Dr. A.

Atapour
Internist
Nephrologist

Nephrology department
Esfahan university of medical sciences
 What is the problem
• The number of patients with chronic
kidney disease (CKD) is increasing

• The National Kidney Foundation (NKF)

– incidence of CVD is higher in patients with
CKD compared to the general population
– Of the traditional risk factors for CVD in
patients with CKD, dyslipidemias may play a
major role
Lipid profile in renal disease
• Stracture
• Methbolism
• Abnormality
• Guidline
• Treatment
 Introduction
• Lipids
– cholesterol
– triglycerides
• insoluble in plasma
• lipid is carried in lipoproteins
• energy utilization
• lipid deposition
• steroid hormone production
• and bile acid formation.
 The lipoprotein

• Protein
– Eesterified and unesterified cholesterol

– Triglycerides

– Phospholipids
 protein components

• apolipoproteins or apoproteins.

• cofactors for enzymes

– ligands for receptors

 CLASSIFICATION
• Chylomicrons

• Very low density lipoprotein

• Intermediate density lipoprotein

• Low density lipoprotein

• High density lipoprotein

 Chylomicrons
– very large particles
– carry dietary lipid
– They are associated with a variety of
apolipoproteins
• A-I
• A-II
• A-IV
• B-48
• C-I
• C-II
• C-III
• E.
 Very low density lipoprotein
• carries endogenous triglycerides
• to a lesser degree cholesterol
• The major apolipoproteins
– B-100
– C-I
– C-II
– C-III
– E
Intermediate density lipoprotein
• Carries cholesterol esters and triglycerides
• apolipoproteins
– B-100
– C-III
– E.
 Low density lipoprotein

• cholesterol esters
• apolipoprotein
– B-100
 High density lipoprotein

• carries cholesterol esters

• associated with apolipoproteins
– A-I
– A-II
– C-I
– C-II
– C-III
– D
– E
 Apolipoproteins
• Defects in apolipoprotein metabolism lead
to abnormalities in lipid handling
• A-I – Structural protein for HDL; activator of
lecithin-cholesterol acyltransferase (LCAT)

• A-II – Structural protein for HDL; activator of

hepatic lipase.

• A-IV – Activator of lipoprotein lipase (LPL) and

LCAT.
• B-100
– Structural protein for VLDL, IDL, LDL, and
Lp(a); ligand for the LDL receptor; required
for assembly and secretion of VLDL.

• B-48
– Contains 48 percent of B-100; required for
assembly and secretion of chylomicrons; does
not bind to LDL receptor.
• C-I – Activator of LCAT.

• C-II – Essential cofactor for LPL.

• C-III
– Interferes with apo-E mediated clearance of
triglyceride-enriched lipoproteins by cellular
receptors
– inhibits triglyceride hydrolysis by lipoprotein
lipase and hepatic lipase
• D – May be a cofactor for cholesteryl ester
transfer protein (CETP).

• E
• Ligand for hepatic chylomicron and VLDL remnant
receptor leading to clearance of these lipoproteins
from the circulation
• ligand for LDL receptor

• Apo(a)
• Structural protein for Lp(a)
• inhibitor of plasminogen activation on Lp(a).
EXOGENOUS PATHWAY OF LIPID METABOLISM
ENDOGENOUS PATHWAY OF LIPID METABOLISM

four common sequence polymorphisms in the hepatic lipase gene promoter

• Most trials of hypolipidemic therapy to
prevent coronary heart disease (CHD)
have evaluated patients with
hypercholesterolemia due to elevations in
LDL-cholesterol.

• What is The role of HDL?

• A growing body of evidence suggests that
HDL cholesterol is an independent risk
factor for CAD

• The combination of high triglycerides and

low HDL levels,
• high serum HDL-cholesterol (>60 mg/dL
is associated with a lower risk of CHD

• One definition of dyslipidemia

– total cholesterol, LDL-cholesterol,
triglyceride, apo-B, or Lp(a) concentrations
above the ninetieth percentile
– HDL-cholesterol apo A-1 concentrations
below the tenth percentile for the general
population
 HDL METABOLISM
• Hepatic and intestinal synthesis of small
nascent HDL particles composed of
phospholipid and apolipoproteins.

• Procurement of surface components

(phospholipids, cholesterol, and
apolipoproteins) from triglyceride-depleted
chylomicron and VLDL remnants.
 HDL subfractions

• HDL2 (density range, 1.063 to 1.125

g/mL)
• HDL3 (density range 1.125 to 1.21 g/mL)

• The clinical importance of the different

HDL subfractions is uncertain.
CLINICAL CLASSIFICATION OF
DYSLIPIDEMIAS
 Fredrickson phenotype
Fredrickson Apo
chylomicrons total ch TG VLDL LDL HDL
phenotype B100

9
I ↑↑ 9%↑ ↑

↑
↑ 90%
IIa 90% ↑ ↑

IIb ↑ ↑ ↑ ↑ ↑

III ↑ ↑ ↑

IV ↑ ↑ ↑ ↓

V ↑ ↑ ↑
Who should be screened for lipid profile
Screening is recommended for men aged 20 to 35 years
and for women aged 20 to 45 years in the presence of
any of the following:

• Diabetes

• A family history of cardiovascular disease before age 50

years in male relatives or age 60 years in female relatives

• A family history suggestive of familial hyperlipidemia

• Multiple coronary heart disease risk factors (eg, tobacco

use, hypertension)
– every patient with renal disease
• initial screening can be done with
nonfasting total and HDL cholesterol.

• Patients with total cholesterol levels > or =

200 mg/dL or HDL cholesterol levels < or
= 35 mg/dL should undergo a fasting lipid
profile.
 Accuracy and reliability of
screening test
• TC, LDL-C, and HDL-C are independent
predictors of coronary heart disease risk,

• The ratios of TC to HDL-C (TC/HDL-C) or

LDL-C to HDL-C (LDL-C/HDL-C) classify
risk better than TC alone.
secondary cause of hyperlipidemia

– Type 2 diabetes mellitus

– Cholestatic liver diseases
– Nephrotic syndrome
– Chronic renal failure
– Hypothyroidism
– Cigarette smoking
– Obesity
– Drugs
 Hyperlipidemia in patients with chronic
renal disease
• The prevalence of hyperlipidemia in CRD
(70 percent to 100 percent)

– high prevalence of increased triglycerides

– usually with a low level of HDL cholesterol
(30 percent to 50 percent).
 CHRONIC RENAL INSUFFICIENCY WITH
NEPHROTIC SYNDROME

• Almost all patients with urine protein

excretion greater than 3 g/24 hr have an
abnormal lipoprotein profile.

• In three studies
– 86 percent of 35 patients had LDL cholesterol levels greater
than 130 mg/dL
• In six studies
– 62 percent of 65 patients had HDL cholesterol levels less than
35 mg/ dL].
 nephrotic syndrome

• the degree of hyperlipidemia

correlates directly with the amount
of proteinuria and inversely with
the level of serum albumin.
 NEPHROTIC SYNDROME

• high serum total and low-density

lipoprotein (LDL) cholesterol
concentrations

• Increased hepatic production

• but diminished lipid catabolism

 CHRONIC RENAL FAILURE
• Dyslipidemia is less prominent in chronic
renal failure

• but hypertriglyceridemia (type IV

hyperlipoproteinemia) occurs in 30 to 50
percent of cases.
 Nephrotic synd renal peritoneal Hemodialysis
transplante dialysis
Total cholestrol ↑↑↑ ↑ ↑ nl

LDL ↑↑↑ ↑ or nl ↑ nl
VLDL ↑↑↑ ↑
HDL ↑ / nl / ↓ ↓ ↓ ↓
HDL2 ↓
HDL3 ↑
Apo A ← ↓ ↓ ↓
APOB ↑↑ ↑ ↑↑ NL
TG ↑ ↑ ↑↑ ↑
 Nephrotic renal peritoneal Hemodialysi
synd transplante dialysis s
LP(a) ↑ ↑ ↑↑ ↑↑

Oxidation ↑ ↑ ↑
LDL

ACTC Upregulate

LCAT ↓

LDL Down
RECEPTOR regulate
HDL Down
RECEPTOR regulate
LPL ↓ activity

CEPT ↓↓
 ‫‪HMG Co A‬‬ ‫هيپوآلبومينمي نقش مهمي در افزايش فعاليت‬
‫‪ reductase‬دارد‬

‫كليرانس ‪ VLDL‬و شيلوميكرونها در سندرم نفروتيك كاهش ميابد‬

‫و احتمال علت اين موضوع كاهش ‪VLDL Receptor‬‬
‫ميباشد‬
‫‪ CETP‬باعث اتصال استر كلسترول از ‪ HDL 2‬به ‪VLDL‬‬
‫‪ remnant‬شده و افزايش ‪ HDL3‬ميگردد‬

‫نسبت كلسترول به فسفوليپيد در سندرم نفروتيك افزايش ميابد‬

 GUIDELINE 1

• All adults and adolescents with CKD should be

evaluated for dyslipidemias.
• For adults and adolescents with CKD, the
assessment of dyslipidemias should include a
complete fasting lipid profile with total
cholesterol, LDL, HDL, and triglycerides
• For adults and adolescents with Stage 5 CKD,
dyslipidemias should be evaluated upon
presentation (when the patient is stable), at 2–3
months after a change in treatment or other
conditions known to cause dyslipidemias; and
at least annually thereafter.
 GUIDELINE 2

• For adults and adolescents with Stage 5

CKD, a complete lipid profile should be
measured after an overnight fast
whenever possible.
• Hemodialysis patients should have lipid
profiles measured either before dialysis, or
on days not receiving dialysis.
 GUIDELINE 3
• Stage 5 CKD patients with dyslipidemias
should be evaluated for remediable,
secondary causes.
 RESEARCH
RECOMMENDATIONS
TREATMENT OF ADULTS
WITH DYSLIPIDEMIAS
 GUIDELINE 4-1
• For adults with Stage 5 CKD and fasting
triglycerides 500
 GUIDELINE 4-2
• For adults with Stage 5 CKD and LDL 100
mg/dL (2.59 mmol/L), treatment should be
considered to reduce LDL to <100 mg/dL
(<2.59 mmol/L)
 GUIDELINE 4-3
• For adults with Stage 5 CKD
• LDL <100 mg/dL (<2.59 mmol/L)
• fasting triglycerides 200 mg/dL (2.26 mmol/L),
• non-HDL cholesterol (total cholesterol minus HDL)
130 mg/dL (3.36 mmol/L)

• treatment should be considered to reduce

non-HDL cholesterol to <130 mg/dL
(<3.36 mmol/L).(C)