How to manage cholesterol levels in patients with nephrotic syndrome?

Management of Hyperlipidemia in Nephrotic Syndrome

Statins should be considered as first-line therapy for persistent hyperlipidemia in patients with nephrotic syndrome, particularly for those with additional cardiovascular risk factors such as hypertension and diabetes. 1

Risk Assessment and Monitoring

• Assess atherosclerotic cardiovascular disease (ASCVD) risk based on LDL-C, Apo B, triglyceride, and Lp(a) levels, age group, and ASCVD risk enhancers 1
• Recognize that reduced eGFR (<60 mL/min/1.73 m²) and albuminuria (ACR >30 mg/g) are independently associated with elevated risk of ASCVD 1
• Monitor lipid levels 4-12 weeks after starting treatment or dose adjustment, and every 3-12 months thereafter based on adherence and safety concerns 1
• Check liver enzymes before treatment and 8-12 weeks after starting therapy or dose increase 2

First-Line Treatment Approach

• Start with lifestyle modifications as foundational therapy for all patients with nephrotic syndrome and hyperlipidemia 1:

  • Restrict dietary sodium to <2.0 g/d (<90 mmol/d)
  • Consider a plant-based diet and avoid red meat
  • Normalize weight
  • Stop smoking
  • Exercise regularly

• For persistent hyperlipidemia despite lifestyle changes, initiate statin therapy with dosage intensity aligned to ASCVD risk 1

• High-quality data are lacking to guide treatment in these patients, but statins have shown efficacy in reducing cholesterol levels 1, 3

• Statins can be initiated in children aged >8 years with concerning family history or extremely elevated LDL-C or Lp(a), in the context of informed shared decision-making 1

Second-Line and Adjunctive Therapies

For patients who cannot tolerate statins or fail to achieve LDL-C or triglyceride goals despite maximally tolerated statin dose, consider:

• Bile acid sequestrants - shown in small studies to reduce serum cholesterol in nephrotic syndrome, but have high rate of gastrointestinal side effects 1, 4, 5
• Fibrates - effective for hypertriglyceridemia and shown to reduce cholesterol in nephrotic syndrome, but will increase serum creatinine due to direct action on the kidney 1, 6
• Ezetimibe - has limited vascular and clinical benefits but is used in statin-intolerant patients 1
• Nicotinic acid - theoretically useful but not well studied in nephrotic syndrome 1, 4
• PCSK9 inhibitors - may be beneficial in nephrotic syndrome; trials ongoing 1
• Lipid apheresis - for severe cases unresponsive to pharmacotherapy 1

Special Considerations and Pitfalls

• Gemfibrozil has been shown to reduce plasma triglycerides by 51% and total cholesterol by 15% in nephrotic patients, with improved HDL levels 6

• Combination therapy with bile acid sequestrants and fibrates may provide additional benefit but can cause significant gastrointestinal side effects 6

• Monitor for potential side effects of lipid-lowering agents 3:

  • Check for elevated liver enzymes
  • Monitor creatinine phosphokinase (CPK) for signs of myopathy
  • Be vigilant for rhabdomyolysis, which could worsen kidney function

• Beyond lipid-lowering effects, statins may provide additional renoprotective benefits through pleiotropic effects including regulation of inflammatory response and improved endothelial function 7

• For patients with congenital nephrotic syndrome, consider statin therapy when fasting LDL cholesterol is persistently >160 mg/dL (4.1 mmol/L) or >130 mg/dL (3.4 mmol/L) in patients with additional cardiovascular risk factors 1

• In patients with cardiac amyloidosis and nephrotic syndrome, management approaches are similar to other glomerulopathies, including dietary sodium restriction and appropriate lipid-lowering therapy 1

Comprehensive Management Algorithm

1. Assess ASCVD risk and baseline lipid profile
2. Implement lifestyle modifications for all patients
3. For persistent hyperlipidemia:
   • Start statin therapy as first-line pharmacological intervention
   • Align statin intensity to ASCVD risk
4. If inadequate response or intolerance to statins:
   • Add or switch to non-statin therapy (bile acid sequestrants, fibrates, ezetimibe)
5. Monitor response and adjust therapy accordingly
6. Consider combination therapy for refractory cases