Glomerular Disease

Question 1

mesangial cells

Answer 1

smooth muscle-like cells that sit between the capillary loops

produce matrix and are required for support of the capillary loop structure

Question 2

slit diaphragm

Answer 2

an extracellular structure that its in the 25-60 nm wide filtration slits created by the podocyte foot processes

Question 3

glomerular endothelial cells

Answer 3

cells that line the inner surface of the glomerular capillaries and form an anticoagulant barrier between blood and tissues

glomerular ECs have a large fenestrated area constituting 20-50% of the entire endothelial surface

Question 4

glomerular endothelial fenestrae

Answer 4

plasma membrane lined trans-cellular pores 60-100

Question 5

NPHS1 (nephrin) mutation

Answer 5

leads to congenital nephropathy of the Finnish Variety (presents in infants)

Question 6

NPHS2 (podocin) mutation

Answer 6

autosomal dominant steroid resistant focal segmental glomerulosclerosis (present in infants)

Question 7

ACTN4 (alpha actinin 4) mutation

Answer 7

autosomal dominant focal segmental glomerulosclerosis (presents in adults)

Question 8

Why is it important to know when kidney failure is caused by a genetic mutation?

Answer 8

mutations in architectural proteins will not respond well to systemic therapies

however, the same disease will not occur after kidney transplantation

occasionally patients will develop antibodies to the “wildtyp, normal” protein expressed by the transplanted kidney such as anti-nephrin antibodies

Question 9

What is the role of VEGF A in podocyte development?

Answer 9

factor secreted by podocytes and acts on receptors expressed by adjacent glomerular endothelial cells

promotes endothelial cell survival, fenestration, and proliferation

when VEGF levels are reduced, this may lead to endothelial cell swelling and cell death

this in turn promotes the formation of microscopic thrombi int he glomerular capillaries which can clog the glomerulus and lead to kidney failure

Question 10

What are some of the side effects of anti-VEGF therapies?

Answer 10

reduction of podocyte VEGF leads to thrombotic microangiopathy

can also happen in pregnant patients with preeclampsia, where the placenta makes large quanities of FLT1, which is a naturally occurring anti-VEGF molecule

Question 11

Nephrin

Answer 11

a very large protein with an extracellular domain that interacts with protein on adjacent podocytes

interacts with a protein called Nck to promote actin polymeraization and podocyte foot process formation

Nck proteins link slit diaphragm to cytoskeleton of podocyte