Effect of urine pH changed by dietary intervention on uric acid clearance mechanism of pH-dependent excretion of urinary uric acid

Abstract

BackgroundThe finding reported in a previous paper - alkalization of urine facilitates uric acid excretion - is contradictory to what one might expect to occur: because food materials for the alkalization of urine contain fewer purine bodies than those for acidification, less uric acid in alkaline urine should have been excreted than in acid urine. To make clear what component of uric acid excretion mechanisms is responsible for this unexpected finding, we simultaneously collected data for the concentration of both creatinine and uric acid in serum as well as in urine, in order to calculate both uric acid and creatinine clearances.MethodsWithin the framework of the Japanese government’s health promotion program, we made recipes which consisted of protein-rich and less vegetable-fruit food materials for H + -load (acidic diet) and others composed of less protein and more vegetable-fruit rich food materials (alkaline diet). This is a crossover study within some limitations. Healthy female students, who had no medical problems at the regular physical examination provided by the university, were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid, titratable acid and all cations (Na+,K+,Ca2+,Mg2+,NH4+) and anions (Cl−,SO42−,PO4−) necessary for the estimation of acid–base balance were measured. In the early morning before breakfast of the 1st, 3rd and 5th experimental day, we sampled 5 mL of blood to estimate the creatinine and uric acid concentration in serum.Results and discussionUrine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated ([SO42−] + organic acid − gut alkali)was linearly related with the excretion of acid (titratable acid + [NH4+] − [HCO3−]), indicating that H + in urine is generated by the metabolic degradation of food materials. Uric acid and excreted urine pH retained a linear relationship, as reported previously. Among the five factors which are associated with calculating clearances for both uric acid and creatinine, we identified a conspicuous difference between acidic and alkaline diets in the uric acid concentration in serum as well as in urine; uric acid in the serum was higher in the acidic group than in the alkaline group, while uric acid in the urine in the acidic group was lower than that in the alkaline group. These changes of uric acid in acidic urine and in serum were reflected in the reduction of its clearance. From these observations, it is considered that uric acid may be reabsorbed more actively in acidic urine than in alkaline urine.ConclusionWe conclude that alkalization of urine by eating nutritionally well-designed alkaline -prone food is effective for removing uric acid from the body.

Effect of immediate and prolonged GLP‐1 receptor agonist administration on uric acid and kidney clearance: Post‐hoc analyses of four clinical trials

“…Hyperuricaemia is frequently observed in patients with pre‐ or recent‐onset T2DM, and increased levels of UA are thought to mediate, in part, cardiovascular and renal risk in T2DM . As GLP‐1‐peptide administration for 10 weeks in diabetic rats reduces UA levels, and GLP‐1RAs exhibit clinically relevant tubular effects in humans, we hypothesized that GLP‐1RA administration lowers plasma UA by increasing kidney UA clearance . Although intravenous exenatide administration rapidly increased UE UA in overweight healthy subjects (Study‐A) and T2DM patients (Study‐B), no reduction in UA‐levels was observed.…”

“…Inhibition of NHE3 by GLP‐1RA may have decreased pH‐dependent organic acid transporter (OAT)‐4 activity, thereby reducing kidney UA reabsorption. In addition, urinary alkalization or increased UE Na may have contributed directly to the uricosuric effect of acute exenatide administration. While high concentrations of urinary glucose may stimulate UE UA via the tubular GLUT9 transporter, we did not observe any relevant glycosuria in our T2DM patient population at baseline or after treatment, which makes such a pathway unlikely.…”

“…4,8 As GLP-1-peptide administration for 10 weeks in diabetic rats reduces UA levels, 20 and GLP-1RAs exhibit clinically relevant tubular effects in humans, [21][22][23][24] we hypothesized that GLP-1RA administration lowers plasma UA by increasing kidney UA clearance. [25][26][27] to decrease the gastric emptying rate and to inhibit areas in the central nervous system involved in hedonic feeding are not sustained during prolonged treatment. 29,30 In line with these observations, we recently suggested that tachyphylaxis and/or induction of compensatory mechanisms at the tubular level explains that only short-acting GLP-1RAs harbour sustained natriuretic and urine-alkalizing actions during prolonged treatment.…”

“…20 As GLP-1RA administration inhibits Na + /H + -exchanger type-3 (NHE3) activity in the proximal tubule, causing natriuresis and alkalization of the urine, [21][22][23][24] we hypothesize that this antihyperglycaemic drug class may reduce plasma UA levels by increasing urinary UA excretion in humans, those with and those without T2DM. [25][26][27] To explore the effects of currently available GLP-1RAs, with clinically relevant differences in their pharmacokinetic profile (see below), on plasma UA and UE UA , we performed a post-hoc analysis of 4 clinical trials that assessed the effects of these drugs on kidney physiology. 21,22,24,28 First, we assessed the immediate effects of intravenous administration of exenatide in healthy overweight men and T2DM patients.…”

Hyperuricemia and acute gout after laparoscopic sleeve gastrectomy

“…The alkalization of urine by the manipulation of foods can promote uric acid excretion. Diets could be designed to promote uric acid removal from the body by alkalinising urine . From our experience, the double boiling of meats, the use of bicarbonated soda in the preparation of legumes, use of lemon and food combination in meals may be effective methods of alkalization.…”