Fogo, Ch. 20 - Allograft rejection

Question 1

What diseases affect the transplant kidney (in addition to primary disease?)

Answer 1

Alloimmune disease, drug toxicity, infection, ischemia, and obstruction.

Question 2

When does acute cellular rejection occur? In how many cases?

Answer 2

Affects 10% of transplants, usually 1-6wks post-transplant.

Question 3

Describe the glomerular LM findings in ACR.

Answer 3

Some cases can have glomerulitis. CMV promotes a rare, disastrous variant.

Question 4

Describe the interstitial LM findings in ACR.

Answer 4

Tubulitis, especially in cortex (>25% involvement is diagnostic of grade I). pleomprhis interstitial infiltrate, edema.

Question 5

Describe the vascular LM findings in ACR.

Answer 5

Endothelialitis (defining of grade II), usually affecting larger arteries and rarely transmural. Necrotizing arteritis notes grade III.

Question 6

What are the IF findings in ACR?

Answer 6

Interstitial fibrin, C4D in peritubular capillaries (notes AMR).

Question 7

What are the EM findings in ACR?

Answer 7

Not very helpful; endothelial injury/reactivity and platelet/fibrin aggregates.

Question 8

Contrast the clinical features of AMR with ACR.

Answer 8

AMR is acute and less responsive to steroids.

Question 9

What are some risk factors for AMR?

Answer 9

Elevated PRA, prior transplant, positive crossmatch

Question 10

What are the LM findings in AMR?

Answer 10

Variable; some have just acute tubular injury or even no LM findings, some have capillary neutrophils or even arterial fibrinoid necrosis and thrombosis.

Question 11

What are the IF findings in AMR? What do they signify?

Answer 11

C4d in peritubular capillaries. Notes local activation of the classical complement pathway (derived from C4b).

Can also have IgG/IgM in fibrinoid necrosis.

Question 12

What is the pathophysiology and presentation of hyperacute rejection?

Answer 12

Preformed anti-HLA or -ABO antigens, resulting in immediate and irreversible graft failure.

Question 13

What are the pathologic findings in hyperacute rejection?

Answer 13

Same as in AMR (PMNs, C4d). IgM antibodies are seen if the reaction is anti-ABO.

Question 14

How long do kidney grafts last? What contributes to their failure?

Answer 14

Around 9 years for DDKT, over 20 for HLA-matched sibling.

Usually due to chronic rejection, CNI toxicity, vascular disease, and chronic infection and/or reflux.

Question 15

What are the glomerular LM findings in chronic AMR?

Answer 15

Transplant glomerulopathy: Doubling of GBM, mesangial hypercellularity, endocapillary monocytes.

Question 16

What are the vascular LM findings in chronic AMR?

Answer 16

Transplant vasculopathy: Intimal thickening with foamy macrophages, sometimes adventitial infiltrate. Spares arterioles?

Question 17

What are the IF findings in chronic AMR?

Answer 17

Usually low-level C4d in PTCs and glomeruli. Maybe some globular Ig and vascular fibrin.

Question 18

What are the EM findings in chronic AMR?

Answer 18

Foot process effacement, mesangiolysis. Loss of endothelial fenestrations and multilayering of BM.

Question 19

Describe the staging of chronic AMR.

Answer 19

I: Evidence of humoral response without graft dysfunction.

II: C4d deposition, still no damage.

III: Clinical evidence of graft dysfunction.

Question 20

What should be considered in the differential diagnosis for chronic AMR?

Answer 20

De novo glomerulonephritides, CIT, post-transplant lymphoproliferative disease.