Organic acid excretion patterns in gout.

The hyperuricaemia associated with gout is believed to be due to overproduction of uric acid, to impaired renal excretion of uric acid, or to alterations in both mechanisms (Seegmiller, 1966). In all likelihood, gout encompasses a heterogeneity of biochemical disorders, the metabolic or enzymatic bases of which with one exception, have not yet been completely delineated. The Lesch-Nyhan syndrome, a familial disorder with overproduction of uric acid, has been shown to be due to deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (Seegmiller, Rosenbloom, and Kelley, 1967). In most instances, it has been shown that overproduction ofuric acid, as measured by incorporation of labelled glycine, is accompanied by increased excretion of uric acid (Seegmiller, Grayzel, Laster, and Liddle, 1961). In a series of 300 patients examined by Gutman and Yu (1957), 67 per cent. were found to be normoexcretors (24-hr urinary urate excretion within the normal range of 418 + 70 mg.), 28&7 per cent. were found to be hyperexcretors, and 4-3 per cent. hypoexcretors. On recalculating these data, Wyngaarden (1960) found that both normoexcretors and hyperexcretors with a normal glomerular filtration rate (GFR) had a reduced urate clearance when compared to normal subjects, implying that some hyperexcretor patients might also have a renal abnormality. It is now assumed that about one-third of gouty patients are overproducers, one-third have impaired renal tubular transport of urate, and one-third have a combined defect (Seegmiller and others, 1961). Rieselbach, Sorensen, Shelp, and Steele (1967) have presented preliminary data indicating that the decreased urate clearance in some gouty patients is due to impaired tubular secretion. Since it has also been previously shown that certain organic acids interfere with urate excretion, presumably by competing with urate for tubular secretion (Gibson and Doisy, 1923; Michael, 1944; Yu, Sirota, Berger, Halpern, and Gutman, 1957; Moller, 1962; Goldfinger, Klinenberg, and Seegmiller, 1965), we were interested in examining the organic acid excretion patterns in gouty patients with both reduced and normal urate clearance. Fractional excretion values for urate in normal control subjects have been calculated by Wyngaarden (1960) as 7-6 ± 2-4 per cent. of the filtered load. Since our gouty patients with normal renal function had a mean GFR of 98 mi./min., we have arbitrarily designated a value of 5-2 ml./min. (i.e. one S.D. below the normal mean) as the dividing line between reduced and normal urate clearance. Patients with reduced GFR were examined separately because of evidence that renal tubular transport of urate is altered in uraemia (Gutman and Yu, 1957).