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Cited by 46Chronic Kidney Disease and DiabetesAcute Kidney Injury ResearchLipoproteins and Cardiovascular Health

The Effect of Fibrates on Kidney Function and Chronic Kidney Disease Progression: A Systematic Review and Meta-Analysis of Randomised Studies

Open access
Hadjivasilis, Alexandros, Kouis, Panayiotis, Kousios, Andreas, Panayiotou, Andrie·2022·Journal of Clinical Medicine
DOI 10.3390/jcm11030768PMC PMC8836930
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Abstract

Aim: Fibrates have proven efficacy in cardiovascular risk reduction and are commonly used, in addition to statins, to control hypertriglyceridaemia. Their use is often limited due to reduction in glomerular filtration rate at treatment initiation. However, recent studies suggest benign changes in kidney function and improvement of proteinuria, an established early marker of microvascular disease and kidney disease progression. We summarize the evidence from existing trials and provide a summary of effects of fibrates, alone or in combination, on kidney disease progression and proteinuria. Methods and Results: Systematic review and meta-analysis of randomized, controlled trials (PROSPERO CRD42020187764). Out of 12,243 potentially eligible studies, 29 were included in qualitative and quantitative analysis, with a total of 20,176 patients. Mean creatinine increased by 1.05 (95% CI (0.63 to 1.46)) units in patients receiving fibrates vs. comparator, and this was similar in all other subgroups. eGFR showed a bigger decrease in the fibrates arm (SMD −1.99; 95% CI (−3.49 to −0.48)) when all studies were pooled together. Notably, short-term serum creatinine and eGFR changes remained constant in the long-term. Pooled estimates show that fibrates improve albuminuria progression, RR 0.86; 95% CI (0.76 to 0.98); albuminuria regression, RR 1.19; 95% CI (1.08 to 1.310). Conclusions: Fibrates improve albuminuria in patients with and without diabetes when used to treat hyperlipidaemia. The modest creatinine increase should not be a limiting factor for fibrate initiation in people with preserved renal function or mild CKD. The long-term effects on kidney disease progression warrant further study.

AI snapshot

Written from the paper’s full text.

TL;DR

This systematic review and meta-analysis of 29 randomized studies (20,176 patients) found that fibrates modestly increase serum creatinine and decrease eGFR, but also improve albuminuria progression and regression. The authors conclude that the creatinine rise should not preclude fibrate initiation in preserved renal function or mild CKD, while long-term kidney disease progression effects remain uncertain.

Key findings

  • Pooled mean creatinine increased by 1.05 mg/dL (95% CI 0.63–1.46) in fibrate vs. comparator arms; eGFR showed a larger decrease with fibrates (SMD −1.99; 95% CI −3.49 to −0.48).
  • Fibrates reduced albuminuria progression (RR 0.86; 95% CI 0.76–0.98) and increased albuminuria regression (RR 1.19; 95% CI 1.08–1.31).
  • Short-term (≤3 months) creatinine and eGFR changes remained relatively constant with long-term use; creatinine elevation was reported as reversible after fibrate discontinuation in FIELD and ACCORD.
  • Data from two studies suggested a possible reduction in ESKD progression with fibrates, but this was not statistically significant (RR 0.85; 95% CI 0.49–1.49).

Methods

  • Systematic review and meta-analysis of randomized controlled trials, registered in PROSPERO (CRD42020187764) and reported per PRISMA; searches of MEDLINE, SCOPUS, Cochrane Library, and clinical trial registers ran from inception to July 2020.
  • From 12,243 potentially eligible studies, 29 RCTs were included, totaling 20,176 patients (10,249 intervention, 9,841 comparator, 86 crossover receiving both); eligible adults had CKD or CKD risk factors, and interventions were fibrates alone or fibrates plus statin versus placebo or statin.
  • Continuous outcomes used generalized inverse variance standardized mean differences with random-effects models; categorical outcomes used relative risks with DerSimonian–Laird random-effects models; heterogeneity was assessed with I² and publication bias graphically with precision funnel plots using STATA v14.

Limitations

  • The authors report large heterogeneity within and between studies for eGFR and creatinine, likely because most included studies did not have kidney-related variables as primary outcomes, used different fibrates/statins and dosages, had small samples and power issues, and often had observation periods under three months.
  • The authors state that the effect of fibrates in patients with eGFR less than 30 was not examined, so results cannot be extrapolated to this population.
  • Evident from the text: most included studies enrolled patients with normal kidney function, with only one study focused exclusively on CKD stage III, and ESKD analyses relied on only two studies, limiting certainty about kidney disease progression.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/jcm11030768

Cites

54 of 54 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

7 of 12 cited sources checked · 4 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    Initial changes in serum creatinine and estimated GFR with fibrates do not affect actual kidney function.

    “Although these initial changes in creatinine levels and estimated GFR are true, newer data from well-designed randomised controlled trials (RCTs) show that these changes do not affect the actual kidney function [6,7,8].”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [6] Keech, 2005, Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): Randomised controlled trial, Lancet source
    • cites [7] The ACCORD Study Group, Ginsberg, H.N., Elam, M.B., Lovato, L.C., Crouse, J.R., Leiter, L.A., Linz, P., Friede-Wald, W.T., Buse, J.B., and Gerstein, H.C. (2010). Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus. N. Engl. J. Med., 362, 1563–1574. source

      The Results (Safety; page unavailable) report an initial creatinine rise with fenofibrate and more dose reductions or discontinuations because of decreased estimated GFR. They also report no significant difference in dialysis or end-stage renal disease, but those outcomes do not establish that the initial changes had no effect on actual kidney function. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [8] Ansquer, 2005, Fenofibrate reduces progression to microalbuminuria over 3 years in a placebo-controlled study in type 2 diabetes: Results from the Diabetes Atherosclerosis Intervention Study (DAIS), Am. J. Kidney Dis. source
  • Premisecitation

    The FIELD, ACCORD and DAIS trials showed a beneficial effect of fibrates on albuminuria in diabetic patients.

    “In fact, the FIELD [6], the ACCORD [7] and the DAIS [8] trials showed a beneficial effect of fibrates on albuminuria in diabetic patients; an established marker of early microvascular disease and a predictor of adverse CVD outcomes and kidney disease progression.”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [6] Keech, 2005, Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): Randomised controlled trial, Lancet source
    • cites [7] The ACCORD Study Group, Ginsberg, H.N., Elam, M.B., Lovato, L.C., Crouse, J.R., Leiter, L.A., Linz, P., Friede-Wald, W.T., Buse, J.B., and Gerstein, H.C. (2010). Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus. N. Engl. J. Med., 362, 1563–1574. source
    • cites [8] Ansquer, 2005, Fenofibrate reduces progression to microalbuminuria over 3 years in a placebo-controlled study in type 2 diabetes: Results from the Diabetes Atherosclerosis Intervention Study (DAIS), Am. J. Kidney Dis. source
  • Premisecitation

    A previous meta-analysis demonstrated efficacy and safety of fibrates on cardiovascular outcomes in people with kidney disease.

    “A meta-analysis previously examined the effect of fibrates on CVD outcomes in people with kidney disease demonstrating efficacy and safety in this patient group [9].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [9] Jun, 2012, Effects of fibrates in kidney disease: A systematic review and meta-analysis, J. Am. Coll. Cardiol. source

      The Abstract and Major Cardiovascular Outcomes section report reduced major cardiovascular events and cardiovascular death in patients with mild-to-moderate kidney disease. The Abstract says there were no clear CKD-specific safety concerns, but safety data were limited; the Discussion also notes a lack of data for severe kidney dysfunction. Thus, the claim overstates how firmly safety was demonstrated across people with kidney disease. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Findingown data

    Mean creatinine increased by 1.05 mg/dL (95% CI 0.63-1.46) in patients receiving fibrates vs. comparator.

    “Mean creatinine increased by 1.05 (95% CI (0.63 to 1.46)) units in patients receiving fibrates vs. comparator, and this was similar in all other subgroups.”
    • Also stated in: § 3.5. Creatinine Change · hedged
      “Creatinine appears to have an increase of 1.05 (95% CI (0.63–1.46)) mg/dL when comparing the mean change of patients receiving fibrates vs. the mean change of patients receiving the comparator.”
    Quote in the paperSubstantial claim
  • Findingown data

    29 studies with a total of 20,176 patients were included in qualitative and quantitative analysis.

    “Out of 12,243 potentially eligible studies, 29 were included in qualitative and quantitative analysis, with a total of 20,176 patients.”
    • Also stated in: § 3.1. Study Selection · plain
      “A total of 29 studies [7,8,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39] were included in the qualitative and the quantitative analysis.”
    Quote in the paperSubstantial claim
  • May combine two claims. 8
  • Classified as probably not a substantial claim. 10

  • May combine two claims.

    Premisecitation

    The previous meta-analysis did not focus on long-term renal outcomes and did not take into account fibrate-statin co-administration.

    “However, the authors did not focus on long-term renal outcomes and did not take into account fibrate–statin co-administration; a common practice in patients with dyslipidaemia.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [9] Jun, 2012, Effects of fibrates in kidney disease: A systematic review and meta-analysis, J. Am. Coll. Cardiol. source

      The Study selection section lists end-stage kidney disease among the outcomes collected, contrary to the claim that the review did not focus on long-term renal outcomes. The Discussion acknowledges that the effects of combined fibrate–statin treatment remain uncertain, but the review did consider co-administration: it included the ACCORD trial, whose participants received statins. Page numbers are not available for these indexed passages. (LLM, conf=0.86)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    A predefined protocol was registered in PROSPERO with registration number CRD42020187764.

    “A predefined protocol was drafted and registered in the Prospective Register of Systematic Reviews (PROSPERO) with registration number CRD42020187764; it can also be found as a publication in a pre-prints platform [12].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [12] Kousios, A., Hadjivasilis, A., Kouis, P., and Panayiotou, A. (2020). The Effect of Fibrates on Kidney Function and Chronic Kidney Disease Progression: Protocol for a Systematic Review, Research Square. source

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    Risk of bias was assessed by two independent reviewers using the Cochrane tool for RCTs, with disagreements resolved by a third reviewer.

    “Two independent reviewers (AH and PK) assessed all included studies for risk of bias using the Cochrane tool for assessing the risk of bias in RCTs [13].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [13] Higgins, 2011, The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials, BMJ source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The study was conducted in accordance with PRISMA guidelines.

    “The study was conducted in accordance with the guidelines from the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) statement [11].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [11] Liberati, A., Altman, D.G., Tetzlaff, J., Mulrow, C., Gøtzsche, P.C., Ioannidis, J.P.A., Clarke, M., Devereaux, P.J., Kleijnen, J., and Moher, D. (2009). The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration. PLoS Med., 6. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    More than half of the participants came from the FIELD and ACCORD studies.

    “Among the included studies more than half of the participants came from the FIELD and the ACCORD studies.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    The majority of included studies (n = 21) examined fenofibrate alone or in combination, and 11 examined fenofibrate vs. placebo.

    “The majority of the studies (n = 21) had examined fenofibrate alone or in combination [7,8,14,15,17,18,20,21,22,24,25,26,27,28,29,30,31,33,34,35,40,41] and 11 of them fenofibrate vs. placebo [8,14,15,17,18,26,27,31,34,35].”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The included studies had 10,249 patients in the intervention arm, 9,841 in the comparator arm, and 86 patients received both interventions in crossover studies.

    “A total of 20,176 patients were included in the eligible studies, 10,249 in the intervention arm and 9841 in the comparator arm while 86 patients received both interventions in the setting of crossover studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Creatinine change in patients with diabetes showed similar increases (all studies SMD 1.49; 95% CI 0.29-2.71; fenofibrate vs. placebo SMD 0.86; 95% CI 0.35-1.37).

    “Creatinine change was also assessed in patients with diabetes with similar results (all studies SMD 1.49 95% CI (0.29–2.71) and in studies examining fenofibrates vs. placebo: SMD 0.86; 95% CI (0.35–1.37)).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Creatinine increased in all arms where fibrates were used, including fenofibrate (all studies SMD 1.34; 95% CI 0.82-1.86), fenofibrate vs. placebo (SMD 1.22; 95% CI 0.74-1.89), fenofibrate plus statin vs. statin (SMD 1.07; 95% CI 0.34-1.79), and bezafibrate vs. comparator (SMD 0.68; 95% CI 0.01-1.34).

    “Creatinine seems to increase in all arms where fibrates were used, whether this was fenofibrate (all studies: standardised mean difference (SMD) 1.34; 95% CI (0.82–1.86), fenofibrate vs. placebo: SMD 1.22; 95% CI (0.74–1.89), fenofibrate plus statin vs. statin: SMD 1.07; 95% CI (0.34–1.79)) or bezafibrate vs. a comparator, SMD 0.68; 95% CI (0.01–1.34).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Publication bias was investigated graphically by precision funnel plots.

    “Heterogeneity between synthesised studies were calculated using the I2 statistic and the presence of publication bias was investigated graphically by precision funnel plots.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Inclusion criteria were predefined using a PICOS model.

    “We developed a PICOS model to predefine our inclusion criteria.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Data extraction was done independently by two reviewers using a predefined Excel sheet.

    “After the screening, extraction of data from all included studies, was done by AH and AK independently in a predefined excel sheet.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    The majority of included studies had low risk of bias in most domains; some had high risk due to unblinded assessors, and some domains were unclear due to insufficient information.

    “As expected, because of the strict methodology RCTs have to follow, the majority of studies had low risk of bias in most of the domains. Some studies examined the results without blinding the assessors and this was considered a high risk of bias. Also, when not enough information was provided in the manuscript, some domains were characterised as not clear.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Two independent reviewers screened all potentially eligible studies against inclusion and exclusion criteria, with disagreements resolved by a third reviewer.

    “Two independent reviewers (AH and AK) screened all potentially eligible studies against the inclusion and exclusion criteria and any disagreement was resolved by a third reviewer (AP).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Suitability of studies for meta-analysis was based on clinical, methodological and statistical homogeneity.

    “Suitability of studies for inclusion in the meta-analysis was based on clinical, methodological and statistical homogeneity.”
    Quote in the paperSubstantial claim
15 of 15

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Creatinine effect is reported in mg/dL despite being a standardized mean difference

    Major

    The methods say the pooled creatinine effect was calculated as a standardized mean difference, which is unitless. The results instead present the pooled value of 1.05 as an increase in mg/dL, changing the interpretation of a principal result.

  • Discussion conflicts with results on publication bias

    Major

    The results say there was no evidence of large publication bias for any outcome, while the discussion says pooled estimates relating to kidney function had high publication bias.

  • Cited biomarker study is instead about hypernatremia correction

    Minor

    The discussion cites reference 43 for urinary biomarkers associated with a creatinine rise. Reference 43's listed subject is the rate of correction of hypernatremia and health outcomes, not those biomarkers.

  • Reference 36 is described as fenofibrate evidence but concerns gemfibrozil

    Minor

    The results attribute the comparison in reference 36 to fenofibrate, whereas the cited study is titled as a study of gemfibrozil.

  • Included eGFR range extends below the exclusion threshold

    Minor

    The eligibility criteria exclude patients with eGFR below 15, but the results describe included studies with an eGFR range starting at 10.

5 of 5

Cites

Flagged first, then by citations

1 of the 55 references couldn’t be matched to a known paper.

Cited by

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Related

Authors
Hadjivasilis, A., Kouis, P., Kousios, A., & Panayiotou, A.
Affiliations
  • Cyprus University of Technology (CY)
  • Cardiovascular Epidemiology and Genetics Research Lab, Cyprus International Institute for Environmental and Public Health, Cyprus University of Technology, Limassol 3036, Cyprus
  • Imperial College Healthcare NHS Trust (GB)
Corresponding author
Kousios, Andreas
ORCID
Venue
Journal of Clinical Medicine
Publisher
MDPI AG
Published
2022-01-31
Volume
11
Issue
3
Pages
768
ISSN
2077-0383 (ISSN-L)
DOI
10.3390/jcm11030768
PMC
PMC8836930
OpenAlex
W4210595976
Semantic Scholar
bee6f4e5f143ae5e3af229b0f2770132994928ee
Cited by
46
References
55
Citations by year
2026: 8 · 2025: 15 · 2024: 13 · 2023: 8 · 2022: 2
FWCI
1.97
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Clinical Medicine (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Ktisis at Cyprus University of Technology (Cyprus University of Technology) (submittedVersion, cc-by-nc-nd)
  • PubMed Central (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
fibrates, chronic kidney disease progression, albuminuria, proteinuria, glomerular filtration rate, serum creatinine, hypertriglyceridemia, hyperlipidemia, diabetes mellitus, renal safety

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

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Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-19.

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