Abstract:

Objective To explore the diagnostic and therapeutic strategies for non-traditional immunoglobulin-related renal amyloidosis by analyzing the clinical management of a patient with heavy and light chain renal amyloidosis and biclonal paraproteinemia. Methods The clinical data of a patient diagnosed with biclonal paraproteinemia and renal amyloidosis at the Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine and long-term follow-up from 2021 to 2024 were collected and analyzed, and relevant domestic and foreign literature was reviewed. Results The main symptoms in a 72-year-old male presented with foamy urine, facial and bilateral lower limb edema. Biclonal (IgM κ and IgA, λ) gammopathy were detected, heavy and light-chain renal amyloidosis (IgA-λ) was diagnosed by renal biopsy. There was no obvious involvement in the heart. A small number of monoclonal CD38⁺ B cells were detected through immunophenotyping in bone marrow, while the L265P mutation of the MYD88 gene was negative in it. There was no lymph node enlargement or extranodal lesions, the underlying hematological disease was a B-lymphocyte proliferative disorder. After initial treatment with a rituximab-based regimen, the treatment was adjusted to daratumumab combined with lenalidomide which was targeting CD38. The patient quickly achieved complete hematological remission and a renal response, and complete renal remission was achieved during subsequent treatment. Literature review showed that there are only a few case reports on biclonal paraprotein associated with renal amyloidosis, and only one case of renal amyloidosis associated with heavy and light-chain. In amyloidosis caused by B cell or lymphoplasmacytic clones, rituximab-based regimens are the main treatment, but hematological and organ responses are not ideal. The daratumumab combination regimen may be effective for patients with pathogenic clones of CD38⁺ B cells. Conclusions There is no consensus or guideline for the diagnosis and treatment of light-chain amyloidosis with biclonal paraprotein. Accurately identifying the pathogenic clone, determining the treatment target, and formulating individualized combination drug regimens are helpful for patients to achieve more profound remission of hematology and organs.

Key words: Light-chain amyloid nephropathy, Light-and heavy-chain amyloidosis, Biclonal gammopathy, Rituximab, Daratumumab