Management of Nephrotic Syndrome

Initial Diagnostic Evaluation

• A thorough diagnostic workup should include blood biochemistry, such as blood count, sodium, chloride, albumin, magnesium, creatinine, urea, protein, cholesterol, triglycerides, and glucose, as recommended by the National Kidney Foundation 1
• Thyroid function, including TSH and free T4, and serum IgG levels should be measured as part of the diagnostic workup 1
• Calcium-phosphate metabolism, including ionized calcium, phosphate, alkaline phosphatase, PTH, and vitamin D, should be assessed 1
• Ultrasound of the abdomen should be performed to evaluate kidney echogenicity, size, and detect ascites or effusions 1
• Cardiac ultrasound should be conducted to check for effusions and left ventricular mass 1
• Genetic testing should be considered as a first-line diagnostic measure, especially in congenital nephrotic syndrome, according to the American Academy of Pediatrics 2

Management Approach

Fluid and Edema Management

• Fluid intake should be restricted when feasible, especially in cases of hyponatremia and severe edema, as recommended by the European Renal Association 1
• Dietary sodium intake should be restricted as a first-line intervention for edema management, according to the American Heart Association 3
• Furosemide should be administered at the end of albumin infusions unless the patient has marked hypovolemia or hyponatremia, as recommended by the National Kidney Foundation 4
• Diuretic dosing should be cautious, with doses >6 mg/kg per day not given for periods longer than 1 week, according to the European Renal Association 4

Albumin Infusions

• Intravenous albumin should be administered only when clinically indicated, or as part of regular albumin infusion protocols, as recommended by the American Academy of Pediatrics 1
• Home administration of albumin infusions by trained parents/caregivers should be considered to improve quality of life and reduce hospitalization, according to the National Kidney Foundation 5
• The purpose of albumin infusion is to support intravascular volume and reduce edema, not to normalize serum albumin levels, as recommended by the European Renal Association 1

Prevention and Management of Complications

• Prophylactic anticoagulation should be considered when central venous access is required, as recommended by the American College of Chest Physicians 5
• Patients with congenital nephrotic syndrome should be referred to specialized teams in tertiary pediatric nephrology centers, according to the American Academy of Pediatrics 2
• A multidisciplinary team, including neonatologists, pediatric nephrologists, nurses, dieticians, surgeons, psychologists, and social workers, should manage patients with congenital nephrotic syndrome, as recommended by the National Kidney Foundation 2
• Ambulatory management should be considered when possible to improve quality of life and reduce risk of nosocomial infections, according to the European Renal Association 5
• Nephrectomy should be considered in patients with persistent hypovolemia, thrombosis, and failure to thrive despite optimal conservative management, as recommended by the American Urological Association 5

Special Considerations for Congenital Nephrotic Syndrome

• A stepwise approach with prolonged conservative management is appropriate for congenital nephrotic syndrome, and routine early nephrectomies should be avoided, as recommended by the National Kidney Foundation 5

Management of Nephrotic Syndrome

Core Management Strategies

• 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, as recommended by the National Kidney Foundation 6, 7
• 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, according to the American Academy of Pediatrics 8
• Consider administering furosemide (0.5-2 mg/kg) at the end of albumin infusions unless the patient has marked hypovolemia or hyponatremia, as suggested by the European Renal Association 8
• Avoid diuretics in patients with evidence of intravascular hypovolemia, as recommended by the National Institute of Diabetes and Digestive and Kidney Diseases 8

Prevention and Management of Complications

• Implement infection prophylaxis measures, especially in children with congenital nephrotic syndrome, as recommended by the American Academy of Pediatrics 8
• Ensure adequate nutrition to prevent malnutrition and support growth, particularly in children, according to the National Kidney Foundation 6
• Consider growth hormone substitution in children with growth impairment, as suggested by the European Society for Pediatric Nephrology 8

Special Considerations for Congenital Nephrotic Syndrome

• Manage with a multidisciplinary team including specialized pediatric nephrology, as recommended by the American Academy of Pediatrics 6
• Ambulatory management is recommended when possible to improve quality of life and reduce risk of nosocomial infections, according to the European Renal Association 8
• Home administration of albumin infusions by trained parents is feasible and safe, as suggested by the National Institute of Diabetes and Digestive and Kidney Diseases 8
• Nephrectomy is not routinely recommended but should be considered in patients with severe complications despite optimal conservative treatment, as recommended by the National Kidney Foundation 6
• Consider nephrectomy before transplantation in patients with persisting nephrotic syndrome and/or WT1-dominant pathogenic variant, according to the European Society for Organ Transplantation 6

Pitfalls and Caveats

• Avoid routine early nephrectomies in congenital nephrotic syndrome, as recommended by the National Kidney Foundation 6
• Do not use immunosuppressive agents for genetic forms of congenital nephrotic syndrome as they are unlikely to respond, as suggested by the European Renal Association 8
• Be cautious with diuretic dosing; doses >6 mg/kg per day should not be given for periods longer than 1 week, according to the American Academy of Pediatrics 8

Congenital Nephrotic Syndrome: Evidence‑Based Diagnostic and Management Recommendations

Genetic Evaluation

• Perform rapid whole‑exome sequencing or an extended podocytopathy gene panel (including at least NPHS1, NPHS2, WT1, PLCE1, LAMB2) as the first‑line diagnostic test for infants who develop nephrotic syndrome within the first 3 months of life. This approach enables early identification of underlying genetic causes and guides subsequent therapeutic decisions. 9

Referral and Specialized Care

• Refer every infant with congenital nephrotic syndrome to a tertiary pediatric nephrology center that provides a dedicated multidisciplinary team. Early referral ensures access to specialized expertise and coordinated care pathways. 10

Multidisciplinary Management Team

• Management should involve a coordinated team comprising neonatologists, pediatric nephrologists, renal nurses, dietitians, pediatric surgeons, psychologists, and social‑work professionals. Such comprehensive care addresses the complex medical, nutritional, surgical, and psychosocial needs of these patients. 10

Early Transplant Planning

• Introduce patients to a kidney transplant program early in the course of chronic kidney disease to reduce the duration of dialysis dependence and improve long‑term outcomes. Early planning facilitates timely evaluation and listing when transplantation becomes appropriate. 10