Thrombotic microangiopathy associated with monoclonal gammopathy

Abstract

Thrombotic microangiopathy (TMA) is a rare disease comprising of a diverse set of disorders linked by a common histologic finding of endothelial injury. Monoclonal immunoglobulins may act as a potential trigger in the pathogenesis of TMA. To determine the prevalence of monoclonal gammopathy and clinicopathological features of TMA associated with monoclonal immunoglobulin, we performed a retrospective study in adults (18 and older) with a clinical diagnosis of TMA. Of 146 patients with TMA, we detected monoclonal immunoglobulin in 20 patients (13.7%). Among patients 50 and older, the prevalence of monoclonal gammopathy was 21%, which is approximately five-fold higher than the 4.2% expected rate in this population. Fifteen patients had monoclonal gammopathy of undetermined significance, one had multiple myeloma, one with smoldering myeloma, two had POEMS syndrome, and one had T-cell lymphocytic leukemia. Renal biopsy was performed in 15 cases, of which six showed thrombi, 11 showed mesangiolysis, and all showed double contours along glomerular capillary walls. Acute tubular injury was present in 12 cases. Treatment options were varied and included therapeutic plasma exchange in 11 patients. Ten patients progressed to end-stage renal disease, of which two received kidney transplant. Thus, our study shows an unexpectedly high prevalence of monoclonal gammopathy in patients with TMA, suggesting a potential pathogenetic mechanism. This study underscores the importance of evaluating for a monoclonal gammopathy in patients with TMA as well as the potential for targeting the underlying hematologic disorder as an approach to treating TMA.

The evaluation of monoclonal gammopathy of renal significance: a consensus report of the International Kidney and Monoclonal Gammopathy Research Group

“…At the 2017 IKMG meeting in New Orleans, two additional subcategories were added to the non-organized and non-immunoglobulin categories of the classification scheme 35 . Thrombotic microangiopathy associated with monoclonal gammopathy was provisionally added as a subcategory of non-immunoglobulin deposits 42 , and a miscellaneous subcategory was added to the non-organized deposit category, which applies to pathological entities that are ultrastructurally similar to a non-monoclonal-immunoglobulin-related disease but are only sometimes associated with a monoclonal gammopathy. The MGRS-associated disorders included in this classification are discussed in more detail below.…”

“…Thrombotic microangiopathy is the endothelial injury seen most commonly in microangiopathy with haemolytic anaemia (MAHA). Thrombotic microangiopathy and MAHA can occur concurrently in patients with monoclonal gammopathies, including MM and WM 13,42,80,81 .…”

The Complexity and Heterogeneity of Monoclonal Immunoglobulin–Associated Renal Diseases

“…A subset of patients with TMA have an associated MIg. 69 MIg can act as a potential trigger of TMA, producing atypical hemolytic uremic syndrome via dysregulation of the alternative pathway of complement, although precise mechanisms remain to be elucidated. 70 Similar to MIg-associated C3 glomerulopathy, it was recently shown that, among patients $50 years of age, the prevalence of monoclonal gammopathy in TMA was much higher than in the general population.…”

Monoclonal gammopathy‐associated thrombotic microangiopathy

“…1 Manifestations of TMA can be divided into peripheral which include thrombocytopenia and microangiopathic hemolytic anemia (MAHA), and renal including vascular thrombosis, mesangiolysis, endothelial swelling, and subendothelial accumulation of cellular material. 2 Malignancyassociated TMAs most commonly involved metastatic solid organ malignancies, usually with bone marrow infiltration. 3 There is a growing interest in the relationship between TMA and monoclonal gammopathies.…”

“…In one study of 146 patients with TMA, monoclonal gammopathy was present in 13.7%. 2 MGUS was the most common diagnosis (n = 15), followed by POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome (n = 2) and smoldering MM (n = 1), MM (n = 1), and 1 with a T-cell lymphocytic leukemia. It is important to note that some of these cases occur after infection, chemotherapy or hematopoietic stem cell transplantation in which the TMA cannot be directed attributed to the monoclonal gammopathy.…”