Does Intravenous Immunoglobulin (IVIG) exacerbate impaired renal function?

From the Guidelines

Intravenous Immunoglobulin (IVIG) may exacerbate impaired renal function, particularly in patients with pre-existing kidney disease or risk factors, and therefore, its use should be approached with caution and careful monitoring of kidney function. According to the 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline for the treatment of interstitial lung disease in people with systemic autoimmune rheumatic diseases 1, IVIG is not the preferred treatment option due to concerns about its potential to worsen renal function. The guideline recommends rituximab and cyclophosphamide over IVIG, but notes that IVIG may be preferred if there is high concern for infection.

Some key points to consider when administering IVIG include:

• Using modern sucrose-free IVIG formulations, which have a lower risk of causing renal impairment
• Providing adequate hydration before and during infusion
• Using slower infusion rates
• Administering the lowest effective dose
• Closely monitoring patients with risk factors, such as diabetes, advanced age, volume depletion, sepsis, paraproteinemia, or pre-existing renal insufficiency
• Regularly assessing serum creatinine and urine output during IVIG therapy, as recommended by the guideline 1.

The mechanism of IVIG-induced renal dysfunction involves precipitation of immune complexes in renal tubules, increased blood viscosity, and complement activation, which can be mitigated with careful patient selection and monitoring 1. Most cases of IVIG-related kidney injury are reversible with discontinuation of the medication and supportive care, though severe cases may require temporary dialysis.

From the FDA Drug Label

Four subjects (9%) had incidences of serum creatinine increases being stable throughout the course of the study. Therefore, these observations were not regarded as indicative of acute renal dysfunction. Renal and urinary disorders Renal failure acute Patients > 65 years of age may be at increased risk for developing certain adverse reactions such as ... acute renal failure Overdose may lead to fluid overload and hyperviscosity, particularly in the elderly and in patients with impaired renal function

Intravenous Immunoglobulin (IVIG) and Renal Function: The FDA drug label reports that 9% of subjects had increases in serum creatinine, but these were stable and not indicative of acute renal dysfunction 2. However, the label also notes that patients with impaired renal function may be at increased risk for adverse reactions, including acute renal failure, particularly if they are elderly or receive an overdose. Therefore, IVIG may exacerbate impaired renal function in certain patients, particularly the elderly or those with pre-existing renal impairment. Key considerations include:

• Patient age: Patients > 65 years may be at increased risk for acute renal failure.
• Renal function: Patients with impaired renal function may be at increased risk for adverse reactions.
• Overdose: Overdose may lead to fluid overload and hyperviscosity, particularly in patients with impaired renal function.

From the Research

Intravenous Immunoglobulin (IVIG) and Renal Function

• IVIG has been associated with impaired renal function, particularly in patients with pre-existing kidney disease or those receiving high doses of IVIG 3, 4, 5, 6, 7
• The exact mechanism of IVIG-induced renal impairment is not fully understood, but it is thought to be related to the osmotic effects of sucrose or other stabilizing agents in the IVIG formulation 5, 6, 7
• Risk factors for IVIG-induced renal impairment include advanced age, pre-existing renal disease, diabetes, and the use of diuretics or other nephrotoxic agents 4, 6, 7

Incidence of Renal Impairment

• The incidence of renal impairment associated with IVIG varies widely, ranging from 1.7% to 13% in different studies 4, 6
• In some cases, renal impairment may be irreversible, highlighting the importance of careful patient selection and monitoring 4

Prevention and Management

• Screening for chronic kidney disease (CKD) and kidney function impairment is essential before initiating IVIG therapy 3
• Patients with impaired renal function should be closely monitored during IVIG therapy, and the dose and infusion rate should be adjusted as needed 3, 7
• Clinicians should be aware of the potential risks of IVIG-induced renal impairment and take steps to prevent and manage it, including discontinuing diuretics, ensuring adequate hydration, and avoiding concomitant use of other nephrotoxic agents 7