Myeloma Kidney : Pathogenesis

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Myeloma patients develop tubulo-interstitial lesions due to light chain deposition in their kidneys, resulting in chronic renal insufficiency over time.

Pathogenesis: Free light chains are filtered by the glomeruli but reabsorbed by the proximal tubular epithelial cells. In myeloma patients, the proximal tubules are unable to cope with the incoming load of excess light chains in the glomerular filterate. The unabsorbed light chains reach distal nephron where they form complexes with urinary glycoproteins and precipitate as large tubular casts (as shown here), blocking the lumen, and inciting an inflammatory response. In addition, light chains are directly toxic to the tubular epithelium.

In up to 25% of myeloma patients, the renal damage is mediated by the development of amyloidosis of AL type due to deposition of free light chains (lambda type) in the interstitium. In some patients, there is deposition of kappa light chains in the glomerular basement membranes, mesangial matrix, as well as in the tubular basement membrane. Besides deposition of light chains, additional renal damage is caused by hypercalemia and hyperuricemia often encountered in myeloma patients.

About the Disease

Plasma cell disorders are B-cell neoplasms composed of plasma cells or lymphocytes that secrete a monoclonal immunoglobulin (Ig) or Ig fragment. They are responsible for about 15% of deaths caused by lymphoid malignancies in the US. The monoclonal Ig, usually identified by serum or urine protein electrophoresis, is known as the M component. Sometimes the M component consists of only light chains or heavy chains. Free light chains are referred to as Bence-Jones proteins when they are excreted in urine. The WHO Classification (2008) of plasma cell neoplasms includes the following: Monoclonal Gammopathy of Undetermined Significance (MGUS): MGUS refers to an asymptomatic patient with an M component (<3 gm/dl) in their blood. It is the most common plasma cell disorder and is seen in about 5% of individuals >70 years of age. About 1% of MGUS patients per year develop multiple myeloma, amyloidosis, macroglobulinemia, or other lymphoproliferative disorder. The median interval between the diagnosis of MGUS and the development of malignancy is about 10.5 years. Plasma Cell Myeloma: Multiple myeloma (MM) is a plasma cell neoplasm of older individuals that is characterized by scattered tumorous masses causing lytic bone lesions in the axial skeleton, hypercalcemia, renal damage, and acquired immune abnormalities. Solitary Plasmacytoma: About 3% to 5% of patients with plasma cell disorders present with solitary bone or soft tissue mass. An M component may be found in serum or urine in a small percentage of cases. Solitary bone plasmacytoma slowly progresses to multiple myeloma in most cases. Extraosseous plasmacytomas involve lungs, nasopharynx, oropharynx, or nasal sinuses and can often be cured by resection. Immunoglobulin Deposition Diseases: This group includes primary amyloidosis (PA) and light- or heavy- chain deposition disease. Immunoglobulins are deposited in various tissues eventually leading to organ failure. About 20% of PA patients have multiple myeloma (MM). The remainder don't meet the criteria for MM but have a small M component and increased plasma cells in bone marrow. Osteosclerotic Myeloma (POEMS Syndrome): Osteosclerotic myeloma is usually associated with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin lesions (POEMS syndrome). Some patients also develop Castleman's disease, serous effusions, and thrombocytosis.

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