What is the management of Nephrotic Syndrome?

From the Guidelines

The management of nephrotic syndrome should focus on treating the underlying cause, reducing proteinuria, and preventing complications, with initial treatment including corticosteroids, such as prednisone at 1 mg/kg/day, and supportive care with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) to reduce proteinuria, as recommended by the KDIGO 2021 clinical practice guideline for the management of glomerular diseases 1.

Key Components of Management

• Initial treatment with corticosteroids, typically prednisone at 1 mg/kg/day (maximum 80 mg) for 4-16 weeks depending on response, followed by a gradual taper 1
• Supportive care with ACEIs like enalapril (5-40 mg/day) or ARBs like losartan (25-100 mg/day) to reduce proteinuria 1
• Diuretics such as furosemide (20-80 mg daily) to manage edema, with loop diuretics as first-line therapy and twice daily dosing preferred over once daily dosing 1
• Dietary sodium restriction (<2 g/day) and moderate protein intake (0.8-1 g/kg/day) are recommended 1
• Anticoagulation with low molecular weight heparin or warfarin may be necessary for patients with severe hypoalbuminemia (<2.0 g/dL) due to thrombosis risk

Monitoring and Adjusting Therapy

• Regular monitoring of renal function, electrolytes, albumin levels, and proteinuria is crucial to assess treatment response and adjust therapy accordingly 1
• Adjusting diuretic therapy based on response, with consideration of combination therapy with other mechanistically different diuretics for synergistic treatment of resistant edema 1
• Monitoring for adverse effects of diuretics, including hypokalemia, hyponatremia, impaired GFR, and hyperkalemia 1

From the FDA Drug Label

1. 3 Edema Associated with Hepatic Cirrhosis or Nephrotic Syndrome Spironolactone tablets are indicated for the management of edema in the following settings: Nephrotic syndrome when treatment of the underlying disease, restriction of fluid and sodium intake, and the use of other diuretics produce an inadequate response.

The management of Nephrotic Syndrome with spironolactone involves:

• Treatment of the underlying disease
• Restriction of fluid and sodium intake
• The use of other diuretics
• Spironolactone tablets may be used when the above measures produce an inadequate response 2

From the Research

General Treatment

• The general treatment of nephrotic syndrome includes administering an appropriate diet (reduced intake of proteins and salt), use of diuretics and lipid-lowering drugs (primarily statins) and initiation of anticoagulant treatment, if required 3
• It is generally necessary to administer angiotensin-convertase-enzyme inhibitors and angiotensin receptor blockers as well as initiate a symptomatic treatment to mitigate the loss of special binding-proteins 3
• The treatment aims to prevent or slow further kidney damage, and involves addressing the underlying medical condition and the treatment of symptoms such as edema, proteinuria, hyperlipidemia, as well as preventing complications like thromboembolic disease, infections or undernutrition 4

Special Treatment

• The special treatment involves the administration of immunosuppressive and cytostatic drugs, which can be initiated only after the evaluation of renal histology and the overall risk status of the patient 3
• Steroids are still the basic immunosuppressive drugs, and their use can be supplemented with other immunosuppressive or cytostatic treatment 3
• In therapy resistant cases, new drugs like mycophenolate mofetil or rituximab can also be applied 3
• Depending on aetiology, specific treatment, often with immunosuppressive agents, may be implemented 5

Recent Advances

• Recent advances in the treatment of primary causes of nephrotic syndrome (idiopathic membranous nephropathy (iMN), minimal change disease (MCD), and focal segmental glomerulosclerosis (FSGS)) have been focused on immunosuppressive treatment and new therapeutic options 6
• Rituximab, a humanized monoclonal antibody (mAb), has emerged as a potential treatment for steroid or calcineurin inhibitor-dependent patients 7
• New therapeutic options, such as mAbs, are being investigated for MCD and FSGS, and ongoing clinical trials are expected to provide further information on the effectiveness of different treatment options for the causative disease 6, 7

Complications

• Urinary protein loss leads to several complications, including water and sodium retention, hyperlipidaemia, increased risk of thromboembolism and infection, anaemia and alteration of mineral metabolism, each of which must be identified and treated 5