Renal function in gout: With a commentary on the renal regulation of urate excretion, and the role of the kidney in the pathogenesis of gout

Abstract

1. 1. A study was made of renal function in some 300 gouty subjects. Standard renal clearance technics were employed in approximately 160 cases, including some asymptomatic hyperuricemic relatives of these gouty subjects. 2. 2. C inulin, C PAH and Tm PAH were for the most part consonant with the values found in normal subjects of equivalent age, but impairment of renal hemodynamics was not infrequent particularly in those of advanced age or with overt renal disease. 3. 3. Determinations of urinary urate excretion, whether measured as UV urate in short clearance experiments or in twenty-four-hour urine collections, gave values within the normal range in most cases. In a significant minority of instances, however, the urinary urate excretion was unequivocally in excess of the limits of normal variation. 4. 4. The filtered urate load was found to be increased in most gouty subjects. The presumptive tubular reabsorption of urate was correspondingly increased but, so far as could be determined, not disproportionately so in relation to the percentage of urate reabsorbed by the tubules at equivalent filtered urate loads in normal man. 5. 5. The results thus indicate essentially normal discrete renal functions in most gouty subjects. With advancing years and disease, however, the glomerular filtration rate progressively declines and some tubules apparently deteriorate. Secondary renal retention of urate then becomes apparent. 6. 6. The data fail to disclose any primary defect in tubular function, specifically of abnormally enhanced tubular reabsorption of urate. On the contrary, the clearance data imply overproduction of urate in gout. This interpretation is supported by reference to metabolic data. 7. 7. The question of tubular excretion of urate is reviewed. The available clearance data are not incompatible with the view that the filtered urate load, assuming complete filtrability of plasma urate, normally is wholly or in very large part reabsorbed by the tubules, and that the excreted urate derives entirely, or for the greater part, from tubular secretion; the analogy with potassium excretion is pointed out. Indirect but not direct support of this postulation is presented. 8. 8. It is concluded that the pathogenesis of hyperuricemia and of the other manifestations of gout cannot be ascribed to any hypothetic primary renal defect, whether of abnormally great tubular reabsorption or deficient tubular secretion of urate.