Hyperuricosuria

Hyperuricosuria and hyperuricemia have occurred with extremely high dosages. 

An alternative to thiazides is allopurinol. Some studies indicate that hyperuricosuria is associated with idiopathic hypercalcemia and that a small nidus of urate crystals could lead to the calcium oxalate stone formation characteristic of idiopathic hypercalcemia. Allopurinol, 300 mg daily, may reduce stone formation by reducing uric acid excretion. 

Pancreatic enzyme supplements are well tolerated. The capsules should be swallowed, not chewed, because pancreatic enzymes may cause oropharyngeal mucositis. Excessive doses may cause diarrhea and abdominal pain. The high purine content of pancreas extracts may lead to hyperuricosuria and renal stones. Several cases of colonic strictures were reported in patients with cystic fibrosis who received high doses of pancrelipase with high lipase activity. These high-dose formulations have since been removed from the market. 

Some investigators believe that urate may potentiate calcium stone formation, although this perception is not universally accepted. However, hyperuricosuria is common in calcium stone-forming patients, and treatment with allopurinol, thereby decreasing urate synthesis, reduces the rate of stone recurrence. Allopurinol treatment is therefore recommended for hyperuricosuric patients with calcium stone disease. The formation and management of pure urate stones are discussed in Chapter 24. 

The most common defect in oxypurine metabolism is that manifested by hypermicemia and hyperuricosuria. The many epidemiological investigations of uric acid levels have shown a distribution of serum uric acid values ranging from approximately 0.5 to 9.5 mg/100 ml of serum (E7, F6, N2). Many of the individuals with extreme levels are perfectly healthy, although there is a correlation between secondary complications and high uric acid values. ... 

In general, hyperuricemia would result from a condition that causes the sudden destruction of tissue in these cases, hyperuricosuria would also result. Interference with renal clearance (referred to in Section 4.1) could also result in hyperuricemia, but in this case there would be a decrease in urinary output. Most reported cases of hyperuricemia, aside from those involving hormonal abnormalities, are most likely related to these changes in renal clearance, possibly resulting from changes in the level of various organic acids (Section 4.1). 

For patients who are unable to swallow capsules, the contents may be emptied into applesauce, jelly, or some other nonalkatine vehicle, provided that the patient does not chew the microencapsulated beads. Side effects of pancreatic enzyme products are uncommon. Perianal irritation resembling diaper rash may occur in infants fed excess quantities of enzyme powders. Hyperuricosuria also has been reported to occur secondary to pancreatic enzyme use, apparently related to their high purine content. Proximal colonic stricture (fibrosing colonopathy) is a dose-related side effect associated with lipase doses in excess of 24,000 units/kg per day. ... 

The toxic effects of FIP can also be exhibited in patients that do not have a deficiency in aldolase B if they are parenterally fed with solutions containing fructose. Parenteral feeding with solutions containing fructose can result in blood fructose concentrations that are several times higher than can be achieved with an oral load. Since the rate of entry into the hepatocyte is dependent on the fructose gradient across the cell, intravenous loading results in increased entry into the liver and increased formation of FIP. Since the rate of formation of FIP is much faster than its further metabolism, this can lead to hyperuricemia and hyperuricosuria by the mechanisms described above. 

Using optimized procedures, up to about 11,000 FIP units of lipase can be extracted from 1 g of pancreas gland. Some pancreatin preparations may contain relatively important amounts of purines, which in patients receiving large doses of drugs can lead to hyperuricosuria and hyperuricemia [75]. 

In general, pancreatic enzyme preparations are tolerated extremely well by patients. For patients with hypersensitivity to pork protein, bovine enzymes are available. Hyperuricosuria... 

D2. Dancis, J., Jansen, V., Berman, P. H., and Balis, M. El., Inosinate pyrophos-phorylase activity in immature blood cells in X-linked congenital hyperuricosuria. Biochem. Genet 3, 311-316 (1969). 

Oligoanuric acute renal failure has been described in patients on phenylbuta-zone ". A pathogenetic mechanism reponsible is the inhibition of the tubular reabsorption of uric acid, which results in hyperuricosuria, uric acid crystallization and, eventually, urethral obstruction. Another form of this syndrome, in which there is no evidence of hyperuricaemia, is felt to be an idiosyncratic reaction. The biopsy picture is consistent with acute tubular necrosis. ... 

Juvenile Gout and Hyperuricosuria Due to Chronic Compensated Hemolytic Syndrome... 

Table 5 Patients with hyperuricemia and hyperuricosuria due to compensated hemolysis...

Hyperuricosuria is a major etiological factor in uric acid lithiasis. In addition, there is evidence for an etiological role of hyperuricosuria in calcium oxalate stone formation (1,2). Indeed, in our stone clinic, a high proportion of hyperuricosuria was also noticed among the patients with calcium urolithiasis. Since the hyperuricosuria in our stone clinic patients was established on the basis of urate determination on urine collections obtained on a regular home diet, the possibility of dietary hyperuricosuria was raised. We have therefore evaluated the contribution of dietary purine intake to uric acid excretion in our stone patients under controlled dietary conditions. 

The results of this study indicate that excessive purine intake is a major cause for hyperuricosuria among stone patients. Therefore, restriction of dietary purines is of therapeutic value in the treatment of nephrolithiasis. 

Coe, F.C., Moran, E. and Kavalach, A.G. The contribution of dietary purine over-consumption to hyperuricosuria in calcium oxalate stone formers. J. Chron. Disease, 29 793-800 (1976). 

It is known, that uric acid seems to be important in the formation of calcium oxalate stones. Robertson has shown in his model of stone formation the decrease of urinary inhibitory activity with high concentrations of uric acid. Thus the effective concentrations of the acid mucopolysaccharide fraction of urine may be reduced, which should favor the risk of stone formation. According to the literature (Table 1), hyperuricosuria is found in 15-40% of all patients with calcium oxalate stones. 

Table 1 Frequency of hyperuricosuria in clacium oxalate stones (literature)...

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