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.     

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.     

Scintigraphic, sonographic, and histologic evaluation of renal autotransplantation in cats.

OBJECTIVE: To determine scintigraphic, sonographic, and histologic changes associated with renal autotransplantation in cats. ANIMALS: 7 adult specific-pathogen-free cats: 5 males, 2 females, 1 to 9 years old. PROCEDURE: Renal autotransplantation was performed by moving a kidney (5 left, 2 right) to the left iliac fossa. Before and at multiple times after surgery, for a total of 28 days, cats were evaluated by B-mode and Doppler ultrasonography, scintigraphy, and renal biopsy. RESULTS: By 24 hours after surgery, a significant decrease (42%) in mean glomerular filtration rate (GFR) and an increase in mean renal size (81% increase in cross-sectional area) were evident in the transplanted kidney, compared with preoperative values. By postsurgery day 28, reduction in GFR was 23%. Significant changes in renal blood flow velocity were identified in both kidneys. Consistent changes in resistive index or pulsatility index for either kidney could not be identified. When all postoperative histologic data were combined, the histologic score, indicating degree and numbers of abnormalities detected, for the transplanted kidney was significantly higher than that for the control kidney. CONCLUSIONS: Significant changes in renal function, size, and histologic abnormalities develop secondary to acute tubular necrosis in cats after uncomplicated renal autotransplantation. CLINICAL RELEVANCE: Evaluation of renal size and function may be of benefit for clinical evaluation of feline renal transplant patients, whereas measurement of the resistive index may be of little clinical value.     

ULTRASONOGRAPHIC EVALUATION OF RENAL AUTOGRAFTS IN NORMAL CATS

The purpose of this study was to determine changes in resistive index (RI) and renal size that occur in normal feline kidney autografts in the immediate post-transplant period. Qualitative changes in renal parenchymal echogenicity and pelvic dilation were also noted, although this was not a major focus of the study. Fourteen domestic short-haired cats underwent bilateral nephrectomies followed by an autograft of the right kidney to either the aorta or external iliac artery. Due to post-operative complications, only nine of these cats completed the study. Ultrasonographic determination of the RI and renal size was made before transplantation and on days 1, 4, 7, 10, and 13 following transplantation. No significant changes in renal RI were identified during the study. Renal size increased significantly, peaking at 63% above baseline on day 7, and stayed elevated at 50% above baseline on day 13. There was no evidence of rejection or other abnormalities found on histologic evaluation of the transplanted kidneys. It was concluded that the RI of normal feline renal autografts does not significantly change in the immediate post-operative period. However, significant renal enlargement, likely due to a combination of post-operative edema and hypertrophy, does occur. This study provides baseline information for comparison with feline allografts in the immediate post-transplant period.     

Evaluation of the Clinical and Histologic Features of Renal Allograft Rejection in Cats

OBJECTIVES: To describe the clinical signs and histopathologic features of renal allograft rejection in cats, and to provide a historical, untreated control group for use in future studies of feline renal allograft rejection. ANIMALS: Fourteen adult research cats. METHODS: Renal transplantation and bilateral nephrectomy were performed in pairs of immunogenically mismatched cats. A physical examination was performed, and packed cell volume, total protein, and plasma creatinine concentrations were measured each day after surgery. The cats were euthanatized when plasma creatinine concentration exceeded 7 mg/dL or when weight loss exceeded 20%. Renal histopathology was scored according to the Banff 97 criteria by 3 pathologists. RESULTS: Nine cats completed the study. Plasma creatinine exceeded 7 mg/dL in 5 cats, weight loss exceeded 20% in 3 cats, and 1 cat was found dead. Clinical signs in cats with rejection were nonspecific or absent. Rectal temperature decreased by 0.8 +/- 0.5 degrees C in the 24 hours before euthanasia. The pathologists agreed on the allograft histopathologic category in 6 of 9 cats. The histologic consensus was acute/active rejection in 8 cats and normal in 1 cat. Median survival time of the 8 cats with histologically confirmed allograft rejection was 23 days (range, 8-34 days). CONCLUSIONS AND CLINICAL RELEVANCE: Renal allograft rejection is associated with minimal clinical signs. Therefore, plasma creatinine concentration should be measured routinely in patients with a functioning allograft. An increase in plasma creatinine concentration is highly suspicious for allograft rejection, although a biopsy of the renal allograft is needed for definitive diagnosis.     

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 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.     

EFFECT OF SEVOFLURANE ANESTHESIA AND BLOOD DONATION ON THE SONOGRAPHIC APPEARANCE OF THE SPLEEN IN 60 HEALTHY CATS

The aims of this prospective study were to describe the normal sonographic size and appearance of the feline spleen, and to test effects of sevoflurane anesthesia and blood collection on sonographic characteristics. Sonographic evaluations were performed in 60 healthy blood donor cats prior to anesthesia and blood collection (baseline), after anesthesia induction, after completion of blood collection while under anesthesia, and 7–10 days after blood collection. Transverse sonographic images of the splenic mid‐body were made. Splenic height, width, cross‐sectional area, echogenicity relative to the left renal cortex, and echotexture were recorded. Height, width, and cross‐sectional area were compared across time periods using linear‐mixed effects models. Holm's method was applied to adjust for multiplicity and control the overall Type 1 error rate at α = 0.05. Normal transverse sonographic splenic measurements (mean ± standard deviation) at baseline were: height 8.2 ± 1.4 mm; width 26.7 ± 4.4 mm; and CSA 1.6 ± 0.5 cm². While there were statistically significant differences in splenic height, width, and cross‐sectional area after sevoflurane anesthesia and/or blood collection, differences were of low magnitude. The spleen was diffusely homogenous and subjectively isoechoic or mildly hyperechoic relative to the left renal cortex. In 77% of castrated male cats, the spleen was isoechoic to the left renal cortex. We conclude that sevoflurane anesthesia and blood donation do not subjectively alter splenic dimensions, echogenicity and echotexture in normal cats.     

Evaluation of plasma clearance of inulin in clinically normal and partially nephrectomized cats

OBJECTIVE: To evaluate accuracy of measuring plasma clearance of inulin as an alternative renal function test for estimation of glomerular filtration rate (GFR) in cats. ANIMALS: 10 cats, first studied with intact kidneys and subsequently studied following partial nephrectomy. PROCEDURE: Clearance studies were performed in 10 clinically normal cats; those same cats then underwent partial nephrectomy, and clearance studies were performed again. Plasma concentration of inulin was determined after administration at 50 mg/kg of body weight to cats while renally intact and 45 mg/kg after the partial nephrectomy. Plasma clearance of inulin (PCin) was determined by dividing the dose by the area under the plasma inulin concentration versus time curve. Results for PCin were compared with values obtained simultaneously for urinary clearance of exogenously administered creatinine (Ccr), a widely accepted method for measurement of GFR in cats with intact kidneys and cats with reduced renal mass. RESULTS: Results of PCin were strongly correlated (r2 = 0.912, P < 0.001) with Ccr. Repeatability of determination of PCin was similar to that of Ccr. Sensitivity and specificity of PCin were superior and equivalent to that of Ccr, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Determination of PCin provides a reliable estimate of GFR in cats and is a promising alternative to determining Ccr in cats.     

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.     

Evaluation of the prevalence of infections in cats after renal transplantation: 169 cases (1987-2003)

OBJECTIVE: To determine the prevalence of infections developing postoperatively, document the contribution of infection to increased risk of death, and identify risk factors associated with the development of infectious complications in cats after renal transplantation. DESIGN: Retrospective study. ANIMALS: 169 cats that received renal allograft transplants. PROCEDURES: Medical records of cats receiving renal transplants at the University of California from January 1987 through December 2003 were reviewed. RESULTS: 47 infections developed in 43 of 169 cats. Bacterial infections were most common (25/47 cats), followed by viral (13/47), fungal (6/47), and protozoal (3/47) infections. The median duration from transplant surgery to development of infection was 2.5 months. Infection was the second most common cause of death after acute rejection of the transplant, accounting for 14% of deaths overall. Cats with concurrent diabetes mellitus had a significantly increased risk of developing an infection after renal transplantation. Sex, increasing age, concurrent neoplasia, and previous treatment for transplant rejection were not associated with development of infection. CONCLUSIONS AND CLINICAL RELEVANCE: Infection was a common complication and an important cause of death or euthanasia in cats after renal transplantation. Development of diabetes mellitus after transplantation significantly increased the risk of infection.     

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.     

Ultrasonographic findings of feline cholangitis

Cholangitis is a common inflammatory disorder of the biliary system in cats. There are two major forms based on the predominate type of inflammatory cell infiltrates: lymphocytic or neutrophilic. Ultrasound is a common imaging modality used in these patients. This retrospective study evaluated the ultrasound examinations of 26 cats with a histologic diagnosis of cholangitis. Most cats with cholangitis had sonographically normal liver size, echogenicity, and normal biliary systems. Statistically significant sonographic changes for cats with cholangitis included hyperechoic liver parenchyma, hyperechoic gallbladder contents, and increased pancreatic size. No statistically significant changes were noted to distinguish lymphocytic and neutrophilic forms of cholangitis. Cats with the sonographic features of diffuse liver hyperechogenicity, gallbladder contents and enlarged pancreas may suggest cholangitis.     

Effects of the angiotensin converting enzyme inhibitor benazepril in cats with induced renal insufficiency

OBJECTIVE: To determine effects of the angiotensin converting enzyme inhibitor benazepril in cats with induced renal insufficiency. ANIMALS: 32 cats. PROCEDURE: Renal mass was surgically reduced, and cats were assigned to 1 of 4 eight-cat groups. Group 1 received placebo, whereas groups 2, 3, and 4 received benazepril hydrochloride orally once daily for approximately 6.5 months at the following doses: group 2, 0.25 to 0.50 mg/kg of body weight; group 3, 0.50 to 1.00 mg/kg; and group 4, 1.00 to 2.00 mg/kg. Arterial blood pressures, glomerular filtration rate (GFR), and renal plasma flow were determined before treatment and during the treatment period. Other determinants of renal hemodynamics were measured by use of micropuncture techniques. Renal biopsy specimens were examined microscopically. RESULTS: Compared with cats that received placebo, mean systolic arterial blood pressure was significantly less and GFR significantly greater in cats that received benazepril. Glomerular capillary pressure and the ratio of efferent to afferent arteriolar vascular resistance were also significantly less in treated cats. However, histologic differences in renal specimens were not detected. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with benazepril sustained single nephron GFR in remnant nephrons of cats with induced renal insufficiency. Administration of benazepril was also associated with a small but significant reduction in degree of systemic hypertension and an increase in whole kidney GFR. Benazepril may be an effective treatment to slow the rate of progression of renal failure in cats with renal disease.     

Possible Hemolytic Uremic Syndrome in Three Cats After Renal Transplantation and Cyclosporine Therapy

OBJECTIVE: To describe the clinical history of 3 cats with possible hemolytic uremic syndrome (HUS) after renal transplantation. STUDY DESIGN: This case series documents historical findings, physical examination findings, clinical pathologic features, necropsy and histopathologic findings of 3 cats with possible HUS. RESULTS: Two cats had chronic renal failure; 1 cat had acute renal failure secondary to ethylene glycol toxicity. A renal transplant was performed in each of the 3 cats without obvious problems. Complications that would support a diagnosis of HUS, including anemia, thrombocytopenia, and azotemia occurred within 24 hours in 1 cat, within 8 days in a second cat, and 2 months after transplantation in the third cat. In 2 cats, HUS was likely secondary to cyclosporine immunosuppression. In the third cat, HUS may have been secondary to allograft rejection. Renal biopsies from all 3 cats were suggestive of HUS. CONCLUSION AND CLINICAL RELEVANCE: In human beings, HUS in transplant recipients may occur secondary to immunosuppressive drugs, vascular rejection, or recurrence of original disease. Graft loss occurred in all 3 cats in this study and the mortality rate was 100%. Clinicians caring for these patients need to be aware of this disorder because early recognition and treatment is critical in the management of post-transplant HUS.     

Retroperitoneal fibrosis in four cats following renal transplantation

Four cats developed fibrosis within the retroperitoneal space following renal transplantation. In human transplant patients, retroperitoneal fibrosis is an uncommon complication following surgery and may be secondary to operative trauma, infection, deposition of foreign material in the operative field, urinary extravasation, and perirenal hemorrhage caused by trauma to the allograft. Possible causes of fibrosis in the cats of this report include abdominal inflammation associated with allograft rejection, pyelonephritis, and septic peritoneal effusion. All of the cats of this report were readmitted to the veterinary teaching hospital following renal transplantation because of recurrence of azotemia 1 to 5 months after transplantation. Abdominal ultrasonography revealed a 2- to 4-mm-thick capsule surrounding the allograft in 2 of 4 cats, hydronephrosis in 4 cats, and hydroureter proximally in 2 cats. An exploratory laparotomy was performed in all cats to remove the fibrotic tissue causing the ureteral obstruction. Normal renal function was restored in all cats following surgery. Histologic evaluation of biopsy specimens revealed smooth muscle (3 cats) and fibrous connective tissue (4). All 4 cats, regardless of the cause, responded well to surgical resection of the scar tissue that was causing a ureteral obstruction. None of the cats had recurrence of obstruction following surgery.     

Single-injection inulin clearance for routine measurement of glomerular filtration rate in cats

Glomerular filtration rate (GFR) was determined in 53 cats using an inulin single-injection method. Thirty healthy young adult cats were used to establish normal values. The procedure was also used in 23 cats that were either older than 10 years or had borderline serum creatinine levels. The total clearance was calculated from the decay of the serum inulin concentration after injection of 3000 mg/m(2)body surface area using a two-compartment model. Concomitant inulin and iohexol clearance in nine cats showed excellent correlation between the two methods. Calculated normal values for GFR in 30 healthy cats were 35.9-58.5 (median 46.0) ml/min/m(2)or 2.07-3.69 (median 2.72) ml/min/kg. A few cats with normal creatinine or blood urea nitrogen levels were detected as having reduced GFR and therefore being in a state of early renal dysfunction. The study indicates that single-injection inulin clearance is a valuable tool for routine GFR measurement in cats. An "inulin excretion test" using only one blood sample 3h after the administration of 3000 mg/m(2)body surface area could prove an attractive alternative for the assessment of renal function in daily practice.     

CHANGES IN RENAL FNCTION IN CATS FOLLOWING TREAMENT OF HYPERTHYROIDISM USING131I

Changes in renal fnction of twenty-two cats treated for hyperthyrodism using radioiodine were evaluated. Serum thyroxine (T₄), serum creatinine, blood urea nitrogen (BUN) and urine specificgravity were measured before treatment and 6 and 30 days after treatment. Twenty-two cats had pretreatment and 21 cats had 6 day posttreatment measurement of glomercular filtration rate (GFR) using nuclear medicine imaging techniques. there were significant declines in serum T₄ at 6 days following treatment, but the changes in GFR, serum creatinine and BUN were not significant. At 30 days following treatment, there were significant increases in BUN and serum creatinine and further significant declines in serum T₄. Nine cats were in renal failure prior to treatment and 13 cats were in renal failure 30 days following treatment. Renal failure was defined as BUN greater than 30 mg/dl and/or serum creatinine greater than 1.8 mg/dl with concurrent urine specific gravity less than 1.035. these 13 cats included eight of 9 cats in renal failure prior to treatment on 9 of these 13 cats indicated that all remained in renal failure. Based on receiver operating curve analysis of pretreatment glomerular filtration rate (GFR) in predicting posttreatment renal failure, a value of 2.25 ml/kg/min as a point of maximum sensitivity (100%) and spefificity (78%) was derived, Fifteen of 22 cats had pretratmentGFR measurements of less than 2.25 ml/kg/min. these 15 cats included all 9 cats in renal failure and 65 cats with normal renal clinicopathologic values prior to treatment. at 30 days following treatment, 13 of these 15 cats were in renal failure. The 2 cats not in renal failure had persistently increased serum T₄ values. seven of 22 cats had pretreatment GFR measurements greater than 225 ml/kg/min. None of these 7 cats was in renal failure at 30 days following treatment, all cats having normal BUN, serum creatinine, and urine specific gravity values. It was concluded that significant declines in renal function occur after treatment of hyperthyroidism and this decline is clinically important in cats with renal disease. Pretreatment measurement of GFR is valuable in detecting subclinical renal disease and in predicting which cats may have clinically important declines in renal function following treatment.     

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.     

EVALUATION OF RENAL HEMODYNAMICS IN AWAKE AND ISOFLURANE-ANESTHETIZED CATS WITH PULSED-WAVE DOPPLER AND QUANTITATIVE RENAL SCINTIGRAPHY

The feasibility and reproducibility of obtaining the pulsed-wave Doppler measurements of resistive index (RI) and pulsatility index (PI) were investigated in intrarenal arteries of normal, nonsedated cats, and cats anesthetized with isoflurane. In addition, relative renal function and relative renal blood flow were evaluated using quantitative renal scintigraphy. The percentage of injected dose uptake, time to peak activity, and two indices of renal blood flow (K/A ratio and flow index) obtained during the first pass of ^99mTc-MAG₃, were determined for both awake and anesthetized cats. Results indicate that measuring RI and PI in nonsedated cats is readily accomplished and that the results are reproducible within an animal. Mean RI and PI values in the awake cats were 0.55 and 0.8, respectively. Significant differences between the awake and anesthetized cats were found for all pulsed-wave Doppler and quantitative renal scintigraphic measurements evaluated.