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Hyperuricemia and hypoalbuminemia predispose to cisplatin-induced nephrotoxicity.

The usefulness of pretreatment biochemical parameters in the prediction of nephrotoxicity associated with cisplatin treatment was studied. Twenty-two patients, who received 29 cycles of cisplatin, were evaluated. Cisplatin was given every 3-4 weeks with saline and mannitol. Azotemia occurred in almost all patients and was transient, peaking 1-2 weeks after therapy. The change in serum creatinine from baseline to peak correlated inversely with pretreatment serum albumin (r = -0.73; P less than 0.01) and with pretreatment uric acid (r = 0.76; P less than 0.01). Ten patients with uric acid levels of less than 6 mg/dl were receiving allopurinol. The competition between organic anions and cisplatin for excretion may, in part, explain the protective effects of hypouricemia. Hypoalbuminemia affects peritubular oncotic pressure and may in turn affect platinum excretion. Hypoalbuminemia also reduces the half-life of cisplatin, exposing the kidney to more of the unbound filterable drug.

Cisplatin↗

[Gout tophi and Heberden nodules in hyperuricemia].

The tophus is a characteristic and pathognomonic sign of chronic gout. Before effective drugs were available for the treatment of hyperuricaemia about 50-60% of patients with gout developed clinically and radiologically apparent urate crystal deposits. Clinical cutaneous manifestations of chronic gout are now rarely observed. However, the presence of degenerative tissues, as in idiopathic osteoarthritis of the fingers, may predispose to the deposition of urate crystals. We report on a patient with secondary--probably diuretic-induced--hyperuricaemia and gout tophiin Heberden's nodes.

Aged↗

Furosemide-induced hyperuricemia, hyperglycemia, hypertension and arterial lesions in nonarteriosclerotic and arteriosclerotic rats.

Male and female, Sprague-Dawley rats, with and without arteriosclerosis, were subjected to chronic treatment with furosemide for 4 weeks. Furosemide-treated rats manifested increased adrenal and kidney weights along with an increase in blood pressure; rats with pre-existing arteriosclerosis showed considerable reduction in heart and body weights. Furosemide-treated animals displayed an increase in circulating levels of creatine phosphokinase, lactic dehydrogenase, free fatty acids, glucose, BUN and uric acid. Circulating levels of triglycerides, total cholesterol, and corticosterone were subnormal, whereas aldosterone was distinctly elevated. Despite these metabolic derangements, de novo arterial disease did not appear in virgin rats without pre-existing arterial disease. However, furosemide-treated virgin rats did develop grossly visible apical and left-ventricular foci of myocardial necrosis, i.e., 12% in males, 9% in female virgins. Breeder rats with pre-existing arteriosclerosis manifested exacerbation of their arterial disease, e.g., intimal calcification of the epicardial coronary arteries along with foci of myocardial fibrosis and islet beta-cell granule depletion. Adrenocortical lipid alterations appeared in all animals treated with furosemide. It is suggested that this spectrum of metabolic and histopathologic degenerative changes may have been caused by secondary aldosteronism due to the chronic treatment with furosemide.

Animals↗