hypothermia decreases cell metabolism and greatly increases the time an organ can be preserved
induced by flushing the blood out of the organ with a cold solution (4° C)
organ is then either stored on ice or machine-perfused at 4° C
one deleterious effect of hypothermia is cell swelling, which results from a decrease in
activity of membrane-bound ion pumps and a decrease in ATP production
in kidney recipients, delayed graft function is significantly more frequent after cold
ischemia times of more than 24 hours
Preservative Solution
greatly increases the ‘shelf life’ of the organ
goal is to create an appropriate physical and biochemical environment for the organ
solution must contain osmotically active agents to suppress cell swelling, electrolytes,
hydrogen ion buffers, metabolic inhibitors (allopurinol), and metabolites to stimulate ATP
synthesis during organ reperfusion (adenosine, glutathione)
University of Wisconsin solution (ViaSpan) is the most common preservative solution in use
Suppression of Cell Swelling
cell swelling is a major detriment of successful organ transplants because it results
in organelle swelling, disruption of the cytoskeleton, and dilution of the
intracellular milieu
preservative solution must contain impermeant molecules that remain outside the cell
and prevent the hypothermically-induced accumulation of water by the cell
saccharides (mannitol, raffinose) or anions (lactobionic acid) are used as the
primary impermeants
osmotic strength of the solution is between 400 and 440 mOsm/L
Kidney Transplantation
Indications and Contraindications
Indications
end-stage renal disease from diabetes and hypertension are the most common indications
other important causes include glomerular disease, polycystic kidney disease, and lupus
Contraindications
absolute contraindications include: active malignancy, active infection, severe cardiac and
pulmonary disease, unreconstructable peripheral vascular disease, drug abuse, and predicted
noncompliance
blood group matching of recipient and donor has been considered essential because preformed antibodies
to these antigens will result in hyperacute rejection
however, desensitization protocols have made ABO-incompatible transplants possible in elective noncadaveric transplants
ABO-Incompatible Kidney Transplants
goal is to remove sensitized B cells by plasmapheresis and B cell-depleting antibodies (rituximab)
high-dose induction immunosuppression is maintained for two weeks
following this protocol, accommodation develops and rising titers of anti-A or anti-B antibodies
don’t harm the transplant
overall results are as good as ABO-compatible transplants
Lymphocytotoxic Crossmatching
sensitization to HLA antigens may occur with pregnancy, blood transfusions, or prior
transplantation
although it is possible to type for 6 antigens (HLA-A, B, C; HLA-DR, DP, DQ), usually only 3
are typed: HLA-A, B, and DR
the closer the HLA match, the better the graft survival
recipient serum is tested against a panel of HLA-typed donor lymphocytes (panel-reactive
antibody assay (PRA)
a high PRA score indicates the likelihood of a positive cross-match with a donor
Panel Reactive Antibody Score
quantifies the risk of transplant rejection by determining the amount of HLA antibody
present in a patient’s serum
6% is considered a high score
patients with a high PRA score wait longer for a suitable organ
Final Crossmatch
cells from a potential donor are incubated with serum from a recipient
antibody binding is detected using a cytotoxic technique
must take place prior to transplantation
Kidney Donors
Living-Related Donors
any 2 siblings have a 25% chance of being HLA-identical, 50% chance of being haploidentical,
and a 25% chance of being completely nonidentical
close to 100% long-term graft survival when a related donor and recipient are HLA identical
advantages of living-related transplants include: excellent immediate graft function, better
short-term and long-term results, preemptive transplantation and avoidance of dialysis, and
reduction of immunosuppression in HLA-identical transplants
Risk to the Living Donor
operative mortality is 0.03%
no long-term morbidities have been identified although trauma to the remaining
kidney remains a concern
Evaluation of Potential Living Donors
complete history and physical examination
laboratory screening to include hepatitis profiles, HIV serology, and EBV,
cytomegalovirus, and varicella serologies
urinalysis and culture
24 hour urine collection for creatinine and protein
EKG and stress tests when indicated
angiogram or CTA to enumerate the renal arteries and veins
IVP or CT to outline the collecting systems, ureters, and bladder
Donor Nephrectomy
left kidney is chosen, if possible, because its longer renal vein facilitates the
anastomosis
if multiple renal arteries are present on one side, the other side is usually chosen
to make the anastomosis simpler
most commonly performed laparoscopically
ureter is mobilized with a generous amount of periureteral tissue and is ligated
close to the bladder
renal artery and vein are not clamped and divided until the recipient iliac vessels
have been prepared
Living-Unrelated Donors
typically are spouses
account for ~ 1% of all renal transplants
graft survival is better than in cadaveric transplants
Cadaveric Donors
account for 75% of all renal transplants
ideal donor is young, normotensive, free of systemic diseases, and brain dead
Recipient Operation
oblique incision is made just above the inguinal ligament and the iliac vessels are exposed in the
retroperitoneum
right side is usually preferred because the right iliac artery and vein are in a more superficial
position
most common arterial anastomosis is an end-to-side anastomosis between the renal artery and the
external iliac artery. The common iliac and internal iliac arteries may also be used
the renal vein is usually connected to the external iliac vein. The common iliac vein or distal IVC
may also be used
the ureter is anastomosed to the recipient’s bladder. A submucosal tunnel is created to prevent
urine reflux
Postoperative Management
Urine Output
a brisk diuresis is expected in the early posttransplant period
live donor kidneys are expected to function immediately
25% of cadaveric kidneys have delayed graft function
urine output is usually replaced cc per cc with 0.45 NS
Management of Anuria or Oliguria
first step is to make sure the Foley catheter is not occluded with clots
second step is to assess the patient’s volume status and correct hypovolemia if
present
if urine output does not increase, then a Doppler ultrasound should be obtained to
assess blood flow in the renal artery and vein
if blood flow is adequate, then urinary obstruction or leak should be evaluated by
a renal scan
if there is no obstruction, then the patient will need dialysis until the graft
begins to function
Pancreas Transplantation
Indications
purpose of pancreas transplantation is to reverse or retard the development of secondary diabetic
complications (neuropathy, retinopathy, coronary and peripheral vascular disease) while avoiding the
risk of severe hypoglycemia
patients with type I IDDM are potential candidates as long as they do not have end-stage secondary
complications
may be performed in 3 different clinical settings: 1) pancreas transplantation alone (PTA),
pancreas transplantation after successful renal transplantation (PAK), and simultaneous pancreas
and kidney transplantation (SPK)
SPK is the most common procedure performed (~80%) and is the procedure of choice in the diabetic
uremic patient with potentially reversible secondary complications
Operative Procedure
Management of the Donor Pancreas
pancreatic blood supply is reconstructed on the back table with a donor iliac artery ‘Y’
graft anastomosed to the splenic artery and superior mesenteric artery
donor external iliac artery is anastomosed end-to-end to the donor SMA, and the donor
internal iliac artery is anastomosed end-to-end to the donor splenic artery
this reconstruction allows the donor common iliac artery to be anastomosed as a single vessel
to the recipient’s common iliac artery
common bile duct is ligated
Back Table Donor Pancreas Arterial Reconstruction
Recipient Operation
performed through a midline transabdominal incision
pancreas is preferentially placed in the right iliac fossa
if a kidney transplant is also being performed, it is placed in the left iliac fossa
arterial anastomosis is performed between the reconstructed donor ‘Y’ graft and the recipient
common iliac artery
venous drainage may be either systemic or portal
exocrine pancreatic secretions may be drained into the bladder or the small bowel
Management of Pancreatic Secretions
in the first procedures performed, the pancreatic duct was simply ligated, but this
lead to a high incidence of graft pancreatitis
Bladder Drainage
decreases the risk of contamination from the native enterotomy required for
enteric drainage
allows for early detection of rejection by monitoring urinary amylase
anastomotic leaks are easy to treat
complications include metabolic acidosis and urinary tract infections
Enteric Drainage
performed by a side-to-side anastomosis between the donor duodenal segment
and the recipient’s jejunum
considered to be more physiologic
avoids the metabolic acidosis and urinary tract complications of bladder
drainage
has not been associated with a higher infection rate
80% of pancreas transplants are performed with enteric drainage
Systemic Venous Drainage vs Portal Drainage
systemic drainage may result in hyperinsulinemia as a result of loss of first-pass
hepatic metabolism
however, no clear advantage has been seen from portal drainage
90% of pancreatic transplants use systemic drainage into the common iliac vein
Postoperative Management
Diagnosis of Rejection
acute rejection occurs in ~ 30% of patients in the first year
timely diagnosis of rejection is a major obstacle to successful pancreas transplantation
in combined kidney-pancreas transplants, renal allograft rejection and a rise in serum
creatinine precedes pancreatic rejection
in isolated or sequential pancreas transplants, the kidney does not serve as a monitor for
rejection
in enteric-drained patients, increased serum amylase and lipase suggests rejection
in bladder-drained patients, a decrease in urinary amylase suggests rejection
histologic confirmation of rejection may be obtained by percutaneous pancreatic graft biopsy
Complications
Graft Thrombosis
most common nonimmunologic cause of pancreas transplant failure
occurs within the first week after transplant
early signs are graft tenderness and elevated amylase and lipase
hyperglycemia is a late sign of graft failure
graft Doppler ultrasound is the diagnostic test of choice
surgical exploration with graft pancreatectomy is usually required
Anastomotic Leaks
Enteric Anastomosis
signs and symptoms include abdominal pain, fever, tachycardia
immunosuppression may mask the presentation
CT with oral contrast is the best diagnostic test
reoperation is almost always required
occasionally, the graft can be salvaged
graft pancreatectomy is mandatory in cases of sepsis, peritonitis, or extensive
necrotic tissue
Bladder Anastomosis
some leaks will resolve with Foley catheter drainage only or direct suture repair
persistent leaks will require conversion to enteric drainage
Urologic Complications
most frequent cause for readmission to the hospital after SPK transplantation performed with
bladder drainage
hematuria, urine leak, UTIs, and urethritis are all common
conversion to enteric pancreatic drainage may be necessary to manage serious or recalcitrant
urine leaks or UTIs (10% to 25% of patients)
Metabolic Complications
after bladder drainage, a majority of patients develop a metabolic acidosis as a result of urinary losses of
bicarbonate-rich pancreatic secretions
most patients can be managed with oral bicarbonate supplementation
Peripancreatic Fluid Collections
should be drained if there is any suspicion of infection
undrained infection may cause erosion of the vascular anastomoses
Graft Pancreatitis
occurs in ~ 35% of patients
early pancreatitis may be related to reperfusion injury
the signs of pancreatitis overlap with acute rejection (pain, hyperamylasemia)
