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

To the uninitiated, the impression may be that once someone receives a new kidney, life is renewed and all the kidney problems are solved. In fact, this is hardly the case. There are immune-suppressive medications needed to prevent the new organ from being rejected, 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, and not every patient is even a candidate, so let’s walk through the main considerations.

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 is 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.

You enter the program with one cat and leave with two cats.

Is Your Cat a Candidate?

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 kidney disease.

Typical screening includes:

1. Basic blood panel (including thyroid level) and urinalysis
   
2. 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)
   
3. Feline leukemia virus and feline immunodeficiency virus screening
   
4. Ultrasound examination of the heart (heart diseases that involve high blood pressure development can damage the new kidney)
   
5. 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.
   
6. Blood typing
   
7. Blood pressure monitoring
   
8. Urine protein to creatinine ratio to evaluate glomerular disease/renal protein loss.
   
9. Teeth cleaning (performed under anesthesia)

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 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, although 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.

An additional problem for dogs worth mentioning is intestinal intussusception. Imagine a telescope. Unfolded, it is basically a cylinder, but folded, and one segment collapses inside an outer segment. Now, imagine this happening to a piece of the intestine. A life-threatening obstruction results. A procedure called enteroplication is given in conjunction with the transplant. In this procedure, the intestines are tacked down with sutures into a formation that precludes any telescoping motions. This procedure, along with proper pain medication post-surgically, seems to prevent intussusception.

Cats with relatively early kidney failure are not yet candidates for transplantation. Cats with advanced kidney failure are not good candidates either, although dialysis (available at advanced critical care facilities such as those that perform kidney transplants) may improve the values.

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, or cats with a creatinine greater than 4.0 mg/dl. The cat should have a decent appetite and be as strong as possible prior to this 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?

Recipient screening is similar to that for the feline patient though heartworm testing is needed. Blood clotting tests are also needed for dogs. Similar conditions will also rule a patient out as a candidate (no cancer, heart disease, amyloidosis, or inflammatory bowel disease.) The adrenal hormone excess known as Cushing’s disease also precludes getting a kidney transplant. 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.

What Kind of Home Care Will the Recipient Require?

The recipient is going to require suppression of his immune system for the rest of his life. This not only requires a substantial financial commitment for the medication but also the ability to give the cat oral medication at least twice a day for the rest of his life. The heart of this therapy is a medication called cyclosporine, a medication that 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 that include:

• Expense
  Cyclosporine is expensive. Concurrent administration of ketoconazole, a medication normally used to treat fungal infection, has the added benefit of “potentiating” cyclosporine. This means that less cyclosporine is needed to achieve the desired effect. As long as ketoconazole is well tolerated, it may become possible to dose the patient only once a day rather than twice. Approximately 30% of transplant patients will not be able to utilize this protocol due to the development of excessive cyclosporine levels or liver enzyme elevations from the ketoconazole.
    
• Expenses for Monitoring
  Periodic blood level monitoring is needed to check that the right dosage is being used. For most drugs, “what you swallow is what your body gets.” For other drugs, there are individual variations in how the medication is absorbed, and cyclosporine is one. When two patients take the same amount of cyclosporine, they may not achieve the same serum levels; some individual fine-tuning is needed.
     
• Long-term use of cyclosporine increases the risk for the development of cancer, specifically lymphoma. At the University of Wisconsin Renal Transplant Center, a 14% incidence of malignant tumor development is reported for cats with post-transplant time (and thus cyclosporine use time) of greater than one year.

In dogs, the chemotherapy agent azathioprine is also regularly used for its immuno-suppressive properties. It’s usually given every other day long term. Medication costs for dogs can vary from $150 per month to $2000 per month depending on the dog’s size.

What are Potential Complications for the Recipient?

• Infection from 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 recur, and they can be severe. In dogs, life-threatening infections can emerge in any organ system.   
• 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 cats. Mostly, males are affected.
• The risk for developing diabetes mellitus increases by approximately five times after a kidney transplant.

What Kind of Survival Time Can You Expect?

In a recent study of feline kidney transplants, 59% of renal transplant patients were still alive 6 months after surgery and 41% were still alive 3 years afterwards. Apparently the first 6 months is a somewhat crucial time in determining long-term survival.

The University of Wisconsin Renal Transplant Center reports 70% survival at 6 months for cats and 50% survival at 3 years. Of the cats that survived to be discharged from the hospital (i.e. they did not succumb to problems directly related to the surgery), 96% survived to 6 months.

The picture is not nearly as bright in dogs. The University of California at Davis program had a success rate of about 40%. 

Kidney transplantation is an expensive undertaking. The University of California at Davis program, for example, required a deposit of $11,000 for cats and $13,000 for dogs. Transplantation involves the adoption of a donor and long-term medication and blood testing for the recipient. If this is something you are seriously considering, be sure to discuss the procedure with the transplant center closest to you as well as with your regular veterinarian.

(Dry eye is formally known as keratoconjunctivitis sicca or KCS)

Why Tears are Good

Tears consist mostly of water, but also of oil and mucus secreted by their respective eyelid glands. The water portion of tears is secreted by two lacrimal glands in dogs and cats: one just above the eye and another in the third eyelid (or so-called nictitating membrane).

“Conjunctivae” are the moist pink membranes of the eye socket. “Itis” means inflammation and “sicca” means dry. Keratoconjunctivitis sicca, abbreviated KCS, means there is an inflamed, dry cornea and conjunctiva. It occurs when there is a deficiency in the water portion of the tear film, which normally accounts for 95% of the tear volume. Without water, one is left with oil and mucus; hence, the gooey yellow eye discharge characteristic of this condition.

Why do Eyes Become this Dry?

There are many causes of dry eye. Some are:

• Canine distemper infection attacks all body interfaces with the environment including the eyes. Dry eye is part of the constellation of symptoms that can occur with canine distemper infection. 
• In cats, herpes upper respiratory infection can lead to chronic dry eye (see more on herpes conjunctivitis).
• There could be a congenital lack of tear-producing gland tissue (as described in certain lines of Yorkshire terriers).
• Exposure to sulfa-containing antibiotics, such as trimethoprim-sulfa combinations, can lead to dry eye. It can be either temporary or permanent and occurs unpredictably.
• Anesthesia will reduce tear function temporarily (thus eyes are lubricated with ointment by the attending nurse).
• During surgery for cherry eye, removal of the third eyelid tear-producing gland, instead of replacing the gland in its proper location, can lead to KCS. So can too much damage to the gland prior to proper gland replacement.
• A knock on the head in the area of one of the tear-producing glands can lead to KCS.
• The most common cause of KCS appears to be immune-mediated destruction of the tear-producing gland tissue. We do not know what causes this type of inflammatory reaction but certain breeds are predisposed: the American Cocker Spaniel, the Miniature Schnauzer, and the West Highland white terrier.

How We Make the KCS Diagnosis

The moisture of the eye will wet the paper. At the end of the 60-second period, the length of the moistened area on the paper is measured. A length of 15mm or more is normal. A length 11 to 14mm is a borderline result. A height of less than 10mm is dry. A height less than 5mm is severely dry.

Cyclosporine is an immunomodulating drug used to prevent organ transplant rejection in people and treat certain immune diseases in dogs and cats. When applied as an eye drop or ointment, it suppresses the immune destruction that is the most common cause of KCS, and tear production is restored.

The success of this treatment plus its convenient dosing interval (1 -3 times daily) has made this medication the primary treatment for KCS.

Animal hospitals used to make their own cyclosporine eyedrops out of oral cyclosporine and vegetable oil, but this largely ended when Optimmune® eye ointment (containing 0.2% cyclosporine) came out. Occasional patients simply do not show a good response to cyclosporine ointment but will respond when the concentration is increased. Higher-concentration products can easily be formulated by compounding pharmacies or one of the alternative medications listed below can be used. Treatment is almost always required for the lifetime of the pet.

After beginning cyclosporine eye drops or ointment, a recheck in three to four weeks is a good idea to check for improvement. If the Schirmer tear test is still showing poor results, the dosing frequency can be increased to three times a day; similarly, if excellent results are seen, the medication can be dropped to once a day.  Periodic rechecks are needed for dose adjustment and some dogs take as long as three to four months to show a response. Dogs with Schirmer tear tests as low as 2 mm still have an 80 percent chance of responding to cyclosporine. This medication has been a miraculous breakthrough in the treatment of KCS.

Tacrolimus is another medication that is an immune modulator. No commercial products are available for use in the eye, so they must be obtained from a compounding pharmacy. It is often tried in cases that are unresponsive or poorly responsive to cyclosporine. It is used in a manner similar to cyclosporine and is generally similar in cost.

Pilocarpine is a cholinergic drug, which means it works on the autonomic nervous system (the part that controls automatic functions such as glandular secretion). This medication can be given for the particular form of dry eye known as neurogenic KCS. In these cases, neurogenic stimulation of the tear gland is absent, so the pilocarpine is given in an attempt to stimulate the gland. Although the drug comes as an eye drop, for KCS it is actually given orally at an increasing dose until side effects are seen (diarrhea, drooling, vomiting). If side effects are encountered, the dose is reduced to that which the animal tolerates. It is continued indefinitely or until the neurogenic KCS subsides, usually twice daily. Neurogenic KCS typically affects only one eye.

Artificial tear solutions, gels, and ointments can be purchased in most drug stores. These can be combined with other therapies and are soothing. Their use is particularly important early in therapy until cyclosporine or tacrolimus takes effect and in eyes that do not respond to these latter medications. Over-the-counter products may be recommended two-12 times daily, depending upon their formulation and the severity of the KCS.

Topical antibiotics are often needed, especially when starting treatment for KCS because secondary infections are common with inadequate tears. These products do not increase tear production but help relieve the thick discharge.

Topical steroids may be beneficial in decreasing the inflammation associated with KCS. Typically they are combined with topical antibiotics in the same solution or ointment, especially when given to dogs.

Surgical Solutions

Parotid duct transposition is a surgical solution to unresponsive, severe KCS, although it is a delicate procedure, usually done by a veterinary ophthalmologist. The parotid duct is the salivary gland on either side of the face/cheek. It produces saliva that is carried to the mouth via a long duct. This duct can be carefully dissected out and moved to the outer corner of the inside of the lower eyelid in order to deliver saliva to the eye. Saliva is a reasonable substitute for tears, although in time some mineral deposits may form on the eye surface. Mineralization of the cornea can range from mild to severe and there is no good way to predict whether mineralization will be a problem prior to the transposition of the duct. The eye may water uncontrollably when the dog is fed and facial wetting may be objectionable in some cases.