Abstract
BackgroundThe C3 glomerulopathies (C3G) are recently defined glomerular diseases, attributed to abnormal complement regulation. Dense deposit disease (DDD) is part of the spectrum of C3G, characterized by electron-dense deposits in the lamina densa of the glomerular basement membrane. Patients with DDD present with hematuria, variable degrees of proteinuria, and kidney dysfunction. Kidney biopsies typically disclose proliferative and inflammatory patterns of injury. Treatment with glucocorticoids and mycophenolate mofetil has been shown to achieve remission of proteinuria in a significant proportion of C3G patients.Case-diagnosis/treatmentWe report two patients with persistent nephrotic syndrome while on immunosuppressive therapy. Repeat kidney biopsies disclosed massive C3 deposits with foot process effacement in the absence of proliferative or inflammatory lesions on light microscopy.ConclusionThese cases, coupled with data from animal models of disease and the variable response to eculizumab in C3G patients, illustrate that two different pathways might be involved in the development of kidney injury in C3G: a C5-independent pathway leading to glomerular capillary wall injury and the development of proteinuria versus a C5-dependent pathway that causes proliferative glomerulonephritis and kidney dysfunction.
Highlights
Dense deposit disease (DDD) is a rare renal disease, within the spectrum of the C3 glomerulopathies (C3G), caused by complement dysregulation [1]
There was C3-dominant staining on immunofluorescence (IF) (Supplementary Fig. S1B), and electron microscopy (EM) was typical for DDD (Supplementary Fig. S1C)
Treatment consisted of methylprednisolone pulses, followed by oral prednisolone and mycophenolic acid (MPA), with improvement of kidney function and complete remission of proteinuria
Summary
These cases, coupled with data from animal models of disease and the variable response to eculizumab in C3G patients, illustrate that two different pathways might be involved in the development of kidney injury in C3G: a C5-independent pathway leading to glomerular capillary wall injury and the development of proteinuria versus a C5-dependent pathway that causes proliferative glomerulonephritis and kidney dysfunction.
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