Colchicine toxicity in patients with chronic renal failure

The therapeutic virtues of colchicine have been known since the 6th century AD, and it has been used since the 19th century for the treatment of gouty arthritis (for historical review see [1]). More recently colchicine became the only efficient treatment for familial Mediterranean fever (FMF) [2] and the rare Muckle-Wells syndrome [3]. This drug, a highly lipophilic alkaloid extracted from Colchicum autumnale (meadow saffron) (Fig. 1), diffuses into all cells, irreversibly impairing microtubule organization and function and arresting the cell cycle at metaphasis. It blocks intracellular protein trafficking, membrane turnover and exocytosis, thereby hampering leukocyte functions, intestinal water and solute reabsorption, bone marrow cytogenesis, muscle contractility and nerve axonal viability [1]. Colchicine is a powerful poison with a narrow margin between efficacy and toxicity. Doses of 1-3 mg/day are usually followed by diarrhoea within a few days [4], and more than 3 mg/day for several days induces profuse diarrhoea, acidosis, dehydration, bone marrow aplasia and cardiac failure. Rapid death may ensue, due to hypovolaemic, cardiogenic and septic shock [5]. Chronic toxicity is rare in patients with no visceral compromise because diarrhoea usually leads to stopping treatment. Conversely, toxic effects appear early in circumstances that impair colchicine excretion [6], such as hepatocellular insufficiency, chronic renal failure and cyclosporin A treatment [7,8]. Chronic toxicity is marked by a particular form of neuromyopathy [9] and often myocardial failure, which entails a dismal prognosis. Despite its hazards in chronic renal patients, colchicine is still used in gouty arthritis and in pseudogout following metastatic calcification.