Kidney disease associated with plasma cell dyscrasias

Abstract

Plasma cell dyscrasias are frequently encountered malignancies often associated with kidney disease through the production of monoclonal immunoglobulin (Ig). Paraproteins can cause a remarkably diverse set of pathologic patterns in the kidney and recent progress has been made in explaining the molecular mechanisms of paraprotein-mediated kidney injury. Other recent advances in the field include the introduction of an assay for free light chains and the use of novel antiplasma cell agents that can reverse renal failure in some cases. The role of stem cell transplantation, plasma exchange, and kidney transplantation in the management of patients with paraprotein-related kidney disease continues to evolve.

Figure 1

Three distinct syndromes account for most cases of Ig-mediated kidney disease but virtually all nephropathologic syndromes have been observed. Panel A shows amyloid. (i) Amyloid fibrils consisting of monoclonal Ig and serum proteins appear here as pink material disrupting glomeruli architecture. (ii) Amyloid is visible on electron microscopy as 7- to 12-nm fibrils. Panel B shows MIDD. Monoclonal light chains kappa (1) or without evidence of lambda (ii) and/or heavy chains (IgG), deposit along glomerular (iii) and tubular basement membranes (iv), altering the glomerular structure and causing dose-dependent proximal tubular toxicity. Panel C shows cast nephropathy. Filtered monoclonal Ig, Tamm-Horsfall, and other proteins form casts, which obstruct tubules and collecting ducts. Casts can rupture and result in interstitial inflammation. Panel D shows interstitial inflammation. Inflammation also results from the processing of filtered monoclonal light chains, which induces NF-κB and other signaling pathways leading to cytokine-mediated inflammatory infiltrate (shown here with a Trichrome stain) and subsequent matrix deposition and fibrosis. Panel E shows glomerular crescent. Virtually every recognized nephropathologic lesion has been described in association with paraproteinemia. Shown here is a glomerular crescent in a patient with Waldenström macroglobulinemia productive of IgMλ and amyloidosis.