Various renal disorders are associated with
monoclonal gammopathies, secondary to tissue deposition or precipitation of a monoclonal
immunoglobulin (Ig) or a fragment thereof (isolated Ig light chain or heavy chain). They are classified according to the localization of renal lesions, either glomerular or tubular and to the pattern of ultrastructural organization of Ig deposits. Renal disease in
monoclonal gammopathies may be isolated, or associated with various systemic symptoms particularly in
AL amyloidosis, Randall-type monoclonal Ig deposition disease and monoclonal
cryoglobulinemias. Except for myeloma cast nephropathy, which occurs in the setting of high-mass myeloma and is recognized after electrophoretic analysis of
proteinuria and
AL amyloidosis, which diagnosis is usually made after pathological examination of non-invasive tissue specimens (i.e. abdominal fat or minor salivary glands), a kidney biopsy is required to identify the other types of renal disorders associated with
monoclonal gammopathies and to estimate renal prognosis. Renal pathological diagnosis is difficult and relies on careful examination of kidney biopsy samples, by light microscopy, immunofluorescence studies using conjugates specific for Ig light and heavy chains,
IgG sub-classes and heavy chain constant domains and by electron microscopy. In some cases, additional studies are required to identify the nature of deposits, such as immuno-electron microscopy or mass spectrometric-based proteomic analysis after
laser dissection. In patients with renal disorders related to Ig light chain precipitation or deposition (myeloma cast nephropathy,
AL amyloidosis, Randall-type light chain deposition disease), measurement of serum free light chains at baseline and throughout follow-up is mandatory to evaluate clonal response to
chemotherapy. A more than or equal to 50% decrease in serum free light chain levels is associated with increased renal and patient survival. In
AL amyloidosis, serum levels of markers of
cardiac disease (
NT-proBNP and
troponin) are also closely associated with prognosis. Efficient
chemotherapy, tailored to the underlying plasma cell or
lymphoproliferative disorder and adapted to renal function, should be promptly introduced, even in the absence of overt malignant haematological disease. Renal prognosis and patient survival (particularly in
AL amyloidosis and cast nephropathy) are closely associated with the rapid achievement of an haematological response. The combination of
melphalan plus
dexamethasone (MDex) is currently used as first-line
chemotherapy in systemic
AL amyloidosis.
Bortezomib-based regimens are commonly employed as first-line treatment in myeloma cast nephropathy and Randall-type monoclonal Ig deposition disease and as second line
therapy in
AL amyloidosis patients with advanced
cardiomyopathy or refractory to previous
chemotherapy. Solid
organ transplantation (heart and kidney) should be considered in patients with
AL amyloidosis or Randall-type monoclonal Ig deposition disease and advanced cardiac or
renal failure. Prolonged graft and patient survival may be obtained, providing that recipients do not have other severe organ involvement or symptomatic myeloma and that haematological remission has been achieved with
chemotherapy before or after
organ transplantation.