Long-term follow-up of drusen-like lesions in patients with type II mesangiocapillary glomerulonephritis

The finding of drusen-like lesions beneath the retina in patients with membranoproliferative (or mesangiocapillary) glomerulonephritis (MPGN) type II, with or without partial lipodystrophy, was first reported in 1989. This was confirmed subsequently and has not been reported in other types of glomerulonephritis. These drusen develop at an early age, often in the second decade of life. Some authors have suggested a correlation between the development of eye changes and the duration of renal disease. Many patients do not develop visual impairment, but some may lose vision as a result of development of choroidal neovascularization (CNV) or central serous retinopathy. D’souza et al. studied four patients who had MPGN type II and these eye changes and were followed up during 14 to 37 yr. Three of them received a kidney transplant. There was no progression of retinopathy during 10 yr in any patient. None developed CNV or central serous retinopathy. Type II MPGN (also called dense-deposit disease [DDD]) is associated in 70% of the cases with an IgG autoantibody named C3 nephritic factor (C3NeF) and low C3 serum level, as a result of uncontrolled alternative pathway C3 activation. This C3NeF is also found in 30% of patients with MPGN type I. The principle function of complement function H is to downregulate alternative pathway complement activation. Regulation of fluid-phase C3 activation requires the N-terminal five short consensus repeat domains of the protein. In contrast, targeting of the protein to cell surfaces (surface recognition function) is mediated by C-terminal domains. Various factor H defects were detected in the whole spectrum of MPGN, with or without C3NeF, called “C3 glomerulopathy” by Pickering and Cook in their excellent review (1). This group included DDD, atypical DDD, and other forms MPGN-like diseases. This brings me back to ophthalmology. Age-related macular degeneration (AMD) is one of the most common causes of visual disability in the elderly in developed countries. The hallmark of early-stage disease is the development of drusen lipoproteinaceous deposits localized between the retinal pigment epithelium and Bruch’s membrane. Subsequently, an extensive atrophy of pigment epithelium and overlaying photoreceptor cells or aberrant choroidal angiogenesis is observed. This CNV under the macular area is a leading cause of blindness. Two major AMD susceptibility loci have been identified. One of these is the complement factor H (CFH) locus. The most studied single nucleotide polymorphism at this locus causes Tyr402His amino acid substitution in CFH. There are also common CFH haplotypes or complement fraction B polymorphisms that are associated with lower risk for AMD. These data are summarized in the comprehensive review by de Cordoba and de Jorge (2). AMD and MPGN type II share pathologic similarities with accumulation of complement-containing debris within the eye and the kidney. The hallmark of AMD is drusen, complementcontaining material that accumulates beneath the retinal pigment epithelial. These similarities are striking. Do not forget to check retinal fundi in patients with C3 glomerulopathy. We should keep our eyes open on the future progress in AMD (and MPGN) pathophysiology.