What is the management of nephrotic syndrome?

Management of Nephrotic Syndrome

Core Management Strategy

The management of nephrotic syndrome requires maintaining intravascular euvolemia, ensuring adequate nutrition, preventing complications (thrombosis, infection, malnutrition), and preserving kidney function while addressing the underlying cause when possible. 1

Initial Diagnostic Workup

Before initiating treatment, establish the etiology and assess disease severity:

• Obtain comprehensive blood work: Complete blood count, serum electrolytes (sodium, chloride, magnesium), kidney function (creatinine, urea), albumin, total protein, lipid panel (cholesterol, triglycerides), and glucose 1
• Assess thyroid function (TSH, free T4) and serum IgG levels, as these proteins are lost in urine 1
• Evaluate calcium-phosphate metabolism: Measure ionized calcium, phosphate, alkaline phosphatase, PTH, and vitamin D 1
• Perform renal ultrasound to assess kidney size, echogenicity, and detect ascites or effusions 1
• Consider cardiac ultrasound to evaluate for pericardial effusions and left ventricular mass 1
• Genetic testing should be first-line in congenital nephrotic syndrome or when clinical features suggest hereditary disease 1
• Renal biopsy may be indicated in adults to confirm underlying disease and guide immunosuppressive therapy, particularly when genetic testing is negative 2

Fluid and Edema Management

Sodium and Fluid Restriction

• Restrict dietary sodium intake as first-line intervention for edema control 1
• Limit fluid intake when feasible, especially with hyponatremia and severe edema 1

Diuretic Therapy

• Administer furosemide (0.5-2 mg/kg per dose, up to six times daily; maximum 10 mg/kg per day) for patients with intravascular fluid overload (evidenced by good peripheral perfusion, hypertension, and edema) and preserved kidney function 3, 1
• Give furosemide (0.5-2 mg/kg) at the end of albumin infusions unless marked hypovolemia or hyponatremia is present 3, 1
• Avoid diuretics entirely in patients with intravascular hypovolemia (poor perfusion, hypotension) 1
• Do not exceed 6 mg/kg per day for longer than 1 week to minimize toxicity 3, 1
• Administer intravenous furosemide over 5-30 minutes to reduce ototoxicity risk 3
• If potassium-sparing diuretics are needed, use amiloride rather than spironolactone 3

Albumin Infusions

• Administer intravenous albumin only when clinically indicated (severe symptomatic hypovolemia, refractory edema with diuretics) or as part of established protocols 1
• The goal is to support intravascular volume and reduce edema, not to normalize serum albumin levels 1
• Home administration by trained parents/caregivers is safe and feasible, improving quality of life and reducing hospitalization 3, 1

Immunosuppressive Therapy

Idiopathic Nephrotic Syndrome in Adults

• Corticosteroids (prednisone) are first-line therapy for idiopathic nephrotic syndrome in adults, particularly for minimal change disease and focal segmental glomerulosclerosis 4, 2
• Prednisone is FDA-approved to induce diuresis or remission of proteinuria in idiopathic nephrotic syndrome or that due to lupus erythematosus 4
• For steroid-resistant cases, consider calcineurin inhibitors (cyclosporine, tacrolimus) 5
• Alternative agents include mycophenolate mofetil, rituximab, or cyclophosphamide depending on the underlying histology 5

Genetic/Congenital Nephrotic Syndrome

• Do not use immunosuppressive agents for genetic forms of nephrotic syndrome, as they are caused by podocyte structural abnormalities that do not respond to immunosuppression 3, 1
• Before considering immunosuppression, obtain negative genetic testing, negative infection screening, and kidney biopsy excluding diffuse mesangial sclerosis 3
• If comprehensive genetic testing and secondary cause screening are negative, a trial of immunosuppressive therapy may be considered 3

Prevention and Management of Complications

Thromboembolism

• Consider prophylactic anticoagulation when central venous access is required 1
• Monitor for thromboembolism, especially with severe hypoalbuminemia (albumin <2.0-2.5 g/dL), though routine prophylactic anticoagulation is not currently recommended in all patients 2

Infection

• Implement infection prophylaxis measures, particularly in children with congenital nephrotic syndrome 1
• Patients on corticosteroids may exhibit diminished response to vaccines and increased infection risk 4
• Defer routine vaccination until corticosteroid therapy is discontinued when possible 4

Nutrition and Growth

• Ensure adequate nutrition to prevent malnutrition and support growth, particularly in children 1
• Consider growth hormone substitution in children with growth impairment 1
• Monitor growth velocity in pediatric patients on corticosteroids, as it may be more sensitive than HPA axis testing for detecting systemic effects 4

Hyperlipidemia

• Address hyperlipidemia as part of comprehensive management to reduce cardiovascular risk 6, 7

Special Considerations for Congenital Nephrotic Syndrome

• Refer patients to specialized tertiary pediatric nephrology centers with multidisciplinary teams (neonatologists, pediatric nephrologists, nurses, dieticians, surgeons, psychologists, social workers) 1
• Pursue ambulatory management when possible to improve quality of life and reduce nosocomial infection risk 3, 1
• Use a stepwise approach with prolonged conservative management; avoid routine early nephrectomies 1
• Consider bilateral nephrectomy and dialysis initiation when the infant weighs 7-9 kg (6-12 months) if persistent hypovolemia, thrombosis, and failure to thrive occur despite optimal conservative management 3, 1
• Nephrectomy before transplantation should be considered in patients with persistent nephrotic syndrome and/or WT1 pathogenic variants 3

Congenital Membranous Nephropathy

• Screen for anti-NEP antibodies in infants with kidney failure at presentation or transient proteinuria that spontaneously resolves, or with family history of congenital membranous nephropathy 3

Critical Pitfalls to Avoid

• Never use diuretics in hypovolemic patients, as this worsens intravascular depletion and can precipitate acute kidney injury 1
• Do not give furosemide doses >6 mg/kg per day for >1 week due to ototoxicity risk 3, 1
• Avoid immunosuppression in genetic nephrotic syndrome without first ruling out genetic causes, as these patients will not respond and face unnecessary toxicity 3, 1
• Do not perform routine early nephrectomies in congenital nephrotic syndrome; prolonged conservative management is appropriate 1
• Aspirin should be used cautiously with corticosteroids in patients with hypoprothrombinemia 4
• Corticosteroids in pregnancy are Category C; use only if benefit justifies fetal risk 4