Biologie und Medizin

Abstrakt

C3 Glomerulonephritis and Plasma Cell Dyscrasia: Expanding the Etiologic Spectrum

Dennis L Cooper, William R Munday and Gilbert W Moeckel

Background: C3 glomerulopathy (C3GP) including dense deposit disease (DDD) is mediated by abnormal activation of the alternative complement pathway (ACP). In children and young adults, mutations of complement or complement regulatory proteins are the major causative factors but in adults there appears to be an increased incidence of monoclonal gammopathy and it has been proposed that the paraprotein is functioning as a C3 nephritic factor or through other unknown mechanisms resulting in abnormal ACP activity. We describe five patients with C3GP and plasma cell dyscrasias including two patients with symptomatic multiple myeloma and three patients with monoclonal gammopathy of renal significance one of whom progressed to symptomatic myeloma. One patient with DDD and elevated C3 nephritic factor responded to myeloma therapy with cyclophosphamide plus bortezomib and dexamethasone while another patient seemed to rapidly worsen both times after receiving lenalidomide, a drug with potent immunomodulatory activity. In two patients, the effect of myeloma therapy was indeterminate secondary to advanced disease. Two patients with renal transplant had recurrence C3GP in the transplanted kidney at 2 months and four years, respectively. Conclusion: Adult patients with C3GP should be screened for plasma cell dyscrasias. Further studies are required to assess the value of myeloma-directed treatment and/or ACP inhibition.