The use of IVIg in Kidney Disease

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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-20th 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.

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