IVIG product labeling carries a box warning on the potential for renal dysfunction or acute renal failure in patients predisposed to renal dysfunction, including those with any degree or preexisting renal insufficiency, diabetes, aged older than 65 years, volume depletion, sepsis, paraproteinemia, or in patients receiving nephrotoxic medications.

The risk occurs more commonly with IVIG products that contain sucrose, which have largely been replaced by sucrose-free products. Despite the removal of sucrose from IVIG formulations, there are still potential risks associated with the use of these agents in patients with impaired kidney function. This particularly applies to the IV formulation of immune globulin, which should be administered at the minimum dose and lowest infusion rate feasible in patients at risk or with impaired renal function. IM and SC immune globulin do not require a dose adjustment in renal impairment.

A recent report was published to increase awareness and to provide recommendations for the assessment, monitoring, and early treatment of kidney injury associated with the use of IVIG in patients with impaired renal function. Patients at increased risk for renal impairment and increased likelihood of adverse events from IVIG include those with pre-existing kidney disease or a family history of kidney disease, those aged 65 years and older, those with diabetes, hypertension, cardiovascular disease and/or obesity, volume depletion, autoimmune diseases (such as systemic lupus erythematosus or vasculitis), infections, paraproteinemia, and those on concomitant and/or past nephrotoxic medications.

These patients should have their renal function assessed prior to starting IVIG therapy with a particular emphasis on the glomerular filtration rate (GFR), albumin, bicarbonate, total calcium, chloride, serum creatinine, glucose, phosphorus, potassium, sodium, and urea nitrogen levels.

Since kidney disease is often undiagnosed, all patients receiving immune globulin should be screened for risk factors for renal impairment. Serum creatinine should be obtained prior to the initiation of immune globulin therapy.

In those with mild-to-moderate renal dysfunction (i.e., GFR 30 to >59 mL/min/1.73m2), GFR should be performed at least quarterly whereas in those with severe renal dysfunction (i.e., GFR <29 mL/min/1.73m2) GFR should be assessed monthly or before every IVIG treatment. All patients with impaired renal function should be monitored for changes in weight secondary to decreases in urine output or edema. Care should be exercised when dosing obese patients. Medications should be reassessed on a regular basis, especially in older adults. Drugs that can worsen renal function (i.e., diuretics, renin-angiotensin inhibitors, and nonsteroidal anti-inflammatory drugs) should be avoided if possible.

Patients should be evaluated for the presence of adverse drug events during and up to 3 days postinfusion. Renal insufficiency typically develops within 1 to 10 days of initiation of IVIG therapy and reverses within 4 weeks of discontinuing treatment. However, hemodialysis is often required. Patients may present with hematuria, mild-to-moderate proteinuria, and elevations in serum creatinine with the latter parameter peaking around Day 5 of therapy. IVIG–related acute kidney injury may progress to chronic kidney disease or renal failure with death occurring in 8% to 15% of patients.

IVIG dosage adjustments (i.e., reducing infusion rate or increasing dosing interval) should be performed if the creatinine clearance decreases by greater than 15%, if the patient experiences a weight gain of more than 2.5 pounds, or if edema is observed. Hydration status and diuretic use should be assessed.

Strategies to minimize the impact of an adverse reaction (depending on the type of event) include adding or adjusting the premedication regimen, changing the concentration or brand of IVIG, altering the administration location, or switching to SC administration that has not been associated with immune globulin-induced nephrotoxicity. Additional considerations include assessing the psychosocial, social, and financial impact of IVIG–related kidney disease.

This article offers pharmacists practical and useful information about screening for risk and for monitoring and managing IVIG–related renal disease.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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