Renal Transplantation Flashcards
What is the recurrence rate of FSGS after renal transplantation?
30% (1 in 3) on first transplant. Up to 70% with the second
What is the most common de novo nephritis to occur in the transplanted kidney?
Membranous occurs in 1 - 2%
What is the most common nephritis (in Australia) that leads to transplant?
IgA disease
What is the recurrence rate of mesangiocapillary disease?
15 - 35% with type 1 90% with type 2, but usually clinically benign
What are the most important HLA for renal transplantation? (in order) and what chromosome are they on?
They are on chromosome 6 DR > B > A
What are the long term risks for a live donor? (kidney)
There is apparently no increase in mortality, no increase in prevalence of hypertension and no increase in glomerular sclerosis
The next slide is important to understand a concept about immunosuppression for transplants. Just stimulating a T cell receptor will not lead to lymphocyte proliferation and cytokine response. There is also a costimulatory signal which is essential for response.
This is important because newer immunosuppressant agents target this costimulatory response. Next picture demonstrates this.
This next slide is an example of the targets for some MAb used in stopping rejection of renal transplantation.
What are some of the causes of early renal transplant failure?
Ischaemia - ATN
immunosuppressant toxicty - cyclosporin and tacro
pre-renal - hypovolaemia
“dead kidneys” (non functioning on transplant)
vascular occlusion
post-renal - obstruction
Hyperacute rejection - very early and uncommon - requires antibodies against donor to be present prior to transplantation
What are the histological signs that one might see in acute renal transplant rejection?
Firstly, there is non-specific cellular infiltrate
Secondly, we see tubulitis (evidence of cellular rejection) and vasculitis (vascular rejection)
this is clinically important, because cellular rejection is less severe. Vascular requires heavy suppression.
What is the treatment of acute rejection?
Initially,
heavy steroid burst (methyl pred)
—- if steroid resistant or vasc rejection, use T cell depletion—
Anti-thymocyte globulin (for polyclonic T cell depletion)
OKT-3 (monoclonal T cell depletion)
Tacrolimus
What is chronic allograft nephropathy?
now also called “interstitial fibrosis and tubular atrophy not otherwise specified”!
it is a chronic fibrosing condition leading to eventual failure. iut is immune or non-immune injury leading to stereotyped T cell and cytokine response in the kidney leading to more inflammation!
it must be differentiated from the following:
Late acute rejection
drug toxicity (e.g. cyclosporine)
urological causes (obstruction)
vasc obstruction
recurrent GN
Where do steroids, MMF, Aza, sirolimus work?
What about cyclosporin and tacrolimus?
what is the standard renal transplant drugs?
The most common is the triple therapy. Each from a slightly different class.
- calcineurin inhibitor - tacrolimus or cyclosporin
- mycophenolatae
- prednisolone
what are the side effects of mycophenolate?
increased GI symptoms compared to azathioprine. This is probably related to the metabolites, not the local drug effect. (happens with IV therapy too)
possible increase in PTLD and CMV
How does cyclosporine work?
what SE?
it is a calcineurin inhibitor. It binds to cyclophilin in the lymphocyte and inhibits calcineurin.
it is nephrotoxic
SE: hair growth (hirsutism), gum hyperplasia, HTN, tremor
occasionally diabetes
How does tacrolimus work?
It is a calcineurin inhibitor too.
it binds to the FK-binding protein and inhibits calcineurin.
it is also a nephrotoxic agent.
It has less of the cyclosporine side effects (less of the hypercholesterolaemia, HTN), but does suffer more diabetes, neurotoxicity. It also causes low magnesium!
possibly 10 - 20% will get DM!
Are there any potential interactions with calcineurin inhibitors? Anything related to metabolism?
They are metabolised by Cyto P450 (3A4)
this means there is an interaction with diltiazem, verapamil, voriconazole, erythro/clarithromycin and grapefruit juice.
What are the M-TOR inhibitors?
They are now being called “proliferation signal inhibitors”
M-TOR = mammalian target of rapamycin
Sirolimus and everolimus are examples.
How does rapamycin (sirolimus) work?
this medication is super weird. It was scaped off a rock on Easter Island. It works similar to tacro (binds to a FK-binding protein) but instead of interfering with IL-2 synthesis, it BLOCKS IL-2 signalling pathway.
BIG SE: hyperlipidaemia and low platelets
What are the anti-T cell medications that we use in transplants?
what are their side effects?
Polyclonal anti-T-cell:
- anti-thymocyte globulin
monoclonal:
OKT-3
SE:
Early side effects include cytokine release (as the cells are just lysed, releasing all their goodness)
Late SE: opportunistic infections and PTLD
Are there any other MAb that one might use around the time of transplantation to minimise acute rejection?
We believe that IL-2 is the most important cytokine for T-LL proliferation.
We have created an antibody for the receptor of this cytokine (CD25)
The available agent is BASILIXIMAB (the basilix!!!) and it is used pre-theatre and day 4 as routine. Good for 3 - 4 months.
What does acute humoral rejection mean to you?
This means acute antibody mediated rejection.
Because of this, it would be reliant on B cells.
Because of this, THEORETICALLY, rituximab (an anti-B-cell) may be useful in treatment of rejection
How does CMV infection cause problems in renal transplantation?
It can cause fever, hepatitis, gastritis and pneumonitis.
Primary infection is most severe. Reactivation is typically less so. It is important to know about donor/recipient status of CMV exposure.
Usually we use prophylaxis now.
