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Background: Although it is a valuable option for children with drug-resistant epilepsy, ketogenic diet (KD) therapy is associated with several side effects. The frequency of kidney stones and risk factors for their development in epileptic children receiving KD is unclear. The aim of this study was to determine the frequency and risk factors for the development of renal stones in children receiving KD therapy., Methods: A total of 95 patients receiving KD were identified. Of these, seven patients were excluded from the study due to the duration of KD being less than 12 months. The remaining 88 children were enrolled in the study., Results: Renal stones were detected in 15 patients (17%), of which 12 (73.3%) received potassium citrate treatment. Two (13.3%) patients needed lithotripsy despite receiving potassium citrate treatment, and one of these, who received potassium citrate treatment for 5 months, developed acute vesicourethral reflux and underwent surgery. No patient discontinued KD due to renal stone development. The serum uric acid concentrations and urine calcium/creatinine ratio did not change significantly over the 24-month follow-up period. Age, gender, etiology, age at seizure onset, duration of KD, mobility status, use of topiramate or zonisamide, and the number of antiepileptic drugs used were not significantly different between patients with and without kidney stones., Conclusion: Renal stone appears to be a common adverse effect of KD therapy. Although adequate hydration and potassium citrate treatment are effective in most patients, lithotripsy and surgery may be required in a minority of patients., Competing Interests: None declared., (Thieme. All rights reserved.)

Oral alkalization with sodium bicarbonate (NaHCO 3 ) or citrate is prescribed for conditions ranging from metabolic acidosis to nephrolithiasis. Although most nephrologists/urologists use this method routinely, extracellular volume (ECV) increase is the main feared adverse event reported for NaHCO 3 . Thus far, no trial has specifically studied this issue in a real-world setting. AlcalUN (NCT03035812) is a multicentric, prospective, open-label cohort study with nationwide (France) enrollment in 18 (public and private) nephrology/urology units. Participants were adult outpatients requiring chronic (>1 month) oral alkalization by either NaHCO 3 -containing or no-NaHCO 3 -containing agents. The ECV increase (primary outcome) was judged based on body weight increase (ΔBW), blood pressure increase (ΔBP), and/or new-onset edema at the first follow-up visit (V1). From February 2017 to February 2020, 156 patients were enrolled. After a median 106 days of treatment, 91 (72%) patients reached the primary outcome. They had lower systolic (135 (125, 141) vs. 141 (130, 150), P = 0.02) and diastolic (77 (67, 85) vs. 85 (73, 90), P = 0.03) BP values, a higher plasma chloride (106.0 (105.0, 109.0) vs. 105.0 (102.0, 107.0), P = 0.02) at baseline, and a less frequent history of nephrolithiasis (32 vs. 56%, P = 0.02). Patients experienced mainly slight ΔBP (< 10 mmHg). The primary outcome was not associated (P = 0.79) with the study treatment (129 received NaHCO 3 and 27 received citrate). We subsequently developed three different models of propensity score matching; each confirmed our results. Chronic oral alkalization with NaHCO 3 is no longer associated with an ECV increase compared to citrate in real-life settings., (© 2021 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: A new prolonged-release formulation of potassium citrate and potassium bicarbonate, ADV7103, has been shown to improve metabolic control, palatability, and gastrointestinal safety in patients with distal renal tubular acidosis (dRTA) when compared to standard of care (SoC) treatments. The present work evaluates safety and efficacy of ADV7103 during 24 months., Methods: Thirty pediatric and adult patients were included in an open-label extension study after a phase II/III trial. Safety and tolerability were assessed. Plasma bicarbonate and potassium levels, as well as urine parameters, were evaluated over time. Acceptability, adherence, and quality of life were also assessed. The evolution of clinical consequences of dRTA in the cohort was explored., Results: There were 104 adverse events (AEs) reported, but only 9 gastrointestinal events observed in five patients (17%) were considered to be related to ADV7103 treatment. There were no AEs leading to treatment discontinuation. Plasma bicarbonate and potassium levels were in the normal ranges at the different visits, respectively, in 69-86% and 83-93% of patients. Overall adherence rates were ≥ 75% throughout the whole study in 79% patients. An average improvement of quality of life of 89% was reported at 24 months of study., Conclusions: Common AEs concerned metabolism and gastrointestinal disorders; the former being related to the disease. Less than half of the gastrointestinal AEs were related to ADV7103 treatment and they were mostly mild in severity. Metabolic parameters were maintained in the normal ranges in most patients. Patient satisfaction was high and adherence to treatment was good and remained stable., Trial Registration Number: Registered as EudraCT 2013-003828-36 on the 3rd of September 2013.

Purpose: To our knowledge it is unknown whether the benefits of medical management of urolithiasis outweigh the potential side effects of the medications used, including potassium citrate and thiazide diuretics. Therefore, we evaluated the relationship between potassium citrate or thiazides and overall stone related health related quality of life., Materials and Methods: Cross-sectional data were obtained on stone forming enrollees in the North American Stone Quality of Life Consortium. We used the WISQOL (Wisconsin Stone Quality of Life) questionnaire to compare health related quality of life between patients treated and not treated with potassium citrate or thiazide type diuretics. Additionally, the likelihood of gastrointestinal complaints was compared between those prescribed and not prescribed potassium citrate. The likelihood of fatigue and sexual complaints was also compared in those prescribed and not prescribed thiazides., Results: Of the 1,511 subjects, including 787 males and 724 females, 279 were on potassium citrate and 238 were on thiazides at study enrollment. Patients prescribed potassium citrate had higher health related quality of life in each domain vs those not prescribed potassium citrate (p <0.001). Patients prescribed thiazides had higher health related quality of life in each domain compared to those not prescribed thiazide (all p <0.01). Those prescribed potassium citrate were less likely than those not prescribed potassium citrate to report nausea, stomach upset or cramps (OR 0.57, p <0.001). Patients prescribed thiazides were less likely than those not prescribed thiazides to report fatigue (OR 0.63, p = 0.004) or reduced sexual interest and/or activity (OR 0.64, p = 0.005)., Conclusions: Among stone formers the use of potassium citrate and thiazides was associated with better health related quality of life across all WISQOL domains without an increased likelihood of gastrointestinal complaints and fatigue or sexual complaints, respectively. These findings may be useful when counseling patients regarding the initiation of potassium citrate or thiazides for medical management of nephrolithiasis., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Patients with cystinuria are often treated with medical alkalization and shock wave lithotripsy, although each treatment is hypothesized to increase the risk of calcium phosphate stones. We performed a multicenter retrospective review to evaluate whether stones of another composition develop in patients with cystinuria and with what frequency., Materials and Methods: We retrospectively reviewed the records of a multi-institutional cohort of patients with cystinuria. We assessed medications, stone analyses, 24-hour urinalyses and types of procedures. We compared patients who formed only cystine stones vs those with noncystine stones., Results: We identified 125 patients from a total of 5 institutions who were followed a mean of 5.2 years (range 0 to 26). Stones with noncystine components were submitted by 37 patients (29.6%). Potassium citrate medication was not associated with a noncystine composition (p = 0.1877). Regarding surgical management 18 patients (13%) underwent at least 1 shock wave lithotripsy session (range 0 to 9) and 79 (63%) underwent percutaneous nephrolithotomy at least once (range 0 to 10). When stratified based on pure cystine vs converted stones, the average total number of shock wave lithotripsy and percutaneous nephrolithotomy procedures was higher in the group with cystine and subsequent noncystine stone compositions (0.94 vs 0.10, p <0.0001, and 1.7 vs 1.5, p = 0.0053, respectively). On logistic regression male gender (OR 3.1, p = 0.0280) and the number of shock wave lithotripsy sessions (OR 3.0, p = 0.0170) were associated with an increased likelihood of the development of stones with a noncystine composition., Conclusions: Stones with noncystine components develop in more than 25% of patients with cystinuria, underscoring the importance of continued stone analysis. In this study prior shock wave lithotripsy was associated with conversion to a noncystine stone composition while urinary alkalization therapy was not associated., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the tolerability of Potassium Citrate (KCit) tablet in patients with kidney stones that were not able to use the powder form of this drug due to unfavorable salty taste and gastrointestinal complications., Materials and Methods: Twenty-three stone formers, with intolerance to potassium citrate powder form, which had referred to Labbafinejad stone preventive clinic (2015), have been included in this study. All of the patients took two Potassium citrate tablets (10 meq), three times a day for two weeks. Spot urine sample and the 24-hour urine collections were performed before and after KCit therapy. In addition, a visual analog taste scale was completed to gauge the taste and palatability of the KCit tablet in comparing with the powder form., Results: All of the patients claimed that they consumed the tablets as prescribed. The urine pH and the 24-hour citrate and potassium were significantly higher after the treatment. In addition, the mean visual analog scale score was significantly improved in KCit therapy with tablet form versus to powder type (good vs. terrible score)., Conclusion: Oral tolerance of KCit therapy is improved with the use of Potassium Citrate tablet, with beneficial effects on 24-hour urine citrate, potassium, and pH.

Background: Nephrolithiasis, or urinary stone disease, in children causes significant morbidity, and is increasing in prevalence in the North American population. Therefore, medical and dietary interventions (MDI) for recurrent urinary stones in children are poised to gain increasing importance in the clinical armamentarium., Objectives: To assess the effects of medical and dietary interventions (MDI) for the prevention of idiopathic urinary stones in children aged from one to 18 years., Search Methods: We searched multiple databases using search terms relevant to this review, including studies identified from the Cochrane Central Register of Controlled Trials (CENTRAL, 2017, Issue 1), MEDLINE OvidSP (1946 to 14 February 2017), Embase OvidSP (1980 to 14 February 2017), International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Additionally, we handsearched renal-related journals and the proceedings of major renal conferences, and reviewed weekly current awareness alerts for selected renal journals. The date of the last search was 14 February 2017. There were no language restrictions., Selection Criteria: Randomized controlled trials of at least one year of MDI versus control for prevention of recurrent idiopathic (non-syndromic) nephrolithiasis in children., Data Collection and Analysis: We used standard methodologic procedures expected by Cochrane. Titles and abstracts were identified by search criteria and then screened for relevance, and then data extraction and risk of bias assessment were carried out. We assessed the quality of evidence using GRADE., Main Results: The search identified one study of 125 children (72 boys and 53 girls) with calcium-containing idiopathic nephrolithiasis and normal renal morphology following initial treatment with shockwave lithotripsy (SWL). Patients were randomized to oral potassium citrate 1 mEq/kg per day for 12 months versus no specific medication or preventive measure with results reported for a total of 96 patients (48 per group). This included children who were stone-free (n = 52) or had residual stone fragments (n = 44) following SWL. Primary outcomes:Medical therapy may lower rates of stone recurrence with a risk ratio (RR) of 0.19 (95% confidence interval (CI) 0.06 to 0.60; low quality evidence). This corresponds to 270 fewer stone recurrences per 1000 (133 fewer to 313 fewer) children. We downgraded the quality of evidence by two levels for very serious study limitations related to unclear allocation concealment (selection bias) and a high risk of performance, detection and attrition bias. While the data for adverse events were incomplete, they reported that six of 48 (12.5%) children receiving potassium citrate left the trial because of adverse effects. This corresponds to a RR of 13.0 (95% CI 0.75 to 224.53; very low quality evidence); an absolute effect size estimate could not be generated. We downgraded the quality of evidence for study limitations and imprecision.We found no information on retreatment rates., Secondary Outcomes: We found no evidence on serum electrolytes, 24-hour urine collection parameters or time to new stone formation.We were unable to perform any preplanned secondary analyses., Authors' Conclusions: Oral potassium citrate supplementation may reduce recurrent calcium urinary stone formation in children following SWL; however, our confidence in this finding is limited. A substantial number of children stopped the medication due to adverse events. There is no trial evidence on retreatment rates. There is a critical need for additional well-designed trials in children with nephrolithiasis.

Rationale: Urinary lithiasis is one of severe postoperative complications in patients undergoing renal transplantation, possibly leading to anuria, urinary infection, or even acute renal failure. Potassium sodium hydrogen citrate (PSHC), a potassium-bearing citrate, is commonly prescribed to prevent stone formation., Patient Concerns: A 25-year-old man (patient 1) and a 31-year-old man (patient 2) receiving renal transplantation for end-stage renal disease (ESRD) were enrolled in this study. They were given 10 g/day of PSHC granules from the ninth day to the 17th day after surgery. Patient 1 presented chest tightness, nausea, muscle weakness, and ascending paralysis on the 10th day. Patient 2 presented weak waves on EGG on the 17th day. Moreover, their serum potassium concentrations (SPCs) were 7.67 and 6.05 mmol/L, respectively., Diagnosis: Acute hyperkalemia., Interventions: Hemo-filtration was performed for patient 1, while patient 2 received 10% calcium gluconate 10 mL, 5% NaHCO3 125 mL, and 10% glucose 500 mL with the addition of 10 units of insulin through intravenous drip., Outcomes: Their SPCs dropped to the normal range., Lessons: Physicians should pay close attentions to potential risks caused by PSHC, and monitor the SPCs to minimize the occurrence of hyperkalemia.

Objective: Diets rich in animal protein, such as the typical American diet, are thought to create a high acid load. An association between acid load and bone loss has led to the idea that providing positive alkaline salt therapy could have beneficial effects on bone metabolism. The objective of this study was to investigate the effects of potassium citrate (K-citrate), 40 mEq daily, over 1 year on bone resorption and formation., Methods: A randomized, double-blind, placebo-controlled trial of 83 women with postmenopausal osteopenia. Levels of bone turnover markers, specifically urinary N-telopeptide of collagen type 1 (u-NTX), amino-terminal propeptide of type 1 procollagen (P1NP), bone-specific alkaline phosphatase (BSAP), and osteocalcin (OC) were compared. Changes in bone mineral density (BMD) were also examined., Results: K-citrate decreased both u-NTX (P = .005) and serum P1NP (P<.001) starting at month 1 and continuing through month 12. No significant change was seen in BSAP or OC. No significant change was seen in lumbar or hip BMD between the 2 groups., Conclusion: In women with postmenopausal osteopenia, treatment with K-citrate for 1 year resulted in a significant decrease in markers of turnover. The effect on markers of bone formation was not consistent. K-citrate may serve as a potential treatment for bone loss that is well tolerated and without any significant known long-term consequences.

Objective: To evaluate the urine metabolic changes induced by sustained potassium citrate (KCit) treatment in patients with either hypocitraturia (HCit) or "unduly acidic urine pH" (UAUpH), and to determine the remission rate in those patients treated for more than 24 months., Methods: We retrospectively reviewed the charts of 215 adult patients with recurrent renal stones whose only urinary metabolic risk factors were either HCit (n = 95) or UAUpH (n = 120) and had been treated with KCit for more than 3 months., Results: In patients with Hcit (55 men and 40 women, mean age was 43 ± 14 years), Kcit therapy (average dose 48 ± 14.7 mEq/d) caused a sustained increase in urinary citrate to normal levels, in urinary potassium and pH and in serum potassium. In patients with UAUpH (73 men and 47 women; mean age 48.7 ± 12 years), Kcit therapy (average dose 42.8 ± 15.5 mEq/d) produced a significant increase in urinary pH, potassium, and uric acid. Remission rate was studied in 35 of these patients, whose median follow-up of 31.6 ± 14.3 months. All of these patients received a mean dose of potassium citrate of 45.4 ± 15.2 mEq/d. In 91% of these patients, there was no stone recurrence, similar for Hcit and UAUpH patients., Conclusions: Treatment with potassium citrate corrects the metabolic abnormalities seen in patients with Hcit and UAUpH. This was associated with a very high remission rate of stone disease., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Medullary sponge kidney is a little known and little understood disease. A patient with a medullary sponge kidney may undergo decades of suffering in the form of infections and pain before any diagnosis is even made. When a diagnosis is made, it is more than likely to be an incidental finding from a test for another problem. However, on diagnosis there are a number of options available to treat this condition. These include non-invasive treatments such as drug therapy, diet or extracorporeal shock wave lithotripsy, to invasive therapies such as percutaneous nephrolithotomy, ureteroscopy and more advanced surgery. The aim of this article is to highlight this little known condition, outline the effects, and discuss the treatment options available to patients.

An 8-year-old girl with left proximal ureteral stone (4 mm) was referred to our hospital to treat with shock wave lithotripsy (SWL). Fifteen days after the first SWL session, a plain film of kidneys, ureters and bladder (KUB) demonstrated a new stone-like opacity (10 mm) on the left kidney location other than previous stone of 4 mm. We counseled with her parents and learned that she took a potassium citrate tablet 2 h before. Potassium citrate is a radio-opaque drug and may cause a stone-like image during the stone management. Urologists should consider this particularity of potassium citrate in patients using this drug to avoid unnecessary interventions. To our knowledge, this is the first case in the literature.

Purpose: We evaluated the effect of calcium citrate supplementation alone or in combination with potassium citrate on the stone forming propensity in healthy postmenopausal women., Materials and Methods: A total of 18 postmenopausal women without stones underwent a randomized trial of 4 phases comprised of 2 weeks of treatment with placebo, calcium citrate (400 mg calcium twice daily), potassium citrate (20 mEq twice daily), and calcium citrate and potassium citrate (at same doses). During the last 2 days of each phase urine was collected in 24-hour pools for complete stone risk analysis., Results: Compared to placebo, calcium citrate increased urinary calcium and citrate but decreased urinary oxalate and phosphate. Urinary saturation of calcium oxalate, brushite and undissociated uric acid did not change. Potassium citrate decreased urinary calcium, and increased urinary citrate and pH. It decreased urinary saturation of calcium oxalate and undissociated uric acid, and did not change the saturation of brushite. When calcium citrate was combined with potassium citrate, urinary calcium remained high, urinary citrate increased even further and urinary oxalate remained reduced from the calcium citrate alone, thereby marginally decreasing the urinary saturation of calcium oxalate. Urinary pH increased, decreasing urinary undissociated uric acid. The increase in pH increased the saturation of brushite despite the decrease in urinary phosphorus., Conclusions: Calcium citrate supplementation does not increase the risk of stone formation in healthy postmenopausal women. The co-administered potassium citrate may provide additional protection against formation of uric acid and calcium oxalate stones.

Background: Potassium citrate is commonly used in combination with a thiazide diuretic in the medical management of recurrent hypercalciuric nephrolithiasis. However, concerns have been raised that administration of this nonchloride potassium alkali with a kaliuretic and natriuretic agent such as thiazide may not be efficacious in correcting or preventing hypokalemia, and may produce hypochloremic metabolic alkalosis. This retrospective analysis was conducted to determine if these two potential complications are encountered in patients on long-term potassium citrate and thiazide therapy., Methods: Data were collected on 95 patients who had been on combination therapy for at least 4 months from the stone clinics of the University of Texas Southwestern Medical Center, Duke University Medical Center, and Ochsner Clinic., Results: Mean serum potassium concentration remained within normal limits without a significant decrease during combined therapy. Serum chloride was significantly lower from pretreatment but by only 1 mEq/L and remained within normal limits throughout treatment. There was a small increase in serum bicarbonate concentration compared to the baseline level of less than 1 mEq/L at 8 to 12 and 18 to 24 months, but not at other treatment periods., Conclusion: Co-administration of potassium citrate did not induce hypokalemia or hypochloremic metabolic alkalosis in our thiazide-treated patient population.

Background: Potassium supplements may cause mucosal damage of the gastrointestinal tract., Aim: To evaluate the effect of a new potassium supplement, potassium-magnesium citrate (K-Mag), on upper gastrointestinal mucosa and to compare it with an older potassium supplement, potassium citrate (Urocit-K)., Methods: A randomized and double-blind study was conducted utilizing 36 healthy adults. Subjects were randomized into three groups: K-Mag (70 mmol/day K, 35 mmol/day citrate and 17.6 mmol/day Mg); Urocit-K (70 mmol/day K and 23.4 mmol/day citrate), and placebo. All subjects took 5 tablets b.d. of the allocated drug and 2 mg t.d.s. of glycopyrrolate for 7 days. On day 8, stool was examined for occult blood, a symptom score was calculated and an oesophagogastroduodenoscopy was performed. Mucosal lesions were scored at five anatomic sites., Results: Demographic characteristics and symptom score were similar in the three groups (< 10% with more than mild symptoms). There were no significant differences in the endoscopic scores at any site examined nor in the total scores among the three groups. Erosion or ulcers were found in 180% of K-Mag, 23% of Urocit-K and 17% of the placebo group., Conclusion: Short-term use of K-Mag does not appear to induce lesions in the upper gastrointestinal mucosa and its oral tolerance is similar to Urocit-K or placebo.

Objective: This study evaluated two possible alternatives of potassium citrate administration-granulate (liquid) and tablet (wax matrix)-versus treatment with diet and/or fluid to prevent recurrence of urinary lithiasis., Methods: The cost-effectiveness of the alternative modalities were analyzed using data from the studies conducted by Barceló (1993), Pak (1985) and Preminger (1985). The variables utilized for effectiveness were 'avoided relapse' and 'avoided intervention'. Since the data from the foregoing studies did not make any distinction between the two alternative forms of potassium citrate administration, the incidence of side effects and the dropout rate were included. These data were obtained from the studies conducted by Barceló (1993). Campoy (1994) and Conte (1994)., Results/conclusion: Potassium citrate is effective in the prevention of recurrence of urinary lithiasis; relapses and interventions were significantly avoided. Both forms of potassium citrate are similarly effective and the only differences found were in regard to the side effects and the dropout rate; however, further studies are warranted to determine the possible differences with more precision. Potassium citrate in granulated form in much more cost-effective than the diet and fluid regimen than the tablet alternative, with a difference significantly in favor of the former in the order of 8:1. Price was the most important variable and therefore it is important to determine the appropriate dosage since it will influence the cost-effectiveness ratio and the allocation of resources.