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Cited by 17Lipoproteins and Cardiovascular HealthChronic Kidney Disease and DiabetesAcute Kidney Injury Research

Renal Safety Assessment of Lipid-Lowering Drugs: Between Old Certainties and New Questions

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Tramontano, Daniele, Bini, Simone, Maiorca, Carlo, Di Costanzo, Alessia, Carosi, Martina, Castellese, Jacopo, Arizaj, Ina, Commodari, Daniela +5 more·2025·Drugs
DOI 10.1007/s40265-025-02158-0PMC PMC12098426
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Abstract

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). Quantitative and qualitative changes in plasma lipoprotein profiles are frequently associated with CKD and represent a significant risk factor for CVD in patients with CKD. Guidelines from the European Society of Cardiology and the European Atherosclerosis Society classify CKD as a condition with high or very high cardiovascular risk and set specific low-density lipoprotein cholesterol targets. Conventional lipid-lowering therapies (LLTs), such as statins, ezetimibe, and fibrates, can control CKD-associated dyslipidemia and, to some extent, prevent major atherosclerotic events in patients with CKD, but their use in clinical practice presents challenges because of the potential renal safety concerns. In recent years, novel therapies with the ability to lower both low-density lipoprotein cholesterol and triglycerides have been introduced to the market (e.g., proprotein convertase subtilisin/kexin type 9 inhibitors, bempedoic acid, lomitapide, volanesorsen) to improve our ability to control lipid abnormalities. However, their impact on kidney functionality has not been fully elucidated. The aim of this review was to examine the renal safety profiles of various LLTs, with special reference to novel medications, and to highlight important considerations and guidance for the use of these medications in overt CKD or in patients with some degree of renal function impairment. We underscore the lack of a comprehensive understanding of kidney safety, particularly for novel LLT therapies, and strongly emphasize the importance of future dedicated research to fully assess the safety and efficacy of these agents in patients with kidney abnormalities.

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  • Fibrates may induce reversible increases in serum creatinine, especially in patients with pre-existing renal impairment, likely reflecting functional changes in renal hemodynamics rather than structural injury.

    “Fibrates may also induce reversible increases in serum creatinine, especially in patients with pre-existing renal impairment, likely reflecting functional changes in renal hemodynamics rather than structural injury [12, 79].”

    From Targeting triglycerides for cardiovascular risk reduction (2026) · cites this paper as [79]

    The Discussion (page unavailable) says fibrate-associated creatinine increases are often hemodynamic and reversible rather than signs of intrinsic kidney injury. The Conventional Triglyceride-Lowering Therapies section likewise reports reversibility and no indication of structural damage. Neither passage establishes that the increases occur especially in patients with pre-existing renal impairment. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Tramontano, D., Bini, S., Maiorca, C., Di Costanzo, A., Carosi, M., Castellese, J., Arizaj, I., Commodari, D., Covino, S., Sansone, G., Minicocci, I., Arca, M., & D’Erasmo, L.
Affiliations
Sapienza University of Rome (IT)
Corresponding author
Tramontano, Daniele
ORCID
Venue
Drugs
Publisher
Springer Science and Business Media LLC
Published
2025-03-19
Volume
85
Issue
6
Pages
755-775
ISSN
  • 0012-6667 (ISSN-L)
  • 1179-1950
DOI
10.1007/s40265-025-02158-0
PMC
PMC12098426
OpenAlex
W4408644910
Cited by
17
References
16
Citations by year
2026: 9 · 2025: 8
FWCI
4.11
Type
journal article
Language
en
Open access
Licence
Locations
  • Drugs (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
Funders
Università degli Studi di Roma La Sapienza
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
Keywords
renal safety, lipid-lowering drugs, chronic kidney disease, cardiovascular risk, dyslipidemia, statins, ezetimibe, fibrates, PCSK9 inhibitors, bempedoic acid, volanesorsen, LDL cholesterol targets, triglyceride-lowering therapy, drug safety in renal impairment
MeSH terms
Hypolipidemic Agents, Cardiovascular Diseases, Humans, Kidney, Dyslipidemias, Renal Insufficiency, Chronic

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