Recurrence of Kidney Disease after Transplantation

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Clinical Kidney, Pancreas and Islet Transplantation

196 calificaciones

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Universiteit Leiden

Clinical Kidney, Pancreas and Islet Transplantation

196 calificaciones

Kidney transplantation is a major advance of modern medicine which provides high-quality of life for patients with end-stage renal disease. What used to be an experimental, risky, and very limited treatment option more than 50 years ago is now routinely performed in many countries worldwide. The number of renal transplants is expected to rise sharply in the next decade since the proportion of patients with end stage renal disease is increasing. Are you interested in clinical kidney, pancreas and islet transplantation? If you are a (bio) medical student or a health care professional who works in the (pre) clinical transplant field this might be the course for you. This course is also for anyone interested in the research and knowledge on clinical transplantation. The course will be taught by a multidisciplinary team of transplant professionals and will give you the state of the art updates. It is divided in 4 modules: 1) Before the transplant 2) The surgical procedures and the challenged patient, including the patient with diabetes 3) Early challenges 4) Late challenges after transplantation. The offered modules will include lectures, interactive patient cases, 3D movies, interviews with well-known experts and with patients and a donor, a serious game to increase knowledge of the field and of course an active forum. Become an expert and join us! The course is endorsed by The European Society of Organ Transplantation (ESOT), The International Society of Nephrology (ISN) and The Transplantation Society (TTS). This MOOC has been accredited for Continuing Medical Education (CME). Health care professionals who works in the (pre) clinical transplant field, other health care professionals and general practitioners can obtain CME credit at 'LUMC-Boerhaave CME' upon passing the course. For more information we like to refer to the "Additional introduction for obtaining CME credit" module in week 1 of the course For another interesting course on organ donation and transplantation, see Organ Donation: From Death to Life from Cape Town University https://www.coursera.org/learn/organ-donation

De la lección

Late Challenges in Transplantation

Now you’ve learned about the challenges in the early period after transplantation. But what about the late period? What is the long term patient and allograft survival? Have we improved in the last decades? What are the main causes for morbidity and mortality? And can we reach tolerance in the future? We invite you to give your opinion in the patient cases and to discuss it on the forum. There are also advanced readings to look at additional subjects, including recurrence of the kidney disease after transplantation, the organization of dermatological care for the transplant recipient and the role of the patient himself in the whole process. The interview about tolerance gives you insight why pregnancy is of interest to understand the concept of tolerance and which steps have been made from lab research to a clinical protocol. In the honors lesson late challenges will be discussed in more detail, with a focus on infections, recurrence of the kidney disease after transplantation and tolerance. Have fun and good luck with this last module.

Recurrence of Kidney Disease after Transplantation8:56

Vaccination and Transplantation8:00

Conoce a los instructores

Marlies Reinders
Dr.
LUMC, Department of Nephrology and Transplantation
Frans Claas
Professor
LUMC, Department of Immunohaematology and Blood Transfusion
Cees van Kooten
Professor
LUMC, Department of Nephrology and Transplantation
Sebastiaan Heidt
Dr.
LUMC, Department of Immunohaematology and Blood Transfusion
Volkert Huurman
Dr.
LUMC, Department of Transplant Surgery
Hans de Fijter
Professor
LUMC, Department of Nephrology and Transplantation
Eelco de Koning
Professor
LUMC, Department of Nephrology and Transplantation and Endocrinology and Metabolism
Andre Baranski
Dr.
LUMC, Department of Transplant Surgery
Ton Rabelink
Professor
LUMC, Department of Nephrology and Transplantation
Aiko de Vries
Dr.
LUMC, Department of Nephrology and Transplantation
Jan Nico Bouwes Bavinck
Dr.
LUMC, Department of Dermatology
Leo Visser
Professor
LUMC, Department of Infectious Diseases
Ingeborg Bajema
Dr.
LUMC, Department of Pathology

Hi, there.

We've already heard in earlier cases that renal disease may recur in the kidney.

Indeed, kidney transplantation is a treatment and it's not a cure.

So it may restore the renal function,

however that does not remove the cause of the original disease.

So do you know which kidney diseases recur in the kidney?

What are actually the risks?

What is the pathophysiology?

What is the treatment?

And what is the prognosis?

So we will ask Professor Rabelink to help us with these questions.

We will start with a patient case.

The patient is a 53 year old male with IgA nephropathy,

as cause of the renal disease.

Two years ago his sister served as the kidney donor.

The patient was preemptive.

His maintenance therapy consists of steroids, tacrolimus, and CellCept.

The serum creatinine is stable with actually a good renal function.

His blood pressure is 150/95 which is a little too high.

Two years after transplantation, a renal biopsy was performed per protocol.

And this demonstrated IgA nephropathy.

Thus there was a recurrence of the primary disease of the patient.

>> Let's first look at the diseases that can recur after renal transplantation.

One can discriminate three types.

The first group are metabolic disorders, such as diabetes mellitus, oxalosis, and

amyloidosis.

Usually, these diagnosis are known before transplantation.

And either consitute a contraindication for transplantation, or

it can be clinically managed so that these are generally are not a threat

to the transplanted organ in the short-term.

The second group are the systemic diseases such as, for

example, systemic lupus erythematosus, abbreviated to SLE,

systemic vasculitis, and Hepatitis C virus associated with nephropathy.

As patients are treated with systemic immune suppression the recurrence rate is relatively low.

For example, the UNOS registry recently showed that

SLE relapse in transplant patients in 2% of the cases.

When it happened it was also associated with rejection and graft failure pointing

to the possibility of non-compliance in these patients with recurrent disease.

And finally there's the group of primary diseases of the glomeruli

called glomerulonephritis that can reoccur.

The original diagnosis may not always have been clear in the patient as

advanced fibrosis and glomerulosclerosis at the time of presentation may

have precluded the interpretation of a kidney biopsy.

You have already seen fibrosis and

glomerulosclerosis in the biopsy of one of the patients earlier in this module.

You still have this pathology in mind.

The four most common forms of recurring glomerulonephritis

that can lead to graft loss include focal segmental glomerulosclerosis,

Immunoglobulin A nephropathy, membranoproliferative glomerulonephritis

due to complement disorders and disregulation and membranous nephropathy.

Details on these kidney diseases you can find in the optional literature.

Let's now focus on recurrent glomerulonephritis.

The risk of recurrent glomerulonephritis increases with younger recipient age

and is directly proportional to the duration of follow up.

The risk of graft loss due to

recurrent disease is highest in focal segmental glomerulosclerosis

where the recurrence risk may be as high as 50% leading to graft loss in

ten years after transplantation in up to 20% of the patients.

The most common recurrent glomerular disease after transplantation is IgA nephropathy.

About half of the patients have again IgA deposition in the transplanted kidney

at five years post-transplantation.

Most of the registries report that between 15 and 25% of the patients

that have IgA deposition, this also results in graft dysfunction or

graft loss over ten years follow-up period.

As with primary IgA nephropathy,

the worst prognosis in patients is with more severe proteinuria, hypertension,

increased body mass, and the presence of histopathological abnormalities.

Since our patient has primary IgA nephropathy and

recurrence in the transplanted kidney.

We will now focus in more detail on this disease

in order to set up a treatment plan.

So what is IgA nephropathy?

In most of the patients, primary IgA nephropathy has a benign course.

But in up to 30% of the cases,

it may gradually lead to renal failure over a period of 20 years.

In this slide, you see a three-dimensional picture of the glomerulus,

the capillary network that together with very specialized epithelial cells,

the podocytes, constitute the filtration barrier.

And if we now take a look at the cross section of the glomerulus,

one can identify the various structures.

The endothelial cells covering the capillary lumen,

the podocytes and the supporting stromal cells the mesangial cells.

In IgA nephropathy immune complexes are deposited in the mesangium and

can elicit a local inflammatory reaction.

So what is of key importance for the disease?

Fundamental to the immune complex formation is the increased synthesis of poorly galactosylated IgA1.

In more popular terms,

this means that the sugar coat of the IgA molecule is slightly modified.

Genetic factors influence the production of this undergalactosylated IgA1.

And familiar clustering as well as clustering in the Asian population

are well known features of the disease.

It is assumed that a second hit is required to the actual

IgA related disease.

The second hit is the formation of auto antibodies against the under

galactosylated IgA1 molecule.

Whether or not the formation of auto antibody IgA complexes indeed leads

to glomerular disease, depends upon the clearance of these complexes and

the response of the mesangial compartment where they get trapped in the kidney.

So, we've seen how IgA nephropathy develops, but what about treatment.

There is currently no proven treatment known to modify the production and

deposition of IgA1.

Although the use of immune suppressive drugs in kidney transplantation

most likely reduces the deposition of IgA complexes,

as well as the renal response to these depositions.

And therefore HLA mismatch, dialysis duration and

steroid use are all strongly associated with reduced risk of recurrence,

suggesting that immune competence is required to get the disease back.

In rare cases,

acute renal failure may develop due to proliferative glomerulonephritis.

In these cases, additional immune suppressive treatment is indicated.

In all other cases, it's recommended to focus on control of blood pressure and

reduction of proteinuria.

Use of antihypertensives that influence the renal angiotensin system

are particularly recommended.

So what should be the treatment in our patient with recurrence of IgA nephropathy

in the graft?

The patient had stable renal function which will be followed up closely,

we kept the immune suppressives since the patient was already in

triple immunosuppression therapy and also had prednisolone.

Because of hypertension, an ACE inhibitor was added to the medication.

What should we learn from this?

Metabolic disorders, systemic and primary glomerular disease may recur in the graft.

The risk for recurrence after transplantation and

the prognosis differ between the various diseases.

IgA nephropathy is the most common glomerulonephritis both as a primary

as well as a recurrent disease.

In IgA nephropathy, immune complexes are deposited in the mesangium and

can elicit a local inflammatory reaction.

There's currently no proven treatment known to modify the production and

deposition of IgA1.

Use of ACE inhibitors are recommended.

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