Urinary citrate excretion in patients with renal stone: roles of leucocyte ATP citrate lyase activity and potassium salts therapy.
BACKGROUND
Hypocitraturia is a major metabolic abnormality in rural Northeast Thais with renal stones. These people also have low serum and urinary potassium and consume a high carbohydrate and low fat diet, which together might influence the intracellular metabolism and urinary excretion of citrate.


METHODS
In Study A, we measured plasma and urinary chemistries and assayed leucocyte ATP citrate lyase (ACL) activity in 30 normal urban control subjects (Group A1) and 30 rural renal stone patients (Group A2) in Northeast Thailand. Some of the subjects from both groups were also used to evaluate the intake of carbohydrate, protein and fat. In Study B, we examined the effects of potassium salts therapy with another group of 30 rural renal stone patients: Group B1 (n = 15) treated with potassium chloride and Group B2 (n = 15) with potassium-sodium citrate (with an aim to achieve 42 mEq potassium, 21 mEq sodium and 62 mEq citrate per day for 1 month).


RESULTS
In Study A, the leucocyte ACL activity of Group A1 was much lower than that of Group A2 (3.2 +/- 0.7 vs. 9.3 +/- 3.8 micromol acetylhydroxamate/mg protein/30 min, p < 0.0001). The plasma potassium, urinary excretions of potassium and citrate in Group A1 were higher than in Group A2. When data of the two groups were combined, urinary citrate excretion was inversely correlated with leucocyte ACL activity (r = 0.6783, p < 0.001). While the dietary protein intake did not differ between Groups A1 and A2, the carbohydrate intake by Group A1 was significantly lower (65.2 +/- 7.9% vs. 83.1 +/- 2.9%, p < 0.01) and fat higher (21.0 +/- 6.4% vs. 6.2 +/- 4.1%, p < 0.002) than Group A2. After treatment with potassium chloride (Group B1), only the potassium was increased (p < 0.001), while those treated with potassium-sodium citrate (Group B2) experienced a significant increase in urinary pH (p < 0.002), potassium (p < 0.001) and citrate (p < 0.001), and a decrease in leucocyte ACL activity (p < 0.001).


CONCLUSIONS
Compared to normal subjects, renal stone patients have low urinary citrate excretion with high leucocyte ACL activity. In Northeast Thailand, low potassium status and a high carbohydrate and low fat diet may cause the increased ACL activity. However, hypokaliuria, hypocitraturia and high leucocyte ACL activity can be corrected by potassium-sodium citrate salt therapy.
D001275:ATP Citrate (pro-S)-Lyase / Q000378:metabolism*; D000328:Adult; D016022:Case-Control Studies; D019343:Citric Acid / Q000652:urine*; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004044:Dietary Proteins; D005260:Female; D006801:Humans; D007669:Kidney Calculi / Q000188:drug therapy / Q000201:enzymology / Q000652:urine*; D007962:Leukocytes / Q000201:enzymology*; D008297:Male; D011188:Potassium / Q000097:blood / Q000652:urine; D017680:Potassium Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D013785:Thailand
D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004044:Dietary Proteins; D017680:Potassium Compounds; D019343:Citric Acid; D001275:ATP Citrate (pro-S)-Lyase; D011188:Potassium