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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 1999  |  Volume : 10  |  Issue : 2  |  Page : 148-151
Hypercholesterolemia in Renal Transplant Recipients; contributing Factors, Effect of Dietary Modification and Fluvastatin Therapy


Department of Internal Medicine, Hamad Medical Corporation, Qatar

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   Abstract 

Hypercholesterolemia which frequently follows renal transplantation, places kidney graft recipients at an increased risk for atherosclerosis and cardiovascular diseases. We attempt in this study to determine the prevalence, and evaluate severity and treatment of hypercholesterolemia in kidney transplant recipients. We studied 78 renal transplant patients with a mean age of 42.1 years and mean transplant duration of 6.2 years (range from six months to 8.5 years). They were on triple immunosuppressive therapy and had serum creatinine level of less than 160µmol/L. Thirty-one patients (39.8%) were found to have blood cholesterol levels > 6.4 mmol/L. Significant positive correlation was found between hypercholesterolemia and cyclosporine blood levels above 200 ng/ml (p<0.0009). Furthermore, proteinuria positively correlated with hypercholesterolemia (p<0.0006). There was no significant correlation between cholesterol blood level and the patient age, sex, presence of diabetes, prednisolone, dose, or treatment with C.-blockers and diuretics. Dietary modification was not effective in reducing the blood cholesterol level in our patients, so we used fluvastatin in a dose of 20 to 40 mg daily for a period of three months. This drug was effective in lowering the mean cholesterol blood levels from 7.1 to 5.2 mmol/L (p<0.005). One out of 19-electromyogram studies showed abnormal pattern. We did not notice change in the levels of creatinine phosphokinase, serum creatinine or lover enzymes. In conclusion, hyper­cholesterolemia is common in stable renal transplant patients. The presence of proteinuria and the high level of blood cyclosporine are significantly associated with hypercholesterolemia. Low-dose fluvastatin was well-tolerated and effective cholesterol lowering treatment.

How to cite this article:
Rahed A, Abbvod O, Taha M, Bedawi O, Hamed A, El Sayed M, Ashour A. Hypercholesterolemia in Renal Transplant Recipients; contributing Factors, Effect of Dietary Modification and Fluvastatin Therapy. Saudi J Kidney Dis Transpl 1999;10:148-51

How to cite this URL:
Rahed A, Abbvod O, Taha M, Bedawi O, Hamed A, El Sayed M, Ashour A. Hypercholesterolemia in Renal Transplant Recipients; contributing Factors, Effect of Dietary Modification and Fluvastatin Therapy. Saudi J Kidney Dis Transpl [serial online] 1999 [cited 2019 May 21];10:148-51. Available from: http://www.sjkdt.org/text.asp?1999/10/2/148/37220

   Introduction Top


An impressive body of evidence from epidemiologic and clinical trials in different populations links hypercholesterolemia to a chain of events that eventually lead to coronary heart diseae. [1] The clinical importance of lipid abnormalities in renal transplant recipients has not been well identified. In the transplant population, limited data exist on the relation­ship between coronary artery disease and hyperlipidemia. However, cardiovascular disease is currently a leading cause of death in renal transplant recipients and is likely to increase as patients and graft survival continue to improve. [2] Evaluation of the factors contributing to hypercholesterolemia and its management by dietary modification with or without the use of lipid lowering agents continues to be an important issue in renal transplant recipients.

In this study we attempt to determine prevalence and contributing factors to hypercholesterolemia, and results of dietary and cholesterol lowering agents in our hypercholesterolemia renal transplant patients.


   Patients and Methods Top


A total of 78 renal transplant patients who had serum creatinine level of less than 160 µmol/L were tested for fasting blood chole­sterol levels. The mean age of the patients was 42.1 years and the mean transplant duration was 6.2 years (range from six months to 8.5 years). Patients with blood cholesterol level of 6.4 mmol/L or more were interviewed by a clinical dietitian and given written instructions for low fat and low cholesterol diet. The initial assessment of serum creatinine, electrolytes, blood cholesterol, liver function, complete blood count and creatinine phosphokinase was repeated two months after implementation of dietary modification. Cyclosporine whole blood level was measured by monoclonal radio immuno assay. Treatment with fluvastatin, a coenzyme-A reductase inhibitor, was initiated in those who did not respond to diet therapy at a dose of 20-40 mg daily. Fluvastatin dose was adjusted in these patients in order to achieve the target of reducing the blood cholesterol to or below 5.2 mmol/L. initial electromyogram was done in 19 patients before commencing patients on fluvastatin. Electromyogram and the pre-viously mentioned blood tests were repeated after three months treatment with fluvastatin.


   Statistical Analysis Top


Chi-square test was used in our study to compare patients with hypercholesterolemia in relation to cyclosporine dose and proteinuria.


   Results Top


Fasting blood cholesterol levels in our study patients showed that 31 (39.8%) of them had cholesterol level > 6.4 mmol/L, 20 (25.6%) had levels of 5.3-6.3 mmol/L and 27 (34.6%) had levels < 5.3 mmol/L.

[Table - 1], shows the characteristics of the patients wit severe hypercholesterolemia (>6.4 mmol/L) and patients with lower blood cholesterol level. Both groups are comparable for age and mean time after transplant. There was a significant asso­ciation of severe hypercholesterolemia (≥ 6.4 mmol/L) with proteinuria more than one grams/24 hours (p<0.0006) and cyclosporine blood levels > 200 ng/L (p< 0.0009). Blood albumin level was no significant correlation between cholesterol blood level and the patients' age, sex, presence of diabetes, prednisolone dose, or treatment with β-blockers and diuretics.

Two months of low fat diet decreased the mean level of blood cholesterol in the group with severe hypercholesterolemia, however not significantly from 7.2 to 6.8 mmol/L.

Fluvastatin in daily dose of 20-40 mg for three months resulted in a drop of the mean cholesterol level to 5.2 mmol/L (p<0.005).

The use of fluvastatin was not associated with any change in liver function test, serum creatinine, and creatinine phospho­kinase or cyclosporine blood level. Further­more, there was no change in the degree of proteinuria with fluvastatin therapy. Out of the 19 patients who had electromyogram before and three months after fluvastatin, only one patients had abnormal electromyo­gram in whom the drug was discontinued.


   Discussion Top


Atherosclerosis is a major cause of morbidity and mortality after renal trans­plantation. Prospective series have revealed that 25 to 42 percent of diabetic transplant candidates have significant coronary artery disease. [3] Lipid abnormalities seen in chronic renal failure include low HDL cholesterol level and hypertriglyceridemia, presumably as results of inhibition of lipoprotein lipase. After transplantation hypertriglyceridemia becomes less pronounced and hypercholesterolemia predominates.[4] One early series that included only non­diabetic patients found no increase in incidence of coronary artery disease post renal transplantation.[5] However, in several large series cardiovascular disease was the major cause of death of long-term transplant survivors regardless of the donor sources. [2]

Prednisone may increase the cholesterol level by stimulating hepatic production of lipoproteins. Several studies have shown a positive correlation between serum cholesterol level and daily prednisone dose.6 Steroid withdrawal has been associated with a 17% reduction in total cholesterol level.[7] How­ever, our results did not show any correlation between serum cholesterol level and predni­sone dose.

Cyclosporine was found to cause an increase in serum cholesterol that was independent of its known suppression of glomerular fifltration. [8] In our study, we found a positive correlation between increased serum cholesterol level and cyclosporine serum level. There are two possible mechanisms that may account for cyclosporine induced hypercholesterolemia. Cyclosporine a lipo­philic endecapeptide that is transported in the blood in association with lipoproteins may enter cells via the LDL receptor; hypercholesterolemia might occur because of an abnormal interaction between LDL and the LDL receptor secondary to the presence of cyclosporine in the LDL particle. Cyclosporine may also inhibit hepatic 26­hydroxylase, an important enzyme in bile acid synthesis and reduce the excretion of free cholesterol in bile, resulting in systemic hypercholesterolemia. The effect of cyclo­sporine appears to be dose dependent, since there is a rough correlation between blood cyclosporine levels and the degree of hypercholesterolemia. [9] McCune et al demonstrated that substitution of cyclosporine with tacrolimus resulted in significant reduction in cholesterol blood level.[10]

Proteinuria, commonly seen in chronic rejection contributes to the association between allograft dysfunction and hyper­cholesterolemia, as was documented in previous studies as well as in our patients. 11 The mechanism of proteinuria-induced hypercholesterolemia in renal transplant recipients has not been studied; however in nephritic syndrome, it has been attribute to hepatic overproduction of apo-protein B.[11]

Diet modification should be used as the first step in reducing cholesterol levels. Previous studies demonstrated that when compliance was good, dietary intervention was effective.[12] We noticed that most of our patients could not restrict fat intake in their meals during the months of diet regime. Hence, there was no significant effect on cholesterol blood level.

There are several precious reports that demonstrate the efficacy of fluvastatin to lower cholesterol in renal transplant patients.[13],[14],[15] Accordingly, we were encouraged to use this drug in our renal transplant recipients. Our results were compatible with the previous experience of reducing serum cholesterol blood level. The side effects in our patients were also minimal. Others have reported mild to moderate elevation of CPK, however, without apparent rhabdo­myolysis or any other serous side effect.[13],[14]

We conclude that hypercholesterolemia is common in renal transplant patients and that fluvastatin may be a tolerated and efficacious drug in lowering serum chole­sterol in renal transplant recipients.

 
   References Top

1.Thelle DS. Hypercholesterolemia. Import­ance as a coronary heart diseae risk factor and rational for treatment. Drug Investigation 1990; (Suppl 2)2:1-8.  Back to cited text no. 1    
2.Ibels LS< Stewart JH, Mahony JF, sheil AG. Deaths from occlusive arterial disease in renal allograft recipients. Br Med J 1974;3:552-4.  Back to cited text no. 2    
3.Wwinrauch L, D'Elia JA, Healy RW, et al. Asymptomatic coronary artery disease; angiographic assessment of diabetics evaluated for renal transplantation. Circulation 1978;58:1184-90.  Back to cited text no. 3    
4.Bagdade JD, Albers JJ. Plasma high-density lipoprotein concentrations in chronic hemo­dialysis and renal transplant patients. N Engl Med 1977;296:1436-9.  Back to cited text no. 4    
5.Thomas FT, Lee HM. Factors in the differential rate of artieriosclerosis (AS) between long surviving renal transplant recipients and dialysis patients. Ann Surg 1976;184:342-51.  Back to cited text no. 5    
6.Gokal R, Mann JI, Moore RA, Moris PJ. Hyperlipidaemia following renal transplantation. A study of the prevalence, natural history and dietary treatment. QJ Med 1979;48:507-17.  Back to cited text no. 6    
7.Hircik De, Bartucci MR, Mayes JT, Schulak JA. The effects of steroid withdrawal on the lipoprotein profiles of cyclosporine treated kidney and kidney­pancreas transplant recipients. Transplantation 1992;54:868-71.  Back to cited text no. 7    
8.Markell MS, Brown CD, Butt KM, Friedman EA. Prospective evaluation of changes in lipid profiles in cyclosporine treated renal transplant patients. Transplant Proc 1989;21:1497-9.  Back to cited text no. 8    
9.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. 9    
10.MeCune TR, thacker LR II, Peter TG, et al. Effects of tacrolius on hyperl-ipidemia after successful renal transplantation: a Southeastern Organ Procurement Foundation multi-center clinical study. Transplantation 1998;65:87-92.  Back to cited text no. 10    
11.Lowry RP, soltys G, Mangel R, Kwiterovitch P, Sniderman AD. Type II Hyperlipoproteinemia, hyperapobetalipoproteinemia and hyperalphalipo-proteinemai following renal transplantation: prevalence and precipitationg factors. Transpalnt Proc 1987;19:2229-32.  Back to cited text no. 11    
12.Shen SY, Lukens CW, Alongi SV, et al. Patient profile and effect of dietary therapy on post-transplant hyperlipidemia. Kidney Int Suppl 1983;16:S 147-52.  Back to cited text no. 12    
13.Locsey L, Asztalos L, Kincses Z, Balazs G. Fluvastatin (Lescol) treatment of hyperlipidemia in patients with renal transplants. Int Urol Nephrol 1997;29(1):95-106.  Back to cited text no. 13    
14.Ausein JL, Shifrin FA, Bartucci Mr, et al. Effects of fluvstatin on hyperlipidemia after renal transplantation: influence of steroid therapy. Ann Pharmacother 1996;30(12):1386-9.  Back to cited text no. 14    
15.Goldberg RB, Roth D. A preliminary report of the safety and efficacy offluvastatin fo rhypercholesterolemia in renal transplant patients receiving cyclosporine. Am J Cardiol 1 1995;76(2):107A-9A.  Back to cited text no. 15    

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Correspondence Address:
Omar Abbvod
Department of Medicine, Hamad General Hospital, P.O. 3050, Doha
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PMID: 18212423

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    Abstract
    Introduction
    Patients and Methods
    Statistical Analysis
    Results
    Discussion
    References
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