What is the diagnosis and treatment for Nephrotic syndrome?

From the Guidelines

Nephrotic syndrome should be initially treated with corticosteroids, as recommended by the most recent guidelines 1. The treatment of nephrotic syndrome depends on the underlying cause, but typically includes corticosteroids like prednisone at 1-2 mg/kg/day for 4-16 weeks for primary causes. Supportive care involves:

• Diuretics such as furosemide 20-80 mg daily to manage edema
• ACE inhibitors or ARBs (like enalapril 5-20 mg daily) to reduce proteinuria
• Statins for hyperlipidemia Dietary modifications include:
• Moderate sodium restriction (2-3 g/day)
• Adequate protein intake (0.8-1 g/kg/day) Patients should monitor daily weight, blood pressure, and watch for signs of infection or thrombosis. In children, minimal change disease is the most common cause and responds well to steroids, while adults may have more complex underlying conditions like membranous nephropathy or focal segmental glomerulosclerosis that might require immunosuppressive medications such as cyclophosphamide, cyclosporine, or rituximab for steroid-resistant cases, with cyclosporine or tacrolimus recommended as initial second-line therapy for children with steroid-resistant nephrotic syndrome 1. The condition results from damage to the glomerular filtration barrier, allowing proteins to leak into urine. Previous guidelines also recommended corticosteroids as initial treatment 1, and highlighted the importance of considering immunosuppressive therapy in specific cases, such as idiopathic FSGS associated with clinical features of the nephrotic syndrome 1. However, the most recent guideline 1 takes precedence, and its recommendations should be followed.

From the FDA Drug Label

Published studies provide evidence of efficacy and safety in pediatric patients for the treatment of nephrotic syndrome (patients >2 years of age) The drug prednisone can be used for the treatment of nephrotic syndrome in pediatric patients older than 2 years of age 2.

• The efficacy and safety of corticosteroids in pediatric patients with nephrotic syndrome have been established.
• Pediatric patients should be carefully observed with frequent measurements of blood pressure, weight, height, intraocular pressure, and clinical evaluation for the presence of infection, psychosocial disturbances, thromboembolism, peptic ulcers, cataracts, and osteoporosis.

From the Research

Definition and Causes of Nephrotic Syndrome

• Nephrotic syndrome is defined by a triad of clinical features: edema, substantial proteinuria (> 3.5 g/24 hours), and hypoalbuminemia (< 30 g/L) 3.
• It is often associated with hyperlipidemia, thromboembolism, and an increased risk of infection 3.
• The most common cause in children is minimal change glomerulonephritis, while in white adults, nephrotic syndrome is most frequently due to membranous nephropathy 3.
• In populations of African ancestry, the most common cause of nephrotic syndrome is focal segmental glomerulosclerosis 3.
• Diabetic nephropathy is the most common multisystem disease that can cause nephrotic syndrome 3.

Diagnosis of Nephrotic Syndrome

• Patients typically present with periorbital edema or dependent pitting edema 3.
• Proteinuria should be documented by a quantitative measurement, such as urine protein: creatinine ratio (PCR) or albumin: creatinine ratio (ACR) 3.
• A renal biopsy is usually performed to establish the form of glomerular disease responsible for the nephrotic syndrome 3.
• Additional tests may be undertaken to assess if nephrotic syndrome is secondary to another disorder, such as systemic lupus erythematosus or amyloidosis 3.

Treatment of Nephrotic Syndrome

• Steroids have been used widely for the treatment of adult-onset minimal change disease 4, 5.
• The optimal agent, dose, and duration of treatment for the first episode of nephrotic syndrome, or for disease relapse(s), have not been determined 4, 5.
• Compared with no specific treatment, it is uncertain whether prednisolone increases the number with complete remission 5.
• Calcineurin inhibitors (CNIs) with reduced-dose prednisolone or without prednisolone probably make little or no difference to the number achieving complete remission 5.
• Enteric-coated mycophenolate sodium (EC-MPS) with reduced-dose prednisolone probably make little or no difference to the number undergoing complete remission 5.
• Further, adequately powered randomized controlled trials are required to determine the relative efficacies of CNIs and EC-MPS and to evaluate these medications in patients with relapsing or steroid-resistant disease 5.

Management of Nephrotic Syndrome

• Management of initial and infrequent recurrences involves reduction of proteinuria with glucocorticoids 6.
• Frequent recurrences and/or the inability to discontinue glucocorticoids requires alternative therapies 6.
• Steroid-resistant nephrotic syndrome also requires the use of alternative therapies 6.
• Long-term management includes dietary sodium restriction, edema management, and blood pressure control 6.
• Thromboembolism prophylaxis should be considered for patients with nephrotic syndrome and high risk of thromboembolism, particularly those with membranous nephropathy 6.