Effect of magnesium citrate and magnesium oxide on the crystallization of calcium salts in urine: changes produced by food-magnesium interaction

The effect of magnesium citrate and magnesium oxide on urinary biochemistry and on the crystallization of calcium salts was examined in 7 normal subjects and 4 patients with recurrent calcium oxalate nephrolithiasis. When magnesium citrate or magnesium oxide was administered on an empty stomach (10 mEq. 4 times per day or 486 mg. magnesium per day for 2 weeks) urinary magnesium increased by only 77 to 79 mg. per day and urinary citrate increased by 98 to 142 mg. per day. However, urinary calcium increased by 21 to 25 mg. per day. No significant changes were noted in urinary saturation of calcium oxalate or brushite or in the limit of metastability (formation product) of these salts. However, when magnesium salts were provided with meals there were more prominent increases in urinary magnesium (by 92 to 96 mg. per day) and in citrate (by 218 to 226 mg. per day). Moreover, urinary oxalate decreased. Owing to these changes the urinary saturation of calcium oxalate decreased and the formation product increased. If magnesium citrate and magnesium oxide are to be used in the management of recurrent calcium oxalate nephrolithiasis, they should be administered with meals.     

Stone forming risk of calcium citrate supplementation in healthy postmenopausal women

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.     

Alkali action on the urinary crystallization of calcium salts: contrasting responses to sodium citrate and potassium citrate

Alkali therapy is used commonly to prevent recurrent stone formation in patients with distal renal tubular acidosis. We compared the effects of potassium citrate to those of sodium citrate in 6 well defined cases of incomplete distal renal tubular acidosis. The patients were studied during a control phase, during potassium citrate treatment (80 mEq. per day) and during sodium citrate treatment (80 mEq. per day) chosen in random order. Potassium citrate caused a decrease in urinary calcium and a significant increase in urinary citrate that resulted in a significant decrease in the urinary saturation of calcium oxalate. It did not alter the saturation of brushite and sodium urate. However, while sodium citrate also was able to increase the urinary citrate level, there was no decrease in the urinary calcium (owing to the increased sodium load). Thus, the urinary saturation of calcium oxalate did not decrease as much as with potassium citrate and the saturation of brushite increased significantly. Moreover, the urinary saturation of sodium urate increased significantly owing to the enhanced sodium excretion. The results suggest that potassium citrate therapy may retard the crystallization of calcium oxalate and may not cause calcium phosphate crystallization. In contrast, sodium citrate may have no effect or it sometimes may accentuate the crystallization of calcium salts. Thus, our study supports the potential clinical advantage of potassium citrate therapy over sodium alkali treatment in patients with incomplete distal renal tubular acidosis and recurrent calcium nephrolithiasis.     

Oral potassium citrate treatment for idiopathic hypocitruria in children with calcium urolithiasis

PURPOSE :We evaluated the clinical and laboratory outcome of oral potassium citrate treatment in children with idiopathic hypocitruria and calcium stones. MATERIALS AND METHODS: The charts of 64 children 1 to 15 years old with hypocitruria and calcium stones (median age 7.2) treated with oral potassium citrate were reviewed. Evaluation parameters were tolerability, adverse reactions, metabolic profile and stone recurrence. RESULTS: No serious adverse reaction due to potassium citrate administration was recorded. Normal citrate excretion was restored in all patients. After treatment median urinary citrate daily plus or minus SD increased from 197 +/- 72 to 632 +/- 218 mg./1.73 m.2 (p <0.001) and mean urinary pH increased from 5.3 +/- 0.3 to 6.2 +/- 0.7 (p <0.01). Mean calcium excretion decreased from 3.5 +/- 2.7 to 2.5 +/- 2.7 mg./kg. (p <0.05). At an average followup of 22 months (range 3 to 67) the recurrence rate in the group overall was 0.07 per patient-year. The previous recurrence rate of 0.32 per patient-year in the 20 children with a history of recurrent stone disease decreased to 0.17 per patient-year after treatment. None of the 44 initial stone formers had recurrent stones. CONCLUSIONS: Our results show the safety and efficacy of oral potassium citrate treatment for restoring normal urinary citrate and suggest a preventive effect for recurrent calcium stone disease in children with hypocitruria and calcium stones.     

Prevention of recurrent calcium stone formation with potassium citrate therapy in patients with distal renal tubular acidosis

Distal renal tubular acidosis is a common cause of intractable calcium nephrolithiasis. We examined the effect of oral potassium citrate therapy in 9 patients with incomplete distal renal tubular acidosis diagnosed on the basis of an abnormal response to an oral ammonium chloride load. Patients were studied during a control phase and after 3 months of potassium citrate treatment (60 to 80 mEq. daily). Potassium citrate caused a significant increase in urinary pH and urinary citrate, and a decrease in urinary calcium. The urinary relative saturation ratio of calcium oxalate significantly decreased during treatment, while that of brushite did not change. Potassium citrate also was shown to inhibit new stone formation. During a mean treatment period of 34 months none of the 9 patients had new stones, although 39.3 plus or minus 79.7 (standard deviation) stones per patient formed during the 3 years preceding treatment. The results support the potential clinical advantage of potassium citrate therapy in patients with distal renal tubular acidosis and recurrent calcium nephrolithiasis.     

Long-term treatment of calcium nephrolithiasis with potassium citrate

The long-term effects of potassium citrate therapy (usually 20 mEq. 3 times daily during 1 to 4.33 years) were examined in 89 patients with hypocitraturic calcium nephrolithiasis or uric acid lithiasis, with or without calcium nephrolithiasis. Hypocitraturia caused by renal tubular acidosis or chronic diarrheal syndrome was associated with other metabolic abnormalities, such as hypercalciuria or hyperuricosuria, or occurred alone. Potassium citrate therapy caused a sustained increase in urinary pH and potassium, and restored urinary citrate to normal levels. No substantial or significant changes occurred in urinary uric acid, oxalate, sodium or phosphorus levels, or total volume. Owing to these physiological changes, uric acid solubility increased, urinary saturation of calcium oxalate decreased and the propensity for spontaneous nucleation of calcium oxalate was reduced to normal. Therefore, the physicochemical environment of urine following treatment became less conducive to the crystallization of calcium oxalate or uric acid, since it stimulated that of normal subjects without stones. Commensurate with the aforementioned physiological and physicochemical changes the treatment produced clinical improvement, since individual stone formation decreased in 97.8 per cent of the patients, remission was obtained in 79.8 per cent and the need for surgical treatment of newly formed stones was eliminated. In patients with relapse after other treatment, such as thiazide, the addition of potassium citrate induced clinical improvement. Thus, our study provides physiological, physicochemical and clinical validation for the use of potassium citrate in the treatment of hypocitraturic calcium nephrolithiasis and uric acid lithiasis with or without calcium nephrolithiasis.     

Can lemon juice be an alternative to potassium citrate in the treatment of urinary calcium stones in patients with hypocitraturia? A prospective randomized study

To investigate that lemon juice could be an alternative to potassium citrate in the treatment of urinary calcium stones in patients with hypocitraturia, 30 patients with hypocitraturic urinary calcium stones were enrolled into study. The patients were divided into three groups equally. Exactly 60 mEq/day fresh lemon juice (≈85 cc/day) and potassium citrate (60 mEq/day) were given to the patients of first and second group, respectively. Dietary recommendations were made for the third group. Blood and 24-h urine tests were performed before treatment and repeated 3 months later. The differences between demographic datas of groups were not significant. There was no significant difference between values of blood tests performed before and after treatment in all groups. Statistically significant differences were found between pre- and post-treatment urine values in each group. Although there was no significant difference between pre-treatment citrate levels of the groups. A significant difference was found between post-treatment citrate levels of the groups. There was 2.5-, 3.5- and 0.8-fold increase in urinary citrate level of lemon juice, potassium citrate and dietary recommendation groups, respectively. Urinary calcium level was decreased only in lemon juice and potassium citrate groups after treatment. While there was no significant difference between pre- and post-treatment urinary oxalate levels in all groups, a significant decrease in urinary uric acid levels was determined in all groups. We suggest that lemon juice can be an alternative in the treatment of urinary calcium stones in patients with hypocitraturia. Additionally, dietary recommendations can increase effectiveness of the treatment.     

Effect of potassium depletion on urinary stone risk factors in Wistar rats

Various studies have suggested that potassium depletion leads to acidosis and hypocitraturia. In Northeastern Thailand, for example, mild hypokalemia and mild hyperoxaluria are observed in most stone formers. However, there are limited reports about the direct link between potassium depletion and the formation of urinary stones, most of which are calcium oxalate stones. Therefore, we studied the direct effect of potassium depletion on the risk factors for calcium oxalate stone formation. Seventy-two rats were fed a control diet or a potassium-deficient diet for 1, 2, or 3 weeks (n = 12 per group). Twenty-four-hour urine collection was done for the measurement of potassium, calcium, oxalate, glycolate, citrate, phosphorus, and magnesium. Lactate dehydrogenase activity was also measured in order to assess renal tubular damage, and kidneys were harvested for histological examination. Furthermore, urinary supersaturation of calcium oxalate was calculated. With potassium depletion, the urinary concentrations of potassium, citrate, magnesium, and phosphorus decreased rapidly. There was no detectable renal damage, renal calcium deposition, and no significant increase of urinary oxalate or calcium. However, the urinary supersaturation index of calcium oxalate increased significantly in rats with potassium depletion. These findings indicate that potassium deficiency may increase the risk of stone formation through enhanced supersaturation.     

Prevention of stone formation and bone loss in absorptive hypercalciuria by combined dietary and pharmacological interventions

PURPOSE: We determined whether dietary restriction of calcium and oxalate, combined with thiazide and potassium citrate treatment, would prevent stone formation and avert bone loss in 18 men and 10 women with type I absorptive hypercalciuria. MATERIALS AND METHODS: Patients were treated with thiazide (20) or indapamide (8) and potassium citrate (average dose 35 mEq. daily) for 1 to 11 years (mean 3.7) while maintained on low calcium oxalate diet. Serum and urinary chemistry studies and bone mineral density were measured at baseline and at the end of treatment. New stones formed were quantitated during 3 years before and during treatment. RESULTS: During treatment urinary calcium significantly decreased (346 +/- 85 to 248 +/- 79 mg. daily, p <0.001) but urinary oxalate did not change. Urinary pH and citrate significantly increased, and urinary saturation of calcium oxalate significantly decreased by 46%. Stone formation rate decreased significantly from 2.94 to 0.05 per year (p <0.001). L2-L4 bone mineral density increased significantly by 5.7% compared to normal peak value, and by 7.1% compared with normal age and gender matched value. Femoral neck bone mineral density also increased significantly. CONCLUSIONS: Dietary restriction of calcium and oxalate, combined with thiazide and potassium citrate, satisfactorily controlled hypercalciuria, prevented the secondary increase in urinary oxalate, reduced urinary saturation of calcium oxalate, virtually eliminated recurrent stone formation, and increased bone density of the spine and femoral neck. Thus, this dietary pharmacological program controlled stone formation as well as bone loss that often accompany type 1 absorptive hypercalciuria.     

Effects of different doses of alkaline citrate on urine composition and crystallization of calcium oxalate

Summary Prophylactic treatment with alkaline citrate in patients with recurrent calcium oxalate (CaOx) stone disease results in reduced CaOx supersaturation and increased urinary citrate. The effects of a single evening dose were compared with those of two and three daily doses in six recurrent CaOx stone formers with hypercalciuria, hypocitraturia or raised calcium/citrate quotients. While on a standardized hospital diet the patients were given 7.5 g (28 mmol) of sodium potassium citrate (URALYT-U) in one, two, and three doses. Fractional urine collections during 24 hours were analyzed for pH, composition, and crystallization risk (CR). All dosage regimens had favourable effects on urinary calcium, citrate, calcium/citrate quotients, and CaOx-CR. The most sustained effect was recorded with three divided doses. Single evening doses resulted in the most pronounced effects between 22.00–06.00 h, thereby counteracting the increased risk of CaOx crystallization during that period. In terms of 24 h urine composition the best effect was recorded with alkaline citrate administered three times daily, but because of the favourable response by a single evening dose between 22.00–06.00 h the assumption was made that this dosage regimen might be sufficient to reduce the risk of CaOx crystallization and stone formation. However, the validity of such an assumption can only be established by long-term clinical studies.     

肾结石大鼠钠/二羧基转运蛋白1的表达及枸橼酸钾防治机制的研究

目的 研究肾组织钠／二羧基转运蛋白1（SDCT1）与低枸橼酸尿的关系以及枸橼酸钾的干预作用，探讨肾结石发病的分子机制和防治措施。方法 雄性Wistar大鼠分为对照组、肾结石组及枸橼酸钾干预组。血、尿枸橼酸和草酸采用酶法测定，Northern blot检测大鼠肾组织SDCT1mRNA水平的改变，免疫组织化学观察SDCT1在肾组织的分布及表达变化。结果 与对照组比较，肾结石组第3天尿草酸水平显著升高，枸橼酸水平显著降低，同时肾组织SDCT1mRNA及其蛋白水平上调。第7天SDCT1mRNA及其表达产物增加更为显著，同时尿枸橼酸水平进一步降低，尿钙排泄显著增加，87.5%大鼠有中－大量的草酸钙结石形成。第14天上述改变更为明显，结石形成率达100％。枸橼酸钾干预组各时间点尿草酸水平与肾结石组差异无显著性意义，但尿枸橼酸水平显著高于肾结石组及对照组，肾组织SDCT1mRNA及蛋白表达显著低于肾结石组，与对照组差异无显著性意义；结石形成率显著低于肾结石组；肾小管扩张、炎细胞浸润等病变也明显减轻。结论 肾组织SDCT1表达上调可能是低枸橼酸尿的重要原因，与肾结石的形成有密切关系。枸橼酸钾可下调肾结石大鼠肾组织SDCT1的表达，对肾结石的形成具有明显的干预作用。     

Citrate (CG-120) therapy in urolithiasis. 2. Effect on urinary and serum biochemistry

The long-term effects of citrate therapy (CG-120, 3 g/day or 4 g/day) were examined in 398 patients with upper urinary tract calculi. We studied the influence of citrate therapy on urinary and blood biochemistry in 353 of them. CG-120 caused a sustained increase in urinary citrate, urinary pH and potassium, but no substantial or significant changes in other urinary parameters (uric acid, phosphate, oxalate, sodium, chloride and urine volume). Although urinary calcium decreased significantly up to the 24th week, it did not change significantly there after and it tended to increase at the 54th week. Urinary creatinine excretion decreased after 34 weeks of administration, but this phenomenon could not be explained, because the level of blood urea nitrogen and serum creatinine was not elevated in any case before administration. There were no changes in the serum calcium, magnesium, phosphate, uric acid, sodium, potassium or chloride level.     

Influence of dietary animal protein on renal stone disease

The effect of dietary protein load on the incidence of nephrolithiasis was studied in rats and men. Three groups of adult male Wister rats were fed with a standard protein diet, a high protein diet, or a low protein diet for 4 weeks. In the high protein group, calcium excretion was significantly increased and citrate excretion was remarkably decreased. This group also exhibited low grade metabolic acidosis due to catabolism of excess amino acids, and increases in urinary cyclic AMP excretion and bone resorption. These findings indicate that protein-induced hypercalciuria is due to low grade metabolic acidosis, which directly affects renal handling of calcium. Long-term calcium loss in the urine may lead to negative calcium balance and hyperfunction of the parathyroid gland may induce bone resorption. The influence of 40 g animal protein load on urinary risk factors of calcium stone formation was investigated in 23 healthy males and 26 patients with nephrolithiasis. All subjects were given control diets each day containing 60 g protein for a week and during the next week each received an additional 40 g animal protein. In the controls, added dietary protein resulted in decreased urinary citrate and increased urinary uric acid, with no change in urinary calcium or cyclic AMP excretion. In contrast, the patients showed increased urinary calcium and cyclic AMP as well as decreased urinary citrate. Further examination of the patients revealed that the significant increases of calcium and cyclic AMP excretion occurred only in hypercalciuric patients, who seemed to be classified into renal hypercalciuria.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of fruits and vegetables on urinary stone risk factors

BACKGROUND: The overall effect of fruit and vegetable intake on urinary stone risk profile is not yet known. METHODS: We studied the effect of a two-week period of fruit and vegetable elimination on urinary stone risk profile in 12 normal adults, and of supplementing the diet with a fair quantity of low-oxalate fruits and vegetables in 26 idiopathic calcium stone formers characterized by hypocitraturia and a very low fruit and vegetable intake in their usual diet. RESULTS: In the normal subjects, the elimination of fruits and vegetables from the diet decreased the urinary excretion of potassium (-62%), magnesium (-26%), citrate (-44%) and oxalate (-31%), and increased that of calcium (+49%) and ammonium (+12%) (P < 0.05 for all). The relative saturation for calcium oxalate and calcium phosphate increased from 6.33 to 8.24 (P = 0.028), and from 0.68 to 1.58 (P = 0.050), respectively. In the hypocitraturic stone formers, the introduction of these foods in the diet increased urinary volume (+64%), pH (from 5.84 to 6.19), excretion of potassium (+68%), magnesium (+23%), and citrate (+68%), while it decreased the excretion of ammonium (-18%) (P < 0.05 for all). The relative saturation for calcium oxalate and uric acid fell from 10.17 to 4.96 (P < 0.001), and from 2.78 to 1.12 (P = 0.003), respectively. CONCLUSION: The total elimination of fruits and vegetables in normal subjects brings about adverse changes in the urinary stone risk profile that are only partially counterbalanced by a reduction in oxalate. In contrast, the addition of these foods to the diet of hypocitraturic stone formers not used to eating them not only significantly increases citrate excretion without affecting oxalate excretion, but also decreases calcium oxalate and uric acid relative saturation.     

Citrate as an inhibitor of stone formation--with reference to intestinal citrate absorption and the influence of citrate on intestinal calcium absorption]

The response of serum citrate to the oral citrate load was studied in seven healthy subjects. Serum citrate was significantly elevated from 15 to 60 min post-load with some individual variations. In 27 stone-formers serum citrate and the response to the oral citrate administration was studied and compared with the results obtained on healthy subjects. The serum citrate concentration of stone-formers was 1.99 +/- 0.49 mg/dl as compared to 1.61 +/- 0.35 mg/dl in healthy subjects. After citrate administration serum citrate increased significantly in both groups, but no significant difference was shown in response to the oral citrate load between these two groups (3.44 +/- 0.94 mg/dl in stone-formers, 3.16 +/- 0.38 mg/dl in healthy subjects). In Sprague-Dawley rats each weighing about 200 g urinary citrate and calcium excretion were studied after administration of sodium citrate or calcium chloride or both. The concomitant equimolar administration of sodium citrate and calcium chloride did not have significant influence on urinary citrate or calcium excretion as compared when citrate or calcium was given alone. However, the calcium excretion was significantly decreased with the administration of citrate and calcium ata molar ratio of 1:2.     

Renal tubular cell damage and oxidative stress in renal stone patients and the effect of potassium citrate treatment

Our objective was to evaluate the oxidative stress and renal tubular cell damage in patients who have renal stones compared to normal subjects. The patients were re-evaluated after 1-months supplementation with potassium citrate. We recruited 30 patients (11 males and 19 females) diagnosed with kidney stones and scheduled for surgical stone removal the following month, and 30 healthy non-stone formers (14 males and 16 females). Two 24-h urine samples and one heparinized blood sample were collected from each subject. Plasma was separated from the erythrocytes and assayed for creatinine, potassium, sodium, calcium, magnesium, phosphate, malondialdehyde (MDA, a lipid peroxidation product) (P-MDA), protein thiol as an indicator of protein oxidation, and vitamin E. Erythrocytes were analysed for MDA (E-MDA), reduced glutathione (GSH) and cellular glutathione peroxidase (cGPx) activity. The urine was analyzed for pH, creatinine, potassium, sodium, calcium, magnesium, phosphate, oxalate, citrate, MDA (U-MDA), total protein (U-protein) and N-acetyl--glucosaminidase (NAG) activity. For the stone patients, urine and blood samples were re-evaluated after supplementation with potassium citrate (60 mEq/day) for 1 month. Renal stone patients had higher plasma creatinine and lower plasma potassium, urinary pH, potassium, magnesium, phosphate and citrate than the controls. The patients had higher P-MDA, E-MDA, U-MDA, U-protein and NAG activity, but lower GSH, cGPx activity, protein thiol and vitamin E, when compared with controls. After potassium citrate supplementation, P-MDA and E-MDA decreased while plasma vitamin E, urinary NAG activity and citrate increased. Renal stone disease is associated with high oxidative stress and damage to renal tubular cells. These abnormalities are coincident with an increase in blood lipid peroxidation products and a decrease in antioxidant status. Although supplementation with potassium citrate improved urinary citrate levels and oxidative stress, it neither reduced urinary lipid peroxidation products nor remedied the damage to renal tubular cells, probably due to the existence of kidney stones.     

Citraturic, alkalinizing and antioxidative effects of limeade-based regimen in nephrolithiasis patients

Potassium citrate has long been used as a prophylactic remedy for nephrolithiasis recurrence. Lemonade consumption is also suggested as an option. We compared the efficacy of consumption of solution containing manufactured lime powder with that of potassium citrate, on the improvement of metabolic risk factors, oxidative stress and renal tubular damage in nephrolithiasis patients. Patients with kidney stone were enrolled and randomly assigned to three treatment programs for 3 month period consisting of consumption of solution containing lime powder (Group 1, n = 13), potassium citrate (Group 2, n = 11) and lactose as placebo regimen (Group 3, n = 7). Lime powder and potassium citrate contained equal amounts of potassium (21 mEq) and citrate (63 mEq). After treatment, there was an increase in urinary pH, potassium and citrate in Group 1 and 2. Increased plasma potassium and red blood cell glutathione (R-GSH) and decreased urinary malondialdehyde were found in Group 1, but not observed in Group 2. R-GSH was decreased in Group 2. Urinary N-acetyl-beta-glucosaminidase activity and fractional excretion of magnesium, as renal tubular damage indicators, were decreased only in Group 1. In Group 3, all measured parameters were unaltered except for an increased urinary chloride. In conclusion, consumption of our in-house lime powder exerted citraturic and alkalinizing actions as efficient as consumption of potassium citrate. In addition, it provided an antioxidative effect and was able to attenuate renal tubular damage. These pharmacological properties may be clinically useful to diminish the stone-forming potential in kidney stone patients and hence for preventing recurrent calculi.     

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/m² (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.     

Biochemical control of bone loss and stone-forming propensity by potassium-calcium citrate after bariatric surgery

BackgroundPatients undergoing Roux-en-Y gastric bypass (RYGB) surgery are prone to developing bone loss and kidney stones. The goal of the present study was to test the hypothesis that an effervescent formulation of potassium calcium citrate (PCC) would avert metabolic complications by providing bioavailable calcium and alkali.MethodsA total of 24 patients with RYGB underwent a 2-phase crossover randomized trial comparing PCC and placebo. During the last 2 days of each 2-week phase, the serum and 24-hour urine samples were analyzed for calcium and bone turnover markers, acid base status, and urinary stone risk factors.ResultsCompared with placebo, PCC marginally reduced the serum parathyroid hormone level and significantly decreased urinary deoxypyridinoline by 12% (P <.001) and serum type 1 collagen C-telopeptide by 22% (P <.01). PCC significantly increased the net gastrointestinal alkali absorption, citrate, and pH and significantly lowered the urinary net acid excretion (P <.001). The urinary saturation of uric acid decreased significantly (P <.001). The supersaturation of calcium oxalate and brushite did not change despite an increase in calcium and pH. In untreated urine samples with citrate concentrations altered to mimic those of placebo and PCC, calcium oxalate agglomeration was significantly inhibited by PCC.ConclusionIn RYGB patients, PCC supplementation inhibited bone resorption by providing bioavailable calcium, reduced the urinary saturation of uric acid, and increased the inhibitor activity against calcium oxalate agglomeration by providing alkali that increased urinary pH and citrate.     

Urinary excretion of citrate, glycosaminoglycans, magnesium and zinc in relation to age and sex in normal subjects and in patients who form calcium stones.

One hundred and ninety-seven healthy subjects and 104 patients with idiopathic calcium stone disease had their urinary excretion of citrate, glycosaminoglycans, magnesium, and zinc measured and the results correlated with sex and age. In normal subjects the daily excretion of citrate, magnesium, and zinc increased with age to a maximum during the fifth decade and remained relatively constant until the eighth decade when they decreased. The daily excretion of magnesium and zinc were higher in men than in women, which was attributed to the higher body weights of the men. The urinary excretion of citrate, magnesium, and zinc related to creatinine remained relatively constant with age in adult life; analyses of magnesium and zinc excretion rates divided by urine creatinine did not distinguish men from women. There was no significant difference between men and women for citrate excretion in 24 hour urine, but the citrate:creatinine ratio was significantly higher in women than men. The higher citrate excretion in women may explain the lower incidence of calcium stones in women. The highest glycosaminoglycan excretion rates were seen during the first two decades which is why children and teenagers are less prone to develop calcium stones in spite of high urinary calcium concentrations. Urinary citrate and magnesium excretion were lower, and glycosaminoglycan and zinc excretion were higher, in stone formers than in controls. It seems that a decreased excretion of citrate and magnesium together with an increased excretion of calcium, may contribute to the formation of calcium stones. The role of urinary glycosaminoglycans and zinc in the formation of calcium stones remains uncertain.