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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2000  |  Volume : 11  |  Issue : 1  |  Page : 25-30
Diabetes and Renal Transplantation: Saudi Experience

1 Saudi Center for Organ Transplantation, Saudi Arabia
2 Jeddah Kidney Center, Saudi Arabia
3 Riyadh Armed Forces Hospital, Saudi Arabia

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We conducted this study to evaluate the prevalence and risk factors of diabetes mellitus (DM) in our renal transplant population. We retrospectively reviewed the records of the active renal transplant patients at two large transplant centers in Riyadh and Jeddah in Saudi Arabia, transplanted between 1979 and November 1998. The recipients were grouped according to the diagnosis of diabetes; group I: diabetes developed before transplantation (BTDM), group II: diabetes developed only after transplantation (ATDM) and group III: did not have diabetes (NDM). There were 1112 patients' records included in the study. The mean age was 38.2 years and the mean duration of transplantation was 66.9 months. There were 113(10.2%) patients in BTDM group, 134 (12.1%) patients in the ATDM group and 865 (77.8%) patients in the NDM group. There was no significant difference in the prevalence of hypertension among the study groups. In comparison to the other groups, the BTDM group had significantly more males (78.8%), more patients who were transplanted after 1990 (pre-cyclosporin era), more patients with grafts from living non-related donors (46%), higher incidence of acute rejection episodes (39%), higher mean serum creatinine and more patients treated with azathioprine (71%). The ATDM group had significantly higher mean age (46.4 years), higher mean duration of transplantation (91.5 months), higher rate of retransplantation (8.2%), higher mean serum cholesterol level (6.0mmol/L) and more frequently abnormal electrocardiogram (24.6%) than the other two groups. The ATDM group had comparable mean weight (70.2 kg) to the BTDM group but significantly higher than the NDM group (66.1kg). The NDM group had significantly higher mean dose of cyclosporine (3.3 mg/kg/day) and higher mean dose of prednisone (0.16 mg/kg/day) than the other groups. The only independent risk factor for developing DM after transplantation was advancing age. The currently used low-dose steroid therapy was not significantly associated with development of DM after renal transplantation. Nevertheless DM is an important co-morbid condition in the transplant population and is associated with increased risk for cardiovascular and cerebrovascular events.

Keywords: Renal Transplantation, Diabetes, Hypertension, Cyclosporine, Therapy, Cardiovascular, Epidemiology.

How to cite this article:
Souqiyyeh MZ, Shaheen FA, Shiek IA, Al-Khader AA, Fedhail H, Al-Sulaiman M, Mousa D, Al-Hawas F. Diabetes and Renal Transplantation: Saudi Experience. Saudi J Kidney Dis Transpl 2000;11:25-30

How to cite this URL:
Souqiyyeh MZ, Shaheen FA, Shiek IA, Al-Khader AA, Fedhail H, Al-Sulaiman M, Mousa D, Al-Hawas F. Diabetes and Renal Transplantation: Saudi Experience. Saudi J Kidney Dis Transpl [serial online] 2000 [cited 2020 Aug 4];11:25-30. Available from: http://www.sjkdt.org/text.asp?2000/11/1/25/36688

   Introduction Top

In the last decade, diabetic nephropathy has become an increasingly important cause of end-stage renal failure (ESRD). [1] Diabetes mellitus (DM) accounts for 25-30% of new patients requiring treatment in USA and Europe, [2],[3] and 30-45% in Saudi Arabia. [4] Renal transplantation is an established method of renal replacement therapy in patients with ESRD. [5] Despite the improve­ment in the overall survival of post­transplant patients and transplanted renal grafts, post-transplant diabetes is a major cause of cardiovascular morbidity. [5],[6]

The etiology of post-transplant diabetes was attributed in the early days of transplantation to the large doses of steroids used in maintenance immunosuppression. In one study diabetes occurred with a frequency of 60-70% of patients. [7] In the cyclosporine era, the use of reduced doses of steroids has decreased the incidence of post-transplant diabetes to a range from 2.5% to 20%. [8],[9],[10] Post-transplant diabetes and contributing factors have not been evaluated in Saudi Arabia.

In this study, we attempt to evaluate the prevalence, and risk factors of post-transplant diabetes in actively followed up renal transplant population in two centers in Saudi Arabia. Furthermore, we attempt to study the impact of diabetes on cardio­vascular system and renal graft function.

   Patients and Methods Top

We reviewed the records of the active renal transplant patients at two large transplant centers in Riyadh and Jeddah in Saudi Arabia transplanted between 1979 and November 1998.

The review of history included type of donor, original kidney disease, state of hyperten­sion and diabetes mellitus before and after transplantation, cardiac and cerebrovascular events, number of acute rejection episodes in the first year, as well as review of immunosuppressive therapy used.

The chart review also included evaluation of blood pressure and body weight state, evaluation of electrocardiograms, as well as the last three consecutive measurements of serum creatinine, blood sugar and plasma cholesterol levels.

The recipients were grouped according to the diagnosis of diabetes (fasting blood glucose more than 7.8 mmol/l); group I: diabetes developed before transplantation (BTDM), group II: diabetes developed for the first time after-transplantation (ATDM) and group III: did not have diabetes (NDM).

   Statistical Methods Top

We used the analysis of variance (ANOVA) to compare the equality of means for any three or more groups of quantitative variables such as age, weight, and plasma creatinine. The two sample independent ­test was used to compare the equality of means for any two groups. Chi-square test was used to compare categorical variables such as sex and type of transplant. The P value was set as significant if below 0.05.

   Results Top

There were 1112 patients' records included in the study. There were 741 (66.6%) males and 371 (33.4%) females with mean age of 38.1 ± 12.3 years (range 4-76 years).

The mean duration of transplantation was 66.9 ± 50.1 months. The renal grafts were from cadaver donors in 288 (25.9%), living related donors in 445 (40%), and living non­-related in 379 (34.1%) recipients. There were 1071 (96.3%) study patients who had renal transplantation for the first time, while in 41 (3.7%) recipients transplantation was attempted more than once.

The mean weight of the patients was 66.9 ± 16.4 Kg. The prevalence of hypertension was 73% before and 85% after transplan­tation (P not significant). The mean serum creatinine was 231.5 ± 207 pmol/L, while the mean serum cholesterol level was 5.7 ± 1.4 mmol/L. Electrocardiogram (ECG) was available on 1069 patients of which 990 (92.6%) were within normal limits, while ECG compatible with left ventricular hypertrophy, ischemia and/or left ventricular strain was evident in 79 (7.4%).

All the study patients were on cyclos­porine except 46 (4.1%). The mean dose of cyclosporine was 3.3 ± 1.7 mg/Kg/day.

There were 644 (57.9%) patients receiving Azathioprine and 22 (1.97%) receiving mycophenolate mofetil.

Of all the study patients acute rejection occurred once in 313 (28.07%) and more than once in 19 (1.71%). There were only five patients with history of cerebro­vascular accidents.

There were 113 (10.2%) patients in the BTDM group, 134 (12.1%) patients in the ATDM group and 865 (77.8%) patients in the NDM group.

[Table - 1] shows comparison of variables between the BTDM and the ATDM groups. In the BTDM group there were significantly more males (78.8%, compared to 61.9%; P=0.004), more patients who were transplanted after 1990 (the cyclosporine era) (80 % versus 56%; P=0.001), more patients with non-related living donors (47% versus 35%; P=0.02), and more patients treated with azathioprine (71% versus 32.8%; P=0.03). The patients in the ATDM group had significantly higher mean age, longer mean duration after trans­plantation and higher number of re­transplantation. Of these factors, only increasing age came up as an independent risk factor for development of diabetes in this group.

The BTDM and ATDM groups had comparable mean body weight (about 70 kg) but significantly higher weight than the NDM group (66.1kg). The NDM group had significantly higher mean dose of cyclosporine (3.3 mg/kg/day).

There was no significant difference in the prevalence of hypertension before or after transplantation among the study groups.

   Discussion Top

As far as we know, this is the first report that evaluates a large number of transplanted patients who developed diabetes mellitus before or after renal transplantation, in this part of the world. Non-diabetic transplanted patients were available for comparison. The percentage of the patients who developed diabetes after transplantation (12.1%) in our study is close to rates reported in previous studies in the cyclosporine era. [8],[9],[10] However, the overall prevalence of diabetes (BTDM plus ATDM) in our transplant population was 23.6 %, which is lower than the 30% prevalence previously reported in the Saudi transplant population. [11] Further­more, we note that rate of transplantation for diabetic patients in the two centers studied tended to be low in comparison to reports from other centers. [4],[12]

It is noteworthy that the prevalence of ATDM in our study is comparable to the prevalence of DM in the general population of the same age group in Saudi Arabia (13.1% Vs 16.4% respectively). [13] This indicates that the variables that accompany the present-day renal transplantation do not seem to be diabetogenic.

The risk various factors for the develop­ment of post-transplant DM have been reevaluated recently. [8],[14] These included older age, male gender, black race, family history of diabetes, duration of trans­plantation, increased body weight, HLA antigens, acute rejection, steroid dose, and cyclosporine dose.

In our study, the patients in the ATDM group were significantly older than controls. This is similar to the findings of other studies. [8],[9],[14] Previous studies reported the male gender as a risk factor for the development of DM after transplantation, though the reason for the male predomi­nance was not clearly explained. [15] How­ever, there was no significant difference of gender in the ATDM group compared to the controls (NDM) in our study.

Family history and race have been included as predisposing factors in ATDM. [8],[15],[16],[17] Our patients were Saudi nationals belonging to the same race group. Unfortunately, detailed family history was not available for analysis.

There was a tendency of 6% of the patients in our study to develop ATDM in the first year after transplantation and increasing by 2% a year in the following years, a finding that is similar to other studies. [8],[18]

The mean weight was significantly higher in the diabetic groups in comparison with the controls. Some studies did not find significant differences in weight, [8] while others had similar findings to ours. [18]

We did not have available results of HLA antigens to analyze the effect of this factor on the development of ATDM. However, recent studies found no significant correlation with HLA antigens and development of ATDM. [8],[19]

Incidence of acute rejection was not found to be a significantly increased in the ATDM patients. [8] Our results are comparable to those previous studies.

The lengthy treatment with high doses of steroids was responsible for the high percentage of post transplant diabetes before the cyclosporine era. [8],[20] However, there is recent experimental evidence indicating that cyclosporine itself may be a risk factor for the development of ATDM. [21] Nevertheless, clinical studies like ours did not find correlation between the dose of cyclosporine and development of ATDM. [8],[22],[23] On the other hand, a predisposing combined effect of steroids and cyclosporine has been suggested. [8]

While the overall prevalence of DM was not much different in our pre and post transplantation groups (10.2% and 12.1% respectively), more of our diabetics in the ATDM group were transplanted before 1990 (the pre-cyclosporine era). This, however, did not come up as an independent risk factor. Moreover, there was a higher mean daily dose of steroids in the non-diabetic patients in our study; indicating that the currently used low-dose steroids did not seem to be a predisposing factor for the development of DM after renal transplantation.

Thus, it seems that, with the current anti­rejection regimes used for transplantation, the development of DM is probably more related to advancing age of patients rather than transplantation per se.

Diabetes is a well known risk factor for cardiovascular disease. [24],[25] Our patients with ATDM had higher level of cholesterol and higher percentage of ECG abnormality compared to non-diabetics. Also they had high prevalence of hypertension, though not different from the non-diabetic transplanted patients. All these factors place these patients at higher risk for cardiovascular and cerebrovascular incidents. This may result in substantial morbidity and mortality. Some studies found significant effect of development of ATDM on renal function. [8],[15] Surprisingly the ATDM patients had a better mean serum creatinine level than the non-diabetic controls.

We conclude that diabetes mellitus is an important problem in the transplant patients in Saudi Arabia and may be associated with significant morbidity and mortality. However, ATDM does not to be directly related to transplantation per se. Further studies would be needed to define the outcome of such group of patients in the presence of new immunosuppressive drugs.

   References Top

1.Raine AE. Epidemiology, development and treatment of end-stage renal failure in type 2 (non-insulin-dependant) diabetic patients in Europe. Diabetologia 1993;36:1099-104.  Back to cited text no. 1  [PUBMED]  
2.Rettig B, Teutsch SM. The incidence of end-stage renal disease in type 1 and type 2 diabetes mellitus. Diabetic Nephr 1984;3:26-7.  Back to cited text no. 2    
3.Challah S, Brunner FP, Wing AJ. Evolution of the treatment of patients with diabetic nephropathy by renal replacement therapy in Europe over a decade: data from the EDTA registry. In: Mogensen CE, ed. The Kidney and Hypertension in Diabetes Mellitus, Boston, Ma: Martinus Nijhoff 1998:365-77.  Back to cited text no. 3    
4.Mitwalli A, Al-Swailem AR, Aziz KMS, et al. Etiology of end-stage renal disease in two regions of Saudi Arabia. Saudi J Kidney Dis Transplant 1997;8(1):16-20.  Back to cited text no. 4    
5.Schnuelle P, Lorenz D, Trede M, Van Der Woude FJ. Impact of renal cadaveric transplantation on survival in end-stage renal failure: evidence for reduced mortality risk compared with hemodialysis during long-term follow-up. J Am Soc Nephrol 1998;9(11):2135-41.  Back to cited text no. 5    
6.Rao M, Jacob CK, Shastry JC. Post-renal transplant diabetes mellitus-a retrospective study. Nephrol Dial Transplant 1992;7: 1039-42.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Arner P, Gunnarsson R, Blomdahl S, Groth CG. Some characteristics of steroid diabetes: a study in renal transplant recipients receiving high dose cortico­steroid therapy. Diabetes Care 1983;6:23-5.  Back to cited text no. 7    
8.Vesco L, Busson M, Bedrossian J, Bitker MO, Hiesse C, Lang P. Diabetes mellitus after renal transplantation: characteristics, outcome and risk factors. Transplantation 1996;61:1475-8.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Roth D, Milgrom M, Esquenazi V, Fuller L, Burke G, Miller J. Post-transplant hyper­glycemia. Increased incidence in cyclos­porine-treated renal allograft recipients. Transplantation 1989;47:278-81.  Back to cited text no. 9    
10.Mejia G, Arbelaez M, Henao JE, Arango JL, Garcia A. Cyclosporine-associated diabetes mellitus in renal transplant. Clin Transplant 1989;3:260.  Back to cited text no. 10    
11.Hussein M, Mooij J, Roujouleh H. Compli­cations in kidney transplant recipients: a single center experience. Saudi J Kidney Dis Transplant 1996;7(2):168-72.  Back to cited text no. 11    
12.Hirschl MM, Heinz G, Sunder-Plassmann G, Derfler K. Renal replacement therapy in type 2 diabetic patients: 10 years expe­rience. Am J Kidney Dis 1992;20:564-8.  Back to cited text no. 12  [PUBMED]  
13.El-Hazmi MAF, Al-Swailem AR, Warsy AS, Al-Sudairy F, et al. The prevalence of Diabetes Mellitus and impaired glucose tolerance in the population of Riyadh. Annals of Saudi Medicine 1995;15:598-601  Back to cited text no. 13    
14.Miles AM, Sumrani N, Horowitz R, et al. Diabetes mellitus after renal transplan­tation, as deleterious as non-transplant­associated diabetes. Transplantation 1998; 65:380-4  Back to cited text no. 14  [PUBMED]  [FULLTEXT]
15.UNOS update: July/August 1996. Richmond; VA: UNOS, 1996.  Back to cited text no. 15    
16.Tornatore KM, Biocevich DM, Reed KA, et al. Post-transplant diabetes mellitus and methyl-prednisolone pharmacokinetics in African-American and Caucasian renal transplant recipients. Clin Transplant 1995;9:289-96.  Back to cited text no. 16  [PUBMED]  
17.Yamamoto H, Akazawa S, Yamaguchi Y, et al. Effects of cyclosporine A and low dosages of steroid on post transplantation diabetes in kidney transplant recipients. Diabetes Care 1991;14:867-70.  Back to cited text no. 17  [PUBMED]  
18.Friedman EA, Shyh TP, Beyer MM, Manis T, Butt KM. Posttransplant diabetes in kidney transplant recipients. Am J Nephrol 1985;5:196-202.  Back to cited text no. 18  [PUBMED]  
19.Ekstrand AV, Ericksson JG, Gronhagen­Riska C, Ahonen PJ, Groop LC. Insulin resistance and insulin deficiency in the pathogenesis of post-transplantation diabetes in man. Transplantation 1992; 53:563-9.  Back to cited text no. 19    
20.Ramirez L, Koffler M, Rios J, et al. Steroid induced diabetes following renal transplan­tation: predisposing factors [Abstract]. Diabetes 1989;38(Suppl 2):77.  Back to cited text no. 20    
21.Garvin PJ, Niehoff M, Staggenborg J. Cyclosporine's effect on canine pancreatic endocrine function. Transplantation 1988; 45:1027-31.  Back to cited text no. 21  [PUBMED]  
22.Pirsch JD, Miller J, Deierhoi MH, Vincent F, Filo RS. A comparison of tarcolimus (FK 506) and cyclosporine for immuno­suppression after cadaveric renal transplan­tation: FK 506 Kidney Transplant Study Group. Transplantation 1997;63:977-83.  Back to cited text no. 22    
23.Hricik DE, Bartucci MR, Moir EJ, Mayes JT, Schulak JA, Influence of corticosteroid withdrawal on post transplant diabetes mellitus in cyclosporine treated renal transplant recipients. Transplant Proc 1991;23:1007-8.  Back to cited text no. 23    
24.Aakhus S, Dahl K, Wideroe TE. Hyper­lipidaemia in renal transplant patients. J Intern Med 1996;239(5):407-15.  Back to cited text no. 24    
25.Paul LC, Sutherland F, Klassen J, Buckle S, Burgess E. Cardiovascular risk impact of cyclosporine immunosuppression in renal transplant recipients. Transplant Proc 1992; 24:2740-1.  Back to cited text no. 25  [PUBMED]  

Correspondence Address:
Muhammad Ziad Souqiyyeh
Saudi Center for Organ Transplantation, P.O. Box 27049, Riyadh 11417
Saudi Arabia
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