Oxalate nephrosis and renal sclerosis after renal transplantation in a cat.

A 10-year-old castrated domestic shorthair cat received two renal allografts, 14 days apart, for the treatment of chronic renal failure. Oxalate nephrosis developed in both allografts, and they became nonfunctional. During the transplantation period, the cat was not exposed to exogenous sources of oxalate, and there was no evidence of primary type 2 hyperoxaluria before surgery. Urologic surgery, in particular renal transplantation, has been identified as a factor that can precipitate renal failure in human patients with decompensated renal function and hyperoxaluria. If hyperoxaluria was present before surgery in this cat, it was most likely caused by increased absorption or decreased metabolism of dietary oxalate.

Evaluation of a method of ureteroneocystostomy in cats.

Renal transplantation is a successful treatment for terminal renal failure in cats. Ureteral obstruction at the bladder wall or stoma has been a technical complication encountered in approximately 50% of clinical transplants. The small (0.4 mm) diameter of the feline ureter makes standard techniques described for ureteroneocystostomy unsatisfactory for cats. In this study, we used microsurgical techniques to oppose ureteral mucosa to intact bladder mucosa in an attempt to form a stricture-free stoma. In each of 5 anatomically normal cats, 1 ureter was microsurgically implanted in the bladder. Ultrasonographic examination of the kidneys, ureters, and bladder was performed twice weekly for 8 weeks. Excretory urography was performed at postoperative weeks 1, 2, 4, 8, and 12. Biopsy specimens were taken from the kidney on the surgically treated side 4 weeks after surgery. At 12 weeks, the kidney, ureter, and ureterovesical junction from the treated side were removed and submitted for histologic evaluation. At 1 week, all cats had enlargement of the kidney, renal pelvis, and ureteral lumen on the treated side. This enlargement gradually decreased, and by week 8, there was no difference in comparison with the control side. Ureteroneocystostomy that requires tunneling of the ureter through the bladder wall may result in hydroureter and hydronephrosis, which may resolve. Recognition of these changes may prevent unwarranted surgical intervention in cases of suspected obstruction. The technique described in this study has been used in 15 cats receiving renal allografts. None required surgical correction of ureteral obstruction.

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.

Definition of the gracilis musculocutaneous flap for distant transfer in cats.

Dissection, injection, and surgical studies in feline cadavers and in anesthetized cats were conducted to determine the feasibility of using the gracilis muscle as the basis for a free musculocutaneous flap. The vascular pedicle of the flap consisted of the femoral artery and vein. Mean length (1.6 +/- 0.2 cm) of the vascular pedicle and mean artery (1.33 +/- 0.19 mm) and vein (2.55 +/- 0.38 mm) diameters were satisfactory for microvascular transfer. Fluorometry revealed overlying cutaneous perfusion in the flaps on the basis of their muscle vascular pedicles. To ensure survival of the flap, the muscular branches of the femoral artery and vein supplying the gracilis muscle had to be carefully preserved during surgical elevation of the flap.

Pathologic studies of acute rejection of mismatched feline musculocutaneous flaps. Effect of cyclosporine and prednisolone.

The gracilis musculocutaneous flap was developed as an allograft model to study acute rejection and immunosuppression in the cat. Twelve adult cats received a MLC incompatible flap. Six of the cats received cyclosporine oral solution and prednisolone (0.5 mg/kg/24 hr) for 100 days and six cats were not treated. Trough whole-blood levels of cyclosporine in the treatment group were maintained at approximately 750 ng/ml for 70 days, then 500 ng/ml for the remaining 30 days. Three flaps failed due to technical problems; 5 flaps were studied in the treatment group and 4 in the untreated group. All 5 flaps in the treatment group survived the 100 day treatment period and were rejected 30 +/- 26 days following cessation of treatment. Prior to discontinuation of treatment, with the exception of one cat, inflammatory changes associated with rejection were not observed in biopsy specimen. The flaps in the untreated group survived 13 +/- 1.5 days. Histopathologic examination of the flaps revealed little difference in the appearance of acute rejection and rejection after cessation of therapy. The most prominent lesion was a vasculitis with extensive perivascular lymphohistocytic inflammation. The lymphoid infiltrates consisted predominantly of T cells of both major classes (CD4 and CD8). Full-thickness epidermal necrosis and subsequent bacterial invasion followed vascular compromise.

Mizoribine serum levels associated with enterotoxicity in the dog.

To prevent or minimize mizoribine enterotoxicity in organ transplant recipients and to differentiate mizoribine enterotoxicity from other causes of enteritis, serum levels of mizoribine that produced subclinical and clinical signs of enterotoxicity were determined in the dog. When mizoribine was administered orally at 12-hr intervals, half the dogs studied showed clinical evidence of gastrointestinal disturbances (vomiting, diarrhea, and anorexia) without histopathologic signs of enterotoxicity. Using a 24-hr oral-dose schedule, clinical signs of gastrointestinal disturbances and histopathologic evidence (mucosal degeneration, crypt degeneration, and necrosis) of enterotoxicity were encountered when the mean 12-hr mizoribine serum level was 0.97 +/- 0.4 microgram/ml or greater. Histopathologic signs of enterotoxicity with repeated positive fecal occult blood assays and without clinical signs of gastrointestinal disturbances occurred when the mean 12-hr serum level was 0.53 +/- 0.17 microgram/ml or greater. Oral administration of cyclosporine did not exacerbate mizoribine enterotoxicity in the dog when administered with mizoribine at a dose that produced histopathologic signs of enterotoxicity.

Identification of muscle flaps in small animals.

Muscle flaps in small animals have been used quite frequently in experimental research. Their use in clinical veterinary surgery, however, has not yet been extensively explored. This paper describes the anatomy and clinical use of some of the muscle flaps that have been investigated and used in small animals.

Use of flaps and/or grafts for repair of skin defects of the distal limb of the dog and cat.

Skin flaps and/or skin grafts can be used to cover wounds of the distal limb of the dog and cat. Flaps are more suitable for poorly vascularized areas, radiation injuries, areas of motion, and pressure points. Reconstruction should not be limited to slowly healing or nonhealing wounds. Skin flaps and grafts can also be used to cover fresh surgical wounds created by excision of large neoplastic or granulomatous lesions.

Preputial reconstruction in a dog.

A 2-year-old dog was examined after a 22-month history of intermittent drying and chafing of the distal portion of the penis after traumatic loss of the cranial portion of the prepuce and fracture of the os penis at 8 weeks of age. A multiple-staged surgical procedure was performed to reconstruct the prepuce, including free buccal mucosal grafting and transfer of a peripreputial bipedicle subdermal plexus flap. Preputial reconstruction provided mucosal and cutaneous coverage of the penis.

Management of tracheal stenosis in a dog.

A 28-month-old Cocker Spaniel was treated for tracheal laceration after bite-wound injury of the ventral area of the neck. Tracheal stenosis developed after surgical repair of the trachea. Bougienage failed to prevent recurrence of clinical signs of upper airway disease associated with tracheal stenosis. Resection of the stenotic lesion and tracheal anastomosis improved tracheal diameter and alleviated clinical signs of upper airway disease. A pulmonary function test (tidal breathing flow-volume loop) was used to assess upper airway function.

Long-term survival of a cat receiving a renal allograft from an unrelated donor.

A 6-year-old, spayed female Persian cat in terminal renal failure was referred to the Veterinary Medical Teaching Hospital for renal transplantation. An allograft from an unrelated donor was placed in the right iliac fossa and cyclosporine and prednisolone were administered as immunosuppressive agents. More than 18 months after surgery the cat was clinically normal and azotemia was absent.

Free jejunal segment for treatment of cervical esophageal stricture in a dog.

A 2-year-old female Chinese Shar Pei was admitted with a 20-cm cervical esophageal stricture that was untreatable by conventional medical and surgical methods. A free jejunal segment was used to replace the strictured portion of the esophagus. Twenty-one months after surgery, the dog was able to eat liquefied canned dog food with minimal regurgitation and was maintaining normal body weight. Free jejunal transfer offers a treatment method for otherwise fatal esophageal lesions that are not responsive to conventional methods of medical and surgical treatment.

Use of magnetic resonance spectroscopy in the evaluation of skin flap circulation.

The assessment of events that occur in elevated skin flaps has been largely by indirect methods. A method was sought that gives direct, reproducible, and accurate data about physiological and biochemical changes that occur during flap elevation and during periods of altered blood flow. Because of its ability to monitor changes in the levels of high energy phosphorus metabolites (ATP or adenosine triphosphate, PCr, or phosphocreatin, Pi, or inorganic phosphate), 31p magnetic resonance spectroscopy (MRS) holds promise of providing direct assessment of the metabolic status and biochemical changes that occur during skin flap elevation. MRS monitoring was performed on raised abdominal skin flaps of 12 rats. Abdominal flaps in 4 animals served as controls with and without total vascular occlusion while arterial blood flow was manipulated in 4 flaps and venous flow in 4 flaps. The results have validated the ability of MRS to determine cellular levels of ATP, PCr, and Pi in skin flaps, and to measure intracellular pH through the chemical shift of the Pi resonance.

Experimental definition of latissimus dorsi, gracilis, and rectus abdominus musculocutaneous flaps in the dog.

Dissection and injection studies in canine cadavers and in anesthetized dogs were conducted to determine the feasibility of using the latissimus dorsi, gracilis, and rectus abdominus muscles as musculocutaneous free flaps. Lengths of vascular pedicles for the latissimus dorsi (2 +/- 0.8 cm), gracilis (1.8 +/- 0.8 cm), and rectus abdominus (1.9 +/- 0.9-cm cranial deep epigastric, 1.7 +/- 0.5-cm caudal deep epigastric), as well as arterial diameters (1.28 +/- 0.31-mm thoracodorsal for the latissimus dorsi, 1.10 +/- 0.33-mm muscular branch for the gracilis, 1.25 +/- 0.25-mm cranial deep epigastric and 1.26 +/- 0.32-mm caudal deep epigastric for the rectus abdominus) were considered satisfactory for microvascular transfer. Fluorometry demonstrated overlying cutaneous perfusion in all flaps based on their muscle vascular pedicles, with the exception of the rectus abdominus flap based on the caudal deep epigastric artery. In this instance, up to 20% of the cutaneous element had questionable or no perfusion.

Effects of combination cyclosporine/mizoribine immunosuppression on canine renal allograft recipients.

Heterotopic renal allografts following bilateral nephrectomies were placed in 21 healthy mongrel dogs. One group of 11 dogs received cyclosporine (5 mg/kg/24 hr, orally), and 1 group of 10 dogs received cyclosporine and mizoribine (5 mg/kg and 3 mg/kg/24 hr, orally). Body weights, blood cell counts, serum chemistry profiles, serum electrolyte levels, urinalysis with cytology and culture, lymphocyte stimulation assays, immunoglobulin levels, whole blood levels of cyclosporine, and serum levels of mizoribine were followed. At the end of each survival period, necropsy and histopathologic examinations were performed. The mean survival time for the cyclosporine group was 12.8 +/- 7 days. The mean survival time for the cyclosporine/mizoribine group was 33.6 +/- 16.4 days, significantly longer (P = .0006) than the cyclosporine group. Death in the cyclosporine/mizoribine group was attributed to the combined effects of renal allograft rejection and development of a mizoribine-dependent enteritis. Serum levels of mizoribine were greater in the last half of the survival period due to compromised renal excretion of the drug. There were no complications due to infection, myelosuppression, or hepatotoxicity. Combination cyclosporine/mizoribine immunosuppression enhanced canine renal allograft survival in this study. Monitoring serum concentrations of mizoribine is imperative to determine toxic (enteritis) levels. Availability of an intravenous form of mizoribine would facilitate immunoregulation during periods of variable intestinal absorption or renal excretion.

Effects of mizoribine on canine renal allograft recipients.

Heterotopic renal allograft transplantation and bilateral nephrectomies were performed on 12 mixed-breed dogs. Histoincompatibility was confirmed by serologically defined and lymphocyte-defined antigen testing. Mizoribine (5 mg/kg, q 24 h) was administered orally starting the day of surgery. Body weights, blood cell counts, serum biochemical and electrolyte values, immunoglobulin concentration, and serum mizoribine concentrations were determined. Complete urinalyses, including bacteriologic culturing and lymphocyte stimulation assays were performed. The mean survival time for the allograft recipients was 20 +/- 14 days; significantly longer than nontreated historic controls surviving 8.1 +/- 0.6 days (P = 0.0098). Death was attributed to the combined effects of renal allograft rejection and development of a mizoribine-dependent gastroenteritis. Serum mizoribine concentrations were greater in dogs undergoing rapid allograft rejection because of compromised renal excretion of the drug. This resulted in a rapid onset of gastroenteritis. There were no complications resulting from infection, myelosuppression, or hepatotoxicosis.

Recovery of free muscle grafts in rat: improvement is associated with an increase in cyclic adenosine monophosphate concentration or use of the condition/test paradigm.

The muscle fibers in freely grafted skeletal muscles degenerate and are replaced by new fibers which develop within the graft. Myogenesis in regenerating muscle recapitulates, to a large extent, developmental myogenesis and may depend on similar modulating influences. In addition to the generation of new fibers, functional recovery of free muscle grafts also requires reinnervation and revascularization of the new fibers. Recovery of function should be improved by enhancing either myogenesis or reinnervation and revascularization. We have used two procedures, shown previously to stimulate peripheral nerve regeneration, to improve the morphologic and functional recovery of free, orthotopic grafts of rat extensor digitorum longus muscle. Each of the procedures was effective, but had potentially different sites of action. The first procedure, the condition/test paradigm, presumably increases the rate and extent of graft reinnervation. The second procedure, continuous infusion of the adenylate cyclase activator forskolin during the first 21 days after grafting, may influence both myogenesis and nerve regeneration. Each procedure increased regenerating muscle fiber size and functional capacity, and forskolin also significantly increased capillary density and fatigue resistance.

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.