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To provide clinical recommendations regarding hyperlipidemia in patients with chronic renal disease.

Article inclusion criteria not specified.

Not specified.

Recruitment

Article selection methods not described.

Design

Systematic Review.

Blinding used (if applicable):  not applicable

Intervention (if applicable):  not applicable

Statistical Analysis:  not applicable 

 

Timing of Measurements:  not applicable

Dependent Variables:  not applicable

Independent Variables:  not applicable

Control Variables:  not applicable

 

Initial N: 117 references cited

Attrition (final N):  117

Age:  not applicable

Ethnicity:  not applicable 

Other relevant demographics:

Anthropometrics:

Location:  Worldwide studies 

 

Introduction

1.  Patients with CRD should be considered to be in the highest risk group for CAD and also at risk for CVD and peripheral vascular disease (PVD).

2.  Patients with CRD often have increased triglycerides and decreased HDL-cholesterol with normal LDL-cholesterol.

Target Population: CRI with Nephrotic Syndrome

Prevalence

1.  Almost all patients with urine protein excretion > 3 g/24 hr have an abnormal lipoprotein profile.

• In 16 studies, 88% of 238 nephrotic patients had serum cholesterol levels > 240 mg/dl
• In 3 studies, 86% of 35 patients had LDL-cholesterol levels > 130 mg/dl
• In 6 studies, 62% of 65 patients had HDL-cholesterol levels < 35 mg /dl
• In 15 studies, 62% of 218 patients had fasting TG levels > 200 mg/dl
• In 5 studies, 60% of 166 patients had lipoprotein (a) levels > 30 mg/dl

CVD and CRD Outcome - Therapy

1.  The degree of hyperlipidemia correlates directly with the amount of proteinuria and inversely with the level of serum albumin.

• Appel et al reported a significant inverse correlation between serum albumin and total cholesterol (r = -0.53, P < 0.05) in 20 consecutive patients with >3 g protein/24 hr urines.
• Kaysen et al found serum total cholesterol to correlate inversely with serum albumin (r = -0.76, P < 0.01) and directly with urine albumin excretion (r= 0.84, P < 0.01).

Target Population:  CRI without Nephrotic Syndrome 

Prevalence

1.  Few controlled, epidemiological studies have examined the relationship between hyperlipidemia and CVD.

• Ordonez et al compared the prevalence of CAD in 142 patients with nephrotic syndrome to an age- and sex-matched control group.  The relative risk (RR) for coronary death (adjusted for hypertension and smoking) was 2.8 (95% CI, 0.7 to 11.3, the RR) and the RR for MI was 5.5 (95% CI, 1.6 to 18.3).

CVD and CRD Outcomes

1.  The first goal would be to safely induce a remission of nephrotic syndrome or at least to decrease urinary excretion of protein; aggressive blood pressure reduction may decrease urinary protein excretion, in addition, HMG-CoA inhibitors may also decrease proteinuria.

2.  ATP III Guidelines should be used for dietary intervention at the same time that lipid-lowering medications are initiated since diet alone usually is inadequate.

• HMG-CoA inhibitors and ACE inhibitors decrease serum LDL cholesterol and TG

3.  In general the prevalence of hyperlipidemia appears to increase with worsening renal function.  However the level of renal insufficiency at which increased lipid levels become more prevalent is not well defined.

• In 4 studies, 33% of 46 patients had total cholesterol > 240 mg/dl
• In 3 studies, 36% of 131 patients had HDL-cholesterol levels > 35 mg /dl
• In 7 studies, 35% of 133 patients had TG levels > 200 mg/dl
• In 1 study, 45% of patients had lipoprotein (a) levels > 30 mg/dl
• Attman et al reported an increase in TG and VLDL-cholesterol but normal LDL-cholesterol in patients with mild to moderate CRI (mean CrCL/body surface area of 37 +/- 14 mL/min).

Therapy

1.  There are few studies examining the relationship between lipid abnormalities and CVD in CRI and there are no prospective intervention trials.

• Jungers et al prospectively examined the relationship between serum lipids and the incidence of MI in 147 patients with CrCl 20 - 50 ml/min; the incidence of MI was 2.5 higher than in the general population.
• The 41 patients who had an MI had decreased HDL-cholesterol and increased levels of TG, LDL-cholesterol, apolipoprotein B, and lipoprotein (a).
• Multivariate analysis demonstrated the correlates of MI to be cigarette smoking, systolic blood pressure, fibrinogen and HDL-cholesterol.

2.  ATP III Guidelines can be used for dietary intervention plus HMG-CoA reductase inhibitors.

Target Population:  Renal Transplant Recipients (RTR)

Prevalence

1.  Over 60% of RTR have hyperlipidemia.

• In 5 studies, 63% of 549 patients had total cholesterol > 240 mg/dl
• In 3 studies, LDL-cholesterol was >130 mg/dl in 60% of 769 patients
• In 4 studies, HDL-cholesterol levels were < 35 mg/dl in 12% of 777 patients
• In 6 studies, TG were > 200 mg/dl in 36% of 1309 patients
• In 5 studies, lipoprotein (a) levels were > 30 mg/dl in 23% of 468 patients

CVD and CRD Outcomes

1.  The results of some cross-sectional epidemiological studies suggest that RTR with hyperlipidemia are more likely to develop CVD.

• Heule et al found increased total cholesterol and TG levels in 36 patients with CVD compared to 36 controls
• Abdulmassih et al found CVD in 25 patients to be associated with increased levels of total cholesterol and TG and decreased levels of HDL-cholesterol compared to 29 controls
• Kasiske found increased total cholesterol levels in 99 patients with CVD compared to 365 controls
• Some investigators have also reported correlations between hyperlipidemia and RTR allograft dysfunction
• Dimeny et al found that pretransplant levels of cholesterol and TG correlates with evidence of vascular intimal hyperplasia on biopsy specimens in 151 patients obtained 6 months after transplantation
• Massy et al found TG to be an independent predictor of graft loss from chronic rejection in a population of 706 patients who survived with a functioning allograft for at least 6 months

Therapy

1.  ATP III guidelines are appropriate for diet therapy for RTR patients plus HMG-CoA reductase inhibitors.

• The dose should be appropriately reduced in patients receiving cyclosporine A.

 

Clinical Recommendations:

1.  The prevalence of increased total or LDL-cholesterol is highest in patients with CRI and nephrotic syndrome, and renal transplant recipients (RTR); all patients with renal failure have increased triglycerides and decreased HDL-cholesterol.

2.  High total or LDL-cholesterol is associated with CVD in CRD; the relationship of increased triglycerides or decreased HDL-cholesterol to CVD in the absence of increased total or HDL-cholesterol is unknown.

3.  It is reasonable to use ATP III Guidelines for initial classification, treatment initiation and target cholesterol levels for diet or drug therapy.

4.  Most patients with CRI will need drug therapy in addition to diet therapy for treating hyperlipidemia.

5.  HBG-CoA reductase inhibitors are the most effective drugs for reducing LDL-cholesterol in CRD and should be the first drug of choice; dosage reduction is required in RTR patients taking cyclosporine or tacrolimus.

6.  Increased triglycerides or decreased HDL-cholesterol without increased LDL-cholesterol should be treated wtih diet and physical activity.

Additional research is needed to better define the relationship between lipid abnormalities and both CVD and renal disease progression, in particular, the role of increased triglycerides, decreased DL and lipoprotein abnormalities.

Intervention trials are needed to determine whether treating hyperlipidemia reduced the incidence of CVD in RTR.  In addition, randomized controlled trials are needed to assess the effect of lipid-lowering strategies on renal allograft function.

University/Hospital:	Division of Nephrology, Hennipin Country Medical Center
In-Kind support reported by Industry:	Yes

Good review of the current (1998) state of knowledge regarding the relationship between CRI, hyperlipidemia, and CVD.  Few research studies have been conducted to evaluate this question; in particular randomized controlled trials are very limited.