| Abstract|| |
Elevated levels of intact parathyroid hormone (iPTH) may play an important role in the pathogenesis of the dyslipidemia in hemodialysis (HD) patients, but the underlying mechanisms are not clearly defined. In this cross-sectional study, we examined the effects of iPTH on dyslipidemia among HD patients by analyzing the data of 51 patients (18 males and 33 females) with combined mean age 51.7 ± 18.3 years (range 22-85 years) who were on HD between April 2009 and April 2010, in the dialysis center of Imam Khomeini Hospital Complex in Iran. On enrollment, we measured lipid profile, apoprotein (apo) A, apo B, alkaline phosphatase, calcium and phosphorus and also recorded the duration that they were on HD, and evaluated the correlation of these with iPTH level using Spearman's rank analysis. The mean duration on HD was 7.07 ± 6.53 years. Except for high-density lipoprotein, there were no changes in the lipid parameters in our HD patients. We also compared lipid profile among subjects, classifying them according to their iPTH levels. There was no correlation between serum lipids and iPTH levels in these groups. A significant positive correlation was found between iPTH and alkaline phosphatase( ALP) (r = 0.333, P = 0.017) between iPTH and HD duration (r = 0.408, P = 0.003), whereas there was a significant negative correlation between iPTH and Ca (r = -0.294, P = 0.037) between iPTH and apo B (r = -0.431, P = 0.002) and between iPTH and Body Mass Index (r = -0.362, P = 0.009). In conclusion, no significant relationship between iPTH and lipids was found in the studied HD patients. These findings suggest that iPTH most probably does not play a significant role in the dyslipidemia of renal failure.
|How to cite this article:|
Ahmadi F, Mirjafari SR, Khatami MR, Khazaeipour Z, Ranjbarnovin N. Relationship between serum parathyroid hormone levels and lipid profile in non-diabetic hemodialysis patients. Saudi J Kidney Dis Transpl 2012;23:1188-95
|How to cite this URL:|
Ahmadi F, Mirjafari SR, Khatami MR, Khazaeipour Z, Ranjbarnovin N. Relationship between serum parathyroid hormone levels and lipid profile in non-diabetic hemodialysis patients. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2022 Oct 3];23:1188-95. Available from: https://www.sjkdt.org/text.asp?2012/23/6/1188/103558
| Introduction|| |
Regardless of age, heart disease is a major cause of morbidity and mortality among patients with renal failure.  The lipid profile of patients undergoing chronic hemodialysis (HD) indicates an increase in triglycerides, , elevated very low-density lipoprotein (VLDL), decreased high-density lipoprotein (HDL) , and increased lipoprotein a.  Total cholesterol levels may be lower in HD patients.  Dyslipidemia is an established cardiovascular risk factor in the general population.  In one study, dyslipidemia predicted cardiovascular disease in patients on HD.  But, other studies have reported uncertainties about this. ,
Intact parathyroid hormone (iPTH) modulates calcium (Ca) and phosphate (P) hemostasis.  Hyperparathyroidism has been found to be associated with cardiovascular disease in the general population. , However, studies in dialysis patients are controversial. ,,,, Several studies have indicated higher risk of death with increased iPTH levels, , whereas another study found no association.  Some others have reported low iPTH being related to a greater risk of adverse outcomes. ,
Dyslipidemia in renal failure patients may be due to increased synthesis, decreased catabolism or a combination of both process.  Suggested underlying mechanisms of the reduced lipolytic activity include depletion of lipoprotein lipase (LPL) stores by repeated adminstration of heparin,  the existence of LPL inhibitors in uremic plasma  and increased levels of apolipoprotein (apo) CIII. 
Although several studies have reported that hyperparathyroidism might play a role in dyslipidemia in dialysis patients, ,,, others have found no relation between dyslipidemia and PTH serum level. , Thus, the relationship between dyslipidemia and iPTH serum levels seems to be controversial. We undertook this study with the purpose to examine the relationship between lipid profile and serum levels of iPTH in chronic kidney disease(CKD) patients undergoing HD treatment.
| Materials and Methods|| |
In this cross-sectional study, 51 patients were recruited who were on dialysis between April 2009 and April 2010 in the dialysis center of Imam Khomeini Hospital Complex in Iran. The patients were dialyzed for 3-4 h, three times a week, with hollow fiber dialysers, either hemophane (GFS-20, Gambro) or polysulfone, against a dialysis bath containing 32-36 mmol/L of bicarbonate, 0.85 mmol/L of magnesium, 1.50 mmol/L of calcium and 2 mmol/L of potassium.
Subjects with the following history were excluded: diabetes mellitus, familial dyslipidemia in the first grade family member, treatment with lipid-lowering drugs, those with Body Mass Index (BMI) <30 and those on HD for acute renal failure. Diabetic patients were excluded from the study because their dyslipidemia and vascular disease are mediated via a different mechanism.
Blood samples were collected after 12 h of fasting. The blood samples were assessed for serum levels of triglyceride (enzymatic Gop-PAP method), total cholesterol (enzymatic-calorimetric CHOP-PAP method), high-density lipoprotein cholesterol (HDLC; direct enzymatic method) and low-density lipoprotein cholesterol (LDLC; calculated with Freidwald equation). All these biochemical assays were done using diagnostic kits made by Bioactiva Diagnostica (Hamburg, Germany). The levels of iPTH were measured by the Electro ChemiLuminescence Immuno Assay (ECLIA) method using Roche Elecsys PTH kits.
The purpose of this study was explained to the subjects and the investigation was carried out with their written consent.
| Statistical Analysis|| |
Descriptive and inferential statistical analysis were performed using SPSS version 16.0. Data are presented as the mean ± standard deviation. Differences were assessed using the Mann-Whitney test (non-parametric). Correlations were analyzed by Spearman's rank analysis and the coefficient of correlation was determined. A P-value of less than 0.05 was considered statistically significant.
| Result|| |
In the study population (n = 51), the mean age was 51.7 ± 18.3 years (range, 22-85 years) and 37.3% of the patients were males. The mean baseline iPTH level was 527.1 ± 528.5 pg/mL (range, 34-2377). Patients were on HD for 0.33-23.75 years, with mean of 7 year ± 6.53. Underlying renal diseases were: hypertension 14 (27.45%), glomerolonephritis 6 (11.76%), unknown causes 18 (35.29%), polycystic nephropathy 7 (13.72%), pyelonephritisinterstitial nephritis 1 (1.96%), congenital renal disease 1 (1.96%) and others 4 (7.84%).
[Table 1] shows baseline demographic and laboratory characteristics of patients. The mean serum values of TG, Chol, LDL, HDL, P, Ca, ALP, PTH, apo A and apo B in the patients are shown in [Table 2]. Patients with iPTH ≤300 had significantly lower HD duration (5.21 ± 6.03, P = 0.02) [Table 3].
|Table 2: Serum values of PTH, Ca, P, ALP, triglyceride, cholesterol, LDL, HDL, apo A, apo B in the patients on hemodialysis.|
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We compared the variables in the study population as two groups, those with iPTH levels ≤ 300 and >300 pg/mL and also ≤ 600 and > 600 pg/mL. Patients with iPTH ≤ 300 had significantly upper serum levels of apo B (mean ± SD, 0.79 ± 0.21) and had significantly lower HD duration (mean ± SD, 5.21 ± 6.03). Mean value of all variables and P-values in the two groups is shown in [Table 4].
|Table 4: Comparison of study variables in the two groups of PTH serum level.|
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A significant positive correlation was found between iPTH and ALP (r = 0.333, P = 0.017) and between iPTH and HD duration (r = 0.408, P = 0.003), whereas there was a significant negative correlation between iPTH and Ca (r = -0.294, P = 0.037), between iPTH and apo B (r = -0.431, P = 0.002) and between iPTH and BMI (r = -0.362, P = 0.009) [Table 5]. Similarly, a significant positive correlation was found between HD duration and ALP (r = 0.358, P = 0.010), whereas there was a significant negative correlation between duration of HD and Ca (r = -0.307, P = 0.029) [Table 5].
|Table 5: Correlation coefficients (r) between PTH, duration of hemodialysis and other variables(a).|
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There was no significant difference in cause of renal failure between the two groups of TG, Chol, HDL and LDL [Table 6].
|Table 6: Cause of renal failure and two groups of HDL, LDL, TG and chol.|
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| Discussion|| |
In our study, HD patients had no hypertriglyceridemia, contrary to other studies ,,, but similar to some other studies. , 94.1% of our patients had Chol ≤ 200. But, this difference, compared with patients with Chol >200, was not significant. Other lipid abnormalities in our study was low HDL level. HDL was similarly found to be low in HD patients by Pennell et al  and also in the CHOICE study.  Piperi et al  also reported significantly low HDL level in their study.
We also observed decreased levels of apo A and apo B in HD patients. In contrast, Kaysen  indicated that apo A levels were elevated in patients with kidney disease. Mean value of BMI in HD patients was 23.1 ± 3.5 kg/m 2 , with high prevalence of patients in the 20.5- 21.5 kg/m 2 group. This also has been reported in other studies. ,, This indicates increased prevalence of malnutrition in our patients according to the World Health Organization guidelines for adults. 
In contrast to some data, ,, we found a positive correlation between HD duration and ALP and a negative correlation between HD duration and serum levels of Ca. In the study of Mekke et al,  hypertriglyceridemia, increases of VLDL and reduction of LPL were correlated with HD duration. Ifudu et al  did not find any change in triglycerides and cholesterol concentrations according to increased HD duration in patients hemodialyed for 10-24 years. The increase in triglyceride and cholesterol concentrations was positively correlated with HD duration in the study of Sobh et al.  Moreover, Paragh et al  showed that TG were positively correlated with HD duration.
In experimental models of uremia, iPTH plays a role for the development of uremic hyperlipemia. Akmal et al  showed that excess iPTH in CRF patients interferes with the ability of the beta cell function to augment insulin secretion appropriately in response to the insulin-resistant state.
In this study, iPTH was found to be positively correlated with HD duration and ALP. iPTH negatively correlated with serum levels of Ca, apo B and BMI. But, iPTH did not correlate with TG, Chol, LDL, HDL, apoA and apoB, as reported in two studies. , In other reports ,,, hyperparathyroidism plays a role in dyslipidemia in HD patients. In the study of Lim et al,  serum PTH correlated inversely with HDL and apo A.
Overall, our main limitation of the study was the lack of a control group of healthy patients for comparison. However, we found that there was no relationship between iPTH and lipids in HD patients. These findings suggest that iPTH most probably does not play a significant role in the dyslipidemia of renal failure.
| References|| |
|1.||Prichard SS. Impact of dyslipidemia in endstage renal disease. J Am Soc Nephrol 2003;14(9 Suppl 4):S315-20. |
|2.||Attman PO, Samuelsson O, Alaupovic P. Lipoprotein metabolism and renal failure. Am J Kidney Dis 1993;21:573-92. |
|3.||Bagdade JD, Porte D Jr, Bierman EL. Hypertriglyceridemia. A metabolic consequence of chronic renal failure. N Engl J Med 1968;279: 181-5. |
|4.||Nestel PJ, Fidge NH, Tan MH. Increased lipoprotein-remnant formation in chronic renal failure.N Engl J Med 1982;307:329-33. |
|5.||Nishizawa Y, Shoji T, Emoto M, et al. Reduction of intermediate density lipoprotein by pravastatin in hemo- and peritoneal dialysis patients. Clin Nephrol 1995;43:268-77. |
|6.||Iseki K, Yamazato M, Tozawa M, Takishita S. Hypocholesterolemia is a significant predictor of death in a cohort of chronic hemodialysis patients. Kidney Int 2002;61:1887-93. |
|7.||Kwan BC, Kronenberg F, Beddhu S, Cheung AK. Lipoprotein metabolism and lipid management in chronic kidney disease. J Am Soc Nephrol 2007;18:1246-61. |
|8.||Hunninghake DB, Stein EA, Mellies MJ. Effects of one year of treatment with pravastatin, an HMG-CoA reductase inhibitor, on lipoprotein A. J Clin Pharmacol 1993;33:574-80. |
|9.||Tonelli M, Moyé L, Sacks FM, Kiberd B, Curhan G; Cholesterol and Recurrent Events (CARE) Trial Investigators. Pravastatin for secondary prevention of cardiovascular events in persons with mild chronic renal insufficiency. Ann Intern Med 2003;138:98-104. |
|10.||Wanner C, Krane V, März W, et al; German Diabetes and Dialysis Study Investigators. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 2005;353:238-48. |
|11.||Kronenberg HM, Brinkhurst FR, Nussbaum S et al. Parathyroid hormone: biosynthesis, secretion, chemistry and action. In: Mundy GR, Martin TJ, eds. Handbook of Experimental Pharmacology of Bone. Heidelberg, Germany: Springer; 1993. p. 185-201. |
|12.||Hedbäck G, Odén A. Increased risk of death from primary hyperparathyroidism--an update. Eur J Clin Invest 1998;28:271-6. |
|13.||Nilsson IL, Yin L, Lundgren E, Rastad J, Ekbom A. Clinical presentation of primary hyperparathyroidism in Europe-nationwide cohort analysis on mortality from nonmalignant causes. J Bone Miner Res 2002;17 Suppl 2: N68-74. |
|14.||Tentori F, Blayney MJ, Albert JM, et al. Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: The Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 2008;52:519-30. |
|15.||Young EW, Albert JM, Satayathum S, et al. Predictors and consequences of altered mineral metabolism: the Dialysis Outcomes and Practice Patterns Study. Kidney Int 2005;67:1179-87. |
|16.||Noordzij M, Korevaar JC, Boeschoten EW, Dekker FW, Bos WJ, Krediet RT; Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) Study Group. The Kidney Disease Outcomes Quality Initiative (K/DOQI) Guideline for Bone Metabolism and Disease in CKD: association with mortality in dialysis patients. Am J Kidney Dis 2005;46: 925-32. |
|17.||Avram MM, Mittman N, Myint MM, Fein P. Importance of low serum intact parathyroid hormone as a predictor of mortality in hemodialysis and peritoneal dialysis patients: 14 years of prospective observation. Am J Kidney Dis 2001;38:1351-7. |
|18.||Guh JY, Chen HC, Chuang HY, Huang SC, Chien LC, Lai YH. Risk factors and risk for mortality of mild hypoparathyroidism in hemodialysis patients. Am J Kidney Dis 2002;39:1245-54. |
|19.||Blankestijn PJ, Vos PF, Rabelink TJ, van Rijn HJ, Jansen H, Koomans HA. High-flux dialysis membranes improve lipid profile in chronic hemodialysis patients. J Am Soc Nephrol 1995;5:1703-8. |
|20.||Eckel RH. Lipoprotein lipase. A multifunctional enzyme relevant to common metabolic diseases. N Engl J Med 1989;320:1060-8. |
|21.||Murase T, Cattran DC, Rubenstein B, Steiner G. Inhibition of lipoprotein lipase by uremic plasma, a possible cause of hypertriglyceridemia. Metabolism 1975;24:1279-86. |
|22.||Staprans I, Felts JM, Zacherle B. Apoprotein composition of plasma lipoproteins in uremic patients on hemodialysis. Clin Chim Acta 1979;93:135-43. |
|23.||Zanos S, Mitsopoulos E, Sakellariou G. Parathyroid hormone levels, calcium-channel blockers, and the dyslipidemia of nondiabetic hemodialysis patients. Ren Fail 2005;27:163-9. |
|24.||Lim PS, Hung TS, Yeh CH, Yu MH. Effects of treatment of secondary hyperparathyroidism on the lipid profile in patients on hemodialysis. Blood Purif 1998;16:22-9. |
|25.||Lacour B, Roullet JB, Liagre AM, et al. Serum lipoprotein disturbances in primary and secondary hyperparathyroidism and effects of parathyroidectomy. Am J Kidney Dis 1986;8:422-9. |
|26.||Heuck CC, Ritz E. Does parathyroid hormone play a role in lipid metabolism? Contrib Nephrol 1980;20:118-28. |
|27.||Navarro JF, Teruel JL, Lasunción MA, Mora-Fernandez C, Ortuño J. Relationship between serum parathyroid hormone levels and lipid profile in hemodialysis patients. Evolution of lipid parameters after parathyroidectomy. Clin Nephrol 1998;49:303-7. |
|28.||Monzani G, Bergesio F, Ciuti R, et al. Lipoprotein abnormalities in chronic renal failure and dialysis patients. Blood Purif. 1996;14: 262-72. |
|29.||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. |
|30.||Maheshwari N, Ansari MR, Laghari MS, Darshana, Lal K, Ahmed K. Pattern of lipid profile in patients on maintenance hemodialysis. Saudi J Kidney Dis Transpl 2010;21: 565-70. |
|31.||Liu Y, Coresh J, Eustace JA, et al. Association between cholesterol leveland mortality in dialysis patients: role of inflammation and malnutritio. JAMA 2004;291:451-9. |
|32.||Longenecker JC, Coresh J, Powe NR, et al. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: The CHOICE Study. J Am Soc Nephrol 2002;13:1918-27. |
|33.||Piperi C, Kalofoutis C, Tzivras M, Troupis T, Skenderis A, Kalofoutis A. Effects of hemodialysis on serum lipids and phospholipids of end-stage renal failure patients. Mol Cell Biochem 2004;265:57-61. |
|34.||Kaysen GA. Hyperlipidemia in chronic kidney disease. Int J Artif Organs 2007;30:987-92. |
|35.||Bednarek-Skublewska A, Baranowicz-Gaszczyk I, JóŸwiak L, Dzik M, Majdan M, Ksiazek A. Comparison of some nutritional parameters in hemodialysis patients over and below 65 years of age. Pol Arch Med Wewn 2005;113:417-23. |
|36.||Basaleem HO, Alwan SM, Ahmed AA, Al-Sakkaf KA. Assessment of the nutritional status of end-stage renal disease patients on maintenance hemodialysis. Saudi J Kidney Dis Transpl 2004;15:455-62. |
|37.||Physical status: The use and interpretation of anthropometry. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser 1995;854:1-452. |
|38.||Sentí M, Romero R, Pedro-Botet J, Pelegrí A, Nogués X, Rubiés-Prat J. Lipoprotein abnor malities in hyperlipidemic and normolipidemic men on hemodialysis with chronic renal failure. Kidney Int 1992;41:1394-9. |
|39.||Elisaf MS, Bairaktari HT, Tziallas CS, Germanos NK, Siamopoulos KC. Atherogenic lipid and lipoprotein parameters in hemodialysis patients. Dial Trans 1995;24:642-60. |
|40.||Ponticelli C, Barbi G, Cantaluppi A, Donati C, Annoni G, Brancaccio D. Lipid abnormalities in maintenance dialysis patients and renal transplant recipients. Kidney Int Suppl 1978; 8:S72-8. |
|41.||Mekki K, Prost J, Remaoun M, Belleville J, Bouchenak M. Long term hemodialysis aggravates lipolytic activity reduction and very low density, low density lipoproteins composition in chronic renal failure patients. BMC Cardiovasc Disord 2009;9:41. |
|42.||Ifudu O, Brezsnyak WF, Reydel C, et al. Pathobiology and functional status of longterm hemodialysis patients. Am J Nephrol 1995;15:379-85. |
|43.||Sobh MA, Shamaa SA, el-Gayar AM, el-Sharabacy MM. Hyperlipidaemia in uraemic patients under chronic haemodialysis. Correlation with serum lipoprotein lipase and insulin levels. Int Urol Nephrol 1989;21:667-74. |
|44.||Paragh G, Balogh Z, Matyus J, et al. Lipid abnormalities in uraemic patients on chronic haemodialysis. Acta Med Hung. 1992-1993;49 (3-4):207-17. |
Research Department, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Keshavarz bulvar, Tehran
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]