Colchicine toxicity in renal patients – Are we paying attention?

Abstract

Colchicine is an approved agent in the management and prophylaxis of gout and familial Mediterranean fever but its therapeutic value is limited by its narrow therapeutic index. Multisystem toxicity is uncommonly reported; and is often associated with renal impairment and/or specific drug interactions. We report two cases of colchicine toxicity marked by severe neuromyopathy in a diabetic with stage 4 chronic kidney disease (CKD) and a renal transplant recipient. Both patients presented with diarrhea, acute on chronic kidney injury and progressive muscle weakness while on colchicine for several weeks or longer. In addition to kidney disease, risk factors for colchicine toxicity included maintenance therapy with simvastatin in the first patient and cyclosporine in the second. Creatine phosphokinase (CPK) was elevated in both cases at presentation and neurophysiologic studies showed a pattern of severe myopathy with axonal sensorimotor neuropathy. The first patient recovered from neurological weakness in a few weeks, but the second patient suffered an extraordinarily protracted and severe neuromuscular disability for a year. The two cases reinforce the need for extra vigilance in prescribing and monitoring colchicine therapy in renal patients with specific attention to drug interactions known to increase the risk of toxicity, thus avoiding such combinations in patients with renal impairment.

Transcriptional induction of the heat shock protein B8 mediates the clearance of misfolded proteins responsible for motor neuron diseases

“…Colchicine is administered orally, and it is usually well tolerated at low doses and shows limited adverse effects at high doses particularly on the gastrointestinal tract 73 . A potential limitation of colchicine has been observed in some patients with advanced renal failure exposed to long-term (prophylactic) oral colchicine treatment, in which a low fraction of colchicine is not metabolized and not removed by hemodialysis, causing cumulative toxicity that resulted in neuromyopathy 75 76 77 . Interestingly, high doses of colchicine combined with starvation enhance the autophagy flux in skeletal muscle of normal mice 78 .…”

An Unexpected Interaction between Sofosbuvir/Ledipasvir and Atorvastatin and Colchicine Causing Rhabdomyolysis in a Patient with Impaired Renal Function

“…Atorvastatin can itself increase levels of colchicine due to P-gp inhibition. Using colchicine in combination with a statin has been reported to cause myotoxicity, especially in the setting of CKD [8]. Atorvastatin 80 mg was used in this patient as it was used for secondary prevention for her coronary artery disease.…”

“…Colchicine is renally eliminated and requires dose adjustments based on renal dysfunction. Thus, this patient's stage III CKD combined with a high colchicine dose and P-gp mediated drug interactions could have played a critical role in increasing the chance of this unanticipated toxicity [8]. There was little concern for mitochondrial toxicity caused by a lactic acidosis as the patient has a normal anion gap and normal lactate levels.…”

A rare case report of heavy dose colchicine induced acute kidney injury

“…Various factors such as depletion of volume/hypotension, rhabdomyolysis and multi-organ failure contribute to renal failure after colchicine intoxication [ 12 ]. Up to 20% of colchicine is excreted by the kidneys [ 13 , 14 ], and this is often associated with renal impairment [ 15 ]. In the current case, depletion of volume/hypotension and rhabdomyolysis was likely to be the primary cause of acute renal insufficiency and continuous anuria.…”