| Renal Transplantation in Cats - Information for Veterinarians | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Article Written by Dr. Daniel A. Degner, Board-certified Veterinary Surgeon (DACVS) |
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Key PointsChronic renal failure in cats usually is progressive and irreversibleRenal transplantation is a viable option to control renal failureTransplantation improves the quality of life of the cat dramatically |
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Introduction Chronic renal failure (CRF) in cats is a progressive, irreversible condition which usually leads to death as a result of uremia months to years after initial diagnosis. Overall, approximately 2% of all cats will be diagnosed with CRF at some point in their life. Chronic renal failure is a very common disease in cats, especially older cats. Recent reports indicate that approximately 10-30% of cats 10-15 years of age and 32% of cats greater than 15 years of age are diagnosed with chronic renal failure. Therefore, this represents a very common disease entity in cats. Cats with mild to moderate CRF may be managed medically with dietary and other forms of symptomatic medical management. However, such forms of therapy are largely ineffective in cats with advanced CRF. Renal transplantation has proven to be a successful alternative form of treatment. Cats do not have as great a problem with allograft rejection as do dogs when treated with immunosuppressive drugs such as cyclosporine and prednisone. The major histocompatibility complex on feline red cells is similar to those found on endothelial cells of the kidney. As a result, only cross-matching is required for donor recipient compatibility. Using this type of donor recipient matching, hyper-acute and acute rejection of renal grafts rarely occur. Failure of renal grafts in cats usually is due to chronic vascular disease, which results in gradual occlusion of the arterial supply of the graft. This may take a number of years to develop.1-4 Definition of Chronic Renal Failure Cats in chronic renal failure have BUN and creatinine levels that are above normal range, specific gravity less than 1.035. Isothenuria is common, however, be aware that specific gravity is not always a clear indicator of renal insufficiency in cats as it is in dogs and humans. The presence of clinical signs which suggest chronic renal disease include weight loss, anemia and small to normal kidney size.
Candidates for Renal Transplantation must be preferably free of underlying diseases. Cardiomyopathy, if present, should not be severe. Mild to moderate hypertrophic changes may result from increased afterload caused by renal-induced hypertension. Hypertension is common in cats that have renal failure due to an imbalance of the angiotension system. Hypertension could lead to seizures, retinal detachment and other significant problems in the postop period. Hypertension should be under control with medication prior to surgery; frequently cats will become normotensive following renal transplantation. If this does not occur, removal of the diseased native kidneys should be considered. Diabetes mellitus is not an absolute contraindication for renal transplantation, however, can lead to other complications such as urinary tract infection. Hyperthyroidism can affect multiple body systems, including heart, blood pressure, renal function and body metabolism, therefore should be under control with medication prior to transplantation; after transplantation has been completed and the cat is stable, I131 therapy should be considered. Nephrolithiasis is not an absolute contraindication for transplantation, however, may increase the risk for urinary tract infection or development of stones in the graft, especially if the cause of the stones is extra-renal. In summary, cats should be preferably free of the aforementioned diseases, however, under the care of an diligent owner and internist, other coexisting diseases can be dealt with in the renal transplant patient. Candidates MUST be free of a number of diseases. Infections such as chronic recurrent upper respiratory viral infection, Feline Leukemia Virus infection, Feline Immunodeficiency Virus infection, Hemobartonella, Toxoplasma, and urinary tract infection to name a few, are contraindications for renal transplantation. Urinary tract infection or previous history of recurrent UTI is a strong indication to be rejected from a renal transplantation program, as these cats develop UTI very readily when immunosuppressed with cyclosporine, which may lead to pyelonephritis and graft dysfunction. Inflammatory bowel disease has a high risk for kidney rejection due to hyperimmunity. No neoplastic or preneoplastic process can be present at all; cyclosporine immunosuppression will result in the cancer going rampant. Renal amyloidosis is contraindicated as amyloidosis of graft will occur. Likewise glomerulonephritis is a systemic disease which will destroy the graft. Notes about co-existing conditions The presence of co-existing does not necessarily preclude a cat from being a suitable transplant candidate. A cat that has had a previous upper respiratory viral infection or a past history or urinary tract infection can be challenged with cyclosporine (with trough blood levels greater than 500ng/ml) for three weeks; if the cat breaks with an infection, it is a poor candidate for transplantation. Cats that have chronic recurrent urinary tract infection are generally not acceptable candidates for transplantation. If a cat develops recurrent urinary tract infections after receiving a renal graft, life-long antibiotic therapy likely will be needed. Recipients should be preferably in an early decompensated state of renal failure. Recipient cats that have not lost more than 20-30% of body weight are better candidates, as loss of a significant amount of weight may coincide with multi-organ disease. We have transplanted patients that had lost about 30 to 40% body weight and they have done well. Anesthetic and surgical risks are increased in these patients. Recipient Preoperative Workup The recipient cat should be blood typed as the first step; the recipient should be type A. If the recipient does not have type A blood, transplantation is not advisable as an acceptable donor will be difficult, if not impossible to identify. Other tests that should be done include major and minor RBC cross-match, complete blood cell count, chemistry, urinalysis, T4, Urine culture (collected by cystocentesis only; do not start antibiotics prior to urine culture), FeLV/FIV tests, Hemobartonella (RIA) test, Bartonella, Toxoplasma titers, echocardiogram, thoracic and abdominal radiographs, renal ultrasound, fundic examination (to evaluate for hypertension), doppler blood pressure (do repeated evaluations under unstressed conditions). All blood and urine testing should be done by a reputable veterinary blood laboratory and not by in-house machines. Recipient Preparation for Surgery Prior to surgery the renal transplant candidate should be in as good nutrition as possible. A good plane of nutrition should be established. Placement of a PEG tube or esophagostomy tube may be important to provide adequate food intake prior to surgery (we routinely place PEG tubes at the time of transplant surgery, if it is not already in place). Anemia should be corrected to at least a PCV of 30%. Erythropoietin 100 U/kg sub-Q three times per week may be administered. An alternative dosage is 100 U/kg daily for the first five days, then a reduced frequency of administration to three times per week. It is important to monitor the PCV closely while using this drug. Poor response or worsening of the anemia suggests that the patient is producing antibodies against the erythropoietin, necessitating discontinuation of the medication. Supplementation with vitamin B complex and iron may also help these patients. Blood transfusions, if needed, should be given 2-3 days prior to surgery; cross-matching is essential. Fluid therapy should be administered to decrease azotemia. Correction of electrolyte and acid/base balance should be done prior to anesthesia. Immunosuppressive therapy should be started two days prior to surgery using Cyclosporine 2 to 5 mg/kg BID PO (put in gel cap - bitter tasting) and Prednisolone 0.25 mg/kg BID PO, starting the day of surgery. Kidney Donors Blood type of a kidney donor must be same as recipient. A donor must be adult, healthy, large (10 pounds), young cat (1-5 years of age), free of FeLV/FIV, urinary tract infection, toxoplasmosis, and major organ disease. Renal function must be normal. The graft must have normal renal architecture on ultrasound imaging. The renal graft must have a single renal artery, as the arterial renal blood supply is segmental. If a kidney has two arteries, ligation of one of these vessels will result in necrosis of a portion of the kidney. In addition, the diameter of each renal artery is usually too small to microsurgically anastomose to the aorta (a typical renal artery is 1.5 mm in diameter). If double renal veins are present, the smaller is ligated and the larger of the two is anastomosed to the cava, as the renal venous drainage system is not segmental. Compatibility of Donor with Recipient The major histocompatibility complex antigens found on feline red blood cells are homologous to those found on the vascular endothelium of the kidneys; therefore, tissue typing has not been traditionally used to identify a suitable donor. To determine compatibility of the donor with the recipient, a major and minor red blood cell cross match is performed. If the cross-matches are compatible, acute rejection is unlikely. In the rare situation, a cat will not cross match with any donor (due to the presence of idiotypic antibodies). Additional testing such as mixed lymphocyte reaction test can be used to further define compatibility of the donor graft, but is generally not needed. Donor Preoperative Workup Blood type and RBC cross match with recipient should be done prior to any further testing; if the donor is a match, additional testing can be done. Additional testing includes CBC, chemistry, urinalysis, urine culture, FeLV/FIV, Hemobartonella test, renal ultrasound, and abdominal radiographs. All blood and urine testing should be done by a reputable veterinary laboratory and not by in-house machines. Owners are to provide a kidney donor. Euthanasia of any kidney donor is strictly in violation of our transplant team’s policy. Surgery Details of renal graft harvest. The left kidney is the preferred graft, as it has longer renal vessels, but the right kidney can also be used. The peritoneum is incised around the entire circumference of the kidney. Using blunt finger dissection, the kidney is liberated from the retroperitoneal fat. The kidney is reflected ventrally; during the entire dissection process, the kidney is handled very gently - minimal pressure. During the dissection, the renal vessels are frequently irrigated with 2% lidocaine to minimize vasospasm (which could contribute to warm ischemia time). The renal artery is exposed on the craniodorsal aspect of the vascular pedicle. The gonadal artery and vein are ligated using fine suture or hemoclips. The fat is cleared from the renal artery and vein taking care to preserve the ureteral artery and vein, which extend off of the parent vessels at the level of the hilus of the kidney. The phrenicoabdominal vein originates at the base of the renal vein and should be preserved. The adventitial is dissected off the renal artery and vein at the proposed region of transection (near the aorta and vena cava).
Postoperative Medications 1. Cyclosporine 2-5 mg/kg BID PO (put in gel cap - bitter tasting) initially. Please note that once a cyclosporine bottle has been opened, it expires after two months. Exposure to air oxidizes the medication and renders it inactive. To extend the life of a 50 ml bottle of cyclosporine, fill 10 ml or 25 ml amber glass bottles to the top, seal and use later. The microemulsion form of cyclosporine (Neoral) is more readily absorbed from the GI tract than the regular form of the cyclosporine (hence the cost to the owner may be reduced). Flavoring the medication has been tried (liver flavor etc), however, in my experience it alters bioavailability of the drug and blood levels drop. The bioavailability of cyclosporine varies from cat to cat, therefore, whole blood cyclosporine levels must be measured. The oral dose of the drug is adjusted to maintain blood levels around 500ng/ml during the first month, then 250 ng/ml for the life of the patient. It is common that the initial cyclosporine blood level will be 1500 to 3000 ng/ml when the cat receives the 5 mg/kg dose. As the liver begins metabolizing the drug, the blood levels will drop quickly without adjusting the oral dose. Be aware that the cyclosporine blood levels do not have a linear relationship with the oral dose. For example, if the blood level is 1000 ng/ml and the oral dose is 20 mg, a reduction of the oral dose to 10 mg will not result in a level of 500 ng/ml, rather the blood level likely will be 100 ng/ml. It is therefore advisable to reduce oral cyclosporine doses by 2 to 4 mg increments, depending on the cyclosporine level. In humans, the dose is reduced in 5% increments. ALWAYS CONSULT WITH A MEMBER OF THE TRANSPLANT TEAM PRIOR TO ADJUSTING THE DOSE OF THE CYCLOSPORIN. The veterinarian caring for a cat that has been transplanted should always have the injectable (IV) form of cyclosporine in their hospital. If a recipient cat becomes ill for any reason...gastroenteritis, pancreatitis, or whatever disease that causes vomiting or stasis of the GI tract and the cat cannot keep the oral cyclosporine down, blood cyclosporine levels may drop to a level that could cause graft rejection. A very transient episode of illness for about 24 hours is likely not going to cause a problem, but beyond that point will cause a problem. In these cases, one third of the usual oral dose of cyclosporine is administered intravenously diluted 1:20 with saline or 5% dextrose fluids over 4 hours. This dose is repeated every 12 hours until the cat can eat again and vomiting has stopped. Trough cyclosporine levels should be measured while the cat is on IV medication if this treatment is expected to continue more than a couple of days. Cyclosporine assays should be high-pressure liquid chromatography (HPLC) or new monoclonal specific radioimmunoassay (mRIA-sp). Cyclosporine is stable in the blood for 1 week when refrigerated. It is a fairly stable chemical and does not need to be shipped on ice. Many drugs will affect the blood levels of cyclosporine; the table below lists some drugs that decrease, increase and have no effect on the cyclosporine levels.
Potential side effects of cyclosporine: urinary and other infections, decreased WBC and platelets, immune-mediated hemolytic anemia, high blood sugar, hypertension, diarrhea, vomiting, lymphoma, renal and liver toxicity (very unusual in cats). Drugs that are known to have potential renal toxicity such as NSAIDs and aminoglycosides should be avoided. Digitalis toxicity can occur with concurrent cyclosporine administration. 2. Ketoconozole 5 to 10 mg/kg q24h PO can be used long term if a cat metabolizes cyclosporine too rapidly. The dose is adjusted to the lowest level needed to maintain adequate cyclosporine levels. Ketoconozole blocks the metabolism of cyclosporine at the level of the liver. This medication is not routinely used. With long-term use, blood dyscrasias (leukopenia, anemia) may result. 3. Prednisolone 0.25 mg/kg BID PO for 1 month, then same dose q24h for the life of the patient. Prednisolone has an additive immunosuppressive effect with the cyclosporine even at this low dose. If the patient becomes hyperglycemic with the use of this medication, it should be discontinued. 4. Clavamox 13.5 mg/kg BID (or 62.5 mg per average size cat) for 14 days. Antibiotics are administered as the cat will be immunosuppressed and susceptible to bacterial infection. 5. Amlodipine (Norvasc) 0.1 mg/kg q24h is administered for hypertension if this is present preop. The dose should be adjusted as needed to normalize blood pressure. Blood pressure frequently will normalize following transplantation and amlodipine can be discontinued with tapering doses over 3 weeks. 6. Enalapril (Enacard) 0.25 mg/kg q24h can be used to help minimize renal hypertension and slow the deterioration of the remaining native kidneys. Cyclosporine and high doses of enalapril may result in excessively high serum K+ levels. Potential Postoperative Complications 1. Complications are frequently related to immunosuppressive therapy 2. Urinary tract infections (most common) 3. Viral upper respiratory infection 4. Fungal infection 5. Hypertension can be a side effect of Cyclosporine: results in seizures or blindness in the immediate postop period 6. Hydronephrosis due to ureteral obstruction (usually occurs within 3 weeks after surgery) 7. Rejection of the transplanted kidney; acute rejection can occur at any time if whole blood cyclosporine levels drop too low (i.e. below 100 ng/ml), hence the importance of good client compliance and frequent measurement of cyclosporine levels). 8. Hemolytic uremic syndrome is a condition in which progressive anemia and potentially icterus develop due to hemolysis of red blood cells. The cause of this syndrome is believed to be related to cyclosporine which causes endothelial injury. CBC shows thrombocytopenia, anemia, and schistocytes; lactic dehydrogenase levels are elevated on biochemical profile. A definitive diagnosis is based on renal graft biopsy which demonstrates glomerular microthrombi. Prognosis is grave. 9. Seizures as a result of the blood being cleansed too rapidly by the kidneys. This may be fatal. As mentioned above hypertension may also cause seizures. Postoperative Expectations We have had a 90% success to get cats through kidney transplantation; it is unusual for a patient to die during surgery and in the perioperative period. Our longest survivor was 8 years. If a cat survives beyond the first 6 months, there is a very good chance that the cat will live for years. My impression is that the cats that do the best are owned by clients that are diligent about follow-up evaluations and administering medications. With successful transplantation and function of the graft, the following clinical and biochemical progress of the recipient should be expected: most grafts begin producing urine within a couple of minutes of being reperfused; within 24 hours after transplantation, the BUN and creatinine are frequently about 1/4 to 1/3 less than the preop levels; BUN, creatinine, and phosphorus return to normal range within 2 to 5 days after surgery. Urine specific gravity may not concentrate to greater than 1.035 during the hospital stay due to diuresis with intravenous fluids. By 2 to 3 weeks after surgery the urine should be concentrated. Resumption of normal appetite and grooming behavior may take place 5-7 days after surgery. The quality of life of the patient returns to normal if the patient does not have any other underlying disease processes (i.e. normal activity level, weight, and appetite). Postoperative Monitoring 1. First Seven Days After Surgery: Complete physical examination, BUN, Creatinine, glucose, PCV, TS, albumin, electrolytes measured daily until renal values are normal, then every second or third day while in our hospital. Whole blood trough cyclosporine levels: Levels are measured on days 0, 3 and at the time of discharge. 2. Release From hospital to 12 Weeks After Transplantation (or until the cyclosporine level is stable): Complete physical examination (including TPR, blood pressure if previously hypertensive, and body weight), chemistry profile, CBC, urinalysis, urine culture, whole blood cyclosporine assays level weekly are performed weekly. Abdominal ultrasound is performed monthly (see table in appendix) Cyclosporine levels must be measured weekly for the first 12 weeks after surgery, then monthly for the next 6 months, then gradually wean down to an evaluation every 3 months. Blood levels must be maintained above 500 ng/ml during the first month and around 250 ng/ml thereafter. 3. Twelve Weeks After Transplantation: Complete physical examination (including TPR, blood pressure if previously hypertensive, and body weight), Chemistry, CBC, urinalysis, urine culture (cystocentesis collection), abdominal ultrasound, and whole blood cylcosporine assay is performed (the frequency of this testing is gradually reduced to once every 3 months). See table in the appendix. Rejection of renal grafts Any signs of illness that the patient exhibits post-operatively may be associated with organ rejection. This could potentially be due to inadequate levels of cyclosporine It is imperative that continuous communication between the owner, the referring veterinarian and the transplant team members must occur in order to assure a successful outcome. If problems arise the following protocol should be used: 1. Contact member of transplant team 2. Refer case back to us nearest specialty referral practice that is capable of managing transplant cases 3. Submit blood for stat measurement of at least the following (if you are not located near a referral center): BUN, creatinine, electrolytes, CBC, cyclosporine blood level, urinalysis, and urine culture 4. Be prepared to treat cat with the following: Cyclosporine 6mg/kg IV q12h; Prednisolone 4 mg/kg IV q24h; Baytril 2.5 mg/kg IV q12h (beware: >5 mg/kg q24h may cause retinal problems in cats especially with renal compromise); Ampicillin 20 mg/kg IV q6h; intravenous fluids; other instructions as directed by the transplant team. 5. Prepare to send patient to a referral center References 1. Gregory CR, et al. Renal transplantation for treatment of end-stage renal failure in cats. J Am Vet Med Assoc 1992;201:285-291. 2. Lulich JP, et al. Status of renal transplantation in the 1990s. Sem in Vet Med and Surg (Sm An) 1992;7:813-186. 3. Gregory CR. Renal transplantation in cats. Comp Cont Ed, 1993;15:1325-1339 4. Gregory CR et al. Renal transplantation in clinical veterinary medicine: In Kirk RW, Bonagura JD (eds): Kirk's Current Veterinary Therapy XI, Small Animal Practice. Philadelphia: WB Saunders Co, 1992, p. 870-875. 5. Degner DA, Walshaw R, Rosenstein D. A new rapid technique for renal transplantation in the cat. Proceedings, 5th Annual Research Day, Phi Zeta, 1994. Appendix Table 1 This table lists the schedule of testing that should be done in a transplant patient in the postop period. This is only a guideline and may be altered according to specific needs of the patient.
….and the testing continues at least every third month for the life of the patient. |
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Frequently Asked Questions After Surgery - General Information When should my cat have the first bowel movement after surgery?
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Board-certification by the American College of Veterinary SurgeonsWhat does it mean? |
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