Renal Vascular Diseases

Question 1

What are the common findings in renal vascular dz?

Answer 1

Microangiopathic hemolytic anemia

Thrombotic microangiopathy

Coagulation

Damage to endothelium

Platelet count falls

Signs of intravascular hemolysis: i.e. LDH high

Question 2

Hemolytic Uremic Syndrome: what causes it? pathogenesis?

Answer 2

Secondary to shiga toxin after E. coli infection

Toxin: A subunit binds ribosome, inhibits protein synthesis

5B subunits bind glycolipid receptors gb3 on surface of colonic epithelium, endothelium, and WBCs

Also causes release of cytokines and vWF

For the kidneys– damage to the endothelium causes microangiopathic hemolytic anemia

Question 3

Hemolytic Uremic syndrome: histological findings

Answer 3

Fibrin/RBC thrombi in glomerulus

Cortical necrosis

Necrotic tubules

No immune deposits, but you see fibrin deposits on immuno stain

Widening of subendothelial space in less severe cases

Question 4

Hemolytic uremic syndrome: typical lab values

Answer 4

Low platelets

High creatinine

High LDH

Question 5

For those with E. coli infection, which factors put you at a higher risk of developing HUS?

Answer 5

Antibiotics

Bloody diarrhea

Fever, vomiting

Leukocytosis

<5 yo

females

Question 6

What is the treatment and course of HUS?

Answer 6

Supportive treatment (antibiotics are controversial)

Outcome of childhood HUS:
50% dialysis
75% transfusions
25% neuro sx- CVA, sz, coma
3-5% die in acute phase
long term renal dysfunction common
3-18% ESRD
10-40% low GFR, proteinurea, chronic renal failure, high bp

Duration of anuria predicts dysfunction

Question 7

Atypical hemolytic uremic syndrome i.e. diarrhea negative hemolytic uremic syndrome: cause/pathogenesis?

Answer 7

It’s a disease of the complement system: continuous activation of the alternate complement system due to genetic defects and/or antibodies that alter the action of these complement regulatory proteins

Factors involved: Factor H, Factor I, or MCP

Question 8

Atypical hemolytic uremic syndrome: treatment

Answer 8

• *Eculizumab**: humanized antibody that binds C5 with high affinity & blocks its activity
• leads to normal platelet count & normal LDH
• elimination of plasma exchange/infusion
• no new dialysis
• proximal functions of complement remain intact

Liver transplant along with kidney transplant
**Replaces the missing complement inhibitor so that you don’t get a recurrence in the transplant patient

Question 9

TTP: cause/pathogenesis?

Answer 9

Reduced levels of ADAMTS13 (enzyme that cleaves vWF) –> huge vWF multimers –>

Can be familial (mutations) or acquired (autoantibody)

Can be single episode or relapsing

Female 2: Male 3, Peak in 3rd decade

CNS & other extrarenal signs often predominate

Acute renal failure (more common in this dz than in the others), microangiopathic hemolytic anemia, thrombocytopenia

** Systemic manifestations are more common in TTP than in HUS **

Question 10

TTP: lab values?

Answer 10

Smear shows microangiopathic hemolytic anemia
- schistocytes

Low platelets

Low hematocrit

Normal PT and normal PTT

Question 11

TTP: treatment?

Answer 11

Plasma exchange = Plasmapheresis

Removes the bad stuff i.e. if you have an antibody against ADAMTS13

Adds back good stuff i.e. VWF, platelets

Question 12

TTP: histological findings?

Answer 12

Glomeruli and arteriole with thrombus in the middle

Thrombi made of platelets and RBC’s

Entrapped RBCs in arteriole wall = multiple layers of myofibroblasts

Feature of both actue thrombosis and chronic organizing

Question 13

Antiphospholipid Antibody Syndrome aka anticardiolipin syndrome - cause?

Answer 13

Antibody (mainly IgG, could also be IgM, IgA) against negatively charged phospholipids

Question 14

What lab findings for antiphosphilipid antibody syndrome?

Answer 14

Positive for antiphospholipid antibodies

• *Prolonged PTT, normal PT**
• this is bc the antibody interferes with the PTT assay in vitro, it has nothing to do with what happens in vivo

Antinuclear antibody (ANA) +

Anti-DNA

Low complements

False positive VDRL

Hypertension, active urinary sediment, elevated crat, proteinurea, nephrotic syndrome: seen in pt’s at biopsy

Question 15

Antiphospholipid andibody syndrome: pathological/histological findings?

Answer 15

Acute and chronic thrombotic angiopathy

Glomeruli show ischemic changes: global wrinkling of glomerular basement membranes, tuft retraction, cystic dilation of Bowman’s space

Glomeruli have intracapillary fibrin & RBC thrombi

Arterioles also have fibrin & RBC thrombi

Mesangiolysis = loose, widened mesangium

Subactue/chronic changes: arteries show widespread luminal narrowing with mucoid intimal fibroplasia and entrapped RBCs

Question 16

Which antibdies can you find in antiphospholipid antibody syndrome?

Answer 16

IgG, IgM, IgA against negatively charged phospholipids that includes:

Lupus anticoagulant: Abs that proling lipid-depending coagulatoin tests, interfere with phospholipid of the prothrombin activator complex

Anticardiolipid antibodies: bind cardiolipin (phospholipid antigen used in tests for syphilis) –> false positive VDRL

** all have a procoagulant effect in vivo

Question 17

Which underlying conditions are associated with antiphospholipid antibodies?

Answer 17

Systemic lupus erythematosus
- full blown lupus

Lupus-like syndrome
- mostly young women

Primary anti-phospholipid antibody syndrome
- mostly older men

Question 18

What are the clinical manifestations of anti-PL ab syndrome?

Answer 18

Recurrent arterial and venous thromboses

Placental thromboses and recurrent abortions

Livedo reticularis

CNS complications

Pulmonary hypertension

Chronic kidney failure

Hypertension

Rarely: catastrophic APL syndrome = actue kidney failure+

Question 19

What is livedo reticularis?

Answer 19

Commonly seen in antiphospholipid antibody syndrome

Question 20

What external manifestations can you seein antiphospholipid antibody syndrome?

Answer 20

CNS dz

DVT

MI

Pulm embolism

Livedo reticularis

Adrenal dz

Aortic thrombosis

Bowl infarction

Miscarriage

Question 22

What is the treatment for antiphospholipid antibody syndrome? What’s the course of the dz?

Answer 22

Treat with anticoagulation therapy

Few have true systemic lupus erythematosus (SLE)

Half have improved renal function

Most have remission of nephrotic syndrome

27% worsening function

15% ESRD

Question 23

Renal atheroembolic dz + hypertensive arterionephrosclerosis- what is it?

Answer 23

• *Renal atheroembolic dz**: cholesterol emboli in small vessels of kidney: frequent complication of pt’s who have severe atherosclerosis & get an invasive procudure i.e. vascular procedures like putting a stent in
• has the same effect as a thrombus: blocks flow into kidneys

Hypertensive arterionephrosclerosis: hypertension –> changes in the kidney: shrunken kidney, finely granular surface grossly, thin renal cortex, normal medulla, thickenend walls of arterioles, narrowed vessels –> chronic ischemia –> wrinkling of mesangium & fibrosis & necrosis

Question 24

What are the clinical features of renal atheroembolic dz?

Answer 24

Acute renal failure

Rash, eosinophilia

Other organs can be involved: skin, GI tract

May develop renal infarction in severe cases

Chronic ischemic nephropathy more commonly