Etiology is idiopathic, autoimmune, infectious (Hepatitis C or chronic bacterial), neoplastic (multiple myeloma, chronic lymphocytic leukemia)
Pathogenesis: Antigens either bind to antibodies and deposit on the subendothelial surface of the GBM, or the antigens get stuck at the GBM and antigens bind to them there. These antigen- antibody complexes activate the classical pathway of the complement system, which activate the membrane attack complexes and cause cellular damage in the glomerulus. Low serum C3, C4 and total complement.
Course: For idiopathic and autoimmune cases, progression is slow, with 30% progressing to ESRD in 10-15 years. For infectious causes, it depends on the treatment of the underlying disease.
Treatment: For idiopathic and autoimmune cases, can treat with steroids, but many patients do not respond and there is not much data to support it. Can also try cyclophosphamide, mycophenolate mofetil. For infectious causes, treat the underlying conditions.
Epidemiology: Most common cause of glomerulonephritis worldwide; appears in 2nd to 3rd decade of life; most prominent in Asian and Caucasian populations
Etiology: Environmental antigens trigger a mucosal immune response that forms IgA antibodies. Antigen may be viral, bacterial, or food. The IgA immune complexes are pathogenic.
Pathogenesis: Formation of IgA immune complexes that are abnormally glycosylated and cannot be cleared by the spleen. The complexes are recognized as abnormal by the immune system and a second antibody, IgG, is formed against it (they recognize the abnormal hinge region where the glycosylation occurs). These large macromolecules then deposit in the mesangium of the kidney. Complement is activated.
Diagnosis: Renal biopsy. Serum complement is normal, as the activation occurs locally and not systemically. Mesangial cells proliferate and make more matrix: more so than usual.
Clinical presentation: ~40% have gross hematuria following Upper Respiratory Infection; synpharyngitic hematuria. ~30% have microscopic hematuria and proteinuria discovered incidentally. 5-10% present with acute nephritic syndrome, and some present with rapidly progressing glomerulonephritis (RPGN). May be associated with skin or GI abnormalities; dermatitis herpetiformis, celiac sprue, cirrhosis
Treatment: Prognosis is variable, with 10-40% progressing to chronic renal failure. If renal function is normal and proteinuria is <500 mg, then no treatment. If proteinuria > 1g, then treat with ACE inhibitors or ARBs. Fish oil. Steroids for patients with proteinuria >1g or with progressive disease (ex: prednisone)
Epidemiology: Most common cause of acute nephritic syndrome. Peak incidence ages 5-12 years, >60 years. More common in developed countries
Etiology: Presents 1-6 weeks following infectious illness: streptococcus pharyngitis, impetigo (skin infection), and others (malaria, toxoplasmosis)
Pathogenesis: specific strains of bacteria are nephritogenic, like Group A beta hemolytic streptococcus. Elevated antibodies against nephritogenic antigens in patients with post-infectious glomerulonephritis. Main antibody is AS0, the antistreptolysin antibody. The first theory is that antigen-antibody complexes circulate and are deposited in the glomerulus, activating complement. The second theory is that these bacteria cause a change in renal proteins that cause them to become recognized as foreign, and cause proliferation of antibodies against them, which then bind and activate the alternative complement pathway.
Diagnosis: Active urine sediment (dysmorphic RBCs, red blood cell casts) - "tea-tinted urine"; may have elevated antibody titers (as above); low C3 and total complement with normal C4 due to activation of alternative pathway. Streptozyme test measures 5 different antibodies.
Treatment: Care is supportive. Treat the underlying infection. Children have an excellent prognosis, with 95% recovering fully. Adults may have slow insidious progression to chronic glomerulonephritis -- can even progress to ESRD.