New aspects on the pathogenesis of renal disorders related to monoclonal gammopathies

Multiple myeloma and other related monoclonal gammopathies are frequently encountered conditions associated with renal damage, especially in elderly population. They are arising from clonal proliferation of plasma cells in bone marrow producing various quantities of abnormal monoclonal immunoglobulins, or their components/fragments.

These abnormal proteins differ from normal immunoglobulins in the amino acid sequence and in the three-dimensional structure of the molecule, which may determine their toxicity. Kidney seems to be a target organ as a major catabolic site. The pathology of renal disease is highly heterogeneous involving a variety of different mechanisms, which are divided into immunoglobulin dependent and immunoglobulin independent mechanisms. The Ig-dependent mechanisms may involve the four components of the kidney parenchyma, and the primary structure of these proteins determine the pattern of renal disease.

This review summarizes the existing literature in the pathobiology of multiple myeloma, and the pathological properties of the M-proteins, focusing on the mechanisms of the renal manifestations related to these abnormal proteins, especially glomerular injury. Also it supports the opinion that monoclonal gammopathy of undetermined significance (MGUS) should not be used in cases where there is proven renal impairment due to these proteins, even if it is mild and does not meet the current criteria.