Uric Acid in Two Patients with Wilson's Disease (Hepatolenticular Degeneration).

Abstract

In the course of a complete laboratory examination of a brother and sister both suffering from Wilson's disease, it was discovered that the serum urate levels in both individuals were unusually low ( 1-2 rng %), according to the colorimetric method ( 1 ) . To elucidate the mechanism of this behavior it was decided to determine uric acid pool size and turnover rate by injecting W5 uric acid in the manner previously described ( 2 ) .The male subject was injected intravenously with 2 1.7 mg of N15 uric acid (14.81 atom 7 0 excess), and all urine was collected ad libitum for 5 days. From these results the pool size was calculated to be 442 mg and the turnover rate, 1.95 pools per day. The mean excretion for 4 days, determined by the isotope dilution method in the period just after the other mea,surements was 848 mg per day.The turnover was 442 x 1.95 = 862 mg and the per cent of the turnover excreted was 848/862 x 100 = 98% (4).A similar study was performed on the female subject, using 19.5 mg of W5 uric acid. The pool size was calculated to be 304 mg and the turnover rate was 1.78 pools per day. The turnover was therefore 541 mg. The *This study was supported in part by a grant-inaid from the National Institutes of Health, Bethesda, Md .mean excretion for 8 days immediately following the test period was 391 mg and the per cent of the turnover that was excreted was 72%.To test the possibility that the kidney tubules were completely inhibited in so far as their resorption of uric acid was concerned, the drug, Benemid, [p (di-n-propylsulfamyl) benzoic acid] was administered to the female subject and the uric acid injection was repeated. Sirota et al. ( 3 ) have demonstrated that this drug selectively inhibits tubular resorption of uric acid. The subject was given 3 X 0.5 g Benemid per day by mouth for 6 days and was then injected intravenously with 20.8 mg of isotopic uric acid. The pool size was determined to be 167 mg and the turnover rate 2.34 pools per day. The turnover was therefore 391 mg and the per cent turnover excreted was 8676, based on a mean excretion of 452 mg during 12 days on Benemid. The mean urinary excretion after Benemid was not statistically different from the control value, the P value for the t test being well above the 1070 level.After Benemid therapy was started on the female subject, her clinical condition became considerably worse. After cessation of the therapy she had not improved. Her present serum uric acid level is approximately 1 mg at UNIV OF MICHIGAN on July 4, 2015 ebm.sagepub.com Downloaded from

Kidney involvement in Wilson's disease: a review of the literature

“…Moreover, renal glycosuria was also observed in half of the patients. Additionally, WD patients frequently exhibit hypouricemia [ 30 , 31 ]. Significant low-weight proteinuria was also noted in 25% of 40 patients in Sözeri's report, mostly in patients with no or short duration of treatment [ 32 ].…”

Urate Excretion

“…Decreased reabsorption of filtered urate with increase of urate clearance is found in many generalized proximal tubular disorders, e.g. in the Fanconi syndrome (Sirota et al 1952), Wilson's disease (Bishop et al 1954), and in cadmium poisoning (Kazantzis et al 1963). The clearance is only slightly below that of inulin, and is not appreciably altered after administration of uricosuric drugs.…”

Wilson's Disease Presenting with Severe Thrombocytopenia and Urinary Symptoms: Case Report and Literature Review

“…Early studies demonstrated excessive urinary excretion of copper, and renal damage was attributed to the deleterious effect of accumulation of copper in the kidneys, resulting into progressive deterioration of tubular functions and also renal plasma flow and glomerular filtration rate, similar to the effects of other heavy metals. Renal tubular dysfunction with consequent aminoaciduria, hypercalciuria and hyperphosphaturia inducing nephrocalcinosis, uricosuria with decreased serum urate level, nephrolithiasis, glucosuria in the absence of hyperglucemia, hypokalaemia and renal tubular acidosis are documented [9,[20][21][22][23][24][25][26][27][28][29][30].…”