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Evolution of lithogenic urinary parameters with a low dose potassium citrate treatment.

The changes in some nocturnal urine urolithogenic parameters in response to the extradietary ingestion of 2.16 g potassium citrate (20 meq) after dinner have been determined. The study included 15 patients (hypocitraturic calcium oxalate stone formers). On the basis of the different pH changes three groups have been differentiated. Different kinetics of citrate metabolism can justify the existence of these three groups. In general, a beneficial effect on urolithogenic parameters was confirmed, and a pH control of patients under treatment was recommended.

Adult↗

New drug therapy for kidney stones: a review of cellulose sodium phosphate, acetohydroxamic acid, and potassium citrate.

Kidney stones have an overall incidence of two to three percent in western countries. In many patients, the disease process is difficult to control and recurrence rates are high: 20 to 50 percent over the subsequent ten years. The pathogenesis and standard methods of treatment for the five major types of stones (i.e., calcium oxalate, struvite, calcium phosphate, uric acid, and cystine) are reviewed. Three new drugs are reviewed in the context of their roles in the selective treatment of kidney stones. Cellulose sodium phosphate (Calcibind) is a nonabsorbable ion-exchange resin with a limited indication for the treatment of calcium stones associated with absorptive hypercalciuria Type I. Acetohydroxamic acid (Lithostat) is an urease-inhibitor that is indicated as adjunctive therapy in patients with chronic urea-splitting urinary tract infections and struvite stones. Potassium citrate (Urocit) is an investigational agent that has clinical efficacy in patients with calcium oxalate and calcium phosphate stones who are hypocitraturic. In addition, potassium citrate is an alkalinizing agent that can be used in patients with uric acid stones.

Adult↗

Use of multiple sensitivity measurements and logit statistical analysis to assess the effectiveness of a potassium-citrate-containing dentifrice in reducing dentinal hypersensitivity.

A potassium citrate-SMFP containing dentifrice was tested in a double-blind 8-week clinical trial on subjects with a history of dentinal hypersensitivity. A dentifrice containing SMFP but no potassium salt was used as the control and a 2nd test dentifrice containing potassium nitrate-SMFP was assessed at the same time. The sensitivity of the subjects was evaluated at 0, 3 and 8 weeks using electrical and tactile methods plus a 1-s air blast. The sensitivity scores for each subject at each examination were summarised as a proportion of the examined teeth deemed sensitive. Assessment of any effects of the dentifrices was via an analysis of covariance of the logit transformation of these proportions with the baseline value as the covariate. The use of this novel method of analysis had the advantage of taking into account changes in sensitivity of all of the teeth, both sensitive and non-sensitive, since electrical measurements indicated effects on both. Of the original 120 subjects, 111 completed the trial and the 3 dentifrice groups remained well balanced for age, sex and sensitivity. All 3 dentifrice groups showed statistically significant reductions in sensitivity over the 8 weeks. However, the potassium citrate-SMFP dentifrice was significantly more effective than either the control SMFP dentifrice, or the potassium nitrate-SMFP dentifrice, at reducing sensitivity after 3 weeks, and this difference plus further sensitivity reduction with all 3 dentifrices was observed after 8 weeks.

Adolescent↗

Long-term follow-up of stone formers treated with a low dose of sodium potassium citrate.

We evaluated the clinical efficacy of long-term preventive treatment with a single evening dose of alkaline citrate. Information was collected from the files of 52 recurrent stone formers prescribed a daily intake of 3.75-5 g of sodium potassium citrate (SPC; 14-18 mmol of citrate). The annual and cumulative rates of stone formation and the rate of recurrence were compared before and during the treatment. A comparison was also made between the patients with (Group R) and without (Group NR) recurrent stone formation during treatment in terms of urine composition and previous history of the disease. For all patients who started the treatment, the number of stones was smaller during treatment (period tT) than during a period of the same length immediately before treatment (period tB), but greater than the number formed during a corresponding period immediately after the diagnosis (period tA). Via questionnaire we found low treatment compliance, with only 62% of the patients reporting consistent taking of their medication (Group T). The patients in Group T had a smaller cumulated number of stones during period tT than that during periods tA and tB, but the Kaplan-Meier curve of the fraction of patients remaining stone-free during treatment was almost identical to that recorded in 446 recurrent stone formers without medical treatment. No significant differences were recorded in terms of relevant pretreatment urinary risk factors between Groups T(R) and T(NR), but numerically higher values of calcium oxalate (CaOx) supersaturation and calcium/citrate quotients were observed in Group T(R). When 9 patients with a daily intake of SPC and a citrate excretion below 2.5 mmol/day were compared with 16 hypocitraturic patients only given drinking advice, the cumulated percentages of patients without recurrent stone formation in the 2 groups after 3 years were 44% and 48%, respectively. Although the number of patients in this study was small, our results indicate poor long-term protection from recurrent calcium stone formation when a single evening dose of only 3.75-5 g of SPC was taken. The rate of stone formation was apparently slightly reduced, but the fraction of patients free of recurrence was no different from that in patients without medical treatment.

Citrates↗

Potassium citrate administration ameliorates tubulointerstitial lesions in rats with uric acid nephropathy.

Although controversial, chronic uric acid nephropathy is a tubulointerstitial disease capable of developing renal function loss. On the other hand, potassium citrate (KCi) administration has demonstrated to be effective in calcium as well as uric acid nephrolithiasis therapy. Therefore, the aim of the present study was to evaluate the possible benefit of KCi treatment in the prevention or amelioration of renal interstitial damage in uric acid nephropathy. Two-month-old male Sprague-Dawley rats were divided into 3 groups: G1 hyperuricemic (HU), G2 hyperuricemic + KCi (HU+KCi), and G3 KCi. G1 and G2 were fed on oxonic acid (inhibitor of rat liver uricase), and a uric acid supplement, during 4 weeks. G2 and G3 were given 2% KCi in drinking water, and G1 regular tap water and standard rat chow. At the end of the study, renal tissue was processed for light and electron microscopy and immunostaining by alpha-smooth muscle actin (SMA). Tubulointerstitial lesions and the amount of alpha-SMA immunostaining in renal tissue were evaluated by histomorphometric quantitation. Rats belonging to the hyperuricemic groups treated with KCi (G2) showed fewer tubulointerstitial lesions as follows: % tubular atrophy: 1.7 +/- 0.3 versus 7.2 +/- 1.2, p < 0.05; inflammatory cells infiltrate (number of cells/area): 0.6 +/- 0.1 versus 2.4 +/- 0.2, p < 0.01; % interstitial fibrosis (cortex): 3.3 +/- 0.3 versus 9.3 +/- 0.5, p < 0.05; % interstitial fibrosis (medulla): 5.2 +/- 0.3 versus 21.9 +/- 1.2, p < 0.01, lower albuminuria (32.8 +/- 11.2 mg/day versus 128.5 +/- 10.4, p < 0.01), higher creatinine clearance ( 1.36 +/- 0.02 ml/min versus 0.74 +/- 0.01, p < 0.01 ) and less percentage of alpha-SMA in renal tissue (1.8 +/- 0.1 versus 10.5 +/- 1.4, p < 0.05), when compared with the hyperuricemic group not treated with KCi (G1). These data suggest that KCi administration could provide a substantial benefit in the regard to tubulointerstitial lesion and progressive renal damage.

Animals↗

The effects of a potassium citrate, cetylpyridinium chloride, sodium fluoride mouthrinse on dentine hypersensitivity, plaque and gingivitis. A placebo-controlled study.

Home-use studies on dentine hypersensitivity have most commonly involved toothpastes and rarely have mouthrinses been employed. Potassium and/or fluoride toothpastes have been shown effective in the treatment of dentine hypersensitivity. The aim of this study was to evaluate the effectiveness of a total formulation, containing potassium citrate, sodium fluoride, cetylpyridinium chloride mouthrinse compared to the base rinse minus actives in the reduction of dentine hypersensitivity. The study was a randomised placebo controlled, double blind parallel design. At a screening visit, 90 adult subjects were recruited who were suffering from dentine hypersensitivity from at least 1 tooth responding to tactile stimulation (45gm pressure) and had at least 2 teeth responding to evaporative stimulation (air blast). During a washout period of 28 days and throughout the 56-day study period, subjects used a soft filament toothbrush and standard fluoride toothpaste. At baseline (day 1), threshold sensitivities to incremental tactile (10 g to 70 g) and evaporative stimuli were determined. Gingival health was assessed by recording bleeding on probing at 25 g pressure at mesiobuccal and lingual sites. Plaque scores from buccal and lingual surfaces of disclosed teeth were also measured. Subjects then used the prescribed rinse, 10 ml for at least 30 s after brushing 2x per day returning on days 28 and 56 for rescoring of sensitivity, gingivitis and plaque. Data from 88 subjects were used with the intent to treat analyses and 83 in the completely evaluable analyses. Groups were well balanced for demographic data and product returns suggested good compliance. Both groups showed highly significant improvements in tooth sensitivity. The pattern was for greater improvement in the test compared to the control group (statistically significant for the plaque score), whereas bleeding scores, already low, showed no change in either group. By definition, the placebo rinse could not have exerted any therapeutic action; the study therefore provides clear direct evidence as to the magnitude (30%-40%) of the little studied, but assumed, placebo response in dentine hypersensitivity trials.

Adolescent↗

A comparison of a reformulated potassium citrate desensitising toothpaste with the original proprietary product.

OBJECTIVES: The recent tendency for toothpaste manufacturers to combine active ingredients for benefits to a number of oral problems requires that such combinations do not vitiate the action of any one agent. The aim of this study was to compare the desensitising effects of a modified formulation with the established product. MATERIALS AND METHODS: The study was a randomised, double blind, two treatment parallel design comparing an existing potassium citrate toothpaste product (Positive Control) with the same formulation to which triclosan and zinc citrate had been added (Test). A total of 56 subjects with dentine hypersensitivity (DH) completed the 8 week study period. At baseline, days 14 and 56 visual analogue scale scores were recorded by the subjects in response to air evaporative and cold water stimuli. RESULTS: Both groups showed improvements, mostly statistically significant, from baseline to day 14 and through to day 56. Most data favoured the Test paste but differences were, for the most part, not significant. CONCLUSIONS: It is concluded that the addition of known anti-plaque agents to an established potassium salt based desensitising toothpaste did not adversely affect the activity of the product in the treatment of DH.

Anti-Infective Agents, Local↗

Agglomeration inhibition reflected stone-forming activity during long-term potassium citrate therapy in calcium stone formers.

OBJECTIVES: The agglomeration of preformed crystals of calcium oxalate has been hypothesized to be the rate-limiting step in renal stone-forming activity (SFA). The effect of urine on the in vitro inhibition of agglomeration of seed crystals of calcium oxalate monohydrate, designated [tm], has been used to monitor SFA in calcium oxalate stone formers (CaOxSF). The objective of the present study was to determine whether [tm] could be used to help monitor the long-term effectiveness of oral potassium citrate therapy (K-Cit-Rx) in CaOxSF. METHODS: Clinic and radiographic (or ultrasound) reports were evaluated for 80 patients, aged 20 to 72 years, 55 men and 25 women, who were treated with oral K-Cit for recurrent calcium oxalate urolithiasis at the Ochsner Stone Clinic between January 1992 and July 1996. Seventy-five of these patients had at least one 24-hour citrate excretion rate of less than 3.0 mm/day before or after K-Cit-Rx. SFA graded on a scale of -2 to +2 by radiographic criteria was combined with information on stone passage to evaluate clinical stone status, and 24-hour urine collections were evaluated for volume, pH, calcium, citrate, uric acid, oxalate, creatinine, and [tm] on free diet before and after 6 to 53 months of K-Cit-Rx. Historical information on procedures performed for urolithiasis before and on K-Cit-Rx was also reviewed. RESULTS: K-Cit-Rx resulted in increased urine pH (P <0.0001) and decreased calcium (P=0.0475), [tm] (P=0.0045), number of stones passed per year (P=0.0016), and remedial procedures per year (P <0.0001). Patients taking allopurinol in addition to K-Cit required higher doses (P <0.0001) of K-Cit to control their disease, had lower pretreatment urine pH (P=0.0493), and showed greater increase in urine citrate (P=0.0092) than those on K-Cit alone. Those taking high-dose K-Cit were younger (P=0.0363) and showed greater decrease in SFA (P=0.0005) than those taking lower doses. A small group of 10 medication refractory patients, who retained (n=9) or increased (n=1) their stone burden during K-Cit-Rx, was identified. Compared with the medication-responsive group, the refractory patients were older (P=0.0124), and had greatly increased SFA (P <0.0001) and higher (P=0.0347) urine pH before and during (P=0.0173) treatment (data not shown). CONCLUSIONS: The data confirm that [tm] can be used not only to verify previously documented stone formation rate but also to help evaluate the long-term effectiveness of therapy. In this report, changes in [tm] after K-Cit-Rx reflected decreased stone formation rate and decreased remedial procedures.

Adult↗

The efficacy of potassium citrate based medical prophylaxis for preventing upper urinary tract calculi: a midterm followup study.

PURPOSE: We examined the efficacy of potassium citrate based medical prophylaxis for preventing upper urinary calculous recurrence, and compared it with the stone recurrence rate in patients who only received intermittent or no medical prophylaxis. MATERIALS AND METHODS: We retrospectively reviewed the records of 493 patients with upper urinary calculi, of whom 237 men and 76 women with a mean age of 56.1 and 51.4 years, respectively, were enrolled in the study. Of the 313 participants 64 (group 1, 20.4%) received regular medical prophylaxis for 24 to 42 months (mean 27.8), 80 (group 2, 25.6%) received intermittent medical prophylaxis for 1.5 to 19 months (mean 7.9) and 169 (group 3, 54%) did not receive any medical prophylaxis. RESULTS: At midterm followup of 24 to 60 months 107 patients (34.2%) had stone recurrence. In group 1 the stone recurrence rate was 7.8%, which was significantly less (p <0.001) than in groups 2 (30%) and 3 (46.2%). Similarly new calculous events in patients with a history of multiple stone recurrence were less frequent in group 1 than in groups 2 and 3 (9.7, 47.4 and 52.2%, respectively, p <0.001). Multiple stone recurrence history, hypercalciuria, hyperuricosuria and calcium oxalate dihydrate calculi were independent risk factors for stone recurrence. CONCLUSIONS: Regular medical prophylaxis may effectively prevent stone recurrence regardless of previous treatment modalities, stone composition, metabolic abnormalities and stone-free status. Cost effectiveness, patient compliance and gastrointestinal upset may limit patient acceptability and clinical use of medical prophylaxis. However, patients with a history of multiple stone recurrence, calcium oxalate dihydrate stones, hypercalciuria and hyperuricosuria benefit from regular medical prophylaxis.

Adult↗

Dietary potassium citrate does not harm the pcy mouse.

Formation of multiple cysts in the kidneys occurs in several inherited diseases and often leads to terminal kidney failure. Because there is no definitive therapy to halt or slow the progression of renal cystic disease in people, numerous studies have examined possible therapies in animal models. Autosomal-dominant polycystic kidney disease (ADPKD) in the Han:SPRD rat is ameliorated when alkalinizing citrate salts are provided in drinking solutions. By contrast, pcy mice with cystic disease fare worse with the same treatment. We tested the hypothesis that pcy mice ingesting citrate salts in the feed would not be adversely affected by this treatment. Male homozygous pcy mice were given regular feed or 6% potassium citrate-supplemented feed and ad libitum access to water starting at 3 weeks of age. The survival curves of the treated and untreated mice were not significantly different. We conclude that treatment with potassium citrate in the feed does not affect the progression of renal cystic disease in the pcy mouse. This model closely resembles human adolescent nephronophthisis (NPHP3). Based on these findings, citrate treatment cannot be recommended for NPHP3. The fact that it did no harm, however, removes a significant barrier to its consideration as a therapy for ADPKD.

Animals↗

A long-term study on the efficacy of a herbal plant, Orthosiphon grandiflorus, and sodium potassium citrate in renal calculi treatment.

The study was performed to compare the efficacy of a herbal plant, Orthosiphon grandiflorus (OG), and the drug sodium potassium citrate (SPC) in treatment of renal calculi. Forty-eight rural stone formers identified by ultrasonography were recruited and randomly assigned to two treatment groups (G1 and G2). For a period up to 18 months, subjects in G1 received 2 cups of OG tea daily, each tea cup made from an OG tea bag (contained 2.5 g dry wt), and G2 received 5-10 g of granular SPC in solution divided into three times a day. Once every 5 to 7 weeks, subjects were interviewed, given an additional drug supply, administered a kidney ultrasound and had spot urine samples collected for relevant biochemical analysis. From the recorded ultrasound images, rates of stone size reduction per year (ROSRPY) were calculated. The mean ROSRPY was 28.6+/-16.0% and 33.8+/-23.6% for G1 and G2, respectively. These two means were not significantly different. ROSRPY values of G1 and G2 were combined and divided into three levels: Level A (ROSRPY > mean + 0.5 SD), Level M (ROSRPY = mean +/- 0.5 SD) and Level B (ROSRPY < mean - 0.5 SD). Dissolution of stones was least in Level B which was related to higher excretions of Ca and uric acid in the urine. After treatment, 90% of the initial clinical symptoms (ie back pain, headaches and joint pain) were relieved. Fatigue and loss of appetite were observed in 26.3% of G2 subjects. Our study indicates that treatment of renal calculi with OG tea is an alternative means of management. Further investigation is needed to improve dissolution of stones with a low ROSRPY.

Adult↗

[Biochemical effects of potassium citrate in the treatment of calcium oxalate lithiasis].

The serum and urinary biochemical changes observed one month and six months after oral potassium citrate therapy (600 mEq/day) in 119 patients with calcium oxalate calculi were compared with those of 16 untreated cases with lithiasis. The patients that received treatment were previously divided into two groups: group A comprised 61 hypocitraturic patients and group B comprised 58 patients with other urinary disorders who were normo or hypocitraturic. The urinary pH increased by approximately half a point in both treated groups. In group A calciuria increased slightly from 180 +/- 8 to 216 +/- 10 mg/24 h but remained within the normal ranges. Creatinuria, oxaluria, uricosuria and diuresis showed no changes. Citraturia increased very significantly in both groups and more markedly in the hypocitraturic group of patients (from 198 +/- 13 to 476 +/- 35 mg/24 h). The LRC (lithogenic risk coefficient = Ca/Cit x Diu) dropped by 50%. The patients tolerated the treatment regimen well; of the 119 treated patients, only 11 abandoned treatment due to GI intolerance.

Adult↗

Combined treatment of medullary sponge kidney by EDTA potassium citrate and extracorporeal shock wave lithotripsy.

A case of successful renal calculus dissolution by the combined treatment which consists of irrigation with ethylenediaminetetraacetic acid (EDTA), potassium citrate, and extracorporeal shock-wave lithotripsy (ESWL) is described here. Renal irrigation via nephrostomy, which was the main treatment, was attempted on a 34-year-old Japanese male who had bilateral nephrocalcinosis caused by type 1 renal tubular acidosis associated with an impacted calculus in the right ureter. Finally, most of the calculi have been dissolved within 1 year.

Adult↗

Effects of acute oral sodium potassium citrate load in healthy males--outlook for treatment of patients with calcium-containing renal stones.

The acute effects of a single (5 g) oral load of sodium potassium citrate (SPC), given together with a liquid test meal, were studied in 6 healthy male volunteers with respect to changes in serum citrate, blood acid base status, urine pH, citrate, calcium and minerals, and oxalate, as well as the calculated relative supersaturation of urine with several stone-forming phases, and the associated crystalluria. It was found that, apart from making the urine more alkaline, SPC induces mild compensated metabolic alkalosis, increases serum and urinary citrate, and reduces fractional urinary calcium excretion, but leaves urinary oxalate and the accompanying crystalluria unchanged. Except for the increase in urinary supersaturation with hydroxyapatite, the supersaturation of other important stone-forming constituents is statistically unchanged. In addition, there are indications that SPC reduces postprandial intestinal calcium absorption without affecting serum parathyroid hormone and 1,25-dihydroxyvitamin D. It is concluded that there is a spectrum of acute effects of oral SPC that may warrant long-term trials on this medication in the metaphylaxis of calcium-containing urinary stones.

Adult↗

The in-vivo effect of sodium-potassium citrate on the crystal growth rate of calcium oxalate and other parameters in human urine.

In this study, an efficient microtechnique (gel crystallization method) was used to investigate the in-vivo effect of sodium-potassium citrate on the crystal growth rate of calcium oxalate (Vcr) in human urine samples of 6 healthy volunteers. With a daily dose of 3 X 11 mmol of alkali citrate, Vcr decreased by 70%. This could have been due to the decrease of calcium excretion, which caused 50-60% of the total change, and to the increase of citrate and pH, each contributing about 20-25% to the decline of Vcr. The findings explain the clinical advantages of alkali citrates in the prevention of recurrent calcium oxalate stone formation.

Adult↗

Impact of sodium-potassium citrate therapy on the circadian rhythm of urinary uric acid and urate saturation in normal individuals.

The circadian rhythm of the urinary saturation of uric acid, sodium acid urate, and ammonium acid urate was studied in 5 normal healthy male volunteers before and during 5 days of treatment with sodium-potassium citrate (1 g t.i.d., 1 g q.i.d., or 3 g t.i.d.). Urinary saturation was estimated on the relative supersaturation scale of Marshall and Robertson. Uric acid relative supersaturation varied during the day (mean +/- SD: -1.297 +/- 1.763) and peaked above the formation product between 5:30 and 8:00 am. The peak level was reduced (but not significantly) by each treatment regimen in comparison with the control day. Overall, critical supersaturation with uric acid was noted in 46 (13%) out of 345 urine specimens, occurring mostly (83%) between 5:30 and 8:00 am. The sodium acid urate relative supersaturation also varied during the day (mean +/- SD: 0.329 +/- 0.305) and peaked below the formation product between 8:00 and 10:30 am. It was increased by each regimen (significantly by the 3 g t.i.d. regimen), but mostly remained in or below the metastable zone. The ammonium acid urate relative supersaturation also varied (mean +/- SD: 0.087 +/- 0.301) and peaked below the formation product between 5:30 and 8:00 am. The level was decreased by each regimen and remained in or below the metastable zone throughout the day. In conclusion, the early morning period was the time with the highest risk of urinary uric acid supersaturation, but this supersaturation could be reduced (although not significantly) by treatment with alkali citrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Calciuric effects of short-term dietary loading of protein, sodium chloride and potassium citrate in prepubescent girls.

OBJECTIVE: Studies using adult human subjects indicate that dietary protein and sodium chloride have negative effects on the retention of calcium by increasing urinary calcium excretion, while alkaline potassium improves calcium retention along with decreasing urinary calcium losses. This study investigated the effect of these dietary factors on acute urinary calcium excretion in 14 prepubescent girls age 6.7 to 10.0 years. METHODS: Subjects provided a fasting urine sample then consumed a meal containing one of five treatments: moderate protein (MP) providing 11.8 g protein, moderate protein plus 26 mmol sodium chloride (MP+Na), high protein (HP) providing 28.8 g protein, high protein plus 26 mmol sodium chloride (HP+Na), or high protein plus 32 mmol potassium as tripotassium citrate (HP+K). Urine was collected at 1.5 and 3.0 hours after the meal. Supplemental protein was given as 80:20 casein:lactalbumin. Test meals were isocaloric, and unless intentionally altered, components of interest except phosphate were equal between treatments. Each subject completed all five treatments. RESULTS: Urinary calcium excretion rose after the meal, peaking at 1.5 hours. There were no significant differences in calcium excretion between treatments at any time point. The high protein treatments did not result in a significant increase in either net acid or sulfate excretion at 1.5 hours compared to moderate protein. Dietary sodium chloride had no effect on urinary sodium or calcium excretion over the 3 hours. After the potassium treatment, sodium excretion increased (p< or =0.002) and net acid excretion decreased (p<0.001) compared to other treatments at 1.5 hours. CONCLUSIONS: In children, a simultaneous increase in protein and phosphorus due to increased milk protein intake did not increase acute urinary calcium excretion. An effect of dietary sodium chloride on acute urinary calcium excretion was not observed. Both these findings were similar to those of adult studies previously conducted in the same laboratory using similar format and treatments. Potassium citrate was not hypocalciuric in children, a response differing from that for adults, who have shown a decrease in acute urinary calcium excretion in response to alkaline potassium treatment. Further characterization of calciuric responses to dietary factors is required for children, who may differ from adults in many respects.

Calcium↗