Nephrotic syndromes Flashcards
Minimal change disease: pathology and causes
Syndrome néphrotique idiopathique de l’enfant
- Type of glomerulonephritis; podocytes in glomeruli get damaged by T cells cytokines -> Foot processes of podocytes damaged, flattened (AKA effacement)
Minimal change disease: causes
- Unknown; T cells release cytokines, may cause effacement of podocytes
Minimal change disease: RF
- Most common nephrotic syndrome in children
- Hematologic malignancies: e.g. Hodgkin’s lymphoma
- Recent infection: immunization; immune stimulus; medications: nonsteroidal anti-infl ammatory drugs (NSAIDs)
Minimal change disease: signs and symptoms
- Proteinuria, hypoalbuminemia, edema, hyperlipidemia, lipiduria, hypercoagulability
- Onset more rapid (days to weeks) than other nephrotic syndromes
Minimal change disease: complications
Relatively benign -> does not affect kidney function
Minimal change disease: Diagnosis
Lab results:
- proteinuria -> > 3.5g/day
Kidney biopsy:
- light microscopy: normal (why it’s called minimal changes)
- electron microscopy: effacement of foot processes
- immunofluorence: -
Minimal change disease: T
- Prednisone
Excellent response, more quickly in children than adults; potential relapse
Focal Segmental Glomerulonephritis (FSGS): pathology and causes
- Foot processes of podocytes damaged → plasma proteins, lipids permeate glomerular filter
- Proteins, lipids trapped → build up inside glomeruli → hyalinosis (hyaline/glassy view on histology) →scar tissue (glomerulosclerosis)
- Affects parts (segmental) of some (focal) glomeruli of nephron; damage, scarring →proteinuria
FSGS: causes
- Primary: unknown
- Secondary: result of underlying cause:
Sickle cell disease, HIV, renal hyperfi ltration (e.g. unilateral renal agenesis), heroin abuse - Genetic forms: FSGS 1–6
FSGS: RF
- More common in black people of African descent/people of Latin American descent
- Morbid obesity
- Chronic kidney disease (congenital malformation)
FSGS: signs and symptoms
- Proteinuria, hypoalbuminemia, edema, hyperlipidemia, lipiduria,
- hypercoagulability
FSGS: complications
- kidney failure
FSGS: diagnosis
Lab results:
- proteinuria > 3.5g/L
Kidney biopsy:
- Light microscopy: segmental sclerosis, hyalinosis of glomeruli
- Electron microscope: effacement of foot processes of podocytes
- Immunofluorescence: nonspecific focal deposits of IgM, complement proteins not always seen (sometimes trapped in hyalinosis)
FSGS: treatment
- Blood pressure reduction- >ACE inhibitors
- Edema -> Diuretics
- Prednisone/calcineurin inhibitors
Membranoproliferative glomerulonephritis (MPGN): Pathology and cause
- Type of nephrotic syndrome; inflammation of glomerular basement membrane, mesangium → decreased kidney function, proteinuria
- Immune complex/complement deposits trigger immune reactions ->
Activates complement system → enzyme cascade → membrane attack complex → damage to podocytes, mesangial cell.
Recruits inflammatory cells → proteases, oxidants release → basement membrane damage → proteins leak into urine → nephrotic syndrome
Membranoproliferative glomerulonephritis (MPGN): types
- Type 1: chronic infection: Hep B, Hep C; inappropriate activation of alternative complement pathway, autoimmune diseases: SLE, scleroderma, Sjorgren syndrome, sarcoidosis
Cancer: leukemia, lymphoma - Type 2: Nephritic factor (C3NeF)
- Type 3: idiopathic
Membranoproliferative glomerulonephritis (MPGN): signs and symptoms
- Nephrotic syndrome: Proteinuria, peripheral edema, foamy urine, hyperlipidemia, lipiduria
- Nephritic syndrome (more common): Hematuria, oliguria (low production of urine), hypertension
Membranoproliferative glomerulonephritis (MPGN): diagnosis
- Kidney biopsy
- Electron microscopy -> depends on the type
Membranous glomerulonephritis: pathology and cause
Also called membranous nephritis
- Inflammation of glomerular basement membrane triggered by immune complex deposits → increased permeability, proteinuria → nephrotic syndrome
- Glomerular basement membrane damaged by immune complex deposits; sandwiched between epithelial cells of podocytes, glomerular basement membrane (subendothelial deposits)
- Autoantibodies target glomerular basement membrane
- > Immune complex deposits → immune reactions -> Activates complement system → enzyme cascade → membrane attack complex → damage to podocytes, mesangial cells -> … damage -> nephrotic syndrome
Membranous glomerulonephritis: primary causes
- Mostly idiopathic
- Associated with human leukocyte antigen (HLA) alleles (e.g. HLA-DQA1)
Membranous glomerulonephritis: secondary causes
- Auto-antibodies generated in response to underlying condition
- Infections: Hepatitis B virus, hepatitis C virus, syphilis
- Medications: NSAIDs, penicillamine, gold
- Autoimmune: Systemic lupus erythematosus
- Malignancy
Membranous glomerulonephritis: RF
- White people of European descent
- increase risk of end-stage renal disease
Membranous glomerulonephritis: signs and symptoms
- Often asymptomatic, discovered incidentally
- Proteinuria, hypoalbuminemia, edema, hyperlipidemia, lipiduria, hypercoagulability; develop gradually over months
Membranous glomerulonephritis: Diagnosis
Lab results:
- proteinuria
Renal biopsy:
- Light microscopy: Diffuse thickening of glomerular basement membrane
- Electron microscopy: “Spike and dome” appearance due to glomerular basement matrix on top of subepithelial deposits; effacement of podocytes
- Immunofluorescence: Deposits appear granular throughout glomerular basement membrane
If kidney biopsy not an option -> Serum: assayed for antibodies associated with membranous glomerulonephritis (anti-PLA2R antibody)
