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Today’s Veterinary Practice November/December 201136
The ability to perform renal
transplantation as a treatment
in cats has been attributed to a
number of factors including the:
•Development of microsurgical techniques in
veterinarypractice
•Ability to use an allograft from an unrelated
donor
•Applicationofthedrugcyclosporineforimmu-
nosuppressivetherapy.3-5
It is estimated that between 400 to 500 cases of
felinerenaltransplantationhavebeenperformedat
a few limited centers around the country (Table).Ina
studycomparingsurvivaltimeofcatsthathadunder-
gone a renal transplant to a control population of cats
treated medically, renal transplantation appeared to
prolongsurvival timeandqualityof lifecompared
withthemedicalmanagementofthedisease.6
Althoughthereisnotaretrospectivestudyencom-
passingallofthecasesthathavebeenperformedto
date, both published and unpublished information
fromdifferentcenterssuggeststhatsurvivaltodis-
chargeandlong-termsurvivalareimproving.6,7 This
is likely related to:
•Morestringentcaseselection
•Surgicalexperience
•Theclinician’sabilitytobetterrecognizeearly,
and treat successfully, both peri-operative as
wellaslong-termcomplications.
Insights into Feline Kidney TransplantsLillian R. Aronson, VMD, Diplomate ACVS
Renal transplantation
continues to remain a viable
treatment option for cats with
early decompensated chronic
kidney disease or irreversible
acute renal failure.1,2
PeeR RevIewed
November/December 2011 Today’s Veterinary Practice 37
InsIghTs InTo FelIne KIdney TransPlanTs |
INDICATIONS
The most common histopathologic diagnosis (identi-
fiedfromnativekidneybiopsysamples)ofcatsneed-
ingarenaltransplantischronicinterstitialnephritis.
Other conditions that have resulted in renal trans-
plants in the cat include:
•Polycystickidneydisease
•Oxalatenephrosis
•Membranousglomerulonephropathy
•Ethyleneglycol&lilytoxicity
•Renalfibrosis
•Amyloidosis
•Pyelonephritis
•Renaldysplasia.
Because of the potential long-term effect on the
allograft, it is unclear whether patients with pyelone-
phritis or amyloidosis are appropriate candidates for
theprocedure.
RECIPIENT SELECTION
Thebest time to intervenewith surgery isnot com-
pletely known in this patient population. Surgical
interventionhasbeenrecommendedincatswithearly
decompensated chronic kidney disease or irrevers-
ibleacuterenalfailure.8,9 Indications of decompensa-
tion include continued weight loss, worsening of the
anemia,andazotemiainthefaceofmedicaltherapy.
It is important to note that some clinically stable can-
didates can rapidly deteriorate and die without prior
evidenceofdecompensation.
Evaluating Potential Candidates
Both physical and biochemical parameters need to be
carefully evaluated when determining a cat’s candi-
dacy for renal transplantation.Currentevaluationat
ourfacilityinvolves:
•Laboratory tests:Completebloodcount,serum
biochemistry profile, blood type and crossmatch,
andthyroidevaluation
•Urinary tract evaluation: Urinalysis, urine cul-
ture, and urine protein:creatinine ratio
•Abdominal evaluation:Abdominalradiographs
and ultrasound
•Cardiovascular disease evaluation: Thoracic
radiography, electrocardiography, echocardiogra-
phy, and blood pressure measurement
•Screening for infectious disease: FeLV, FIV,
Toxoplasmatiter(IgG,andIgM).
Based on historical experience, cats that are FeLV
positiveorhaveanactiveFIVinfection,patientswith
recurrent urinary tract infections that have failed a
cyclosporine challenge (see Why a Cyclosporine
Challenge?), and those with underlying neoplasia are
declinedascandidatesfortheprocedure.
Risk & Survival Factors
Limitedinformationexistsregardingriskfactorsasso-
ciatedwithmorbidityandmortalityinthesepatients.
Table. Feline renal Transplantation Centers in the U.s.
Veterinary Hospital Contact
Michigan Veterinary specialistsmichvet.com
daniel a. degner, dVM, diplomate aCVs
north Carolina state University College of Veterinary Medicinecvm.ncsu.edu/index.html
Kyle g. Mathews, dVM, diplomate aCVs
University of Florida College of Veterinary Medicinevetmed.ufl.edu
gary ellison, dVM, Ms, MrCVs, diplomate aCVs
University of georgia school of Veterinary Medicinevet.uga.edu
Chad schmeidt, dVM, diplomate aCVs
University of Pennsylvania school of Veterinary Medicinevet.upenn.edu
lillian r. aronson, VMd, diplomate aCVs
University of Wisconsin school of Veterinary Medicinevetmed.wisc.edu/home
Jonathan F. Mcanulty, dVM, Ms, Phd
WHy A CyCLOSPORINE CHALLENgE?a cyclosporine challenge is performed prior to renal transplantation to help determine if a patient is harboring an infection that may be detrimental to the patient, resulting in morbidity and mortality after renal transplantation and immunosuppression.
To perform a cyclosporine challenge, the patient is started on oral cyclosporine (2–5 mg/kg depending on patient’s appetite) at a dose necessary to obtain therapeutic levels (300–500 ng/ml). once therapeutic levels are obtained, the patient is kept on the medication for ~2 weeks. during that time, the patient is evaluated for any recurrence of infection.
| InsIghTs InTo FelIne KIdney TransPlanTs
•The degree of anemia, azotemia, urine spe-
cificgravity,andagedonotdetermineasuitable
patient for transplantation, although azotemia
hasbeenidentifiedwithcomplications.
•The degree of azotemia prior to surgery was
foundtobeariskfactorin1study.6 In a second
study,thelevelofazotemiasignificantlyincreased
the risk of neurologic complications in the periop-
erativeperiod, butwasnot related to long-term
survival.11
•In 3 separate studies, age was identified as a
factor associated with survival following dis-
charge.6,11,12Preoperativebloodpressure,duration
ofanesthesia, andweighthavealsobeenshown
toinfluenceoverallsurvival.6,12
Objective information is still needed for a number
of gray areas, including cats with echocardiographic
abnormalities, hyperthyroidism, diabetes, inflamma-
tory bowel disease, and upper respiratory infections.
Additionally,questionsregardingtheappropriatenutri-
tionalstatusforthesepatientscomesuprepeatedly.
POTENTIAL DONOR EVALUATION
Kidney donors are young (1–3 years of age) and in
excellenthealth.Standardscreeningincludes:
•Complete blood count and serum biochemistry
profile
•Urinalysisandculture
•FeLVandFIV testingandToxoplasma titer (IgG
andIgM).
To determine compatibility, a blood type and red cell
crossmatch are performed between the feline kidney
donor and recipient. Although rare, incompatible
crossmatch tests between AB compatible donor and
recipientpairshavebeenidentified.13Additionally,we
Today’s Veterinary Practice November/December 201138
AN ImPERATIVE INCLUSION:
ImmUNOSUPPRESSIONCurrent immunosuppression in the cat includes a combination of the calcineurin inhibitor—cyclosporine (neoral, pfizer.com)—and the glucocorticoid—prednisolone. These drugs are used together for their synergistic effects.
Cyclosporine
• Atourfacility,cyclosporineisbegun24to96H
priortotransplantationatadoseof1to4mg/kg
Po Q 12 h, depending on the patient’s appetite. • A12-hourwhole-bloodtroughconcentration
is obtained the day prior to surgery to adjust the oral dose for surgery. Ideally, through the useofhigh-pressureliquidchromatography,a
target12-hourtroughconcentrationof300to
500 ng/ml prior to surgery is the goal. • Thislevelismaintainedforapproximately2to
3 months and then tapered to approximately 250 ng/ml for maintenance therapy.
Prednisolone • Prednisoloneisadministeredbeginningthe
morning of surgery.• Itisstartedatadoseof0.5to1mg/kgPOQ12
Hforthefirst3months;thentaperedtoQ24H.
Azathioprine
It is important to note that protocols for both cyclosporine and prednisolone vary between transplantation facilities. If renal function starts to deteriorate in the first weeks to months following transplantation, azathioprine (0.3 mg/kg Q 72 h) may be added to the immunosuppressive protocol. Cats receiving azathioprine should have their white blood cell count monitored regularly.
Ketoconazole
another option for immunosuppression currently inclinicaluseisaprotocolforonce-a-day
administration of ketoconazole:•Ketoconazole,10mg/kgPOQ24H,is
administered in addition to the cyclosporine and prednisolone.1,2
•Onceketoconazoleisaddedtothe
immunosuppressive protocol, cyclosporine and prednisolone are administered once a day and cyclosporine doses are adjusted intothetherapeuticrangebymeasuring24H
whole blood trough levels.•Ifsignsofhepatotoxicityareidentified,
ketoconazole administration should be discontinued.
1. Katayama M, McAnulty JF. Renal transplantation in cats:
Techniques, complications, and immunosupression.
Compend 24:874, 2002.
2. McAnulty JF, Lensmeyer GL. The effects of ketoconazole
on the pharmacokinetics of cyclosporine A in cats. Vet Surg
28:448,1999.
Figure 1. Arterial phase of CT angiography; this
technique allows accurate evaluation of the renal
vasculature of the donor cat prior to nephrectomy
November/December 2011 Today’s Veterinary Practice 39
InsIghTs InTo FelIne KIdney TransPlanTs |
currently perform computed tomography (CT) angi-
ographytoevaluatetherenalvasculatureandparen-
chyma for abnormalities (Figure 1).14Thistechnique
has allowed us to identify patients unsuitable for dona-
tion prior to surgery, including patients with renal
infarctsaswellasthosewithmultiplerenalarteries.
Although, inmy experience, renal donation does
notappeartoaffectnormallifeexpectancy,long-term
monitoringisrecommended.
TRANSPLANT SURgERy
Preoperative Care
Preoperativecarewillvarydependingonthestability
ofthepatient.
•Hemodialysis may be necessary in some cases in
ordertostabilizethepatientpriortosurgery.
•Intravenous fluid therapy of a balanced electro-
lytesolution(1.5–2×dailymaintenancerequire-
ments)isadministeredtomostpatients.However,
underlying cardiac disease may preclude this rate
of fluid therapy due to development of pulmo-
naryedemaandpleuraleffusion.
•Whole blood transfusions or packed red cells
may be used to correct anemia (depending on
the stability of the cat) prior to or at the time of
surgery. The first unit that is administered is a
unitthathadbeenpreviouslycollectedfromthe
crossmatchcompatibledonorcat.Ithasbeensug-
gested that the administration of a unit of blood
from the donor cat may decrease the incidence of
allograftrejection.
•Hormonal therapy, including darbopoietin or
erythropoietin, can be administered if a delay
in the transplant procedure is expected. This
therapy can greatly reduce the need for blood
products at time of surgery.
Although uncommon, antibod-
iestoerythropoietinhavebeen
identified in cats and owners
should be cautioned that this
could result in significant mor-
bidity and increase in cost dur-
ing the postoperative period.
The current risk with darbopoi-
etin is unknown at this time,
but thought to be less than with
erythropoietin.
•Calcium channel blocker
amlodipine (Norvasc, Pfizer.
com)maybe indicated (0.625
mg/catPOQ24H)ifthecatis
hypertensive.
•Gastrointestinal protectants
and phosphate binders are
given if deemed necessary; a
nasogastric or esophagostomy
tube may be placed prior to
surgeryifthecatisanorectic.
Figure 2. Image of the surgical set up for the transplant procedure; in our
facility, the donor and recipient surgeries are performed simultaneously
Figure 3. Isolation of the donor renal artery (A)
and vein (B) for nephrectomy
A
B
Today’s Veterinary Practice November/December 201140
| InsIghTs InTo FelIne KIdney TransPlanTs
•Immunosuppression is begun in our facility
24 to 96 H prior to transplantation. See An
Imperative Inclusion: Immunosuppression
(page 38) for a complete discussion on this criti-
calaspectoftransplantation.
Surgery
Currently,atourfacility,3surgeonsareinvolvedwith
each transplant procedure: 2 surgeons to perform
the procedure on the donor and recipient and a third
surgeon to close the donor following nephrectomy
(Figure 2,page39).
Donor Surgery
Thedonorisbroughtintothesurgicalsuiteapproxi-
mately 45 min prior to the recipient to allow prepara-
tionofthedonorkidneyforthenephrectomy.
1.The left and right kidneys are examined for a
vascular pedicle that consists of a single artery.
Theleftkidneyispreferredbecauseitprovidesa
longerveinthantherightkidney(Figure 3, page
39). The renal artery and vein are cleared of as
muchfatandadventitiaaspossible.
2.Theureterisdissectedfreetothepointwhereit
joins thebladder.Thenephrectomywill beper-
formedwhentherecipientispreparedtoreceive
thekidney.
3.At thetimeof theoriginal incision, thedonor is
given a doseofmannitol (0.25 g/kg IV). Fifteen
min prior to nephrectomy, an additional dose (1
g/kgIV)isgiventothedonorcat.
4.Mannitol is used to reduce the incidence and
duration of acute tubular necrosis that can occur
duringwarmischemia.
Recipient Surgery
The majority of the recipient surgery is performed
usinganoperatingmicroscope.
1.Inthecurrentsurgicalprocedure,therenalartery
is anastomosed end-to-side to the caudal aorta
(proximal to the caudalmesenteric artery), and
therenalvein isanastomosedend-to-side to the
caudalvenacava(Figure 4).
2.Partial occlusion clamps are used to obstruct
blood flow in both vessels. Using templates
madefromthedonorvessels,windowsarecre-
atedthatmatchthesizeoftherenalarteryand
vein,respectively.Nylonsuture(8-0)isusedfor
the arterial anastomosis and silk (7-0) for the
venous anastomosis. Suture size and type may
vary depending on the facility performing the
procedure.
CLIENT EDUCATIONIt is important for clients to understand that they are embarking on a commitment that exists for the lifetime of their cats. In addition, while renal transplantation is a treatment option for cats in renal failure, it is not a cure.
Candidacy: not every cat is a candidate for the procedure and an owner needs to be informed that his or her cat may be turned down for treatment if the cat fails any aspect of the screening process.
Risks: The owner needs to be aware of risks that can occur in the immediate perioperative period and months to years following surgery. a veterinaryhospitalthatcanprovide24-hourcare
must be identified as well as a veterinarian who is willing to care for a renal transplant recipient.
medical Therapy: although medical therapy, including subcutaneous fluid therapy, low protein diets, phosphate binders, hormonal therapy, antihypertensive medication, and gastrointestinal protectants can often be discontinued following transplantation, clients need to realize that their pets will need to be on immunosuppressive therapy for life.
Cost: additionally, the owner must be made awareofbothshort-andlong-termcosts,
including the cost of the transplant procedure and additional costs once the cat leaves the transplant facility, such as repeated veterinary visits, treatment of potential complications, and lifelong medical therapy.
Donor Adoption: Finally, one of the most important aspects of any transplant program is donor adoption. The client must be willing to provide a lifelong home for the donor animal regardless of the outcome of the transplant procedure.
Figure 4. Image of the native and allograft
kidney. The native kidney can be seen on the left
adjacent to the gloved finger. The suture in the
native kidney marks the location of a renal biopsy.
The allograft is on the right. The native kidneys
are usually left in situ to act as a reserve if graft
function is delayed.
November/December 2011 Today’s Veterinary Practice 41
InsIghTs InTo FelIne KIdney TransPlanTs |
3.Oncethevascularanastomosisisfinished,aure-
teroneocystotomyisperformedusingatechnique
to appose ureteral and bladder mucosa. Three
techniqueshavebeendescribedandarecurrently
being performed at different centers around the
country.Atourfacility,anintravesicularmucosal
appositiontechniqueisused.15Twoextravesicular
techniqueshavealsobeendescribed,includinga
techniqueinwhichtheentireureterandureteral
papillafromthedonorisharvested.16,17
4.Prior toclosure,1of thenativekidneys isbiop-
siedandtheallograftispexiedtotheabdominal
wall using 6 interrupted sutures of 5-0 prolene to
preventtorsionandavulsion.Thenativekidneys
arenotremovedatthistimesincetheycanactas
areserveifgraftfunctionisdelayed.Ifwarranted,
thenativekidneyscanberemovedatalaterdate.
Postoperative Care
•Therecipientisadministeredabalancedelectro-
lytesolutionuntilwaterandfoodareaccepted.
•Blood analysis, including a packed cell volume,
total protein, renal panel, and blood cyclosporine
levelarecheckedevery2to4days.
•Broadspectrumantibioticsareadministered.
•Voidedurineiscollectedandassesseddaily.
•Central venous pressure is measured continu-
ouslyuntilfluidbalancestabilizesandthepatient
canbeweanedfromfluidtherapy.
•Duringthefirst48hours,bloodpressureismonitored
every1to2hoursforthedevelopmentofhypertension.
» If the systolic blood pressure is ≥ than 180 mm
Hg,hydralazine(2.5mgSCforanapproximately
4-kgcat)isadministered.
» Ifthecatisrefractorytohydralazine,aceproma-
zine(0.005mg/kgIV)hasbeenused.
COmPLICATIONS
Peri-Operative Complications
Typically, azotemia resolveswithin the first24 to72
Hfollowingsurgery.Ifimprovementinrenalfunction
doesnotoccuror improvement is initially identified
butthenworsens,anultrasonographicexaminationof
the allograft is recommended:
•The allograft should be evaluated for adequate
blood flow as well as any signs of a ureteral
obstruction including hydronephrosis and/or
hydroureter. If repeat ultrasonographic evalua-
tions reveal worsening hydronephrosis, then a
ureteral obstruction should be suspected and the
cattakenbacktosurgery.
•If graft perfusion has ceased, torsion of the
allograft or thrombosis of the renal artery with
vascular obstruction may have occurred. If no
sign of urine flow obstruction is present and graft
perfusionisadequatethendelayedgraftfunction
shouldbeconsidered.
Following discharge, the cat should be examined
weeklyuntilcyclosporinelevelshavestabilized(typi-
cally6–8weeks).Duringeachexamination,renalfunc-
tionandurineshouldalsobeevaluated.Theintervals
between veterinary visits are increased once the cat
stabilizes(4×/yearinstablepatients).
Long-Term Complications
Long-term complications that still challenge us include
those associated with the allograft and complications
secondarytochronicimmunosuppressivetherapy.
Renal Complications
Renalcomplicationsfollowingtransplantationinclude:
•Acuteandchronicrejection
•Calciumoxalatenephrosis
A B
Figure 5. Gastrointestinal lymphosarcoma in a
cat (A) 4 years following renal transplantation with
metastasis to the renal allograft (B); note the 2 native
polycystic kidneys in B
Today’s Veterinary Practice November/December 201142
| InsIghTs InTo FelIne KIdney TransPlanTs
•Allograftrupture
•Delayedgraftfunction
•Hemolyticuremicsyndrome
•Ureteralcomplications,includingretroperitoneal
fibrosis.
Suspectedacuterejectionepisodesaretreatedwith
intravenousadministrationofcyclosporine,6.6mg/kg
Q24Hover4to6H,andprednisolone,10mg/kgIV
Q12H.Thistreatmentcanberepeatedifnecessary.
Immunosuppressive Complications
Complicationssecondarytochronicimmunosuppres-
sivetherapyinclude:
•Developmentofinfections(includingopportunis-
tic infections)
•Diabetesmellitus
•Neoplasia.
Toxoplasma gondiiseropositivecatsremainaccept-
ablecandidatesfortransplantation,butshouldreceive
lifelong prophylactic chemotherapeutics to prevent
fatal infections.Theprevalenceofmalignantneopla-
sia in cats following renal transplantation has been
reportedfrom9.5%to24%,withlymphomabeingthe
most common type reported (Figure 5,page41).18,19
Turntopage16toreadthearticle
Lymphoma in Dogs & Cats: What’s the
Latest. dr. erika Krick, who specializes in feline lymphoma, presents the latest information regarding diagnostics and therapy for this common neoplasia.
CONCLUSION
Renal transplantation has become a life-savingmea-
sureforcatswithrenalfailure.
Based on published and unpublished reports of cats
havingundergonerenaltransplantation,70%to92%
weredischargedfromthehospitalandmediansurvival
timesrangedfrom360to613days.6,7,20Currentinforma-
tion suggests that survival times followingdischarge
areimproving.3,6,7,20
Continued clinical experience in themanagement
of both short- and long-term complications, as well
as the ability to identify specific risk factors both pre-
andpostoperativelywillhopefullycontinuetoimprove
long-termoutcomeinthesepatients.■
CT = computed tomography; FelV = feline leukemia virus; FIV = feline immunodeficiency virus; Igg = immunoglobulin g; IgM = immunoglobulin M
References
1. Gregory CR, Bernsteen L. Organ transplantation in clinical veterinary
practice. In Slatter dH (ed): Textbook of Small Animal Surgery.
Philadelphia: wB Saunders, 2000, p 122.
2. Mathews KG. Renal transplantation in the management of chronic
renal failure. In August J (ed): Consultation in Feline Internal Medicine,
4th ed. Philadelphia: wB Saunders, 2001, p 319.
3. Gregory CR, Gourley IM, Taylor NJ, et al. Preliminary results of clinical
renal allograft transplantation in the dog and cat. J Vet Intern Med
1987; 1:53.
4. Gregory CR, Gourley IM. Organ transplantation in clinical veterinary
practice. In Slatter dH (ed): Textbook of Small Animal Surgery.
Philadelphia: wB Saunders, 1993, p 95.
5. Gregory CR. Renal transplantation. In Bojrab MJ (ed): Current
Techniques in Small Animal Surgery. 4th ed. Philadelphia: Lippincott,
williams and wilkins, 1998, p 434.
6. Schmeidt Cw, Holzman G, Schwarz T, et al. Survival, complications
and analysis of risk factors after renal transplantation in cats. Vet Surg
2008; 37:683.
7. Mathews KG, Gregory CR. Renal transplants in cats: 66 cases (1987-
1996). JAVMA 1997; 211:1432.
8. Gregory CR, Bernsteen L. Organ transplantation in clinical veterinary
practice. In Slatter dH (ed): Textbook of Small Animal Surgery.
Philadelphia: wB Saunders, 2000, p 122.
9. Mathews KG. Renal transplantation in the management of chronic
renal failure. In August J (ed): Consultation in Feline Internal Medicine,
4th ed. Philadelphia: wB Saunders, 2001, p 319.
10. Katayama M, McAnulty JF. Renal transplantation in cats: Patient
selection and preoperative management. Compend 24:868, 2002.
11. Adin CA, Gregory CR, Kyles Ae, et al. diagnostic predictors and
survival after renal transplantation in cats. Vet Surg 2001; 30:515.
12. Snell w, Aronson LR, Beale L, et al. Retrospective descriptive
evaluation of the anesthetic records of 100 cats undergoing renal
transplantation surgery: Preliminary results. Unpublished manuscript.
13. weinstein NM, Blais MC, Harris K, et al. A newly recognized blood
group in domestic shorthair cats: The Mik red cell antigen. J Vet Intern
Med 21:287, 2007.
14. Bouma JL, Aronson LR, Keith dM, et al. Use of computed
tomography renal angiography for screening feline renal transplant
donors. Vet Radiol Ultrasound 2003; 44:636.
15. Gregory CG, Lirtzman R, Kochin eJ, et al. A mucosal apposition
technique for ureteroneocystostomy after renal transplantation in cats.
Vet Surg 1996; 25:13.
16. Hardie RJ, Schmiedt C, Phillips L, et al. Ureteral papilla implantation as
a technique for neoureterocystotomy in cats. Vet Surg 34:393, 2005.
17. Mehl ML, Kyles Ae, Pollard R, et al. Comparison of 3 techniques for
ureteroneocystostomy in cats. Vet Surg 34:114, 2005.
18. Schmeidt Cw, Grimes JA, Holzman G. Incidence and risk factors for
development of malignant neoplasia after feline renal transplantation and
cyclosporine-based immunosuppression. Vet Comp Oncol 2009; 7:45.
19. wooldridge J, Gregory CR, Mathews KG, et al. The prevalence of
malignant neoplasia in feline renal transplant recipients. Vet Surg 2002;
31:94.
20. Aronson LR. Renal transplantation. Unpublished manuscript, 2009.
Lillian R. Aronson, VMD,
Diplomate ACVS, is an
associate professor of
surgery and the coordinator
and founder of the Feline
Renal Transplant Program
in the Soft Tissue Surgery
Service at University of
Pennsylvania’s Matthew J.
Ryan Veterinary Hospital.
Dr. Aronson successfully
initiated the Feline Renal Transplant Program
in 1998, after serving as the coordinator of the
renal transplant program for animals at University
of California–Davis. In addition to feline renal
transplantation, her research expertise includes
canine renal transplantation, feline lymphocyte
proliferation and cytokine gene expression, and
microvascular surgery. Dr. Aronson received her
veterinary degree and completed an internship
at UPenn and completed a small animal surgical
residency at UCDavis.