Smith RJH et al. (2007) New approaches to the treatment of dense deposit disease. J Am Soc Nephrol 18: 2447–2456

Dense deposit disease (DDD; also known as membranoproliferative glomerulonephritis type II) has a prevalence of just 2–3 cases per million individuals, and as a result it has been difficult to evaluate potential therapies in randomized controlled trials. Recently, Smith and colleagues have used available animal, genetic and molecular data to develop a diagnostic and treatment algorithm for the disease.

The authors recommend that all patients with biopsy-proven DDD should be assayed for C3 nephritic factor (C3NeF; an autoantibody against C3 convertase), tested for serum markers of complement activity, and screened for mutation of the factor H gene, CFH. These tests are intended to evaluate abnormalities in the alternative complement pathway. If the C3NeF assay is positive, plasma exchange or infusion should be considered, as should administration of anti-B-cell agents such as rituximab. If a pathologic CFH mutation is found, plasma infusion should be performed to provide functional factor H. Depending on pathophysiology, administration of eculizumab (an anti-C5 antibody) or sulodexide (a heparanase inhibitor) can be considered. More generally, nonspecific treatments, including aggressive blood pressure control and reduction of proteinuria with angiotensin-converting-enzyme inhibitors and angiotensin-receptor blockers, might slow progression of renal damage. Treatment success should be defined as retardation of progressive kidney dysfunction, and secondarily as normalization of alternative complement pathway activity.

Reporting of DDD treatments and outcomes to the DDD Outcomes Database, a resource available to all health-care personnel at http://genome.uiowa.edu/ddd, will facilitate evidence-based management of this rare disorder.