Approach to the treatment of C3 glomerulopathy in adults and children

DDD: dense deposit disease; C3: complement C3; C3GN: C3 glomerulonephritis; GN: glomerulonephritis; MMF: mycophenolate mofetil; IV: intravenous; RPGN: rapidly progressive glomerulonephritis.

* Patients with C3 glomerulopathy and a monoclonal gammopathy should be evaluated for an underlying pathologic plasma cell or B cell clone or evidence of other end-organ involvement and treated accordingly. In the absence of an assay to confirm that the monoclonal gammopathy is responsible for complement dysregulation, treatment is based upon this presumption given the unusually strong association between monoclonal gammopathy and C3 glomerulopathy in older patients. The treatment of C3 glomerulopathy associated with monoclonal gammopathy is primarily directed against the pathologic clone responsible for producing the monoclonal protein. Refer to UpToDate content on the treatment of C3 glomerulopathy with monoclonal gammopathy for more details.

¶ Clinical decisions regarding initial therapy are based upon an arbitrary proteinuria threshold of 1.5 g/day. There is no evidence to support this (or any other) proteinuria threshold in patients with C3 glomerulopathy, and this threshold is largely based upon the clinical experience of the authors and editors of this topic.

Δ All patients with C3 glomerulopathy, regardless of disease severity, can also be encouraged to participate in a clinical trial, if available.

◊ Supportive measures include dietary sodium and protein restriction, blood pressure control, reduction of proteinuria with renin-angiotensin inhibition, and treatment of dyslipidemia, if present. Other aspects of therapy include diuretics to control edema and maintenance of adequate nutrition. Refer to UpToDate content on supportive measures in all patients with DDD or C3GN.

§ Refer to UpToDate content for information on dosing of immunosuppressive agents inpatients with DDD or C3GN.

¥ Supportive evidence for the efficacy of MMF and glucocorticoids in patients with C3 glomerulopathy is stronger for those with C3GN than for those with DDD since these studies included predominantly patients with C3GN and only a few patients with DDD.

‡ In addition to immunosuppressive therapy, some experts would also administer eculizumab. If there is no evidence of disease stabilization or improvement after 3 months of therapy, eculizumab should be discontinued. Refer to UpToDate content on the use of eculizumab in patients with C3 glomerulopathy and RPGN.

† In patients with identified genetic defects in factor H, plasma infusion or plasma exchange can be administered to replace the missing or mutant factor H protein. Plasma infusion or exchange should not be given to patients with genetic defects in complement regulators other than factor H; such patients can be treated with eculizumab.