The use of IVIg in Kidney Disease

It’s time for a quick nephro-centric summary of immune globulin use. Immune globulin, usually administered intravenously (IVIg), is made from pooled human plasma and used for a wide variety of human disease. It contains mostly IgG with various IgA concentrations depending on the preparation and different stabilizers (see sucrose nephropathy below). IVIg has various anti-infections and anti-inflammatory effects via mechanisms that are still incompletely understood. The sphere of renal transplantation is where most nephrologists will see it being administered.

HLA Desensitization

IVIg is incorporated into various desensitization protocols which may decrease preformed anti-HLA antibodies and render a previous positive crossmatch negative. Two broad regimes are (a) high dose IVIg at 2g/kg single dose or monthly and (b) plasmapheresis with low dose IVIg 100mg/kg after each session. The latter regime is likely more beneficial when an appreciable level of sensitization is present and rituximab may be also be added. The immunomodulatory mechanisms at play may include neutralizing donor-reactive antibodies, reducing anti-HLA antibody formation and the inhibition of complement-dependent endothelial injury.

Antibody-Mediated Rejection (AMR)

IVIg is generally incorporated into a multi-targeted regimen for AMR, usually at least 1g/kg given after plasmapheresis. My own experience is with 2g/kg at the end of the final plasmapheresis sessions. It must be noted that IVIg may interfere with anti-HLA titers, causing false-positive results so it is important to send levels before administering IVIg.

Transplant Infectious Disease

BK Polyoma virus nephropathy (PVN): IVIg may have a role in the treatment of (PVN), particularly in cases where acute rejection co-exists or is suspected. IVIg presumably contains anti-BK antibodies, as the virus is ubiquitous in the general population. However, whether these antibodies are neutralizing or not is unknown. As the cornerstone of PVN treatment is immunosuppression reduction, coexistent acute rejection presents a difficult scenario with IVIg being attractive due to its anti-infective and immunomodulatory properties. Other post-transplant infectious complications where IVIg may be useful include Parvovirus B19 (which may cause severe anemia or an FSGS renal lesion) and possibly resistant CMV infection. The use of IVIg in these settings is usually in conjunction with a decrease in the burden of immunosuppression.

Glomerular disease

IVIg has been used without much convincing evidence for a variety of glomerular pathologies. These include an uncontrolled series of 11 patients with severe IgA Nephropathy given monthly doses of 2g/kg. A decrease in proteinuria and stabilization of GFR was observed. Other unconvincing reports for IVIg use in glomerular disease include a small study in idiopathic membranous nephropathy as well as in lupus nephritis and ANCA associated vasculitis (ref).

Adverse Renal Events

It should be noted that IVIg preparations may uncommonly cause AKI (<1% of infusions). This almost always happens with use of high sucrose-content preparations. IV Sucrose was used in the mid-20^th century for treatment of various edematous states and was associated with AKI, via an osmotic effect causing proximal tubular cell swelling and vacuolization (see JAMA paper from 1942!). IVIg may also cause hyponatremia, as discussed by Nate previously.