We thank Dr. Peter Simkin's for his comments. Nevertheless, some points should be emphasized.
First, we used 700 mg/day/1.73 m2 as the cut-off value for 24-hour urinary uric acid because it is widely used in clinical practice and only to ascertain if it was an appropriate cut-off point for classifying patients with gout. I agree with Dr. Simkin that 880 mg/day/1.73 m2 may be a more appropriate value. Indeed, we designed the study because we thought that 700 mg/day/1.73 m2 was not the proper cut-off point.
Second, the fact that the clearance of uric acid did not change significantly in patients taking allopurinol may be interpreted as follows. Our patients did not have exogenously induced hyperuricemia or hypouricemia after high doses of allopurinol, and data were strictly paired, contrary to other studies (1). Thus, the levels of serum uric acid during therapy were within those observed in clinical practice during urate-lowering therapy. Indeed, we have recently published a retrospective study on the long-term efficacy of urate-lowering therapy in a large cohort of renal transplant patients. Again, clearance of urate was unchanged in patients on allopurinol therapy (2). Dr. Simkin's hypothesis suggesting that the tubular transporter for reabsorption may be an inducible one is attractive and surely warrants further investigation to ascertain if this is true in any range of serum urate level.
Third, I also agree with Dr. Simkin about the usefulness of the excretion of uric acid per volume of glomerular filtration (EuGF) test in everyday clinical practice—easy to do, cheap, and showing a good correlation with other parameters—but related to renal function (3–5). In fact, since the serum creatinine to urinary creatinine ratio (Pcr/Ucr) quotient may rise in patients with significant renal function impairment, this increase may result in a high EuGF result. Thus, patients showing moderate to severe renal function impairment may show EuGF > 0.6 mg/dl and may be misclassified as overproducers. They are not actually overproducers, but relative good excretors when considering the low glomerular filtration rate, as it occurs with fractional excretion of urate in patients with significant renal function impairment. Figure 1 shows the good correlation between 24-hour urinary uric acid and EuGF when patients are stratified according to clearance of creatinine in our cohort of 404 gouty patients (unpublished data). Nearly 50% of the patients with apparent overproduction according to EuGF due to renal insufficiency will not show serum creatinine values >1.5 mg/dl (most of them older patients with low body mass index). Thus, patients showing EuGF > 0.6 mg/dl, even with “normal” serum creatinine, should be tested with 24-hour urinary samples, and clearance of urate and creatinine should be calculated.
Finally, the suggestion of eliminating the term “underexcretion” is certainly plausible, but “overexcretion” should also be eliminated. Indeed, patients with overproduction and normal renal function will show apparent overexcretion if compared at hyperuricemia with normal controls at normal serum urate levels (6), but similar uric acid excretion when both groups show similar glomerular filtered load of urate (6). Thus, we suggest that “inefficient excretion” and “efficient excretion” may be more proper physiopathologic terms than “underexcretion” or “overexcretion,” respectively, when we are talking about renal handling of uric acid.
In addition, we suggest that EuGF should be changed to Simkin's Index as a tribute to Dr. Simkin's work in this, most of the times undervalued, field of gout.