IMMUNOSUPPRESSIVE THERAPY FOR THE FELINE TRANSPLANT PATIENT
All transplant patients must be on lifelong immunosuppressive drug therapy to prevent rejection of the transplanted kidney. Although it is true that rare case in cats and humans are able to maintain their grafts without such drugs, it must be recognized that such cases are rare and you should assume your cat is not one of those cases. Taking your cat off immunosuppressive drugs is extremely risky and will almost always result in destruction of the transplanted kidney.
There are two immunosuppressive drug regimens used at the UW-VMTH. The standard regimen involves oral cyclosporine and prednisolone given twice a day (prednisolone is changed to once a day after the first month). We try to achieve blood trough levels (levels measured in the blood just before the next dose is given) of 500 ng/ml in the first month and then 250 ng/ml after that. Trough levels will vary. Levels below 200 ng/ml begin to put the patient at risk for rejection (levels around 100 ng/ml are a high risk for rejection).
Higher levels than our target trough levels present several potential problems. Cyclosporine can be toxic to the kidneys. This is especially true in humans. Most cats are not susceptible to cyclosporine nephrotoxicity. However, there are cats that will have increases in serum creatinine if the cyclosporine levels go above 700-800 ng/ml or more. This toxicity has always been reversible in our experience when the cyclosporine levels are reduced. There are also patients that have systemic effects of cyclosporine toxicity. This most commonly presents as loss of appetite, malaise, vomiting, or diarrhea. It can look like rejection but the serum creatinine levels will not be elevated.
A triple-agent once-a-day immunosuppressive regimen is also available. This involves giving cyclosporine, ketoconazole and prednisolone once a day. Ketoconazole prolongs the time cyclosporine A remains in the blood and can allow once a day dosing in many cats. Ketoconazole may also be used to reduce the dose of cyclosporine A when given twice a day if a patient requires inordinately high doses of cyclosporine to maintain their blood levels. This adjunct may be useful to reduce the costs of medication, when medicating a patient is very difficult and so it is desirable to reduce the frequency of pill administration or if the lifestyle of the owner dictates that a once-a-day regimen is needed
This regimen is not used if:
- the patient presents with elevated liver enzymes.
- the patient is very sensitive to cyclosporine (either gets easily toxic or achieves very high blood levels on relatively low doses of cyclosporine).
Approximately half of our patients end up on this once-a-day regimen. We have had patients that have been on it for up to 3 years. Patients are withdrawn from this regimen if they have:
- persistent elevations in liver enzymes
- evidence of weight loss without any obvious medical reasons for this to occur
- difficulty with regulating cyclosporine levels (ie. they are persistently too high)
This regimen is advantageous for many clients but needs to be closely monitored.
Monitoring is done at the 24 hour time point (before the next dose) rather than at 12 hours as is done with the twice a day regimen. Cats that poorly tolerate this regimen are placed on the conventional twice-a-day therapy with cyclosporine and prednisolone.