Paraprotein Mediated Disease Following Kidney Transplantation

Fig 1 Batal et al AJKD

Fig 1 Batal et al AJKD, ©National Kidney Foundation

In a recent article published by AJKD, Batal et al describe a patient whose kidney allograft biopsy 7 years after transplantation revealed IgG1 kappa monoclonal glomerular deposits causing proliferative glomerulonephritis. Proliferative glomerulonephritis with monoclonal IgG deposition (PGNMIGD) is an increasingly recognized disease entity that can recur after transplantation, but may also appear de novo in kidney allografts. PGNMIGD was overlooked until immunofluorescence with antibodies to the IgG subclasses was introduced in several renal pathology laboratories. Previously, most of these kidney biopsies were diagnosed as membranoproliferative glomerulonephritis. Diagnosing glomerular monoclonal immunoglobulin deposition can be difficult using only the routine immunofluorescence panel, which includes antibodies to IgG, IgA, IgM, and kappa and lambda light chains, in addition to antibodies to complements, fibrinogen, and albumin. Nonspecific glomerular deposition (entrapment) of the IgM macromolecule in a variety of glomerular diseases is well known. These nonspecific glomerular IgM deposits may cause a diagnostic problem because the polyclonal IgM molecules contains both kappa and lambda light chains, masking the monoclonality of the IgG deposits. Thus, unless IgG subclass immunofluorescence is applied, the monoclonal nature of the IgG deposits can be missed.

Batal et al make a strong case for pathologists to stain kidney biopsies with IgG-dominant glomerular deposits with antibodies to the IgG subclasses. Nephrologists and pathologists need to be aware of this entity and suspect it if a kidney biopsy with proliferative glomerulonephritis shows IgG dominant glomerular deposits in the absence of systemic lupus erythematosus. Unlike monoclonal heavy chain deposition disease, the deposits in PGNMIGD are almost always localized to the glomeruli; tubular basement membrane and vascular deposits are not seen. In PGNMIGD, the glomerular deposits resemble discrete electron dense immune-type deposits by electron microscopy; they do not typically have the finely granular continuous deposits along the glomerular and tubular basement membranes seen in heavy chain deposition disease. Although in our experience only approximately 30% of patients with PGNMIGD have an underlying detectable monoclonal gammopathy, the correct diagnosis may have important therapeutic implications and should initiate a hematologic workup.

Tibor Nadasdy, MD
eAJKD Contributor
and AJKD Kidney Biopsy Teaching Case Advisory Board member

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