Apostila 1 - Clinical Transplantation

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ORGAN TRANSPLANTATION – CLINICAL RENAL TRANSPLANTATION IN THE DOG AND CAT Clare R. Gregory, DVM, Diplomate ACVS The Comparative Transplantation Laboratory in the Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, California 95616-8745 1

Transcript of Apostila 1 - Clinical Transplantation

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ORGAN TRANSPLANTATION – CLINICAL RENAL TRANSPLANTATION IN THE

DOG AND CAT

Clare R. Gregory, DVM, Diplomate ACVS

The Comparative Transplantation Laboratory in the Department of Surgical and Radiological

Sciences, School of Veterinary Medicine, University of California, Davis, Davis, California

95616-8745

Clinical Renal Transplantation in Cats

Criteria for the renal recipient.1, 2, 3, 4,5

Renal transplantation is one method of treatment for renal insufficiency. It cannot be

regarded as an emergency treatment or "last-ditch" effort to save the life of a critically ill,

malnourished patient. Surgical intervention has to take place before all medical means of

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therapy have been exhausted. The authors consider body weight to be a very important

indication of the status of the renal transplant candidate. If a cat has been in compensated renal

failure and starts to lose body weight, or presents in renal failure with a history of chronic weight

loss, transplantation should be considered as an option before further weight loss occurs. In the

critically ill human surgical patient, maximum physical performance deteriorates after a 10%

loss in normal body weight. Greater than a 40% weight loss is usually lethal. Previous attempts

by the authors to alter the course of physical deterioration due to decompensated renal failure via

enteral or parenteral alimentation prior to transplantation have failed. Hemodialysis, however, is

very effective in managing severely uremic patients several days prior to surgery. The authors

use hemodialysis to correct electrolyte and acid/base imbalances and lower the blood urea

nitrogen concentration to 100 mg/dl or less. Blood urea nitrogen concentrations greater than 100

mg/dl predispose cats to postoperative cerebral edema and seizures due to rapid clearance of the

blood urea nitrogen by a normally functioning renal graft. Age, plasma creatinine, blood urea

nitrogen, and other clinical pathologic assessments of renal function cannot in themselves select

a suitable patient for transplantation. All physical and biochemical parameters must be assessed

to determine the overall suitability of a candidate.

Feline candidates for renal transplantation should be free of Feline Leukemia Virus

infection, active Acquired Immunodeficiency Syndrome and free of other complicating diseases.

It appears that renal insufficiency can produce systemic hypertension in the feline patient leading

to congestive heart failure. Cats in renal failure often have systolic murmurs secondary to

anemia that may not represent significant cardiac disease. Cardiac enlargement determined by

ultrasonographic examination, gallop rhythms, and/or electrocardiographic abnormalities are

possible indications to decline a candidate for transplantation. An abdominal ultrasonographic

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examination and intestinal biopsies should be performed if neoplasia or inflammatory bowel

disease is suspected. Immunosuppression often enhances tumor growth and inflammatory bowel

disease appears to promote acute allograft rejection.

The feline renal donor/recipient pair do not have to be related or tissue matched, but they

must be blood cross matched. The antigens present on red blood cells are also present on the

endothelium of the graft blood vessels. Preformed antibodies to these antigens will cause

clotting of the graft vessels and infarcts of the organ at the time of surgery. The feline renal

recipient must also be blood cross matched to 2 to 3 blood donor cats. The primary reason for

this is the anemia that accompanies chronic renal failure. Following rehydration of a patient

prior to surgery, packed red blood cell volumes may fall as low as 12 to 15%. One hundred

eighty to 250 milliliters of whole blood may be required to attain a packed red blood cell volume

of 30% in the renal recipient prior to surgery. Also, in our experience, some cats in chronic renal

failure are unable to accept blood transfusions, i.e. all cross match assays show agglutination of

donor red cells. In two instances, the renal disease was secondary to Lupus erythematosus. In

one other, however, no cause for the coagulopathy could be found. All cats were of the same

blood type (A). This is an important consideration if the transplant patient is traveling a great

distance to the transplant clinic. Cross matching should be done locally to ensure transfusions

can be given prior to surgery. Erythropoietin can be very helpful in controlling the anemia

associated with renal failure. Administration of erythropoietin starting 1 to 2 months prior to

surgery can greatly reduce the need for blood products.

Renal diseases successfully treated by renal transplantation in the cat include

membranous glomerulonephropathy, chronic tubulointerstitial nephritis, polycystic renal disease,

and ethylene glycol toxicosis. Cats with a suspected history of bacterial urinary tract infection

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should have a renal biopsy performed and be subject to a 2 week cyclosporine challenge prior to

surgery. Cyclosporine is administered orally at 4 mg/kg twice daily and urine cultures are

performed 7 and 14 days following the initiation of cyclosporine treatment. Latent infections

will often become active once cyclosporine is administered. Currently we are recommending

renal transplantation for cats whose renal failure was secondary to obstruction by calcium

oxalate uroliths. However, clients must be warned that some of these cats may form additional

uroliths following transplantation that may obstruct and injure or destroy the transplanted kidney.

Cats with renal failure whose kidneys are of normal or increased size should have a biopsy

performed to rule out lymphosarcoma.

In the past, cats that had positive serum titers for Toxoplasmosis, either IgG or IgM, were

not considered candidates for immunosuppression and transplantation. Both cats and dogs have

developed fatal Toxoplasmosis infections following renal transplantation and

immunosuppression6. Currently animals with positive serum titers that undergo transplantation

are administered clindamycin or trimethoprim/sulfadiazine prior to surgery and for the life of the

patient. (LR Aronson, University of Pennsylvania, personal communication).

Trimethoprim/sulfadiazine must be used with care since this drug can enhance cyclosporine

nephrotoxicity.

Criteria for the renal donor.

The renal donor should be in excellent health and have no evidence of renal insufficiency

based on clinical pathologic testing; complete blood count, serum chemistry panel, urinalysis and

urine bacterial culture. An intravenous pyelograph is performed to assure that the donor has

two, normally shaped, and well vascularized kidneys. The feline donor should be free of Feline

Leukemia virus infection, and be blood cross match compatible and of similar weight and body

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size of the recipient. The renal donor should have a normal life expectancy following unilateral

nephrectomy.7 Elevation in serum creatinine levels and proteinuria have been reported in human

kidney donors, and long-term monitoring of renal function has been recommended.

Preoperative preparation of the recipient.

Prior to surgery, the renal recipient is given balanced electrolyte solutions subcutaneously

or intravenously at 1.5 to 2 times daily maintenance requirements. Whole blood or packed red

blood cell transfusions are administered until a packed red cell volume of 25- 30% is achieved.

Hemodialysis is employed for cats that maintain a blood urea nitrogen concentration > 120

mg/dl despite aggressive fluid diuresis. Forty-eight hours prior to surgery, cyclosporine oral

solution (Neoral) is administered at a dose of 3-5 mg/kg every 12 hours. The cyclosporine oral

solution should be placed in gelatin capsules prior to administration. Capsule sizes #0 or #1

work well for most cats. Cyclosporine oral solution has a very unpleasant taste that causes some

cats to salivate profusely, resulting in partial loss of the dose. Clindamycin is administered to

animals with positive serum titers for Toxoplasmosis.

The morning of surgery, a blood sample is taken from the recipient 12 hours following

the last oral dose of cyclosporine. This will give a 12 hour trough blood concentration. The

authors follow whole blood concentrations of cyclosporine assayed by High Pressure Liquid

Chromatography. In cats, a concentration of 500ng/ml is maintained for the first 30

postoperative days, reducing to 250ng/ml by three months after transplantation. Prednisolone, 1

mg/kg/12 hours, orally, is also started the evening following surgery and is reduced to 0.5 to 1

mg/kg/24 hours by 1 month postoperatively if renal function is normal. If renal function starts to

deteriorate in the first weeks to months following transplantation, i.e. serum creatinine

concentrations begin to rise above 2 mg/dl, azathioprine (0.3 mg/kg/72hours) is added to the

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immunosuppressive protocol. Cats receiving azathioprine should have blood cell counts and

serum chemistry profiles performed weekly until a safe and effective dose is found. White blood

cells counts should be maintained at >3000 /l and serum chemistry profiles should be evaluated

for evidence of hepatitis or pancreatitis.

Surgery.2,3,5,8

Two teams perform renal transplantation; one team harvests the donor kidney and closes

the abdominal wound, and one team prepares the recipient vessels and receives the kidney. The

two team approach minimizes the warm ischemia time of the donor kidney, which should be kept

to less than 60 minutes, unless preservation protocols are employed 9. The authors have not used

perfusion solutions to maintain the kidney prior to vascularization, but iced heparinized saline

solution is used to flush blood from the kidney following harvest. It is important to thoroughly

cool the kidney immediately following excision from the donor. Cold sponges should be placed

on the kidney during the implantation procedure to keep it from prematurely warming.

Anesthesia protocols vary with each patient. In general, the recipient receives atropine

(.03mg/kg) and oxymorphone (.05mg/kg) subcutaneously prior to induction. The cat is mask or

boxed induced and anesthesia is maintained using isoflurane or sevoflurane inhalant anesthesia

and oxygen. During the procedure, balanced electrolyte solutions and/or whole blood/packed red

blood cells are administered intravenously. Systemic arterial pressure is monitored via direct

arterial catheterization or by indirect measurement using Doppler ultrasonography. Hypotension

can be managed using dopamine (5g/kg/minute intravenously) and fluid boluses as necessary.

Both cats receive broad spectrum antibiotics administered intravenously just prior to surgery. As

the abdominal incision is made, the donor cat should receive mannitol ( 0.5 g/kg as a bolus

followed by a constant infusion of 1mg/kg/minute) to protect the kidney to be transplanted

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during harvest. Mannitol significantly reduces the incidence and duration of acute tubular

necrosis associated with warm ischemia.

The donor nephrectomy is performed via a ventral midline celiotomy. Magnifying

loupes providing 3.3X to 4.5X magnification are recommended for the vascular dissection. The

vascular pedicle of the donor kidney can contain only one artery. Renal arteries may bifurcate

close to the aorta. A length of .5 cm or more is required for arterial anastomosis. If two or more

veins are present, the largest is saved for venous anastomosis. The vascular pedicle should

contain the longest vein possible, so the left kidney is explored first.

Once the kidney to be harvested is selected, the recipient team should be informed so

they can prepare the recipient vessels. It is very important to clean the donor renal artery and

vein of as much fat and adventitia as possible. The large fat pad in the renal pelvis should be

removed, being careful not to damage the ureter. Removal of the fat and adventitia from the

vessels prior to nephrectomy reduces warm ischemia time. The renal vein diameter is measured

and a sterile paper template is made to guide the size of the venotomy in the recipient’s caudal

vena cava. The ureter is isolated to the bladder. Donor nephrectomy is performed when the

recipient team is prepared to receive the kidney. Anastomosis of the renal vessels and the ureter

in the small dog and cat requires 3X to 10X magnification. The higher magnification is

necessary to suture the ureter to the bladder. The authors use an operating microscope.

The recipient post renal aorta and vena cava area isolated via a ventral midline celiotomy.

The kidney is implanted between the left renal artery and the caudal mesenteric artery. First the

aorta is occluded using vascular occlusion clamps. Using an arterotomy clamp, a 1.5 to 2 mm

defect is created in the aortic wall. The lumen of the aorta is flushed with heparinized saline

solution. The caudal vena cava is then occluded adjacent to the arterotomy site in the aorta.

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Using the template created by measuring the donor renal vein, an oval defect is created in the

caudal vena cava. The vena cava is flushed with heparinized saline solution.

Once the recipient vessels have been prepared for implantation of the graft, the donor

kidney is harvested. The kidney is flushed with iced heparinized saline. The renal artery is

gently dilated and adventitia is excised from the distal end. The artery is anastomosed to the

aorta, end-to-side, using 8-0 nylon in a simple continuous pattern. The renal vein is then

anastomosed to the vena cava using 7-0 silk or 8-0 nylon, depending on the size of the vein, in a

simple continuous pattern. Due to a lack of visibility of the wall adjacent to the aorta, the first

side of the vein closest to the aorta is sutured inside the lumen of the vessels (back-wall

technique). Once the first side is sutured, the side away from the artery is sutured in a

conventional manner.

As soon as both the renal artery and vein are sutured, the venous occlusion clamp is

removed, followed by the arterial occlusion clamp. Hemorrhage is controlled by pressure, or by

the addition of simple interrupted sutures if needed.

The ureter is sutured to the bladder in the following manner.1,10.11 A 1 centimeter incision

is made in the seromuscular layer of the bladder on the ventral surface. The mucosa will bulge

through the incision. A 3 to 4 mm incision is made in the mucosa at the caudal aspect of the

seromuscular incision. The periureteral fat is excised from the distal 5 mm of the ureter, and the

end of the ureter is spatulated. Using 8-0 vicryl in a simple interrupted pattern, the mucosa of the

ureter is sutured to the mucosa of the bladder. The proximal and distal sutures are placed first.

A 5-0 polypropylene stent is used to check patency of the stoma. Once the mucosal layers are

opposed, the seromuscular layer is closed over the ureter using 4-0 absorbable suture in a simple

interrupted pattern.

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The kidney capsule is fixed to the abdominal wall by creating a peritoneal/transversus

abdominus muscle flap based on a ventral pedicle. The flap is sutured to the renal capsule using

simple interrupted sutures of 5-0 polypropylene. Fixing the kidney to the abdominal wall

prevents torsion of the kidney on its pedicle with resulting ischemia and loss of the graft. To

provide nutritional support during the postoperative period, a gastrostomy or esophagostomy

tube is placed prior to recovery from anesthesia.

In dogs, the transplanted kidney can be placed in the iliac fossa of the recipient. The

renal vein is anastomosed end-to-side to the external iliac vein using 4-0 or 5-0 silk in a

continuous pattern. The renal artery is anastomosed end-to-end with the external iliac artery

using 4-0 or 5-0 polypropylene suture in a simple interrupted pattern. As in the cat, a

peritoneal/muscle flap is used to secure the kidney to the abdominal wall. The iliac vessels are

no longer used as recipient vessels for feline transplant patients. While not a problem in dogs,

loss of the iliac blood supply in cats can result in ipsilateral hind limb weakness, paralysis and

ischemia.8

Unless there is evidence of bacterial nephritis or severely enlarged polycystic kidneys,

the authors do not remove the recipient’s native kidneys at the time of transplantation. These

kidneys are available to provide some support if the transplanted organ should fail, and can be

removed at a later date if indicated.

Postoperative care of the renal recipient.

During and following surgery, it is imperative to keep the transplant patient warm and

the hematocrit and systolic blood pressure within normal limits. Avoid unnecessary stress and

handling. Postoperative pain is controlled by the administration of oxymorphone (0.05 mg/kg

subcutaneously) as needed. The recipient receives balanced electrolyte solutions supplemented

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to correct electrolyte or acid/base abnormalities.1,11 Urine specific gravity is followed twice daily

via free catch of the urine. Urine specific gravity is usually > 1.020 by the third postoperative

day. Packed blood cell volume, total plasma protein level, serum electrolyte levels and the

plasma creatinine concentration are assessed 3 to 4 times daily until renal function is stable.

During the early postoperative period needless venapuncture, blood sampling and patient

handling should be avoided. If the surgery is a technical success, the urine specific gravity will

be increased, and the plasma creatinine will be decreased by the third postoperative day. The

recipient will look clinically improved and normal appetite usually returns by postoperative day

3 to 5. If the graft has failed or has delayed function, the recipient will be depressed and

anorectic. The urine will remain isosthenuric. Approximately 3 days following surgery, an

ultrasonographic examination of the transplanted kidney and ureter can be performed if renal

function is not returning to normal. If there is good perfusion of the graft without evidence of

hydronephrosis or hydroureter secondary to obstruction, the graft may have suffered acute

tubular necrosis consistent with delayed graft function. As long as the kidney remains perfused,

function can start as late as 3 weeks following surgery.

Hypertension is a common complication that can occur within the first 72 hours after

surgery.13,14 Cats can develop hypertension (systolic blood pressure > 170 mm/Hg) and are at

higher risk for neurologic disorders such as ataxia, blindness, seizures and stupor. Occasionally,

uncontrollable seizures and death can result. Controlling hypertension has significantly reduced

the frequency of these complications. Indirect, systolic blood pressure is measured by ultrasonic

Doppler every hour for at least 24 hours after surgery, and then at decreasing intervals over the

next 48 hours. When the systolic blood pressure is > 170 mm/Hg, hydralazine (2.5 mg total

dose/subcutaneously) is given. If the systolic blood pressure has not decreased to normal within

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15 to 20 minutes, a second dose is given. In the rare case that the hypertension is refractory to

hydralazine therapy, acetylpromazine (0.01 mg/kg, intravenously, subcutaneously) is

administered. Rarely, transplant patients can develop a lethal sensitivity to cyclosporine termed

hemolytic uremic syndrome. 15 Cats become uremic with a coexisting hemolytic anemia and

thrombocytopenia. The transplanted kidney is lost to ischemia produced by diffuse vascular

thrombosis. Currently there is no treatment for this syndrome in cats.

If the transplant recipient is not eating well by 24 hours following surgery, feedings

are begun using the gastrostomy or esophagostomy tube. Normal caloric intake is attained over

24 to 48 hours. Cyclosporine is administered at levels necessary to achieve trough whole blood

concentrations of 500 ng/ml. Prednisolone is administered at 1.0 mg/kg/12 hours, orally, and is

tapered to 0.5 to 1 mg/kg/24 hours by four weeks postoperatively. Erythropoietin can be

administered if the hematocrit remains below 25%.

Transplant recipients are discharged from the hospital when they have achieved an

adequate nutritional intake and the cyclosporine blood level has stabilized. The feeding tube is

left in place until the cat has completely acclimated at home.

Long-term management of the renal recipient.

Management of the transplant patient must be coordinated with the client, the local

veterinarian(s), and the transplant center. Examinations are initially performed weekly by the

local veterinarian. Packed blood cell volume, total serum protein concentration, plasma

creatinine concentration, whole blood cyclosporine concentration and a urinalysis are performed.

Periods between examinations are gradually extended to 3 or 4 weeks. The authors recommend

that a complete blood count should be performed monthly, and a serum chemistry panel,

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urinalysis with urine culture and cardiac consult be performed 3 times a year.

During the first year after transplantation, the most common complications that occur are

acute rejection, infections, and the development of cancers.6,16,17,18,19,20 Acute rejection can often

be attributed to poor owner compliance in giving medications and having cyclosporine blood

concentration assays performed on a regular basis. Acute rejection is an emergency situation

that must be treated quickly and aggressively with injectable cyclosporine (Sandimmune,

[Norvartis AG, Basel, Switzerland], 6.6 mg/kg once daily over 4 to 6 hours), corticosteroids and

the intravenous administration of balance electrolyte solutions. Cats do not show illness

associated with acute rejection, so rising creatinine concentrations are considered grounds for

treatment unless obstructive uropathy can be proven by ultrasonographic evaluation of the

kidney and ureter.21,22 In cats, slow, chronic elevations of serum creatinine, in the face of

adequate blood levels of cyclosporine, are treated with the addition of azathioprine (0.3

mg/kg/72 hours) to the immunosuppressive protocol. The white blood cell count and hepatic

enzyme concentrations must be monitored and the dose adjusted as necessary to prevent severe

leukopenia (<3000 cells/l) or hepatitis.

Transplant patients are susceptible to infections. Viral, bacterial, parasitic, coccidian,

protozoal, and fungal infections can all develop. When treating bacterial infections,

aminoglycoside and trimethoprim/sulfa antibiotics must be avoided as they are nephrotoxic when

combined with cyclosporine. When adding any medication to the immunosuppressive protocol,

check the drug insert that is provided with cyclosporine. Many agents can raise or lower

cyclosporine whole blood concentrations by interfering or promoting cytochrome P-450 enzyme

activity.

Immunosuppressed patients are also at an increased risk for the development of cancer.

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The most common types are lymphoma and squamous cell carcinoma. Transplant recipients also

develop diabetes mellitus with an increased frequency. Diabetes can be temporary or a chronic

problem. Insulin therapy can provide long-term control.

Clinical Renal Transplantation in the Dog

There are only a few differences in the technical aspects of renal transplantation between the

dog and the cat. Most dogs, due to their size, do not require magnification for anastomosis of the

vessels, although 2X to 3X magnifying loops are very helpful. . In addition to implanting the

graft on the terminal aorta and vena cava, the external iliac artery and vein can be used as

recipient vessels for the transplanted kidney. The iliac vessels should not be used for the

recipient vessels in cats since loss of the iliac blood supply in cats can result in rear limb

weakness, paralysis or ischemia. 8

For ease of anastomosis, a left donor kidney is placed in the right iliac fossa of the recipient,

and vise versa. If necessary, a donor kidney can be placed in the ipsilateral iliac fossa of the

recipient, however, the arterial anastomosis will be more difficult to perform. The chosen iliac

fossa is prepared for end to end anastomosis of the renal artery to the iliac artery and end to side

anastomosis of the renal vein to the iliac vein. The iliac artery is isolated, and a bulldog or other

vascular clamp is used to occlude it near the aortic bifurcation. The iliac artery is then ligated

distally, near the femoral ring, and is severed. The free length of the artery is flushed clean of

blood using heparinized saline solution. The end of the artery is gently dilated and the adventitia

is excised from the proximal 3-5 mm. The iliac vein lies deep to the artery in fat and adventitia.

It is isolated over the same area as the artery, gaining as much free length as possible. The iliac

vein has multiple tributary veins in this region that must be ligated. Careful inspection dorsal and

caudal to the vein will reveal these branches. Once the tributary veins have been ligated, two

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vascular clamps are placed on the iliac vein as far apart as possible. The first is placed distally,

and the second is placed proximately. A section of the wall is excised from the iliac vein that is

slightly larger than the diameter of the donor renal vein. It is important to create a defect in the

vein wall and not just a slit. The vein is flushed clean of blood using heparinized saline solution.

Two 4-0 to 6-0 sutures of silk are placed at each end of the defect in the vein wall. Each

suture is subsequently placed at the cranial or caudal aspect of the renal vein and tied. The renal

vein is then anastomosed to the iliac vein using a simple continuous pattern on both the medial

and lateral sides of the vessels.

Following completion of the venous anastomosis, the renal artery and iliac artery are

isolated near the midline of the recipient. The arteries are anastomosed using 5-0 to 8-0 nylon or

polypropylene in a simple interrupted pattern. Once arterial anastomosis is complete, the

vascular clamps are removed from the vein, and then the artery. Some hemorrhage is expected,

can be controlled with light pressure, and should stop within a few minutes. Large defects in the

arterial anastomosis will have to be controlled by placement of additional sutures.

Ureteroneocystostomy is performed using the same method described for the cat. The kidney

capsule is attached to the adjacent abdominal wall using simple interrupted sutures of 3-0

polypropylene or a peritoneal/transversus abdominis muscle flap.

Following renal transplantation, dogs are highly likely to develop intestinal

intussusceptions. Two treatments have resulted in the prevention of this condition that develops

post-operatively. First, morphine, 0.5 mg/ml is administered subcutaneously as a premedication

and postsurgically at 0.5 mg/kg subcutaneously every 3 to 4 hours to control pain.23 Second,

enteroplication is performed after the renal transplant procedure is completed. The seromuscular

layers of the bowel are joined using simple interrupted sutures of 3-0 polydioxanone. 24

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Due to the difficulty of immunosuppressing the dog rejection response, few renal

transplants have been performed clinically for canine renal failure patients. The primary

difference in transplantation between the dog and cat is selection of the donor. Using

cyclosporine and prednisolone to achieve immunosuppression, the authors will only use mixed

lymphocyte response matched, related donors. The new formulation of cyclosporine, with

conventional or newly developed agents, has proven to successfully control the canine rejection

response.25,26 With the use of MHC-nonmatched donors, the authors employ one of two

immunosuppressive protocols: 1)cyclosporine and leflunomide (4-6 mg/kg/24 hours) or 2)

cyclosporine (Neoral), azathioprine (1-5 mg/kg every 48 hours) and prednisolone (1 mg/kg/24

hours). Cyclosporine is administered at a dose that will achieve a trough whole blood level of

500 ng/nl. Leflunomide is administered at a dose necessary to maintain a trough plasma blood

concentration of 20 g/ ml. Azathioprine dosage is adjusted to avoid leukopenia and hepatitis.

The dose of prednisolone is reduced over 1 to 3 months depending on the serum creatinine

concentration and degree of side effects suggestive of Cushing’s Syndrome. In a long on-going

study, Mathews et al employed antithymocyte serum, cyclosporine, azathioprine and

prednisolone for immunosuppression of unrelated dog donor-recipient pairs. A median survival

time of 8 months was achieved with 2 dogs surviving more than 2 years.27 In a recently

completed clinical study, the authors found that the combination of cyclosporine, azathioprine

and prednisolone prevented renal allograft rejection in 15 dogs. Three dogs are currently alive

24 to 50 months following surgery. Five of the dogs died in the perioperative period due to the

development of systemic thromboembolism. Four of the dogs died due to the development of

lethal bacterial infections. Renal allograft rejection can be controlled in the dog. However, a

balance must be maintained between the control of rejection and the development of lethal

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infections. Due to the hypercoagulable state present in the canine renal failure patient,

perioperative anticoagulation therapy must be employed (Gregory CR et al. Unpublished paper

in review).

Canine renal transplantation is still in the development phase. The work of Mathews et al

and our own studies have been invaluable in highlighting the techniques and the difficulties, both

clinically and financially. Over the next several years, case selection, immunosuppressive

management and anticoagulation strategies will be further refined, and outcomes will improve.

Client Education

Before performing renal transplantation for the dog or cat, clients must be fully

informed of the risks, responsibilities and costs associated with the procedure. Clients must be

able to administer medications orally two times a day for the life of their pet. Fractious cats and

dogs are not good candidates because of the extensive nursing required in the perioperative

period and the need for regular examinations by the local veterinarian. Clients must have access

to a 24 hour emergency facility. Finally, clients must understand that no matter how carefully

selected and managed, their cat or dog may die due to the stress of the procedure or failure of the

graft to function.

Feline and canine renal transplantation is becoming more widely available

in the United States and is also performed in Australia, Japan and Europe. Survival rates have

improved with careful patient selection, better perioperative care and monitoring, and the

introduction of the microemulsified form of cyclosporine (Neoral). Renal transplantation can

offer long-term survival with a normal quality of life for cats and dogs with renal failure.

References:

Bernsteen L, et al. Renal transplantation in cats. Clin Tech Sm An Prac

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15:40, 2000

2 . Gregory CR: Renal transplantation in the cat. Comp Cont Ed Pract Vet

15:1325, 1993

3. Gregory CR, Gourley IM: Organ transplantation in clinical veterinary

medicine. In: Slatter D (ed): Textbook of Small Animal Surgery, 2nd

Ed, WB Saunders Company, Philadelphia, 1993, pp 95-101.

4. Kochin E.J. and Gregory CR: Renal transplantation:patient selection

and postoperative care. In: Consultations in Feline Internal Medicine, 2nd Ed, WB Saunders

Company, Philadelphia, 1993 pp 339-342.

5. Gregory CR, Bernsteen L: Organ Transplantation in Clinical Veterinary Practice. In Slatter

D, ed.: Textbook of Small Animal Surgery, 3rd ed. Philadelphia, WB Saunders Co, 2003, p

122.

6. Bernsteen L, et al: Acute toxoplasmosis following renal transplantation in

three cats and a dog. JAVMA 215: 1123, 1999.

7. Lirtzman R A, Gregory CR. Long-term renal and hematologic effects of

uninephectomy in healthy feline kidney donors. JAVMA 207: 1044,

1995.

8. Bernsteen L, et al: Comparison of two surgical techniques for renal transplantation in

cats. Vet Surg 28:417, 1999

9. McAnulty JF: Hypothermic storage of feline kidneys for transplantation: successful ex

vivo storage up to 7 hours. Vet Surg 27:312, 1998

10. Kochin E.J. and Gregory CR. Evaluation of a method of ureteroneocystotomy

in the cat. JAVMA 202: 257,1993.

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11. Gregory CR et al: A mucosal apposition technique for ureteroneocystostomy after renal

transplantation in cats. Vet Surg 25:13, 1995.

12. Wooldridge JD, Gregory CR: Ionized and total serum magnesium concentrations in

feline renal transplant recipients. Vet Surg 28:31, 1999.

13. Gregory CR et al: Central nervous system disorders after renal

transplantation in cats. Vet Surg 26:386, 1997

14. Kyles A E, et al: Management of hypertension controls postoperative

neurologic disorders after renal transplantation in cats. Vet Surg 28:436, 1999.

15. Aronson LR, Gregory CR: Possible hemolytic uremic syndrome in three

cats after renal transplantation and cyclosporine therapy. Vet Surg 28:135,

1999.

16. Gregory CR et al. Preliminary results of clinical renal allograft transplantation

in the dog and cat. J Vet Int Med 1:53, 1987

17. Gregory CR et al: Feline leukemia virus-associated lymphosarcoma

following renal transplantation in a cat. Transplantation 52(6):1097, 1991

18. Gregory CR et al: Renal transplantation for treatment of end-stage renal

failure in cats. JAVMA 201:285, 1992

19. Gregory CR et al: Oxalate nephrosis and renal sclerosis after renal

transplantation in a cat. Vet Surg 22:221, 1993

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