| Abstract|| |
Lipid profile abnormality places kidney graft recipients at an increase risk for cardiovascular diseases.This study was undertaken to determine the impact of cyclosporine A (CsA) on lipid profile of transplant patients in Gezira Hospital for Renal Diseases, Medani, Sudan. We studied 78 renal transplant patients with mean age of 42.1 years and mean transplant duration of 3.8 years. Cyclosporine A (CsA), total cholesterol (Tch), triglyceride (TG), HDL cholesterol (HDLch), LDL cholesterol (LDLch), and VLDL cholesterol (VLDLch) were estimated. 62.8% of the patients showed significant lipoprotein abnormalities. Renal allograft recipients showed significantly high levels of TG (p< 0.002), Tch (p< 0.00), LDLch (p< 0.01), and VLDLch (p< 0.05) compared with age and sex matched normal subjects. Increased CsA was reported in females and hypertensive patients. A significant negative correlation was noted between posttransplant duration and VLDLch. The study confirms the existence of dyslipidemia in renal transplant patients in our patients.
Keywords: Renal allograft recipient, Cholesterol, Triglyceride, HDL cholesterol, LDL cholesterol, Cyclosporine A
|How to cite this article:|
Suleiman B, El Imam M, Elsabigh M, Eltahir K, Eltahir A, Miskeen E. Lipid profile in post renal transplant patients treated with cyclosporine in Sudan. Saudi J Kidney Dis Transpl 2009;20:312-7
|How to cite this URL:|
Suleiman B, El Imam M, Elsabigh M, Eltahir K, Eltahir A, Miskeen E. Lipid profile in post renal transplant patients treated with cyclosporine in Sudan. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2016 May 2];20:312-7. Available from: http://www.sjkdt.org/text.asp?2009/20/2/312/45589
| Introduction|| |
Renal transplantation is an established method of renal replacement therapy in patients with end stage renal failure.  Despite the improvement, after transplantation, in the overall survival of patients and renal grafts, cardiovascular disease still is the prime cause of death accounting for almost 50% of mortality in this population. , The effect on progressing of cardiovascular disease may be due to multiple factors such as hypertension, diabetes, age, male gender, and smoking.  Cyclosporine A (CsA) is a powerful immunosuppressive agent which is now widely used in all organ transplantation such as the kidney and liver. Marketed initially as Sandimmune (SIM) in 1984, its use has considerably improved graft and patient survival after renal transplantation.  The incidence of post transplant hyperlipidemia has been studied primarily in patients managed on cyclosporine A (CsA)-based immunosuppressive regiment. ,, The prevalence of post-transplantation hyperlipidemia ranges from 16 to 78%. Reported changes in serum lipid levels include elevation of levels of both triglycerides and total cholesterol. The correlation between high lipid levels and cardiovascular mortality is well established in the general population. There is increasing evidence that post-transplant lipoprotein abnormalities may contribute to the development of cardiovascular and peripheral vascular diseases. , Accelerated atherosclerosis accounts for a major proportion of morbidity and mortality in renal transplant recipients. Vascular disease, common to hyperlipidemic patients, is responsible for 10-40% deaths after renal transplantation though significant post-transplant hyperlipidemia has been widely documented. The incidence of Hypercholesterolemia ranges from 16 to 78% and that of hypertriglyceridemia between 9 to 66% in conventionally treated renal allograft recipients. It must however be noted that criteria used for defining hyperlipidemia is not uniform.  Since, there is no local record available from Sudan for lipid profile in post renal transplant patients treated with CsA it is important to assay the level of lipid profiles in order to reduce morbidity and motility associated with hyperlipidemia.
The objective of this study was to determine the impact of cyclosporine A (CsA) on lipid profile of renal transplant patients in Gezira Hospital for Renal Diseases, Medani, Sudan.
| Patients and Methods|| |
A total of 78 renal transplant patients (M: 46; F: 32) were included in the study. 30 sex and age matched volunteers were considered as control group. The patients were distributed and followed up regularly in four different hospitals (A. Gasim = 32, Gezira = 17, Kidney dialysis and transplantation center-University of Khartoum = 17, and Ibn Sina = 12). The mean age of the patients was 42.1 years (12-70 years), and the mean transplant duration was 45.3 (4-192) months, the detailed demographic and clinical data is shown in [Table 1]. All the study patients were on cyclosporine A (CsA) with starting dose of 5-6 mg/kg gradually reduced to about 3 mg/kg at 6 months.
A questionnaire was designed to include information about age, sex, date and place of transplantation, and history of diabetes and hypertension. The review of physical examination included the measurement of blood pressure and body weight.
For lipid profile analysis, 6 mL heparinised blood was collected by venepuncture after an over night fasting. The plasma was separated by centrifugation at 4000 rpm. The total cholesterol (Tch) was estimated by cholesterol esterase method.  The triglycerides were estimated by the enzymatic hydrolysis of triglyceride with subsequent enzymatic determina tion of liberated glycerol by colorimetry. ,
To estimate high density lipoprotein cholesterol (HDLch) and low density lipoprotein cholesterol (LDLch) were first precipitated by adding phosphotungstic acid and magnesium ions to the samples. HDLch was then estimated in the supernatant by the method of Burstein et al.  The LDLch was measured using LDLch kits as described by Assmann et al.  The very low density lipoprotein cholesterol (VLDLch) was calculated by using the following equation:
Total cholesterol = LDLch + HDLch + VLDLch VLDLch = total cholesterol - (LDLch + HDLch)
Cyclosporine whole blood level was measured by monoclonal radio immunoassay as described by Holt and David in 2002. 
Lipid profile levels were compared with age and sex matched healthy subjects and the reference value as well. Lipid profiles levels exceeding mean ± SD for age and sex matched healthy subjects was considered abnormal.
Different variables presented as mean ± SD. We used Chi squire and T-test for the analysis of variance between two groups, and (ANOVA) to compare the equality of means for any three or more groups of quantitative variables. The P value less than 0.05 were considered significant.
| Results|| |
Seventy eight patients with renal transplant were included in the study. 42.3% did the renal transplant operation inside the country, while the rest did it outside. The characteristics of those patients are shown in [Table 1].
The analysis of CsA and lipoprotein parameters indicate that 66.7% of patients had low cyclosporine A levels, however hyperlipidemia was noted in 62.8% of renal transplant patients with main normality in TG level which was found higher in 47.4% of renal transplant patients [Table 2].
CsA, TG, Tch and LDLch levels were found insignificantly high in renal transplant males compare with females, however, VLDLch level was found high in females than in males [Table 3].
As compared to age and sex matched normal subjects [Table 4], renal allograft recipients showed significantly higher levels of total cholesterol (p< 0.00), triglyceride (p< 0.002), LDLch (p< 0.01), and VLDLch (p< 0.05). The difference in HDLch was not significant.
According to the level of measured blood pressure, there were 38 (48.7%) normotensive, and 29 (37.2%) hypertensive renal transplant patients. CsA and lipoprotein levels were high in hypertensive compared with non hypertensive patients with no significant difference, however, only VLDLch reported significant difference [Table 5].
Statistically negative correlation was seen between post-transplant duration and VLDLch. Tch, TG, HDLch and LDLch levels did not show such a correlation. Conversely, lipoprotein levels showed no correlation with CsA levels.
| Discussion|| |
The present study highlighted the occurrence of lipid abnormalities in renal allograft recipient and the pattern of hyperlipidemia was also defined. The overall number of patients who did their renal transplantation outside the country was higher, in male than in females. Vascular disease, common to hyperlipidemic patients, is responsible for 10-40% deaths after renal transplantation. ,,, Though, significant post-transplant hyperlipidemia has been widely documented, ,,, still normal lipid profile also has been reported too. , In this study, hyperlipidemia was noted in 62.8% of renal transplant patients with the main abnormality being hypertriglyceridemia, 47.7%. Total cholesterol was reduced in 13 (17%) patients. These finding agree with other studies. ,,,,, Compared to healthy controls lipoproteins levels (Tch, TG, LDLch, and VLDLch) showed significant high levels in renal transplant patients. These results are in line with others. , In contrast, HDLch level was low with insignificant stage. Indeed an increase in HDLch is beneficial for renal transplant patients, because HDLch is protective against coronary heart diseases.  So, the presence of low levels of HDLch in renal transplant subjects will probably increase the risk of allograft loss. Despite the above findings, it must be noted that criteria used for defining hyperlipidemia are not uniform. , In agreement with Gunjotikar et al,  VLDLch reported negative correlation with duration of transplantation.
The role of cyclosporine in post-transplant hyperlipidemia is still unclear although some workers have implicated in its causation. ,, Others indicated that, cyclosporine contributes to hypercholesterolemia in renal transplant patients. , In the present study, we reported significant high levels of Tch and TG in all patients under cyclosporine regimen as compared with healthy subjects. Cyclosporine levels reported no correlation with lipid profile levels in agreement with other studies showing no correlation between TG and Tch levels with cyclosporine dose, , The reported low concentration of cyclosporine in 52 (67%) renal transplant patients in this study may explain the presence of weak correlation between cyclosporine level and lipid profiles, thus the long duration of treatment by cyclosporine rather than its level may affect the lipid profile in post-transplant patients, and could explain the discrepancy between results.
Hypertension is an important factor causing or aggravating the dysfunction of the renal graft, and is also caused or aggravated by the dysfunction of the renal graft. , Previous reports showed an escalating effect of administration of cyclosporine on prevalence of hypertension. , In this study, we observed an increase correlation between hypertension and mean dose of CsA, but this association was statistically not significant. One likely justification for a weak association between CsA and hypertension is the low concentration of CsA in majority of patients. This study confirms the existence of a post-transplant dyslipidemia in Sudanese renal transplant patients. However, the role of cyclosporine needs to be evaluated further.
| References|| |
|1.||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. |
|2.||Geerlings W, Tufveson G, Ehrich JH, et al. Report on management of renal failure in Europe, XXIIIII. . Nephrol dial Transplant 1994;9 (Suppl 1):6-25. |
|3.||United State Renal Data System. 1998 annual data report. Causes of death. Am J Kidney Dis 1998;32(Suppl 1):81-8. |
|4.||De Lemos JA, Hillis LD. Diagnosis and management of coronary artery disease in patients with end-stage renal disease on hemodialysis. J Am Soc Nephrol 1996;7(10): 2044-54. |
|5.||Nampoory MR, Johny KV, Costandi JN, Al Muzaire RA, Gupta RK, Nair MP. Cyclosporine neoral: a Local experience. Saudi J Kidney Dis Transpl 1999;10(1):26-30. |
|6.||Verlius DJ, Wenting GI, Derkey FH, Schalekamp MA, Jeekle J, Weimas W. Who should be converted from cyclosporine to conventional immunosuppression in kidney transplantation and why? Transplantation 1987;44: 387-9. |
|7.||Markell MS, Brown CD, Butt KM, Friedman EA. Prospective evaluation of changes in lipid profiles in cyclosporine treated renal transplant patients. Transplant Proc 1989;21(1Pt 2):14979. |
|8.||Ballantyne CM, Podet EJ, Patsch WP, et al. Effects of cyclosporine therapy on plasma lipoprotein levels. JAMA 1989;262(1):35-56. |
|9.||Kasike BL, Guijarro C, Massy ZA, et al cardiovascular diseases after renal transplanttation. J Am Sec Nephrol 1996;7:159-65. |
|10.||Shaheen FM, Basri N, Mohamed Z, et al. Experience of renal transplantation at King Fahad Hospital, Jeddah, Saudi Arabia. Saudi J Kidney Dis Transpl 2005;16(4):562-72. |
|11.||Gunjotikar RV, Taskar SP, Almeida AF, Acharya VN. Dyslipoproteinemia in renal transplantation. J Postgrad Med 1994;40:1. |
|12.||Allain CC, Pool LS, Chen CS, Richmond W, Fu PD. Enzymatic determination of total serum cholesterol. Clin Chem 1974;20(4):470-5. |
|13.||Buccolo G, David M. Quantitative determination of serum triglycerides by use of enzyme. Clin Chem 1973;19:476-82. |
|14.||Fossati R, Prencipe L. Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. Clin Chem 1982;28(10):2077-80. |
|15.||Burstein M, Scholnick HR, Morphin R. Rapid methods for the isolation of Lipoproteins from human serum by precipitation with polyanions. J Lipid Res 1970;11:583-95. |
|16.||Assmann G, Jabs H, Kohnert U, Nolte W, Schriewer H. LDL-cholesterol determination in blood serum following precipitation of LDL with polyvinylsulfate. Clin Chim Acta 1984; 140:77-83. |
|17.||Holt DW. Therapeutic drug monitoring of immunosuppressive drugs in kidney transplantation. Curr Opin Nephrol Hypertens 2002;11 (6):657-63. |
|18.||Markell MS, Freidman EA. Hyperlipidemia after organ transplantation. Am J Med 1989; 87(5N):61N-7N. |
|19.||Kasiske BL, Umen JL. Persistent hyperlipidemia in renal transplant patients. Medicine 1987;66:309-16. |
|20.||Isbel LS, Alfrey AC, Weil R. hyperlipidemia in pediatric, adult and diabetic renal transplant recipients. Am J Med 1978;64:634-42. |
|21.||Vatsala A, Weinberg RB, Scheenberg L. lipid abnormalities in cyclosporine prednisolone treated renal transplant recipients. Transplantation 1989;48:37-43. |
|22.||Ghosh B, Evan DB, Tomilnson SA, Calne RY. Plasma lipids following renal transplantation. Transplantation 1973;15:521-3. |
|23.||Cattran DC, Steiner G, Wilson DR, Fenton SS. Hyperlipidemia after renal transplantation: Natural history and pathophysiology. Ann Intern Med 1979;91:554-9. |
|24.||Beaumont JE, Calla JH, Luke RG, Ress DE, Siegel RR. Normal serum lipids in renal transplant patients. Lancet 1975:1:599-601. |
|25.||Raine AG, Morris PJ. Hyperlipidemia after renal transplantation. Lancer 1988;2:391. |
|26.||Markell MS, Brown CD, Butt KM. Prospective evaluation of changes in lipid profiles in cyclosporine treated renal transplant patients. Transplant Proc 1989;21:1497-9. |
|27.||Ballantyne CM, Podet EJ, Patch WP. Effects of cyclosporine therapy on plasma lipoprotein levels. JAMA 1989;262:35-56. |
|28.||Awad R, Omar A, Mostafa T, et al. Hypercholesterolemia in renal transplant recipients; Contributing factors, effect of dietary modification and fluvastatin therapy. Saudi J Kidney Dis Transpl 1999;10(2):148-51. |
|29.||Kuster GM, Drexel H, Blesch JA, et al. Relation of cyclosporine blood levels to adverse effects on lipoproteins. Transplantation 1994; 57:1479-83. |
|30.||Paul LC, Benediktsson H. Post-transplant hypertension and chronic renal allograft failure. Kidney Int Suppl 1995;52:S34-7. [PUBMED] |
|31.||Perz FM, Rodriquez CA, Bouza P, et al. Outcome of grafts with long-lasting delayed function after renal transplantation. Transplantation 1996;62(1):42-7. |
|32.||Sandrini S, Gaggia P, Bracehi M, Gaggiotti M, Brunori G, Maiorca R. Arterial hypertension in renal transplantation. Contrib Nephrol 1996;119:16-25. |
|33.||Sutherland F, Burgess E, Klassen J, Buckle S, Paul LC. Post-transplant conversion from cyclosporine to azathioprine: Effect on cardiovascular risk profile. Trans Int 1993;6(3):129-32. |
Mohamed El Imam
Urologist and Transplant Surgeon, Deputy Dean, Faculty of Medicine, University of Gezira, P.O. Box 20 Medani
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]