Hyperuricemic Nephropathy

  • Moufid N. Nemeh
  • Edward J. Weinman


Uric acid is the end product of purine metabolism in man. The majority of urate production occurs by de novo synthesis by defined metabolic pathways. The dietary intake of purine contributes a relatively minor amount to the metabolic pool of urate. There is no uric acid, per se, in the diet. Elimination of urate from the body occurs predominantly by renal excretion (1). The secretion of uric acid into the intestine and subsequent lysis of uric acid by bacteria account for a small fraction of uric acid excretion in healthy individuals (2). Uric acid is nearly freely filtered at the glomerulus; that is, binding of urate to plasma proteins is less than 10% (3,4). In the proximal tubule, uric acid undergoes bi-directional transport. In humans, a number of presumed genetic disorders or unusual clinical/experimental conditions have documented that the fractional excretion of urate may exceed 100% of the filtered load—a finding consistent with the presence of a secretory flux (5). The secretory flow occurs via an anion exchange mechanism at the basolateral side of the cell that mediates the uptake of urate from the peritubular capillary into the cell. A similar but not identical anion exchanger at the luminal membrane facilitates the movement of urate from the cell into the lumen (6,7). Other anions such as lactate and drugs such as diuretics may increase the serum concentration of uric acid by inhibiting the secretory flux. The reabsorptive flux of urate from the tubular fluid occurs by an anion exchange mechanism and, perhaps, by “urate” channels located in the luminal membrane of the proximal tubules (8–10). The net effect of reabsorption versus secretion varies in different species. In humans, the major direction of urate transport is in the absorptive direction. The calculated fraction of filtered urate that is excreted in the urine is less than 10% (11). This calculation ignores the amount of urate that is secreted into the lumen and subsequently back-reabsorbed. A number of factors influence the rate of reabsorption of filtered urate. Perhaps the most important factor clinically is the state of hydration of the extracellular fluid volume (12). Expansion of the extracellular fluid volume decreases the tubular reabsorption of uric acid and enhances its excretion. Contraction of the extracellular fluid volume enhances the reabsorption and decreases the excretion of uric acid. The net effect of these changes is an increase in the serum concentration of uric acid.


Uric Acid Acute Renal Failure Proximal Tubule Tumor Lysis Syndrome Gouty Arthritis 
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Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Moufid N. Nemeh
    • 1
  • Edward J. Weinman
    • 1
  1. 1.Department of MedicineUCLA/San Fernando Valley Program, VA Medical CenterSepulvedaUSA

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