KIDNEY TRANSPLANTS IN PETS

Kidney transplantation is something everyone has heard of for human patients, but may not have considered possible for pets. In fact, while transplantations are confined to specialized facilities with experienced surgeons, successful kidney transplants in cats have been going on since the mid-1980's. Canine programs have been less successful but are also available in limited facilities.

The recipient has an additional kidney added in. The new kidney is on the right (yellow arrow)
while the original kidney (green arrow) is on the left.
(Photocredit: Dr. Lillian Aronson)

To the uninitiated, the impression may be that once one receives a new kidney, life is renewed and all one’s kidney problems are solved. In fact, this is hardly the case. There are immune-suppressive medications needed to prevent rejection of the new organ, not to mention potential for infection, on-going screening tests and other issues. A kidney transplant is a very big deal regardless of the species of the recipient and not every patient is even a candidate so let's walk through the main considerations.

WHERE DO THE DONORS COME FROM & WHAT HAPPENS TO THEM AFTER?

This is an important ethical question for everyone involved in the transplantation program. It is no one’s wish to harm the donor animal who cannot voluntarily become an organ donor in the way a human can, nor is there a mechanism to harvest organs from comatose brain-damaged patients as might be done for humans.

The kidney transplant team in action.
(Photocredit: Dr. Lillian Aronson)

Feline kidney donors usually come from research facilities. These cats are classified as “specific pathogen free” which means they are free from infectious diseases. They are matched by blood typing and potentially by tissue-typing depending on the transplant program. A research cat is selected and a kidney removed for the recipient. After the procedure, the owner of the recipient cat must adopt the donor.

Some transplantation programs allow the owner of the recipient cat to provide the donor. Donors must be young adults, generally at least 10 pounds in size, be free of infectious diseases such as Feline Immunodeficiency Virus, Feline Leukemia Virus, and Toxoplasmosis, and must have excellent kidney function. Basic blood testing and urine cultures must be normal. The donor cat is screened further with a CT scan of the kidneys to check for extra blood vessels, evidence of kidney disease, or other issues that might exclude a cat as a donor candidate. If no exclusions are found, the donor is set to provide one kidney to the recipient.

One enters the program with one cat and leaves with two cats.

For dogs, the owner of the recipient is generally responsible for finding the donor. The University of California transplant program has been on hold since 2007, but as an example, their former donor guidelines were these: the donor must be less than 6 years of age, of similar size as the recipient (and preferably of the same breed), and, if the donor is not related to the recipient, special tissue matching is needed. Screening tests for the canine donor are similar to those for the feline donor but also include heartworm testing.

IS YOUR CAT A CANDIDATE FOR A NEW KIDNEY? Kidney transplantation is not a procedure that is left until all medical therapies have been exhausted. The best candidate is free from other medical problems besides the kidney disease and is not in an advanced state of debilitation. If the kidney disease is too advanced at the time that transplant is being contemplated, it must be controlled before proceeding. Most cats are in IRIS Stage 3 or 4 at the time of transplant surgery. Further, the potential recipient must be screened for an assortment of conditions that might complicate or even preclude the transplant. Typical screening includes:

(Photocredit: Morguefile.com)

• Basic blood panel (including thyroid level) and urinalysis.
• Urine culture (elimination of latent infection is crucial and often a trial of immune-suppressive drugs is used after an infection has been cleared to ensure that the infection does not come back).
• Feline Leukemia Virus and Feline Immunodeficiency Virus screening.
• Ultrasound examination of the heart (heart diseases that involve high blood pressure development can damage the new kidney).
• Screening for Toxoplasmosis (the immune suppressive drugs needed to maintain the new kidney could reactivate a latent infection with this parasite). A positive test for Toxoplasma does not preclude the transplant but a positive donor must be selected. Recipient cats testing positive for Toxoplasma are generally kept on clindamycin for life. Recipient cats testing negative will be periodically screened for Toxoplasma for the rest of their lives.
• Blood typing.
• Blood pressure monitoring (hypertension is not only a common complication of kidney disease but it is a special pitfall after kidney transplant so the cat's status must be regularly tracked).
• Urine protein to creatinine ratio to evaluate glomerular disease/renal protein loss.

Different programs may have additional required screening tests such as kidney biopsy, intestinal biopsy to rule out Inflammatory Bowel Disease, test doses of immune-suppressive medications, etc. Obviously the details would be provided by the specific program being considered.

If the cause of the recipient's kidney failure is felt to be something that would lead the new kidney to fail as well, this may disqualify the patient from the program. Such conditions would include: renal lymphoma or other cancer, amyloidosis (a malignant protein deposition), and pyelonephritis (a deep kidney infection though if the infection is truly felt to have been eliminated, the patient might still qualify). Again, each program will indicate what conditions might serve to automatically disqualify a recipient.

Cats with relatively early kidney failure are not yet candidates for transplantation. Cats with advanced kidney failure are not good candidates either, though, through dialysis (available at advanced critical care facilities such as those that perform kidney transplants) the values may be improved. The best candidates are those with an acute cause of kidney failure (such as a poisoning), cats who do not respond well to the usual medical management, and/or cats with a creatinine >4.0 mg/dl and a BUN < 100 mg/dl. (Cats with higher toxin levels have an increased risk for brain edema so the kidney disease must be controlled well enough to bring these values into an acceptable range prior to transplant). Anemic cats (cats with low red blood cell counts) are commonly treated with special hormones for several weeks prior to transplant so that they will have an acceptable blood count before surgery. Cross matching with blood donors is also performed in preparation for the big day. The cat should have a decent appetite and be as strong as possible prior to this very major surgery.  Again, each transplant center will have its own criteria.

Prior to surgery, the recipient cat should be made as stable as possible.
Usually a blood transfusion is needed to correct the renal failure associated anemia.
Sometimes dialysis is also needed.

IS YOUR DOG A CANDIDATE? Kidney transplants in the dog are more complicated and survival times are substantially lower than in the cat. Only a few programs are in operation. That said, kidney transplants are being performed in dogs. Recipient screening is similar to that for the feline patient though, again, heartworm testing is needed. Blood clotting tests are also needed for dogs as they have more complications with embolism/abnormal blood clots. Similar conditions will also rule a patient out as a candidate (no cancer, significant heart disease, or amyloidosis.) The adrenal hormone excess known as Cushing’s Disease also precludes participation in the kidney transplant program. Kidney transplants for dogs are generally not as successful as for cats so be sure you understand what you are getting into and the likelihood of obtaining the outcome you are hoping for. The patient should not be in an advanced state of disease and may need dialysis to be returned to an early IRIS stage.

(Photocredit: Morguefile.com)

WHAT KIND OF HOME CARE WILL THE RECIPIENT REQUIRE?

The recipient is going to require suppression of his or her immune system for the rest of his or her life. This not only requires a substantial financial commitment for the medication but also the ability to give the pet oral medication at least twice a day for the rest of his or her life. The heart of this therapy is a medication called “Cyclosporine,” a medication which has revolutionized organ transplantation for humans. Prednisolone, a commonly used cortisone derivative, is typically used as well at least to start.

Cyclosporine is typically given twice a day with the lowest blood level of the day being approximately 500 ng/ml around the time of surgery and lowering to 250 ng/ml after a month or so of recovery after surgery. (Rejection of the new kidney occurs when levels dip below 200 ng/ml).

Cyclosporine has some disadvantages which include:

• Expenses for the Drug
  Cyclosporine is an expensive medication, especially since generic versions are generally not equivalent to brand name products. Cyclosporine expenses are less for cats simply because of their size but canine patients are generally larger and the cyclosporine expense can be very great. A pharmacological trick can be used to exploit a drug interaction between cyclosporine and an antifungal medication called ketoconazole, such that the ketoconazole serves as a booster for cyclosporine allowing for a smaller amount of cyclosporine to go farther. Approximately 30% of transplant patients are able to take advantage of this cost cutting measure though good liver function is necessary to make it work.
  
  In the dog, azathioprine, an agent of chemotherapy, is also regularly used for its immuno-suppressive properties. It is usually given every other day long-term. Medication costs for dogs can vary from $150 per month to $2000 per month depending on the size of the dog.
  
  
• Expenses for Monitoring
  For most drugs “what you swallow is what your body gets” and the dose is simply determined by the size of the patient. For other drugs such as cyclosporine there are individual variations in how the medication is absorbed into the body which means blood levels are not entirely predictable. In other words, when two patients take the same amount of drug, they may not achieve the same serum levels; some individual fine-tuning is needed. Periodic cyclosporine blood level monitoring is needed to check that the right dosage is being used.

WHAT ARE POTENTIAL COMPLICATIONS TO THE RECIPIENT?

It is not surprising that a major procedure such as a receiving a new kidney would have associated complications. The main issues stem from rejection of the new kidney, infections related to the immunosuppressive drugs, and scarring from the surgery itself. Here are some of the concerns that kidney recipients must contend with:

Rejection of the new kidney (which can occur at any point after transplantation). When a kidney is rejected, the pet will go back into kidney failure and suffer all the toxic symptoms that accompany that diagnosis (nausea, malaise etc.) If therapy (i.e. more aggressive immune suppression) is initiated quickly, the kidney can be saved. Rejection can also be a more chronic and insidious process, gradually destroying the new kidney over years. This phenomenon is not well understood and it is not known how commonly this occurs. Acute rejection (i.e. rejection in the first few months, which is when most rejections become evident) occurs in 13-26% of cats. Many patients do not show symptoms which one of the reasons that cyclosporine blood testing is so important. Stricture (narrow scarring) of the ureter, which is the tiny tube that carries urine from the new kidney to the urinary bladder. If this occurs, another surgery is needed to trim the scarred area and re-attach the ureter to the urinary bladder. The original kidneys are generally not removed unless there is a reason to do so. The new kidney is simply an extra one. There is an approximately 21% incidence of this complication in the first 62 days post-operatively in the cat. Mostly males are affected. Infection from the immune-suppressive therapy is the second most common cause of transplant-associated death (rejection being the first). In cats, Toxoplasma infection is of particular concern and, while preoperative testing may have already been negative, some cats turn positive after the immune suppression begins. Also in cats, old viral upper respiratory infections can be expected to recrudesce and they can be severe. In dogs, life-threatening infections can emerge in any organ system. Feline transplant patients have a 5 fold increase in risk for the development of diabetes mellitus. The cats that become diabetic then have a second serious condition to contend with as well an increased risk for infections as described above. Feline transplant patients have a 6 fold increase in risk for the development of lymphoma, lymphocytic cancer.There is an additional problem for dogs that is worth mentioning and that is intestinal intussusception. Imagine a telescope. Unfolded, it is basically a cylinder but folded, one segment collapses inside an outer segment. Now imagine this happening to a piece of intestine. A life-threatening obstruction results. To prevent this, the canine kidney patient has a procedure called "enteroplication" in conjunction with the transplant. In this procedure, the intestines are tacked down with sutures into a formation that precludes any telescoping motions. This, along with proper pain medication post-surgically, seems to prevent intussusception.

WHAT KIND OF SURVIVAL TIME CAN YOU EXPECT?

The first six months after surgery is a somewhat critical period as this is where most complications strike. Between 70 and 93% of cats will survive their surgery and be discharged from the transplant center. The median survival time for cats has been reported as 360-653 days, with 6 month survival rates of 59% and 79% reported by different transplant centers. Three year feline survival rates were reported as 32%-50% depending on which transplant center is reporting.

The canine situation is not as positive. Published statistics have been as low as 24 days median survival but this study included dogs receiving kidneys from unrelated donors. Until there is a breakthrough in immunosuppression for the dog, the kidney donor must be a genetic family member for a fair expectation of success.

Kidney transplant is a very expensive undertaking and is likely to require travel or even relocation to the area of a transplant center. The following programs are currently performing kidney transplants:

University of Pennsylvania
School of Veterinary Medicine
3900 Delancey St.
Philadelphia, Pennsylvania 19104
(215) 898-4680
Lynn Beale, Transplant Coordinator
e-mail: lbeale@vet.upenn.edu
(215) 573-0206
Dr. Lillian Aronson, DVM
e-mail: laronson@vet.upenn.edu

University of Georgia
College of Veterinary Medicine
Department of Small Animal Medicine and Surgery
501 DW Brooks Dr.
Athens, GA, 30602
Phone: (706) 542-3221
Fax: (706) 542-6460
Chad Schmiedt DVM, DACVS
e-mail: cws@uga.edu

University of Wisconsin
Veterinary Medical Teaching Hospital
School of Veterinary Medicine
University of Wisconsin
2015 Linden Dr. W.
Madison, Wisconsin 53706
(608) 262-6512
Gerianne Holzman, CVT, Transplant Coordinator
e-mail:holzmang@svm.vetmed.wisc.edu
Dr. Jonathan McAnulty, DVM, MS, PhD
e-mail:mcanultj@svm.vetmed.wisc.edu

This article reviews some of the information presented above but also includes a list of kidney transplant programs around the country:

https://todaysveterinarypractice.com/insights-into-feline-kidney-transplants/

This page is also part of the Chronic Renal Failure Center.
Other Pages in the Chronic Renal Failure Center:

• Kidney Failure: Where to Begin
• Fluid Therapy In Renal Insufficiency
• Dietary Therapy
• Appetite Management
• Renal Anemia/Red Blood Blood Cell Loss
• High Blood Pressure
• Calcium/Phosphorus Balance
• Glomerular Disease: Urinary Protein Loss
• Dialysis
• Kidney Transplants (this page)
• External Links for Further Information

Last updated: 6/23/2021