Kidney and lipids: novel potential therapeutic targets for dyslipidemia in kidney disease?

ABSTRACT

Introduction

Altered lipid distribution and metabolism may lead to the development and/or progression of chronic kidney disease (CKD). Dyslipidemia is a major risk factor for CKD and increases the risk of cardiovascular events and mortality. Therefore, lipid-lowering treatments may decrease cardiovascular risk and prevent death.

Areas covered

Key players involved in regulating lipid accumulation in the kidney; contribution of lipids to CKD progression, lipotoxicity, and mitochondrial dysfunction in kidney disease; recent therapeutic approaches for dyslipidemia.

Expert opinion

The precise mechanisms for regulating lipid metabolism, particularly in kidney disease, are poorly understood. Guidelines for lipid-lowering therapy for CKD are controversial. Several hypolipemic therapies are available, but compared to others, statin therapy is the most common. No clinical trial has evaluated the efficacy of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in preventing cardiovascular events or improving kidney function among patients with CKD or kidney transplant recipients. Attractive alternatives, such as PCSK9-small interfering RNA (siRNA) molecules or evinacumab are available. Additionally, several promising agents, such as cyclodextrins and the FXR/TGR5 dual agonist, INT-767, can improve renal lipid metabolism disorders and delay CKD progression. Drugs targeting mitochondrial dysfunction could be an option for the treatment of dyslipidemia and lipotoxicity, particularly in renal diseases.

KEYWORDS:

• Chronic kidney disease
• dyslipidemia
• lipids
• therapeutic targets

Article highlights

• Altered lipid metabolism may contribute to the development and progression of kidney diseases.

• Early lipid-lowering treatment may decrease cardiovascular risk and prevent cardiovascular death in patients with kidney disease.

• Trials on new hypolipemic agents in CKD patients are eagerly awaited.

• Statins, ezetimibe, and PCSK9 inhibitors are in use; however, basic research has revealed several promising agents, including cyclodextrins, that improve renal lipid metabolism disorders and delay the progression of CKD.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Geolocation information

Poland, Europe (EU)

Additional information

Funding

This paper was not funded.