Subject : APPLIED PATHOLOGY 2

Lecture : KIDNEY TRANSPLANTATION

Date : 20/11/2018
Professor : Sandro Mazzaferro
Sbobinatore : Georgios Anthymiadis
Reviewer : Amir Khan

DEFINITION AND INTRODUCTION OF KIDNEY TRANSPLANTATION

The retroperitoneal approach for kidney removal increases the risk for
the patient because the procedure is much more invasive, that’s why a
kidney transplant through the pelvis is preferred. For this procedure you
simply need to do an anastomoses of 3 tubes: the renal artery, renal
vein and the ureter. This is not actually as pleasant as he describes it,
as we leave behind the lymph nodes. As result this can cause a surgical
complication that is called Lymphocele (a condition characterized by a
collection of lymphatic fluid within the body not bordered by epithelial
lining. It is usually a surgical complication seen after extensive pelvic
surgery and is most commonly found in the retroperitoneal space).
Technically speaking the anastomoses between tubes is a difficult
procedure because it requires as much tissue as possible (not in the
case of live donor) and the presence of good vessels (not
atherosclerotic or calcified). During the procedure you clamp the
hypogastric artery, you cut it and anastomose it by sewing it.
Consequently, there is the possibility of scar formation due to inflammatory processes and the sewed region will
be reabsorbed. This at least guarantees the connection of the cut vessels, but the scarring formation can also
lead to stenosis of the vessel causing significant ischemia. Today a laparotomic approach is also used for taking
the kidney from the donor.
The length of the ureter and of vessels is quite important cause during the anastomoses the amount of tissue
may not be enough if the length is smaller than needed. Due to anatomical variability, some patients have
extensive blood supply to the distal 1/3 of the ureter, making the transplantation even more difficult because of
the possibility for necrosis of the distal ureter. Necrosis of distal ureter after some days may cause Uroperitoneum
that can lead to Septic Peritonitis. Since you have edema in ureter that can lead to the obstruction and later can
cause Post renal/Acute renal insufficiency.
Question: Where do you think we put the ureter in the bladder? Near the older one
Question: What is the relevant physiological role of the ureter in the bladder? It needs to guarantee the valve
mechanism that avoids Vesicular Ureteral Reflux (VUR).
If we make a urine culture taken from the bladder, the result will be sterile. How is that? It’s important for the
bacteria to be eliminated before they establish an infection. If not efficiently eliminated, it’s possible that the
infection could be transmitted to the kidneys e.g. pyelitis, tubular interstitial nephritis, scarring of some pyramids
etc. In inborns due to some anatomical abnormality the VUR can be responsible for the progressive Bilateral
kidney scarring (remember that this is not a rare disease especially in babes-so it’s important to search for it in
any child that develops renal fevers).
To solve this problem there is a new technique called Uretherovesical Anastomotique (by Gregoir-Lich). This
technique allows ureters to have some submucosal trajectory (is not a direct implantation) that allows some
tunnel between or within the wall of the bladder. When the bladder is filled with the urine, increases in pressure
stretches and push this tunnel and becomes a mechanism of anti-reflux. This operation involves only the upper
part of the bladder dome so is less invasive technique than opening completely the bladder.

Transplantation Immunology
Immune rejection of the transplanted kidney is a very common event. There are several types of immune
rejection. Which kind of immune response does the transplanted kidney cause from a biological point of view?
Production of antibodies could cause the rejection of the transplant. The production of the Abs will start on
average after 1 or 2 weeks. But there is also a case of rejection that is called Hyperacute rejection that may start
within a minute to hours after the host blood vessels are anastomosed to graft vessels. This type of rejection is
due to the presence of native Abs that preexist in the host circulation and binds to donor endothelial antigens.
These antigens are members of the MHC group of antigens
(HLA), when native Abs (also called circulating alloantigen
specific Abs) binds to the alloantigen this can cause
Complement activation, Endothelial damage, Inflammation and
Thrombosis of the vessels. These days to avoid rejection we
check for these native Abs against the donor antigens prior to
transplantation. It’s important to know that patients that
undergo hemodialysis and are in the list of renal transplantation
used to send samples of serum to the transplantation center to
check the presence of these Abs.
Types of donors
What are the clinical characteristics for the donor and the
receiver?
In the past donors used to be younger than 50, today this is not the case. Also, the ABO group matching is not
anymore, a contraindicate factor for the transplantation. HIV positive patient can still donate a kidney (he said
that in the beginning, then he changed to that is a kind of contraindication but not absolute). Patients with viral
infections like Hepatitis B or C can’t be donors. In the past only patient younger than 50 could receive a transplant,
today there is no numerical limit. Today it’s more a matter of biological age than a real age of a patient. But an
absolute contraindication for transplantation is the ‘’Prognosis’’, because of the limited number of available
organs.
Why do we need to think about opportunistic infections? Because we know that after the transplantation the
patient is required to be immunosuppressed, and thus is prone to opportunistic infections. Some of the viruses
that can be opportunistic are CMV and EBV. Transplanted patients that are immunocompromised for extended
time and are infected with EBV can develop Lymphoma. Also, CMV can be responsible for Acute /Chronic
rejection, Pneumonia, Endocarditis, GI bleeding and perforation. So, it’s important to check every patient that is
going to receive a transplant for all these viruses and avoid any post complications (ex. losing a transplanted
kidney).
Cadaveric donors are the most common technique in our days.
Cadaveric donor evaluation:
 Cadaver = cerebral death (according to local laws) + Consent to donation.
 Clinical suitability (kidney function, absence of communicable diseases)
 History: (life style, drugs, chronic diseases, infections, tumors, transfusion, etc.);
 Objective examination;
 Instrumentals: EKG, Chest Rx, Abdominal Echo, Other;
 Biochemicals: Viral markers; renal function, enzymes, others.

Contraindication of cadaveric donation:

What happens when we are dealing with the deceased donor? First, we must refrigerate the kidney to stop any
metabolic activity. After the kidney is removed there is a fluid that is employed that contains glucose and other
substances. We use a pump to infuse the kidney with this fluid in order to reduce the metabolic rate and to allow
some metabolic activity. The kidney is then put in a refrigerator box and sent for transplantation, it can stay there
for 24-48h before being transported to a specific hospital for transplantation. The longer the attending time before
transplantation, the higher the chance for kidney damage which is mostly tubular damage (acute tubular
necrosis). If for example there is a delay let’s say 72h, after the transplantation is performed there will be a
chance for oliguria and anuria that present as a complication due to tubular damage. But after a week or more
the regeneration of tubules will stabilize the kidney function to normal.
Living donor evaluation:
• ABO Compatibility
• HLA Compatibility
• History and complete clinical evaluation
• Blood and Urine chemistries
• Arteriography
• Urography

There is a kidney biopsy for all kidneys available for donation- a 24h system that evaluates the kidney by using
several parameters to present with a specific score. This score is more important for kidneys donated from older
people. Another point is that in case of a kidney that has some degree of renal insufficiency, the receiver of that
kidney will be selected according to its needs (ex. elderly patient).
What about Tuberculosis? When there is donor with tuberculosis let’s say a ‘’miliary’’ form that is very severe,
there will be complete evaluation of the kidney before performing a donation by several tests.
Contraindication of Living donor:

When we remove one kidney from a living donor we half the number of nephrons, in order to avoid any possibility
to have a new renal patient we considered donor to be acceptable if both kidneys are perfectly normal and
functioning. The most common side effect for the donor is some degree of hypertension, that can cause renal
damage later.
Complications During Renal Transplantation:

Survival of the transplant is very high- around 90% after 12 months. But the more frequent are the follow ups,
the higher is the likelihood for some renal damage. There is possibility for recurrence of preexisting
glomerulonephritis. There is also significant cardiovascular morbidity that involves the kidneys. There is also
several significant infections and risks of developing neoplasia, mainly Lymphoma but also other kinds of
neoplasia that are more frequent in transplanted patients that receive immunosuppressive therapy.
Transplanted kidneys can last 10-30 years but even more. Transplantation can also be repeated twice or even
3 times.
During the renal transplantation do we always remove the damaged kidney? The only reason when the kidney
is removed from the patient is when there is a clinical or surgical reason (ex. inflammation or necrosis of the
kidney), but if there is only a shrinkage of the kidney or a kind of scarring that doesn’t affect clinically the patient
then the transplanted kidney can remain inside.