Home About us Current issue Back issues Submission Instructions Advertise Contact Login   

Search Article 
  
Advanced search 
 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 52 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 
 


 
RENAL DATA FROM THE ASIA - AFRICA Table of Contents   
Year : 2009  |  Volume : 20  |  Issue : 2  |  Page : 312-317
Lipid profile in post renal transplant patients treated with cyclosporine in Sudan


1 Department of Biochemistry, Faculty of Applied Medical Sciences, University of Gezira, Sudan
2 Faculty of Medicine, University of Gezira, Sudan
3 Gezira Hospital for Renal Diseases, University of Gezira, Sudan
4 Educational Development and Research Centre, University of Gezira, Sudan

Click here for correspondence address and email
 

   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 2014 Jul 30];20:312-7. Available from: http://www.sjkdt.org/text.asp?2009/20/2/312/45589

   Introduction Top


Renal transplantation is an established method of renal replacement therapy in patients with end stage renal failure. [1] 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. [2],[3] The effect on progressing of car­diovascular disease may be due to multiple factors such as hypertension, diabetes, age, male gender, and smoking. [4] 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. [5] The inci­dence of post transplant hyperlipidemia has been studied primarily in patients managed on cyclosporine A (CsA)-based immunosuppressive regiment. [6],[7],[8] 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. [9],[10] 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. [11] 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 Top


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. [12] The triglycerides were esti­mated by the enzymatic hydrolysis of trigly­ceride with subsequent enzymatic determina­ tion of liberated glycerol by colorimetry. [13],[14]

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. [15] The LDLch was measured using LDLch kits as described by Assmann et al. [16] 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. [17]

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.

Statistical Methods

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 Top


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 Top


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. [18],[19],[20],[21] Though, significant post-transplant hyperlipidemia has been widely documented, [19],[20],[22],[23] still normal lipid profile also has been reported too. [23],[24] 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. [18],[19],[20],[21],[22],[23] 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. [19],[21] 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. [19] 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. [19],[21] In agreement with Gunjotikar et al, [11] 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. [6],[24],[25] Others indicated that, cyclosporine contributes to hypercholesterolemia in renal transplant patients. [26],[27] 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, [28],[29] 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. [30],[31] Previous reports showed an escalating effect of admi­nistration of cyclosporine on prevalence of hypertension. [32],[33] 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 Top

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.  Back to cited text no. 1    
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.  Back to cited text no. 2    
3.United State Renal Data System. 1998 annual data report. Causes of death. Am J Kidney Dis 1998;32(Suppl 1):81-8.  Back to cited text no. 3    
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.  Back to cited text no. 4    
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.  Back to cited text no. 5    
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.  Back to cited text no. 6    
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.  Back to cited text no. 7    
8.Ballantyne CM, Podet EJ, Patsch WP, et al. Effects of cyclosporine therapy on plasma lipoprotein levels. JAMA 1989;262(1):35-56.  Back to cited text no. 8    
9.Kasike BL, Guijarro C, Massy ZA, et al cardiovascular diseases after renal transplant­tation. J Am Sec Nephrol 1996;7:159-65.  Back to cited text no. 9    
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.  Back to cited text no. 10    
11.Gunjotikar RV, Taskar SP, Almeida AF, Acharya VN. Dyslipoproteinemia in renal transplantation. J Postgrad Med 1994;40:1.  Back to cited text no. 11    
12.Allain CC, Pool LS, Chen CS, Richmond W, Fu PD. Enzymatic determination of total serum cholesterol. Clin Chem 1974;20(4):470-5.  Back to cited text no. 12    
13.Buccolo G, David M. Quantitative determination of serum triglycerides by use of enzyme. Clin Chem 1973;19:476-82.  Back to cited text no. 13    
14.Fossati R, Prencipe L. Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. Clin Chem 1982;28(10):2077-80.  Back to cited text no. 14    
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.  Back to cited text no. 15    
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.  Back to cited text no. 16    
17.Holt DW. Therapeutic drug monitoring of immunosuppressive drugs in kidney transplan­tation. Curr Opin Nephrol Hypertens 2002;11 (6):657-63.  Back to cited text no. 17    
18.Markell MS, Freidman EA. Hyperlipidemia after organ transplantation. Am J Med 1989; 87(5N):61N-7N.  Back to cited text no. 18    
19.Kasiske BL, Umen JL. Persistent hyperlipi­demia in renal transplant patients. Medicine 1987;66:309-16.  Back to cited text no. 19    
20.Isbel LS, Alfrey AC, Weil R. hyperlipidemia in pediatric, adult and diabetic renal transplant recipients. Am J Med 1978;64:634-42.  Back to cited text no. 20    
21.Vatsala A, Weinberg RB, Scheenberg L. lipid abnormalities in cyclosporine prednisolone treated renal transplant recipients. Transplan­tation 1989;48:37-43.  Back to cited text no. 21    
22.Ghosh B, Evan DB, Tomilnson SA, Calne RY. Plasma lipids following renal transplantation. Transplantation 1973;15:521-3.  Back to cited text no. 22    
23.Cattran DC, Steiner G, Wilson DR, Fenton SS. Hyperlipidemia after renal transplantation: Natural history and pathophysiology. Ann Intern Med 1979;91:554-9.  Back to cited text no. 23    
24.Beaumont JE, Calla JH, Luke RG, Ress DE, Siegel RR. Normal serum lipids in renal transplant patients. Lancet 1975:1:599-601.  Back to cited text no. 24    
25.Raine AG, Morris PJ. Hyperlipidemia after renal transplantation. Lancer 1988;2:391.  Back to cited text no. 25    
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.  Back to cited text no. 26    
27.Ballantyne CM, Podet EJ, Patch WP. Effects of cyclosporine therapy on plasma lipoprotein levels. JAMA 1989;262:35-56.  Back to cited text no. 27    
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.  Back to cited text no. 28    
29.Kuster GM, Drexel H, Blesch JA, et al. Rela­tion of cyclosporine blood levels to adverse effects on lipoproteins. Transplantation 1994; 57:1479-83.  Back to cited text no. 29    
30.Paul LC, Benediktsson H. Post-transplant hypertension and chronic renal allograft failure. Kidney Int Suppl 1995;52:S34-7.  Back to cited text no. 30  [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.  Back to cited text no. 31    
32.Sandrini S, Gaggia P, Bracehi M, Gaggiotti M, Brunori G, Maiorca R. Arterial hypertension in renal transplantation. Contrib Nephrol 1996;119:16-25.  Back to cited text no. 32    
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.  Back to cited text no. 33    

Top
Correspondence Address:
Mohamed El Imam
Urologist and Transplant Surgeon, Deputy Dean, Faculty of Medicine, University of Gezira, P.O. Box 20 Medani
Sudan
Login to access the Email id


PMID: 19237829

Get Permissions




 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

Top
 
 
    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
  Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  
 


 
    Abstract
    Introduction
    Patients and Methods
    Results
    Discussion
    References
    Article Tables
 

 Article Access Statistics
    Viewed2127    
    Printed70    
    Emailed0    
    PDF Downloaded376    
    Comments [Add]    

Recommend this journal