Feline Health Topics for veterinarians

Volume 11, Number 2

Summer 1996

Hyperthyroidism and the Feline Kidney T hom as K. G raves, D .V .M ., D .A .C .V .I.M .

Hyperthyroidism and renal failure are two of the most common diseases of cats, and are of major impor­ tance in feline geriatric medicine. Recent attention has focused on a possible relationship between these two diseases. Many veterinary clinicians perceive a high incidence of renal failure following treatment of hyperthyroidism. Until recently, the only evidence for posthyperthyroidism renal impairment in cats has been anecdotal. However, recent studies have shown that there may indeed be important effects of thyro­ toxicosis on the feline kidney.

The Effects of Kidney Disease on Hyperthy­ roidism Peterson and Gamble reported serum thyroid hor­ mone concentrations in a variety o f nonthyroidal illnesses. They found that nearly 80 percent of cats with renal diseases have low serum concentrations of thyroxine (T4). M ost o f the remainder of cats with renal disease have low-normal serum concentrations of T4. The reason for this abnormality in thyroid hormone concentrations is unknown, but may be related to decreased thyroid hormone-carrier protein

Inside this issue ... H yperthyroidism and the Feline K idney

page 1

R ecom m endations for FIV T esting

page 4

Feline H ealth C enter Funds Projects

page 5

Research Briefs

page 6

complexes. The vast majority o f circulating thyroid hormone in the serum is bound to carrier proteins, with unbound (free) hormone occurring in very low concentrations. Free hormones are metabolically ac­ tive, whereas protein-bound hormones are not. Se­ rum concentrations of free thyroid hormones have not been studied extensively in cats with hyperthy­ roidism, and have not been evaluated in cats with renal disease.

Hypertension and the Kidney Hypertension is often overlooked in the evaluation of veterinary patients. Arterial blood pressure can be quite difficult to measure reliably in cats, especially in cachexic, fractious hyperthyroid cats. However, research has shown that cats with hyperthyroidism are likely to have severe elevations in systemic arte­ rial pressure. Kobayashi et al. studied the prevalence of hypertension in cats with hyperthyroidism and cats with chronic renal failure. In that study, both groups of cats had significantly increased systolic and dias­ tolic pressures when compared to normal cats (table 1). However, the cats with hyperthyroidism gener­ ally had higher blood pressure than the cats with renal disease. Adverse effects of hypertension include retinal detachment as well as neurologic, cardiovascular, and renal complications. Hypertension leads to vas­ cular lesions which result in ischemia, decreased perfusion, and hemorrhage in a variety o f organs including the kidney. Reduction of blood pressure can slow the progression of renal failure in human

Feline Health Topics

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evidenced by increases in creatinine and inulin clear­ ances, and decreased serum concentrations of creatinine. Diastolic Pressure Systolic Pressure BU Nxreatinine ratios are in­ (mean + SD) (mean + SD) creased in people with hyper­ thyroidism versus norm al 83.8 * 12.2 Normal 118.4 * 10.6 people. In human patients, (n = 33) these changes reverse follow­ 96.6*15.2 Renal Disease 146.61 25.4 ing treatment of hyperthyroid­ (n = 28) ism. However, changes in re­ 111.6*21.5 Hyperthyroid 167.9*28.9 nal function have been studied (n = 39) (From reference 2) only in human patients with Graves’ disease, the most com­ beings, but data are lacking in the effects of hyperten­ mon form of hyperthyroidism in people. Patients sion on renal failure in the cat. w ith G rav es’ disease are generally young or middle-aged adults, and correlation should probably Glomerular Filtration Rate in Hyperthy­ not be drawn between these patients and hyperthy­ roidism roid cats. Hyperthyroidism occurs in relatively older W hether in human beings or in veterinary patients, patients with the likelihood of at least some extent of there are very few published studies of the effects of nephron loss. The effects of hyperthyroidism on renal thyrotoxicosis on renal function. Increased renal blood function have not been studied in geriatric human flow and glomerular filtration rate (GFR) have been patients with Plum mer’s disease, the human analog described in people with hyperthyroidism. This is of feline hyperthyroidism. Table 1. D oppler U ltrasonic Blood Pressure M easurem ents in N orm al Cats, C ats w ith C hronic R enal Failure, and Cats with H yperthyroidism

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Feline Health Topics A publication for veterinary professionals T he u ltim a te p u r p o se o f the C orn ell F eline H ealth Center is to im p r o v e the h ealth o f cats ev ery w h e re, b y d e v e lo p in g m eth o d s to p rev en t or cu re felin e d isea ses, an d b y p r o v id in g con tin u in g ed u cation to veterin arian s an d cat ow n ers. A ll con trib ution s are ta x-d ed u ctible. D ir e c t o r : Fred W . S cott, D .V .M ., P h .D A s s is t a n t D ir e c t o r : Ja m es R. R ich ard s, D .V .M . E d it o r : Ju n e E. T u ttle S e c re t a rie s : G w e n Frost

M arsh a J. L eonard Sheryl A. T hom as © 1996 b y C orn ell U n iv ersity on b eh alf of the C ornell F eline H ea lth C enter, C o lleg e of V eterin ary M ed icin e, Ithaca, N Y 14853. Phone: (607) 253-3414 Fax: (607) 253-3419 A ll righ ts reserved . P erm ission to reprint se ­ lected p o rtio n s m u st b e ob tain ed in w riting. C ornell U n iv ersity is an eq u al op p ortu n ity, a ffirm ative action ed u cator an d em p loyer. Printed on recycled paper.

Recent studies have shown that cats with hyper­ thyroidism experience a significant drop in GFR following treatment and the return to euthyroidism. In our study, GFR was measured by plasma disap­ pearance of radio-labeled Tc-DTPA in 13 cats before and after treatment of hyperthyroidism. All cats with hyperthyroidism experienced a drop in GFR follow­ ing treatment. The mean percent drop in GFR was 42 percent, with decreases ranging from 15 to 74 per­ cent. All of the cats studied experienced increases in serum concentrations of creatinine and BUN as well. While all cats in that study were nonazotemic prior to treatment of hyperthyroidism, two were in overtrenal failure one month following treatment. Subsequent investigations are ongoing at several universities. Preliminary results (table 2) indicate that most hyper­ thyroid cats experience a decline in renal function following treatment regardless of the mode of treat­ ment used.

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Table 2. C hanges in Renal Function A ssociated with T reatm ent o f H yperthyroidism in Cats

(± 0.27)

(± 0.50)

Hyperthyroid Dav 0 2.51 (± 0.69 )

Mean Creatinine (+ SD) mg/dl

1.45 (± 0 .20)

1.54 (± 0.27)

1.26 (± 0.34)

2.05 (± 0.60)

Mean BUN (+ SD) mg/dl

25.73 (± 3.04)

25.82 ("2.14)

26.62

34.92

(± 6.83)

(* 8.95)

Mean GFR (± SD) ml/kg/mi n

Controls (n = 11) Dav 0 Dav 30 2.02 2.18

(n = 13) Dav 30 fpost-Tx) 1.40 (* 0.41)

(From reference 4)

These results suggest that hyperthyroidism can mask underlying chronic renal failure in the cat. There are however, several important questions yet to be answered. For example, is the drop in GFR perma­ nent? Are there ways o f determining which thyroid cats are at risk of developing overt renal failure following treatment? W hat is the mechanism of al­ tered GFR in hyperthyroidism? The possibility o f posttreatment renal failure makes treatment decisions much less straightforward than has traditionally been the case. In fact, there may be some hyperthyroid cats in which treatment should not be recommended. In any cat with questionable renal health, for instance, careful consideration of posttreatment complications is warranted. Pretreat­ ment workup should include a complete blood count, serum biochemistry profile, urinalysis, and urine culture to rule out underlying renal disease before treatment of hyperthyroidism is undertaken. In some cases it might be better to manage some of the adverse effects of hyperthyroidism than to treat the hyperthy­ roidism itself. For instance, tachycardia and hyper­ tension might best be treated with a calcium-channel blocking drug in an azotemic cat with concurrent cardiomyopathy and hyperthyroidism, even if hyper­ thyroidism is the underlying cause of the cardiomy­ opathy. In other instances, reversible modes of treat­

ment (i.e., antithyroid drugs) might best be used to facilitate reversal of post-treatment azotemia. In ad­ dition to these issues, the effect of exogenous thyroid hormone supplementation on maintenance or im­ provement o f posttreatment renal function needs investigation. ■ This article has been reprintedfrom the proceedings o f the 87th Annual Conference fo r Veterinarians at Cornell University with permission from the author. Dr. Thomas Graves received h isD .V M . degree from Cornell University. Currently he works in the depart­ ment o f pharmacology and physiology, School o f Medicine, University o f Rochester, NY.

References * Peterson ME, Gamble DA. Effect o f nonthytoidal illness on serum thy­ roxine concentrations in cats: 494 cases (1988). J Am V et Med A ssoc 197:1203, 1990. ^ Kobayashi DL, Peterson ME, Graves TK, Lesser M, N ichols CE. Hyper­ tension in cats with chronic-renal failure or hyperthyroidism. J Vet Intern Med 4:58, 1990. Graves TK. Complications o f treatment and concurrent illness associated with feline hyperthyroidism. In:: Current Veterinary Therapy XII: Small Animal Practice, Bonagura JD, Kirk RW (eds). W .B. Saunders Co., Phila­ delphia, (369-372), 1995. ^ Graves TK, Olivier N B , Nachreiner RF, Kruger JM, W alshaw RW, Stickle RS. Changes in renal function associated with treatment o f hyper­ thyroidism in cats. Am J Vet Res

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Recommendations for Feline Immunodeficiency Virus Testing The follow ing recom m endations for feline im m u­ nodeficiency virus testing w ere developed by the A m erican A ssociation o f F eline P ractition ers (AAFP) and the A cadem y o f Feline M edicine (A FM ), and have been reprinted w ith their per­ m ission. T hese recom m endations are based on sound principles, research, exp erience and technical ju dgm ents w hen w ritten. W hile the inform ation is intended to be accurate, thorough and com pre­ hensive, it is subject to change in light o f develop­ m ents in research, technology and experience. These recom m endations are not exclusive, and other techniques and procedures m ay also be available. A A FP and AFM expressly disclaim any w arranties or guarantees, express or im plied, and shall not be liable for dam ages o f any kind in connection w ith the m aterial, inform ation, tech­ niques, or procedures set forth in the recom m en­ dations.

1. The feline immunodeficiency virus (FIV) an­ tibody status o f all cats over 6 months o f age should be known. Epidemiologic studies continue to indi­ cate the global nature of this infection in the cat population.1,2 Prevalence may be higher than previ­ ously suspected.3 2. Testing and identifying positive cats is the only means by which FIV disease can be controlled. The best means o f preventing disease is by preventing exposure to FIV-infected cats. Testing should occur in the following: a. cats or new kittens over 6 months o f age before introduction into a household to pre­ vent exposing existing cats

b. cats or newly adopted kittens over 6 months of age, even if they are the only cat in the household c. cats in existing households where the FIV status is not known because carriers can re­ main asymptomatic for years and expose other cats d. cats in which a recent exposure (known or potential) occurs, regardless of previous nega­ tive test results, because the FIV status can change e. ill cats since FIV has been associated with a great variety o f illnesses in cats2,4 3. Available FIV diagnostic tests (ELISA and Western Blot) detect antibodies against the virus (in contrast to the FeLV test which detects antigen). Tests are only diagnostic for FIV infections that have stimulated detectable antibody; they are not diagnos­ tic for clinical disease. There is high correlation between the presence of antibodies to FIV and persis­ tent infection. FIV-antibody-positive cats, confirmed by Western Blot, are presumed to be persistently infected and a persistent source of virus. 4. The ELISA test is recognized as the preferred screening test for FIV. The Western Blot is most appropriate as a confirmatory test. 5. All positive results for FIV should be con­ firmed by W estern Blot. 6. No test is 100% accurate at all times and under all conditions; therefore, a critical decision about the care of a patient, whether healthy or ill, should never be based solely on a single test result.5

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7. Passively acquired maternal antibody in young kittens interferes with the interpretation of diagnostic antibody tests for FIV .1,3 In addition, early virus infection before seroconversion and false positive test results make interpretation of FIV-antibody tests in kittens less than 6 months of age difficult. Infection rate and course o f disease in kittens are not clearly understood. The meaning of maternal antibodies as it relates to infection in the kitten is unclear; these need to be elucidated before we can interpret FIV testing in kittens. If kittens less than six months of age are tested— whether a positive or a negative test result— retesting after 6 months of age must be done.3 8. Adult cats and kittens over 6 months of age that test negative, but with a known or suspected exposure to FIV, should be retested. The testing is repeated because a negative result may be obtained when testing is done early in the viral infection before seroconversion. The determining retest should be at least 120 days postexposure. Clients should be coun­ seled on the potential risk of FIV exposure when adding a cat with one negative test result to an FIV-negative household. 9. Annual testing o f cats “at risk” of infection is justifiable. Cats “at risk” are defined as those with known or potential exposure to FIV. These include: outdoor cats; fighting cats; strays; cats with bite wounds; escapees; recently mated females if the FIV status of the male is unknown; cats in open multiple-cat households; cats in closed multiple-cat households with any other cats of unknown FIV status; cats in households having a known FIV positive cat. 10. FIV infection generally carries a more favor­ able prognosis than does FeLV infection. Therefore, a continued positive FIV antibody status has uncer­ tain relevance to the prognosis and therapeutic man­ agement, but does indicate potential for virus trans­ mission. 11. FIV-positive healthy cats may live formonths to years. Effective FIV case management involves measures aimed at preserving the health of the in­

fected cat; preventing the spread of FIV infection; and early recognition and aggressive treatment of FIV-associated disease. The quality o f life and clini­ cal status of FIV-positive cats can be enhanced through the concerted efforts o f the pet owner and the attend­ ing veterinarian.6 ■

References 1 Colloquium on FeLV/FTV: Tests and Vaccination, J Am Vet Med A ssoc, 199(10):1275-1276, 1991. 2 M acy, DW: Feline Im m unodeficiency Virus, In: The Cat: D iseases and Clinical Management, (Ed.) Robert Sherding, Churchill Livingstone, New York, Second Edition, 1994, pp. 433-445. ^ Sellon, RK: Feline Im m unodeficiency Virus Transmission: An Update, in Proc. 12th ACVIM, San Francisco, CA, 1994, pp. 116-118. ^ Sparger, EE: Feline Immunodeficiency Virus, In: Consultations in Feline Internal M edicine, (Ed.) John August, W .B. Saunders Company, 1991, pp. 543-550. ^ Barr, MC: Feline Immunodeficiency Virus Tests and their Interpretation, Feline Health Topics, Cornell Feline Health Center, 8 (3 ):l-5 , 1993. 6 Shelton, GH: Management o f the Feline Im m unodeficiency Virus- Posi­ tive Patient, In: Consultations in Feline Internal M edicine, Volum e 2, (Ed.) John August, WB Saunders, Philadelphia, 1994, p. 31.

F eline H ealth C enter F unds N ew Studies Faculty and clinicians who are participants of the Feline Health Center applied this summer for funding of their feline studies. Grants were awarded for pro­ jects that would be most beneficial to the veterinary practice of feline medicine. Three projects were funded by the Center— Examination o f Blood Pressure in Cats with Cardiac Disease (Dr. Anna Gelzer, Dr. N. Sydney Moise) Kitten Temperament Test: Value as a Predictor o f Adult Cat Behavior (Dr. Katherine A. Houpt) Elicitation o f Infection o f Humoral Immune Re­ sponse by D irect Inoculation o f Cats with FIV Proviral DNA Clones (Dr. Margaret C. Barr, Dr. Roger J. Avery) The projects are funded by the generous contribu­ tions made by veterinarians, alumni, cat owners, and cat breeders. Progress reports on these and other projects will be published in future newsletters. ■

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Research Briefs E xperim ental T ransm ission o f Bartonella henselae by the C at Flea (Authors: B B . Chomel, R.W. Kasten, K. FloydHawkins, etal.)— Bartonella henselae is an emerging bacterial pathogen, causing cat scratch disease and bacillary angiomatosis. Cats bacteremic with B. henselae constitute a large reservoir from which hu­ mans become infected. Prevention of human infec­ tion depends on elucidation of the natural history and means of feline infection. Researchers studied 47 cattery cats in a private home for 12 months to determine the longitudinal prevalence of B. henselae bacteremia, the prevalence of B. henselae in the fleas infesting these cats, and whether B. henselae is trans­ mitted experimentally to cats via fleas. Vector-mediated transmission o fB. henselae iso­ lates was evaluated by removing fleas from the natu­ rally bacteremic, flea-infested cattery cats and trans­ ferring these fleas to specific-pathogen-free (SPF) kittens housed in a controlled, arthropod-free univer­ sity animal facility. B. henselae bacteremia was de­ tected in 90% of the 47 naturally infected cattery cats. A total of 132 fleas were removed from cats whose blood was simultaneously cultured during different seasons and were tested individually for the presence o f B. henselae DNA by polymerase chain reaction (PCR). B. henselae DNA was detected in 34% of 132 fleas, with seasonal variation, but without an associa­ tion between the presence of the level of bacteremia in the corresponding cat. Cat fleas removed from bac­ teremic cattery cats transmitted B. henselae to five SPF kittens in two separate expereiments; however, control SPF kittens housed with highly bacteremic kittens in the absence of fleas did not become infected. These data demonstrate that the cat flea readily trans­ mits B. henselae to cats. Control of feline infestation

with this arthropod vector may provide an important strategy for the prevention of infection of both hu­ mans and cats.— (Resource: J Clin M icrobiol 34:1952-1956,1996)

C om parison o f Seven D ifferent Suture M aterials in the Feline O ral C avity (Authors: G .A. DeNardo,N.O. Brown, S. TrenkaBenthin, S.M. Marretta)— Seven different suture materials were implanted into the oral tissues of 12 cats. The sutures and surrounding tissues were re­ trieved en bloc from each of two cats on days one, three, seven, 14,21, and 28 postimplantation. Tissue reaction and suture duration were evaluated by gross visual observation and historlogical examination. Chromic gut disappeared between days three and seven; polyglactin 910 disappeared between days 14 and 21; and polyglycolic acid disappeared as early as seven to 14 days. Polydioxanone still was intact at day 28 and is recommended as an absorbable mate­ rial for procedures in which longer healing time is anticipated. All the nonabsorbable suture materials (i.e., polypropylene, stainless steel, and nylon) were intact at day 28 postimplantation. Visual inspection showed polypropylene to have the least tissue reac­ tion.— (J Am Anim Hosp Assoc 32:164-172,1996)

R accoon-poxvirus-feline-panleukopeniavirus-V P2 R ecom binant P rotects Cats A gainst FPV C hallenge (Authors: L B . Hu, J J . Esposito, F.W. Scott)— An infectious raccoon poxvirus (RCNV) was used to express the feline panleukopenia virus (FPV) open reading frame VP2. The recombinant, RCNV/FPV, was contracted by homologous recombination with a chimeric plasmid for inserting the expression cas­ sette into the thymidine kinase (TK) locus of RCNV.

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Expression o f the VP2 DNA was regulated by the vaccinia virus late promoter P -l 1. Southern blot and polymerase chain reaction (PCR) analyses confirmed the cassette was in the TK gene of the RCNV genome. An immunofluorescent antibody assay using feline anti-FPV polyclonal serum showed the expressed viral antigen in the cytoplasm of infected cells. Radioimmunoprecipitation with the same anti serum detected a 67-kDa VP2 protein which exactly matched the migration of the authentic FPV-VP2 protein by SDS-polyacrylamide gel electrophoresis.

Fitzgerald SD, Johnson CA, Peck EJ: A fatal case of intrathoracic cuterebriasis in a cat. J Am Anim Hosp Assoc 32:353-357,1996.

Nine five-month-old cats were vaccinated and 21 days later were boosted with the recombinant virus. Peroral FPV challenge two weeks after the booster showed that the cats were fully protected as measured by examining clinical signs and total white blood cell counts in peripheral blood. Cats not immunized de­ veloped low to very low leukocyte counts following peroral FPV challenge. The nine vaccinated cats showed high FPV neutralization antibody prior to challenge, whereas nonvaccinated cats formed antiFPV antibodies only after challenge. (Resource: Aca­ demic Press, Inc., 1996)

Harder TC, Kenter M, Vos H, et. al.: Canine distem­ per virus ffom diseased large felids: Biological prop­ erties and phylogenetic relationships. J Gen Virol 77:397-405,1996.

Other Research Articles of Interest Brockman DJ, Pardo AD, Conzemius MG, et al.: O m entum -enhanced reconstruction o f chronic nonhealing wounds in cats: Techniques and clinical use. Vet Surg 25:99-104, 1996. Davies C, Forrester SD: Pleural effusion in cats: 82 cases (1987 to 1995). J Small Anim Pract 37:217224,1996. Dubey JP, Matrix ME, Lipscomb TP: Lesions of neonatally induced toxoplasmosis in cats. Vet Pathol 33:290-295,1996.

Gasper PW, Rosen DK, Fulton R: Allogeneic mar­ row transplantation in a cat with acute myeloid leuke­ mia. J Am Vet Med Assoc 208:1280-1284, 1996. G reene CE, M cD erm o tt M, Jam eson PH , et al.:Bartonella henselae infection in cats: Evaluation during primary infection, treatment, and rechallenge infection. J Clin Microbiol 34:1682-1685, 1996.

Inada S, Mochizuki M, Izumo S, et al.: Study of hereditary cerebellar degeneration in cats. Am J Vet Res 57:296-301, 1996. Kim SW, Rogers QR, Morris JG: Dietary antibiotics decrease taurine loss in cats fed a canned heatprocessed diet. J Nutr 126:509-515,1996. Kruger JM, Osborne CA, Lulich JP: Management of nonobstructive idiopathic feline lower urinary tract disease. Vet Clin North Am Small Anim Pract 26:571 588,1996. Lamb CR, Forster-van Hijfte MA, White RN, et al.: Ultrasonographic diagnosis of congenital porto-systemic shunt in 14 cats. J Small Anim Pract 37:205209, 1996. Lane IF: Pharmacologic management o f feline lower urinary tract disorders. Vet Clin North Am Small Anim Pract 26:515-533, 1996. (continued on page 8)

Feline Health Topics

Langley-Hobbs SJ, Carmichael S, McCartney W: Use o f external skeletal fixators in the repair of femoral fractures in cats. J Small Anim Pract 37:95101,1996. Lulich JP, Osborne CA, Kruger JM: Biologic behav­ ior o f feline lower urinary tract diseases. Vet Clin North Am Small Anim Pract 26:207-215, 1996. Strieker MJ, Morris JG, Feldman BF, Rogers QR: Vitamin K deficiency in cats fed commercial fishbased diets. J Small Anim Pract 37:322-326,1996. Thoresen SI, Bredal WP: Clinical usefulness of fructosamine measurements in diagnosing and moni­ toring feline diabetes mellitus. J Small Anim Pract 37:64-68, 1996. ■

C o r n e ll F e lin e H e a lth C e n t e r C o r n e ll U n iv e r s ity C o lle g e o f V e te r in a r y M e d ic in e Ith a ca , N e w Y o rk 1 4 8 5 3

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Photocopies o f the above articles are available by making your request via mail to the FlowerSprecher Library, College of Veterinary Medi­ cine, Ithaca, NY 14853; or by telephone at (607) 253-3510; or by fax at (607) 253-3080. There is a charge for this service. The total charged is based on the number of pages copied, New York state sales tax of 8% if applicable, and delivery method (e.g., U.S. mail, Federal Express or fax). V _________________

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