Abstract and Introduction
AL amyloidosis (light chain; previously also called primary amyloidosis) is a systemic disease characterized by an amyloid deposition process affecting many organs, and which still has unsatisfactory survival of patients. The monoclonal light chains kappa (κ) or lambda (λ) or their fragments form the fibrils that deposit and accumulate in different tissues. Renal involvement is very frequent in AL amyloidosis and can lead to the development of nephrotic syndrome followed by renal failure in some cases. AL amyloidosis ultimately leads to destruction of tissues and progressive disease. With recent advances in the treatment, the importance of an early diagnosis of amyloidosis and correct assessment of its type is high. Histologic confirmation is based on Congo red detection of amyloid deposits in tissues but AL amyloidosis must also be distinguished from other systemic forms of amyloidoses with renal involvement, such as AA amyloidosis, amyloidosis with heavy chain deposition, fibrinogen Aα or ALECT2 (leukocyte chemotactic factor 2) deposition. Immunofluorescence (IF) plays a key role here. IF on formalin-fixed paraffin-embedded tissue after protease digestion, immunohistochemistry or laser microdissection with mass spectrometry should complete the diagnosis in unclear cases. Standard treatment with melphalan and prednisolone or with cyclophosphamide and dexamethasone has been replaced with newer drugs used for the treatment of multiple myeloma—bortezomib, carfilzomib and ixazomib or thalidomide, lenalidomide and pomalidomide. High-dose melphalan supported by autologous stem cell transplantation remains the therapeutic option for patients with low-risk status. These new treatment options prolong survival from months to years and improve the prognosis in a majority of patients.
Amyloidoses are disorders of diverse aetiology in which deposits of abnormally folded proteins with fibrillar ultrastructure infiltrate extracellular spaces of affected organs. Currently, >32 different proteins (and many more variants) are known to be involved in amyloidoses and additional protein types are continually being added to this list. The International Society of Amyloidosis initiated development of a modern nomenclature of amyloidoses, which is based on the type of protein involved. The latest version was published in 2014 and the most frequent systemic amyloidoses are described in Table 1.
AL amyloidosis is a result of clonal plasma cell disorder with an incidence of ~10 persons per million per year. The disease is caused by a usually small and low proliferating bone marrow plasma cell clone (infrequently a B-cell clone) secreting an unstable, amyloidogenic immunoglobulin light chain (LC). The probability of AL amyloidosis occurrence significantly increases with age and people >65 years are at the highest risk. It is the most common and most severe form of systemic amyloidosis. Amyloid deposits containing LCs infiltrate the tissues and can cause their dysfunction and failure. The most frequently affected organs are kidneys (74%), heart (60%), gastrointestinal tract (10–20%), liver (27%) and autonomous nervous system (18%). At the time of diagnosis, 69% of patients have more than one affected organ. There is no doubt that cardiac involvement is the main prognostic determinant in AL amyloidosis and the leading cause of death, if diagnosed late and not responding to therapy, in a majority of patients. The optimal management of patients with AL amyloidosis requires an early diagnosis, correct assessment of the type of amyloid, effective treatment with supportive therapy and very careful follow-up.
Nephrol Dial Transplant. 2019;34(9):1460-1466. © 2019 Oxford University Press