Understanding the complement‐mediated glomerular diseases: focus on membranoproliferative glomerulonephritis and C3 glomerulopathies

Abstract

An enhanced understanding of the role of complement in the pathogenesis of membranoproliferative glomerulonephritis has led to reclassification of the latter into immunoglobulin-mediated and non-immunoglobulin-mediated disease. The new classification schema resulted in improved diagnostic clinical algorithms, while it brought into light again the diseases, which are characterized by the presence of glomerular deposits, composed predominantly by C3, in the absence of significant amounts of immunoglobulins in renal biopsy, namely, C3 glomerulopathies (dense deposit disease and C3 glomerulonephritis). Despite the lack of randomized controlled trials following the advances in the understanding of the pathogenetic pathways involved in membranoproliferative glomerulonephritis, it is important that the new mechanistic approach has opened new roads for the exploration and discovery of targeted therapies.

Delayed type III hypersensitivity reaction with acute kidney injury in two dogs following administration of concentrated human albumin during treatment for hypoalbuminemia secondary to septic peritonitis

“…Dog 2 also had minimal labeling for immunoglobulins but had positive staining for C3, indicating complement activation. A category of C3 glomerulonephritis in people can have membranoproliferative findings, with C3 immunofluorescence and lack of immunoglobulin, similar to what was found in the kidneys of dog 2 23 . As reported by Powell et al, 13 the skin and lip histopathology from dog 2 was characterized by multifocal perivascular leukocytoclastic vasculitis, consistent with a type III immune complex reaction.…”

Clinical and Pathophysiological Insights Into Immunological Mediated Glomerular Diseases in Childhood

“…The important prognostic factors, reported in both adults and children, include deterioration of renal function, overt nephrotic syndrome (NS), severe glomerular hematuria (>50 red blood cells per high power field) and the presence of crescents or chronic lesions on kidney histology. Conversely, in secondary forms, identification of the underlying disease represents a favorable prognostic factor as it leads to the possibility of specific treatments (16). In pediatric patients, large population studies are lacking.…”

“…Immune complex-mediated MPGN is typically caused by a chronic antigen stimulus with persistence of CICs (11,16,69,70). The most frequent underlying disorders include chronic infections (hepatitis B/C, streptococcal and mycoplasma infections), autoimmune diseases (SLE, scleroderma, Sjögren syndrome) (60, 71-79), while monoclonal gammopathies are exceptional in children (80,81).…”

“…Patients with IC-MPGN secondary to chronic infection or other autoimmune/myeloproliferative disorders should be treated for the underlying disease ( Table 3) (16). There is no available adult or pediatric randomized trial data upon which to base treatment for patients with idiopathic IC-MPGN.…”

“…The Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend, on limited evidence (17), inhibition of the renin-angiotensin-aldosterone system (RAAS) in mild cases of the disease, with low proteinuria (<500 mg/day) and normal renal function, in both adults and children. In cases of nephrotic proteinuria with normal renal function, a course of prednisone (1 mg/kg/day for 12-16 weeks) is suggested (16), even if in the literature there are no confirmatory RCTs (18). RAAS blockers and cyclosporine should be considered in instances of steroid-resistance.…”