Figure 1146

Factors reported in the literature to be associated with development of the different renal lesions in patients with myeloma are summarized. The amyloidogenic potential is enhanced by certain amino acids that promote unfolding of the light chain and by the X isotype of the light chain. In amyloidosis, the variable regions of the light chains are deposited predominantly after metabolization by macrophages. A number of factors have been characterized that enhance the binding of light chains to Tamm-Horsfall protein (THP), which is a critical event in the development of cast nephropathy. In monoclonal immuno-globulin deposition diseases, the granular deposits are composed mainly of the constant regions of light (and seldom heavy) chains.

Hypercalcemia, which frequently occurs in patients with myeloma and results from increased interleukin-6-mediated bone resorption, can contribute to renal impairment by way of different mechanisms: dehydration (hyperemesis and nephrogenic diabetes insipidus), induction of nephrocalcinosis, and enhancement of light chain aggregation with THP. All other factors either diminish tubular flow or increase distal tubular sodium concentration, thereby again enhancing cast formation.

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