Renal Function in Wilson's Disease1

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Abstract
Renal clearance studies (11) were carried out in 9 patients with Wilson''s disease in various stages of the disorder. The inulin clearance was below the lower limits of normal in 8 patients. CPAH was decreased in every instance. Tubular secretory capacity, as measured by TmPAH was reduced in the 6 patients examined. When TmpAH was very low, probenecid (p-(dipropylsul-famyl)-benzoic acid) elicited little further decrease. Tubular reabsorp-tion of alpha-amino nitrogen, urate, phosphate, and glucose was defective, as indicated by the generally increased clearance ratios. Serum inorganic phosphate levels were in the lower range of normal or reduced, and may account for the osteomalacia occasionally encountered in Wilson''s disease. The blood glucose tended to be low in the 4 patients so studied, probably explaining the occasional glycosuria in this disorder. Serum urate levels were consistently low. Probenecid elicited a uricosuric response in most instances but this was least pronounced in those subjects who initially had the most impaired tubular reabsorp-tion of urate. The urine pH tended to be more alkaline than normal, owing to slight urinary excretion of bicarbonate at plasma bicarbonate levels not ordinarily associated with renal loss of bicarbonate. The response of 2 subjects to ammonium chloride-induced acidosis was essentially normal in respect to mechanisms for acidification of the urine. Results indicate progressive deterioration of certain discrete tubular functions, and also of glomerular filtration and renal plasma flow, with advance of the disease. It is suggested that these renal changes may reasonably be ascribed to the deleterious effects of the accumulation of Cu in the kidneys; such effects are known to accompany the deposition of other heavy metals in this organ. In this view the renal abnormalities described are secondary to a disturbance in Cu metabolism rather than a direct consequence of the abnormal gene on renal function.