Year : 2008 | Volume
: 19 | Issue : 2 | Page : 183--188
Effect of Sevelamer on Mineral and Lipid Abnormalities in Hemodialysis Patients
Fethi Ben Hamida, Lilia Ben Fatma, Samia Barbouch, Hayet Kaaroud, Imed Helal, Hafedh Hedri, Taieb Ben Abdallah, Hedi Ben Maiz, Adel Kheder
Department of Nephrology, Charles Nicolle Hospital, Tunis, Tunisia
Fethi Ben Hamida
Department of Nephrology, Charles Nicolle Hospital, Tunis
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.
|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;19:183-188
|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 Jun 27 ];19:183-188
Available from: https://www.sjkdt.org/text.asp?2008/19/2/183/39027
Patients with advanced Chronic Kidney Disease (CKD) usually develop hyperphosphatemia, which is associated with severe complications such as secondary hyperparathyroidism and metastatic calcifications. 
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. ,
Aluminum salts are effective phosphate binders, however, aluminum accumulates in the tissues of CKD patients, and it is associated with significant toxicity. , Calcium salts are also effective as phosphate binders, however, calcium can lead to hypercalcemia as well as soft tissue calcification in some patients. ,
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. ,
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
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 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 phosphorus 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  Second, lowering serum phosphorus might have improved the calcemic response to PTH.  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.  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. ,
Serum intact PTH levels significantly decreased during sevelamer treatment. This decline was anticipated because serum calcium and phosphorus are known to regulate PTH secretion.  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. , To minimize the possibility of this effect, a new salt form of sevelamer has been developed in which carbonate replaces the chloride ion. 
Sevelamer treatment reduced both serum total cholesterol and LDL cholesterol.  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. ,,
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.
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