What is the diagnosis and treatment for Nephrotic Syndrome?

From the Guidelines

Nephrotic syndrome should be initially treated with corticosteroids, as recommended by the KDIGO practice guideline on glomerulonephritis 1.

Treatment Overview

Nephrotic syndrome is a kidney disorder characterized by heavy proteinuria (>3.5g/day), hypoalbuminemia, hyperlipidemia, and edema. Treatment depends on the underlying cause, with initial management focusing on symptom control and preventing complications.

First-Line Therapy

First-line therapy typically includes:

• Angiotensin-converting enzyme inhibitors (ACEIs) like enalapril (10-40mg daily) or angiotensin receptor blockers (ARBs) such as losartan (50-100mg daily) to reduce proteinuria.
• Diuretics like furosemide (20-80mg daily) help manage edema.
• Dietary sodium restriction (<2g/day) and moderate protein intake (0.8-1g/kg/day) are recommended.

Immunosuppressive Therapy

Immunosuppressive therapy varies by cause:

• Minimal change disease often responds to prednisone (1mg/kg/day for 4-16 weeks).
• Focal segmental glomerulosclerosis may require calcineurin inhibitors like cyclosporine (3-5mg/kg/day), especially in patients with relative contraindications or intolerance to high-dose corticosteroids 1.
• Membranous nephropathy might be treated with cyclophosphamide plus steroids or rituximab (375mg/m² weekly for 4 weeks).

Additional Considerations

Prophylactic anticoagulation with low molecular weight heparin may be needed if serum albumin is <2.0g/dL due to thrombosis risk. Regular monitoring of kidney function, proteinuria, and medication side effects is essential, as nephrotic syndrome increases infection risk and can progress to kidney failure if inadequately treated. Some patients may require alternative first-line therapy, such as calcineurin inhibitors, due to contraindications or intolerance to corticosteroids 1.

From the FDA Drug Label

To induce a diuresis or remission of proteinuria in the nephrotic syndrome, without uremia, of the idiopathic type or that due to lupus erythematosus

• Nephrotic syndrome is an indicated condition for the use of prednisone.
• The drug is used to induce a diuresis or remission of proteinuria in this condition.
• It is specifically indicated for idiopathic type or lupus erythematosus-related nephrotic syndrome, without uremia 2.

From the Research

Definition and Treatment of Nephrotic Syndrome

• Nephrotic syndrome is a kidney disorder characterized by excessive excretion of protein in the urine, leading to complications such as edema, hypertension, and hyperlipidemia 3.
• The treatment of nephrotic syndrome depends on the underlying cause, with corticosteroids being the first-line therapy for minimal change disease, the most common cause of nephrotic syndrome in children 4.

Corticosteroid Treatment

• Corticosteroids, such as prednisone, are effective in inducing remission in most cases of minimal change nephrotic syndrome, with response rates of 93% in children and 81% in adults 5.
• The standard dose of prednisone is 60 mg/m2/day, but lower doses of 1-1.5 mg/kg/day may be equally effective in achieving remission with fewer side effects 6.
• Treatment with corticosteroids should be initiated at doses of 60 mg/m2 per day (2 mg/kg per day) administered for 4 to 6 weeks, followed by 40 mg/m2 per dose (1.5 mg/kg) every other day for at least 6 to 8 weeks 4.

Alternative Therapies

• Alternative therapies, such as cyclophosphamide and cyclosporine, may be used in cases of corticosteroid-dependent or corticosteroid-resistant nephrotic syndrome, but caution must be exercised due to potential toxic side effects 5, 4.
• A 6-month regimen of cyclophosphamide and steroids has been shown to induce remissions in a high proportion of patients with idiopathic membranous nephropathy, a common cause of nephrotic syndrome in adults 7.

Management of Complications

• Patients with nephrotic syndrome are prone to complications such as deep vein thrombophlebitis, renal vein thrombosis, and pulmonary emboli, and should be treated with a low-salt diet, diuretics, and statins to reduce edema and normalize serum lipid concentrations 3.
• Additional treatment may include angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and mycophenolate, depending on the underlying condition 3.