Renal Allograft Survival in Outbred Mongrel Dogs Using Rabbit Anti-Dog Thymocyte Serum in Combination With Immunosuppressive Drug Therapy With or Without Donor Bone Marrow

Therapeutic renal transplantation in dogs is currently being investigated as a treatment for end-stage renal disease. This pilot study examines the effect of donor bone marrow (DBM) infusion and antithymocyte serum (ATS) in combination with immunosuppressive drug therapy in prolonging renal allograft survival in dogs. Seven normal outbred mongrel dogs received an unmatched renal allograft. All dogs received rabbit anti-dog thymocyte serum (RADTS), prednisone (Pr), cyclosporine-A (CsA) and azathioprine (Aza). In addition, three dogs (group 1 test) received DBM and four dogs (group 2 control) did not receive DBM. Serum CsA levels were measured throughout the study. Immunosuppressive therapy was gradually reduced with Pr, CsA, and Aza withdrawn at 200,450, and 680 days, respectively. Allograft rejection was treated with prednisolone sodium succinate. One dog in group 1 and one in group 2 died as a result of infectious canine rhinotracheitis and rejection early in the study. Renal allograft torsion occurred in one group 1 dog. The remaining four dogs survived the 2 years of the study. The dogs in group 2 (three dogs) all rejected the renal allograft after total drug withdrawal, the surviving dog in group 1 did not. This study demonstrates that RADTS, Pr, CsA, and Aza in combination can prolong renal allograft survival in mongrel dogs, whereas DBM may enhance the unresponsive state.     

Kidney transplantation in dogs with naturally occurring end-stage renal disease

Renal allografts were performed between unrelated donors and 15 dogs with naturally occurring end-stage renal disease. Donor selection was based on compatible dog erythrocyte antigen typing and cross-matching. An immunosuppressive protocol consisting of rabbit antidog antithymocyte serum, cyclosporin-A, azathioprine, and prednisone was used to control postoperative rejection of the donated kidney. Although seven animals died because of technical failures or rejection episodes, a median survival time of eight months has been achieved, with two dogs living for longer than five years after surgery. Long-term survivors have died from a variety of problems not related to renal allograft rejection.     

Pharmacokinetics of tacrolimus after multidose oral administration and efficacy in the prevention of allograft rejection in cats with renal transplants

OBJECTIVE: To describe pharmacokinetics of multi-dose oral administration of tacrolimus in healthy cats and evaluate the efficacy of tacrolimus in the prevention of allograft rejection in cats with renal transplants. ANIMALS: 6 healthy research cats. PROCEDURE: Cats received tacrolimus (0.375 mg/kg, PO, q 12 h) for 14 days. Blood tacrolimus concentrations were measured by a high performance liquid chromatography-mass spectrometry assay. Each cat received an immunogenically mismatched renal allograft and native kidney nephrectomy. Tacrolimus dosage was modified to maintain a target blood concentration of 5 to 10 ng/mL. Cats were euthanatized if plasma creatinine concentration exceeded 7 mg/dL, body weight loss exceeded 20%, or on day 50 after surgery. Kaplan-Meier survival curves were plotted for 6 cats treated with tacrolimus and for 8 cats with renal transplants that did not receive immunosuppressive treatment. RESULTS: Mean (+/- SD) values of elimination half-life, time to maximum concentration, maximum blood concentration, and area under the concentration versus time curve from the last dose of tacrolimus to 12 hours later were 20.5 +/- 9.8 hours, 0.77 +/- 0.37 hours, 27.5 +/- 31.8 ng/mL, and 161 +/- 168 hours x ng/mL, respectively. Tacrolimus treated cats survived longer (median, 44 days; range, 24 to 52 days) than untreated cats (median, 23 days; range, 8 to 34 days). On histologic evaluation, 3 cats had evidence of acute-active rejection, 1 cat had necrotizing vasculitis, and 2 cats euthanatized at study termination had normal appearing allografts. CONCLUSIONS AND CLINICAL RELEVANCE: Tacrolimus may be an effective immunosuppressive agent for renal transplantation in cats.     

Results of clinical renal transplantation in 15 dogs using triple drug immunosuppressive therapy

OBJECTIVE: To evaluate outcome of renal transplantation in dogs administered cyclosporine, azathioprine, and prednisolone immunosuppression. STUDY DESIGN: Prospective clinical study. ANIMALS: Fifteen dogs with chronic renal failure. RESULTS: Nine dogs died within 1 month of surgery; 5 died from complications associated with generalized thromboembolism. Three dogs survived for 6-25 months. Three dogs alive at the time of this report have survived 22-48 months; however, all 3 dogs have had bacterial infections that responded to antibiotic therapy. There was no biochemical evidence of acute allograft rejection in any dog. Perioperative use of enoxaparin may have prevented thromboembolism in 5 dogs. CONCLUSIONS: Triple drug immunosuppressive therapy used in this study prevented acute renal allograft rejection in 6 dogs that survived >4 weeks; however, immunosuppression was excessive, resulting in an unacceptable frequency of infection and other drug-related complications. Perioperative anticoagulation therapy seem to be warranted. CLINICAL RELEVANCE: Survival time and quality of life for this group of dogs was poor; however, there was no evidence of acute rejection in the dogs surviving >4 weeks. This protocol should only be used if the degree of immunosuppression is reduced, and early evidence of allograft rejection is monitored by renal biopsy or markers of lymphocyte activation.     

Use of capecitabine to prevent acute renal allograft rejection in dog erythrocyte antigen-mismatched mongrel dogs

OBJECTIVE: To assess efficacy and toxicity of a capecitabine (CAP)-based regimen for preventing rejection of renal allografts in dog erythrocyte antigen (DEA)-mismatched mongrel dogs. STUDY DESIGN: Prospective, pilot study. ANIMALS: Eight healthy, unrelated, DEA mismatched, adult mongrel dogs. METHODS: All dogs received CAP, starting at 50 mg/m2 PO b.i.d. 4 days preoperatively, increasing to 200 mg/m2 PO b.i.d. by the day of surgery. All dogs received cyclosporine-A (CsA) and prednisolone starting 2 days preoperatively. Standard heterotopic renal transplantation with native nephrectomy was performed. After 90 days, surviving dogs were euthanatized and histopathologic examination was performed. RESULTS: Two of 8 dogs developed acute neurotoxicity leading to death or euthanasia within 5 days of surgery. For the 6 remaining dogs, there were no statistically significant changes in complete blood count or serum biochemical values. No opportunistic infections developed during the study period. Five of 6 dogs had no to minimal evidence of graft rejection. Two of 6 dogs developed superficial and pigmentary keratitis. Significant histopathologic findings in all dogs included mild lymphoplasmacytic gastroenteritis, steroid hepatopathy, and corneal epithelial thinning. One dog had moderate interstitial nephritis and pyelitis. CONCLUSIONS: In this experimental model, a CAP-CsA-prednisolone immunosuppressive regimen was effective in preventing rejection of allografts in DEA-mismatched dogs. Severe, unpredictable neurotoxicity and variable ocular toxicity significantly limit clinical applications at this time. CLINICAL RELEVANCE: A CAP-CsA-prednisolone protocol is an effective, oral immunosuppressive regimen for prevention of allograft rejection in DEA-mismatched mongrel dogs. For clinical application, identification of patients susceptible to toxic side effects would be necessary.     

Renal allograft histopathology in dog leukocyte antigen mismatched dogs after renal transplantation

OBJECTIVE: To evaluate allograft histopathology in dog leukocyte antigen (DLA)-mismatched dogs undergoing renal transplantation, with transient immunosuppression. STUDY DESIGN: Prospective study. ANIMALS: Ten healthy adult mongrel dogs. METHODS: Reciprocal renal transplantation and bilateral nephrectomy were performed. Immune conditioning consisted of nonmyeloablative (200 cGy), total body irradiation (TBI), bone marrow transplantation (BMT; 7 dogs), cyclosporine (CSA; 15 mg/kg every 12 hours), mycophenolate mofetil (MMF; 10 mg/kg every 12 hours) and intermittent prednisone (1 mg/kg every 12-24 hours). Biopsies were collected at transplantation, during full immunosuppression (44-90 days), and once medications were reduced or discontinued (228-580 days). Biopsies were evaluated for interstitial, tubular, vascular, and glomerular lesions. Blood urea nitrogen, creatinine, serum CSA concentrations, and clinical score were determined at each biopsy. RESULTS: Seven dogs survived >200 days (mean, 380 days). Transient CSA toxicity was suspected in 6 dogs. Lymphocytic, plasmacytic interstitial inflammation, and tubulitis progressed when immunosuppressive medications were decreased. All 7 dogs had histologic lesions consistent with some degree of allograft rejection at study end. CONCLUSION: Nonmyeloablative TBI, BMT, and short-term immunosuppression with CSA, MMF, and prednisone allowed renal allograft function and dog survival for >200 days. It appears unlikely that total drug withdrawal will be possible in unrelated DLA-mismatched dogs using this protocol. CLINICAL RELEVANCE: Transient immunosuppression with MMF, CSA, and prednisone along with BMT and nonmyeloablative TBI may make kidney transplantation a clinical reality for treatment of kidney failure in dogs. Initiating both MMF and CSA at lower dosages may potentially eliminate early renal allograft injury.     

An evaluation of combined immunosuppression with MNA 715 and microemulsified cyclosporine on renal allograft rejection in mismatched mongrel dogs

OBJECTIVE: To evaluate a combination of MNA 715 and microemulsifed cyclosporine for the prevention of renal allograft rejection in mismatched mongrel dogs. STUDY DESIGN: Randomized, experimental study. ANIMALS: Fourteen female mismatched mongrel dogs. METHODS: Heterotopic renal transplantation and bilateral nephrectomy were performed in each dog. Dogs were randomly assigned to receive either MNA 715 and cyclosporine (n = 8) or cyclosporine alone (n = 6). Dogs were killed at 100 days after transplantation or when plasma creatinine exceeded 7 mg/dL. RESULTS: In the cyclosporine and MNA 715 group: 4 dogs survived to 100 days with normal plasma creatinine concentrations; 2 dogs with intestinal intussusceptions were killed at 5 and 8 days, 1 dog with a wound infection and sepsis was killed at 14 days, and 1 dog with a serum creatinine concentration >7 mg/dL was killed at 51 days postoperatively. In the cyclosporine-alone group: 3 dogs with acute rejection were killed at 6 to 9 days and 3 dogs survived to 100 days. In dogs treated with cyclosporine and MNA 715, survival to histologically confirmed acute rejection was significantly longer (P =.044) and the degree of mononuclear cell infiltration was significantly reduced (P =.040), compared with dogs treated with cyclosporine alone. CONCLUSIONS: MNA 715 combined with cyclosporine prolonged allograft survival and reduced the severity of histologic rejection in a clinically relevant renal transplant model. CLINICAL RELEVANCE: An immunosuppressive regimen consisting of MNA715 and microemulsified cyclosporine may be effective in preventing allograft rejection in canine renal transplant patients.     

Use of capecitabine after renal allograft transplantation in dog erythrocyte antigen-matched dogs

OBJECTIVES: To investigate the use of a capecitabine (CAP)-based regimen after renal transplantation in dogs. STUDY DESIGN: Prospective, pilot study. ANIMALS: Healthy, unrelated, dog erythrocyte antigen (DEA)-matched, adult beagles. METHOD: Standard heterotopic renal transplantation with native nephrectomy was performed in 7 dogs. Dogs received oral, twice daily, CAP (250 mg/m2), cyclosporine-A (CsA) (4 mg/kg), ketoconazole (5 mg/kg), and prednisolone (0.25 mg/kg). After 90 days the surviving dogs were euthanatized and complete necropsy was performed. RESULTS: Seven transplants were performed. All dogs survived surgery. Six dogs had acute neurotoxicity, which resulted in death or euthanasia of 2 dogs within 2 days of surgery. In the remaining dogs, toxicity resolved rapidly with cessation of drug administration. Thereafter, modification of the regimen minimized toxicity. The 5 remaining dogs survived to study end; 4 dogs had no evidence of graft rejection. Necropsy examination was mostly unremarkable in all dogs. There were no major changes in CBC or biochemical values, except for a significant increase in serum calcium. CONCLUSIONS: CAP appeared well tolerated in most dogs. Toxicity occurred but abated with modification of the drug regimen. Efficacy for postoperative immunosuppression cannot be determined by this study, although results are promising. CLINICAL RELEVANCE: CAP-CsA-prednisolone is an effective, oral immunosuppressive regimen for prevention of acute allograft rejection in DEA-matched beagles. Further studies on dose, toxicity, and efficacy compared with current immunosuppressive regimens are needed before use in clinical practice.     

Lesions in dogs following renal transplantation and immunosuppression

Renal allografts were transplanted into 20 dogs (12 beagles, eight mongrels) following a prescribed protocol for pre-transplantation blood transfusions and kidney exchange. Immunosuppressive therapy (azathioprine and prednisone) was modified as needed for each dog. Seven of the beagle dogs survived for 1 year and were then euthanized; all other dogs died or were euthanized prior to 1 year post-transplantation. Graft rejection and renal failure were the greatest causes of mortality. Renal lesions which contributed to the death of some animals included renal vein thrombosis, nephrosis, and pyelonephritis. Inflammation of the lower respiratory tract (bronchitis, pneumonia, and pleuritis) was a contributory cause of death in some dogs. Cystitis and ureteritis occurred in almost half of the dogs. Prostatitis was seen in six of the 16 male dogs. Adrenal cortical atrophy, parathyroid gland hyperplasia, and bone marrow hypocellularity were seen in a majority of the dogs which survived 1 year.     

Microemulsified cyclosporine-based immunosuppression for the prevention of acute renal allograft rejection in unrelated dogs: preliminary experimental study

OBJECTIVES: To determine whether the microemulsified formulation of cyclosporine (MCsA; Neoral; Novartis A.G.), combined with azathioprine (Imuran; Glaxo Wellcome), and prednisolone (Delta-Cortef; Upjohn), would be effective in preventing acute renal allograft rejection in unrelated mongrel dogs. To document any toxic effects associated with this drug combination. STUDY DESIGN: rospective, pilot study. ANIMALS: Four healthy, adult, mongrel, canine renal allograft recipients. METHODS: Heterotopic renal transplantation, with bilateral nephrectomy, was performed in 4 dogs. Allografts were harvested from 2 unrelated dogs that were to be euthanatized for reasons unrelated to this study. The dogs were treated for 100 days or until signs of illness or allograft rejection required euthanasia. Microemulsified cyclosporine (20 mg/kg/day), azathioprine (5 mg/kg every other day), and prednisolone (1 mg/kg/day) were administered for the prevention of acute rejection. Body weight, serum biochemistry profiles, complete blood counts, and trough whole-blood cyclosporine concentrations were measured throughout the study. Cyclosporine dose was adjusted to maintain a trough concentration of 400-500 ng/mL. Azathioprine dose was decreased if evidence of hepatotoxicity developed or if the total blood white cell count was <4,000 cells/micro L. The prednisolone was tapered by 0.25 mg/kg increments every 3 weeks and discontinued 14 days before the end of the study in the surviving dogs. Complications were recorded. A complete necropsy and histopathologic examination were performed in each recipient. RESULTS: Two of the 4 dogs survived the 100-day period. One dog was euthanatized at 8 days because of an intestinal intussusception. One dog was euthanatized at 64 days because of a severe upper respiratory infection. At the time of death, these 2 dogs had plasma creatinine concentrations of 1.5 and 2.6 mg/dL, respectively, with no histopathologic evidence of allograft rejection. All dogs had transient weight loss (range, 4.6%-17.7% of preoperative body weight) between days 7 and 14. Two dogs had evidence of hepatotoxicity. The 2 dogs surviving to 100 days had normal serum creatinine concentrations and no clinical signs of rejection. One of these dogs had evidence of a grade IIa acute/active rejection based on the modified BANFF 97 histopathologic classification. The second dog had no evidence of rejection or inflammation within the allograft. CONCLUSIONS: This preliminary experimental study shows that immunosuppression using MCsA, combined with azathioprine and prednisolone, may be effective in preventing acute renal allograft rejection in unrelated mongrel dogs for 100 days. Complications included ileocolic intussusception, upper respiratory infection, weight loss, and transient hepatotoxicity. CLINICAL RELEVANCE: Immunosuppression using MCsA, azathioprine, and prednisolone may be effective in preventing acute renal allograft rejection in unrelated, mongrel dogs. This triple drug protocol is cost-effective and was easy to administer. Further investigation is warranted to minimize toxic effects and to determine the efficacy of prophylactic renal biopsies to detect and treat subclinical acute/active rejection.     

Fluconazole decreases cyclosporine dosage in renal transplanted dogs

The effect of fluconazole (Fcz) on the cyclosporine (CsA) dosage was investigated in renal transplanted dogs receiving CsA-based immunosuppressive therapy. Initially, CsA was administered orally twice daily to raise the blood trough level between 400 and 600 ng/ml. After the addition of Fcz, the CsA dosage was adjusted to maintain its therapeutic blood concentration. Fcz significantly decreased CsA dosage in both normal and renal transplanted dogs, but a higher dosage of CsA was needed in renal transplanted dogs. In conclusion, Fcz decreases required CsA dosage and thereby reduces the cost of immunosuppressive therapy in canine renal transplantation.     

Evaluation of oxidative stress markers for the early diagnosis of allograft rejection in feline renal allotransplant recipients with normal renal function

The purpose of this study was to identify oxidative damage to renal allografts during graft rejection by evaluating changes in oxidative markers and plasma lactate levels in feline renal allotransplant recipients. Heterotopic renal allotransplantations were performed between 8 adult feline cross-matched donors. Following 14 d of immunosuppression, the drugs were discontinued to allow allograft rejection. Baseline and serial postoperative evaluations of serum creatinine, plasma lactate, plasma thiobarbituate reactive substances (TBARS), plasma creatol, urine creatol, and renal sonographic cross-sectional area were performed. When sonographic evaluation revealed the absence of blood flow to the allograft, the rejected kidney was nephrectomized and evaluated histopathologically. Allograft rejection occurred in all cats by day 26. A significant elevation in body temperature occurred during the rejection period. No significant change was observed between any of the time periods for plasma TBARS, creatol, or urine creatol. There was a significant decrease in plasma lactate levels throughout the study. Markers of oxidative stress from venous blood did not reflect renal allograft rejection in cats with a normally functioning native kidney. Renal allograft rejection may be associated with significant increases in body temperature and warrants further investigation.     

Preliminary Results of Clinical Renal Allograft Transplantation in the Dog and Cat

Renal allograft transplantation was performed as treatment for terminal renal failure in six veterinary patients. Three patients failed to survive the postsurgical period, one patient died due to acute allograft rejection, one patient died subsequent to complications of previous parenteral hyperalimentation and infection, and one patient was euthanatized due to the inability of the clients to maintain the effort necessary to manage a transplant recipient. Further clinical studies are necessary to determine if renal transplantation with cyclosporine (cyclosporin A)/prednisolone immunosuppression has the potential to provide practical treatment of terminal renal disease in clinical veterinary medicine. Pharmacologic and immunologic monitoring of transplant recipients with individualized immunosuppression is imperative. Careful surveillance is necessary to identify and eliminate nosocomial sources of infection. Candidates for transplantation cannot be critically ill or malnourished prior to surgery, and pet owners must be prepared for the financial and time commitments associated with caring for a renal allograft recipient.     

Urinary tract manifestations of protothecosis in dogs

Records of 13 dogs with systemic infection with Prototheca sp. from 3 veterinary teaching hospitals were reviewed. Acute renal failure secondary to disseminated infection with Prototheca zopfii was diagnosed in 2 dogs. In 1 dog, acute renal failure developed during administration of immunosuppressive drugs for treatment of anterior uveitis. During diagnostic evaluation of this dog, Prototheca sp. organisms were noted in urine sediment and renal biopsy specimens. In the 2nd dog, acute renal failure was diagnosed after treatment for bacterial cystitis. After diagnosis of protothecosis, organisms were successfully isolated by aerobic urine culture. Both dogs with acute renal failure did not respond to conventional medical therapy. In total, Prototheca sp. was noted in urine sediment in 4 of 8 dogs and successfully cultured from urine in 5 of 7 dogs. Four of 5 dogs had organisms noted in the kidneys on histopathologic examination. In all dogs, the species identified was P zopfii. Sensitivity testing of 3 isolates revealed wide differences in in vitro drug resistance. Examination and culture of urine is recommended as a practical method for diagnosis of systemic infection with Prototheca sp.     

Renal transplantation for treatment of end-stage renal failure in cats.

Renal transplantation was performed as treatment of end-stage renal failure in 23 cats. Twenty-two cats had chronic renal disease and 1 cat had acute renal disease associated with ethylene glycol-induced toxicosis. Sixteen cats were discharged from the hospital. Nine survived a mean of 8.4 +/- 6.5 months, and 7 cats continue to survive at the time of this report (mean 12.6 months). Seven cats died within 2 weeks of surgery. All renal allografts were obtained from unrelated blood-crossmatch-compatible donors. No deaths were attributable to acute renal allograft rejection, demonstrating the successful maintenance of renal allografts by use of cyclosporine and prednisolone immunosuppression in cats.     

SONOGRAPHIC AND SCINTIGRAPHIC EVALUATION OF ACUTE RENAL ALLOGRAFT REJECTION IN CATS

The sonographic features of acute renal allograft rejection in humans and dogs are manifested by increase in renal cross-sectional area and reduction in renal cortical blood flow. These changes have not been investigated in cats. The objectives of this study were to evaluate sonographic and scintigraphic changes during acute renal allograft rejection in cats. Eight SPF, intact, adult, male cats received heterotopic renal allotransplantations. Immunosuppressive doses of cyclosporine and prednisolone were administered for 14 days and then discontinued to allow acute allograft rejection to occur. Serial measurements of renal cross-sectional area, resistive index (RI), echogenicity, and glomerular filtration rate (GFR) were performed to evaluate changes during acute rejection. Upon sonographic confirmation of absent diastolic blood flow or a 20% increase in cross-sectional area of the allograft, a nephrectomy and histopathologic evaluation were performed. Acute allograft rejection was confirmed histologically in all cats. Significant increases in renal cross-sectional area (P < 0.001) occurred postoperatively and during rejection. There were no significant changes in RI (P = 0.43) at any time. A subjective increase in medullary echogenicity and a decrease in corticomedullary demarcation were observed in the rejection period. While GFR decreased significantly in the immediate postoperative period (P < 0.001), no further change occurred during rejection (P = 0.42). Changes in RI and GFR do not appear to be sensitive indicators of acute renal allograft rejection in cats. Serial measurements of renal cross-sectional area appear to be a sensitive method for the early diagnosis of allograft rejection in feline renal transplant recipients.     

ULTRASONOGRAPHIC EVALUATION OF RENAL SIZE IN DOGS WITH ACUTE ALLOGRAFT REJECTION

The purpose of this study was to determine the best method to ultrasonographically monitor renal size changes associated with acute allograft rejection in dogs. Qualitative changes in renal cortical and medullary echogenicity were also evaluated, although this was not a major focus of the study. Four unrelated, mixed-breed dogs underwent bilateral nephrectomies and heterotopic renal allograft transplantation. Ultrasound examinations of transplanted kidneys were initiated at 3 days after surgery and continued at 2–3 day intervals until death (38±2 days). Ultrasound measurements of kidney length, width, height, cross-sectional area, and estimated volume were used to assess relative changes in renal size associated with transplantation and rejection. Transplanted kidneys had a rapid increase in volume and cross-sectional area that averaged 103% and 83% above baseline levels, respectively, by 17 days after transplantation. The increased size was attributed to a combination of hypertrophy and acute rejection, the latter of which was confirmed at postmortem. Kidney volume decreased to approximately 35% above baseline volume by day 34 as rejection became more advanced. Qualitative changes associated with rejection included medullary enlargement with decreased echogenicity early in the study, followed by increased cortical thickness and echogenicity with poor cortical medullary definition in the latter stages of the survival period. It was concluded that relative changes in renal allograft size can be easily monitored with ultrasound. In regard to linear measurements, changes in renal width were more pronounced than changes in height or length with acute rejection. Therefore measurements that incorporate the width, namely volume or cross-sectional area, appear to be the most sensitive for monitoring changes in allograft size. Renal cross-sectional area measurements are preferred because they are simple to perform using the automated calculation capability of most newer ultrasound units.     

Neonatal hyperleukocytosis and regenerative anemia in a septic puppy

This paper reports a case of neonatal hyperleukocytosis in a dog due to a bacterial infection. A 3-week-old, mixed-breed dog was brought to a veterinary college referral center with a history of weight loss despite a good appetite. Clinical and laboratory examinations included: physical examination, complete blood (cell) count (CBC), serum biochemistry profile, abdominal ultrasound examination, and cytology of liver and bone marrow aspirates.The CBC showed hyperleukocytosis of 158.0 × 10⁹/L (RI: 2.1 to 21.2 × 10⁹/L) and hematocrit of 0.19 L/L (RI: 0.21 to 0.34 L/L). The strong leukemoid reaction was comprised of neutrophils, monocytes, and lymphocytes. The dog was diagnosed with Staphylococcus pseudointermedius liver infection based on liver aspirates and culture. Amoxicillin-clavulanic acid was prescribed. A recheck abdominal ultrasound and CBC repeated 4 wk after initial examination were unremarkable. Neonatal hyperleukocytosis is well-described in human medicine but veterinary studies in small animal neonates are scarce.Key clinical message:Hyperleukocytosis in adult dogs may be caused by leukemia or leukemoid reactions. Generalized sepsis is a leading cause of leukemoid reactions in adult dogs and cats. In puppies, neoplasia is less likely, and other causes should be investigated. Similar to human neonates, puppies can mount a strong leukemoid reaction during an infection, even if it is not a generalized septic process.     

Acute toxoplasmosis following renal transplantation in three cats and a dog.

Three cats and 1 dog that had undergone renal transplantation because of end-stage renal disease were examined because of complications 3 to 6 weeks after surgery. One cat died prior to treatment of the complications; Toxoplasma cysts were found in sections of the renal allograft, and Toxoplasma tachyzoites were found in other organs. The other 2 cats and the dog died despite treatment, and protozoal cysts, as well as tachyzoites, were identified in other organs but not within the allografts, suggesting that reactivation of latent infection following immunosuppression was the most likely cause of disseminated toxoplasmosis. These cases illustrate that toxoplasmosis can be a fatal complication in renal transplant recipients. We currently recommend that feline and canine donors and recipients undergo serologic testing for toxoplasmosis prior to surgery. In addition, we suggest that seropositive donors not be used for seronegative recipients and that seropositive recipients and that seropositive recipients be monitored closely after surgery for clinical signs of toxoplasmosis.     

Histopathologic findings and classification of feline renal transplants

Seventy-seven feline transplant kidney specimens, obtained from 1 to 3,183 days (9 years) after transplantation, were reevaluated histologically and classified on the basis of the Banff '97 guidelines for human renal transplant kidneys. Overall, this classification system appeared useful in detecting rejection reactions and confirmed the finding in humans that biopsies can diagnose subclinical rejection and therefore are an important diagnostic tool for the follow up of renal transplants. However, on the basis of serum creatinine values, the severity of the acute or active and chronic lesions was not accurately reflected by this scoring system. This is thought to be due to the significant differences in histologic rejection patterns, especially in acute or active rejection, in cats when compared with humans. Tubulitis, lymphocytic glomerulitis, and vasculitis, which are the main pillars of the Banff '97 acute or active rejection scoring system, are either rare or not found in cats. The presence of significant necrotizing glomerulitis and vasculitis in feline renal transplants might imply that the rejection is complicated by acute antibody-mediated rejection. Alternatively, cyclosporine toxicity also should be considered because some of these kidneys show other signs of cyclosporine toxicity. Finally, the significance of subcapsular and interlobular phlebitis, rarely described in human rejection reactions but a distinct entity in cats, is unknown. From this study, it is clear that there are significant differences in the histology of acute or active rejection between humans and cats and that a better understanding of the histologic appearance of renal allografts will be especially beneficial for treatment and prognostic purposes.