h urine collection, urinary citrate excretion increased 102 mg/d within 2 weeks. CONCLUSIONS: Hypocitraturia from topiramate is rapid and progressive. This should be taken into account when starting therapy, particularly in patients with a history of urolithiasis or with identifiable lithogenic risk factors. Potassium citrate should be considered as adjunctive therapy in select individuals, and urinary citrate excretion should be monitored to ensure therapeutic effect.

Cost-effectiveness of the preventive treatment of urolithiasis with potassium citrate

Objectives To determine whether the potassium citrate therapy is more cost-effective than diet alone. Methods Effectiveness was rated in terms of ‘avoided recurrences’ for both interventions. Costs were calculated on the basis of the patient's perspective. The time horizon for this analysis was 3 years, considering the follow-up period for patients included in this clinical trial. Key findings Those patients who did not show evidence of de novo stone images avoided six recurrence episodes by using potassium citrate and a change in diet. In those patients who showed evidence of de novo stone images with either of the two interventions, we assumed that recurrence would not be avoided (0 avoided recurrences). The cost per individual treated with potassium citrate who showed de novo lithiasis was US$2086 while that for untreated individuals who showed de novo lithiasis was US$1096 under the assumption that recurrence would not be avoided in any case with de novo lithiasis. We calculated a cost-effectiveness (C-E) ratio of US$360 for the intervention with potassium citrate and a C-E ratio of US$3795 for the dietary intervention alone. The incremental C-E ratio indicated that it is necessary to pay US$193 for every additional recurrence avoided with potassium citrate. Conclusions Intervention with potassium citrate proved to be more cost-effective than changes to diet alone. Two sensitivity tests proved the robustness of these results.

Pharmacotherapy of urolithiasis: evidence from clinical trials

Urolithiasis is a worldwide problem with significant health and economic burdens. Medical therapy that alters the course of stone disease has enormous medical and financial impact. Urolithiasis is a final manifestation of a broad range of etiologies and pathogenesis. The modest progress in understanding the pathophysiology has hampered successful development of targeted therapy. Current regimens are based mostly on rational alteration of urinary biochemistry and physical chemistry to lower the risk of precipitation. In terms of pharmacotherapy, there are drugs to successfully improve hypercalciuria, hypocitraturia, aciduria, hyperuricosuria, and hypercystinuria. These agents have been proven to be effective in randomized controlled trials in improving urinary biochemical and physicochemical risk factors, as well as clinical outcomes. Although our current regimens have clearly improved the management and lives of stone formers, there are still clearly identifiable immense voids in the knowledge of pathophysiology of stone disease that can be filled with combined basic science and clinical studies.

Patients With and Without Prior Urolithiasis Have Hypocitraturia and Incident Kidney Stones While on Topiramate

To determine the effect of topiramate (TPM) on 24-hour urinary parameters in stone formers. TPM is frequently prescribed for epilepsy, migraine headaches, and eating disorders. Twelve stone-forming patients who were prescribed TPM between 2003 and 2008 were identified from our stone clinic. Of these, 9 patients (M:F, 4:5; 47 ± 7.1 y SEM) underwent a full metabolic workup (UroRisk Diagnostic Profile, Mission Pharmacal Reference Laboratory, San Antonio, TX) and were included for review. Parameters examined include duration and dose of the drug, 24-hour urine calcium, oxalate, citrate, volume, and pH. If available, urine parameters before taking TPM and after either stopping it or receiving potassium citrate therapy were recorded. Mean duration taking TPM was 17 ± 5.2 months (range, 3-43) months and median dose was 100 mg (range, 25-300) daily. Mean urinary citrate excretion was 136 ± 29 mg/d (range, 30-280) in all patients taking the drug. Three patients were either taken off the drug or placed on potassium citrate, resulting in a mean increase in urinary citrate of 374 mg/d (65%). TPM dosage correlated inversely with urinary citrate excretion (Pearson correlation coefficient = -0.73). TPM therapy is associated with a profound, dose-dependent decrease in urinary citrate, leading to increased lithogenic risk. This hypocitraturia persists even after long periods of taking the drug. Urologists should be aware of the stone-forming risk of this medication. Strategies to maintain therapeutic urinary citrate concentrations in patients on TPM are needed.

Fanconi Syndrome and CKD in a Patient With Paroxysmal Nocturnal Hemoglobinuria and Hemosiderosis

Fanconi syndrome and chronic kidney disease associated with paroxysmal nocturnal hemoglobinuria is rarely reported. We describe a 51-year-old woman with glomerular filtration rate decrease and hypokalemia, glucosuria, and proteinuria during a 4-year period. Paroxysmal nocturnal hemoglobinuria was diagnosed 17 years earlier, and she has received multiple blood transfusions because of hemolytic episodes during the last 5 years. Deteriorating kidney function and persistent Fanconi syndrome were accompanied by a progressive increase in serum ferritin levels. Laboratory studies showed proximal renal tubular acidosis, hypophosphotemic hyperphosphaturia, normoglycemic glucosuria, and aminoaciduria. Serologic testing, tumor markers, Bence-Jones protein, and heavy-metal screening results were negative. Abdominal magnetic resonance imaging showed characteristic features of iron deposition in the bilateral renal cortices. Kidney biopsy showed chronic interstitial nephritis with prominent hemosiderin deposition in the proximal tubules. With potassium citrate, calcitriol, and deferoxamine therapy, Fanconi syndrome persisted, but kidney function was stable. Renal hemosiderosis secondary to both chronic repetitive hemolytic episodes and transfusion-related iron overload in patients with paroxysmal nocturnal hemoglobinuria can lead to Fanconi syndrome and chronic kidney disease.