What is the management of nephrotic syndrome?

Management of Nephrotic Syndrome

The management of nephrotic syndrome requires a comprehensive therapeutic approach focused on maintaining intravascular euvolemia, adequate nutrition, preventing complications, and preserving kidney function while addressing the underlying cause when possible. 1

Initial Assessment and Diagnosis

• Nephrotic syndrome is characterized by nephrotic-range proteinuria, hypoalbuminemia, edema, and often hyperlipidemia 2
• In children, minimal change disease and focal segmental glomerulosclerosis (FSGS) are most common causes 2, 3
• In adults, FSGS and membranous nephropathy are the most common primary causes, with diabetes being the most common secondary cause 2, 4
• Genetic testing and kidney biopsy are warranted in steroid-resistant cases to determine the specific diagnosis 2, 3

Core Management Strategies

Fluid and Sodium Management

• Restrict dietary sodium to control edema 4
• Administer diuretics (primarily furosemide 0.5-2 mg/kg per dose up to six times daily) for patients with intravascular fluid overload and preserved kidney function 1
• Consider administering furosemide (0.5-2 mg/kg) at the end of albumin infusions unless the patient has marked hypovolemia or hyponatremia 1
• Avoid diuretics in patients with evidence of intravascular hypovolemia 1

Proteinuria Reduction

• For children with idiopathic nephrotic syndrome, glucocorticoids are the cornerstone of treatment 2, 3
• In adults, angiotensin-converting enzyme inhibitors are recommended to reduce proteinuria 4
• Prednisone is indicated to induce diuresis or remission of proteinuria in idiopathic nephrotic syndrome or that due to lupus erythematosus 5

Prevention and Management of Complications

Thromboembolism Prophylaxis

• Consider anticoagulation prophylaxis for patients at high risk of thromboembolism, particularly those with membranous nephropathy 2
• Monitor for signs of venous thromboembolism, which is a common complication 4

Infection Prevention

• Implement infection prophylaxis measures, especially in children with congenital nephrotic syndrome 1
• Monitor closely for signs of infection, as patients are at increased risk due to urinary loss of immunoglobulins 6

Hyperlipidemia Management

• Address hyperlipidemia, which is a common feature of nephrotic syndrome 6, 7
• Consider lipid-lowering therapy in persistent cases 7

Nutritional Support

• Ensure adequate nutrition to prevent malnutrition and support growth, particularly in children 1, 3
• Consider growth hormone substitution in children with growth impairment 1

Special Considerations for Congenital Nephrotic Syndrome

• Manage with a multidisciplinary team including specialized pediatric nephrology 1
• Ambulatory management is recommended when possible to improve quality of life and reduce risk of nosocomial infections 1
• Home administration of albumin infusions by trained parents is feasible and safe 1
• Nephrectomy is not routinely recommended but should be considered in patients with severe complications despite optimal conservative treatment 1
• Consider nephrectomy before transplantation in patients with persisting nephrotic syndrome and/or WT1-dominant pathogenic variant 1

Treatment Based on Response Pattern

Steroid-Sensitive Nephrotic Syndrome

• Initial and infrequent recurrences can be managed with glucocorticoids 3
• For frequent relapses or steroid dependence, consider steroid-sparing agents such as levamisole, mycophenolate mofetil, calcineurin inhibitors, anti-CD20 monoclonal antibodies, or cyclophosphamide 3

Steroid-Resistant Nephrotic Syndrome

• Consider calcineurin inhibitors as second-line therapy 3
• For multidrug-resistant cases, prepare for potential progression to kidney failure 3
• Genetic testing is important as up to one-third of steroid-resistant cases have a monogenic origin 3

Monitoring and Follow-up

• Regularly monitor blood pressure, fluid status, proteinuria, and kidney function 2, 3
• In children, monitor growth velocity as it may be affected by corticosteroid treatment 5
• Watch for medication side effects, particularly with long-term steroid use 3

Pitfalls and Caveats

• Avoid routine early nephrectomies in congenital nephrotic syndrome 1
• Do not use immunosuppressive agents for genetic forms of congenital nephrotic syndrome as they are unlikely to respond 1
• Be cautious with diuretic dosing; doses >6 mg/kg per day should not be given for periods longer than 1 week 1
• In pediatric patients, recognize that growth velocity may be a more sensitive indicator of systemic corticosteroid exposure than laboratory tests of HPA axis function 5
• Consider the increased risk of diabetes mellitus, fluid retention, and hypertension in elderly patients treated with corticosteroids 5