Uric acid, as the end-product of
purine metabolism in humans, presents a clinical problem because of its relative insolubility, particularly in the
acid environment of the distal nephron of the kidney. As a result, states of enhanced
purine catabolism increase the
urate load on the kidney, leading to intrarenal precipitation. Major causes of increased
purine metabolism are
malignancies with rapid cell turnover, such as
leukemias and
lymphomas, and the added acceleration of cell lysis that occurs with
chemotherapy and radiation. Serum
urate levels rise rapidly, and
acute renal failure occurs as a consequence of tubular deposition of
urate and
uric acid. The keys to the diagnosis of acute
uric acid nephropathy are the appropriate clinical setting of increased cell lysis,
oliguria, marked
hyperuricemia, and hyperuricosuria. A urinary
uric acid-to-
creatinine ratio greater than 1 helps to distinguish acute
uric acid nephropathy from other catabolic forms of
acute renal failure in which serum
urate is elevated. Preventive treatment involves pharmacologic
xanthine oxidase inhibition with
allopurinol and alkaline diuresis. Occasionally,
acute renal failure occurs despite
allopurinol because of the tubular precipitation of the precursor metabolites, such as
xanthine, which accumulate with
xanthine oxidase inhibition. Dialysis
therapy may be required both to correct
azotemia and to reduce the body burden of
urate.
Hemodialysis is preferred because it can achieve greater clearance than other dialysis modes.