NEPHRITIC SYNDROMES Rapidly progressive Glomerulonephritis (RPGN) (Following Goodpasteur’s syndrome) Berger disease (IgA Nephropathy) #1 most common Typical Patient Males 20-40 years Males > Females In Goodpasteur: Antibodies Vs Collagen IV α3 subunit Adolescents after Gi or upper resp infection Same day of mucosal infection patient pees blood Membranoprolipherative Glomerulonephritis (MPGN) Low yield. Type 1: “Tram track” Type 2: C3 nephritic factor Alport Syndrome (COL4A5 mutation) X-linked dominant Collagen IV α5 subunit defect Children Acute poststreptococcal glomerulonephritis In children after a strep infection of skin or pharynx By S. pyogenes M12 infection (but not the only one) (#1 in children) Clinical Features Nephritic syndrome that progresses to renal failure in weeks or months, may be secondary to other glomerulonephritis Renal Biopsy LM: Hypercelullarity, crescents, fibrin deposits and macrophages, compressed capillaries IF: Smooth and linear pattern of IgG and C3 in BM. EM: No deposits Recurrent Gross hematuria after mucosal infection Progresses to renal failure in 25 years LM: Mesangial prolipheration IF: IgA immune complexes and C3 in mesangium EM: Immune complex deposits Most common cause of glomerulonephritis in the world Associated with Celiac sprue and Henoch Schönlein purpura Nephritic or nephrotic (or mixed) CKD in 10 years LM: Lobulated appearance of glomeruli, splitting of BM: “Tram track” seen in silver stain and PAS (+) IF: Type 1: Gtanular pattern, C3 IgG, C1q and C4 deposits. Type 2: Granular pattern, C3 deposits. EM: Type 1: Subendothelial and mesangial immune complex deposits. Type 2: Dense deposits in BM LM: “Basketwave” appearance IF: Clean EM: Alternating thickening and thinning of BM with splitting of lamina densa Secondary to many disorders (SLE, endocarditis, HBV, HCV, HIV, CLL) Low serum C3 LM: Enlarged glomeruli and hypercellularity IF: “Starry sky” granular appearance and “Lumpy bumpy” IgG, IgM and C3 deposits EM: Subepithelial immune complex humps 25% of adults progress to RPGN Associated with serum DNAse B and high ASO titers “Can’t see, can’t pee, can´t hear a bee” Isolated hematuria, ocular abnormalities and sensorineural deafness Peripheral and periorbital edema with cola coloured urine and Hypertension Image Comments Treat: Plasmapheresis, steroids, sytotoxic drugs Poor prognosis Differentials: Goodpasteurs (also involves alveoli) Wegener (cANCA/PR3-ANCA) NEPHROTIC SYNDROMES Minimal Change dieseae (Lipoid nephrosis or Nil disease) Primary Disorders #1 Cause of nephrotic syndrome in children Clinical Features Selective proteinuria (loss only of albumin and antithrombin III) Renal Biopsy LM: Lipid accumulation in proximal tubule IF: No findings EM: Effacement of podocytes Overall, the filtration barrier loses negative charge and allows albumin to be filtrated 1st cause in African americans and Hispanics Poor response to steroids LM: Focal segmental sclerosis and hyalinization of glomeruli IF: IgM, C1 and C3 deposits in sclerotic segments EM: Effacement of podocytes in nonsclerotic regions and mesangial matrix prolipheration in sclerotic regions Membranous glomerulonephritis 1st cause in Caucasians May regress spontaneously May progress to CKD May cause persistent proteinuria LM: Thick glomerular membrane IF: IgG and C3 subepithelial immune complex deposits in granular and linear pattern EM: Subepithelial deposits in “Spike and dome” in silver stain, effacement of podocytes Diabetic glomerulonephritis (Nodular glomerulosclerosis) Long term diabetics Efferent arteriole is more affected, leading to high GF pressure Microalbuminuria that may progress to nephrotic syndrome Hematuria Nephritic/Nephrotic syndrome Hypertension Renal failure LM: Hyaline arteriolosclerosis, GBM thickening, Kimmelstiel-Wilson nodules Focal segmental glomerulosclerosis Secondary Disorders Typical Patient Children age 2-6 Associated with Lipoprotein L1 allele Systemic Lupus Erithematosus nephropathy PAS (+) Immune complexes deposit in glomeruli Image Comments Most common nephrotic syndrome in children In adults it associates with Hodgkin’s lymphoma Good response to steroids Etiology may be: Ideopathic IgA nephropathy Sickle cell anemia Heroin AIDS Obesity Patients with kidney transplant Poor response to steroids 85% idiopathic. May associate to: HBV/HCV Solid tumors (Lung/colon) SLE NSAID Penicillamine Poor response to steroids ACEI slow down progression because of efferent arteriole dilation NEPHROTIC SYNDROMES
