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 Diagnostic Workup

Before initiating treatment, establish the diagnosis and etiology through:

• Blood biochemistry: Complete blood count, sodium, chloride, albumin, magnesium, creatinine, urea, protein, cholesterol, triglycerides, and glucose 1
• Thyroid function: TSH and free T4, plus serum IgG levels 1
• Calcium-phosphate metabolism: Ionized calcium, phosphate, alkaline phosphatase, PTH, and vitamin D 1
• Imaging: Abdominal ultrasound to evaluate kidney echogenicity, size, and detect ascites or effusions 1
• Cardiac evaluation: Echocardiogram to check for effusions and left ventricular mass 1
• Genetic testing: Consider as first-line diagnostic measure, especially in congenital nephrotic syndrome 1
• Renal biopsy: May be useful to confirm underlying disease or identify idiopathic disease more likely to respond to corticosteroids 2

Fluid and Edema Management

First-Line Interventions

• Restrict dietary sodium intake as the primary intervention for edema management 1
• Restrict fluid intake when feasible, especially in cases of hyponatremia and severe edema 1

Diuretic Therapy

• Administer furosemide 0.5-2 mg/kg per dose (up to six times daily) for patients with intravascular fluid overload and preserved kidney function 1
• Give furosemide at the end of albumin infusions unless the patient has marked hypovolemia or hyponatremia 1
• Avoid diuretics entirely in patients with evidence of intravascular hypovolemia 1
• Limit high-dose diuretics: Doses >6 mg/kg per day should not be given for periods longer than 1 week 1
• Consider additional diuretics: Thiazide and potassium-sparing diuretics may be added for intractable edema 3

Albumin Infusion Protocol

• Administer intravenous albumin only when clinically indicated or as part of regular albumin infusion protocols 1
• The purpose is to support intravascular volume and reduce edema, not to normalize serum albumin levels 1
• Consider home administration by trained parents/caregivers to improve quality of life and reduce hospitalization 1

Immunosuppressive Therapy

Corticosteroids

• Corticosteroids are the first-line therapy for many forms of nephrotic syndrome 4
• Prednisone is effective and safe in pediatric patients >2 years of age for treatment of nephrotic syndrome 5
• Monitor carefully for blood pressure changes, weight gain, intraocular pressure elevation, infection, psychosocial disturbances, thromboembolism, peptic ulcers, cataracts, and osteoporosis 5
• In pediatric patients, titrate to the lowest effective dose to minimize growth suppression effects 5

Steroid-Resistant Cases

• For steroid-resistant cases, consider calcineurin inhibitors (cyclosporine or tacrolimus) 4
• Alternative options include: Mycophenolate mofetil, rituximab, or cyclophosphamide depending on the underlying cause 4

Genetic Forms

• Do NOT use immunosuppressive agents for genetic forms of congenital nephrotic syndrome as they are unlikely to respond 1

Prevention and Management of Complications

Thromboembolism

• Consider prophylactic anticoagulation when central venous access is required 1
• Monitor for thromboembolism, especially with significant hypoalbuminemia 4

Infection Prevention

• Implement infection prophylaxis measures, especially in children with congenital nephrotic syndrome 1
• Prophylactic antibiotics are not currently recommended routinely 2
• Consider ambulatory management when possible to reduce risk of nosocomial infections 1

Nutritional Support

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

Renal Protection

• Use angiotensin-converting enzyme inhibitors as part of standard treatment 2

Special Considerations for Congenital Nephrotic Syndrome

• Refer patients to specialized teams in tertiary pediatric nephrology centers 1
• Manage with a multidisciplinary team including neonatologists, pediatric nephrologists, nurses, dieticians, surgeons, psychologists, and social workers 1
• Use a stepwise approach with prolonged conservative management; routine early nephrectomies should be avoided 1
• Consider nephrectomy only in patients with persistent hypovolemia, thrombosis, and failure to thrive despite optimal conservative management 1
• Consider nephrectomy before transplantation in patients with persisting nephrotic syndrome and/or WT1-dominant pathogenic variant 1

Critical Pitfalls to Avoid

• Never give diuretics to hypovolemic patients as this worsens intravascular depletion 1
• Do not use immunosuppression for genetic forms as it provides no benefit and exposes patients to unnecessary toxicity 1, 4
• Avoid routine early nephrectomies in congenital nephrotic syndrome 1
• Do not use prophylactic anticoagulation routinely outside of specific indications like central venous access 2
• Be cautious with aspirin when using corticosteroids in patients with hypoprothrombinemia 5
• Defer routine vaccination until corticosteroid therapy is discontinued if possible, as patients may exhibit diminished response 5