Abstract

An increased risk of cardiovascular disease, independent of conventional risk factors, is present even at minor levels of renal impairment and is highest in patients with end-stage renal disease (ESRD) requiring dialysis. Renal dysfunction changes the level, composition and quality of blood lipids in favour of a more atherogenic profile. Patients with advanced chronic kidney disease (CKD) or ESRD have a characteristic lipid pattern of hypertriglyceridaemia and low HDL cholesterol levels but normal LDL cholesterol levels. In the general population, a clear relationship exists between LDL cholesterol and major atherosclerotic events. However, in patients with ESRD, LDL cholesterol shows a negative association with these outcomes at below average LDL cholesterol levels and a flat or weakly positive association with mortality at higher LDL cholesterol levels. Overall, the available data suggest that lowering of LDL cholesterol is beneficial for prevention of major atherosclerotic events in patients with CKD and in kidney transplant recipients but is not beneficial in patients requiring dialysis. The 2013 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Lipid Management in CKD provides simple recommendations for the management of dyslipidaemia in patients with CKD and ESRD. However, emerging data and novel lipid-lowering therapies warrant some reappraisal of these recommendations.

Key points

  • An independent, graded inverse relationship exists between cardiovascular risk and estimated glomerular filtration rate (eGFR); patients with end-stage renal disease (ESRD) are at extremely high risk of cardiovascular events.

  • In chronic kidney disease (CKD) and ESRD, dysregulation of lipid metabolism results in increased levels of triglycerides and oxidised lipoproteins and reduced levels of HDL cholesterol; LDL cholesterol levels are usually normal.

  • As eGFR declines, there is a trend towards smaller relative risk reductions for major vascular events with statin-based therapy with little evidence of benefit in patients on dialysis.

  • Deteriorating renal function results in a unique cardiovascular phenotype with an increasing proportion of cardiovascular deaths due to heart failure and arrhythmias, rather than due to atherosclerotic events.

  • Several novel therapies are being developed to treat dyslipidaemias and their associated risks; most of these agents are biologics, which are very expensive to produce.

  • Currently there is very little evidence to support the use of novel lipid-lowering agents in patients with CKD or ESRD; however, a need exists for further studies of these therapies.

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Acknowledgements

A.O.’s work was supported by Spanish Government ISCIII FEDER funds (PI16/02057, ISCIII-RETIC REDinREN RD16/0009) and Community of Madrid (B2017/BMD-3686 CIFRA2-CM). P.R.’s work is supported by a public grant overseen by the French National Research Agency (ANR) as part of the second “Investissements d’Avenir” program FIGHT-HF (reference: ANR-15-RHU-0004) and by the French PIA project “Lorraine Université d’Excellence”, reference ANR-15-IDEX-04-LUE.

Reviewer information

Nature Reviews Nephrology thanks N. Vaziri and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Author information

Affiliations

  1. Department of Renal Medicine, University Hospitals Birmingham, Edgbaston, Birmingham, UK

    • Charles J. Ferro
  2. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK

    • Patrick B. Mark
  3. Department of Medicine, Division of Nephrology, Koc University School of Medicine, Istanbul, Turkey

    • Mehmet Kanbay
  4. Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

    • Pantelis Sarafidis
  5. Saarland University Medical Center, Internal Medicine IV–Nephrology and Hypertension, Homburg, Germany

    • Gunnar H. Heine
  6. Centre d’Investigation Clinique Plurithématique Pierre Drouin - INSERM CHU de Nancy, Nancy, France

    • Patrick Rossignol
  7. Hopital Ambroise Paré, Paris Ile de France Ouest (UVSQ) University, Paris, France

    • Ziad A. Massy
  8. CNR-IFC, Clinical Epidemiology and Pathophysiology of Hypertension and Renal Diseases, Ospedali Riuniti, Italy

    • Francesca Mallamaci
    •  & Carmine Zoccali
  9. Vascular and Renal Translational Research Group, UDETMA, REDINREN del ISCIII, IRBLleida, Lleida, Spain

    • Jose M. Valdivielso
  10. Department of Nephrology, Dialysis Therapy and Internal Medicine, Warsaw Medical University, Warsaw, Poland

    • Jolanta Malyszko
  11. Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands

    • Marianne C. Verhaar
  12. Faculty of Medicine, Maribor University, Maribor, Slovenia

    • Robert Ekart
  13. Nephrology Section, Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium

    • Raymond Vanholder
  14. Service de Néphrologie, Hôpital Manhès, Fleury Mérogis, France

    • Gerard London
  15. IIS-Fundacion Jimenez Diaz, School of Medicine, University Autonoma of Madrid, FRIAT and REDINREN, Madrid, Spain

    • Alberto Ortiz

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Contributions

C.J.F., P.B.M., M.K., R.V., C.Z. and A.O. researched the data and wrote the article. All authors made substantial contributions to discussions of the content and reviewed or edited the manuscript before submission.

Competing interests

A.O. is a consultant for Sanofi Genzyme and has received speaker fees from Amgen. Z.A.M. has received grants for CKD REIN and other research projects from Amgen, Baxter, Fresenius Medical Care, GlaxoSmithKline, Merck Sharp and Dohme-Chibret, Sanofi-Genzyme, Lilly, Otsuka and the French government, as well as fees and grants to charities from Amgen and Daichii. P.R. has consulted for Novartis, Relypsa, AstraZeneca, Grünenthal, Stealth Peptides, Fresenius, Idorsia, Vifor Fresenius Medical Care Renal Pharma, Vifor and CTMA, has received lecture fees from Bayer and CVRx and is a cofounder of CardioRenal. The other authors declare no competing interests.

Corresponding author

Correspondence to Charles J. Ferro.

Glossary

Hypertriglyceridaemia

Normally defined as a fasting plasma triglyceride level ≥2.3 mmol/l (200 mg/dl).

LDL subfractions

Subfractions of LDL particles are defined based on their size and density; small dense LDL particles are generally associated with high cardiovascular risk.

Atheroma

An abnormal mass of fatty or lipid material with a fibrous covering that exists as a discrete, raised plaque within the intima of an artery.

Chylomicron

A lipoprotein with a core of triglycerides surrounded by cholesterol, phospholipids and apolipoproteins that transports dietary fats from the small intestine to tissues after a meal.

Fibrinolysis

The process of enzymatic breakdown of fibrin, mainly by plasmin, that is the usual mechanism for the removal of fibrin clots.

About this article

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DOI

https://doi.org/10.1038/s41581-018-0072-9