Hypouricemia secretion

Some drugs, such as the two-substituted thiodiazole and acetazolamide (Diamox), increase serum uric acid by stimulating uric acid synthesis (K9). Others, such as chlorothiazide (Diuril), increase uric acid retention by decreasing uric acid excretion (K9). Hydrochlorothiazide inhibits tubular secretion and has been shown to increase pretreatment mean uric acid values from 6.5 mg/100 ml to 10.3 mg/100 ml by the third treatment day. In a patient with gout, the level increased from 8 mg/100 ml to 12 mg/100 ml (H6). In a single case a paradoxical hypouricemia occurred (H6). 

Previously, the disordered renal transport of uric acid in patients with renal hypouricemia had been explained by a 4-component model. In our review, 59% of the patients with ALPE and renal hypouricemia were classified as the presecretory reabsorption defect type, followed by the total defect in uric acid transport (no secretion and no reabsorption) and total reabsorption defect types (Table 8). 

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. 

Table 1. Uricemia, uricosuria, presecretory reabsorption, tubular secretion, and postsecretory reabsorption of normal males in the states of hyperuricemia, normouricemia, and hypouricemia.

UAp Uric acid filtered. UAg Uric acid secreted. p<0.01, with respect to the normouricemia state. p<0.05, with respec to the hypouricemia state. 

When plasma urate concentrations increase to around 10 mg/dl, tubular secretion and postsecretory reabsorption modulate serum uric acid levels by a slight increment of the first and a marked diminution of the second, thus increasing uricosuria and lowering uricemia. The inverse mechanism was not evident in the hypouricemia state, possibly because low urate filtrable load is undoubtedly less pernicious than hyperuricemia. 

Hypouricemia could be the result of diminished uric acid production, excess urate excretion, or a combination of these mechanisms. Recently, hypouricemia has been noted in a few patients with neoplastic diseases, particularly Hodgkin s disease and pulmonary tumors. In many cases, renal leak of uric acid was responsible for the low serum uric acid values due to structural tubulopathies, inappropriate ADH secretion, or an hypothetical production of a tumoral uricosuric substance that still remains speculative. ... 

We have studied a patient with thyroid carcinoma and renal hypouricemia that could be attributed to increased calcitonin secretion. 

It has also been suggested that hypervolemia secondary to inappropriate ADH secretion was responsible for the increased uric acid clearance in two patients with pulmonary tumors. In other cases of paraneoplastic hypouricemia, tumoral secretion of an hypothetic uricosuric substance has been related to disease activity, but the existence of this uricosuric substance remains speculative. ... 

Our patient had basal hypouricemia due to renal urate overexcretion. Renal leak of other substances and inappropriate secretion of ADH were ruled out. Pentagastrin injection elevated plasma calcitonin with simultaneous increment of urate fractional excretion and diminution of serum uric acid, lending support to the hypothesis... 

SUPPRESSION OF URIC ACID SECRETION IN A PATIENT WITH RENAL HYPOURICEMIA... 

Clearly the consistently higher ratios we observed indicate that urate secretion in our patient is almost always greater than 8% of glomerular filtration and may reach 100% or more of that filtered. Similar data have been reported from the two other known cases of renal hypouricemia. 

---