Urate overproduction renal disease

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. 

Hyperuricaemia and gout from whatever cause (e.g. metabolic, renal disease, neoplasia) depends essentially on two processes, (1) overproduction and (2) underexcretion of urate. Both mechanisms may operate in the same patient but decreased renal clearance contributes to hyperuricaemia in most patients with gout. Drugs may influence these processes as follows ... 

Gout is a metabolic disease characterized by recurrent episodes of acute arthritis, usually monoarticular, and is associated with abnormal levels of uric acid in the body, particularly the presence of monosodium urate crystals in synovial fluid. Primary gout is a hereditary disease in which hyperuricemia is caused by an error in uric acid metabolism—either overproduction or an inability to excrete uric acid. Secondary gout refers to those cases in which hyperuricemia is caused by an acquired disease or disorder, such as chronic renal disease, lead poisoning, or myeloproliferative disorders. Gout generally occurs in... 

Renal Disease and Uric Acid Lithiasis in Urate Overproduction... 

AN INTEGRATIVE HYPOTHESIS FOR THE RENAL DISEASE OF URATE OVERPRODUCTION... 

Consider briefly the disease gout, which is characterized by the precipitation of urates in tissues and by the presence of hyperuricemia. Bauer and Klemperer state, 11 "The etiology of the disease is unknown." As has been pointed out by other writers, the presence of high concentrations of uric acid in the blood may be due to (1) overproduction, (2) lowered excretion, (3) lowered destruction, or, of course, any combination of the three. Let us consider two hypothetical individuals, A and B, 30 years of age who have exactly the same uric acid blood level (4 mg. per cent) and exactly the same amount of blood (8 liters). The total uric acid in their respective bloods is 320 mg. Let us suppose further that the rate of production of uric acid in the two individuals is continuously exactly the same, the rate of destruction in the two is continuously the same, and that they consume exactly the same food. One hypothetical individual, A, however, continuously excretes on the average 0.1 mg. less uric acid per day than the other. This is very little, compared with the usual total excretion of 700 mg. per day. In the course of 10 years, A s uric acid blood level will, however, have more than doubled, due to this increased retention, and he will be in the range of "gouty" as contrasted with "normal" individuals. This could happen by a very gradual increase, in one individual, of the renal threshold for uric acid. Whether excretion, production, or destruction is responsible for the difference between individuals, the total accumulation of uric acid in hyperuricemia is small. 

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