There are several theories of the pathogenesis of urate 2 accumulation in patients with gout. A disturbance of elimination of this substance by the kidneys is probably the most popular. This has been challenged, however, in a previous communication from this laboratory (1), since it appears to be inconsistent with certain experimental data. Whether or not this theory is valid, it deserves serious consideration because urates as naturally occurring end-products of purine metabolism are disposed of by the body largely by excretion through the kidneys. If one pursues the hypothesis to a logical conclusion, any defect of elimination might be inherited or it might be an acquired phenomenon following damage to the functioning units of the kidneys.The accepted theory (2, 3) of renal physiology in man assumes that urates are present in glomerular urine as are other ultrafiltrable substances and reabsorbed in part by the cells lining the tubules. If the kidneys were primarily at fault in the gouty diathesis, accumulation of urate might be attributed either to (a) a reduction of the number of functioning glomeruli or (b) an increased reabsorption by the tubules. Both of these phenomena are partially susceptible of quantitative analysis now that improved methods for the study of kidney function are available.A presentation and discussion of kidney function data, as determined by five experimental procedures, are contained in this communication. These include tests for the excretion of substances normally present in the body such as urea, creatinine, urate, sodium and chloride and for the excretion of foreign substances introduced parenterally such as phenolsulphonphthalein, neo-iopax 1 This investigation was supported in part by a grant from the Corn Industries Research Foundation.2 The term urate is preferable to uric acid in a consideration of acid-base equilibrium of biological media just as chloride is preferable to hydrochloric acid and phosphate is preferable to phosphoric acid. and inulin. Studies were made of normal persons and of patients suffering from diseases other than gout, as well as of patients with classical gout. The action of drugs used therapeutically in the treatment of acute and chronic gouty arthritis was investigated. SUBJECTSThirty-one persons acted as experimental subjects. Twenty-two were afflicted with gout; six were patients with diseases other than gout; three were normal persons. The patients with gout were selected without regard to extent of disease or duration of symptoms. It was necessary only that the criteria for the diagnosis of gout were satisfied (1, 4, 5) and that the patients consented to hospital admission for study. All except K. He. were males. Their ages varied from 28 to 81 years. Each patient had had two or more attacks of acute arthritis, and on two or more occasions the concentration of fasting serum urate had been greater than 6.0 mgm. per 100 cc. Osseous or cartilagenous tophi were suspected from the roentgenogram in thirteen. Subcutaneous tophi were present in seventeen....

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