Kidney Transplantation

INFORMATION FOR VETERINARIANS

 

Feline Renal Transplantation

Kidney transplantation offers cats hope from the inevitable progression of chronic kidney failure. Chronic renal failure (CRF) is a common problem in the geriatric cat, although it can affect the young and middle aged cat as well. After reaching a certain level of dysfunction, progression is inevitable, even in the few situations where there is an inciting event that can be effectively treated. Thus, cats with CRF have been sentenced with an inexorable deterioration. No treatment will reverse the disease.
 
In order to ameliorate the signs of renal failure, a wide variety of symptomatic treatments have been advocated. Subcutaneous fluid administration helps combat dehydration secondary to the polyuria. Histamine blockers treat the gastric ulcers that arise from the uremic toxins. Low protein diets provide less nitrogen to be excreted by the kidneys. Phosphorus binders prevent absorption of dietary phosphorus from the intestinal tract. Potassium supplements are frequently needed. Erythropoietin injections may be needed to treat anemia, and iron supplementation must be provided for an effective response. Antiemetics may be utilized to combat nausea. Antihypertensives are used for high blood pressure. There may be a role for ACE inhibitors beyond blood pressure control. For many cats and many owners, the time and effort of these treatments limit therapy, and none of these treatments reverses or halts the progression of renal failure.
 
Renal transplantation, by supplying the cat with a fully functional kidney, eliminates the need for these treatments. Dietary restrictions are lifted, hydration status is maintained by the kidney without fluid administration, and the underlying cause of the other signs mentioned is removed, thus negating the need for medications to control those symptoms. Renal transplantation has the potential to reduce the medications from many to two, and the cats enjoy a normal quality of life when the transplant is successful.
 

Candidates for renal transplantation

Kidney transplants have been clinically available for cats for about a decade, although facilities skilled in providing this technique have been limited until several years ago. An acceptable candidate for kidney transplantation has no disease of systems other than the kidneys. Any cat with a disease that could potentially affect the transplanted kidney (like pyelonephritis) should not be transplanted. Cats with disease such as idiopathic chronic interstitial nephritis, glomerulosclerosis, a previous irreversible toxic insult, or polycystic kidney disease can make excellent candidates. Transplantation should be considered when the cat is in early stages of decompensation, usually signified by weight loss.
 
Cats who have decompensated and need hospitalization and aggressive support are not transplant candidates until they have been stabilized. If they cannot be stabilized medically, they are poor surgical risks. Transplantation is never an emergency surgery. With acute anuric renal failure, the patient can be stabilized with hemodialysis. In antifreeze intoxication, the toxic metabolites of ethylene glycol must be removed (by excretion or dialysis) prior to transplantation to avoid damage to the allograft, with surgery to follow in 1 to 2 weeks.
 
The Animal Medical Center is now offering renal transplantation for cats. While kidney transplants are available in many locations for cats, there are only two institutions who will consider canine transplants in special cases (University of Ontario, Guelph and University of California, Davis). Unrelated dogs require more intensive immunosuppression than cats, which frequently has unacceptable side effects (particularly gastrointestinal toxicity and infectious complications). We do not offer renal transplantation for dogs.
 

Contraindications to Renal Transplantation

Because immunosuppression is needed to prevent rejection, cats with previous or current urinary tract infections are not acceptable candidates. Despite aggressive antibiotic therapy and apparent resolution, infection tends to reactivate with the immunosuppression, leading to pyelonephritis and subsequent failure of the transplanted kidney or to overwhelming septicemia. Cats with pyelonephritis or a previous positive urine culture are disqualified. Heart disease of any variety greatly complicates the anesthesia and immediate post operative recovery, and many of these cats succumb to the heart disease rather than recovering. Even though these cats may be in end stage renal failure, they may be able to survive at home with conservative therapy for a short period of time. Inflammatory bowel disease has been linked with a heightened immune responsiveness leading to a high probability of graft rejection. Cats with feline leukemia virus infection have not fared well with the necessary immunosuppression and are rejected as candidates. The same is not true of feline immunodeficiency virus infected cats; some of these have had long term survival (6 years), so while the preference is to not transplant FIV positive cats, it is not an absolute disqualification. Disease of systems other than the kidneys is likely to complicate recovery and management of the transplant recipient, so patients with other diseases must be disqualified. Because immunosuppression is tantamount to preserving renal function, an inability to administer medication, whether due to the cat or the owner, prohibits transplantation. Intensive handling and monitoring will be necessary in the perioperative period and for long term follow-up; aggressive cats cannot receive the optimal level of care they need and should not be transplanted.
 

Pretransplant Evaluation of Recipient

A thorough evaluation of the potential candidate is necessary to detect any underlying conditions that may prevent successful transplantation. The standard screening includes a serum chemisty panel, a complete blood count, feline leukemia and feline immunodeficiency virus serology, urinalysis, urine culture, thoracic and abdominal radiographs, an abdominal ultrasound, echocardiogram, and a thyroid level in cats over 8 years of age (see table). A kidney biopsy is not necessary in most cases, although a biopsy will be performed at the time of transplant. Human recombinant DNA erythropoietin (EpogenÒ) or blood transfusions will be used to correct anemia prior to surgery.
 

Donor Cats

Because ½ of one normal kidney provides adequate renal function, healthy cats can donate a kidney without adverse effect to their own health or longevity while improving the quality and quantity of life to the recipient. The family of the kidney recipient cat is required to adopt the donor cat. Our donor cats were homeless abandoned cats. They are young adult cats with a pleasant demeanor. They have been extensively quarantined and screened for infectious diseases and adequate renal function. In addition to the screening laboratory tests, an intravenous pyelogram is performed to evaluate for any structural anomalies. A crossmatch with the intended recipient is performed to evaluate compatibility.
 

The Transplant Surgery

Two teams of surgeons work simultaneously. The donor team prepares the kidney by clearing fat and fascia from the vessels and ureter. The right kidney is usually harvested, unless the renal artery is short or branched. While the kidney is being prepared, the graft site in the recipient is prepared. Mannitol is given to the donor 20 minutes before the kidney is harvested to decrease acute tubular necrosis. Once the kidney is removed from the donor, it is flushed with saline. The renal vein is anastomosed to the caudal vena cava and the renal artery to the aorta under an operating microscope. When both anastomotic sites are complete, the vascular clamps are released to allow venous flow and then arterial flow. Warm ischemia time (time without blood flow to the kidney) must remain under an hour to prevent damage to the kidney. The ureter is then implanted in the bladder and the kidney is tacked to the body wall to prevent torsion. A esophagostomy or gastrotomy tube is routinely placed in the recipient and the native kidney is biopsied. Recipient nephrectomy is rarely performed; the native kidneys may provide some renal function if there is delayed graft function or during rejection episodes. Careful attention to body temperature, blood pressure, fluid balance and electrolyte status is necessary in the immediate postoperative period.
 
Many transplanted kidneys will begin functioning immediately, but a delay up to 72 hours is not abnormal. Once kidney function is established, intravenous fluids are discontinued. Tube feeding is started if the patient will not eat voluntarily. Most cats are discharged within a week of surgery.
 

Immunosuppression

Suppression of the immune system is necessary to prevent rejection of the transplanted kidney. The development of cyclosporine A (CyA) heralded the advent of clinically feasible transplantation in cats. This drug works by blocking the synthesis of interleukin 2 (IL2), which prevents T cell proliferation. Because graft rejection is a cell-mediated immune response, CyA is an effective agent in this setting. It is started 24 hours prior to surgery, and trough levels are monitored every few days until stable. CyA is a lifelong drug in transplant recipients. If trough levels decrease below the recommended level, due to missed doses poor absorption, drug interactions, or otherwise, rejection can occur. There are many drug interactions between CyA and other drugs commonly used in renal disease that may increase or decrease plasma CyA levels.
 
Prednisone is used in conjunction with CyA in transplant recipients. It has many effects on the immune system, including suppression of cytokine production, suppression of arachidonic acid metabolism and alteration in chemotaxis of cells of the immune system. Prednisone is started immediately postoperatively. It is usually tapered and discontinued after 6 months.
 

Aftercare

After surgery, close monitoring of the creatinine, cyclosporine level, and urine is necessary. Initially, recipients are checked weekly for a month, then monthly for six months, then every 3 months thereafter. Optimal trough cyclosporine levels are maintained by dose adjustments as needed. Once the cat is eating well on his own, usually within a month of surgery, the gastrostomy tube is removed.
 
An episode of acute rejection may begin with nonspecific signs of lethargy with or without azotemia. Immediate therapy with intravenous cyclosporine and glucocorticoids can reverse rejection and salvage the graft. Owners are instructed to locate a 24 hour emergency facility that can manage a rejection episode, with guidance from the transplant team. Chronic rejection has a more insidious course, which can lead to long term graft dysfunction.
 
The estimated cost for transplantation ranges around $8000, baring complications. This estimate is for the surgery and perioperative hospitalization. On-going cost for follow-up and medications is estimated to be $3000 for the first year and $2000 per year thereafter.
 
Approximately 75% of cats survive the surgery and perioperative period. Of these, 60% have good graft function at 6 months, with an overall 40% 3 year survival. Many cats have lived 4 to 6 years with their graft.
 
To obtain more information about our feline renal transplant program, you can call the Renal Medicine Service at (212)838-8100, ext. 8618, e-mail us at hemodialysis@amcny.org. To schedule an appointment for consultation with the nephrologist or transplant surgeon, have your client call (212) 838-0753.