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IOSR Journal Of Pharmacy
(e)-ISSN: 2250-3013, (p)-ISSN: 2319-4219
www.iosrphr.org Volume 5, Issue 6 (June 2015), PP. 30-32
30
New Onset diabetes after kidney transplantation.
Z.Amrani1
, K.Lahlou1
, H. El Ouahabi1, 3, 4
, M.Ezziani2
, T.Sqalli2
, M.Arrayhani2
,
F.Ajdi1, 3, 4
1- Department of Endocrinology and Metabolism- University Hospital Hassan II Fez- Morocco.
2- Department of nephrology University Hospital Hassan II Fez- Morocco
3- Science team medicines - Medical Center of Biomedical and Translational Research. Faculty of
Medicine and Pharmacy of Fez- Morocco.
4- Pharmacology Department medical central laboratory for medical analyses. Faculty of Medicine and
Pharmacy of Fez- Morocco.
ABSTRACT: Introduction. The occurrence of the new-onset diabetes after kidney transplantation is common
and represents a risk factor for decreased survival of the graft and the patient.
Case presentations. We report 6 cases of diabetes appeared in post renal transplantation. Treatment after
kidney transplantation was based on corticosteroids associated with immunosuppressive therapy in all cases.
Diabetes appeared after renal transplantation in 30% of cases, it was discovered during a systematic
examination. The treatment consisted of insulin therapy for 3 patients, oral anti-diabetic for a patient and 2
patients had normalized their blood glucose levels after discontinuation of corticosteroids and
immunosuppressive therapy adjustment.
Conclusion. Immunosuppressive therapy associated with multiple risk factors presented by patients favor the
occurrence of this diabetes.
KEYWORDS: diabetes, renal transplantation, immunosuppressive therapy, corticosteroids.
I. INTRODUCTION.
The occurrence of secondary diabetes is common after renal transplantation. This complication is due
to immunosuppressive therapy and would be supported by multiple risk factors.
The aim of our study was to determine the incidence and to describe the clinical, biological and therapeutic
characteristics of patients with diabetes appeared after kidney transplantation and to detail the
pathophysiological mechanisms of its appearance.
II. CASE PRESENTATIONS :
It is a descriptive study of 6 patients with diabetes appeared after renal transplantation, collected from
20 renal transplant patients followed in nephrology department of the Hassan II University Hospital in Fez. It
corresponds to a frequency of 30%.
The average age of our patients was 49 years. Our patients had received a kidney transplant from a
living donor in all cases.
After kidney transplantation treatment was based on corticosteroids at a dose of 1mg/kg/day, in combination
with immunosuppressive therapy in all cases.
Figure 1: Treatment given after kidney transplantation.
Fasting glucose levels before transplantation was normal for all patients. Diabetes appeared after renal
transplantation, the time of its appearance was on average 5 months (between 1 and 9 months). Diabetes was
found in our patients in a systematic examination.
Table 1: Characteristics of the population.
The treatment consisted of insulin therapy for 3 patients, oral anti-diabetics for a patient and 2 patients had
normalized their blood glucose levels after discontinuation of corticosteroids and immunosuppressive therapy adjustment.
The average hemoglobin A1C of our diabetic patients under treatment was 7.5%.
New Onset diabetes after kidney transplantation
31
III. DISCUSSION:
The fear after organ transplantation is the acute or chronic graft rejection. This complication is getting
better controlled by improved immunosuppressive treatment. However, we should remain vigilant to the risk of
complications of immunosuppressive therapy, notably the occurrence of a secondary diabetes which can quickly
become life-threatening. Indeed, the immunosuppressive therapy associated with multiple risk factors presented
by patients, favor the occurrence of this type of diabetes. [1]
The incidence of appearance of a diabetes after renal transplantation varies between 2% to 53%
depending on the series; it occurs, usually within 6 months after transplantation, a period when
immunosuppressive therapy are at high doses, which emphasizes the importance of diabetes screening measures
before and after kidney transplantation, especially in patients at risk. [2,3,4]
The risk factors for the occurrence of a diabetes after kidney transplantation are : age greater than 45
years, high body mass index, African or Hispanic ethnicity, family history of type 2 diabetes, history of
gestational diabetes, presence of metabolic syndrome, positive serology of hepatitis C, variant-T of the gene
TCF7L2 (transcription factor 7-like 2) and finally hypomagnesemia. [1,5]
In 67% of cases our patients were older than 45 years at the discovery of diabetes, diabetic heredity was found
in 50% of cases and 67% of our patients were overweight.
Immunosuppressive drugs, by inducing a defect in insulin secretion (toxicity to β Langerhans cells) and
an insulin resistance, probably act as triggers for abnormalities of glucose metabolism in patients at risk. [2]
Several meta-analyzes have shown that the risk of diabetes was significantly higher for patients on
tacrolimus versus cyclosporine and a complete remission or significant improvement of diabetes is seen after the
passage from tacrolimus to cyclosporine in renal transplant patients.[1]
Tacrolimus has been prescribed for 4 of our patients, while one patient was put under rapamycin and
one patient was put under cyclosporine. After installation of diabetes, tacrolimus was replaced by cyclosporine
for two patients with good evolution of the glycemic control.
The latest recommendations for screening the diabetes after kidney transplantation are the dosage of
fasting blood glucose at least weekly for 4 weeks and then every 3 months for one year and then annually. [1,3]
The criteria for diagnosis of diabetes after a renal transplantation are those issued by the American
Diabetes Association (ADA) in 2003. The hemoglobin A1C test is not recommended for the diagnosis but must
be used for monitoring diabetes. The goal of A1C is 7%. A1C should be interpreted with caution for patients
with anemia. [3,6,7]
The choice of immunosuppressive treatment must first consider the immunologic risk of patients to
prevent the acute rejection. The scheme of adjustment of immunosuppressive treatment proposed by the ADA in
2012, to reduce the risk of developing diabetes and to improve diabetes already installed, is: [1]
- For patients with a high immunological risk, treatment by tacrolimus is preferred.
- For patients who developed diabetes, a progressive reduction of immunosuppressive therapy should be done
carefully and progressively.
- For tacrolimus-treated patients whose diabetes is difficult to control a passage to cyclosporine may be
considered in cases of high immunologic risk, while the transition to belatacept could also be considered in
cases of low immunological risk.
Data from various studies indicate that new-onset diabetes after kidney transplantation affects medium and long-
term morbidity and mortality of transplant patients, by the risk of serious infections, especially in the first 6 months, and the
risk of developing or worsening of cardiovascular pathologies. However, these data suggest that the risk is less if good
glycemic control is maintained. [8,9,10]
Regarding the pharmacological treatment of hyperglycemia, it is considered that patients with an A1C assay higher
than 6.5% should start a hypoglycemic treatment. As for type 2 diabetes, a progressive approach should be adopted. The first
step includes lifestyle measures (weight reduction, balanced diet and exercise). The second step is the start of monotherapy.
[1]
Almost all oral anti-diabetics can be used, with the exception of first generation sulphonylureas given the risk of
hypoglycemia and biguanides given the risk of lactic acidosis. Biguanides should be avoided if the glomerular filtration rate
is less than 60ml/min. The Gliquidone, is the most prescribed agent for renal transplant patients: it is efficient, well tolerated
and did not interact with immunosuppressive therapy. The third step is a combination of oral agents with different
mechanisms of action and the last step is the administration of insulin with or without oral agents. [1,11,12,13].
New Onset diabetes after kidney transplantation
32
IV. CONCLUSION:
The application of a good monitoring helps to anticipate and optimize the management of renal transplant
patients. Therapeutic adjustments of immunosuppressive therapy to reduce the risk of diabetes while avoiding
the risk of rejection, are proposed.
Competing interests :
We declare that we have no competing interests.
REFERENCES:
[1]. L. Ghisdal, S. Van Laecke et al. New-Onset Diabetes After Renal Transplantation. Consensus Reports/ADA Statement, Diabetes care,
Volume 35, JAN 2012.
[2]. Tokodai K1, Amada N et al. Insulin resistance as a risk factor for new-onset diabetes after kidney transplantation. Transplant
Proc. 2014 March ;46(2):537-9.
[3]. F. Hadj Kacem, F. Mnif et al. Diabète et transplantation rénale. Diabetes & Metabolism, Volume 39, Numéro S1, pages A47-A48 (mars
2013).
[4]. Kesiraju S, Paritala P et al. New onset of diabetes after transplantation an overview of epidemiology, mechanism of development and
diagnosis. Transpl Immunol. 2014 Jan; 30(1).
[5]. Augusto JF, Subra JF et al. Relation between pre transplant magnesemia and the risk of new onset diabetes after transplantation within
the first year of kidney transplantation. Transplantation. 2014 Jun 15;97(11):1155-60.
[6]. Tokodai K, Amada N et al. The 5-time point oral glucose tolerance test as a predictor of new-onset diabetes after kidney
transplantation. Diabetes Res Clin Pract. 2014 Feb;103(2).
[7]. Wiwanitkit S et al. New-onset diabetes after transplantation and oral glucose tolerance test. Saudi J Kidney Dis Transpl. 2014
May;25(3):657.
[8]. Maamoun HA1, Soliman AR et al. Diabetes mellitus as predictor of patient and graft survival after kidney transplantation. Transplant
Proc. 2013, Nov;45(9):3245-8.
[9]. Burroughs TE, Swindle J, et al. Diabetic complications associated with new-onset diabetes mellitus in renal transplant recipients.
Transplantation. 2007 Apr 27; 83(8):1027-34.
[10]. I.Oueslati, K. Khiari et al. Diabète de novo après transplantation rénale : impact sur la morbimortalité. Diabetes and metabolism., vol
39, supplement 1, march 2013, page A 85.
[11]. Juan Khong, Ping Chong et al. Prevention and management of new-onset diabetes mellitus in kidney transplantation. Neth J Med. 2014
Apr;72(3):127-34.
[12]. Boerner B, Miles C et al. Efficacy and safety of sitagliptin for the treatment of new-onset diabetes after renal transplantation.
International Journal of Endocrinology, Volume 2014 (2014), 9 pages.
[13]. 13)- Tufton N1, Ahmad S et al. New-onset diabetes after renal transplantation. Diabet Med. 2014 Nov; 31(11):1284-92.
Figure 1: Treatment given after kidney transplantation.
Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6
Age 45 years 50 years 61 years 59 years 31 years 48 years
Sexe Male Male Male Male Male Male
Diabetic heredity no no yes no yes yes
BMI 25 27 24 23 26 26
fasting blood glucose 0,98 1,20 1,10 1,43 1,35 1,66
hemoglobin A1C 5,4% 7,5% 6% 7,1% 6,9% 8,5%
Table 1: Characteristics of the population.

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New Onset diabetes after kidney transplantation.

  • 1. IOSR Journal Of Pharmacy (e)-ISSN: 2250-3013, (p)-ISSN: 2319-4219 www.iosrphr.org Volume 5, Issue 6 (June 2015), PP. 30-32 30 New Onset diabetes after kidney transplantation. Z.Amrani1 , K.Lahlou1 , H. El Ouahabi1, 3, 4 , M.Ezziani2 , T.Sqalli2 , M.Arrayhani2 , F.Ajdi1, 3, 4 1- Department of Endocrinology and Metabolism- University Hospital Hassan II Fez- Morocco. 2- Department of nephrology University Hospital Hassan II Fez- Morocco 3- Science team medicines - Medical Center of Biomedical and Translational Research. Faculty of Medicine and Pharmacy of Fez- Morocco. 4- Pharmacology Department medical central laboratory for medical analyses. Faculty of Medicine and Pharmacy of Fez- Morocco. ABSTRACT: Introduction. The occurrence of the new-onset diabetes after kidney transplantation is common and represents a risk factor for decreased survival of the graft and the patient. Case presentations. We report 6 cases of diabetes appeared in post renal transplantation. Treatment after kidney transplantation was based on corticosteroids associated with immunosuppressive therapy in all cases. Diabetes appeared after renal transplantation in 30% of cases, it was discovered during a systematic examination. The treatment consisted of insulin therapy for 3 patients, oral anti-diabetic for a patient and 2 patients had normalized their blood glucose levels after discontinuation of corticosteroids and immunosuppressive therapy adjustment. Conclusion. Immunosuppressive therapy associated with multiple risk factors presented by patients favor the occurrence of this diabetes. KEYWORDS: diabetes, renal transplantation, immunosuppressive therapy, corticosteroids. I. INTRODUCTION. The occurrence of secondary diabetes is common after renal transplantation. This complication is due to immunosuppressive therapy and would be supported by multiple risk factors. The aim of our study was to determine the incidence and to describe the clinical, biological and therapeutic characteristics of patients with diabetes appeared after kidney transplantation and to detail the pathophysiological mechanisms of its appearance. II. CASE PRESENTATIONS : It is a descriptive study of 6 patients with diabetes appeared after renal transplantation, collected from 20 renal transplant patients followed in nephrology department of the Hassan II University Hospital in Fez. It corresponds to a frequency of 30%. The average age of our patients was 49 years. Our patients had received a kidney transplant from a living donor in all cases. After kidney transplantation treatment was based on corticosteroids at a dose of 1mg/kg/day, in combination with immunosuppressive therapy in all cases. Figure 1: Treatment given after kidney transplantation. Fasting glucose levels before transplantation was normal for all patients. Diabetes appeared after renal transplantation, the time of its appearance was on average 5 months (between 1 and 9 months). Diabetes was found in our patients in a systematic examination. Table 1: Characteristics of the population. The treatment consisted of insulin therapy for 3 patients, oral anti-diabetics for a patient and 2 patients had normalized their blood glucose levels after discontinuation of corticosteroids and immunosuppressive therapy adjustment. The average hemoglobin A1C of our diabetic patients under treatment was 7.5%.
  • 2. New Onset diabetes after kidney transplantation 31 III. DISCUSSION: The fear after organ transplantation is the acute or chronic graft rejection. This complication is getting better controlled by improved immunosuppressive treatment. However, we should remain vigilant to the risk of complications of immunosuppressive therapy, notably the occurrence of a secondary diabetes which can quickly become life-threatening. Indeed, the immunosuppressive therapy associated with multiple risk factors presented by patients, favor the occurrence of this type of diabetes. [1] The incidence of appearance of a diabetes after renal transplantation varies between 2% to 53% depending on the series; it occurs, usually within 6 months after transplantation, a period when immunosuppressive therapy are at high doses, which emphasizes the importance of diabetes screening measures before and after kidney transplantation, especially in patients at risk. [2,3,4] The risk factors for the occurrence of a diabetes after kidney transplantation are : age greater than 45 years, high body mass index, African or Hispanic ethnicity, family history of type 2 diabetes, history of gestational diabetes, presence of metabolic syndrome, positive serology of hepatitis C, variant-T of the gene TCF7L2 (transcription factor 7-like 2) and finally hypomagnesemia. [1,5] In 67% of cases our patients were older than 45 years at the discovery of diabetes, diabetic heredity was found in 50% of cases and 67% of our patients were overweight. Immunosuppressive drugs, by inducing a defect in insulin secretion (toxicity to β Langerhans cells) and an insulin resistance, probably act as triggers for abnormalities of glucose metabolism in patients at risk. [2] Several meta-analyzes have shown that the risk of diabetes was significantly higher for patients on tacrolimus versus cyclosporine and a complete remission or significant improvement of diabetes is seen after the passage from tacrolimus to cyclosporine in renal transplant patients.[1] Tacrolimus has been prescribed for 4 of our patients, while one patient was put under rapamycin and one patient was put under cyclosporine. After installation of diabetes, tacrolimus was replaced by cyclosporine for two patients with good evolution of the glycemic control. The latest recommendations for screening the diabetes after kidney transplantation are the dosage of fasting blood glucose at least weekly for 4 weeks and then every 3 months for one year and then annually. [1,3] The criteria for diagnosis of diabetes after a renal transplantation are those issued by the American Diabetes Association (ADA) in 2003. The hemoglobin A1C test is not recommended for the diagnosis but must be used for monitoring diabetes. The goal of A1C is 7%. A1C should be interpreted with caution for patients with anemia. [3,6,7] The choice of immunosuppressive treatment must first consider the immunologic risk of patients to prevent the acute rejection. The scheme of adjustment of immunosuppressive treatment proposed by the ADA in 2012, to reduce the risk of developing diabetes and to improve diabetes already installed, is: [1] - For patients with a high immunological risk, treatment by tacrolimus is preferred. - For patients who developed diabetes, a progressive reduction of immunosuppressive therapy should be done carefully and progressively. - For tacrolimus-treated patients whose diabetes is difficult to control a passage to cyclosporine may be considered in cases of high immunologic risk, while the transition to belatacept could also be considered in cases of low immunological risk. Data from various studies indicate that new-onset diabetes after kidney transplantation affects medium and long- term morbidity and mortality of transplant patients, by the risk of serious infections, especially in the first 6 months, and the risk of developing or worsening of cardiovascular pathologies. However, these data suggest that the risk is less if good glycemic control is maintained. [8,9,10] Regarding the pharmacological treatment of hyperglycemia, it is considered that patients with an A1C assay higher than 6.5% should start a hypoglycemic treatment. As for type 2 diabetes, a progressive approach should be adopted. The first step includes lifestyle measures (weight reduction, balanced diet and exercise). The second step is the start of monotherapy. [1] Almost all oral anti-diabetics can be used, with the exception of first generation sulphonylureas given the risk of hypoglycemia and biguanides given the risk of lactic acidosis. Biguanides should be avoided if the glomerular filtration rate is less than 60ml/min. The Gliquidone, is the most prescribed agent for renal transplant patients: it is efficient, well tolerated and did not interact with immunosuppressive therapy. The third step is a combination of oral agents with different mechanisms of action and the last step is the administration of insulin with or without oral agents. [1,11,12,13].
  • 3. New Onset diabetes after kidney transplantation 32 IV. CONCLUSION: The application of a good monitoring helps to anticipate and optimize the management of renal transplant patients. Therapeutic adjustments of immunosuppressive therapy to reduce the risk of diabetes while avoiding the risk of rejection, are proposed. Competing interests : We declare that we have no competing interests. REFERENCES: [1]. L. Ghisdal, S. Van Laecke et al. New-Onset Diabetes After Renal Transplantation. Consensus Reports/ADA Statement, Diabetes care, Volume 35, JAN 2012. [2]. Tokodai K1, Amada N et al. Insulin resistance as a risk factor for new-onset diabetes after kidney transplantation. Transplant Proc. 2014 March ;46(2):537-9. [3]. F. Hadj Kacem, F. Mnif et al. Diabète et transplantation rénale. Diabetes & Metabolism, Volume 39, Numéro S1, pages A47-A48 (mars 2013). [4]. Kesiraju S, Paritala P et al. New onset of diabetes after transplantation an overview of epidemiology, mechanism of development and diagnosis. Transpl Immunol. 2014 Jan; 30(1). [5]. Augusto JF, Subra JF et al. Relation between pre transplant magnesemia and the risk of new onset diabetes after transplantation within the first year of kidney transplantation. Transplantation. 2014 Jun 15;97(11):1155-60. [6]. Tokodai K, Amada N et al. The 5-time point oral glucose tolerance test as a predictor of new-onset diabetes after kidney transplantation. Diabetes Res Clin Pract. 2014 Feb;103(2). [7]. Wiwanitkit S et al. New-onset diabetes after transplantation and oral glucose tolerance test. Saudi J Kidney Dis Transpl. 2014 May;25(3):657. [8]. Maamoun HA1, Soliman AR et al. Diabetes mellitus as predictor of patient and graft survival after kidney transplantation. Transplant Proc. 2013, Nov;45(9):3245-8. [9]. Burroughs TE, Swindle J, et al. Diabetic complications associated with new-onset diabetes mellitus in renal transplant recipients. Transplantation. 2007 Apr 27; 83(8):1027-34. [10]. I.Oueslati, K. Khiari et al. Diabète de novo après transplantation rénale : impact sur la morbimortalité. Diabetes and metabolism., vol 39, supplement 1, march 2013, page A 85. [11]. Juan Khong, Ping Chong et al. Prevention and management of new-onset diabetes mellitus in kidney transplantation. Neth J Med. 2014 Apr;72(3):127-34. [12]. Boerner B, Miles C et al. Efficacy and safety of sitagliptin for the treatment of new-onset diabetes after renal transplantation. International Journal of Endocrinology, Volume 2014 (2014), 9 pages. [13]. 13)- Tufton N1, Ahmad S et al. New-onset diabetes after renal transplantation. Diabet Med. 2014 Nov; 31(11):1284-92. Figure 1: Treatment given after kidney transplantation. Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Age 45 years 50 years 61 years 59 years 31 years 48 years Sexe Male Male Male Male Male Male Diabetic heredity no no yes no yes yes BMI 25 27 24 23 26 26 fasting blood glucose 0,98 1,20 1,10 1,43 1,35 1,66 hemoglobin A1C 5,4% 7,5% 6% 7,1% 6,9% 8,5% Table 1: Characteristics of the population.