Renal failure clofibrate

Clofibrate causes a necrotizing myopathy, particularly in patients with renal failure, nephrotic syndrome or hypothyroidism. The myopathy is painful and myokymia of unknown origin is sometimes present. The mechanism of damage is not known, but p-chlorophenol is a major metabolite of clofibrate and p-chlorophe-nol is a particularly potent uncoupler of cellular oxidative phosphorylation and disrupts the fluidity of lipid membranes. Muscle damage is repaired rapidly on the cessation of treatment. 

All fibrates increase the lithogenicity of bile. Clofibrate has been associated with increased risk of gallstone formation gemfibrozil and fenofibrate reportedly do not increase biliary tract disease. Renal failure and hepatic dysfunction are relative contraindications to fibrate therapy. Combined statin-fibrate therapy should be avoided in patients with impaired renal function. Gemfibrozil should be used with caution and at a reduced dosage to treat the hyperlipidemia of renal failure. Fibrates should not be used by children or pregnant women. 

This syndrome of myalgia, stiffness, weakness and malaise, commonly with an increase in serum enzymes, is well-recognized (SED VIII, p. 934), and in the past evidence has been advanced that it may be more common in patients with the nephrotic syndrome. In 1975, Pierides et al. pointed to the possible complications if the drug is used in chronic renal faUure. When treating 5 uraemic patients with 1 -2 g clofibrate daily, they recorded muscle weakness and tenderness as weU as a rise in serum creatine kinase. Excessive accumulation of both total and free serum chlorophenoxyisobutyric acid (C.P.I.B.), the active metabolite of clofibrate, was found in the 3 patients in whom it was sought (4 ). Their view that clofibrate should in renal failure be used very cautiously or not at all is supported by the report from Spain on a similar case where administration of 1.5 g clofibrate daily for 9 days to a patient undergoing dialysis resulted in a muscular syndrome with elevation of SCOT, SGTP, CPK, LDH and aldolase (5 ). 

Dosa, S., Mallick, N. P. and Slotki, I. N. (1976) Acute-on-chronic renal failure precipitated by clofibrate. Lancet, 1, 250. 

The most common cause of hyponatremia in hospital patients is SIADH. However, other disorders can cause dilutional hyponatremia and must be differentiated from SIADH. These conditions include (1) congestive heart failure, (2) renal insufficiency, (3) nephrotic syndrome, (4) liver cirrhosis, and (5) hypothyroidism. Excessive administration of hypotonic fluids and treatment with drugs that stimulate AVP (e.g., chlorpropamide, vincristine, clofibrate, carbamazepine, nicotine, phenothiazines, and cyclophosphamide) can cause dilutional hyponatremia as well. Hyponatremia may also occur from renal or extrarenal sodium losses (depietional hyponatremia) as a result of vomiting, diarrhea, excessive sweating, diuretic abuse, saltlosing nephropathy, or mineralocorticoid deficiency. 

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