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.