Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations

Table 1 Classification of Hemolytic uremic syndrome, thrombotic thrombocytopenic purpura and related disorders

Etiology identified	Etiology unknown
HUS infection-induced	HIV infection
(1) Shiga and shiga-like toxin producing bacteria, Enterohemorrhagic Escherichia Coli, Shigella dysenteriae type 1 (2) Streptococcus pneumoniae
HUS induced by disorders of complement regulation	Malignancy, cancer chemotherapy, ionizing radiation
(1) Genetic (2) Acquired
ADAMTS13 deficiency (1) Genetic (2) Acquired	Calcineurin inhibitors and transplantation
Defective cobalamin metabolism	Pregnancy, HELLP syndrome, contraceptive pill
	Systemic lupus erythematosus, anti-phospholipid antibody syndrome
	Glomerulopathy
	Drug induced

HIV: human immunodeficiency virus; HELLP: Hemolysis elevated liver enzymes low platelets; HUS: Hemolytic uremic syndrome.

Table 2 Development of Shiga-toxin-associated hemolytic uremic syndrome

Pathogenetic steps	Clinical
Ingestion of Escherichia Coli through contaminated food or patient to patient transmission or transmission from animal to man	Colonization of the gut
Diarrhoea	Local tissue damage
Bloody diarrhoea	Systemic toxinemia
Generation of host cytokines and chemokines	Endothelia cell damage, activation of local thrombosis in kidneys and in other organs
Renal involvement→ HUS	Damage to glomerular endothelial cells, arteriolar damage, mesangial cell activation/damage, podocyte injury, tubular damage
Renal Insufficiency	Acute renal failure
	Chronic renal failure
	Arterial hypertension, proteinuria, hematuria

HUS: Hemolytic uremic syndrome.

Table 3 Gene mutation rate of different complement factors according r-hemolytic uremic syndrome registries data

Abnormality	Gene locus	Atypical HUS rate
Factor H	CFH (RCA:1q32)	11%-29%
Membrane co-factor protein	MCP (RCA)	3%-17%
Factor I	CFI (4q25)	2%-17%
C3	C3 (19p13)	2%-17%
Factor B	CFB (6p21)	0%-5%
Thrombomodulin	THBD (20p11)	0%-5%
Anti factor H autoantibodies		4%-13%

HUS: Hemolytic uremic syndrome.

Table 4 Main clinical characteristics of patients with atypical hemolytic uremic syndrome according complement abnormality

Gene	Atypical HUS incidence	Risk of death or renal failure within 1 yr	Risk of relapse	Relapse after transplantation	Plasma-therapy indication
CFH	20%-30%	50%-70%	50%	75%-90%	Yes
CFI	4%-10%	50%	10%-30%	45%-80%	Yes
MCP	5%-15%	0%-6%	70%-90%	< 20%	???
C3	2%-10%	60%	50%	40%-70%	Yes
CFB	1%-4%	50%	100%	100%	Yes
THBD	3%-5%	50%	30%	1%	Yes
Anti-CFH Ab	6%	30%-40%	40%-60%	Yes	Yes

HUS: Hemolytic uremic syndrome