Paraprotein-Related Kidney Disease: Kidney Injury from Paraproteins-What Determines the Site of Injury?

Abstract

Disorders of plasma and B cells leading to paraproteinemias are associated with a variety of renal diseases. Understanding the mechanisms of injury and associated nephropathies provides a framework that aids clinicians in prompt diagnosis and appropriate adjunctive treatment of these disorders. Glomerular diseases that may be associated with paraproteinemias include amyloid deposition, monoclonal Ig deposition disease, proliferative GN with monoclonal Ig deposits, C3 glomerulopathy caused by alterations in the complement pathway, immunotactoid glomerulopathy, fibrillary GN, and cryoglobulinemia. Tubular lesions include the classic Fanconi syndrome, light-chain proximal tubulopathy, interstitial fibrosis, and cast nephropathy. These paraproteinemic renal diseases are distinct in their pathogenesis as well as their urinary and kidney biopsy findings. Renal pathology is usually initiated by deposition and direct involvement of the intact monoclonal Ig or Ig fragments with resident cells of the nephron. Our review summarizes current insights into the underlying molecular pathogenesis of these interesting kidney lesions.

Keywords: Kidney Diseases; Myeloma Proteins; Paraproteins; amyloidosis; glomerular disease; immunoglobulin free light chains; immunoglobulins; kidney; multiple myeloma; multiple myeloma M-proteins; paraproteins; tubular epithelium.

Figure 1.

Patterns of nephron injury associated with paraproteins. As predicted from the glomerular handling of macromolecules, high molecular weight paraproteins, such as IgG, IgA, and IgM, may interact only with the glomerulus to promote disease. Monoclonal free light chains may promote glomerular injury, but only these low molecular weight paraproteins are also associated with diseases of the tubular nephron and represent the classic Bence Jones proteinuria observed clinically. AH, heavy chain associated; AL, light chain associated; HCDD, monoclonal Ig heavy–chain deposition disease; LCDD, monoclonal Ig light–chain deposition disease; LHCDD, monoclonal Ig light– and heavy–chain deposition disease; MIDD, monoclonal Ig deposition disease. Adapted from reference .