Home   Chapter Home   Jobs   Conferences   Fellowships   Books



Advertisement

Kidney non-tumor

Associated with systemic conditions

Hemolytic uremia syndrome / thrombotic thrombocytopenic purpura (HUS/TTP)


Reviewers: Nikhil Sangle, M.D. (see Reviewers page)
Revised: 8 December 2014, last major update November 2012
Copyright: (c) 2003-2014, PathologyOutlines.com, Inc.

General
=========================================================================

● Thrombosis in capillaries and arterioles throughout the body, microangiopathic hemolytic anemia, thrombocytopenia, renal failure with platelet-fibrin thrombi in interlobular renal arteries and glomeruli, necrosis and thickening of vessel walls
● Morphologic changes resemble malignant hypertension, but usually no pre-existing hypertension
● HUS and TTP are usually considered part of clinical spectrum, in which disease manifestations depend on distribution of microangiopathy (but see Arch Pathol Lab Med 2003;127:834)
HUS: fibrin / red cell rich thrombi, largely confined to kidney and often severe; usually no pancreas, adrenal gland, brain or heart involvement
● Atypical HUS: due to excessive complement activation in microvasculature; inherited and acquired abnormalities affecting components of the alternative complement pathway are found in 60% (Hematology Am Soc Hematol Educ Program 2011;2011:15)
TTP: platelet rich thrombi in myocardial arteries; also pancreas, kidney, adrenal gland or brain; usually no permanent kidney damage
Pathophysiology: endothelial injury by toxins (certain strains of E. coli 0157:H7 producing shiga-like toxin, Hum Pathol 1988;19:1102)) or antibodies and activation cause intravascular thrombosis and platelet aggregation, which causes vascular obstruction and vasoconstriction, affects predominantly the renal vessels; TTP occurs due to enhanced platelet aggregation, e.g., metalloproteinase activity causing abnormal vWF-cleavage

Childhood HUS
=========================================================================

● 75% of cases occur after shiga-toxin producing E coli O157:H7 infection (also called verocytotoxin because it damages Vero cells in culture)
● Main cause of childhood acute renal failure
● Usually infants and young children, may occur at any age
Symptoms: sudden onset of influenza, bleeding (hematemesis or melena), severe oliguria, hematuria, microangiopathic hemolytic anemia, neurologic changes in 1/3 and hypertension in 50%
Pathogenesis: related to Shiga-like toxin, which promotes adhesion of white blood cells to endothelium; also increases endothelin and decreases nitrous oxide production, causing vasoconstriction

Adult HUS/TTP
=========================================================================

● Poor prognosis with high mortality due to CNS disease or uncontrollable bleeding; survivors develop chronic renal failure
Causes: typhoid fever, E. coli (enterohemorrhagic strains), viral infections, shigellosis, antiphospholipid syndrome (primary or secondary to SLE), postpartum or after placental hemorrhage, vascular renal diseases such as scleroderma or malignant hypertension, drugs (mitomycin C, cyclosporine, bleomycin, cisplatin) and various malignancies
● Lupus patients may have more severe disease (Am J Med Sci 2009;338:343, Nephron Clin Pract 2009;112:c177)

Idiopathic HUS/TTP
=========================================================================

● More common in women age 40 years or less; mortality 50%
Symptoms: CNS involvement dominant (fever, neurologic symptoms), hemolytic anemia, thrombotic thrombocytopenic purpura and renal involvement in only 50% (thrombi in glomerular capillaries and afferent arterioles)

Case reports
=========================================================================

● 17 year old girl with TTP and ANCA-associated vasculitis (Pediatr Nephrol 2011;26:1317)
● 18 year old man with C1q nephropathy with acute HUS (Saudi J Kidney Dis Transpl 2012;23:556)
● 23 year old man with TTP-HUS and post-ERCP pancreatitis (Eur J Gastroenterol Hepatol 2011;23:825)
● 32 year old pregnant woman with renal grant, acute T-cell-mediated rejection and TTP (Clin Transplant 2010;24 Suppl 22:66)
● 39 year old man with resistant TTP that presented with concomitant severe rhabdomyolysis (Int J Gen Med 2011;4:687)
● 48 year old woman presenting with myocardial infarction (J Cardiovasc Dis Res 2012;3:167)
● Association with mitomycin in four patients (Arch Pathol Lab Med 1984;108:959)
● Death due to diffuse myocardial necrosis (Arch Pathol Lab Med 1999;123:937)

Treatment
=========================================================================

● HUS: supportive therapy (Am J Kidney Dis 2009;53:259)
● TTP: plasmapharesis, steroids; possibly Rituximab (anti-CD20) or Eculizumab (anti-C5) in severe cases (Dtsch Med Wochenschr 2010;135:71, Hong Kong Med J 2009;15:201, Am J Kidney Dis 2012;59:707)
● TTP relapse occurs in 36%, death in 4% (Transfusion 2010;50:868)

Gross description
=========================================================================

● Patchy or diffuse renal cortical necrosis

Micro description
=========================================================================

Early:
● Fibrin deposits in capillary lumina
● Fibrinoid necrosis of larger vessels, thrombosis and endothelial cell proliferation in small arteries and arterioles
● Ischemic changes in glomeruli with endothelial swelling and capillary luminal narrowing
● Expanded mesangial thrombi appear red on trichrome stain, thrombi are not essential for a pathologic diagnosis

Later:
● Intense basophilic thickening in small arteries and arterioles which restricts lumen, aneurysmal dilatation and proliferation of arterioles at hilus of glomerulus
● May have double contour of glomerular basement membrane

Micro images
=========================================================================


   
HUS: kidney


Atypical HUS: kidney


TTP: kidney


TTP: lesions of myocardium, adrenal gland, CNS, pancreas, other

Virtual slides
=========================================================================



DIC and microthrombi

Immunofluorescence
=========================================================================

● Demonstrates fibrin and fibrinogen, irregular staining for IgM, C3 and C1q, negative for IgA and IgG

Electron microscopy description
=========================================================================

● Widening of subendothelial space, filled with pale, finely particulate or fibrillar material (fibrinogen) and intraluminal platelet microthrombi causing narrowing of capillary lumen
● Swollen mesangial cells with numerous phagolysosomes
Later: mucinous, onion skin-type obliterating endarteritis

Differential diagnosis
=========================================================================

Malignant hypertension: similar vascular lesions but different clinical presentation
Systemic sclerosis: similar vascular lesions but different clinical presentation
Antiphospholipid antibody syndrome: thrombosis in veins, arterioles, capillaries with glomerular subendothelial expansion

End of Kidney non-tumor > Associated with systemic conditions > Hemolytic uremia syndrome / thrombotic thrombocytopenic purpura (HUS/TTP)

Ref Updated: 7/27/12


This information is intended for physicians and related personnel, who understand that medical information is often imperfect, and must be interpreted in the context of a patient's clinical data using reasonable medical judgment. This website should not be used as a substitute for the advice of a licensed physician.

All information on this website is protected by copyright of PathologyOutlines.com, Inc. Information from third parties may also be protected by copyright. Please contact us at copyrightPathOut@gmail.com with any questions (click here for other contact information).