Hyperlipidemia in patients with chronic renal failure.
With the improvement in conservative management and dialysis, the life span of patients with chronic renal failure (CRF) has increased. As the patient's survival has approached the 10 year mark, there is an increasing indication that accelerated atherosclerosis may remain a major unresolved problem threatening the longevity of CRF patients. With the implication of plasma lipids in the pathogenesis of atherosclerosis and ischaemic heart disease, it becomes worthwhile to study the behaviour of various lipid fractions in C.R.F. patients. Hyperlipidemia in C.R.F. patients, whether on regular dialysis or being managed conservatively, is well known in the western population., , , ,  However, the two studies conducted so far in India have failed to show any lipid abnormality in C.R.F. patients.,  In view of these conflicting findings the present study was undertaken and the findings reported.
Forty patients of chronic renal failure who were either admitted or being followed up in the nephrology department of the K.E.M. Hospital, Bombay were studied. Twenty normal persons were included as healthy controls (Group I). Out of the 40 patients, 20 were undialysed patients, being managed conservatively (Group II) and the other 20 were on regular hemodialysis (Group III). The 3 groups of patients studied were comparable as regards to the age and sex distribution. The male to female ratio in the 3 groups was 2.3:1. Their ages varied between 16 and 55 years.
Patients having a proteinuria of 3 gm or more per day or serum albumin of less than 3 gm % were excluded from the study since nephrotic syndrome itself is known to produce lipid abnormalities. Similarly, diabetic patients and persons who were obese (body weight > ideal body weight by 10%), were not included in the study. Patients who were on drugs like steroids which are known to alter serum lipids were excluded from the study. All patients of C.R.F. were stable (their body weight was more or less the same over a period of 7 days). They were not having any infection and were on good oral intake without vomiting. In majority of patients, the C.R.F. was due to tubulointerstitial disease or, chronic glomerulonephritis.
In the dialysed group, patients had received, on an average, twenty hemodialyses at the time of the study. All these patients were dialysed with Meltec (1 sq.m.) or TMI (0.6 sq.m.) parallel flow dialysers for 6 hours per dialysis, using glucose and acetate-free dialysate. 5000-8000 units of heparin were injected during each dialysis.
A detailed dietetic history was recorded in all the patients. Blood was collected after an overnight fast of 12 hours, for estimations of cholesterol, triglycerides, free fatty acids, lipoproteins and blood sugar. Ten units of heparin per kg. of body weight were injected intravenously and blood was collected 10 minutes later for estimation of post-heparin lipolytic activity (PHLA). All blood samples were collected with proper anticoagulants and transported immediately to the laboratory. The plasma lipids were estimated by the following methods.
1. Plasma cholesterol was estimated by the method of Abell et al.
2. Plasma triglycerides were estimated by the method of Van Handel.
3. Free fatty acids were estimated in Doles' extract by using cobalt soap formation method.13
4. Lipoprotein electrophoresis was performed on agarose gel using barbitone buffer (pH = 8.6, ionic strength µ = 0.05). Slides were stained by Sudan Black and scanned on Joyce-Lobel Chromoscan.
5. Post-heparin lipolytic activity (PHLA) was measured using corn oil and tween 60 as substrate. The activity was expressed in terms of free fatty acids released per minute after the incubation of plasma with the substrate at 370C (pH: 8.5) for 1 hour.
Lipid abnormalities in C.R.F.
As seen in [Table - 1] the levels of fasting free fatty acids were significantly lower in the dialysed group of patients (p < 0.05). The fasting serum triglycerides were significantly elevated in both the groups of renal failure patients (p < 0.02). The percentage of alpha lipoproteins and PHLA were significantly lower in the undialysed group of patients (p < 0.02 and < 0.001 respectively).
Considering the individual values, 50%of the patients in the undialysed group and 35% in the dialysed group had elevated serum triglycerides [Table - 2] and [Table3]
In Group II out of the 10 patients having hypertriglyceridemia, 6 had elevated prebeta lipoproteins indicative of Type IV hyperlipoproteinemia of Fredrickson's classification. The remaining 4 had Type IIb pattern. In group III, out of the 7 patients having hypertriglyceridemia, 4 had elevated prebeta lipoproteins indicative of Type IV pattern and the other three had Type IIb pattern of hyperlipoproteinemia. The most striking result was the low values of PHLA in 90% of the patients in Group II and 45% of patients in Group III [Table - 2] and
[Table - 3].
As seen in [Table - 4] there was no statistically significant correlationship between the hypertriglyceridemia and the caloric intake in both the groups of patients. However, the intake of saturated fats was more in patients with hyperlipidemia.
Hyperlipidemia, manifested as turbidity of plasma after an overnight fast, has been recognised in patients with uremia over a century. However, only recently it has been possible to identify the exact type of lipid abnormality and the underlying mechanism. Fasting hypertriglyceridemia is a well known abnormality in C.R.F. patients of western population., , ,  The majority of these patients belong to Type IV pattern of hyperlipoproteinemia., ,  Bagdade et al originally found both increased synthesis and decreased clearance of very low density lipoprotein (VLDL), in uremic patients as a cause of hypertriglyceridemia. Although the relative importance of increased synthesis versus decreased clearance of VLDL has not been quantified, recent emphasis has shifted towards the latter. Decreased lipoprotein lipase detected as PHLA, has been confirmed in both dialysed and undialysed patients and appears to be one of the most consistent findings., 
In India, Mani et a1 did not find any lipid abnormality in patients of chronic renal failure either on regular hemodialysis or being managed conservatively. They attributed this to the low calories derived from carbohydrates and the high intake of polyunsaturated fatty acids in the diet. (Ratio of polyunsaturated fatty acids to saturated fatty acids was 1.26:1). Similarly, Sharma et a1 also did not find any lipid abnormality in patients of C.R.F. being managed conservatively. The caloric intake of these patients was quite low (1000-1500 K.Cal./day). In both these studies PHLA was not measured.
On a close scrutiny, the results of the present study are not grossly different from the previous two Indian studies [Table - 1]. Although a significant proportion of the patients (50% in the undialysed group and 35% in the dialysed group) had hypertriglyceridemia, the mean values of triglycerides in the undialysed group was only 150 mg% (S.D. ± 66.17 mg%) compared to 144.65 mg% (S.D. ± 51.45 mg%) in the dialysed group. Also the highest values of triglycerides in the undialysed group was 269 mg% and in the dialysed group 300 mg%. Hence it can be seen that the degree of hypertriglyceridemia in our population is less although the type of hyperlipoproteinemia is same as in the western population., , ,  This may be related to the dietary pattern in the form of high intake of polyunsaturated fatty acids. It can be postulated from the Indian studies including the present one that diet apparently plays an important role in the genesis of hyperlipidemia in C.R.F.
We thank Dr. C. K. Deshpande, Dean, Seth G.S. Medical College and K.E.M. Hospital, for allowing us to publish this paper.