Uric acid renal handling

Grantham JJ and Chonko AM. Renal handling of organic anions and cations Excretion of uric acid. In Brenner BM and Rector FC (eds.).7 The Kidney (4th ed). Philadelphia Saunders, 1991. 

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. 

Fanelli GM (1976) Drugs affecting the renal handling of uric acid. In Martinez-Maldonado M (ed) Methods in Pharmacology. Vol 4A Renal Pharmacology. Chapter 9. Plenum Press, New York, London, pp 269-292 Friedman M, Byers SO (1948) Observations concerning the causes of the excess excretion of uric acid in the Dalmatian dog. J Biol Chem 175 727-735... 

Renal handling of uric acid is complex and involves four sequential steps (1) glomerular filtration of virtually aU the uric acid in capillary plasma entering the glomerulus (2) reabsorption in the proximal convoluted tubule of about... 

Diuretics alter the excretion of Na+ and also may modify renal handling of other cations (e.g., K+, H+, Ca +, and Mg +)> anions (e.g., Cl , HCO3, and HjPO "), and uric acid. In addition, diuretics may alter renal hemodynamics indirectly. Talale 28-1 compares the general effects of diuretics classified according to mechanism of action. 

Sorensen, L.B., Levinson, D.J. Evidence for four compartments in the renal handling of uric acid in man. In Amino Acid Transport and Uric Acid Transport. (Eds. S. Silbernagl, F. Lang, R. Gre-ger) Georg Thieme Publishers, 1976, pp 243-247. 

This workshop included reviews from some of the leading authorities on the various aspects of uric acid metabolism in man biochemistry, pathology, renal handling, nutrition, etc., and these reviews and results of new studies are presented here. 

RENAL HANDLING OF URIC ACID IN NORMAL SUBJECTS ITS BEHAVIOUR WITH RESPECT TO DIFFERENT FILTERED LOADS... 

The investigation was conducted with the voluntary cooperation of 10 normal males (mean age, 33 years) who were placed on an essentially purine-free diet during the study. Renal handling of uric acid was examined by means of the pyrazinamide (PZA) and probenecid (PB) tests, performed in three uricemia states normouricemia 3.6 to 6.4 mg/dl), allopurinol-induced hypouricemia (under 3.5 mg/dl), and hyperuricemia after oral administration of RNA monosodium salt (over 6.5 mg/dl). 

Table 1 shows daily uric acid excretion, serum urate levels, and the different tubular phases of the renal handling of uric acid under the three uricemia states. Presecretory reabsorption of filtered uric acid was always above 99%. Tubular secretion of uric acid expressed as the percentage of filtered urate, was significantly higher in hyperuricemia with respect to the hypouricemia state. Tubular reabsorption of secreted uric acid was similar in normouri-cemia and hypouricemia, but in the sate of hyperuricemia a significant diminution of uric acid postsecretory reabsorption could be evidenced. 

RENAL HANDLING OF URIC ACID IN NORMAL SUBJECTS... 

D. J. Levinson, and L. B. Sorensen, Renal handling of uric acid in normal and gouty subjects evidence for a 4-component system, Ann. Rheum. Dis. 39 173 (1980). 

A group of patients forming calcium oxalate stones are hyperuri-cosuric and it is thought that their excessive urate excretion contributes to calcium-stones formationl. The pathomechanisms invoked are dietary purine excess and endogenous uric acid overproduction, being defective tubular reabsorption of urate "unattractive because uricemia was found to be normal in patients with recurrent calcium nephrolithiasis (RCN) and hyperuricosuria. Current studies were undertaken to define the incidence, role of diet, abnormalities of the renal handling of urate, and associated metabolic disturban-c"es in patients with RCN and hyperuricosuria. 

Fifty patients (22 males and 28 females mean age 46 years) were consecutively referred to our Metabolic Unit for the evaluation of recurrent nephrolithiasis. Diagnosis was made on the basis of spontaneous emission or chirurgical extraction of two or more calculi with an interval superior to one year. In every patient we performed a metabolic study and the results were compared with those obtained in 20 controls (10 males and 10 females mean age 33 years) Hyperuricosuria was defined as daily uric acid excretion above 800 mg for men and 750 mg for woman, while on a purine-free diet. Renal handling of uric acid ms evaluated by means of pyrazinamide (PZA) and probenecid (PB) tests. ... 

Data concerning renal handling of uric acid appears in Table 2. The administration of an essentially purine-free diet normalized uricosuria in 4 patients. PZA and PB tests were within normal limits in these patients, suggesting that hyperuricosuria could be related to purine overingestion. Five patients remained hyperuricosuric even under an essentially purine-free diet, and 2 were hypo-... 

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. 

Renal handling of uric acid was examined in 30 patients with primary gout (mean age, 44 years), and in 10 normal controls (mean age, 33 years). A normal GFR, as assessed by means of endogenous creatinine clearance, was a pre-requisite for being included in the... 

Twenty-four hour urinary urate excretion, when expressed in mg/day or mg/Kg, is valuable to ascertain whether a patient underexcretes uric acid or not, but in a particular case may not differentiate patients with normal renal handling of uric acid from those with reduced tubular secretion of urate. 

According to the four-component model for the renal handling of urate, renal uric acid wasting might result from defects either of of presecretory or postsecretory reabsorption, or enhaced secretion of urate in the tubule. Future studies are required in order to delineate the tubular phases that may account for the uricosuric action of calcitonin. 

The clinical manifestations of gout, i.e. articular and renal disease, are intimately connected with hyperuricemia and/or particularities of renal handling of uric acid. It is well established that normalization of plasma uric levels will cure the joint disease. The diminution of renal uric acid excretion by administration of allopurinol will cure nephrolithiasis in its uncomplicated forms. One may presume that the other manifestations of the gouty kidney (i.e. parenchymal renal disease, hypertension and azotemia) will also be influenced by a therapy reducing urinary uric acid however no reliable reports exist as yet on this point. 

Unfortunately, at the present time there appears to be no alternative method for evaluating the renal transport of uric acid in man which is superior to the PZA suppression test. It would therefore appear reasonable to determine if a process is or is not blocked by PZA pretreatment. However, we would recommend that interpretation of the response be limited and that one not attempt to associate any response with a specific abnormality of transport. Perhaps, an effect blocked by PZA should be considered a Type A response and an effect not blocked by this agent a Type B response. Hopefully, in the future we will have the additional data necessary to determine the molecular or at least physiological basis for a Type A and Type B response. Indeed, with the recent demonstrations that the New World Monkey, a species that does not have uricase activity, handles uric acid in a similar if not identical manner to man, it may be possible to design micropuncture, isolated tubule and other in vitro experiments that will provide direct data on the sites and mechanisms concerned with uric acid transport in the kidney. 

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