Kidney Transplantation (Pathophysiology)

ID the most common solid organ transplant?

1. Liver

2. Heart

3. Kidney

4. Pancreas

5. Lung

Kidney

Which donor kidneys generally last longer, living or deceased?

living

What are the top 3 (in order) leading causes of ESRD, which can lead to kidney transplantation?

1. DM

2. HTN

3. glomerulonephritis

The physiologic consequence of transplantation ______ quality of life and survival when compared with _______

improved, dialysis

What improves immediately after transplantation?

GFR

What improves days after transplantation?

SCr, BUN

What improves weeks after transplantation?

anemia, calcium/phosphate imbalance (CKD), altered lipid profiles

Why does SCr and BUN not improve immediately after transplants even though they are used to measure kidney function?

SCr and BUN are waste products that the kidney is tasked with filtering out. They are not only affected by the extent of kidney function, which leads to the lag in SCr and BUN after any change to the kidneys.

Correctly order the sequence of events of kidney transplant rejection:

1. initiation of immune effector mechanisms

2. recognition of histocompatibility (MHC) differences between donor and recipient

3. graft destruction

4. recruitment of activated lymphocytes

2, 4, 1, 3

The first step of graft rejection: recognition of _________ (___) differences between donor and recipient

histocompatibility (MHC)

The second step of graft rejection: recruitment of activated __________

lymphocytes

The third step of graft rejection: initiation of ______________________

immune effector mechanisms

The fourth step of graft rejection: _____ destruction

graft

In the activation of T cells, what is the preliminary step (step 0)?

MHC II molecule complexes recognizes by T cell recognition complex (TCR)

In the activation of T cells, what is the first step?

A costimulatory signal initiates signal transduction

In the activation of T cells, what is the second step?

Activation of calcineurin and dephosphorylation of NFAT

In the activation of T cells, what is the third step?

NFAT facilitates IL-2 gene transcription

In the activation of T cells, what is the fourth step?

IL-2 activates IL-2 receptor

In the activation of T cells, what is the fifth step?

IL-2 receptor signaling pathway

In the activation of T cells, what is the sixth step?

T cell proliferation and production of cytokines specific to T cell

Which step of T cell activation is Box A

step 0: MHC II molecule complexes recognizes by T cell recognition complex (TCR)

Which step of T cell activation is Box B

step 4: IL-2 activates IL-2 receptor

Which step of T cell activation is Box C

step 6: T cell proliferation and production of cytokines specific to T cell

Which step of T cell activation is Box D

step 5: IL-2 receptor signaling pathway

Which step of T cell activation is Box E

step 2: Activation of calcineurin and dephosphorylation of NFAT

Which step of T cell activation is Box F

step 3: NFAT facilitates IL-2 gene transcription

Which step of T cell activation is Box G

step 1: A costimulatory signal initiates signal transduction

What is hyperacute rejection?

can take minutes, donor-specific antibodies are present in the recipient

What is acute cellular rejection (ACR)?

can take few months, alloreactive T cells that appear in the circulation and infiltrate the allograft through the vascular endothelium

What is antibody-mediated rejection (AMR)?

can take months to years, vascular or humoral rejection characterized by the presence of antibodies directed against HLA antigens on teh donor vascular endothelium

What is chronic rejection?

can take months to years, cell and/or antibody mediated rejection; irreversible by immunosuppressants (major cause of graft loss)

What is the number one cause of ESRD?

DM

What kind of rejection irreversible by immunosuppressants?

1. Antibody-mediated rejection (AMR)

2. Acute cellular rejection (ACR)

3. Hyperacute rejection

4. chronic reaction

chronic rejection

How long after transplantation does GFR improve?

minutes

How long after transplantation does SCr improve?

days

How long after transplantation does BUN improve?

days

How long after transplantation does anemia improve?

weeks

How long after transplantation does Ca/Phos imbalance (CKD) improve?

weeks

How long after transplantation does altered lipid profiles improve?

weeks