The evolving spectrum of kidney amyloidosis: advances in diagnosis, typing and treatment.

Abstract

Kidney amyloidosis encompasses a spectrum of heterogeneous conditions in which damage is caused by the deposition of various misfolded proteins that aggregate into fibrils. The main form of renal amyloidosis in Western countries is immunoglobulin light chain (AL) amyloidosis, which is usually secondary to a plasma cell clone or less frequently a B-cell clone, while rarer causes include AA amyloidosis, ALECT2 and hereditary amyloidoses. The main renal manifestations include nephrotic syndrome and kidney dysfunction with modest or absent proteinuria. The course is progressive and renal and overall survival is reduced in many patients. While biopsies are usually positive by Congo Red staining in all types of amyloidosis, precise identification of the amyloid fibril protein is essential and is best achieved with immunohistochemistry or proteomic studies, such as mass spectrometry. This method also allows the discovery of novel amyloidogenic proteins and has contributed to expand the list of amyloid types. The current treatment strategy is based on suppressing new amyloid fibril production through chemotherapy in AL amyloidosis, control of inflammation in AA amyloidosis and 'gene silencing' therapies in hereditary forms, such as the one linked with transthyretin. Novel approaches aim at enhancing natural amyloid clearance in order to reduce the rate of organ failure. Kidney transplantation in patients who achieved response has shown outcomes comparable to the general transplant population. In this review, we present the key aspects of renal amyloidosis and discuss novel concepts in this evolving field.