Impact of fibrates on circulating cystatin C levels: a systematic review and meta-analysis of clinical trials
Open accessAbstract
Aims: To assess the effect of fibrates on circulating cystatin C levels.Material and methods: Clinical studies evaluating the effect of a fibrate on circulating cystatin C levels were searched in PubMed-Medline, SCOPUS, Web of Science, and Google Scholar databases. A random-effect model and generic inverse variance method were used for quantitative data synthesis, sensitivity analysis conducted using the leave-one-out method, and weighted random-effects meta-regression performed to evaluate potential confounders on cystatin C levels.Results: This meta-analysis of data from nine published studies (16 treatment arms) involved a total of 2195 subjects. In a single-arm analysis of clinical trials (without control group; eight studies comprising 14 treatment arms), fibrate therapy increased circulating cystatin C concentrations (WMD: 0.07 mg/dL, 95% CI: 0.04, 0.10, p < .001; I2 = 82.66%). When the analysis was restricted to randomized controlled trials (four studies comprising six treatment arms), again elevation of circulating cystatin C levels was observed (WMD: 0.06 mg/L, 95% CI: 0.03, 0.09, p < .001; I2 = 42.98%). Elevated cystatin C levels were only seen with fenofibrate and not with other fibrates.Conclusions: The results suggest that fenofibrate treatment adversely affects cystatin C levels and might partially explain the limited efficacy of fenofibrate in reducing cardiovascular events.Key messageFenofibrate treatment adversely affects cystatin C levels and might partially explain the limited efficacy of fenofibrate in reducing cardiovascular events.
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Fibrates cause side effects such as liver dysfunction and increased creatinine levels.
“However, fibrates were demonstrated to cause side effects such as liver dysfunction and increase in creatinine levels, and thus large-scale clinical trials of fibrates have shown negative results for prevention of ASCVD.”
From Pemafibrate, a new selective PPARα modulator: drug concept and its clinical applications for dyslipidemia and metabolic diseases (2020) · cites this paper as [82]
Pemafibrate improves liver function test values and is less likely to increase serum creatinine or decrease eGFR compared with available fibrates.
“Although available fibrates showed worsening of liver and kidney function test values, pemafibrate indicated improved liver function test values and was less likely to increase serum creatinine or decrease estimated glomerular filtration rate (eGFR).”
From Pemafibrate, a new selective PPARα modulator: drug concept and its clinical applications for dyslipidemia and metabolic diseases (2020) · cites this paper as [82]
Fenofibrate administration increased serum levels of creatinine and cystatin C and decreased eGFR during treatment, but these changes were much smaller in the pemafibrate-treated group.
“While fenofibrate administration increased serum levels of creatinine and cystatin C and decreased eGFR during the treatment, these changes were much smaller in the pemafibrate-treated group.”
From Pemafibrate, a new selective PPARα modulator: drug concept and its clinical applications for dyslipidemia and metabolic diseases (2020) · cites this paper as [82]
Fibrates are known to worsen kidney function test values, including serum creatinine and cystatin C levels, and estimated glomerular filtration rate.
“Fibrates are known to worsen kidney function test values, including serum creatinine and cystatin C levels, and estimated glomerular filtration rate (eGFR) [82–84].”
From Pemafibrate, a new selective PPARα modulator: drug concept and its clinical applications for dyslipidemia and metabolic diseases (2020) · cites this paper as [82]
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- Authors
- Sahebkar, A., Simental-Mendía, L. E., Pirro, M., Montecucco, F., Carbone, F., Banach, M., Barreto, G. E., & Butler, A. E.
- Affiliations
- Mashhad University of Medical Sciences (IR)
- Mexican Social Security Institute, Biomedical Research Unit, Durango, México;
- University of Perugia (IT)
- Ospedale Policlinico San Martino (IT)
- University of Genoa (IT)
- Medical University of Lodz (PL)
- Pontificia Universidad Javeriana (CO)
- Anti-Doping Laboratory (QA)
- Corresponding author
- Butler, Alexandra E.
- ORCID
- Venue
- Annals of Medicine
- Publisher
- Informa UK Limited
- Published
- 2018-08-18
- Volume
- 50
- Issue
- 6
- Pages
- 485-493
- ISSN
- 0785-3890 (ISSN-L)
- 1365-2060
- OpenAlex
- W2809788304
- Cited by
- 9
- References
- 40
- Citations by year
- 2025: 1 · 2023: 2 · 2022: 1 · 2020: 1 · 2019: 3 · 2017: 1
- FWCI
- 0.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annals of Medicine (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial Research Information System (University of Genoa) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- fibrates, cystatin C, fenofibrate, drug-induced nephrotoxicity, renal function, cardiovascular risk, statin adverse effects
- MeSH terms
- Hypolipidemic Agents, Cardiovascular Diseases, Clinical Trials as Topic, Humans, Cholesterol, LDL, Hypertriglyceridemia, Treatment Outcome, PPAR alpha, Cystatin C, Fibric Acids
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