How should I manage a patient with nephrotic syndrome?

Management of Nephrotic Syndrome

The management of nephrotic syndrome requires a comprehensive approach focused on maintaining intravascular euvolemia, preventing life-threatening complications (particularly thromboembolism and infection), and addressing the underlying cause through appropriate diagnostic workup including renal biopsy in most adults and genetic testing in congenital cases. 1, 2

Initial Diagnostic Workup

Essential Laboratory Evaluation

• Obtain complete blood biochemistry including hemogram, sodium, chloride, albumin, magnesium, creatinine, urea, total proteins, cholesterol, triglycerides, and glucose 1, 2
• Measure thyroid function (TSH and free T4) and serum IgG levels, as hypothyroidism and immunoglobulin loss are common complications 1, 2
• Assess calcium-phosphate metabolism including ionized calcium, phosphate, alkaline phosphatase, PTH, and vitamin D levels 1, 2
• Perform abdominal ultrasound to evaluate renal echogenicity, size, and detect ascites or effusions 1, 2

Determining Underlying Etiology

• In children younger than 12 years, initiate glucocorticoid therapy empirically without biopsy, as minimal change disease is most likely 3
• If pediatric patients fail to respond to steroids, proceed with genetic testing and kidney biopsy 3
• In adults, renal biopsy is typically indicated for diagnosis, except when serum anti-phospholipase A2 receptor antibodies are positive, which is diagnostic of membranous nephropathy 3
• For congenital nephrotic syndrome (onset within first 3 months of life), perform genetic screening as a first-line diagnostic measure using rapid whole-exome sequencing or extended podocytopathy gene panel (minimum: NPHS1, NPHS2, WT1, PLCE1, LAMB2) 4

Fluid and Edema Management

Sodium and Fluid Restriction

• Restrict dietary sodium intake as the first-line intervention for edema management 1, 2
• Restrict fluid intake when feasible, especially in cases of hyponatremia and severe edema 1, 2

Diuretic Therapy

• Administer furosemide (0.5-2 mg/kg per dose, up to six times daily) for patients with intravascular volume overload and preserved renal function 1, 2
• Consider administering furosemide (0.5-2 mg/kg) at the end of albumin infusions unless the patient has marked hypovolemia or hyponatremia 1, 2
• Avoid diuretics entirely in patients with evidence of intravascular hypovolemia 1, 2
• Do not give diuretic doses >6 mg/kg per day for periods longer than 1 week 2

Albumin Infusions

• Administer intravenous albumin only when clinically indicated (severe hypovolemia, refractory edema), not routinely to normalize serum albumin levels 2
• The purpose is to support intravascular volume and reduce edema temporarily, not to correct hypoalbuminemia 2
• Consider home administration of albumin infusions by trained parents/caregivers in congenital cases to improve quality of life and reduce hospitalization 2

Prevention and Management of Complications

Thromboembolism Prevention

• Monitor closely for thromboembolic events, which occur in 26.7% of adults and 2.8% of children with nephrotic syndrome 5
• Consider prophylactic anticoagulation when central venous access is required, particularly in patients with severe hypoalbuminemia 1, 5
• Thromboembolism prophylaxis should be strongly considered for patients with membranous nephropathy and high-risk features 3

Infection Prevention

• Implement infection prophylaxis measures, especially in severe cases and children with congenital nephrotic syndrome 1, 2
• Patients have high risk of infections from encapsulated bacteria due to urinary immunoglobulin loss 5
• Provide prompt and adequate antibiotic therapy for acute bacterial infections 5

Metabolic and Nutritional Support

• Ensure adequate nutrition to prevent malnutrition and support growth, particularly in children 1, 2
• Supplement with vitamin D (colecalciferol or calcifediol) and calcium (250-500 mg/day) in cases of low 25-OH-D3 and/or low ionized calcium and/or elevated PTH levels 1
• Consider using statins when LDL cholesterol is persistently elevated in patients with additional cardiovascular risk factors 1
• Monitor and treat iron deficiency; administer erythropoietin in patients with anemia despite iron supplementation 1
• Consider growth hormone substitution in children with growth impairment 2

Renal Protection and Blood Pressure Control

• Use SGLT2 inhibitors for renal protection in patients with focal segmental glomerulosclerosis and eGFR ≥20 mL/min/1.73 m² and UACR ≥200 mg/g 1
• Use angiotensin-converting enzyme inhibitors for blood pressure control and proteinuria reduction 6

Immunosuppressive Therapy

Corticosteroids

• Glucocorticoids are the first-line therapy for children younger than 12 years with presumed minimal change disease 3
• Corticosteroids are frequently first-line therapy for many forms of nephrotic syndrome in adults, though evidence is limited 1, 6
• For frequent recurrences or inability to discontinue glucocorticoids, alternative therapies are required 3

Alternative Immunosuppression

• For steroid-resistant nephrotic syndrome, consider calcineurin inhibitors, mycophenolate mofetil, or rituximab 7
• Do not use immunosuppressive agents for genetic forms of congenital nephrotic syndrome, as they are unlikely to respond 2

Special Considerations for Congenital Nephrotic Syndrome

Multidisciplinary Management

• Refer all patients with congenital nephrotic syndrome to specialized teams in tertiary pediatric nephrology centers 4, 2
• Manage with multidisciplinary teams including neonatologists, pediatric nephrologists, nephrology nurses, renal dieticians, pediatric surgeons, psychologists, and social workers 4, 2
• Introduce patients to a transplant center early in CKD progression to minimize time on dialysis 4

Conservative vs. Surgical Management

• A stepwise approach with prolonged conservative management is appropriate; avoid routine early nephrectomies 2
• Consider nephrectomy only 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-dominant pathogenic variant 2
• Ambulatory management is preferred when possible to improve quality of life and reduce risk of nosocomial infections 2

Critical Pitfalls to Avoid

• Never use diuretics in patients with intravascular hypovolemia, as this can precipitate acute kidney injury 1, 2
• Do not perform routine early nephrectomies in congenital nephrotic syndrome 2
• Avoid prolonged high-dose diuretics (>6 mg/kg/day for >1 week) due to ototoxicity and electrolyte complications 2
• Do not use albumin infusions to normalize serum albumin levels; use only for acute volume support 2
• Recognize that intravenous albumin, prophylactic antibiotics, and prophylactic anticoagulation are not routinely recommended for all patients 6