A Quick & High-Yield Breakdown of Nephritic Syndrome

Nephritic syndrome key characteristics

  • Hypertension
  • Hematuria, oliguria (symptoms you can see with your eyes)
  • Disruption/inflammation of glomeruli! If bad enough, can lead to glomerular basement membrane rupture and rapid loss of kidney function.
  • RBCs, WBCs, and RBC casts present on urine microscopy.
  • Proteinuria can be anywhere from sub-nephrotic proteinuria to nephrotic proteinuria.

Common (and testable) causes of nephritis

Alport Syndrome (hereditary nephritis)

  • Caused by mutations in alpha 3, alpha 4, or alpha 5 type IV collagen
  • Typically X-linked dominant inheritance (COL4A5), and rarely can be autosomal recessive or dominant (COL4A3 or COL4A4).
  • “Can’t see, can’t pee, can’t hear a bee” (ocular disturbance, isolated hematuria, and sensorineural hearing loss)
  • Typically with isolated hematuria at a young age. However, progresses to proteinuria and kidney failure in adulthood. 
  • On Kidney biopsy, the light microscopy can look normal at the early stages.
  • On EM, the GBM can look diffusely thin early in the disease. Later, the GBM has irregular appearance, alternating between thick and thin areas in a so-called  “basket-weave” appearance. 
  • No immune complexes are seen on IF. 

IgA Nephropathy 

  • GN caused by IgA deposition in the mesangial areas.
  • Can have a variable presentation and kidney biopsy: could present as isolated hematuria and mild mesangial expansion all they way to diffuse proliferative disease, glomerulosclerosis, and rarely cellular crescents. 
  • Shares features with Henoch-Schonlein Purpura (hematuria, recent viral URI, purpuric rash, abdominal pain).

Post-infectious Glomerulonephritis, including Post-streptococcal Glomerulonephritis (PSGN) 

  • Type III Hypersensitivity reaction (immune complex deposition of IgG or IgM in the glomerular membrane).
  • Decreased C3 due to consumption/activation of complement.
  • With PSGN, it occurs 2-3 weeks after Strep pyogenes (GAS) infection as cola colored urine, hypertension, and periorbital edema.
  • Can happen with many other infections; don’t think this is just a streptococcal thing!
  • Hypercellular, inflamed glomeruli on H&E.
  • “Lumpy-bumpy” Immune complex deposition under epithelial cells.
  • Granular IF and subepithelial ‘humps’ on EM.

Membranoproliferative Glomerulonephritis (MPGN)

  • This is the confusing one because it can present many ways: either microscopic hematuria with variable proteinuria (up to the nephrotic syndrome!), or gross hematuria/nephritis. In other words, it’s the disease that will have features of nephritic and nephrotic syndromes combined. (It can ‘do anything’).
  • It is typically secondary to other disease processes like Hepatitis B & Hepatitis C, Cryoglobulinemia, and some cancers like CLL.
  • Key word on the path: “Tram track appearance” on H&E, this means the process is slow enough that cells are laying down a new layer of GBM and mesangial cells can sometimes be seen squeezing between the two GBM layers.  
  • There is immune complex deposition leading to a thick GBM.
  • On immunofluorescence there is Granular staining for IgG and Complement (C3). 

Lupus Nephritis

  • Lupus can do lots of stuff in the kidney. If a patient has hematuria or proteinuria, you will always be correct to say “Lupus Nephritis” on the DDX.
  • Type III Hypersensitivity reaction
    • Immune complex deposition of IgG, IgA, or IgM in the glomerulus.
      • These complexes can deposit in the mesangium or capillary loops.
  • Key word: “full house” of Immunofluorescence staining. In other words, everything is being deposited: polyclonal IgG, IgA, IgM, C3, and C1q. 
  • Immune complexes activate complement, recruit inflammatory cells.
  • There is decreased C3 and C4 due to consumption/activation of complement.
  • On kidney biopsy, we can determine which class of Lupus nephritis is present:
    • Class I: Only mesangial deposits, everything else normal.
    • Class II: Mesangial deposits and mesangial hypercellularity.
    • Class III: Inflammatory injury to <50% of the glomeruli, this could be cellular crescent formation, fibrinoid necrosis, or subendothelial immune deposits.
    • Class IV: same as III but affecting >50% of the glomeruli.
    • Class V: Features of Membranous Nephropathy (See the Nephrotic Syndrome post).
    • Class VI: Advanced glomerulosclerosis. In other words, the ship has sailed and therapy is not likely to be effective.

Anti-GBM Disease

  • If isolated to the kidney, we call it Anti-GBM disease.
  • When it involves kidney AND lung, it is Goodpasture Syndrome.
  • Type II Hypersensitivity reaction (immune reaction against cellular antigens or extracellular matrix).
  • Anti-GBM antibodies are against Type IV collagen of basement membrane.
  • Linear IgG staining on immunofluorescence (looks like a continuous ribbon).

ANCA Vasculitis

  • Autoimmune disease where autoantibodies (anti-neutrophilic cytoplasmic antibodies) direct neutrophils to auto-activate and attack tissues.
  • The autoantibodies are directed against neutrophils, NOT the kidney. So, there will be no staining for immune complexes on kidney biopsy (“pauci-Immune”)
  • This category contains other diseases: 
    • Granulomatosis with polyangiitis
      • Involves the nasopharynx, lungs, and kidneys and has a positive c-ANCA.
    • Microscopic Polyangiitis
      • Involves the skin, kidneys, lungs, nerves and has a positive p-ANCA
  • When it only affects the kidney, we call it “Renal-limited ANCA vasculitis.”

Rapidly Progressive Glomerulonephritis (RPGN)

  • This is really just a generic term for any nephritic process that is acute and rapidly injuring the kidney. 
  • Can be caused by many renal diseases: typically anti-GBM disease, ANCA vasculitis, Lupus Nephritis, or Post-infectious GN. 
  • When it’s rapidly progressing, you’re more likely to see crescentic glomerulonephritis on biopsy (crescents comprised of fibrin and macrophages).

Check out NephSim for some practice cases!

Author:

Danae Olaso, MS2

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s