Retinal drusen in glomerulonephritis with or without immune deposits suggest systemic complement activation in disease pathogenesis

Abstract

Retinal drusen are characteristic of macular degeneration and complement activation, but also occur in C3, lupus and IgA nephropathy. This cross-sectional observational study compared drusen counts in different forms of glomerulonephritis. Consecutive individuals with glomerulonephritis attending a general renal or transplant clinic underwent retinal imaging with a non-mydriatic camera. Drusen were counted in deidentified images by trained graders, compared with matched hospital patients, and correlated with clinical features. Eighty-four individuals with glomerulonephritis had a mean drusen count of 10 ± 27 compared with 3 ± 8 in hospital controls (p = 0.007). Fourteen individuals with glomerulonephritis (17%) and 4 hospital controls (4/49, 8%) had increased drusen counts (≥ 10) (p = 0.20). Increased drusen counts ≥ 10 were present in 13 (13/63, 21%) of those with glomerulonephritis and immune deposits [membranous (n = 8), antiglomerular basement membrane nephritis (n = 6), FSGS (n = 49)], and one of the 21 (5%) with glomerulonephritis without immune deposits [ANCA-associated (n = 15), minimal change disease (n = 6)]. In antibody-mediated glomerulonephritis (n = 14), mean drusen counts were 2 ± 3 in individuals with normal kidney function, 16 ± 41 with impaired function and 5 ± 7 with kidney failure . Mean counts were 24 ± 56 in individuals with glomerular IgG deposits and 1 ± 1 in those without (p = 0.76), and 23 ± 60 with complement deposits and 4 ± 8 in those without. Drusen counts were also less in immunosuppressed individuals (p = 0.049). The demonstration of retinal drusen in some forms of glomerulonephritis is consistent with systemic complement activation, and suggests that treatment targeting the complement pathways is worthwhile.