Dyslipidemia in patients with chronic renal failure and in renal transplant patients.B Shah, S Nair, RA Sirsat, TF Ashavaid, K Nair
Nephrology Section, PD Hinduja National Hospital's Research Centre, Mahim, Bombay.
Indian studies on lipid profile abnormalities in chronic renal failure (CRF) have varied from no abnormalities at all to significant abnormality (hypertriglyceridemia and reduced HDL) as described in the Western literature. Moreover, there is no Indian study on the effect of renal transplantation on the abnormal lipid profile of CRF. The aim of our study was to determine the lipid profile of CRF patients on conservative treatment, end stage renal disease (ESRD) patients on maintenance hemodialysis (HD) treatment and renal transplant patients. We also looked at the effect of fish oil rich in polyunsaturated fatty acids (Max-EPA) on hypertriglyceridemia of CRF. The study included 4 groups; Gp I: control subjects (n = 9, age = 30 +/- 5 yrs), Gp II: CRF patients on conservative treatment (n = 9, age = 49 +/- 17 yrs), Gp III: ESRD patients on HD for at least 3 months (n = 19, age = 53 +/- 9 yrs), Gp IV: 3 months post-renal transplant patients (n = 9, age 31 +/- 11 yrs). The lipids and lipoproteins analysed include total cholesterol, HDL, LDL, triglycerides, Apo A1 and Apo B. It was observed that in Gp II patients triglycerides were significantly elevated (p < .05) and Apo A1/Apo B significantly abnormally lower (p < .001) compared to Gp I. In Gp IV patients, there was no significant difference in lipid profile compared to Gp I. With the use of Max-EPA in 5 patients with hypertriglyceridemia, there was a significant improvement in hypertriglyceridemia (p < .05). Our study suggests: 1) significant hypertriglyceridemia does develop in a majority of CRF patients. The abnormality probably improves with dialysis treatment and renal transplantation. 2) A lower Apo A1/Apo B ratio in CRF patients may account for higher risk of atherosclerosis. 3) Fish oil rich in polyunsaturated fatty acids improves hypertriglyceridemia of CRF.
Keywords: Adult, Aged, Female, Fish Oils, therapeutic use,Human, Hyperlipidemia, blood,etiology,Hypertriglyceridemia, diet therapy,India, Kidney Failure, Chronic, blood,complications,therapy,Kidney Transplantation, Lipids, blood,Male, Middle Age, Renal Dialysis,
The risk of atherosclerotic cardiovascular disease in end stage renal disease (ESRD) patients on prolonged dialysis treatment has been reported to be many times higher than for normal and hypertensive groups of comparable age. In an analysis of ESRD patient initiating maintenance dialysis treatment at our centre, we observed that 44%of the deaths in these patients were due to acute mycocardial infarction and cerebrovascular accident. Since one of the important risk factors of atheroscierosis is hyperlipidemia, an abnormality commonly reported in patients of chronic renal failure (CRF), the increased risk of atheroscierotic cardiovascular disease in CRF patients may be due to hyperlipidemia.
Indian studies on lipid profile in CRF have not been consistent. Sharma, et al and Kunde et al observed no hyperlipidemia in patients of CRF. On the other hand, Gupta and Das et al observed lipid abnormalities similar to those reported in Western studies i.e. hypertriglyceridemia and reduced high density lipoprotein (HDL),. In view of the inconsistency in Indian reports, we decided to study the lipid profile in our patients with chronic renal insufficiency.
In order to understand the influence of dialysis and transplantation on the lipid profile, the patients were divided into three groups: those on conservative treatment, those pn maintenance hemodialysis and those who had a successful renal transplant. Further, in patients with hypertriglyceridemia, we studied the effect of fish oil rich in polyunsaturated fatty acids (Maxepa).
The study included 45 patients divided into 4 groups. Group 1: nine healthy subjects (M : F = 4 : 5; age range 24 40 yrs; mean = 30 + 5).
Gp II: nine patients of CRF on conservative treatment (M : F = 6.9: range = 9.65 yrs : mean = 49 + 17). Two patients had diabetic nephropathy (DN). 1 had chronic glomerulonephritis (CGN) and 6 had chronic interstitial nephritis (CIN). All of these patients were predominantly vegetarians and were not on a protein-restricted diet.
Gp III: nineteen patients of ESRID, on maintenance haemodialysis for at least 6 months (M:F = 13:6; age range = 33 75 yrs; mean = 53 + 9). The etiology of ESFID was DN (n=5), CGN (n=3), hypertensive nephrosclerosis (n=3), miscellaneous and unknown (n=8).
Gp IV: eight patients at least 6 months post renal transplant (M1 = 5:3; age range = 20 50 yrs ; mean = 31 + 11). The etiology of ESIRD in these patients was CGN (n=S), DN (n=l), polycystic kidney disease (1) and reflux nephropathy (n=l).
The blood samples of all the patients were collected after an overnight fast for lipid profile analysis which included total cholesterol ITC), triglycerides (TG), high density lipoprotein (HDL) low density lipoprotein (LDL), Apo A1 and Apo B.
The total cholesterol was estimated by CHOD PAP method of Trinder et al. The triglycerides were estimated by the enzymatic hydrolysis of triglycerides with subsequent enzymatic determination of liberated glycerol by colimetry. To estimate HDL cholesterol, chylomicrons, VLDL and LDL were first precipitated by adding phosphotungstic acid and magnesium ions to the sample. HDL cholesterol was then estimated in the supernatant by the method of Trinder et al. The LDL was calculated by using the formula described by Friedwald et al, Apo A1 and Apo B were estimated using the immunochemical method. This method is based on the measurement of immuno-precipitation at 340 nm where in the conditions of antibody excess, the amount of precipitate is proportional to the apoprotein concentration in the serum.
Lipoprotein electrophoresis was also performed on each sample to correlate the lipoprotein electrophoretic pattern with the actual enzymatic estimations in 8 patients with hypertriglyceridemia (5 patients on conservative treatment, 2 patients on dialysis treatment and 1 renal transplant patient) effect of fish oil rich in polyunsaturated fatly acids (PU FA) was studied.
Three patients were lost to follow up. The fish oil was administered as Max EPA brand capsules. Each 1000mg Max EPA capsule contained 180mg eicosapentaenoic acid and 120mg docosah exaenoic acid. The daily dosage was 4 capsules in two divided doses taken with meals. The triglyceride levels were repeated after Max EPA treatment for at least 12 weeks.
Statistical Methods: Means and SD ware calculated by conventional methods. Student's t test for paired and independent samples was used for testing the significance of differences between the means. A p value < 0.05 was considered statistically significant.
The etiology of CRF was diabetic nephropathy in 2 out of 9 cases (22%) on conservative treatment for CRF, in p < 0.05 5 out of 19 cases (26%) on dialysis treatment and in 1 out of 8 cases (12.5%) of renal transplantation. Of these 8 cases of diabetic nephropathy, 4 (50%) had abnormal lipid profile. Of 28 cases with non diabetic cases, of CRFu 9 (31%) had abnormal lipid profile.
[Table - 1] shows the lipid, lipoprotein and apoprotein levels in the 4 groups.
The total cholesterol, HDL and LDL level was not significantly different in the patient groups (Gp II, Gp III, Gp IV) compared to the control subjects. The triglyceride level was significantly higher in the Gp II patients (CRF patients on conservative treatment). However, TG level was not significantly different in dialysis and transplant patients. The Apo A1 / Apo B ratio was lower in the 3 patient groups than in the control subjects. The difference was statistically significant in CRF patients on conservative treatment and in dialysis patients but not in the transplant patients. [Table - 2] shows the triglyceride level in 5 patients before and after 12 weeks of Max EPA therapy.
There was a statistically significant (p < 0.05) decrease in triglyceride level after the Max EPA therapy.
The present study demonstrates that CRF is commonly accompanied by lipid abnormality in the form of hypertriglyceridemia. This is similar to the observations made in Western studies and recent Indian studies,,,. This lipid abnormality could be due to increased hepatic synthesis of VLDL triglycerides and/or defective triglyceride rernoval . We have no explanation why such an abnormality was not observed in earlier Indian studies,. Sharma et al suggest that low calorie and low carbohydrate diet of their pratient population could be the reason for lack of lipid abnormality in their patients of CRF.
While hypertriglyceridemia was observed in 6 out of 9 cases (67 %) of CRF on conservative treatment, it was observed in only 2 out of 19 cases (11 %) on dialysis and 1 out of 8 (12.5%) renal transplant patients. This is unlike the observation in most other studies where hypertriglyceridemia has been reported even in dialysis patients As in our study, Ibels et al also reported decrease in hypertriglyceridemia after initiation of dialysis. This may be due to improved triglyceride removal by increased post heparin lipolytic activity and decreased peripheral resistance to insulin after initiation of dialysis.
In patients with successful renal transplant, the renal function is returned to normal. This could explain the lack of hypertriglyceridemia in transplant patients. The only transplant patients in our series who had hypertriglyceridemia had diabetes which itself could have been the cause of his lipid abnormality. The most common lipid abnormality observed in renal transplant patients is hypetcholesterolemia. This was observed in 37.5% of our cases. The cause for hypercholesterolemia is multi-factorial, but steroids appear to be the main cause since hypercholesterolemia improves with the reduction in dosage of steroids. Cyclosporine also contributes to hypercholesterolemia in renal transplant patients,.
Most studies have reported reduced HDL levels in patients with CRF. This however was not our observation. The HDL levels in the patient groups were not significantly different from those in the control group.
It is suggested that apolipoproteins may be better predictors of coronary artery disease than lipids. Apo AI / Apo B is the most commonly used parameter in clinical practice. The lower the ratio, the greaterthe risk of coronary artery disease. We found that the Apo AI / Apo B was lower in all patient groups compared to the control subjects. The difference was statistically significant in patients on, conservative treatment and dialysis treatment.
A diet rich in polyunsaturated fatty acids (PUFA) leads to an overall decrease in serum triglyceride level. Such an effect has also been described in patients with CRF. The triglyceride level tells in all 5 patients with hypertriglyceridemia treated with PUFA in the form of Max EPA.
In summary, hypertriglyceridemia is the most common form of lipid abnormality seen in patients with CRIF. This abnormality seems to improve after initiation of dialysis and after renal transplantation. The Apo A1 /Apo B ratio is lower in CRF patients than in normal healthy subjects and this may explain a high risk of atherosclerotic cardiovascular disease in CRF patients.
[Table - 1], [Table - 2]