Management of Cholesterol Complications in Nephrotic Syndrome
Statins should be considered as first-line pharmacological therapy for persistent hyperlipidemia in patients with nephrotic syndrome, particularly for those with additional cardiovascular risk factors. 1
Pathophysiology and Risk Assessment
- Nephrotic syndrome causes profound alterations in lipid metabolism characterized by elevated total cholesterol, LDL cholesterol, apolipoprotein B-containing lipoproteins, and often hypertriglyceridemia as the disorder progresses 2
- Reduced eGFR (<60 mL/min/1.73 m²) and albuminuria (ACR >30 mg/g) are independently associated with elevated risk of atherosclerotic cardiovascular disease (ASCVD) 1
- The lipid profile should be assessed based on LDL-C, Apo B, triglyceride, and Lp(a) levels, along with age and other ASCVD risk enhancers 3
Treatment Algorithm
Step 1: Lifestyle Modifications (First-line for all patients)
- Restrict dietary sodium to <2.0 g/d (<90 mmol/d) 3
- Consider adopting a plant-based diet and avoiding red meat 3
- Normalize weight through appropriate dietary measures 3
- Stop smoking and exercise regularly 3
- Monitor response to lifestyle changes with lipid panels 1
Step 2: Pharmacological Therapy for Persistent Hyperlipidemia
- Statins as first-line drug therapy:
- Align statin dosage intensity to ASCVD risk 3
- Pravastatin has been shown to reduce total cholesterol by 22% and LDL cholesterol by 28% in nephrotic patients 4
- Monitor lipid levels 4-12 weeks after starting treatment or dose adjustment 1
- For children >8 years with concerning family history or extremely elevated LDL-C, statins can be initiated with appropriate shared decision-making 3
Step 3: Second-Line and Combination Therapy
- For patients who cannot tolerate statins or fail to achieve lipid goals despite maximum tolerated statin dose, consider: 3, 1
- Bile acid sequestrants (e.g., colestipol) - shown to lower total cholesterol by approximately 20% in nephrotic patients 5
- Ezetimibe - useful in statin-intolerant patients 1
- Fibrates - effective for hypertriglyceridemia but will increase serum creatinine 1
- PCSK9 inhibitors - may be beneficial in nephrotic syndrome 1
- Nicotinic acid - theoretically useful but limited testing in nephrotic syndrome 6
Special Considerations and Monitoring
- High-quality data are lacking to guide treatment of hyperlipidemia specifically in nephrotic syndrome 3
- Monitor lipid levels and safety indicators every 3-12 months after initial stabilization 1
- Bile acid sequestrants and fibrates have high rates of gastrointestinal side effects, potentially limiting their use 3
- Fibrates increase serum creatinine due to direct action on the kidney - use with caution in patients with compromised renal function 1
- For children with congenital nephrotic syndrome, consider statin therapy when fasting LDL cholesterol is persistently >160 mg/dL or >130 mg/dL with additional cardiovascular risk factors 1
Potential Complications of Untreated Hyperlipidemia
- Increased risk of atherosclerosis and cardiovascular disease 6, 2
- Potential contribution to progression of renal failure 6, 7
- Reduction of body mass and impaired exercise capacity due to limited delivery of lipid fuel to muscles 2