Thrombotic microangiopathy after kidney transplantation: Expanding etiologic and pathogenetic spectra

Table 1 Etiology and classification of thrombotic microangiopathies

Primary TMAs
	Shiga toxin-producing E. Coli-associated HUS
	Thrombotic thrombocytopenic purpura
	Atypical HUS or complement-mediated
Secondary TMAs
	Infections including viral, fungal, and bacterial
	Drugs including immunosuppressants and chemotherapeutic agents
	Autoimmune diseases
	Malignant hypertension
	Malignancy
	Metabolic defects
	Pregnancy
	Transplantation, both hematopoietic stem cell transplantation and solid organ transplantation
	Disseminated intravascular coagulation
	Radiation

TMAs: Thrombotic microangiopathies.

Table 2 Etiology of post-transplant thrombotic microangiopathies

Recurrent TMA, rare (5%-10% of cases)

Mutations in complement regulatory factor genes [e.g., factor H, factor I, membrane cofactor protein, etc.]

Mutations in complement genes (e.g., C3)

TMA associated with autoantibodies (anti-factor H antibodies, anti-ADAMTS13 antibodies, antiphospholipid antibodies)

TMA associated with autoimmune diseases (scleroderma and systemic lupus erythematosus)

De-novo TMA, common (90%-95% of cases)

Associated with the type of donor and organ procurement procedure, e.g. Ischemia reperfusion injury

Drugs

I: Calcineurin inhibitors-associated TMA

II: Mammalian target of rapamycin inhibitors-associated TMA

Antibody-mediated rejection associated TMA

Infection-associated TMA

I: Viral, e.g. hepatitis C virus, parvovirus B19, and cytomegalovirus)

II: Fungal

III: Bacterial

Other rare causes, such as malignancy, other drugs, and pregnancy

ADAMTS13: A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13; TMA: Thrombotic microangiopathy.

Table 3 Morphological features of thrombotic microangiopathies

Active lesions
	1 Glomerular lesions (Light microscopy):
		Intraluminal thrombi
		Endothelial swelling or denudation
		Endothelial swelling or denudation
		Subendothelial space widening (bloodless glomeruli)
		Mesangiolysis
		Microaneurysms
	2 Arteriolar lesions:
		Intraluminal thrombi
		Endothelial swelling or denudation
		Intramural fibrin
		Fragmented red blood cells
	3 Arterial lesions:
		Intraluminal thrombi
		Intimal edema
		Myxoid intimal swelling
		Myocyte necrosis
		Intramural fibrin
		Fragmentation of red blood cells
Chronic lesions
	1 Glomerular lesions (Light microscopy):
		Double contours of peripheral capillary walls, with variable mesangial interposition
	2 Arteriolar lesions:
		Hyaline deposits
	3 Arterial lesions:
		Fibrous intimal thickening with concentric lamination (onion-skining)