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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2008  |  Volume : 19  |  Issue : 2  |  Page : 183-188
Effect of Sevelamer on Mineral and Lipid Abnormalities in Hemodialysis Patients

Department of Nephrology, Charles Nicolle Hospital, Tunis, Tunisia

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We conducted a prospective study in hemodialysis patients to assess the safety and efficacy of sevelamer, a non-absorbable phosphate binding polymer free of calcium and aluminum, in lowering serum phosphorus, serum intact parathyroid hormone, and serum lipids. Phosphate binders were discontinued during a two-week washout period. We considered the patients with serum phosphorus levels more than 1.8 mmol/l during the washout period eligible for treatment. Sevelamer was administered to 29 hemodialysis patients for eight weeks. Sevelamer reduced the mean serum phosphorus levels to 1.8 mmol/l by the end of the eight-week treatment period (p < 0.0001). Two weeks after the completion of the sevelamer study the mean serum phosphorus levels increased to 2.09 mmol/l (p < 0.02). Mean serum calcium levels did not significantly change during sevelamer trial. Mean serum intact parathyroid hormone declined from 501 pg/ml at the start of the study to 425 pg/l at the end of the eight week treatment period (p = 0.05). In addition, sevelamer reduced the mean serum total cholesterol levels from 5.22 mmol/l to 4.26 mmol/l (p < 0.0001), and the mean serum low density lipoprotein cholesterol from 3.56 mmol/l to 2.79 mmol/l (p < 0.0001) at the end of the study. However, the mean serum levels of high density lipoprotein and triglycerides did not change during the study period. We conclude that sevelamer can control serum phosphorus and reduce the level of intact parathyroid hormone and cholesterol without inducing hypercalcemia or other side effects.

Keywords: Renal failure, hyperphophatemia, phosphate binder, sevelamer, serum cholesterol

How to cite this article:
Hamida FB, Fatma LB, Barbouch S, Kaaroud H, Helal I, Hedri H, Abdallah TB, Maiz HB, Kheder A. Effect of Sevelamer on Mineral and Lipid Abnormalities in Hemodialysis Patients. Saudi J Kidney Dis Transpl 2008;19:183-8

How to cite this URL:
Hamida FB, Fatma LB, Barbouch S, Kaaroud H, Helal I, Hedri H, Abdallah TB, Maiz HB, Kheder A. Effect of Sevelamer on Mineral and Lipid Abnormalities in Hemodialysis Patients. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2022 Aug 18];19:183-8. Available from: https://www.sjkdt.org/text.asp?2008/19/2/183/39027

   Introduction Top

Patients with advanced Chronic Kidney Disease (CKD) usually develop hyperphos­phatemia, which is associated with severe complications such as secondary hyperpara­thyroidism and metastatic calcifications. [1]

To decrease the absorption of the dietary phosphorus load, patients with advanced CKD are prescribed phosphorus-restricted diets, which is usually insufficient and most patients require phosphate binders to control the serum phosphorus levels. [1],[2]

Aluminum salts are effective phosphate binders, however, aluminum accumulates in the tissues of CKD patients, and it is asso­ciated with significant toxicity. [3],[4] Calcium salts are also effective as phosphate binders, however, calcium can lead to hypercalcemia as well as soft tissue calcification in some patients. [5],[6]

Sevelamer, a cross-linked poly allylamine hydrochloride, is a non-absorbable calcium­and aluminum-free phosphate binder. Seve­lamer binds preferentially to trivalent anions, such as phosphate and citrate. It also binds bile acids, which results in improved fecal bile acid excretion and lower low density lipo­protein (LDL) cholesterol serum levels. [7],[8]

In this study, we evaluate the safety and efficacy of sevelamer to decrease serum phosphorus (sPho) and serum intact para­thyroid hormone (PTH), and improve the serum lipid profile in hemodialysis patients.

   Patients and Methods Top

The study included chronic hemodialysis patients, 18 years of age or older, and on therapy for a minimum of three months with adequate dialysis prescription. Inclusion crite­ria required stable dosage of calcium-based phosphate binder and vitamin D supple­mentation for at least one month. Over the course of the study, patients were strongly advised not to consume antacids that contained aluminum or magnesium and to avoid inten­tional changes in diet. After initial screening of the patients, we discontinued the calcium phosphate binders, vitamin D, fibrates, and statins followed by a two-week washout period (week 1 and 2 of the study). Patients who increased their serum phosphorus levels to > 1.8 mmol/l during this washout period were eligible to receive sevelamer for eight weeks (weeks 3 to 10 of the study). To establish that serum phosphorus control was due to sevelamer treatment, the levels of the phosphorus and calcium were checked after discontinuation of the drug (week 11 to 12 of the study).

Sevelamer was administered as 800 mg tablets. The starting dose was two, three, or four tablets three times per day with meals based on the washout serum phosphorus levels (WSPL): two tablets if WSPL ranged from 1.8-2.2 mmol/l, three tablets if WSPL ranged from 2.3- 2.7 mmol/l, and four tablets if WSPL was > 2.8 mmol/l. The sevelamer dose could be increased one tablet per meal (three tablets per day) every two weeks as necessary to achieve serum phosphorus level < 1.8 mmol/l. Blood samples were collected every two weeks prior to dialysis after the longest interdialytic interval. All samples were analyzed at Charles Nicolle hospital laboratory using standard clinical laboratory methods. Intact PTH was measured by immunologic assay (upper limit of normal was 65 pg/ml). Each patient was interviewed seven times during the 12 weeks of the study: every two weeks after the collection of blood samples.

   Statistical Methods Top

Comparisons between groups were per­formed using non paired Student's "t" test for continuous variables. P values of < 0.05 were considered significant.

   Results Top

A total of 44 patients qualified initially for study. However, post-baseline serum phos­phorus data were not available for 14 patients.

In addition 1 patient did not complete the eight-week treatment period due to the occurrence of weakness. Only 29 patients completed the eight-week treatment period. [Table - 1] summarizes the demographic charac­teristics of the study patients. No serious adverse events occurred during the study. Only 1 patient discontinued sevelamer because a complaint of weakness. There was no evidence that sevelamer treatment was associated with any adverse effects.

[Figure - 1] displays the mean sPho throughout the study. The mean sPho levels increased from 2.15 ± 0.51 mmol/l at pre-washout to 2.35 ± 0.49 mmol/l after washout. Upon initia­tion of sevelamer treatment, the mean sPho levels declined immediately to 1.8 ± 0.38 mmol/l, and maintained this effect until the discontinuation of the drug at week 10 (p < 0.0001). Two weeks after the discontinuation of sevelamer, the post treatment washout period, the mean sPho significantly increased to 2.09 ± 0.54 mmol/l (p < 0.02), establishing that sPho control was most likely due to sevelamer treatment. [Figure - 1] also displays the mean serum calcium (sCa) levels during the study. The mean sCa levels remained not significantly different from the starting mean levels of 2.31 ± 0.3 mmol/l throughout the period of sevelamer intake. However, it dec­lined after discontinuing sevelamer to 2.22 ± 0.25 mmol/l (p < 0.04). The mean calcium­phosphorus product decreased from 5.45 mmol 2 /L 2 after the initial washout period to 4.14 mmol 2 /L 2 after eight weeks of sevelamer treatment.

The mean serum intact PTH levels over the course of the study are displayed in [Figure - 2]. Mean serum intact PTH levels increased during the washout period from 442 pg/ml to 501 pg/ml (p <0.03). After the initiation of sevelamer treatment, the mean serum intact PTH levels declined immediately, reaching 425 pg/ml by the end of the eight-week treatment period (p=0.05). Two weeks after the discontinuation of sevelamer, the mean serum intact PTH increased to 596 pg/ml (p < 0.03).

[Figure - 3] shows that sevelamer treatment significantly reduced the mean serum total cholesterol from 5.22 ± 0.96 mmol/l to 4.26 ± 0.87 mmol/l after eight weeks of treatment (P < 0.0001), primarily because of the decrease of the mean LDL from 3.56 ± 0.63 mmol/l to 2.79 ± 0.83 mmol/l (p < 0.0001). However, the mean high-density lipoprotein (HDL) cholesterol and triglycerides did not change during the study.

   Discussion Top

Our results demonstrate that sevelamer significantly reduced serum phosphorus in hemodialysis patients. Mean serum phos­phorus significantly decreased during eight weeks of sevelamer treatment and there was a significant rebound two weeks after the dis­continuation of the drug establishing that the observed lowered mean serum phosphorus levels was due to sevelamer treatment.

The onset of sevelamer efficacy was rapid. The initial prescribed sevelamer dose of two, three, or four tablets three times a day with meals substantially reduced serum phosphorus levels within two weeks. Titration of the drug after two and four weeks of treatment led to further reductions.

Despite the fact that calcium carbonate and vitamin D were discontinued during the washout period, serum calcium did not decrease. Serum calcium levels remained stable after completion of sevelamer treat­ment. Several factors could explain this absence of decrease of the mean serum calcium. First, lowering the serum phos­phorus with sevelamer could have corrected the high calcium phosphorus product leading to less precipitation of serum calcium. [9] Second, lowering serum phosphorus might have improved the calcemic response to PTH. [10] Third, intestinal phosphate binding by sevelamer could have increased the intestinal absorption of calcium.

Because sevelamer is a calcium-free drug, physicians should be able to prescribe calci­triol with less frequent episodes of hyper­calcemia, which is a hindering adverse effect during the treatment of hyperpara­thyroid CKD patients with a combination of calcium based phosphate binder and calcitriol. [11] Furthermore, the recent treatment of secondary hyperparathyroidism with calcimimetics decreased serum calcium levels, which may decrease the incidence of hypercalcemia secondary to the use of calcium based binders. [12],[13]

Serum intact PTH levels significantly decreased during sevelamer treatment. This decline was anticipated because serum calcium and phosphorus are known to regulate PTH secretion. [14] As expected, the increase in serum phosphorus during the washout period prompted a corresponding increase of intact PTH.

The currently pharmaceutical form of seve­lamer, sevelamer hydrochloride, is accom­panied by a reduction in serum levels of bicarbonate in some patients. [15],[16] To minimize the possibility of this effect, a new salt form of sevelamer has been developed in which carbonate replaces the chloride ion. [17]

Sevelamer treatment reduced both serum total cholesterol and LDL cholesterol. [18] How­ever, sevelamer treatment did not affect HDL cholesterol and triglycerides. The cholesterol­ lowering effect of sevelamer is probably caused by bile acid binding. Increased fecal excretion of bile acids leads to LDL receptor up-regulation in the liver similar to the mechanism of action of the lipid-lowering drugs cholestyramine and colestipol. This side-effect may prove to be beneficial in dialysis patients, who may have atherogenic lipid profiles and/or may suffer from athero­sclerosis, a major cause of morbidity and mortality in this population. [19],[20],[21]

We conclude that sevelamer, a non absor­bable aluminum and calcium-free phosphate binder, safely and effectively reduced serum phosphorus in dialysis patients. Sevelamer was well tolerated without hypercalcemia episodes. In addition, it significantly decreased serum intact PTH, and reduced total and LDL cholesterol. This phosphate binder may great potential in the management of CKD patients.

   References Top

1.Delmez JA, Slatopolsky E. Hyperphosphatemia: Its consequences and treatment in patients with chronic renal disease. Am J Kidney Dis 1992;19(4):303-17.  Back to cited text no. 1    
2.Ross Morton, Hercz G, Coburn JW. Control of hyperphosphatemia in chronic renal failure. Semin Dial 1990;4:219-23.  Back to cited text no. 2    
3.Hercz G, Goburn JW. Prevention of phosphate retention and hyperphosphatemia in uremia. Kidney Int Suppl 1987;22:S215-20.  Back to cited text no. 3    
4.Alfrey AC. Aluminium toxicity in patients with chronic renal failure. Ther Drug Monit 1993;15(6):593-7.  Back to cited text no. 4    
5.Ramirez JA, Emmett M, White MG, et al. The absorption of dietary phosphorus and calcium in hemodialysis patients. Kidney Int 1986;30(5):753-9.  Back to cited text no. 5    
6.Sperschneider H, Gunther K, Marzoll I, Kirchner E, Stein G. Calcium carbonate (CaCO3): An efficient and safe phosphate binder in haemodialysis patients? A 3-year study. Nephrol Dial Transplant 1993;8(6):530­-4.  Back to cited text no. 6    
7.Burke SK, Slatopolsky EA, Goldberg DI. Renagel®, a novel calcium-and aluminium free phosphate binder, inhibits phosphate absorption in normal volunteers. Nephrol Dial Tranplant 1997;12(8):1640-4.  Back to cited text no. 7    
8.Slatopolsky EA, Burke SK, Dillon MA. Renagel®, a nonabsorbed calcium and aluminium-free phosphate binder, lowers serum phosphorus and parathyroid hormone. Kidney Int 1999;55(1):299-307.  Back to cited text no. 8    
9.Katz AI, Hampers CL, Merrill JP. Secondary hyperparathyroidism and renal osteodystrophy in chronic renal failure. Medicine 1969;48 (5):333-74.  Back to cited text no. 9    
10.Rodriguez M, Martin-Malo A, Martinez MD, Torres A, Felsenfeld AJ, Llac F. Calcemic response to parathyroid hormone in renal failure: Role of phosphorus and its effects on calcitriol. Kidney Int 1991;40 (6):1055-62.  Back to cited text no. 10    
11.Salusky IB, Goodman WG, Sahney S, et al. Sevelamer controls parathyroid hormone­induced bone disease as efficiently as calcium carbonate without increasing serum calcium levels during therapy with active vitamin D sterols. J Am Soc Nephrol 2005; 16(8):2501-8.  Back to cited text no. 11    
12.Moe SM, Chertow GM, Coburn JW, et al. Achieving NKF-K/DOQI TM bone metabolism and disease treatment goals with cinacalcet HCI. Kidney Int 2005;67(2):760-71.  Back to cited text no. 12    
13.Moe SM, Cunningham J, Bommer J, et al. Long-term treatment of secondary hyper­parathyroidism with the calcimimetic cinacalcet HCI. Nephrol Dial Transplant 2005;20(10):2186-93.  Back to cited text no. 13    
14.Coburn JW, Slatopolsky E. Vitamin D, parathyroid hormone and renal osteodystrophy. In the Kidney (4 th ed), edited by Brenner BM, Rector FCJ R , Philadelphia, Saunders 1991:2036-122.  Back to cited text no. 14    
15.Sonikian MA, Pani IT, Iliopoulos AN, Koutala KG, Marioli SI, Vlassopoulos DA. Metabolic acidosis aggravation and hyper­kaliemia in hemodialysis patients treated by sevelamer hydrochloride. Ren Fail 2005; 27(2):143-7.  Back to cited text no. 15    
16.Brezina B, Qunibi WY, Nolan CR. Acid loading during treatment with sevelamer hydrochloride: Mechanisms and clinical implications. Kidney Int 2004;66(Suppl 90):S39-45.  Back to cited text no. 16    
17.Duggal A, Hanus M, Zhorov E, et al. Novel dosage forms and regimens for sevelamer­based phosphate binders. J Ren Nutr 2006; 16(3):248-52.  Back to cited text no. 17    
18.Yamada K, Fujimoto S, Tokura T, et al. Effect of sevelamer on dyslipidemia and chronic inflammation in maintenance hemodialysis patients. Ren Fail 2005;27(4):361-5.  Back to cited text no. 18    
19.Bomer J, Stroheck E, Goerich J, Babner M, Zuna I. Arteriosclerosis in dialysis patients. Int J Artif Organs 1996;19(11):638-44.  Back to cited text no. 19    
20.United States Renal Data System: USRDS 1997 Annual Report. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Disease, Bethesda, MD, 1997:93.  Back to cited text no. 20    
21.Ferramosca E, Burke S, Chasan-Taber S, Ratti C, Chertow GM, Raggi P. Potential antiatherogenic and anti-inflammatory properties of sevelamer in maintenance hemodialysis patients. Am Heart J 2005; 149(5):820-5.  Back to cited text no. 21    

Correspondence Address:
Fethi Ben Hamida
Department of Nephrology, Charles Nicolle Hospital, Tunis
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Source of Support: None, Conflict of Interest: None

PMID: 18310864

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  [Figure - 1], [Figure - 2], [Figure - 3]

  [Table - 1]

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