What is the approach to managing 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 Evaluation

• Complete a thorough diagnostic workup including blood biochemistry (blood count, sodium, chloride, albumin, magnesium, creatinine, urea, protein, cholesterol, triglycerides, glucose) 2
• Measure thyroid function (TSH, free T4) and serum IgG levels 2
• Assess calcium-phosphate metabolism (ionized calcium, phosphate, alkaline phosphatase, PTH, vitamin D) 2
• Perform ultrasound of abdomen to evaluate kidney echogenicity, size, and detect ascites or effusions 2
• Conduct cardiac ultrasound to check for effusions and left ventricular mass 2
• Consider genetic testing as a first-line diagnostic measure, especially in congenital nephrotic syndrome 2
• In adults, kidney biopsy is typically indicated for diagnosis, except in patients with positive anti-phospholipase A2 receptor antibodies (diagnostic of membranous nephropathy) 3
• In children with suspected minimal change disease, a trial of steroids may be initiated without biopsy; if no response, proceed to genetic testing and kidney biopsy 3

Management Approach

Fluid and Edema Management

• Restrict fluid intake when feasible, especially in cases of hyponatremia and severe edema 2
• Restrict dietary sodium intake as a first-line intervention for edema management 2
• 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 2
• Avoid diuretics in patients with evidence of intravascular hypovolemia 1
• Be cautious with diuretic dosing; doses >6 mg/kg per day should not be given for periods longer than 1 week 2

Albumin Infusions

• Some centers administer intravenous albumin only when clinically indicated, while others use regular albumin infusion protocols (1-4 g/kg/day) 2
• Consider home administration of albumin infusions by trained parents/caregivers when appropriate to improve quality of life and reduce hospitalization 2, 1
• The purpose of albumin infusion is not to normalize serum albumin levels but to support intravascular volume and reduce edema 2

Pharmacological Treatment

• For children with minimal change disease, corticosteroids are the first-line therapy 3, 4
• For steroid-resistant cases, consider calcineurin inhibitors (cyclosporine, tacrolimus), mycophenolate mofetil, rituximab, or cyclophosphamide depending on the underlying cause 3, 4
• Do not use immunosuppressive agents for genetic forms of nephrotic syndrome as they are unlikely to respond 2, 1
• Use ACE inhibitors to reduce proteinuria and preserve kidney function 5
• For membranous nephropathy in adults, a combination of steroids and alkylating agents may be effective 6

Prevention and Management of Complications

• Implement infection prophylaxis measures, especially in children with congenital nephrotic syndrome 1
• Monitor for thromboembolism, particularly in patients with severe hypoalbuminemia or membranous nephropathy 3
• Consider prophylactic anticoagulation when central venous access is required 2
• Ensure adequate nutrition to prevent malnutrition and support growth, particularly in children 1
• Consider growth hormone substitution in children with growth impairment 1
• Monitor for hyperlipidemia and consider lipid-lowering agents when appropriate 5, 7

Special Considerations for Congenital Nephrotic Syndrome

• Refer all patients with congenital nephrotic syndrome to specialized teams in tertiary pediatric nephrology centers 2
• Manage with a multidisciplinary team including neonatologists, pediatric nephrologists, nurses, dieticians, surgeons, psychologists, and social workers 2
• Consider ambulatory management when possible to improve quality of life and reduce risk of nosocomial infections 2
• Consider nephrectomy in patients with persistent hypovolemia, thrombosis, and failure to thrive despite optimal conservative management 2
• Consider nephrectomy before transplantation in patients with persisting nephrotic syndrome and/or WT1 pathogenic variant 1

Pitfalls and Caveats

• Avoid routine early nephrectomies in congenital nephrotic syndrome; an individualized, stepwise approach with prolonged conservative management is appropriate 2
• Be cautious with pediatric patients receiving corticosteroids as they may experience decreased growth velocity even at low systemic doses 8
• Monitor for steroid side effects, including diabetes mellitus, fluid retention, and hypertension, especially in elderly patients 8
• Watch for worsening of proteinuria and kidney function to avoid missing the opportunity to provide appropriate immunosuppressive therapy 9
• Recognize that patients on corticosteroid therapy may exhibit a diminished response to vaccines due to inhibition of antibody response 8