Recurrence of Kappa monoclonal gammopathy after kidney transplantation

Membranoproliferative glomerulonephritis on kidney biopsy.

Monoclonal gammopathies generally arise from the development of an abnormal clone of B-cell lineage. The monoclonal protein can be intact immunoglogulin (often associated with free light chain), free light chain (FLC) in isolation, or more rarely immunoglobulin heavy chain, either in isolation or with associated free light chain. Monoclonal light chains have the ability to self-aggregate and form tissue deposits either in the form of beta-pleated fibrils (amyloid) or not (non-amyloid deposits).

Monoclonal gammopathies may lead to kidney injury through a variety of mechanisms, depending on the biochemical properties of the light chain and/or immunoglobulin. These include: cast nephropathy (usually kappa); monoclonal immunoglobulin deposition disease; crystal-storing tubulopathy; amyloidosis (usually lambda), cryoglobulinemia or MPGN (membranoproliferative glomerulonephritis).

Monoclonal gammopathies can frequently recur after transplant (Sethi et al. CJASN 2010). In a cohort of transplant recipients in our center, Dr Batal had reported 8 cases of IgG/Kappa MPGN, of which 3 failed post-transplant while 2 were still functioning; 3 were lost on follow up (Batal et al. AJKD 2014).

Recently, a 65 year-old Female with CKD secondary to MPGN/IgG Kappa monoclonal gammopathy underwent a living-unrelated kidney transplant. Creatinine came down to nadir of 1.2mg/dl three days after transplant and then started to rise up to 2.5mg/dl. An emergent kidney biopsy was performed which revealed aggressive MPGN (view picture above). Immunofluorescence staining was negative for IgG, kappa or lambda. However, when the biopsy sample was treated with pronase and restained, suddenly diffuse Kappa staining was uncovered, confirming recurrence of her primary disease. Pronase digestion has a denaturing effect on cell membranes, which may unveil sequestered antigenic sites. This was previously shown to be useful in other forms of monoclonal gammopathies such as in crystal-storing tubulopathy. Electron microscopy may also help in identifying the deposits and triggering additional tests to elucidate the composition of those. Unfortunately, prognosis of early recurrence is not good and requires aggressive treatment against the possible source of light chain (abnormal plasma cells) and removal of light chains from the circulation through plasmapheresis.

To learn more about glomerular disease recurrence after transplantation, refer to Kidney Transplant iBook (Chapter 4/Section 8); Ponticelli et al. CJASN 2010; Ponticelli et al. CJASN 2011; and MPGN classification on Sethi, Fervenza. NEJM 2012.

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