Alteration of urate metabolism by weight reduction

Summary: Urate kinetics within the body were defined on two occasions in a patient with gout. On the first occasion, he was obese and urate metabolism was abnormal, whereas on the second occasion, after 18 kilogrammes weight loss, urate metabolism was within the normal range. This alteration was due to two changes, firstly, a rise in the renal clearance of urate without change in glomerular filtration rate, possibly related to an associated fall of his previously elevated blood pressure to normal, and secondly, a reduction in the rate of urate production from a high initial level to one within the normal range. This study emphasises the importance of acquired factors in the development of gout and that correction of these may obviate the need for pro‐longed drug therapy

Isolation of crystalline uric acid from urine, for urate pool or turnover measurements

A technique is described for the isolation of crystalline uric acid from urine by adsorption on an anion-exchange resin column and elution by a pyridine-formate solution. This method yields good recoveries of uric acid and provides crystals even when the urinary uric acid excretion is low

Purine synthesis de novo in cultured lymphoblast cells derived from patients with gout

Rates of de novo purine synthesis in lymphoblast cell cultures derived from ten patients with gout were compared with those from control individuals. Since the rate of de novo purine synthesis was dependent on the growth rate of the culture, an assay procedure was developed to account for the variation in lymphoblast growth rates and to permit valid quantitative comparison between purine synthesis in each cell line. Clear differences were demonstrated between the rates of purine synthesis in cells from normal control subjects and those from patients with a deficiency of hypoxanthine-guanine phosphoribosyltransferase activity (HPRT-deficient). Lymphoblasts from the gouty patients showed purine synthesis either within the normal range or intermediate between this and the HPRT-deficient cells. In patients having normal renal function, de novo purine synthesis of lymphoblast cells correlated with the degree of urate production as reflected by the urinary excretion of urate over a 24 h period. Three patients, with demonstrable excessive production of urate in vivo, exhibited increased purine synthesis in lymphoblasts. This increased synthesis did not appear to result from any of the enzyme mutations currently recognized as responsible for abnormal purine metabolism

Abnormal renal urate homeostasis in systemic disorders

Abnormalities of renal handling of urate occur in a wide variety of physiological and pathological conditions and are mediated by factors including renal blood flow, glomerular filtration rate, urine flow rate, urinary constituents, metabolites, hormones and drugs. The determination of the aetiological factors in each abnormal situation is complex and the problem is discussed in relation to a variety of conditions including renal tubular disorders and metal intoxications, hypertension, toxaemia of pregnancy, glycogen storage disease, fructose administration, hereditary fructose intolerance, as well as obesity, regular alcohol consumption and hyperlipoproteinaemia. Apart from those diseases, usually genetically determined, which are associated with excessive production of urate, the most common causes of hyperuricaemia act at a renal level and result in a reduction in the net renal excretion of urate

Adenine phosphoribosyltransferase deficiency: its inheritance and occurrence in a female with gout and renal disease

Summary: Adenine phosphoribosyltransferase deficiency: its inheritance and occurrence in a female with gout and renal disease. B. T. Emmerson, R. B. Gordon and L Thompson, Aust. NX. J. Med., 1975,5, pp. 440–446