Abstract
Background. The data on lipid profile in renal transplant recipients from the Indian subcontinent is scant. Methods. Lipid profile was studied in 30 consecutive patients of end stage renal disease before renal transplantation (0 month) and prospectively posttransplantation at 1, 3, and 6 months. The results were compared with 30, age and sex matched, healthy controls. All the patients received triple immunosuppression (prednisolone, azathioprine and cyclosporine). Results. Pretransplantation, the hypertriglyceridemia and hypercholesterolemia was present in 20% and 7% of the patients and the difference (elevation) in the mean values of various lipid fractions was not significant compared to healthy controls except a fall in HDL (p<.01). After renal transplantation, there was a significant elevation in the mean values of total cholesterol, triglycerides, VLDL, and LDL cholesterol at 1, 3, and 6 months. HDL cholesterol levels remained significantly lower as compared to healthy controls. Although, the mean values of serum triglycerides and cholesterol were significantly higher in diabetic end stage renal disease compared to nondiabetic ESRD, however there was insignificant difference in the lipid profile amongst diabetic and nondiabetic renal allograft recipients. Conclusion. Our data shows distinct elevation in the lipids and lipoproteins after renal transplantation and immunosuppressive drugs seem to be the culprit.
Introduction
Deranged lipids and lipoprotein metabolism occurs in 20 to 70% of patients of chronic renal failure. Hypertriglyceridemia is the most common lipid abnormality reported with the elevation occurring primarily in the very low-density lipoproteins (VLDL).Citation[[1]] After renal transplantation, various metabolic derangements of chronic renal failure reverse but lipid abnormalities appear to progress in a large fraction of patients.Citation[[2]] Hyperlipidemia is linked closely to cardio-vascular disease (CVD) and CVD is linked to renal transplant mortality.Citation[[3]] Besides other contributing factors posttransplant dyslipidemia may be related to immunosuppressive treatment.Citation[[4]], Citation[[5]] Although the impact of dyslipidemia on long-term graft and patient survival is generally accepted,Citation[[6]] the influence of immunosuppressive drugs, mainly cyclosporine, on dyslipidemia is distrust controversiallyCitation[[7]] and the mechanism of posttransplant dyslipidemia are only poorly understood.Citation[[8]] The opinions in the literature differ concerning the prevalence and type of lipoprotein abnormality and the data on the lipid profile in renal transplant recipients from the Indian subcontinent is scant. This study was designed to assess the lipid profile in renal transplant recipients longitudinally in comparison with matched controls in a North Indian tertiary hospital.
Material and Methods
Thirty consecutive patients of end stage renal disease admitted, for renal transplantation, to the Nephrology unit of Dayanand Medical College and Hospital, Ludhiana, Punjab, North India, were included in this study.
Over night fasting lipids were studied before renal transplantation (0) and repeated after renal transplantation at 1, 3, and 6 months. The estimation of lipids was done using kits from Boehringer Mannheim on multi-channel Autoanalyzer Hitachi-911.
A detailed record of the etiology of chronic renal failure, number of dialysis required before transplantation, details of immunosuppressive drugs used, graft function, anti hypertensive drugs, diuretics, episodes of acute rejection, urinary protein excretion and smoking and alcohol intake, was kept in each patient.
For comparison, the lipids were also estimated in 30 age and sex matched healthy individuals as controls. The values were depicted as mean ± S.D. and student t test of significance was used to compare the results.
Results
Thirty consecutive renal allograft recipients consisted of 25 males and 5 female with mean age of 37.7 years. Chronic glomerulonephritis was the leading cause of end stage renal disease in this study, followed by diabetic nephropathy, hypertensive nephrosclerosis and polycystic kidney disease (). All patients had received live related renal allografts. All patients received triple immunosuppression i.e., prednisolone (30 mg daily for 2 weeks and then tapered to 10 mg daily by 3rd month). cyclosporine (7 mg/kg per day—1st month, 6 mg/kg per day 2nd month, 5 mg/kg per day 3rd month and 4 to 5 mg/kg thereafter) and azathioprine (1.5 mg/kg per day). The dose of cyclosporine was adjusted individually according to the cyclosporine levels. None of the patients in the study were smokers, alcoholic or obese. No patient had significant proteinuria in the posttransplant follow-up study period. No patient was given diuretics or beta blockers for blood pressure control. Two patients had acute cellular rejection on day 8 and 12 respectively and responded to 3 doses of 0.5 gm IV methyl prednisolone. All patients maintained normal graft function. No patient received lipid-lowering drugs during the study period.
Figure 1.
Compared to healthy controls, the patients of end stage renal disease showed insignificant rise in the mean values of serum triglycerides (TG) and low density lipoprotein (LDL) cholesterol, no change in serum cholesterol and VLDL cholesterol and a significant fall in HDL cholesterol. After renal transplantation, there was a significant rise in the mean values of serum TG, serum cholesterol, LDL cholesterol, and VLDL cholesterol when compared to both the healthy controls as well as pretransplant values (0). The mean values of HDL cholesterol remained significantly lower as compared to healthy controls ().
Table 1. Serum lipids in renal allograft recipients and healthy controls
The incidence of hypertriglyceridemia and hypercholesterolemia was 20% and 6.6% in patients of ESRD and after renal transplantation this increased to 40%, 46.7%, 53.3% and 40%, 66.7%, 33.3% respectively at 1, 3, and 6 months.
There was a significant elevation in the mean values of serum TG, serum cholesterol and HDL cholesterol in diabetics with ESRD as compared to nondiabetics, however after renal transplantation lipid profile in both the groups was not significantly different ().
Table 2. Lipid profile in diabetics and nondiabetic patients
Discussion
This longitudinal prospective study demonstrates distinct changes in the serum lipid and lipoprotein concentration and composition in renal transplant patients. Although the previous studies focused mainly on the elevation of serum cholesterol, however our data in addition underlines the remarkable progressive increase in triglycerides after renal transplantation. Hypertriglyceridemia is considered an independent risk factor for cardiovascular disease.Citation[[9]]
The potential causes of dyslipidemia in renal transplant recipients include dietary indiscretion and the use of atherogenic immunosuppressive drugs; steroids>cyclosporine>sirolimus>Tacrolimus>azathioprine>mycophenolate mofetil.Citation[[5]] The other contributing factors, none operable in our study, include renal insufficiency, obesity, lack of exercise, smoking, diabetes, drug therapy for hypertension (beta-blockers and diuretics) and proteinuria.Citation[[10]], Citation[[11]] Immunosuppressive drugs and dietary indiscretion seem to be the only factors operable in our patients. Even though the other observations are consistent with our data, some authors failed to provide a significant association with posttransplant dyslipidemia and the administration of cyclosporine.Citation[[7]]
The significance of these lipid abnormalities after transplantation is not known but patients who had myocardial infarction during a follow-up period of 5 years had higher serum cholesterol levels than those who did not.Citation[[12]] Hyperlipidemia may also contribute to chronic allograft nephropathy.Citation[[13]] Additionally, recent studies showed that patients, who had experienced first year acute rejection episode and who had hypercholesterolemia (≥250 mg/dl), had significantly increased graft loss.Citation[[14]] Therefore, aggressive treatment of posttransplant hyperlipidemia is clearly indicated.
Treatment of hyperlipidemia is not suggested until a stable steroid dose is achieved.Citation[[15]] In general, dietary manipulation alone has not been shown to lower LDL cholesterolCitation[[16]], Citation[[17]] and a large number of renal allograft recipients probably require pharmacologic agents and dietary modification to control hyperlipidemia.Citation[[3]] Several small studies have documented the efficacy of various drugs in treating posttransplant hyperlipidemia. Patients on cyclosporine have a risk of myopathy and rhabdomyolysis with high dose statins, however, a low dose of statins may be used with little risk of muscle injury.Citation[[18]], Citation[[19]] In our institute we have used atorvastatin (10–20 mg) to control posttransplant dyslipidemia without any significant side effects.
In conclusion, our study depicts the lipid profile in pre and post-renal transplant patients from the Indian subcontinent. In addition to the contribution mainly by the immunosuppressive drugs, dietary habits in our population could also be playing a role in the abnormal lipid profile particularly hypertriglyceridemia.
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