The Complexity and Heterogeneity of Monoclonal Immunoglobulin–Associated Renal Diseases

Abstract

Monoclonal gammopathies are characterized by the overproduction of monoclonal Ig (MIg) detectable in the serum or urine resulting from a clonal proliferation of plasma cells or B lymphocytes. The underlying hematologic conditions range from malignant neoplasms of plasma cells or B lymphocytes, including multiple myeloma and B-cell lymphoproliferative disorders, to nonmalignant small clonal proliferations. The term MGUS implies presence of an MIg in the setting of a "benign" hematologic condition without renal or other end organ damage. The term MGRS was recently introduced to indicate monoclonal gammopathy with MIg-associated renal disease in the absence of hematologic malignancy. Most MIg-associated renal diseases result from the direct deposition of nephrotoxic MIg or its light- or heavy-chain fragments in various renal tissue compartments. Immunofluorescence microscopy is essential to identify the offending MIg and define its tissue distribution. Mass spectrometry is helpful in difficult cases. Conditions caused by direct tissue deposition of MIg include common disorders, such as cast nephropathy, amyloidosis, and MIg deposition diseases, as well as uncommon disorders, such as immunotactoid glomerulopathy, proliferative GN with MIg deposits, light-chain proximal tubulopathy, and the rare entities of crystal-storing histiocytosis and crystalglobulinemia. Indirect mechanisms of MIg-induced renal disease can cause C3 glomerulopathy or thrombotic microangiopathy without tissue MIg deposits. Treatment of MIg-associated renal disease is aimed at eliminating the clonal plasma cell or B-cell population as appropriate. Both the renal and the underlying hematologic disorders influence the management and prognosis of MIg-associated renal diseases.

Incidence and risk factors for acute kidney injury following autologous stem cell transplantation for multiple myeloma

“…The differences in incidence and severity between our study and the results of Fadia et al may be due to the fact that AL amyloidosis is a systemic disease, with frequent involvement of the kidney and heart, preexisting conditions which increase the likelihood of kidney injury after ASCT. It is estimated that around 10% of patients with MM have coexisting AL amyloidosis . In our cohort of patients, AL amyloidosis secondary to MM was diagnosed in 12.5% of patients and coexistence of these two conditions was associated with a fivefold higher risk of AKI following ASCT.…”

Noninfectious mixed cryoglobulinaemic glomerulonephritis associated with monoclonal gammopathy of undetermined significance

“…It remains unclear from our study whether the identification of MGUS in a patient with noninfectious mixed CGN provides any guide to treatment and prognosis. A designation of MGRS would imply the need for clonally targeted therapies to be considered in preference to conventional immunosuppression, with the primary aim of improving renal outcomes (24). Evidence for this approach in patients with noninfectious mixed CGN consists largely of retrospective studies of rituximab, mostly involving patients with type 2 CGN and a monoclonal IgM-k cryoglobulin (11,28,29,39).…”

Tubular Injury and Dendritic Cell Activation Are Integral Components of Light Chain–Associated Acute Tubulointerstitial Nephritis

“…The authors recognize that in rare instances a process initially considered as LC-ATIN may progress to or be later characterized as LCDD with prominent tubulointerstitial involvement as additional evidence becomes available, as demonstrated by the case report of Takahashi et al 41 This represents an additional example of the complexity and heterogeneity of renal lesions associated with nephrotoxic light chains, which essentially depend on the extremely varied physicochemical characteristics of light chains involved. 42 The conceptual understanding of the intricacies of these diseases is still evolving. Basic research will continue providing crucial information that will allow us to better understand this complex group of diseases.…”