RPGN

Question 1

Causes of RPGN

Answer 1

1. Anti-GBM antibody mediated crescentic GN
   o linear deposits of IgG and C3 on the GBM.
   o Seen in goodpasture syndrome.
   o Importantly, Plasmapheresis is effective
   therapy for anti-GBM antibodies driving RPGN.
   o Crescent proliferation occurs, but mesangial
   and endothelial proliferation is not significant
2. Immune complex mediated crescentic GN
   o Can occur as a result of any immune complex associated disease,
   SLE,
   IgA nephropathy and Henoch Schonlein purpura after non-specific upper respiratory infections
   Post-infectious RPGN, after specific group A strep, or sometimes S. aureus.
   Idiopathic IC mediated RPGN
   o Can be from in situ IC formation against planted antigens, or from circulating antigens
   o Involves crescent, mesangial, and endothelial proliferation.
3. Pauci-immune, ANCA associated crescentic GN
   o Occurs in the absence of anti-GBM antibodies or immune complex deposition (paucity of imune characteristics)
   o Usually, ANCA antibodies, Anti-neutrophil cytoplasmic antibodies are found in the serum.
   o It is thus often a component of Systemic Vasculitis syndromes
    microscopic polyangitis
    Wegener granulomatosis
    Churg-Strauss syndrome
   o It can also occur in isolation of these syndromes and is called idiopathic pauci-immune crescentic GN.

Question 2

Signs and symptoms of RPGN

Answer 2

Rapid loss of GFR, days/weeks/months

• Oliguria/Anuria
• Severe Azotemia, BUN, creatinine increase
• Na+ and H2O retention- periorbital edema
• Variable degrees of proteinuria
• Hypertension

Urinary sediments
RBC, leukocyte casts, dysmorphic RBCs.

Systemic symptoms
- Fever, especially Chronic fever or subfebrility.
Signs of vasculitis, arthritis, pneumonitis/hemoptysis

Question 3

What are the ANCA positive, pauci-immune RPGNs

Answer 3

Wegener’s Granulomatosis

Churg-Strauss syndrome

Microscopic polyangitis

Goodpasture may be.

Question 4

Granulomatosis with polyangitis, aka Wegener’s granulomatosis

Answer 4

Wegener’s granulomatosis is an c-ANCA/PR3-ANCA positive, necrotizing vasculitis that affects the nose, lungs, kidneys and other organs. Due to its end‐organ damage, it is life threatening and requires long term immunosuppression.
triad of:
1. Acute necrotizing granulomas of the upper or lower respiratory tract (ear, nose, sinuses,
throat, and lungs) – Large nodular consolidations on chest x-ray.
2. Necrotizing (ulcerating) or granulomatous vasculitis affecting small to medium‐sized vessels (capillaries, venules, arterioles and arteries), most prominent in the lungs and upper airways.
3. Renal disease in the form of focal, segmental, necrotizing, often crescentic,
glomerulonephritis.

Skin rash in 30-50% ulcerative or petechia/purpura

Question 5

Indications for kidney biopsy

Answer 5

Nephritic or syndrome

Nephrosis or proteinuria > 1-2g/day with decreased GFR

Glomerular hematuria and proteinuria > 0.5g/day

AKI of unknown etiology with ATN ruled out.

Post-transplantation with renal dysfunction.

Question 6

Contraindications for kidney biopsy

Answer 6

Patient uncooperative

High bleeding risk

Unmanaged hypertension >140/90

Anemia, Hb < 100g/l

Hydronephrosis or acute pyelonephritis

Polycystic kidney

End stage, small fibrotic kidney.

Question 7

IgA nephropathy aka

Answer 7

Berger disease

If there are systemic lesions outside of the kidney
–>
Henoch-Schonlein purpura.

Question 8

IgA nephropathy microscopic description

Answer 8

Circulating IC deposits stick in the mesangium. Causing complement activation, and mesangial proliferation and infiltration.

Question 9

IgA nephropathy prognosis and treatment

Answer 9

About 35% progress to dialysis in 20 years, but can also cause RPGN.

treatment: Based on proteinuria

All patients:
ACE or ARBs to manage hypertension

High proteinuria:
2-3 years of steroids tapered down.

If there are crescents or progressive GFR decline:
Steroids plus cyclophosphamide