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.     

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.     

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.     

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.     

Reduction of renal stone risk by potassium-magnesium citrate during 5 weeks of bed rest

PURPOSE: Exposure to the microgravity environment of space increases the risk of kidney stone formation, particularly for calcium oxalate and uric acid stones. This study was performed to evaluate the efficacy of potassium alkali as potassium-magnesium citrate in reducing renal stone risk and bone turnover. MATERIALS AND METHODS: This study was performed as a double-blind, placebo controlled trial. We studied 20 normocalciuric subjects randomized to either placebo or potassium-magnesium citrate (42 mEq potassium, 21 mEq magnesium, 63 mEq citrate per day) before and during 5 weeks of strict bed rest. The study was performed in the General Clinical Research Center and under a controlled dietary regimen composed of 100 mEq of sodium, 800 mg of calcium, 0.8 gm/kg animal protein and 2,200 kcal per day. Two 24-hour urine collections were obtained under oil each week for assessment of stone risk parameters and relative saturation of calcium oxalate, brushite and undissociated uric acid. Blood was also collected for determination of serum immunoreactive parathyroid hormone and vitamin D metabolites. RESULTS: Bed rest promoted a rapid increase in urinary calcium excretion of approximately 50 mg per day in both groups. Despite this increase subjects treated with potassium-magnesium citrate demonstrated significant decreases in the relative saturation of calcium oxalate and in the concentration of undissociated uric acid compared to placebo. Immunoreactive parathyroid hormone, serum 1,25-dihydroxyvitamin D and intestinal calcium absorption all decreased in both groups with no difference in response between the 2 treatment arms. CONCLUSIONS: Provision of alkali as potassium-magnesium citrate is an effective countermeasure for the increased risk of renal stone disease associated with immobilization. Despite an increase in urine calcium concentration, the relative saturation of calcium oxalate decreased due to citrate chelation of calcium and the concentration of undissociated uric acid decreased due to the significant increase in urine pH.     

Effect of meal on the physiological and physicochemical actions of potassium citrate

The effect of meals on the physiological and physicochemical actions of potassium citrate was examined in 8 patients with nephrolithiasis maintained on a constant metabolic dietary regimen. Potassium citrate (20 mEq. 3 times per day), whether given with food or on an empty stomach, significantly increased urinary pH, citrate and potassium, and decreased urinary calcium and ammonium. Moreover, potassium citrate decreased urinary saturation of calcium oxalate and uric acid, although it slightly increased that of brushite. However, there was no significant difference in these measures when the drug was given with meals from the time when it was given on an empty stomach. Thus, the effect of potassium citrate on urinary risk factors is unaffected by food.     

远端肾小管酸中毒的诊断和治疗

报告远端肾小管酸中毒１６例，其中完全型２例，不完全型１４例。完全型有高氯低钾性酸中毒，不完全型无酸中毒，但氯化铵负荷试验阳性。在口服枸橼酸钾期间，两型均观察到尿钙明显降低，尿ｐＨ和枸橼酸显著升高，完全型代谢性酸中毒得到纠正。对远端肾小管酸中毒的诊断和治疗进行了讨论。     

Physicochemical action of potassium-magnesium citrate in nephrolithiasis.

Effect of potassium-magnesium citrate on urinary biochemistry and crystallization of stone-forming salts was compared with that of potassium citrate at same dose of potassium in five normal subjects and five patients with calcium nephrolithiasis. Compared to the placebo phase, urinary pH rose significantly from 6.06 +/- 0.27 to 6.48 +/- 0.36 (mean +/- SD, p less than 0.0167) during treatment with potassium citrate (50 mEq/day for 7 days) and to 6.68 +/- 0.31 during therapy with potassium-magnesium citrate (containing 49 mEq K, 24.5 mEq Mg, and 73.5 mEq citrate per day). Urinary pH was significantly higher during potassium-magnesium citrate than during potassium citrate therapy. Thus, the amount of undissociated uric acid declined from 118 +/- 61 mg/day during the placebo phase to 68 +/- 54 mg/day during potassium citrate treatment and, more prominently, to 41 +/- 46 mg/day during potassium-magnesium citrate therapy. Urinary magnesium rose significantly from 102 +/- 25 to 146 +/- 37 mg/day during potassium-magnesium citrate therapy but not during potassium citrate therapy. Urinary citrate rose more prominently during potassium-magnesium citrate therapy (to 1027 +/- 478 mg/day from 638 +/- 252 mg/day) than during potassium citrate treatment (to 932 +/- 297 mg/day). Consequently, urinary saturation (activity product) of calcium oxalate declined significantly (from 1.49 x 10(-8) to 1.03 x 10(-8) M2) during potassium-magnesium citrate therapy and marginally (to 1.14 x 10(-8) M2) during potassium citrate therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

An evaluation of the physicochemical risk for renal stone disease during pregnancy

Seventeen subjects were studied during the third trimester of pregnancy (PG) and post partum (NPG) to evaluate the effect of pregnancy on the physicochemical risk of renal stone disease. Levels of urinary saturation for calcium oxalate (CaOx), brushite (Br), uric acid (UA), and monosodium urate (NaU) were determined as well as urinary excretions of stone-forming elements. In addition to urinary calcium excretion, assessment of calcium metabolism included serum calcium and parathyroid hormone. Urinary calcium excretion was 251 +/- 127 mg/day during pregnancy and 121 +/- 67 mg/day post partum (p < 0.001). This was associated with a higher intake of dietary calcium and altered renal handling of calcium with an increase in the filtered load and a decrease in renal tubular reabsorption. The increase in urinary calcium resulted in a higher level of saturation of the urine for calcium oxalate (NPG 2.1 +/- 1.0 vs PG 3.0 +/- 1.1, p < 0.02) and brushite (NPG 1.2 +/- 0.9 vs PG 1.9 +/- 1.1, p < 0.05) compatible with an increased risk of stone formation.     

Graphic display of urinary risk factors for renal stone formation

From the analysis of various urinary constituents and the estimation of urinary saturation of stone-forming salts, it is now possible to identify risk factors responsible for or contributing to stone formation. Metabolic factors included calcium, oxalate, uric acid, citrate and pH. Environmental factors were total volume, sodium, sulfate, phosphate and magnesium. Physicochemical factors represented saturation of calcium oxalate, brushite, monosodium urate, struvite and uric acid. A scheme for graphic display of risk factors was developed to allow ready visual recognition of important risk factors presumed to cause stone formation. This graphic display had diagnostic use as well as practical value in following response to treatment. For example, a low urinary pH and high urinary concentration of undissociated uric acid could be discerned readily in cases of uric acid lithiasis, as were high urinary pH and exaggerated urinary supersaturation of struvite in cases of infection lithiasis. In a patient with absorptive hypercalciuria and hypocitraturia treatment with thiazide and potassium citrate could be shown to abolish high risks (hypercalciuria, hypocitraturia and relative supersaturation of calcium oxalate) displayed before treatment.     

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.     

Seasonal variations in urinary risk factors among patients with nephrolithiasis

Twenty-four hour urine specimens from 5,677 stone-forming patients throughout the United States were analyzed for seasonal variations in urinary risk factors for nephrolithiasis. Determinations were performed for urine volume, pH, calcium, oxalate, phosphorus, sodium, magnesium, citrate, sulfate, uric acid, and the relative supersaturation (RS) of calcium oxalate, brushite, monosodium urate, and uric acid. Criteria for significant seasonal variation included a significant difference in monthly means of risk factors, seasonal grouping of the data by the Student-Newman-Keuls multiple range test, consistent year-to-year trends and a physiologically significant range. Minimum urine volume of 1.54 +/- 0.70 SD L/day occurred in October while a maximum urine volume of 1.76 +/- 0.78 SD L/day was observed during February. Minimum urine pH of 5.94 +/- 0.64 SD was observed during July and August while a maximum pH of 6.18 +/- 0.61 SD was observed during February. Daily urinary excretion of sodium was lowest during August, 158 +/- 74 SD mEq/day and highest during February 177 +/- 70 SD mEq/day. The RS of brushite and uric acid were found to display significant pH-dependent seasonal variation with a maximum RS of uric acid 2.26 +/- 1.98 SD in June and a low of 1.48 +/- 1.30 SD in February. Maximum RS of brushite 2.75 +/- 2.58 was observed during February. Minimum RS of brushite 1.93 +/- 1.70 SD was observed in June. Phosphorus excretion displayed seasonal variation about a spring-fall axis with a maximum value 1042 +/- 373 SD mg/day in April and a minimum value of 895 +/- 289 SD mg/day. Urine volume, sodium, and pH were significantly lower during the summer (June, July, August) than in the winter (December, January, February). The RS of uric acid was higher, but that of brushite and monosodium urate was lower in the summer than in the winter. The seasonal changes observed in urine volume, pH, sodium, and the RS of brushite and uric acid are consistent with summertime sweating and increased physical activity. Seasonal variations in phosphorus excretion are probably dietary in origin. The summertime was characterized by an increased propensity for the crystallization of uric acid but not of calcium oxalate or calcium phosphate.     

Biochemical and physicochemical presentations of patients with brushite stones

PURPOSE: We determined whether the biochemical and physicochemical backgrounds of patients with brushite stones differ from those with hydroxyapatite and calcium oxalate stones. MATERIALS AND METHODS: From a computer data base of patients completing ambulatory evaluation 19 with brushite stones, 24 with hydroxyapatite stones and 762 with calcium oxalate stones were identified with the specified composition in greater than 70% of stones. RESULTS: Absorptive hypercalciuria type I was present in 63% of patients with brushite, 17% with hydroxyapatite and 30% with calcium oxalate stones. Distal renal tubular acidosis was noted in 32% of patients with brushite, 42% with hydroxyapatite and 3% with calcium oxalate stones. Mean urinary calcium in the brushite group was significantly higher than in the hydroxyapatite and calcium oxalate groups (265 +/- 125 vs 186 +/- 103 and 187 +/- 95 mg daily, respectively). Urinary pH in the brushite group was slightly but significantly higher than in the calcium oxalate group (6.15 +/- 0.30 vs 5.91 +/- 0.42). The brushite relative saturation ratio in the brushite group was marginally higher than in the hydroxyapatite group and significantly higher than in the calcium oxalate group (3.25 +/- 2.03 vs 2.34 +/- 1.51 and 1.83 +/- 1.66, respectively). CONCLUSION: Patients with predominantly brushite stones could be distinguished from those with predominantly hydroxyapatite and calcium oxalate stones by higher urinary saturation with respect to brushite due mainly to hypercalciuria from absorptive hypercalciuria.     

Effect of dietary calcium and magnesium on experimental renal tubular deposition of calcium oxalate crystal induced by ethylene glycol administration and its prevention with phytin and citrate

Oral administration of ethylene glycol to rats, and the resultant intratubular depositions of microcrystals of calcium oxalate were studied investigating the influences of dietary calcium or magnesium and assessing the protective efficacies against the crystallizations by treatment with phytin and sodium citrate. With increase of calcium intake and consequent increase of urinary calcium excretion there was a marked increase in the amount of tubular deposit of calcium oxalate crystal and in the calcium content of renal tissue. Although magnesium deficiency accelerated renal tubular calcium oxalate deposition, the protection against the crystal formation was not observed with excessive dietary magnesium. When rats were fed a high-calcium diet supplemented with phytin, a significant inhibition of the intratubular crystallization was observed. It appeared obvious that a hypocalciuric action of phytin was attributed to the effect of the prevention. There was vigorous protection of crystal formation by treatment with sodium citrate, which correlated with the level of citrate concentration in the drinking water.     

Calcium nephrolithiasis and distal tubular acidosis in type 1 glycogen storage disease

A 36-year-old man was admitted to hospital due to right flank pain as a result of ureteral stones. He had been followed up for type 1 glycogen storage disease since the age of 11 years. He had four episodes of spontaneous stone birth during the previous 2 years, and each stone was composed mainly of calcium oxalate. Intravenous pyelography showed right hydronephrosis due to ureteral stones and bilateral multiple renal stones. We carried out transurethral ureterolithotripsy (TUL) on the right ureteral stones. The composition was a mixture of calcium oxalate and calcium phosphate. Laboratory evaluation demonstrated the association of distal renal tubular acidosis (RTA). These observations suggest that hypocitraturia and distal RTA are strongly correlated to recurrence of calcium nephrolithiasis. The patient's serum uric acid and urinary citrate excretion levels normalized after allopurinol and potassium citrate administration.     

Laxative abuse as a cause for ammonium urate renal calculi

Nine women with laxative abuse and predominantly ammonium urate renal calculi underwent metabolic studies to identify common chemical abnormalities and determine pathophysiology. The 24-hour urine studies demonstrated marked decreases in volume (902 cm.3), sodium (28 mEq.), citrate (116 mg.) and potassium (21 mEq.). A significant elevation in ammonium urate supersaturation was found compared to control subjects when studied by the computer model EQUIL 2. Of the patients 7 had 1 or more urine specimens positive for phenolphthalein. Gastrointestinal loss of fluid and electrolytes allowed for chronic extracellular volume depletion. Intracellular acidosis was present as judged by low urinary citrate and potassium. The fact that the ion product for ammonium urate is increased significantly compared to controls reflects the stated pathophysiological changes. Laxative abuse should be suspected whenever a woman has an ammonium urate renal calculus in sterile urine.     

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.     

Low urinary citrate excretion in nephrolithiasis

The urinary citrate excretion was examined in patients with nephrolithiasis who were categorized on the basis of different physiologic or metabolic abnormalities. A wide prevalence of low citrate excretion (hypocitraturia) was observed, with over one half of our patients with stones exhibiting it. Hypocitraturia was found in all patient categories except primary hyperparathyroidism and hyperuricosuric calcium oxalate nephrolithiasis. As expected, hypocitraturia was present in renal tubular acidosis and in enteric hyperoxaluria. However, urinary citrate was also low in absorptive and renal hypercalciurias, and in patients in whom an acid-base disturbance was clearly excluded.     

Effects of potassium-magnesium citrate supplementation on cytosolic ATP citrate lyase and mitochondrial aconitase activity in leukocytes: A window on renal citrate metabolism

BACKGROUND: An increase in urinary citrate excretion is associated with a decrease in activity of renal cortical cytosolic ATP citrate lyase (ACL) and mitochondrial aconitase (m-aconitase). Because potassium-magnesium citrate causes an increase in urinary citrate excretion, we decided to assess its effects on ACL and m-aconitase in the leukocytes of renal stone patients. METHODS: Twenty male renal stone patients were supplemented with potassium-magnesium citrate twice daily (i.e. 42 mEq potassium, 21 mEq magnesium, and 63 mEq citrate per day) for a period of 1 month. Two 24-h urine and one 15-mL heparinized blood samples were collected from each patient before and after supplementation. Urine samples were analyzed for relevant biochemical compositions. Leukocytes were separated from blood samples by centrifugation and assayed for ACL and m-aconitase activity. RESULTS: Supplementation with potassium-magnesium citrate significantly increased urinary pH (P < 0.005) and excretions of potassium (P < 0.001), magnesium (P < 0.001) and citrate (P < 0.0001). The activity of both ACL and m-aconitase were significantly decreased (P < 0.004 and P < 0.02 respectively). The decrease in ACL activity was inversely correlated with an increase in urinary excretion of both potassium (r = -0.620, P < 0.0001) and citrate (r = -0.451, P < 0.004). A similar inverse correlation was observed between m-aconitase activity and urinary excretion of citrate (r = -0.322, P < 0.043). CONCLUSION: Changes in enzyme activity, related to citrate metabolism in leukocytes, might reflect the status of renal tubular cells.