Kidney transplantation, a modern miracle. Intro, immunology, immunosuppression. 60 mins. Mainly principles, not details of surgery or of pre- or post-op care. Pairs with a tutorial – see below.
Neil Turner, Professor of Nephrology.
This page pairs with a tutorial: a session at which you get some more information, and work in groups through a series of real clinical scenarios. These will be core material and extensions, and cover likely exam questions. Make sure you work through this page in advance.
How much do I need to know? Undergrads in Medicine and some others need some understanding of the immunology behind transplantation, which is also relevant to understanding of autoimmune diseases. Patients on immunosuppressive agents for other reasons share susceptibility to a range of usual and unusual infections.
A short background to transplantation
The first successful human transplant in 1954 was between identical twins, because the immunology of rejection was not understood and could not be overcome. Now transplantation is much more successful, and it is the aspiration for most patients with permanent kidney failure. You can’t avoid meeting people with transplants now, and may well be working alongside some. It’s been a long slow learning process but it is a remarkable success story.
Intro (27 mins). You can move or hide the talking head with the controls at the top right
if you are on full-screen view.
Core immunology for understanding transplantation
You should understand antibodies, T cells (CD8, CD4), basic concepts of immune tolerance. Four key elements for understanding transplantation are
- Blood groups – ABO compatibility is usually necessary, but not rhesus compatibility. ABO incompatibility is likely to result in hyperacute rejection. Transplantation across ABO barriers may be possible if antibody levels in the recipient can be lowered far enough. ABO restricted allocation of deceased donor organs is practised so as not to disadvantage group O recipients – as group O organs could go to any recipients, but they cannot take from other blood groups. Wikipedia on blood groups is quite good.
- HLA (MHC) – what these molecules do, and how they affect transplantation. MHC on Immunopaedia – full discussion with more detail than essential, but also extending to cover the next topic …
- Antigen presentation – nice summary of antigen presention in BiteSized Immunology
- Cells of the immune system – excellent 5 min intro to cells of the immunes system by Brittany Anderton (iBiology channel as below, YouTube)
- T cell activation – nice short summary of three signals leading to T cell activation in BiteSized Immunology, though this is also described in the next section
The immunology of rejection is covered in in more detail in some of the broader resources linked below the next video.
Principles of immunosuppression in transplantation
An explosion of agents (7 mins). Approaches to immunosuppression and key mechanisms.
Oh my, I need to refresh my basic immunology … see Further Info at the foot of this page.
Drugs for preventing rejection
We haven’t yet cracked how to induce tolerance, so drugs to suppress immune responses are necessary life-long to prevent rejection. These have moved on to an extraordinary degree since the first discoveries in the 1960s.
The video (20 mins) gives more detail of the main classes of anti-rejection therapies, how they work, some key side effects, and how they are used. Possibly more information than some will need, but it’s not too long, and good to know.
The video above was created a few years ago, so there is new information about several aspects. Some key points are:
- MMF has got less expensive and is standard Rx in most protocols now. Downsides: it is still twice a day, and it is fetotoxic.
- Tacrolimus has largely replaced cyclosporine as the calcineurin inhibitor of choice in modern multi-drug regimens.
- ATG has largely replaced the use of OKT3.
- Best therapy of antibody-mediated rejection is no clearer, and most of the approaches said to be promising have not proved beneficial.
What’s coming?
Things everyone asks about:
- Why can’t we induce tolerance to the donor organ? Then they might not need to be on immunosuppression for the rest of their lives, with all their side effects. It’s proved harder to do this in humans than in rodents. It still feels a long way off.
- Xenotransplantation – taking organs from animals. Other species organs look very ‘immunologically different’ from human organs. Some progress has been made in preventing immediate (hyperacute) rejection, including by deleting or altering key molecules using transgenic techniques. But we are a very long way from a solution that will work for decades.
- Growing kidneys in the lab from stem cells. Progress has been made with bone marrow and liver cells, but the architecture of the kidney is a real challenge. We’re still nowhere near seeing a way through for kidneys.
So in the next decade or two, progress seems likely to depend on continuing to refine what we do now. Fortunately that approach has been fantastically successful already, the outlook for transplant recipients is so much better.
Further info
- More Renal things from medcal
- Like the historical approach? More on the development of dialysis and transplantation at the HistoryofNephrology blog.
- Oh my, I need to refresh my basic immunology. Try these free yet excellent resources:
- Immunopaedia is a South African site giving an excellent written account of basic immunology. Recommended.
- Bitesized Immunology from the British Society for Immunology. Look in particular at Cells (pick out T, B) and some of the Molecules. There’s a short (but complicated) summary on Transplant rejection under Tissues.
- Longer reads: Immunology of Transplantation (30 mins video by Megan Sykes, Columbia University). She also has two more advanced talks on iBiology’s YouTube channel, and discusses xenotransplantation. iBiology also provides several more talks covering basic immunology. Allow a few hours to cover all.
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