Nephrotic syndromes

Question 1

Minimal change disease: pathology and causes

Answer 1

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)

Question 2

Minimal change disease: causes

Answer 2

• Unknown; T cells release cytokines, may cause effacement of podocytes

Question 3

Minimal change disease: RF

Answer 3

• 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)

Question 4

Minimal change disease: signs and symptoms

Answer 4

• Proteinuria, hypoalbuminemia, edema, hyperlipidemia, lipiduria, hypercoagulability
• Onset more rapid (days to weeks) than other nephrotic syndromes

Question 5

Minimal change disease: complications

Answer 5

Relatively benign -> does not affect kidney function

Question 6

Minimal change disease: Diagnosis

Answer 6

Lab results:
- proteinuria -> > 3.5g/day

Kidney biopsy:

• light microscopy: normal (why it’s called minimal changes)
• electron microscopy: effacement of foot processes
• immunofluorence: -

Question 7

Minimal change disease: T

Answer 7

• Prednisone

Excellent response, more quickly in children than adults; potential relapse

Question 8

Focal Segmental Glomerulonephritis (FSGS): pathology and causes

Answer 8

• 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

Question 9

FSGS: causes

Answer 9

• 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

Question 10

FSGS: RF

Answer 10

• More common in black people of African descent/people of Latin American descent
• Morbid obesity
• Chronic kidney disease (congenital malformation)

Question 11

FSGS: signs and symptoms

Answer 11

• Proteinuria, hypoalbuminemia, edema, hyperlipidemia, lipiduria,
• hypercoagulability

Question 12

FSGS: complications

Answer 12

• kidney failure

Question 13

FSGS: diagnosis

Answer 13

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)

Question 14

FSGS: treatment

Answer 14

• Blood pressure reduction- >ACE inhibitors
• Edema -> Diuretics
• Prednisone/calcineurin inhibitors

Question 15

Membranoproliferative glomerulonephritis (MPGN): Pathology and cause

Answer 15

• 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

Question 16

Membranoproliferative glomerulonephritis (MPGN): types

Answer 16

• 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

Question 17

Membranoproliferative glomerulonephritis (MPGN): signs and symptoms

Answer 17

• Nephrotic syndrome: Proteinuria, peripheral edema, foamy urine, hyperlipidemia, lipiduria
• Nephritic syndrome (more common): Hematuria, oliguria (low production of urine), hypertension

Question 18

Membranoproliferative glomerulonephritis (MPGN): diagnosis

Answer 18

• Kidney biopsy

- Electron microscopy -> depends on the type

Question 19

Membranous glomerulonephritis: pathology and cause

Answer 19

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

Question 20

Membranous glomerulonephritis: primary causes

Answer 20

• Mostly idiopathic

- Associated with human leukocyte antigen (HLA) alleles (e.g. HLA-DQA1)

Question 21

Membranous glomerulonephritis: secondary causes

Answer 21

• 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

Question 22

Membranous glomerulonephritis: RF

Answer 22

• White people of European descent

- increase risk of end-stage renal disease

Question 23

Membranous glomerulonephritis: signs and symptoms

Answer 23

• Often asymptomatic, discovered incidentally

- Proteinuria, hypoalbuminemia, edema, hyperlipidemia, lipiduria, hypercoagulability; develop gradually over months

Question 24

Membranous glomerulonephritis: Diagnosis

Answer 24

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)

Question 25

Membranous glomerulonephritis: Treatment

Answer 25

Primary cause:
- For the symptomatic therapy: Diuretics (furosemide), ACE inhibitors, heparin, antibacterial drugs

• if at low risk of end-stage renal disorder (i.e. proteinuria < 3.5g/day -> Close observation, no immunosuppression
• If at moderate/high risk of end-stage renal disorde -> Prednisone + calcineurin inhibitor (e.g. tacrolimus, cyclosporine)/cytotoxic agent (e.g. cyclophosphamide)
• Rituximab

Secondary cause:
- treat the underlying condition

Question 26

Membranous glomerulonephritis: other interventions

Answer 26

Lifestyle changes:

- Medical nutrition therapy, reduce cholesterol, saturated fat intake