BAFF in IGA NEPHROPATHY (IGAN)
IgA nephropathy (also known as Berger’s disease) is the most common cause of primary glomerulonephritis worldwide, occurring more frequently in Asia than in Europe or North America. IgAN is characterized by IgA deposition in the kidney causing blood and protein to leak into the urine. The disease typically progresses slowly but as many as 40-50% of adults will eventually develop end-stage-renal disease and require dialysis or kidney transplant. The current management of IgAN is non-specific treatment aimed at blood pressure control and reduction of proteinuria with angiotensin converting enzyme inhibitors (ACEI) and/or angiotensin II receptor blockers (ARBs). Corticosteroids and immunosuppressive therapy are used in some patients. However, recent data from the STOP-IgAN study showed the addition of immunosuppressives to standard-of-care did not significantly improve outcomes.
Evidence for a role of BAFF in IgAN disease pathology is observed in patients and animal models. Elevated serum concentrations of BAFF are reported in patients with IgAN, and these correlate with histological disease severity. In addition, BAFF is known to stimulate the production of immunoglobulins, and mice that over express BAFF have elevated levels of circulating IgA along with IgA deposits in the kidney. Collectively, these data provide the basis for the use of blisibimod as the first potential targeted therapy to reduce production of IgA-containing immune complexes and thereby prevent kidney damage and disease progression.