Renal transplantation in cats

Feline renal transplantation can offer long-term survival with a normal quality of life for cats with renal failure. However, it is important to remember that renal transplantation is a treatment option and not a cure. Renal transplantation is never performed on an emergency basis or prophylactically. Feline renal transplantation requires special microvascular instruments and an operating microscope. Careful patient selection and perioperative monitoring have improved the success rate. The new microemulsified form of cyclosporine is recommended for immunosuppression. As survival times have steadily improved, long-term complications, such as diabetes and neoplasia, are now being recognized.     

The Prevalence of Malignant Neoplasia in Feline Renal-Transplant Recipients

OBJECTIVE: To determine the prevalence of malignant neoplasia in a group of feline renal-transplant recipients (FRTR). STUDY DESIGN: Retrospective clinical study. ANIMALS: Ninety-five consecutive client-owned FRTR treated at the University of California, Davis, between 1987 and 1997. METHODS: Medical records of the 95 cats were examined. The time to occurrence and type of malignant neoplasia, if present, was determined. RESULTS: Nine of 95 cats (9.5%) developed apparently de novo malignant neoplasia after receiving renal allografts. The predominant type of neoplasm was lymphoma. The median time to diagnosis of neoplasia in these 9 patients was 9.0 months after transplantation, whereas the median survival time was 14.0 months after transplantation. This compares with a median survival time of 22 months after transplantation for cats that died for reasons other than development of malignant neoplasia. CONCLUSIONS: Although these transplant recipients were not compared with a control population, it would appear that, as in humans, malignant neoplasia is encountered with greater-than-expected frequency after renal transplantation and immunosuppression in cats. CLINICAL SIGNIFICANCE: The apparent propensity to develop malignant neoplasia after renal transplantation and immunosuppression in cats is a fatal complication of which owners and clinicians should be aware.     

Gingival overgrowth in dogs associated with clinically relevant cyclosporine blood levels: observations in a canine renal transplantation model

Objective— To investigate the development of gingival hyperplasia in dogs after renal transplantation and administration of microemulsified cyclosporine A (MCsA).
Study Design— Experimental study.
Animals— Healthy adult mongrel dogs (n=5).
Methods— As part of study on renal transplantation, dogs administered MCsA (20 mg/kg/day), azathioprine, and prednisolone to prevent graft rejection were monitored for development of gingival changes. Prednisolone was discontinued after 3 months. MCsA dose was adjusted to maintain whole blood trough concentration of 400–700 ng/mL. Gingival change was evaluated by weekly examination and photodocumentation, and gingival biopsy for histopathology was performed at 28 weeks.
Results— One dog was lost because of acute graft rejection. Gingival hyperplasia developed in 3 of 4 dogs. The earliest gingival changes occurred in the interdental papillae at 20 weeks after transplantation. On histopathology, the underlying connective tissue was thickened and contained increase numbers of fibroblasts and inflammatory infiltrates.
Conclusions— Long-term immunosuppression with an MCsA-based treatment likely induces substantial gingival hyperplasia when therapeutic, immunosuppressive blood levels of MCsA were maintained for 32 weeks.
Clinical Relevance— MCsA is used for immune-mediated diseases and preventing rejection after transplant in dogs. MCsA blood levels, and gingival hyperplasia should be monitored by routine examination of the interdental papilla in dogs administered MCsA for long periods.     

Incidence of and risk factors for diabetes mellitus in cats that have undergone renal transplantation: 187 cases (1986-2005)

OBJECTIVE: To compare incidence of diabetes mellitus in cats that had undergone renal transplantation with incidence in cats with chronic renal failure, compare mortality rates in cats that underwent renal transplantation and did or did not develop diabetes mellitus, and identify potential risk factors for development of posttransplantation diabetes mellitus (PTDM) in cats. DESIGN: Retrospective case series. ANIMALS: 187 cats that underwent renal transplantation. PROCEDURES: Medical records were reviewed. RESULTS: 26 of the 187 (13.9%) cats developed PTDM, with the incidence of PTDM being 66 cases/1,000 cat years at risk. By contrast, the incidence of diabetes mellitus among a comparison population of 178 cats with chronic renal failure that did not undergo renal transplantation was 17.9 cases/1,000 cat years at risk, and cats that underwent renal trans-plantation were 5.45 times as likely to develop diabetes mellitus as were control cats with chronic renal failure. The mortality rate among cats with PTDM was 2.38 times the rate among cats that underwent renal transplantation but did not develop PTDM. Age, sex, body weight, and percentage change in body weight were not found to be significantly associated with development of PTDM. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that cats that undergo renal transplantation have an increased risk of developing diabetes mellitus, compared with cats with chronic renal failure, and that mortality rate is higher for cats that develop PTDM than for cats that do not.     

Pyogranulomatous cystitis associated with Toxoplasma gondii infection in a cat after renal transplantation

CASE DESCRIPTION: An 8-year-old spayed female domestic shorthair cat was evaluated for azotemia and a suspected mass in the urinary bladder 6 weeks after receiving a renal transplant. Ultrasonography revealed a mass at the ureteroneocystostomy site, and the mass was excised. Both the donor and recipient cats were seronegative for Toxoplasma gondii-specific IgG antibodies prior to transplantation. CLINICAL FINDINGS: Histologic evaluation of the mass revealed lesions indicative of extensive necrotizing pyogranulomatous cystitis with numerous intralesional T gondii tachyzoites and bradyzoite cysts. TREATMENT AND OUTCOME: Treatment with clindamycin was initiated; however, the cat's clinical condition continued to decline, and it was euthanized 9 days after the mass was excised. Necropsy revealed T gondii cysts within the renal allograft and the transplanted ureter, with no evidence of systemic spread of organisms. CLINICAL RELEVANCE: Toxoplasmosis should be considered as a differential diagnosis for azotemia in feline renal transplant recipients regardless of the results of assays for T gondii antibodies in the serum of donors or recipients. This report illustrated the need for improved screening of donor and recipient cats and the importance of minimizing exposure to potential sources of T gondii after transplantation.     

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.     

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.     

Hypercalcemia following renal transplantation in a cat

An 11-year-old 3.0-kg (6.6-lb) neutered male Persian was referred for renal transplantation. Serum total calcium concentration was slightly high prior to surgery, but the week after surgery, total and ionized calcium concentrations were extremely high, and a small mass was palpable on the right side of the trachea at the level of the thyroid and parathyroid glands. Exploratory surgery of the ventral aspect of the neck was performed, and a right external parathyroid mass was removed. One hour after surgery, the serum ionized calcium concentration was within reference limits, and the serum calcium concentration remained normal for the next 14 months without any specific treatment. The gross and histologic appearance of the mass, combined with the rapid decrease in serum calcium concentration following its removal, confirmed that the mass was a functional parathyroid adenoma. Although a common postoperative complication in people, hypercalcemia following renal transplantation appears to be a rare complication in cats. Surgery should be considered if the condition is a result of a parathyroid adenoma.     

Evaluation of erythropoiesis and changes in serum erythropoietin concentration in cats after renal transplantation

OBJECTIVE: To investigate the clinicopathologic patterns of the erythropoietic response after renal transplantation in cats with chronic renal failure (CRF). ANIMALS: 14 cats with CRF undergoing renal transplantation. PROCEDURE: Before and at intervals during a 6-month period after transplantation, serum creatinine and erythropoietin concentrations, Hct, erythrocyte indices, aggregate reticulocyte percentage, and iron variables were measured. Additionally, the number of transfusions administered to and any complications that developed in each cat were recorded. RESULTS: In all cats, preoperative azotemia resolved within 6 days after renal transplantation. Two cats had a temporary increase in serum creatinine concentration secondary to an acute graft rejection episode. Anemia (defined as Hct < 28%) resolved in 10 cats 3 to 49 days after surgery. Resolution of anemia was delayed in 2 cats that had acute rejection episodes. Serum erythropoietin concentration and reticulocyte percentage were low preoperatively; values after surgery were highly variable. Compared with preoperative values, serum erythropoietin concentration increased 1 to 4 days after surgery in 11 cats; between days 5 and 58, another increase was detected in 9 cats. Serum iron concentrations were generally low before and 14 days after transplantation. CONCLUSION AND CLINICAL RELEVANCE: The erythropoietic response was highly variable in cats after renal transplantation, but anemia typically resolved within 1 month after surgery. A delay in resolution of anemia in cats may indicate poor graft function and inadequate iron stores, suggesting the need for further evaluation for concurrent illness.     

Screening criteria for feline renal transplant recipients and donors

Renal transplantation is associated with several potential complications. Early selection and appropriate screening of candidates has reduced the morbidity and mortality associated with this procedure in human beings. In veterinary medicine, the important process of identification and screening of candidates for renal transplantation occurs primarily in private general or specialty practice. This article reviews guidelines for screening of candidates for renal transplantation and related publications in both veterinary and human literature in an attempt to provide comprehensive information to practitioners involved in the selection process. It is anticipated that early referral of stable cats for renal transplantation will further improve the likelihood of a successful outcome.     

Diagnostic Predictors of Complications and Survival after Renal Transplantation in Cats

OBJECTIVE: To identify preoperative diagnostic results that predict postoperative complications and survival in feline renal-transplant recipients. STUDY DESIGN: Retrospective clinical study. ANIMALS: Sixty-one feline renal allograft recipients. METHODS: Medical records for 61 consecutive cats that underwent renal allograft transplantation between January 1, 1996, and December 1, 1999, were reviewed. Age, diagnosis, body weight, body condition score, preoperative medical treatment, systolic blood pressure, packed cell volume, biochemical parameters at admission and at the time of surgery, postoperative complications, and postoperative survival were recorded. Associations of preoperative data with the occurrence of postoperative complications were determined using logistic regression. Postoperative survival was graphed using a Kaplan-Meier cumulative-survival plot. Associations of covariates with postoperative survival were analyzed using Cox proportional hazards analysis. RESULTS: Two parameters were significantly associated with occurrence of postoperative central nervous system (CNS) disorders: blood urea nitrogen concentration (odds ratio = 1.083; 95% CI = 1.018 to 1.148) and serum creatinine concentration (odds ratio = 1.8; 95% CI = 1.413 to 2.187) at the time of surgery. Postoperative survival 6 months after transplantation was 59%, though 3-year survival remained at 42%. Of all covariates investigated, only recipient age (relative hazard = 1.183; 95% CI = 1.039 to 1.334) was significantly associated with survival. CONCLUSION AND CLINICAL RELEVANCE: Standard measures of preoperative renal dysfunction do not predict postoperative survival in cats after renal transplantation, although an increase in the degree of preoperative azotemia is associated with an increased risk of CNS disorders after surgery. Increased recipient age is associated with decreased survival after renal transplantation.     

Ultrasonographic determination of resistive index and graft size for evaluating clinical feline renal allografts.

Ultrasonographic examination is a commonly employed technique for postoperative renal allograft evaluation after transplantation. Allograft size and resistive index (RI) are two objective ultrasonographic measures that may help establish a diagnosis and direct postoperative management for grafts with suboptimal function but their diagnostic efficacy has not been evaluated in clinical veterinary patients. Results of 69 feline renal transplant ultrasonographic examinations and RI determinations were studied. Based on clinical parameters at the time of the ultrasonographic examination, patients were grouped into six clinical/functional categories including evaluations of clinically normal grafts, delayed graft function, ureteral obstruction, uroabdomen, graft thrombosis, and rejection. RI, graft size (length, cross-sectional area, and volume), cyclosporine A whole blood trough concentration, Doppler blood pressure, creatinine concentration, and days from transplantation were compared between these categories and associations with each other were examined. RI was of little value in differentiating among the clinical categories with the exception of graft thrombosis. Graft volume and time from transplantation were significantly greater in grafts with signs of rejection and ureteral obstruction compared to clinically normal ultrasound examinations. Graft volume, cross-sectional area and length were generally associated. Cyclosporine A blood concentrations was associated with RI in both the pooled data and in the delayed graft function category. These results indicate RI should be used only as part of a larger clinical picture and in light of other factors including cyclosporine A concentration and the timing of the study relative to the implantation surgery for the diagnosis of postoperative transplantation complications. Graft volume may provide a more sensitive, albeit, nonspecific, indicator of allograft dysfunction.     

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.     

Management of hypertension controls postoperative neurologic disorders after renal transplantation in cats

OBJECTIVES: To determine the prevalence and describe the management of hypertension and central nervous system (CNS) complications after renal transplantation in cats. We also compared the prevalence of CNS complications between cats monitored and treated for postoperative hypertension and a previously described, historical control group of cats not monitored or treated for postoperative hypertension. STUDY DESIGN: Retrospective clinical study. ANIMALS OR SAMPLE POPULATION: A total of 34 client-owned cats that received renal allografts for the treatment of end-stage renal failure. METHODS: Medical records were reviewed. Data obtained included preoperative and postoperative systolic blood pressures, antihypertensive therapy, response to treatment, neurologic signs, and clinical outcome. The results were compared with a historical control group of feline renal allograft recipients that were neither monitored nor treated for postoperative hypertension. RESULTS: Severe postoperative hypertension occurred in 21 of 34 of cats. Hypertension was treated in all 21 cats with subcutaneously administered hydralazine which reduced systolic blood pressure to less than 170 mm Hg in 15 minutes in 20 of 21 cats; hydralazine produced hypotension in one cat and failed to control hypertension in 1 cat. After transplantation, seizures were observed in one cat and other neurologic complications (stupor, ataxia, and central blindness) were observed in three cats. The prevalence of seizures and neurologic complication-related deaths after transplantation was significantly reduced with treatment of postoperative hypertension. CONCLUSIONS AND CLINICAL RELEVANCE: Hypertension is a major contributing factor to postoperative seizure activity after renal transplantation in cats; treatment of hypertension reduces the frequency of neurologic complications.     

桑螟食叶量测定及其防治指标的研究

测定了桑螟幼虫一生的食桑量,以及食下量与发育历期的关系,为确定桑螟的防治适期及防治指标提供了科学依据。经过分析得出:桑螟的防治最佳时期应该为3龄以前;春夏季的防治指标为1200～1600头/亩,秋季的防治指标为1800～3200头/亩。     

Techniques of wound closure

Although many wounds in horses heal successfully by second-intention healing or delayed closure, some wounds can be sutured primarily, with reasonably high expectations of first-intention healing. To expect to achieve these results, one needs to have a rational treatment plan. Such a plan should be based on a working knowledge of the biology of tissue repair and tissue infection. Treatment decisions should be based more on results of experimental and clinical trials rather than on testimonials of other practitioners.     

TIME-RESOLVED RENAL CONTRAST-ENHANCED MRA IN NORMAL DOGS

In humans, contrast-enhanced magnetic resonance angiography (CE-MRA) is a documented method to quantitatively and qualitatively evaluate renal vessels. It offers a safer alternative to computed tomography angiography. The aim of this study was to establish a renal MRA protocol in dogs using a 3D multiphase Fast Spoiled Gradient Recalled echo CE-MRA sequence (3D FSPGR CE-MRA). We used an elliptical centric ordering of k -space to acquire the contrast-sensitive data faster. Four to five consecutive 3D dorsal slabs, encompassing both kidneys, could be acquired in 40–65 s. The renal arterial and venous phases were obtained separately during phases 1 or 2, and 2 or 3, respectively without the need for any contrast medium bolus timing. The renal arteries and veins were clearly visualized. In conclusion, multiphase FSPGR 3D CE-MRA with an elliptical centric k -space ordering allows distinguishing renal arterial and venous phases in dogs, and can be used as a noninvasive diagnostic imaging alternative to map renal vessels in this species. Potential applications include the screening of renal donors in renal transplantation programs, and the pretreatment evaluation of animals with invasive renal neoplasia or renal vascular anomalies when surgery or embolization are contemplated.     

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.     

Reconstruction of the lower eyelid by third eyelid lateral advancement and local transposition cutaneous flap after "en bloc" resection of squamous cell carcinoma in 5 cats

OBJECTIVE: To describe a novel technique for blepharoplasty to cover a tissue defect involving >/=50% of the lower eyelid. STUDY DESIGN: Prospective clinical study. ANIMALS: Five cats with lower eyelid squamous cell carcinoma (SCC). METHODS: En bloc resection of SCC by removing >/=50% of the lower lid with either the medial or lateral canthus was performed without other adjunctive treatment for SCC. The lid defect was reconstructed with a transposition skin flap derived from the frontal (medial defect) or temporal (lateral defect) region. The third eyelid was advanced laterally without dissection from its insertion; its outer conjunctival layer was removed, and the skin flap was sutured with single interrupted sutures dorsally over the nictitating membrane, ventrally to the cutaneous edge of the surgical wound and medially or laterally (depending on the canthus removed) to the skin of the remaining lower lid. RESULTS: Satisfactory cosmetic and functional results were achieved and the Schirmer tear tests were normal. In 2 cats, the skin flap needed monthly hair trimming to avoid corneal lesions. CONCLUSIONS: After en bloc resection of SCC involving >/=50% of the lower eyelid, reconstruction can be achieved by relocation of the third eyelid and use of a cutaneous transposition flap sutured to the scarified external surface of the third eyelid. Eyelid apposition and lacrimal function were preserved. CLINICAL RELEVANCE: Blepharoplasty using a cutaneous transposition flap sutured to the scarified surface of a relocated third eyelid should be considered for reconstruction of lower eyelid defects with >/=50% tissue loss of the lid margin.     

Bursting tension of medium and large canine arteries sealed with ultrasonic energy or suture ligation

OBJECTIVE: To compare bursting tension of arteries > or =3 mm in diameter sealed with ultrasonic energy (UE) with arteries ligated with suture. STUDY DESIGN: Experimental, nested factorial design. SAMPLE POPULATION: Vascular segments from canine cadavers. METHODS: Arterial segments (12) were collected from each of 16 canine cadavers and equally divided into 2 groups based on vessel diameter (medium, 3.0- < 4.5 mm; large, 4.5 - < or =6.0 mm). Arterial specimens (3) from each group were sealed with either UE (Harmonic Scalpel, HS, power level 3) or suture ligation. The mean bursting pressure and tension were determined and compared. RESULTS: Bursting tension was significantly higher (P< .0001) for sutured arteries than UE-occluded arteries, irrespective of size. Bursting tension was significantly higher (P=.0013) for medium than large UE-occluded arteries, whereas there was no difference associated with size for ligated arteries. UE energy failed to seal 1 medium artery and 7 large arteries. Compared with normal blood pressure, bursting pressures were 3.5 times greater for sutured arteries irrespective of size, 1.8 times greater for medium UE-occluded arteries, and approached normal blood pressure for large UE-occluded arteries. CONCLUSION: At the power level tested, UE should not be used to seal arteries > 4.5 mm in diameter. Suture provided an optimal seal for arteries < or =6.0 mm in diameter. CLINICAL RELEVANCE: Use of UE to occlude arteries during laparoscopic surgery is advantageous because only 1 instrument is required to simultaneously cut and coagulate tissue, but care should be exercised where large arteries might be encountered.