A proposal for identifying the low renal uric acid clearance phenotype

Hyperuricaemia, defined as a plasma concentration of urate (used interchangeably with uric acid) greater than 0.42 mmol/L (7.0 mg/dL) [1], is the major risk factor for gout. Impaired renal clearance of urate, or 'under-excretion', accounts for up to 90% of hyperuricaemia cases. In the remainder, the mechanism is excessive production of urate due to purine synthetic enzymatic abnormalities, haematological malignancies [2] or dietary excess. Under-excretion and over-production of urate can co-exist [3].Investigation of the molecular basis of low renal urate clearance ought to be conducted in individuals where low clearance has been proven but most studies have used hyperuricaemia alone as the inclusion criterion, thereby reducing the power of the study [4-7].Simkin and colleagues proposed a spot morning urine test of urate excretion normalised to glomerular filtration rate (GFR) to identify 'over-producers' of urate [8]. We propose an amendment to the Simkin Index in order to focus upon abnormalities in renal tubular urate transport causal for 'under-excretion' of urate. We suggest that renal uric acid clearance be normalised to the individual's GFR, as estimated by the creatinine clearance, to give the fractional clearance of urate (FCU). FCU has been used in physiological studies but usually employing 24-hour collections of urine [3,6]. We propose that FCU calculated from spot urine samples be used as the inclusion criterion in studies examining the genetic basis for relatively low renal clearance of urate. A renal lesion(s) that reduces the ability of the kidney to clear uric acid, but not creatinine, will manifest as a low FCU relative to normal.FCU is calculated using the formula:By contrast, the Simkin Index does not include plasma urate concentrations:The concentrations of plasma and urinary creatinine (Pcreat; Ucreat) and urate (PUA; UUA) are readily obtained. Measurement of the volume of urine is not required, which is a significant practical advantage [8]. W