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How High Urine Uric Acid Levels Can Lead To Gout and Kidney Disease

The distinction has already been drawn between the concentration of uric acid or urate in the blood plasma and tissue fluid and that in the urine. A high concentration of uric acid in urine can occur without the presence of gout or even, in the early stages, without the presence of hyperuricemia.

Accordingly, a high concentration of uric acid in urine (which can easily result from a high uric acid gout diet) is in itself a risk factor for the development of kidney disease, separate from a high urate concentration in the blood.

There are four main situations when a high urine uric acid will occur and may cause kidney damage:
genetic overproduction or inherited over-excretion of urate
increased breakdown of cell nuclei
uricosuric therapy, and
high dietary purine consumption.

Genetic Overproduction Or Inherited Over-Excretion Of Urate

Genetic over-production of urate has already been referred to as occurring in HPRT deficiency. It can also occur in rare inherited disorders of the kidney tubules where urate cannot be reabsorbed and where there is a very high urine urate.

These situations are rare and would not be seen in 99 per cent of gout sufferers. However, the study of rare conditions such as these can aid understanding of the more common disease mechanisms.

Increased Breakdown Of Cell Nuclei
Increased breakdown of cell nuclei is most commonly seen following chemotherapy for cancers. Chemotherapy acts by destroying the cancerous cells and, when the nuclei of these cells are degraded, it results in a great increase in the production of urate. This large urate load needs to be disposed of, and the greatest part of it is eliminated by the kidney The load may be so great that some of the kidney tubules are blocked by uric acid crystal deposits, preventing their particular nephrons from functioning. This problem is now usually anticipated during chemotherapy and is prevented by judicious use of the drug allopurinol (to suppress the urate production) and maintenance of a large volume of alkaline urine (to increase the solubility of the urate and reduce crystal formation).

Uricosuric Therapy

Uricosuric drug treatment lowers the serum urate by increasing the urine uric acid excretion.
The increased urinary uric acid excretion may be a problem if the uric acid concentration and pH of the urine are such as will allow uric acid crystals to form within the tubule or collecting duct. Usually preventative strategies are put in place, but the potential for crystal formation may still persist. The increase in urinary uric acid is only mild when the patient is stabilised on the uricosuric drug, but the risk of crystal formation from a high urinary uric acid may recur if therapy is stopped and re-started.

High Dietary Purine Consumption

A large intake of purines or increased urate production such as can occur after heavy alcohol consumption can lead to a sudden load of urate being presented to the kidneys for elimination. This creates the same potential for uric acid crystals to form within the renal tubule as high urate concentrations from any other cause.