|Year : 2019 | Volume
| Issue : 2 | Page : 89-94
Atherogenic ratios and serum lipid levels in patients with end-stage renal disease on continuous ambulatory peritoneal dialysis
Sulochana Narasimha1, N Harini Devi2, Alok Sachan3, V Siva Kumar4
1 Department of Community Medicine, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
2 Department of Biochemistry, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
3 Department of Endocrinology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
4 Department of Nephrology, Sri Venkateswara Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
|Date of Submission||15-Nov-2018|
|Date of Acceptance||26-Jun-2019|
|Date of Web Publication||30-Jul-2019|
Dr. N Harini Devi
Department of Biochemistry, SVIMS, Tirupati, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Background: Patients with end-stage renal disease (ESRD) on continuous ambulatory peritoneal dialysis (CAPD) often have an atherogenic lipid profile. Lipid disturbances that have been observed in patients with ESRD on CAPD include hypercholesterolemia, hypertriglyceridemia, and decreased high-density lipoprotein cholesterol (HDL-c).
Aim and Objectives: To study the atherogenic ratios and serum lipid levels in patients with ESRD on CAPD and compare with healthy controls.
Materials and Methods: This study included 30 patients with ESRD before and after the initiation of continuous ambulatory peritoneal dialysis and 30 healthy controls. Thirty patients with ESRD after the start of peritoneal dialysis were regularly followed up for 3rd, 6th, 9th, 12th, and 15th months. The biochemical parameters were measured in baseline and follow-up samples.
Results: The concentrations of (TC), serum triglycerides (TGs), very low-density lipoprotein cholesterol (VLDL-c), and atherogenic ratios were increased and levels of serum TC, low-density lipoprotein cholesterol (LDL-c), and HDL-c were decreased significantly during 3rd and 6th months. However, after 1 year of CAPD, the serum TGs, VLDL-c, TC, and LDL-c levels were significantly higher than the baseline values and HDL-c was significantly lower than the baseline values.
Conclusion: The present study findings conclude that the continuous peritoneal absorption of glucose during CAPD contributes to alteration in serum lipids. However, the changes are fluctuating as an adaptation to the peritoneal absorption of glucose.
Keywords: Continuous ambulatory peritoneal dialysis, end-stage renal disease, glucose, lipids
|How to cite this article:|
Narasimha S, Devi N H, Sachan A, Kumar V S. Atherogenic ratios and serum lipid levels in patients with end-stage renal disease on continuous ambulatory peritoneal dialysis. J NTR Univ Health Sci 2019;8:89-94
|How to cite this URL:|
Narasimha S, Devi N H, Sachan A, Kumar V S. Atherogenic ratios and serum lipid levels in patients with end-stage renal disease on continuous ambulatory peritoneal dialysis. J NTR Univ Health Sci [serial online] 2019 [cited 2020 Jan 19];8:89-94. Available from: http://www.jdrntruhs.org/text.asp?2019/8/2/89/263628
| Introduction|| |
End-stage renal disease (ESRD) is known to be associated with alteration in the composition of serum lipids and lipoproteins. The main factor in the pathogenesis of atherosclerosis and CVD is abnormalities of lipid metabolism and serum lipid profile in ESRD. A traditional dyslipidemia of ESRD is characterized by increased total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), triglycerides (TGs), and decreased high-density lipoprotein cholesterol (HDL-c). In addition to traditional parameters, atherogenic ratios were calculated to assess the risk of atherosclerosis. These changes might worsen in patients on dialysis with predominance of the atherogenic triad, characterized by increased TG, very low-density lipoprotein cholesterol (VLDL-c), and decreased HDL-c. Continuous ambulatory peritoneal dialysis (CAPD) has gained attention as an alternative modality of therapy to hemodialysis (HD) in dialysis population. Several factors have an impact on lipid metabolism and serum lipid profile in ESRD such as renal replacement modality-dependent changes in serum lipids as seen in PD and renal transplantation, preexisting genetic disorders unrelated to kidney disease, inflammation, malnutrition, and treatment with lipid-modifying medications. However, patients with ESRD on CAPD seem to have a more altered lipid profile than those on HD. Several studies had observed that once dialysis commences, patients with ESRD on CAPD develop a more atherogenic lipoprotein profile compared with HD patients., Not all studies agree on the differences between the two treatment modalities, but a majority of the studies are from ethnically and geographically distinct populations who had reported these differences between the two treatment modalities. The common lipid or lipoprotein profile in patients with ESRD on CAPD reported are 20%–40% of elevated levels of TC and LDL-c, and 25%–50% of TG, Lp (a), and apolipoprotein B (apoB) and low levels of HDL-c and apolipoprotein A1 (apoAI). Not all these abnormalities are found in all patients. ESRD is associated with deficiency and dysfunction of lipoprotein lipase (LPL). Under normal conditions, LPL mediates the hydrolysis of the TG of VLDL and chylomicrons thereby allowing the release and uptake of fatty acids by myocytes and adipocytes resulting in reduced expression of LPL in adipose tissue, skeletal muscle, and myocardium. The hypertriglyceridemia, seen in PD, results from the increased hepatic synthesis of VLDL-c due to deficiency in LPL or may also be partial deficiency of hepatic lipase. ESRD may not be associated with elevated serum concentrations of LDL-c, but there is abnormal LDL metabolism, and LDL-c has been shown to be qualitatively different from normal LDL-c in that there is an increased concentration of TG-rich and cholesterol-poor small dense LDL particles together with high apoB; increased oxidized LDL levels and Lp (a) levels have been reported in 42% of patients. ESRD is associated with a significant reduction in serum concentrations of apoAI and HDL particle. This is accompanied by reduced HDL-c content and altered lipid and protein composition including enrichment with TGs and proinflammatory proteins. The mechanisms and pathogenesis underlying altered lipid metabolism in patients with ESRD on CAPD are not completely understood, but the use of glucose-based PD solutions and drugs such as β-blockers might lead to alterations. Glucose, as an osmotic agent in PD, may contribute to the pathogenesis of this atherogenic dyslipoproteinemia. PD patients can absorb up to 200 g of glucose from the dialysis fluid per day based on the glucose concentration and membrane transport status. The increased glucose load can increase hepatic fatty acid synthesis and consequently increase hepatic TG synthesis and secretion resulting in increased VLDL-c and LDL-c particles. Because each VLDL-c and LDL-c particle contains one molecule of apoB, plasma apoB levels increase in parallel. Compared to the large data on lipid abnormalities in patients on HD, there are only fewer studies in PD patients, which have shown sequential changes in the lipid profiles. Hence, the present study was taken up to measure the serum lipid levels and atherogenic ratios in patients with ESRD on CAPD.
| Materials and Methods|| |
The present study was carried out in the Department of Nephrology at SVIMS, Tirupati, during the period between June 2013 and October 2015. The study included 30 patients with ESRD before the initiation of peritoneal dialysis as baseline group and 30 apparently healthy controls. All patients and controls had given written informed consent prior to study enrolment. Thirty baseline patients with ESRD after the start of peritoneal dialysis were regularly followed up for 3rd, 6th, 9th, 12th, and 15th months. The baseline biochemical parameters and patients' details were noted during the initial screening period in 30 patients with ESRD before the initiation of peritoneal dialysis. The biochemical parameters for the 3rd, 6th, 9th, 12th, and 15th months were also measured. Exclusion criteria for cases included acute renal failure, acute chronic kidney disease, patients with ESRD on HD, smoking, pediatric age group (<18 years), pregnant women, diabetes mellitus, vasculitis, liver disease, malignancy, history of alcohol abuse, and unwilling patients. Controls included healthy individuals from among the patients' relatives and hospital staff, who were nonsmokers, nondiabetics as per ADA criteria, and nonhypertensive as per Joint National Committee 8 guidelines who were included after informed consent.,
Atherogenic ratios were calculated using the indices as follows:
1. Castelli index 1: TC/HDL-c. 2. Castelli index 2: LDL-c/HDL-c. 3. Atherogenic coefficient (AC): non-HDL-c/HDL-c (non-HDL-c = TC − HDL-c). 4. TG/HDL-c. 5. Lipoprotein combine index: TC × TG × LDL-c/HDL-c.
A total of six samples were collected from each patient with ESRD before the start of peritoneal dialysis as 0 month or baseline sample followed by 3rd, 6th, 9th, 12th, and 15th months from the start of peritoneal dialysis, respectively. Five milliliters of fasting venous blood was collected in additive free tubes for biochemical investigations. The blood samples were allowed to stand for 30 min, centrifuged at 3000 rpm for 15 min, and the separated serum was stored at −80°C until further analysis. Serum TC, TG, HDL-c, albumin, and random blood sugar were estimated using commercial kits. All the above parameters were analyzed on clinical chemistry Auto analyzer Beckman Coulter DXC 600 Synchron (USA). Atherogenic ratios were calculated using the respective formulas. LDL-c and VLDL-c were calculated by Freidewald's equation.
All continuous variables were tested for normal distribution with Kolmogorov–Smirnov test. Normally distributed values were presented as mean ± standard deviation. Unpaired Student's t-test was used for comparison of means between controls and cases. Comparison of means across the groups was done by repeated measures analysis of variance (ANOVA). Statistical analysis was performed using Microsoft Excel spreadsheets and SPSS Version 22.0. A P value of <0.05 was considered statistically significant.
| Results|| |
All patients enrolled in the study are from the Department of Nephrology, Sri Venkateswara Institute of Medical Sciences. Thirty patients with ESRD and thirty controls were included in the study. The mean ± standard error of mean (SEM) of the baseline demographic data of the 30 controls and 30 patients with ESRD was done using unpaired t-test [Table 1].
|Table 1: The Mean±Sd Values Of Baseline Demographic Data In Patients With ESRD And Controls|
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The mean ± SEM of the baseline lipid parameters of the 30 controls and 30 patients with ESRD before initiation of peritoneal dialysis was performed using unpaired t-test [Table 2]. There was significant increase in serum cholesterol and LDL-c levels along with lipid ratios in patients with ESRD when compared with the controls (P = 0.001). Serum TGs and VLDL-c did not show any significant difference in patients when compared with the controls (P > 0.05). There was decrease in HDL-c levels in 30 patients with ESRD when compared with the controls but not stastically significant.
|Table 2: The Mean±Sem Values Of Lipid Profile In Patients With ESRD And Controls|
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The mean ± SEM of the atherogenic ratios of the 30 controls and 30 patients with ESRD before initiation of peritoneal dialysis was done using unpaired t-test [Table 3]. There was significant increase in lipid ratios in patients with ESRD when compared with the controls (P = 0.001). Patients with ESRD before initiation of peritoneal dialysis showed increased levels of serum TC/HDL-c, TG/HDL-c, LDL-c/HDL-c, non-HDL, and AC when compared with controls which was found to be stastically significant.
|Table 3: The Mean±Sem Values Of Atherogenic Ratios In Patients With ESRD And Controls|
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Statistical analysis using repeated measures of ANOVA for comparison of change in the mean concentrations of the lipid parameters at different time periods among patients with ESRD was performed [Table 4] and [Table 5]. All the parameters showed stastically significant change when compared with baseline values except for serum TC. At the start of CAPD, the serum concentrations of serum TG, VLDL-c, and LDL-c along with lipid ratios were increased and levels of serum TC and HDL-C were significantly decreased during 3rd and 6th months. However, after 1 year of CAPD (12th and 15th months), serum levels of VLDL-c, LDL-c, TG, and TC remained significantly higher than the baseline values and HDL-c concentration is significantly decreased than the baseline values. Box plots were plotted to show the comparison of various biochemical parameters among patients with ESRD on CAPD for 1 year and more than 1 year of CAPD [Figure 1]. The mean ± SEM values of biochemical parameters in patients with ESRD on CAPD for 1 year and more than 1 year of CAPD with the direction of change were analyzed [Table 6]. All the lipids and atherogenic ratios showed statistically significant change among patients with ESRD on CAPD for 1 year when compared with patients with ESRD on CAPD for more than 1 year of CAPD.
|Table 4: Sequential Comparison Of Serum Lipids Among Patients With ESRD In Different Time Periods Using Repeated Measures ANOVA|
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|Table 5: Sequential Comparison Of Atherogenic Ratios In Patients With ESRD At Different Time Periods Using Repeated Measures ANOVA|
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|Figure 1: Box plots showing the comparison of serum lipids among patients with ESRD on CAPD for 1 year and more than 1 year of CAPD|
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|Table 6: The Mean±Sem Values Of Serum Lipids And Atherogenic Ratios In Patients With ESRD On CAPD For 1 Year And In Patients With ESRD ON CAPD For More Than 1 Year|
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| Discussion|| |
In the present study, it was observed that patients with ESRD on CAPD had an altered lipid profile, with elevations of TC, TG, and LDL-c levels along with atherogenic ratios and decrease in HDL-c levels. The results of the present study are in accordance with those reported by others, with elevated cholesterol levels, hypertriglyceridemia, and decreased HDL-c levels in CAPD patients compared with the general population., After the first year on CAPD, the present study patients developed increased TG, VLDL-c, and LDL-c levels and decreased HDL-c levels, and an increased ratio of serum TC/HDL-c, TG/HDL-c, LDL-c/HDL-c, non-HDL-c, and AC. With these findings, it could be suggested that CAPD patients might be at greater risk from vascular disease and such lipoprotein changes have been reported to indicate an increased risk of developing atherosclerotic cardiovascular disease.
The mechanisms underlying altered lipid metabolism in CAPD patients are not completely understood. A number of factors may be important in producing. Many factors contribute to abnormal lipid metabolism and more atherogenic lipoprotein profile in CAPD patients. These differences may be attributed to PD per se and may also be associated with the modality of dialysis. Metabolically, CAPD patients differ from HD patients. Primarily, these patients have increased availability of lipoprotein substrate through glucose uptake from the peritoneal dialysis fluid, which might contribute to an increased synthesis of apoB-containing lipoproteins. The second mechanism might be related to the loss of large molecular weight substances in the peritoneal dialysis fluid. The macromolecular clearance in the peritoneal dialysate may in certain aspects be similar to that of the nephrotic syndrome and include liporegulatory substances. The decreased clearance of TGs results from reduced activity of LPL and hepatic lipase which are involved in TG removal. Excessive peritoneal glucose absorption from highly concentrated glucose-containing CAPD solutions may enhance metabolic disturbances. The increased absorption of glucose from dialysate and the loss of protein via peritoneal cavity during PD might also contribute to dyslipidemia. A reduction in cholesterol, TG, and LDL-c levels has been reported based on 6 months of treatment with icodextrin. Amino acid–based dialysate might also reduce glucose-related elevations of lipids. A reduction in serum HDL-c concentration is commonly observed because of its loss in spent dialysate. It also suggests that hyperlipidemia, which is common in CAPD patients, may not be solely attributed to the dialysate type alone. It remains to be clarified whether patients on maintenance CAPD treatment, with cluster of cardiovascular risk factors, have a more pronounced and accelerated development of subclinical atherosclerosis than HD patients with further large trials. Accordingly, limiting the amount of glucose in the PD prescription might improve the atherogenic lipoprotein profile in PD patients, as suggested by previous studies.,
| Conclusion|| |
The results of the present study conclude that serum TC, LDL-c, and atherogenic ratios were significantly higher and HDL-c was significantly lower in patients with ESRD on CAPD when compared with controls. CAPD treatment is associated with more pronounced alterations of the lipid metabolism due to peritoneal absorption of glucose. These findings may be important for selecting and monitoring the appropriate preventive measures for normalizing dyslipidemia and to reduce the risk of cardiovascular disease in patients with ESRD on CAPD.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Pennell P, Leclercq B, Delahunty MI, Walters BA. The utility of non-HDL in managing dyslipidemia of stage 5 chronic kidney disease. Clin Nephrol 2006;66:336-47.
Vaziri ND. Dyslipidemia of chronic renal failure: The nature, mechanisms, and potential consequences. Am J Physiol Renal Physiol 2006;290:F262-72.
Cofan F, Vela E, Cléries M. Collaborative Study Group for Dyslipidemia. Analysis of dyslipidemia in patients on chronic hemodialysis in Catalonia. Atherosclerosis 2006;184:94-102.
Gokal R. Taking peritoneal dialysis beyond the year 2000. Perit Dial Int 1999;19:35-43.
Steele J, Billington T, Janus E, Moran J. Lipids, lipoproteins and apolipoproteins A-I and B and apolipoprotein losses in continuous ambulatory peritoneal dialysis. Atherosclerosis 1989;79:47-50.
Borazan A, Üstün H, Yilmaz A. The effects of haemodialysis and peritoneal dialysis on serum lipoprotein (a) and C-reactive protein levels. J Int Med Res 2003;31:378-83.
Anwar N, Bhatnagar D, Short CD, Mackness MI, Durrington PN, Prais H, et al.
Serum lipoprotein (a) concentrations in patients undergoing continuousambulatory peritoneal dialysis Nephrol Dial Transplant 1993;8:71-4.
Sniderman AD, Zhang Z, Cianflone K. Divergent responses of the liver to increaseddelivery of glucose or fatty acids: Implications for the pathogenesis of type IV hyperlipoproteinemia. Atherosclerosis 1998;137:291-301.
Vaziri ND, Moradi H. Mechanisms of dyslipidemia of chronic renal failure. Hemodial Int 2006;10:1-7.
Vaziri ND, Liang K. Down-regulation of tissue lipoprotein lipase expression in experimental chronic renal failure. Kidney Int 1996;50:1928-35.
Bredie SJ, Bosch FH, Demacker PN, Stalenhoef AF, van Leusen R, et al
. Effects of peritoneal dialysis with an overnight icodextrin dwell on parameters of glucose and lipid metabolism. Perit Dial Int 2001;21:275-81.
Homma K, Homma Y, Shiina Y, Wakino S, Suzuki M, Fujishima S, et al
. Skew of plasma low- and high density lipoprotein distributions to less dense subfractions in normotriglyceridemic chronic kidney disease patients on maintenance hemodialysis treatment. Nephron Clin Pract 2013;123:41-5.
Rubinow KB, Henderson CM, Robinson-Cohen C, Himmelfarb J, de Boer IH, Vaisar T, et al
. Kidney function is associated with an altered protein composition of high-density lipoprotein. Kidney Int 2017;92:1526-35.
Kanbay M, Bavbek N, Delibasi T, Koca C, Kaya A, Altay M, et al
. Effect of peritoneal dialysis solution type on serum lipid levels in end-stage renal disease. Ren Fail 2007;29:309-13.
Shurraw S, Tonelli M. Statins for treatment of dyslipidemiain chronic kidney disease. Perit Dial Int 2006;26:523-39.
Holmes CJ. Reducing cardiometabolic risk in peritoneal dialysis patients: Role of the dialysis solution. J Diabetes Sci Technol 2009;3:1472-80.
Burkart J. Metabolic consequences of peritoneal dialysis. Semin Dial 2004;17:498-504.
Sniderman AD, Williams K, Contois JH, Monroe HM, Mcqueen MJ, de Graff J, et al
. A meta-analysis of lowdensity lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk. Circ Cardiovasc Qual Outcomes 2011;4:337-45.
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2016;31:55-60.
James PA, Oparil S, Carter BL, Cushman WC, Himmelfarb D, Handler J, et al
. 2014 evidence-based guideline for the management of high blood pressure in adults: Report from the panel members appointed to the Eighth Joint National Committee. JAMA 2014; 311:507-20.
Zhu L, Lu Z, Zhu L, Ouyang X, Yang Y, He W, et al
. Lipoprotein ratios are better than conventional lipid parameters in predicting coronary heart disease in Chinese Han people. Kardiol Pol 2015;73:931-8.
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.
Attman PO, Samuelsson O, Johansson AC Moberly JB, Laupovic P. Dialysis modalities and dyslipidemia. Kidney Int 2003;63:S110-2.
Kanbay M, Delibasi T, Kaya A, Aydogan T, Koca C, Akcay A, et al
. Effect of dialysis type on serum lipids, apolipoproteins, and lipoproteins. Renal Failure 2006;28:567-71.
Johansson AC, Samuelsson O, Attman PO, Haraldsson B, Moberly J, Knight-Gibson C, et al
. Dyslipidemia in peritoneal dialysis – Relation to dialytic variables. Perit Dial Int 2000;20:306-14.
Shoji T, Nishizawa Y, Nishitani H, Yamakawa M, Morii H. Impaired metabolism of highdensity lipoprotein in uremic patients. Kidney Int 1992;41:1653-61.
Wheeler DC, Bernard DB. Lipid abnormalities in the nephrotic syndrome: Causes, consequences, and treatment. Am J Kidney Dis 1994;23:331-46.
Delarue J, Maingourd C, Couet C, Vidal S, Bagros P, Lamisse F. Effects of oral glucose on intermediary metabolism in continuous ambulatory peritoneal dialysis patients versus healthy subjects. Perit Dial Int 1998;18:505-11.
Bredie SJ, Bosch FH, Demacker PN, Stalenhoef AF, van Leusen R. Effects of peritoneal dialysis with an overnight icodextrin dwell on parameters of glucose and lipid metabolism. Perit Dial Int 2001;21:275-81.
García-López E, Lindholm B, Davies S. An update on peritoneal dialysis solutions. Nat Rev Nephrol 2012;8:224-33.
Horkko S, Huttunen K, Laara E, Kervinen K, Kesaniemi YA. Effects of three treatment modes on plasma lipids and lipoproteins in uraemic patients. Ann Med 1994;26:271-82.
Al-Hwiesh A. Study of lipid abnormalities in patients maintained on haemodialysis or automated peritoneal dialysis in the Eastern Province of Saudi Arabia. Open Access Sci Rep 2012;1:346.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]