Renal disease, serum urate

Gouty arthritis is an inflammatory response to the deposition of monosodium urate monohydrate crystals secondary to hyperuricemia. It is called monosodium urate crystal deposition disease. Hyperuricemia is a serum urate concentration > 7 mg% in males and >6 mg% in females. Hyperuricemia results from overproduction (10-15% of individuals) or a renal excretion of urate lower than 400 mg uric acid/24 hours (85-90% of individuals). The urate under-excretors have a urate clearance of <6 ml/min or a urate to creatinine clearance ratio of <6%. The combination of a relative excess of dietary purine consumption together with urate under-excretion is often the basis for hyperuricemia. 

The term gout describes a disease spectrum including hyperuricemia, recurrent attacks of acute arthritis associated with monosodium urate crystals in leukocytes found in synovial fluid, deposits of monosodium urate crystals in tissues (tophi), interstitial renal disease, and uric acid nephrolithiasis. Hyperuricemia may be an asymptomatic condition, with an increased serum uric acid concentration as the only apparent abnormality. A urate concentration greater than 7.0 mg/dL is abnormal and associated with an increased risk for gout. 

There have been reports in the literature of hypouricemia coincident with specific inborn metabolic errors, but many of these cases are attributable to defects in the kidney leading to failure of renal tubular reabsorption. It was mentioned above that the excretion of uric acid by the Dalmatian coach hound can be attributed to such a mechanism (Fll). Similarly, the hypouricemia found in the Fanconi syndrome (L4) and Wilson s disease (B12) can be attributed to kidney malfunction. These are not true examples of underproduction of oxypurines, including uric acid, since the daily output of uric acid is normal. The large number of healthy people who have extremely low serum urate values, however, may indicate that there are individuals who underproduce oxypurines but suffer no ill effects because of this. The one well-documented inborn error that results in underproduction of uric acid is xanthinuria. It has been reported in relatively few cases, probably because individuals with this metabolic abnormality who suffer no ill effects would not come to the attention of a physician. 

BEHAVIOUR OF SERUM URATE IN RENAL DISEASE OF VARYING ETIOLOGY... 

Among the renal patients hospitalized in our Unit, a wide range of serum urate levels (sUr) was observed to be associated with similar degrees of renal function impairment. Thus, a retrospective study was undertaken in order to elucidate the various types of correlation between sUr and serum creatinine concentrations (sCr) in patients affected by renal diseases of different etiology. 

Gout is a metabolic disease characterized by recurrent episodes of acute arthritis due to deposits of monosodium urate in joints and cartilage. Uric acid renal calculi, tophi, and interstitial nephritis may also occur. Gout is usually associated with hyperuricemia, high serum levels of uric acid, a poorly soluble substance that is the major end product of purine metabolism. In most mammals, uricase converts uric acid to the more soluble allantoin this enzyme is absent in humans. While clinical gouty episodes are associated with hyperuricemia, most individuals with hyperuricemia may never develop a clinical event from urate crystal deposition. 

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. ... 

Subjects from two phase 3 trials were enrolled in a phase 3, long-term, open-label study (EXCEL) to assess the impact of urate-lowering therapy on renal function. Study subjects enrolled (n=1086) were treated with febuxostat 80 mg or febuxostat 120 mg or allopurinol 300mg daily. In the first 6 months of treatment subjects were allowed to switch between doses in order to achieve and maintain a serum uric acid level >3 to <6mg/dL. The most common adverse event was liver enzyme elevation. Eight study subjects died during the study, of whom five deaths were attributed to CV events sustained by subjects with extensive histories of CV disease... 

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