Incidence of and risk factors for diabetes mellitus in cats that have undergone renal transplantation: 187 cases (1986–2005)

Joseph B. Case Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, CA 95616

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Andrew E. Kyles Departments of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616

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Richard W. Nelson Departments of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616

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Lillian Aronson Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104

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Philip H. Kass Departments of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616

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Tyler C. Klose Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, CA 95616

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Nathan L. Bailiff Departments of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616

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Clare R. Gregory Departments of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616

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Abstract

Objective—To compare incidence of diabetes mellitus in cats that had undergone renal transplantation with incidence in cats with chronic renal failure, compare mortality rates in cats that underwent renal transplantation and did or did not develop diabetes mellitus, and identify potential risk factors for development of posttransplantation diabetes mellitus (PTDM) in cats.

Design—Retrospective case series.

Animals—187 cats that underwent renal transplantation.

Procedures—Medical records were reviewed.

Results—26 of the 187 (13.9%) cats developed PTDM, with the incidence of PTDM being 66 cases/1,000 cat years at risk. By contrast, the incidence of diabetes mellitus among a comparison population of 178 cats with chronic renal failure that did not undergo renal transplantation was 17.9 cases/1,000 cat years at risk, and cats that underwent renal trans-plantation were 5.45 times as likely to develop diabetes mellitus as were control cats with chronic renal failure. The mortality rate among cats with PTDM was 2.38 times the rate among cats that underwent renal transplantation but did not develop PTDM. Age, sex, body weight, and percentage change in body weight were not found to be significantly associ-ated with development of PTDM.

Conclusions and Clinical Relevance—Results suggest that cats that undergo renal transplantation have an increased risk of developing diabetes mellitus, compared with cats with chronic renal failure, and that mortality rate is higher for cats that develop PTDM than for cats that do not.

Abstract

Objective—To compare incidence of diabetes mellitus in cats that had undergone renal transplantation with incidence in cats with chronic renal failure, compare mortality rates in cats that underwent renal transplantation and did or did not develop diabetes mellitus, and identify potential risk factors for development of posttransplantation diabetes mellitus (PTDM) in cats.

Design—Retrospective case series.

Animals—187 cats that underwent renal transplantation.

Procedures—Medical records were reviewed.

Results—26 of the 187 (13.9%) cats developed PTDM, with the incidence of PTDM being 66 cases/1,000 cat years at risk. By contrast, the incidence of diabetes mellitus among a comparison population of 178 cats with chronic renal failure that did not undergo renal transplantation was 17.9 cases/1,000 cat years at risk, and cats that underwent renal trans-plantation were 5.45 times as likely to develop diabetes mellitus as were control cats with chronic renal failure. The mortality rate among cats with PTDM was 2.38 times the rate among cats that underwent renal transplantation but did not develop PTDM. Age, sex, body weight, and percentage change in body weight were not found to be significantly associ-ated with development of PTDM.

Conclusions and Clinical Relevance—Results suggest that cats that undergo renal transplantation have an increased risk of developing diabetes mellitus, compared with cats with chronic renal failure, and that mortality rate is higher for cats that develop PTDM than for cats that do not.

Renal transplantation is an established treatment for end-stage renal disease in cats.1 Cats that have decompensated renal disease and are free from systemic disease, such as neoplasia and diabetes mellitus, are considered to be candidates for renal transplantation.2 After transplantation, lifelong immunosuppressive therapy is needed to prevent acute allograft rejection, and cats that have undergone renal transplantation are maintained on a combination of cyclosporine and glucocorticoids.3-5 Cyclosporine concentrations are periodically measured and adjusted to maintain a trough concentration within a therapeutic range of 250 to 400 ng/mL.3 Cyclosporine concentrations less than this therapeutic range are associated with an increased risk of allograft rejection; concentrations greater than this therapeutic range are associated with an increased risk of infection and neoplasia.4,5

In humans, there is a significantly increased risk of developing diabetes mellitus following renal transplantation.6-8 In a recent retrospective study7 of 386 human patients who underwent renal transplantation between 1995 and 2001, for instance, the cumulative incidence of PTDM over a period of 8.5 years was 9.8%. Immunosuppressive drugs are believed to be responsible for development of PTDM in human patients because they can cause pancreatic beta cell toxicosis, increase hepatic gluconeogenesis, and induce insulin resistance.6

There is a paucity of information on development of diabetes mellitus following renal transplantation in cats. The purposes of the study reported here were to compare incidence of diabetes mellitus in cats that had undergone renal transplantation with incidence in cats with chronic renal failure, compare mortality rates in cats that underwent renal transplantation and did or did not develop diabetes mellitus, and identify potential risk factors for development of PTDM in cats. We hypothesized that the incidence of diabetes mellitus would be higher in cats that underwent renal transplantation than in cats with chronic renal failure; that mortality rate would be higher in cats that underwent renal transplantation and subsequently developed diabetes mellitus than in cats that underwent renal transplantation and did not develop diabetes mellitus; and that age, body weight, and sex would be risk factors for development of PTDM.

Criteria for Selection of Cases

Medical records of all cats that underwent renal transplantation at the University of California–Davis Veterinary Medical Teaching Hospital between January 1986 and May 2003 or at the University of Pennsylvania Veterinary Medical Teaching Hospital between May 1998 and February 2005 were reviewed. Cats were excluded if they did not survive the initial 30 days after undergoing renal transplantation or if diabetes mellitus had been diagnosed prior to renal transplantation.

Procedures

Information collected from the medical records of cats included in the study consisted of signalment; date of renal transplantation; age at the time of renal transplantation; and, for cats that had died, date of death. For cats that developed diabetes mellitus, information was obtained on date of diagnosis and treatment.

In all cats that underwent transplantation, treatment with cyclosporine (3 to 6 mg/kg [1.4 to 2.7 mg/ lb], PO, q 12 h) was begun 2 days before surgery. Trough blood cyclosporine concentration (ie, concentration 12 hours after administration of a dose of cyclosporine) was periodically measured by means of high-pressure liquid chromatography, and cyclosporine dosage was adjusted to maintain a trough cyclosporine concentration within the therapeutic range of 250 to 400 ng/mL.3 In addition, in all cats that underwent transplantation, treatment with prednisone (2.5 mg, PO, q 12 h) was begun the day after surgery.

Cats that underwent renal transplantation were periodically reexamined after surgery at the University of California or University of Pennsylvania or by the referring veterinarian. For the present study, historical and physical examination findings recorded during follow-up examinations were obtained, along with results of initial and follow-up clinicopathologic testing. Diabetes mellitus was diagnosed on the basis of various combinations of the following signs: persistent hyperglycemia (ie, blood glucose concentration > 250 mg/dL), polyuria and polydipsia, glucosuria, and serum fructosamine concentration > 450 μmol/L (reference range, 190 to 365 μmol/L).

Control population—For comparison purposes, a control population of cats with chronic renal failure that had not undergone renal transplantation and had been examined between January 1995 and December 2002 was included in the study. In these cats, a diagnosis of renal failure had been made on the basis of typical clinical signs (ie, polyuria and polydipsia) and high serum creatinine concentration (> 2.2 mg/ dL; reference range, 1.1 to 2.2 mg/dL) with urine specific gravity < 1.030. Cats were excluded if they were determined to have acute, rather than chronic, renal failure; if they subsequently underwent renal transplantation; if diabetes mellitus was diagnosed before or at the same time that chronic renal failure was diagnosed; or if follow-up information was not available. Medical records of control cats included in the study were reviewed. Data gathered from the medical record included age, sex, breed, date of diagnosis of chronic renal failure, date of diagnosis of diabetes mellitus, and time of follow-up.

Data analysis—The χ2 test of homogeneity was used to compare distributions of categorical variables between groups. The Student t test was used to compare mean values of continuous variables between groups.

To determine whether percentage change in body weight over time was associated with the incidence of diabetes mellitus, a nested case-control study of cats that underwent renal transplantation and for which body weight information had been recorded was performed. Cases were defined as cats that developed diabetes mellitus after undergoing renal transplantation; controls were defined as cats that underwent renal transplantation but did not subsequently develop diabetes mellitus. Cases and controls were matched on the basis of age at the time of renal transplantation, body weight at the time of transplantation, and duration of follow-up. Conditional logistic regression was used.

Cox proportional hazards regression was used to determine whether development of diabetes mellitus was a prognostic factor for survival; time to development of diabetes mellitus was treated as a time-dependent covariate in this analysis.

Standardized morbidity ratios and their 95% CIs were calculated to determine whether cats that had undergone renal transplantation were more likely to develop diabetes mellitus than were cats with chronic renal failure that had not undergone renal transplantation. The age distribution for control cats was used as the standard. For cats for which only the year, rather than the specific date of birth, was recorded, date of birth was considered to be June 1st of the recorded year. For cats for which only the month and year of birth were recorded, date of birth was considered to be the 15th of the reported month.

Standard statistical softwarea,b was used for all analyses. Results of statistical analyses are given as ORs or mortality rate ratios with their 95% CIs. For all analyses, values of P < 0.05 were considered significant.

Results

During the study period, 181 cats underwent renal transplantation at the University of California and 61 cats underwent renal transplantation at the University of Pennsylvania. Of these, 187 (131 that underwent surgery at the University of California and 56 that underwent surgery at the University of Pennsylvania) met the criteria for inclusion in the study; the remaining cats were excluded from the study because they did not survive the initial 30 days after surgery. Follow-up time for cats included in the study ranged from 30 days to 13 years (median, 1.4 years).

Cats included in the study consisted of 42 spayed females, 2 sexually intact females, 86 castrated males, and 1 sexually intact male that underwent surgery at the University of California and 20 spayed females and 36 castrated males that underwent surgery at the University of Pennsylvania. Of the 187 cats included in the study, 150 were domestic mixed-breed cats. The remainder represented a variety of breeds, including Abyssinian, American Shorthair, Himalayan, Manx, Persian, Ragdoll, Siamese, and Tonkinese. Forty-five of the 187 (24%) cats had undergone renal transplantation because of acute renal failure; the remainder had undergone renal transplantation because of end-stage chronic renal failure. Age at the time of renal transplantation ranged from 1 to 16 years (mean, 7.7 years). Age at the time of the study ranged from 1 to 19 years (mean, 9.8 years).

Diabetes mellitus was diagnosed in 26 of the 187 (13.9%) cats included in the study. Incidence of diabetes mellitus among cats that underwent surgery at the University of California (15/131 [11%]) was not significantly (P = 0.17) different from incidence among cats that underwent surgery at the University of Pennsylvania. For 21 of the 26 cats that developed diabetes mellitus, mean ± SD blood glucose concentration at the time of diagnosis was 403 ± 126 mg/dL; blood glucose concentration prior to institution of treatment for diabetes mellitus was not available for the remaining 5 cats. Glucosuria and ketonuria were observed at the time of diagnosis in 12 of 13 cats and in 1 of 12 cats, respectively.

The date of diagnosis was not recorded for 1 of the 26 cats that developed PTDM. For the remaining 25 cats, mean age at the time diagnosis was 10.8 years (range, 1 to 15 years) and median time to diagnosis following renal transplantation was 287 days (range, 31 days to 10.7 years). Incidence of PTDM was 66.0 cases/1,000 cat years at risk. The incidence was 48.6 cases/1,000 cat years at risk for cats that underwent surgery at the University of California and 129.4 cases/1,000 cat years at risk for cats that underwent surgery at the University of Pennsylvania.

During the study period, there were 397 cats examined because of chronic renal failure that did not undergo renal transplantation. Of these, 100 were eliminated because no follow-up information was available, 80 were eliminated because they were determined to have acute renal failure, 30 were eliminated because they eventually underwent renal transplantation, and 9 were eliminated because they had diabetes mellitus at the time chronic renal failure was diagnosed. The remaining 178 cats were included in the present study as a control population. Follow-up time for control cats included in the study ranged from 3 days to 7.9 years (median, 117 days). There were 89 spayed females, 2 sexually intact females, 83 castrated males, and 4 sexually intact males. One hundred thirty-eight were domestic mixed-breed cats; the remainder represented a variety of breeds, including Abyssinian, American Shorthair, Angora, Balinese, Birman, Burmese, Devon Rex, Himalayan, Maine Coon, Persian, and Siamese. Age of the control cats at the time of the study ranged from < 1 to 20 years (mean, 11.8 years).

Diabetes mellitus was diagnosed in 3 of the 178 (1.7%) control cats. Incidence of diabetes mellitus among control cats was 17.9 cases/1,000 cat years at risk. Cats that underwent renal transplantation were 5.45 (95% CI, 3.52 to 8.04) times as likely to develop diabetes mellitus as were control cats with chronic renal failure.

Overall, 167 of the 187 (89.3%) cats that underwent renal transplantation were treated with prednisone after surgery, with most of these cats receiving prednisone at a dosage of 2.5 mg, PO, every 12 hours. Twenty-one of the 26 (81%) cats that developed PTDM received prednisone at this dosage prior to developing diabetes mellitus. Prednisone dosage was not recorded for 3 of the remaining 5 cats; 1 cat was receiving prednisone at a dosage of 1.25 mg, PO, every 12 hours, and 1 cat was receiving prednisone at a dosage of 0.5 mg, PO, every 12 hours. Treatment with prednisone (yes vs no) was not significantly associated with development of diabetes mellitus (yes vs no).

All 187 cats that underwent renal transplantation were treated with cyclosporine. Trough cyclosporine concentration ranged from < 100 to > 6,000 ng/mL. The effect of trough cyclosporine concentration on the development of diabetes mellitus could not be evaluated because trough concentrations were frequently outside the therapeutic range, even in cats that did not develop diabetes mellitus.

Cats > 10 years old at the time of renal transplantation did not have a significantly increased risk of developing diabetes mellitus following renal transplantation, compared with cats < 10 years old at the time of renal transplantation (OR, 2.2; 95% CI, 0.77 to 5.70; P = 0.12). The percentage of female cats that became diabetic within 2 years of renal transplantation (9/64 [14.1%]) was not significantly (OR, 1.39; 95% CI, 0.56 to 3.44; P = 0.7) different from the percentage of male cats that did (13/123 [10.6%]). Information concerning body weight at the time diabetes mellitus was diagnosed was available for 17 of the 26 cats. For these 17 cats, mean ± SD body weight increased from 4.1 ± 1.1 kg (9.0 ± 2.4 lb) to 5.0 ± 1.6 kg (11.0 ± 3.5 lb). Mean ± SD percentage weight change was 22.7 ± 31% (range, −26% to 100%). Body weight at the time of renal transplantation and percentage weight change after renal transplantation were not significantly associated with an increased risk of developing diabetes mellitus.

Nineteen of the 26 cats that developed PTDM required insulin therapy at some time for glycemic control. For 5 of the remaining cats, no information on treatment was available. One cat was never treated with insulin, and 1 cat was treated with glipizide, PO.

Information regarding alterations in prednisone dosage subsequent to diagnosis of diabetes mellitus was available for 8 cats with PTDM. Administration of prednisone was discontinued in 6 cats, and the dosage was decreased from 2.5 mg, PO, every 12 hours to 1.25 mg, PO, every 12 hours in the other 2. Clinical signs resolved in 3 cats after prednisone therapy was discontinued, and these cats no longer required insulin therapy. The other 3 cats continued to require insulin therapy after discontinuation of prednisone therapy. In the 2 cats in which prednisone dosage was decreased, insulin therapy was eventually discontinued. All control cats that developed diabetes mellitus received insulin for glycemic control.

Results of histologic examination of pancreatic specimens were available for only 4 of the cats that developed PTDM. One cat that was examined 4.8 years after diabetes mellitus had been diagnosed and that had been treated with insulin long-term and a reduced prednisone dosage had islet amyloidosis and multiple areas of pancreatic necrosis with septic abscesses. Two cats that were examined 4.5 years and 9 months after diabetes mellitus had been diagnosed and that had been treated with insulin short-term and a reduction in prednisone dosage (1 cat) or discontinuation of prednisone administration (1 cat) had interstitial pancreatic fibrosis and nodular hyperplasia. One cat that was examined 1.6 years after diabetes mellitus had been diagnosed and that had been treated with insulin short-term had nodular areas of exocrine pancreatic hyperplasia.

Twenty of 26 cats that developed PTDM died or were euthanized prior to the present study. Three died or were euthanized as a result of infection (feline infectious peritonitis [n = 1], pneumonia [1], and systemic mycotic infection [1]). Other causes of death included neoplastic disease such as lymphoma or carcinoma (7 cats), uremic pneumonitis (1), urolithiasis (1), and diabetic coma (1). Cause of death in the remaining 7 cats was not determined or not available. For the cats with PTDM that died, median time between renal transplantation and diagnosis of diabetes mellitus was 132 days (range, 13 to 961 days) and median time between diagnosis of diabetes mellitus and death was 275 days (range, 0 to 1,646 days). The mortality rate among cats with PTDM was 2.38 (95% CI, 1.17 to 4.84) times the rate among cats that did not develop PTDM.

Discussion

Results of the present study suggest that cats that undergo renal transplantation have an increased risk of developing diabetes mellitus, compared with cats with chronic renal failure. In addition, mortality rate was higher for cats that developed PTDM than for cats that did not. However, we were not able to identify risk factors for the development of PTDM in cats.

Because most cats that undergo renal transplantation have chronic renal failure, a control population of cats with chronic renal failure that did not undergo transplantation was used in the present study to control for the effect, if any, that chronic renal failure may have on development of diabetes mellitus. To our knowledge, there are no studies that document an increased risk of diabetes mellitus among cats with chronic renal failure. The incidence of diabetes mellitus among the general population of cats in North America has been estimated to be 2.45 cases/1,000 cat years at risk,9 which is lower than the incidence of 17.9 cases/1,000 cat years at risk found for control cats in the present study. Nevertheless, the incidence of diabetes mellitus among control cats in the present study was significantly lower than the incidence among cats that underwent renal transplantation (66 cases/1,000 cat years at risk).

The reasons for the increased risk of diabetes mellitus following renal transplantation are not known, although it seems likely that factors associated with the immunosuppressive drug protocol play a role in the development of PTDM. In human renal transplant recipients, immunosuppressive regimens that include cyclosporine and prednisone are associated with an increased risk of PTDM.6 In dogs and cats, glucocorticoid administration is associated with development of diabetes mellitus.10,11 In fact, cats given multiple doses of glucocorticoids and growth hormone readily develop diabetes mellitus.10 Immunosuppression with calcineurin inhibitors, such as cyclosporine and tacrolimus, has been implicated as an important cause of PTDM in humans, likely resulting from the toxic effects of these drugs on the pancreatic beta cells.6,12 It seems logical that administration of prednisone and cyclosporine, either separately or in conjunction, plays a role in the development of PTDM in cats. Unfortunately, the individual effects of cyclosporine and prednisone could not be adequately examined in the present study, and prospective studies are needed to determine the roles of cyclosporine and prednisone in the development of PTDM in cats.

The fact that in some cats in the present study, insulin therapy could be discontinued after glucocorticoid administration was discontinued provides additional evidence for a role for glucocorticoids in the development of diabetes mellitus. Because glucocorticoids are insulin antagonists, glucocorticoid administration should be discontinued or minimized in cats that develop PTDM. In a study6 of human patients with PTDM, glucocorticoid treatment was discontinued prospectively in 7 patients, 6 of which subsequently had evidence of resolution of the diabetes mellitus. Similarly, in the present study, 5 of 8 cats had resolution of diabetes mellitus following discontinuation of prednisone administration or a reduction in the dosage of prednisone. Although the number of cats was small, these findings suggest that discontinuing or minimizing prednisone administration should be recommended for cats that develop PTDM. Caution should be taken when reducing the prednisone dosage in these cats, and serum creatinine concentration should be monitored for early signs of allograft rejection.

A reduction in the cyclosporine dosage should also be considered for cats with PTDM. Although we were unable to identify any association between trough blood cyclosporine concentration and development of PTDM in the present study, human renal transplant recipients treated with drug protocols that exclude glucocorticoids can still develop PTDM. If attempts are made to reduce the cyclosporine dosage in cats with PTDM, care should be taken to maintain trough concentrations within the therapeutic range. Currently, trough cyclosporine concentration is used in cats for therapeutic drug monitoring. However, in humans, trough cyclosporine concentration has been shown to correlate poorly with the development of adverse events, and the concentration 2 hours after administration of a dose of cyclosporine is considered a better predictor. Similarly in cats, a recent study13 has demonstrated that blood cyclosporine concentration 2 hours after administration of a dose correlates with drug availability better than trough concentration.

Age, sex, and body weight are risk factors for diabetes mellitus in cats, with older, heavier male cats more likely to develop the disease.9 Increased body weight has previously been reported to be a risk factor for development of PTDM in human renal transplant recipients.8 In the present study, age, sex, body weight at the time of renal transplantation, and change in body weight after transplantation were not found to be risk factors for development of PTDM. However, the power of the study was low, and studies involving larger numbers of cats with PTDM are needed to determine whether age, sex, and body weight are risk factors for development of PTDM. Two potential risk factors that could not be evaluated in the present study were breed and neuter status. The low numbers of cats of particular breeds and the low number of sexually intact cats precluded meaningful analysis of these factors.

Pancreatic amyloidosis has been suggested to be an important contributing factor in the development of diabetes mellitus in cats.10 Amyloidosis is characterized by the deposition of amylin in and around the islet cells, thereby acting to decrease the insulin-secreting ability of the pancreas. Because amylin is normally cosecreted with insulin and has been found to have insulin-antagonistic properties, production of a persistent hyperglycemic state through use of an immunosuppressive protocol incorporating glucocorticoids acts to increase deposition of amylin in the pancreas,14 which may hasten the development of diabetes mellitus. Although recent studies10,14 have reported pancreatic amyloidosis in up to 80% of cats with spontaneously occurring diabetes mellitus and in up to 90% of human patients with diabetes mellitus, its specific role in the development of the disease is currently not known. In the present study, only 1 of the 4 cats with PTDM for which results of histologic examination were available had pancreatic amyloidosis. Although the number of cats that underwent histologic examination was small, this finding suggests that PTDM in cats may not be related to pancreatic amyloidosis.

Morbidity and mortality rates for cats with diabetes mellitus are high.15 Common complications of diabetes mellitus in cats include peripheral neuropathies, pancreatitis, infection, and ketoacidosis.16 In the present study, the mortality rate for cats that developed PTDM was significantly higher than the rate for cats that underwent renal transplantation and did not subsequently develop diabetes mellitus. This finding mirrors the situation for human renal transplant recipients, for whom the survival rate has been shown to be significantly decreased among patients who develop PTDM, compared with those who do not.17 One possible reason for the increased mortality rate in cats with PTDM is an increased susceptibility to infection, which was the cause of death in at least 3 of the cats that developed PTDM. Cats that develop PTDM have been shown to have an increased risk (OR, 5.9) of infection, compared with cats that do not. Infection is commonly observed in cats that have undergone renal transplantation and is the second most common cause of death or euthanasia in these patients, regardless of diabetic status.4

The retrospective nature of the present study imposed a number of limitations. Cats were generally managed by the referring veterinarians, and follow-up information was sometimes incomplete. However, a questionnaire detailing relevant clinical and clinicopathologic information was required with each blood sample submitted for determination of cyclosporine concentration. This permitted establishment of a database on each cat following transplantation.

Diabetes mellitus is a challenging and life-threatening disease in cats. With current immunosuppression protocols, the risk for developing diabetes mellitus is higher in cats that undergo renal transplantation than in cats that do not, and owners should be warned of this increased risk when they are considering renal transplantation. Periodic monitoring for diabetes mellitus should be performed in all cats that undergo renal transplantation. The etiology of PTDM in cats is unclear, but our findings suggest that the dosage of glucocorticoids administered to cats with PTDM should be minimized. However, this may increase the risk of allograft rejection, and these cats should be carefully monitored, including serial measurements of serum creatinine concentration. Although the present study was unable to document that cats with high cyclosporine concentrations were at increased risk of developing PTDM, given findings in human patients, it would be prudent to minimize the dosage of cyclosporine while maintaining blood cyclosporine concentration within the target therapeutic range.

ABBREVIATIONS

PTDM

Posttransplantation diabetes mellitus

CI

Confidence interval

OR

Odds ratio

a.

Excel 2003, Microsoft, Redmond, Wash.

b.

Egret for Windows, version 2.0.1, Cytel Software Corp, Cambridge, Mass.

References

  • 1

    Matthews KG, Gregory CR. Renal transplants in cats: 66 cases (1987–1996). J Am Vet Med Assoc 1997;211:14321436.

  • 2

    Adin CA, Gregory CR, Kyles AE. Diagnostic predictors of complications and survival after renal transplantation in cats. Vet Surg 2001;30:515521.

    • Search Google Scholar
    • Export Citation
  • 3

    Bernsteen L, Gregory CR, Kyles AE, et al. Renal transplantation in cats. Clin Tech Small Anim Pract 2000;15:4045.

  • 4

    Kadar E, Sykes JE, Kass PH, et al. Evaluation of the prevalence of infections in cats after renal transplantation: 169 cases (1987–2003). J Am Vet Med Assoc 2005;227:948953.

    • Search Google Scholar
    • Export Citation
  • 5

    Wooldridge JD, Gregory CR, Matthews KG, et al. The prevalence of malignant neoplasia in feline renal-transplant recipients. Vet Surg 2002;31:9497.

    • Search Google Scholar
    • Export Citation
  • 6

    Schulak JA. Steroid immunosuppression in kidney transplantation: a passing era. J Surg Res 2004;117:154162.

  • 7

    Gourishankar S, Jhangri GS, Tonelli M, et al. Development of diabetes mellitus following kidney transplantation: a Canadian experience. Am J Transplant 2004;4:18761882.

    • Search Google Scholar
    • Export Citation
  • 8

    Baltar J, Ortega T, Ortega F, et al. Posttransplantation diabetes mellitus: prevalence and risk factors. Transplant Proc 2005;37:38173818.

    • Search Google Scholar
    • Export Citation
  • 9

    Panciera DL, Thomas CB, Eicker SW, et al. Epizootiologic patterns of diabetes mellitus in cats: 333 cases (1980–1986). J Am Vet Med Assoc 1990;197:15041508.

    • Search Google Scholar
    • Export Citation
  • 10

    Hoenig M, Hall G, Duncan F, et al. A feline model of experimentally induced islet amyloidosis. Am J Pathol 2000;157:21432150.

  • 11

    Peterson ME. Diagnosis and management of insulin resistance in dogs and cats with diabetes mellitus. Vet Clin North Am Small Anim Pract 1995;25:691713.

    • Search Google Scholar
    • Export Citation
  • 12

    Sulanc E, Lane JT, Puumala SE, et al. New-onset diabetes after kidney transplantation: an application of 2003 International Guidelines. Transplantation 2005;80:945952.

    • Search Google Scholar
    • Export Citation
  • 13

    Mehl ML, Kyles AE, Craigmill AL, et al. Disposition of cyclosporine after intravenous and multi-dose oral administration in cats. J Vet Pharmacol Ther 2003;26:349354.

    • Search Google Scholar
    • Export Citation
  • 14

    Powell DS, Maksoud H, Charge SB, et al. Apolipoprotein E genotype, islet amyloid deposition and severity of Type 2 diabetes. Diabetes Res Clin Pract 2003;60:105110.

    • Search Google Scholar
    • Export Citation
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    Goossens M, Nelson R, Feldman E, et al. Response to insulin treatment and survival in 104 cats with diabetes mellitus (1985–1995). J Vet Intern Med 1998;12:16.

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    Feldman EC, Nelson RW. Canine and feline endocrinology and reproduction. Philadelphia: WB Saunders Co, 2004;576577.

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    Revanur VK, Jardine AG, Kingsmore DB, et al. Influence of diabetes mellitus on patient and graft survival in recipients of kidney transplants. Clin Transplant 2001;15:8994.

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    • Export Citation
  • 1

    Matthews KG, Gregory CR. Renal transplants in cats: 66 cases (1987–1996). J Am Vet Med Assoc 1997;211:14321436.

  • 2

    Adin CA, Gregory CR, Kyles AE. Diagnostic predictors of complications and survival after renal transplantation in cats. Vet Surg 2001;30:515521.

    • Search Google Scholar
    • Export Citation
  • 3

    Bernsteen L, Gregory CR, Kyles AE, et al. Renal transplantation in cats. Clin Tech Small Anim Pract 2000;15:4045.

  • 4

    Kadar E, Sykes JE, Kass PH, et al. Evaluation of the prevalence of infections in cats after renal transplantation: 169 cases (1987–2003). J Am Vet Med Assoc 2005;227:948953.

    • Search Google Scholar
    • Export Citation
  • 5

    Wooldridge JD, Gregory CR, Matthews KG, et al. The prevalence of malignant neoplasia in feline renal-transplant recipients. Vet Surg 2002;31:9497.

    • Search Google Scholar
    • Export Citation
  • 6

    Schulak JA. Steroid immunosuppression in kidney transplantation: a passing era. J Surg Res 2004;117:154162.

  • 7

    Gourishankar S, Jhangri GS, Tonelli M, et al. Development of diabetes mellitus following kidney transplantation: a Canadian experience. Am J Transplant 2004;4:18761882.

    • Search Google Scholar
    • Export Citation
  • 8

    Baltar J, Ortega T, Ortega F, et al. Posttransplantation diabetes mellitus: prevalence and risk factors. Transplant Proc 2005;37:38173818.

    • Search Google Scholar
    • Export Citation
  • 9

    Panciera DL, Thomas CB, Eicker SW, et al. Epizootiologic patterns of diabetes mellitus in cats: 333 cases (1980–1986). J Am Vet Med Assoc 1990;197:15041508.

    • Search Google Scholar
    • Export Citation
  • 10

    Hoenig M, Hall G, Duncan F, et al. A feline model of experimentally induced islet amyloidosis. Am J Pathol 2000;157:21432150.

  • 11

    Peterson ME. Diagnosis and management of insulin resistance in dogs and cats with diabetes mellitus. Vet Clin North Am Small Anim Pract 1995;25:691713.

    • Search Google Scholar
    • Export Citation
  • 12

    Sulanc E, Lane JT, Puumala SE, et al. New-onset diabetes after kidney transplantation: an application of 2003 International Guidelines. Transplantation 2005;80:945952.

    • Search Google Scholar
    • Export Citation
  • 13

    Mehl ML, Kyles AE, Craigmill AL, et al. Disposition of cyclosporine after intravenous and multi-dose oral administration in cats. J Vet Pharmacol Ther 2003;26:349354.

    • Search Google Scholar
    • Export Citation
  • 14

    Powell DS, Maksoud H, Charge SB, et al. Apolipoprotein E genotype, islet amyloid deposition and severity of Type 2 diabetes. Diabetes Res Clin Pract 2003;60:105110.

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