Monday, 12 November 2012

How Genetic Under-Excretion Of Urate Can Cause Hyperuricaemia

When the body is in a stable state with a stable serum urate concentration, the amount of urate excreted in any day equals the amount produced during that day.

The ability of the kidneys to clear urate is often referred to as the renal clearance of urate or the urate clearance. This can be measured fairly simply by measuring serum urate and the amount of urate eliminated in the urine in a certain period, typically 24 hours (a timed collection). It can also be related to the amount of urate filtered in the given time period, referred to as the fractional excretion of urate. Many patients with gout show either reduced urate clearance or reduced fractional excretion of urate. This usually coincides with a diet high in the type of foods to avoid with gout as described at (in case you were interested).

Similar values for the urate clearance (or the fractional excretion of urate) tend to run in families so the average value for any particular family may be lower or higher than for other families.
Thus, sometimes, a patient with gout will have a poor ability to eliminate a urate load (urate under-excretion) and a similar deficiency can be shown in his son or his nephew. Identical twins (who have identical genes) have much greater similarity in their renal handling of urate than do non-identical twins (who have slightly different genes). This pattern of renal under-excretion of urate is very common and is probably the most important genetic factor which controls the serum urate concentration.

The range of urate clearance in the population is wide and although the average in a large healthy population is approximately 10 ml per minute, the range is between 5 and 15 ml per minute. Thus, members of a family whose urate clearances were between 5 and 6 ml per minute would have much more difficulty in eliminating a urate load than a family who had inherited a urate clearance of 14 to 15 ml per minute, i.e. who had three times the ability to excrete urate.