Kidney Transplantation

Chapter 151 Kidney Transplantation



Lillian R. Aronson, VMD, DACVS



KEY POINTS



• Kidney transplantation is a viable option for cats in both acute and chronic renal failure.

• Careful case selection of a potential recipient is critical to prevent both short-term and long-term complications.

• Cats with a history of recurrent urinary tract infections or those with significant cardiac disease are not typically good candidates for the procedure.

• Lifelong immunosuppression is necessary and consists of a combination of the calcineurin inhibitor, cyclosporine (CsA), and a glucocorticoid, such as prednisolone.

• Postoperative hypertension is managed with hydralazine (2.5 mg SC for a 4-kg cat) to prevent central nervous system complications (i.e., seizures).

• If acute rejection is suspected, treatment should be initiated immediately to prevent graft loss.

• Treatment of complications secondary to long-term immunosuppressive therapy including mycobacterial infections, toxoplasmosis, and neoplasia have been largely unsuccessful.


INTRODUCTION


Kidney transplantation is an accepted treatment option for cats in both acute and chronic renal failure. Since its introduction to the veterinary community in 1987 by Drs. Clare Gregory and Ira Gorley from the University of California, Davis, School of Veterinary Medicine, it is estimated that over 400 cases of feline renal transplantation have been performed at various centers around the country. Information from different centers suggests that survival times are continuing to improve; however these cases remain a challenge for the veterinary clinician. This chapter will discuss the most up-to-date information with regard to case selection, preoperative and postoperative care, anesthetic and surgical management, and handling of the most common long-term complications.



CASE SELECTION


Thorough screening for a potential feline renal transplant recipient is critical to decrease the incidence of morbidity and mortality that can occur following the procedure. Although the best time to intervene with surgery is still subjective, clinicians with experience treating these patients suggest that the best candidate for renal transplantation is one in early decompensated renal failure.1,2 Indications of decompensation include worsening of azotemia and anemia, as well as continued weight loss while receiving medical therapy. Some clinicians have been successful in altering the physical deterioration of individual patients for up to 2 years with either a percutaneous endoscopic gastrostomy or esophagostomy feeding tube2 (KG Mathews, personal communication, 1998).


Both physical and biochemical parameters need to be evaluated carefully to determine if a cat is a suitable candidate. Cats should be free of other disease conditions including significant heart disease, recurrent urinary tract infections, uncontrolled hyperthyroidism, and underlying neoplasia. Cats with a fractious temperament are also often declined as candidates. Not enough information exists to determine if cats with diabetes or inflammatory bowel disease should be declined as potential candidates. Preoperative examination involves various laboratory tests including a complete blood count, biochemical evaluation, blood type, thyroid function studies, evaluation of the urinary tract (urinalysis, urine culture, urine protein-to-creatinine ratio, abdominal radiographs, abdominal ultrasonography), evaluation for cardiovascular disease (thoracic radiography, electrocardiography, echocardiography, blood pressure), and screening for infectious disease including feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), Toxoplasma titer, and immunoglobulin (Ig) G and IgM3,4 (Box 151-1). There is no age restriction for a potential transplant recipient. The feline recipient must also have compatible blood (via crossmatch) to a prospective kidney donor and to two or three blood donor cats.



Box 151-1 Preoperative Screening for a Potential Feline Renal Transplant Recipient


IgG, Immunoglobulin G; IgM, immunoglobulin M.



• Complete blood count

• Serum chemistry profile

• Blood type and crossmatch

• Thyroid hormone

• Urinalysis, urine culture, urine protein-to-creatinine ratio

• Abdominal radiography

• Abdominal ultrasonography

• Thoracic radiography

• Electrocardiography, echocardiography, blood pressure

• Feline leukemia virus, feline immunodeficiency virus

• Toxoplasmosis titer, IgG and IgM


Evaluation of the Urinary Tract


Evaluation of the urinary tract is essential, particularly to rule out any underlying infection or neoplastic disease. If abdominal ultrasonography of the kidneys leads to a suspicion of feline infectious peritonitis (FIP) or neoplasia, a fine-needle aspirate or biopsy is recommended. If a patient has recently been treated for a urinary tract infection or has had recurrent urinary tract infections, but at the time of arrival has negative urine culture results, then a cyclosporine (CsA) (Neoral, Novartis) challenge is recommended before transplantation to determine if the cat will “break” with an infection. To perform this challenge, CsA is administered for approximately 2 weeks at the recommended dosage for transplantation immunosuppression. The urine is evaluated for infection after therapeutic CsA blood levels have been achieved and at the end of the 2-week period. It is important to note that a negative urine culture result following a challenge will not guarantee that a patient will remain infection free following surgery and during long-term immunosuppression.


Finally, if unilateral or bilateral hydronephrosis is identified in any patient during the screening process, a pyelocentesis and culture are recommended before transplantation. The author has identified five cats with obstructive calcium oxalate urolithiasis that have had a negative culture result from urine collected via cystocentesis and a positive culture result from urine collected by pyelocentesis (LR Aronson, unpublished data, 2005). Immunosuppression in a patient harboring an infection can not only potentiate the rejection process, but also lead to increased morbidity and mortality.



Cardiovascular Disease


At the time of presentation for transplantation, a systolic murmur may be auscultated on physical examination. These are often physiologic murmurs associated with the anemia of chronic renal failure and may not represent significant heart disease.1 In a recent study from the University of California, Davis, evaluating cardiac abnormalities in 84 potential transplant recipients, 78% of patients had abnormalities including both papillary muscle and septal muscle hypertrophy. The authors suggested that these changes may be related to hypertension, chronic uremia, age, or early changes of hypertrophic cardiomyopathy.5 Cats with diffuse hypertrophic cardiomyopathy or those with congestive heart failure are declined as candidates for renal transplantation at our facility. A decision is made on a case-by-case basis in those cats with less severe disease.



Infectious Disease


If a cat’s test results are positive for FeLV or the animal has an active FIV infection, it is declined as a candidate for transplantation. Additionally, all potential donors and recipients undergo serologic testing (IgG and IgM) for toxoplasmosis. Toxoplasma gondii can cause significant morbidity and mortality in both human and veterinary immunocompromised patients. As a matter of policy at our facility, seropositive donors are not used and seropositive recipients are placed on lifelong prophylactic clindamycin (25 mg PO q12h), which is started when immunosuppression is initiated. If the cat does not tolerate the clindamycin, other antibiotics such as trimethoprim-sulfamethoxazole (Tribrissen) have been used.



DONOR SELECTION


Kidney donors are typically between 1 and 3 years of age and in excellent health. Standard evaluation includes a complete blood count, serum chemistry profile, urinalysis and culture, FeLV and FIV testing, and a toxoplasmosis titer (IgG and IgM). The feline kidney donor must also have a compatible blood crossmatch to the recipient and be of a similar size. Additionally, we perform computed tomographic angiography on all of the donors to evaluate the renal vasculature and the renal parenchyma for any abnormalities that may preclude successful transplantation.6



PREOPERATIVE MANAGEMENT


On admission to the transplant facility, intravenous fluid therapy is begun with a balanced electrolyte solution at 1.5 to 2 times the daily maintenance requirements. This rate may vary in cases of severe dehydration or in cats with underlying cardiac disease. At some centers, hemodialysis is performed before transplantation for cats that are anuric or those with severe azotemia (blood urea nitrogen >100 mg/dl, creatinine >8 mg/dl).7 Additionally, if the cat is hypertensive, the calcium channel blocker amlodipine (Norvasc, 0.625 mg/cat PO q24h) may be indicated before surgery. Anemia is typically corrected at the time of surgery with crossmatch-compatible whole blood or packed red blood cell transfusions. The first unit that is administered is one that has been previously collected from the kidney donor. If the patient has evidence of decreased oxygen delivery from the anemia, blood products can be given at the time of admission to the transplant facility. If a delay in the transplant procedure is expected, erythropoietin (Epogen) can be administered and may greatly reduce the need for blood products at the time of surgery. Dosage is 100 IU/kg 3 times per week for the first 1 to 2 weeks and then tapered accordingly. Phosphate binders and gastrointestinal protectants are given if deemed necessary (see Chapter 181, Gastrointestinal Protectants). If the cat is anorectic, a nasogastric, esophagostomy, or percutaneous endoscopic gastrostomy tube may be placed for nutritional support before surgery (see Chapter 13, Enteral Nutrition).



Immunosuppression for the Feline Renal Transplant Recipient


The immunosuppressive protocol used at our facility consists of a combination of the calcineurin inhibitor, CsA, and the glucocorticoid, prednisolone. Because of the small dosage of CsA that cats often require for immunosuppression, the liquid microemulsified formulation, Neoral (100 mg/ml), is recommended so that the dosage can be titrated for the individual cat.


CsA administration is begun 72 to 96 hours before transplantation at a dosage of 1 to 4 mg/kg PO q12h depending on the cat’s appetite. In the author’s experience, cats that are anorexic or are eating a minimal amount have a much lower drug requirement to obtain appropriate drug levels before surgery. Additional agents that inhibit P-450 may alter drug concentrations and should be used with caution in these patients. A 12-hour whole blood trough concentration is obtained the day before surgery so that the dosage can be adjusted preoperatively if necessary. The drug level is measured using high-pressure liquid chromatography. The goal is to obtain a trough concentration of 300 to 500 ng/ml.4 This level is maintained for approximately 1 to 3 months following surgery and is then tapered to approximately 200 to 250 ng/ml for maintenance therapy. Prednisolone is administered beginning the morning of surgery. At our facility, prednisolone is started at a dosage range of 0.5 to 1 mg/kg PO q12h for the first 3 months and then tapered to q24h. It is important to note that protocols for both CsA and prednisolone vary among transplantation facilities.


A second protocol used by some clinicians for feline immunosuppression combines the antifungal medication ketoconazole (10 mg/kg PO q24h) with CsA and prednisolone.8,9 Ketoconazole can affect CsA metabolism by inhibiting both hepatic and intestinal cytochrome P-450 oxidase activity, resulting in increased blood CsA concentrations.9 Once ketoconazole is added to the immunosuppressive protocol, CsA and prednisolone are administered once a day, and CsA dosage is adjusted into the therapeutic range by measuring whole blood trough levels daily. This protocol may reduce the cost of CsA and be more appealing for owners whose work schedule does not permit twice daily medication administration.

Related posts:

  1. Deteriorating Mental Status
  2. Hyperthermia and Fever
  3. Ventilator-Associated Lung Injury
  4. Allergic Airway Disease in Dogs and Cats and Feline Bronchopulmonary Disease

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Sep 10, 2016 | Posted by in SMALL ANIMAL | Comments Off on Kidney Transplantation

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