Kidney thrombotic microangiopathy with concurrent monoclonal gammopathy

BACKGROUND: The concurrence of monoclonal gammopathy and thrombotic microangiopathy (TMA) has been suggested in a few studies. However, the complement activation was not fully studied in previous cases. In this study, we aimed to determine the complement activation in these group of patients and the association with clinical, laboratory and pathological features. METHODS: Between 2007 and 2020, 20 patients with biopsy-proven renal TMA and monoclonal gammopathy in Peking University First Hospital were included in the study. Complement activation was tested by enzyme-linked immunosorbent assay. Associations with clinical features, pathological data and laboratory findings were further investigated. RESULTS: Among renal TMA patients beyond 50 years of age, the prevalence of monoclonal gammopathy was 16.51% (18/109) which is almost 4-fold greater than the expected rate in population (4.2%). Eleven patients had acute kidney injury, and two patients required dialysis. Hematological diagnosis was consistent with monoclonal gammopathy of undetermined significance (MGUS) (n = 10), unconfirmed MGUS (n = 3), POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) syndromes (n = 4), Castleman's disease (n = 2) and chronic lymphocytic leukemia (n = 1). A majority of patients (84.2%) showed the activation of complement classical pathway. Fifteen percent (3/20) of patients received conservative therapy, 5% (1/20) received steroid only, 30% (6/20) with immunosuppression and 50% (10/20) received clone-targeted chemotherapy. During a median 56 months of follow-up, end-stage renal disease developed in two patients, and five patients died mainly because of hematological progression. CONCLUSION: This study found the dysregulation of complement activation, especially the classical pathway, involved in the pathogenesis of biopsy-proven renal TMA and monoclonal gammopathy.