This document discusses dyslipidemia and its treatment in chronic kidney disease (CKD). It notes that cardiovascular disease is a major cause of mortality in CKD patients and dyslipidemia is a risk factor. It then describes abnormalities in lipoprotein metabolism that occur in CKD, including elevated LDL and triglycerides as well as low HDL. The document reviews guidelines for treating dyslipidemia in CKD with statins and other drugs. It concludes that disturbances in lipid levels occur even in early CKD and progress as kidney function declines. While statins can lower lipids and reduce cardiovascular risk in pre-dialysis CKD patients, they are not recommended for those on dialysis.

1. Dyslipidaemia in Chronic Kidney Disease:
An Approach to Pathogenesis and
Treatment
Dr. Nayan Ray
MBBS
Mymensingh Medical College and Hospital

2. • Cardiovascular disease (CVD) is a major cause of
mortality in patients with mild to moderate chronic
kidney disease (CKD) and end-stage renal disease (ESRD).
• Dyslipidemia has been established as a well-known
traditional risk factor for CVD in the general population
and it is well known that patients with CKD exhibit
significant alterations in lipoprotein metabolism.
Introduction

3. CHRONIC KIDNEY DISEASE (CKD)
• Chronic kidney disease (CKD) is defined as renal impairment greater
than 3 months duration that results in an estimated glomerular filtration
rate (eGFR) < 60ml/min/1.73m.
• CKD is a world-wide health problem with rising incidence and
prevalence. CKD, especially in the early stages is often asymptomatic;
thus, the actual prevalence may be even higher than estimated
• End stage renal disease(ESRD) is defined as needing dialysis or
transplant, and the prevalence and incidence of ESRD have doubled over
the past 10 years.
National Kidney Foundation. KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012 Update. Am J
Kidney Dis. 2012;60:850–886. [PubMed: 23067652]

4. Stages of CKD
NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA):
MDText.com, Inc.; 2000-.

5. Development of atherosclerosis in CKD

6. Lipoprotein in CKD
• Renal dysfunction is also associated with many perturbations
in lipoprotein metabolism leading to dyslipidaemia and
accumulation of atherogenic particles.
• CKD is associated with dyslipidaemia associating
hypertriglyceridemia, elevated LDL cholesterol, an
accumulation of apolipoprotein B (Apo B) containing
lipoproteins, increased concentrations of lipoprotein(a)
particles, and low HDL levels.
Blood Purif 2018;46:144–152 DOI: 10.1159/000488816

7. Lipoprotein in CKD
• In CKD, HDL metabolism is impaired and HDL-3 are not
maturated into HDL-2 due to a lecithin-cholesterol acyl-
transferase (LCAT) deficiency.
• In CKD, there is substantial evidence that those ox LDL
accumulate, especially in HD patients.
• All these changes relate to oxidative stress and in-creased
cardiovascular mortality in CKD patients.
Blood Purif 2018;46:144–152 DOI: 10.1159/000488816

8. Lipoprotein Abnormality in
Nephrotic Syndrome
• Dysregulated lipid metabolism leading to dyslipidemia is an
often under-recognized, but a nearly universal, complication
of persistent nephrotic syndrome.
• Lip-id and lipoprotein metabolism is altered in nephrotic
syndrome even without CKD, and the extent of altered lipid
metabolism in nephrotic syndrome correlates with the
magnitude of proteinuria.
Blood Purif 2018;46:144–152 DOI: 10.1159/000488816

9. Lipoprotein Abnormality in
Nephrotic Syndrome
• The extent of altered lipid metabolism in nephrotic syndrome
correlates with the magnitude of proteinuria.
• In nephrotic syndrome, cholesterol, triglycerides, and Apo B-
containing lipoproteins (including VLDL, intermediate-density
lipoprotein (IDL) and lipoprotein (a)) are elevated, whereas the
concentration of HDL cholesterol and the content of Apo A-I and
Apo A-II apolipoproteins are very similar in healthy individuals.
• Thus, lipoprotein abnormalities, al-though are similar with CKD
and nephritic syndrome, may also have some differences.
Blood Purif 2018;46:144–152 DOI: 10.1159/000488816

10. The Significance of HDL Cholesterol Dysfunction
and Deficiency in CKD
HDL cholesterol deficiency and dysfunction in CKD patients play a
significant effect on the formation of atherosclerosis through
various mechanisms.
HDL cholesterol shows anti-oxidant and anti-inflammatory
characteristics, and also hinders the formation of atherosclerosis
by decreasing the monocyte infiltration in artery intimal walls.
Blood Purif 2018;46:144–152 DOI: 10.1159/000488816

11. The Significance of HDL Cholesterol Dysfunction
and Deficiency in CKD
• HDL cholesterol carries the peripheral cholesterol to the liver, which is called
reverse cholesterol transport and prevents the cholesterol from being taken
up by the macrophages and formation of foamy cells.
• ApoA-1 deficiency can impair the binding of HDL to ATP binding cassette
transporter A-1 and this impaired step causes a dysfunction in free
cholesterol efflux from macrophages to HDL cholesterol.
• The accumulation of free cholesterol in macrophages produces foamy cells
in vessels and causes formation of atherosclerotic plaques.
Blood Purif 2018;46:144–152 DOI: 10.1159/000488816

12. LDL Cholesterol Dysfunctions in CKD
• In patients with nephrotic syndrome, serum VLDL cholesterol, IDL cholesterol,
and triglyceride levels are in-creased due to impaired urinary clearance, LCAT en-
zyme, and acquired hepatic LDL receptor dysfunction.
• Since hepatic lipase has an important function in the removal of the triglyceride
content of the IDL cholesterol and conversion of IDL cholesterol to LDL
cholesterol, hepatic lipase deficiency in nephrotic syndrome leads to in-creased
serum levels of atherogenic IDL cholesterol and triglyceride enrichment of the
LDL cholesterol.
• In-creased apoB-100 levels due to impaired clearance and increased production
also result in high LDL cholesterol levels in patients with nephrotic syndrome.
Blood Purif 2018;46:144–152 DOI: 10.1159/000488816

13. LDL Cholesterol Dysfunctions in CKD
• HDL cholesterol dysfunction with LDL receptor-related protein
(LRP) deficiency increases the chylomicron remnant and IDL
cholesterol levels and is another factor underlying the formation
of small dense LDL (sdLDL) in CKD patients.
• Although serum LDL cholesterol levels can be normal ranges,
sdLDL level – a highly atherogenic subtype of LDL that can be
easily oxidized – in-creases in serum as kidney function worsens.
• There-fore, both the IDL cholesterol and sdLDL cholesterol can
trigger the formation of atherosclerotic plaques even when LDL
cholesterol levels are in normal range.
• This also shows the importance of the analysis of detailed lipid
profile in patients with CKD.
Blood Purif 2018;46:144–152 DOI: 10.1159/000488816

14. Summary of Lipid Changes
in Kidney diseases
Blood Purif 2018;46:144–152 DOI: 10.1159/000488816

15. Drug Therapies for
Dyslipidemia in CKD

16. Use of Statins in Various CKD Subgroups
https://www.ncbi.nlm.nih.gov/books/NBK305899/?report=printable

17. Completed large studies on lipid modification in patients with CKD

18. Completed large studies on lipid modification in patients with CKD

19. Statin Dosing in CKD
NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA):
MDText.com, Inc.; 2000-.

20. Non-Statins in CKD
NCBI
Bookshelf.
A
service
of
the
National
Library
of
Medicine,
National
Institutes
of
Health.
Feingold
KR,
Anawalt
B,
Boyce
A,
et
al.,
editors.
Endotext
[Internet].
South
Dartmouth
(MA):
MDText.com,
Inc.;
2000-.

21. Summary of KDIGO
Guidelines Recommendation
Statements

22. Chapter 1: Assessment of lipid status in adults
with CKD
1.1: In adults with newly identified CKD (including those treated with
chronic dialysis or kidney transplantation), we recommend evaluation
with a lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol,
triglycerides). (1C)
1.2: In adults with CKD (including those treated with chronic dialysis
or kidney transplantation), follow-up measurement of lipid levels is
not required for majority of patients. (Not Graded)

23. Chapter 2: Pharmacological cholesterol-lowering
treatment in adults
2.1.1: In adults aged Z50 years with eGFRo60 ml/min/1.73 m2 but not
treated with chronic dialysis or kidney transplantation (GFR categories G3a-
G5), we recommend treatment with a statin or statin/ezetimibe
combination. (1A)
2.1.2: In adults aged Z50 years with CKD and eGFRZ60 ml/min/1.73m2 (GFR
categories G1-G2) we recommend treatment with a statin. (1B)

24. Chapter 2: Pharmacological cholesterol-lowering
treatment in adults
2.2: In adults aged 18–49 years with CKD but not treated with chronic dialysis
or kidney transplantation, we suggest statin treatment in people with one or
more of the following (2A):
• known coronary disease (myocardial infarction or coronary
revascularization)
• diabetes mellitus
• prior ischemic stroke
• estimated 10-year incidence of coronary death or non-fatal myocardial
infarction 410%

25. Chapter 2: Pharmacological cholesterol-lowering
treatment in adults
2.3.1: In adults with dialysis-dependent CKD, we suggest that statins or
statin/ezetimibe combination not be initiated. (2A)
2.3.2: In patients already receiving statins or statin/ezetimibe combination at
the time of dialysis initiation, we suggest that these agents be continued. (2C)
2.4: In adult kidney transplant recipients, we suggest treatment with a statin.
(2B)

26. Chapter 3: Assessment of lipid status in children
with CKD
3.1: In children with newly identified CKD (including those treated with chronic
dialysis or kidney transplantation), we recommend evaluation with a lipid
profile (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides). (1C)
3.2: In children with CKD (including those treated with chronic dialysis

27. Chapter 4: Pharmacological cholesterol-lowering
treatment in children
4.1: In children less than 18 years of age with CKD (including those treated with
chronic dialysis or kidney transplantation), we suggest that statins or
statin/ezetimibe combination not be initiated. (2C)

28. Chapter 5: Triglyceride-lowering treatment in
adults
5.1: In adults with CKD (including those treated with chronic dialysis or kidney
transplantation) and hypertriglyceridemia, we suggest that therapeutic lifestyle
changes be advised. (2D)

29. Chapter 6: Triglyceride-lowering treatment in
children
6.1: In children with CKD (including those treated with chronic dialysis or
kidney transplantation) and hypertriglyceridemia, we suggest that therapeutic
lifestyle changes be advised. (2D)

30. Conclusion
• Dyslipidemia represents an integral component of CKD.
• Disturbances in lipoprotein metabolism are evident even at the early stages
of CKD and usually follow a downhill course that parallels the deterioration
in renal function.
• The use of statins has been shown to be safe and efficacious in lipid
lowering in CKD, and of benefit in reducing CVD events in individuals with
pre-end stage CKD, or post renal transplant, but not in dialysis patients.
• In patients that cannot tolerate or who have contra-indications to statin
therapy, there may be some benefit from use of Ezetimibe, PCSK9
inhibitors, fibrates niacin or newer therapies such as bempedoic acid and
inclisiran.

31. Thank You