Fenofibrate and the kidney: an overview

Abstract

Fenofibrate has been used for the management of atherogenic dyslipidaemia for many years. Reports of fenofibrate-associated increases in serum creatinine (SCr) levels raised concerns regarding deleterious effects on renal function. In this narrative review, we discuss available literature on the effect of fenofibrate on the kidney. Most clinical studies showed a rapid (within weeks) raising effect of fenofibrate on SCr levels. This was often accompanied by declined estimated glomerular filtration rate. Risk predictors of this adverse effect might include increased age, impaired renal function and high-dose treatment. Also, the concomitant use of medications affecting renal hemodynamics (e.g. angiotensin-converting enzyme-inhibitors (ACEi) and angiotensin receptor blockers) may predispose to fenofibrate-associated increased SCr levels. Interestingly, SCr increases by fenofibrate were transient and reversible even without treatment discontinuation. Furthermore, fenofibrate was associated with a slower progression of renal function impairment and albuminuria in a long-term basis. Also, fenofibrate might be protective against pathological changes in diabetic nephropathy and hypertensive glomerulosclerosis. In this context, it is uncertain whether fenofibrate-associated increase in SCr levels mirrors true renal function deterioration. Several theories have been expressed. The most dominant one involved the inhibition of renal vasodilatory prostaglandins reducing renal plasma flow and glomerular pressure. Increased creatinine secretion or reduced creatinine clearance by fenofibrate was also suggested. These hypotheses should be settled by further studies. Fenofibrate may not be a nephrotoxic drug. However, a close monitoring of SCr levels is relevant especially in high-risk patients. Increases in SCr levels ≥30% can impose treatment discontinuation.