From the Guidelines
Fenofibrate is the preferred fibrate option for patients with chronic kidney disease stage 3 (CKD 3), but dose adjustment is necessary, starting at a reduced dose of 48 mg daily, as indicated in the 2012 KDOQI guideline 1. When considering fibrate options for CKD 3, it's essential to weigh the benefits and risks, particularly the potential for myopathy and further kidney injury.
- Fenofibrate has less renal excretion in its active form compared to other fibrates and demonstrates better overall tolerability in reduced kidney function.
- Gemfibrozil is an alternative option, but it carries a higher risk of drug interactions, particularly with statins, making it less ideal for patients on multiple medications.
- Regular monitoring of kidney function, creatinine, and lipid levels is essential, with assessments recommended at baseline, 4-6 weeks after initiation, and then every 3-6 months, as suggested by the 2015 KDOQI commentary 1.
- If GFR drops below 30 ml/min (progressing to CKD 4), fibrates should generally be discontinued due to increased risk of myopathy and further kidney injury.
- For patients with CKD 3 who need triglyceride lowering, omega-3 fatty acids may be considered as an alternative or adjunct therapy with fewer renal concerns, as mentioned in the 2007 KDOQI guidelines 1. The most recent and highest quality study, the 2015 KDOQI commentary 1, supports the use of fenofibrate in CKD 3 patients, but with caution and close monitoring due to the potential risks.
From the FDA Drug Label
Treatment with fenofibrate tablets should be initiated at a dose of 54 mg per day in patients having mild to moderately impaired renal function and increased only after evaluation of the effects on renal function and lipid levels at this dose. The use of fenofibrate tablets should be avoided in patients with severe renal impairment [see Use in Specific Populations (8. 6) and Clinical Pharmacology (12.3)].
For patients with Chronic Kidney Disease (CKD) stage 3, the recommended initial dose of fenofibrate is 54 mg per day. The dose may be increased after evaluating the effects on renal function and lipid levels. Fenofibrate is a suitable option for these patients. 2 2 2
From the Research
Fibrate Options for CKD 3
- Fenofibrate has been shown to delay the need for dialysis and reduce cardiovascular risk among patients with advanced CKD 3.
- Fibrates, in general, improve lipid profiles and prevent cardiovascular events in people with CKD, and they reduce albuminuria and reversibly increase serum creatinine 4.
- The combination of fenofibrate and high-intensity statins may have additional benefits in reducing cardiovascular risk 3.
- Pemafibrate use, but not bezafibrate or fenofibrate use, was significantly associated with a decreased risk of major adverse cardiovascular events (MACE) in patients with CKD 5.
- Fibrate use was significantly associated with a decreased risk of MACE, particularly for current and recent use 5.
Mechanism of Action
- The exact mechanism of how fibrates affect kidney function is not fully understood, but it is thought to involve the inhibition of renal vasodilatory prostaglandins, reducing renal plasma flow and glomerular pressure 6.
- Increased creatinine secretion or reduced creatinine clearance by fenofibrate has also been suggested as a possible mechanism 7, 6.
Safety and Efficacy
- Fenofibrate-associated increases in serum creatinine levels are often accompanied by declined estimated glomerular filtration rate, but these increases are usually transient and reversible 6.
- Risk predictors of fenofibrate-associated increased serum creatinine levels include increased age, impaired renal function, and high-dose treatment 6.
- Close monitoring of serum creatinine levels is relevant, especially in high-risk patients, and increases in serum creatinine levels ≥30% can impose treatment discontinuation 6.