Feline Renal Transplantation: What the Practitioner Needs To Know

John D. Wooldridge, DVM, Dipl. ACVS

 

Renal transplantation is a proven means of treatment for chronic feline renal failure. A successful renal transplant will extend and afford a good to excellent quality of life, and there are now approximately 8 major centers in the U.S. offering this procedure. As the expectations and awareness of pet owners for advanced treatment options increase, it is likely that the demand for feline renal transplantation will also increase.

It is important to bear in mind that renal transplantation is another form of treatment for end stage renal failure, and that it is not a cure. It is also important to realize that renal transplantation is not performed as a “last ditch” emergency effort in an attempt to save an unstable patient, nor is it performed as a prophylactic measure. The goal of renal transplantation is to provide a good quality of life for a cat that would otherwise be unable to survive.

Clinical feline renal transplantation was first performed at the University of California at Davis in 1987. Advances in patient selection, surgical techniques, anesthetic management, and pre- and post-operative management have increased the success of the procedure; currently, approximately 70% of cats survive more than 12 months after transplantation.

The most common pathologic conditions leading to renal transplantation are chronic interstitial nephritis, polycystic kidney disease, membranous glomerulopathy, obstructive uropathy, and ethylene glycol toxicity.

In general, all candidates for renal transplantation must be free of any systemic disease other than renal failure. Every case is given individual consideration; although the oldest cat transplanted was 16 years old, there is no absolute age restriction as long as the cat meets all other criteria for transplantation.

The following diagnostic tests should all be performed during workup prior to transplantation: complete blood count, serum chemistry profile, urinalysis, urine culture and sensitivity, thyroid (T4) levels, FeLV/FIV tests, electrocardiogram and echocardiogram, thoracic radiographs, abdominal ultrasound, toxoplasma titers, blood typing.

 Diagnostic test results or physical examination findings that would preclude renal transplantation include: cardiac disease (any type), urinary tract infection, poor body condition/cachexia, FeLV positive status, uncontrolled hyperthyroidism, active FIV infection, inflammatory bowel disease, neoplasia, diabetes, fractious temperament

Cats that are identified with urinary tract infections should be treated appropriately with antibiotics for 2 weeks minimum, and then be placed on a “cyclosporine challenge” for 1-2 weeks (dose below). A repeat urine culture after this immunosuppression is then re-evaluated to insure that there is no occult infection present.

At the transplant center, immediate preoperative management includes fluid replacement as needed (subcutaneously or intravenously), nutritional support (may require placement of a gastrostomy or esophagostomy tube preoperatively), and blood transfusions as required to achieve a hematocrit of at least 30% prior to surgery. Blood cross matching is performed to several cats for kidney and blood donation. Intravenous fluid therapy or hemodialysis is necessary to attain blood urea nitrogen levels of 100 mg/dl or less prior to transplantation.

Generally, transplant recipient candidates are administered microemulsified cyclosporine (Neoralâ: Novartis Pharma AG) orally at a dose of 3 to 4 mg/kg every 12 hours beginning 48 hours prior to surgery (this protocol may vary between transplant centers). Cyclosporine whole blood concentrations are determined prior to surgery and at regular intervals in the early post-operative period. Cyclosporine dosage is then adjusted as necessary to maintain cylosporine 12 hour trough concentrations of 300-500 ng/ml. Prednisolone, at a dose of 1 mg/kg every 12 hours, is administered orally beginning on the day of surgery.

Renal allograft harvest and transplantation are generally performed by 2 surgical and anesthetic teams working together in the same operating theatre. This approach minimizes the warm ischemia time of the renal allograft, and decreases the length of anesthesia and surgical time to both the donor and the recipient. Anesthetic management involves careful attention to direct and indirect arterial blood pressures, blood gas analysis and correction, maintenance of normothermia, if possible, mannitol infusions to both donor (immediately prior to allograft harvest) and recipient, and availablility of whole blood for transfusion to the recipient, if necessary.

Renal transplantation in cats requires microvascular surgical technique. Final vascular clamping and donor nephrectomy is performed when the recipient is fully prepared to receive the kidney. Anastomosis is performed to either the recipient’s external iliac vessels in the iliac fossa, or to the caudal aorta and caudal vena cava This latter technique uses partial occlusion clamps to obstruct blood flow in both the aorta and the caudal vena cava, and appears to allow a shorter warm ischemia time. Generally, the length of time for the anastomosis of the renal vein and artery should be 60 minutes or less to ensure normal function of the transplanted kidney. Uretererneocystostomy is then performed. A gastrostomy feeding tube is placed in all transplant recipients if not already present, to allow adequate nutritional support in the post-operative period. Intestinal and native kidney biopsies are obtained from the recipient prior to closure. The native kidneys are not removed, as it is likely that they will provide some support in the event that allograft function is delayed. Occasionally, native nephrectomy may be performed at a later time, if indicated.

Intensive post-operative management of the transplant recipient is vital. Hypertension, which can lead to neurologic disorders and seizures, is aggressively monitored and controlled with the use of hydralazine (2.5 mg total dose, subcutaneously). Post-operative pain management is critical, and initially electrolytes, creatinine, blood urea nitrogen, and hematocrit are measured every 6 hours. Gastrostomy tube feedings are begun the day following surgery, with careful provision for adequate nutritional support. Intravenous fluid therapy is continued until the recipient is eating and drinking. Transplant recipients are moved to an isolation ward as soon as acute intensive care is no longer necessary. The normal post-operative hospitalization period ranges from 7-14 days.

Initial cyclosporine whole blood concentrations are measured and adjusted to maintain 12 hour trough concentrations of 300-500 ng/ml. As cyclosporine absorption and metabolism can vary among patients, trough concentrations are initially measured weekly until stable. Eventually, cyclosporine blood concentrations are tested at intervals of no less than 3 months for the remainder of the cat’s life. Prednisolone is tapered to a dosage of 1 mg/kg once daily over the first 4 weeks following surgery. Routine monitoring of complete blood count and serum chemistry profiles are recommended at the same time as the whole blood cyclosporine trough concentrations.

Owners of transplant recipients are asked to monitor their cat’s body weight, appetite, and attitude carefully. Weight loss and gain are both important and may require medical attention and/or adjustment of the cyclosporine dosage.

Acute rejection of the transplanted kidney requires rapid identification and institution of therapy to prevent loss of the allograft. Anorexia, intractable vomiting, gastroenteritis, etc. are all potential reasons that cyclosporine blood concentrations may drop dangerously low and precipitate a rejection episode; it is important not to “wait” for increasing azotemia before beginning treatment for rejection, or the allograft may be irreversibly damaged. Injectable cyclosporine (Sandimmuneâ: Novartis Pharma AG) is administered intravenously at a dose of 6.6 mg/kg (diluted into 100 ml of Dextrose 5% water or 0.9% NaCl) over 4-6 hours every 24 hours. Prednisolone sodium succinate at a dose of 10 mg/kg is also administered intravenously every 12 hours, until plasma creatinine and blood urea nitrogen concentrations return to normal. Balanced electrolyte fluid diuresis is maintained throughout this period, until the recipient is able to eat and drink, and to return to oral medication.