Why is the immune system compromised in nephrotic syndrome?

From the Guidelines

The immune system is compromised in nephrotic syndrome primarily due to the loss of important immune proteins through the damaged kidneys, as well as the use of potent immunosuppressive agents in treatment. In nephrotic syndrome, the glomerular filtration barrier becomes leaky, allowing proteins like immunoglobulins (antibodies) and complement proteins to escape into the urine 1. This urinary loss of immunoglobulins, particularly IgG, significantly reduces the body's ability to fight infections. Additionally, some treatments for nephrotic syndrome, such as corticosteroids and immunosuppressive medications, can further suppress immune function, highlighting the need for careful management to prevent infections 1.

Key factors contributing to the compromised immune system in nephrotic syndrome include:

• Loss of immune proteins like immunoglobulins and complement proteins in the urine
• Use of immunosuppressive agents in treatment
• Potential for zinc deficiency, which can impair T-cell function and wound healing
• Edema creating a favorable environment for bacterial growth

Given the increased risk of infections, it is crucial to follow guidelines for vaccinating against encapsulated organisms and to consider prophylactic antimicrobial therapy in patients receiving high-dose immunosuppression 1. Screening for latent diseases such as tuberculosis, hepatitis B and C viruses, human immunodeficiency virus, and syphilis is also an important consideration in the management of patients with nephrotic syndrome 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Immune System Compromise in Nephrotic Syndrome

The immune system is compromised in nephrotic syndrome due to various factors, including:

• Increased permeability to proteins at the level of the glomerulus, leading to proteinuria, edema, and hypoalbuminemia 2
• Dysregulation of coagulation and immunity, resulting from proteinuria and subsequent clinical complications 2
• The effectiveness of immunosuppressive treatment in idiopathic nephrotic syndrome, suggesting a crucial role of the immune system in the disease pathogenesis 3, 4, 5, 6
• Associations with systemic infections and hematologic malignancies, indicating a link between the immune system and the development of nephrotic syndrome 3

Role of Immune Cells and Molecules

The immune system compromise in nephrotic syndrome involves:

• T cells, which have been implicated in the pathogenesis of idiopathic nephrotic syndrome, with changes in the dynamics of T lymphocytes, especially regulatory T cells 4, 5, 6
• B cells, which have gained attention due to the therapeutic response of rituximab, an anti-CD20 antibody, in the treatment of idiopathic nephrotic syndrome 6
• The complement system, which has been involved in the pathophysiology of idiopathic nephrotic syndrome, although the pattern of immune response is still not clearly defined 5
• Podocytes, which can act as antigen-presenting cells under inflammatory stimuli and play a direct role in activating cellular pathways that cause proteinuria 4, 6

Implications for Diagnosis and Treatment

Understanding the immune system compromise in nephrotic syndrome may lead to:

• Better diagnostic approaches, by identifying specific immune cells and molecules involved in the disease pathogenesis 3, 4, 5, 6
• More tailored therapeutic approaches, targeting specific components of the immune system, such as T cells, B cells, and podocytes 3, 4, 5, 6