Uric acid renal tubular transport

A decline in the urinary excretion of uric acid to a level below the rate of production leads to hyperuricemia and an increased miscible pool of sodium urate. Almost all the urate in plasma is freely filtered across the glomerulus. The concentration of uric acid appearing in the urine is determined by multiple renal tubular transport processes in addition to the filtered load. Evidence favors a four-component model including glomerular filtration, tubular reabsorption, tubular secretion, and postsecretory reabsorption. ... 

Drugs that decrease renal clearance of uric acid through modification of filtered load or one of the tubular transport processes include diuretics, nicotinic acid, salicylates (less than 2 g/day), ethanol, pyrazinamide, levodopa, ethambutol, cyclosporine, and cytotoxic drugs. 

Renal handling of uric acid. Uric acid may be actively reabsorbed from the ultrafiltrate following its glomerular filtration or it may be secreted from the blood across the basolateral membrane into the proximal tubular cell. Both passive and active transport mechanisms are involved in the handling of urate. Uricosuric drugs at appropriate doses interfere with these processes. 

Loop diuretics exacerbate gout, because these drugs enter the tubule lumen through the organic acid secretory system. Because uric acid utilizes this system for transport into the renal tubule and subsequent elimination, competition exists for the transporter. This results in both increased levels of uric acid and increased plasma drug levels. In the same way, the drug interferes with the tubular secretion of probenecid, which is used in the therapy of gout. 

Dietary habits and tubular transport defects of urate explain the excessive uric acid excretion of patients with RCN. An alteration of the renal handling of uric acid may be suspected when hyperuricosuria concurs with hypouricemia normal serum uric acid does not exclude a tubular transport defect of urate. 

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