What are the treatment options for Nephrotic Syndrome?

From the Guidelines

The treatment for nephrotic syndrome should prioritize the use of cyclosporine or tacrolimus as initial second-line therapy for steroid-resistant cases, as recommended by the 2021 KDIGO clinical practice guideline 1.

Introduction to Treatment Options

The management of nephrotic syndrome involves a multifaceted approach, focusing on reducing proteinuria, controlling edema, and addressing the underlying cause. Initial therapy typically includes corticosteroids, with prednisone being a common choice, usually starting at 1 mg/kg/day (maximum 80 mg) for 4-16 weeks, depending on the specific cause and response 1.

First-Line and Supportive Therapies

• Diuretics such as furosemide (20-80 mg daily) help manage edema.
• ACE inhibitors or ARBs (like enalapril 5-40 mg daily or losartan 25-100 mg daily) reduce proteinuria by decreasing glomerular pressure.
• Supportive care involves sodium restriction (2-3 g/day), moderate protein intake (0.8-1 g/kg/day), and sometimes anticoagulants if there's a high risk of thrombosis.
• Statins help manage hyperlipidemia, which commonly occurs in nephrotic syndrome.

Second-Line Therapies for Steroid-Resistant Cases

For patients who are steroid-resistant, cyclosporine or tacrolimus are recommended as initial second-line therapies 1. Other options may include mycophenolate mofetil, with a combination of mycophenolate mofetil and high-dose dexamethasone showing promise in inducing remission in steroid-resistant cases 1.

Monitoring and Adjustment

Treatment duration varies based on the underlying cause, with minimal change disease often responding within weeks, while other conditions may require months of therapy. Regular monitoring of kidney function, protein levels, and medication side effects is essential throughout treatment to adjust therapies as needed and prevent progression to chronic kidney disease.

Key Considerations

• The choice of immunosuppressive medication should be guided by the side-effect profile and the specific characteristics of the patient.
• Cyclosporine and tacrolimus must be used with caution in patients with significant vascular or interstitial disease on renal biopsy and in those who have decreased estimated glomerular filtration rate (eGFR) 1.
• The recent guideline recommendations should be considered in the context of individual patient needs and responses to therapy 1.

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 treatment option for Nephrotic Syndrome is corticosteroids, such as prednisone, which has been shown to be effective in pediatric patients over 2 years of age 2.

From the Research

Treatment Options for Nephrotic Syndrome

The treatment options for Nephrotic Syndrome can be categorized based on the severity and type of the condition.

• For steroid-sensitive nephrotic syndrome (SSNS), the mainstay of treatment is oral corticosteroids, with most patients responding within 4 weeks to an oral course of prednisone (PDN) 3.
• However, corticosteroids have important side effects, and 60-80% of patients relapse, developing frequently relapsing or steroid-dependent forms, which may require second-line steroid-sparing immunosuppressive medications 3.
• In adults with idiopathic nephrotic syndrome, treatment options include corticosteroids, immunosuppressive agents, and alternative therapies such as intravenous high-dose steroid pulses, alternate-day prednisone, and short courses with cytotoxic agents 4.
• A study comparing low-dose corticosteroid plus enteric-coated mycophenolate sodium versus standard corticosteroid treatment for minimal change nephrotic syndrome in adults found no significant difference in complete remission rates between the two groups 5.

Steroid Dosing for Relapses

• Traditionally, relapses of steroid-sensitive nephrotic syndrome are treated with prednisone 2 mg/kg/day or 60 mg/m2/day, but retrospective data support the use of lower doses 6.
• A prospective randomized pilot study found that treatment of childhood steroid-sensitive nephrotic syndrome relapse with prednisone 1-1.5 mg/kg/day led to a significantly lower cumulative dose than the standard dose, with no significant difference in efficacy 6.
• Another study suggested that initial episodes of nephrotic syndrome are best treated with "long" courses of prednisone therapy, while relapses do as well with "short" courses 7.

Alternative Therapies

• Some patients with steroid-resistant nephrotic syndrome may require alternative therapies such as alkylating agent therapy, angiotensin-converting enzyme inhibitors, or cyclosporine 7.
• A protocol involving multiple infusions of high-dose methylprednisolone and oral alkylating agent therapy has been used to treat patients with focal segmental glomerulosclerosis, with some improvement in outcome 7.