C3 glomerulopathy and post-infectious glomerulonephritis

C3 glomerulopathy (C3G) is a disease caused by abnormal activation of alternative complement pathway, usually by genetic defect of proteins controlling the pathway or antibodies to them. Post-infectious GN (PIGN) is a disease caused by overactivation of alternative complement pathway by bacterial-immunoglobulin immune complex depositing in glomeruli. Before C3 glomerulopathy has been recognized, patients with the disease were diagnosed with atypical PIGN because of similar clinico-pathologic findings.
Al-Ghaithi et al. studied 33 children with PIGN and found almost one fourth of them could be reclassified as C3G. These patients had slow progressive clinical course and lacked classic subepithelial deposits or humps by electron microscopy (EM). Although some PIGN cases showed no IgG staining by immunofluorescence, the humps were identified by EM.

Bacterial infection-related glomerulonephritis in adults

Nasr et al.

Infection-related glomerulonephritis occurring in patient with
 diabetic glomerulosclerosis. Mesangial nodules due to
diabetes are seen.

Acute poststreptococal glomerulonephritis (PSGN) is common in children. In the past 3 decades, the number of adults with infection-related glomerulonephritis (IRGN) has been increased. IRGN in adults has a number of differences from PSGN in children:

• Adults with IRGN usually have concurrent bacterial infection while children with PSGN, as the name implies, have renal disease after the infection subsided. Immunosuppressants are not recommended in the former group.
• IRGN are usually caused by non-streptococcal bacteria
• A large percentage of adults with IRGN are immunocompromised, especially diabetics and elderlies. These patients had poor disease outcome.
• Both adults with IRGN and children with PSGN present with acute nephritis, but elderly patients with IRGN have more severe complication such as heart failure, acute renal failure requiring dialysis, than children or younger adults. This most likely reflects more chronic condition such as diabetes, atherosclerosis in elderlies.

Traditionally, the pathogenesis model of PSGN is deposition of circulating immune complex to the glomerular capillary walls. Newer evidence points to the in situ immune complex formation and molecular mimicry. Host factor has been indicated. Defect in alternative pathway of complement are recognized in some patients.

Atypical postinfectious glomerulonephritis and the alternative complement

Atypical postinfectious glomerulonephritis is associated with abnormalities in the alternative pathway of complement

10 of 11 patients who were diagnosed by kidney biopsy as atypical postinfectious glomerulonephritis (APGN) had abnormalities in alternative pathway of complement. APGN is characterized clinically by persistent hematuria and proteinuria and histologically by diffuse proliferative glomerulonephritis, C3 with/without immunoglobulin staining and subepithelial humps.

Post-streptococcal glomerulonephritis and chronic kidney disease (CKD)

Hoy et al studied risk for CKD from post-streptococcal glomerulonephritis (PSGN) in a remote Aboriginal community. The study showed that people who had history of PSGN had increased risk in developing CKD (albuminuria, decreased GFR) later in life. Although PSGN is increasingly uncommon in developed countries, it is still prevalent in developing countries or in this case poor communities in developed country. The risk factor was scabies which leaded to skin infection with streptococci.