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product showed no significant change by

sevelamer in either the VD(+) subgroup of patients receiving hemodialysis with








dialysate calcium of 2.5 mEq/L (DCa2.5) or


those receiving hemodialysis with dialysate
calcium of 3.0 mEq/L (DCa3.0), while serum
phosphorus and calcium-phosphate product
decreased in both the VD(-) subgroups.

Serum calcium decreased in the DCa2.5


subgroup and did not change in the DCa3.0
subgroup in both the VD(+) and the VD(-)
subjects. PTH and alkaline phosphatase

increased in the DCa2.5 subgroup and did


not change in the Ca 3.0 subgroup in the

VD(+) subjects. Serum calcium decreased in both subgroups in the VD(-) subjects. PTH obtained after sevelamer administration in the VD(-) group was within the target range of the K/DOQI guidelines. In conclusion, the concomitant use of sevelamer as a

phosphate binder and the dialysate of
calcium concentration of 2.5 mEq/L have

possibilities for worsening SHPT in patients receiving intravenous vitamin D.

Ogata H, Koiwa F, Shishido K, et al.
Combination therapy with sevelamer

hydrochloride and calcium

carbonate in Japanese patients with long-term hemodialysis: Alternative approach for optimal mineral

management. Therapeutic


Apheresis & Dialysis. Vol. 9(1)(pp 11-15), 2005.

We evaluated the effects of combination therapy with sevelamer and calcium

carbonate (CaCO3) on mineral metabolism
in Japanese hemodialysis patients, as an
alternative form of P management. A total of
210 hemodialysis patients were enrolled,

and were given a small dose of sevelamer (0.75-1.5 g/day) on CaCO3 treatment.

Sevelamer dose was gradually increased, while CaCO3 decreased during 24 weeks. Five patients discontinued sevelamer

treatment because of severe constipation, anorexia, and parathyroidectomy for severe SHPT. After 24 weeks, the dose of

sevelamer was significantly increased to

3.29 g/day (initial dose: 1.47 g/day), while


CaCO3 was decreased by 54%. Adjusted
serum Ca significantly decreased (9.63 +/-

0.57-9.45 +/- 0.67 mg/dL; P = 0.0012),


although serum P increased (5.89 +/- 1.32-

6.25 +/- 1.32 mg/dL; P = 0.017). Serum


intact PTH (iPTH) significantly increased in
patients with a low or normal iPTH level
(≤300 pg/mL), while it did not change in
patients with SHPT (>300 pg/mL). The
results suggest that the therapeutic regimen is more tolerant and reduces Ca load in

Japanese hemodialysis patients while


avoiding hypocalcemia. In addition, the

mitigated Ca overload could improve PTH


hyposecretion in patients with adynamic
bone disease, which is associated with soft
tissue calcification and higher mortality in
uremia.

Sturtevant JM, Hawley CM, Reiger K, et al.


Efficacy and side-effect profile of

sevelamer hydrochloride used in combination with conventional

phosphate binders. Nephrology. Vol. 9(6) (pp 406-413), 2004.

Dialysis patients meeting the following


inclusion criteria participated in this study: (i)
hyperphosphataemia >1.8 mmol/L (5.6
mg/dL); and (ii) an inability to tolerate
currently available binders. The trial was
conducted in three phases each lasting 3
months: (i) an observation phase (patients
continued on their regular phosphate
binders); (ii) a titration phase (sevelamer
was added at a dose of 403 mg three times
daily with meals, titrated to a maximum of
1209 mg three times daily); and (iii) a
maintenance phase. Results: Twenty-five
patients were recruited into the study.
Eighteen patients completed all three trial
phases. Mean serum phosphate dropped
from 2.11 +/- 0.06 mmol/L (6.6 +/- 0.2
mg/dL) during the observation period to 1.91
+/- 0.01 mmol/L (5.9 +/- 0.003 mg/dL) during
the maintenance phase (P = 0.02). calcium-
phosphate product fell from 5.49 +/- 0.17
mmol2/L2 (68.64 +/- 2.11 mg2 dL2) to 4.89 +/-

0.27 mmol2/L2 (61.36 +/- 3.35 mg2 dL 2) (P =

0.02). There was no significant change in serum calcium or PTH. Total serum

cholesterol fell from 3.8 mmol/L (3.4-4.37)


147 mg/dL (131-169) to 3.55 mmol/L (2.97-

4.2) 137 mg/dL (115-162) (P = 0.02). Serum


low-density lipoprotein cholesterol also fell
significantly from 1.67 +/- 0.10 mmol/L (65
+/- 4 mg/dL) to 1.52 +/- 0.11 mmol/L (59 +/-

4 mg/dL) (P = 0.04). The average prescribed dose of sevelamer was 2.4 g/day. Elemental calcium dropped from 3.4 g/day (1.4 to 4.6) to 1.2 g/day (0.6-2.4) (P = 0.04). Seventy-


two per cent of patients reported mild

flatulence, nausea and indigestion. Three


patients discontinued treatment because of
adverse effects. Conclusions: Sevelamer in
combination with conventional phosphate






binders is effective in lowering serum phosphate and calcium-phosphate product in patients with refractory

hyperphosphataemia. Beneficial effects on lipid profile were also observed. Mild

gastrointestinal upset is common.


Braun J, Asmus H-G, Holzer H, et al.
Long-term comparison of a calcium-

free phosphate binder and calcium carbonate - Phosphorus metabolism and cardiovascular calcification.

Clinical Nephrology. Vol. 62(2)(pp 104-115), 2004.

114 adult hemodialysis patients were


randomly assigned to open label sevelamer
or CaCO3 for 52 weeks. Study efficacy
endpoints included changes in serum
phosphorus, calcium, calcium-phosphate
product, and lipids. In addition, initial and
sequential electron beam computerized
tomography scans were performed to
assess cardiovascular calcification status
and change during follow-up. Safety
endpoints were serum biochemistry, blood
cell counts and adverse events. Results:
Patients receiving sevelamer had a similar
reduction in serum phosphorus as patients
receiving CaCO3 (sevelamer -0.58 +/- 0.68
mmol/l, CaCO3 -0.52 +/- 0.50 mmol/l; p =

0.62). Reductions in calcium-phosphate


product were not significantly different

(sevelamer -1.4 +/- 1.7 mmol2/12, CaCO3 -

0.9 +/- 1.2 mmol2/12; p = 0.12). CaCO3
produced significantly more hypercalcemia
(> 2.8 mmol/l in 0% sevelamer and 19%
CaCO3 patients, p < 0.01) and suppressed
intact PTH below 150 pg/ml in the majority
of patients. Sevelamer patients experienced
significant (p < 0.01) reductions in total (-1.2
+/- 0.9 mmol/1, -24%) and LDL cholesterol (-

1.2 +/- 0.9 mmol/1, -30%). CaCO3 patients had significant increases in coronary artery (median +34%, p < 0.01) and aortic

calcification (median +32%, p < 0.01) that
were not observed in sevelamer-treated
patients. Patients on sevelamer required
more grams of binder (sevelamer 5.9 g vs.
CaCO3 3.9 g) and experienced more

dyspepsia than patients on calcium


carbonate. Conclusions: Sevelamer is an effective phosphate binder that unlike
calcium carbonate is not associated with progressive cardiovascular calcification in hemodialysis patients.
Shaheen FA, Akeel NM, Badawi LS, et al.
Efficacy and safety of sevelamer.

Comparison with calcium carbonate in the treatment of

hyperphosphatemia in hemodialysis patients. Saudi Medical Journal. Vol. 25(6) (pp 785-791), 2004.

Due to race differences we performed a


short-term study on the Saudi hemodialysis patients and compared sevelamer with a
standard calcium-based phosphate binder. Methods: An open-label, randomized, cross-
over study was performed to evaluate the safety and effectiveness of sevelamer
hydrochloride in controlling

hyperphosphatemia in hemodialysis


patients. After a 2-week phosphate binder
washout period, stable hemodialysis
patients were given either sevelamer or
calcium carbonate, and the dosages were
titrated to achieve phosphate control over an
8-week period. After a 2-week washout
period, patients crossed over to the alternate
agent for 8 weeks. Twenty patients from the
Dialysis Unit of King Fahd Hospital, Jeddah,
Kingdom of Saudi Arabia, were recruited for
the study between March 2003 and June
2003. Results: There was a similar decrease
in serum phosphate values over the course
of the study with both sevelamer (-3.3 +/-

2.2 mg/dL) and calcium carbonate (-3.9 +/-

2.8 mg/dL). Fifty-two percent of patients
developed serum calcium greater than 2.75 mmol/L (11.0 mg/dL) while receiving calcium carbonate versus 26% of patients receiving sevelamer (p<0.05). The incidence of
hypercalcemia for sevelamer was not
different from the incidence of

hypercalcemia during the washout period. Patients treated with sevelamer also

sustained a 13% mean decrease in serum cholesterol levels. Conclusion: Sevelamer was effective in controlling

hyperphosphatemia without resulting in an increase in the incidence of hypercalcemia seen with calcium carbonate. This agent appears quite effective in the treatment of hyperphosphatemia in hemodialysis

patients, and its usage may be

advantageous in the treatment of dialysis patients.

Almirall J, Lopez T, Vallve M, et al.
Safety and efficacy of sevelamer in

the treatment of uncontrolled hyperphosphataemia of








haemodialysis patients. Nephron Clinical Practice. Vol. 97(1)(pp c17-


c22), 2004.

We identified 34 patients with a maintained serum phosphorus concentration >6.5 mg/dl and/or toxicity related to standard

phosphorus-binding treatment (aluminium or
calcium based). Sevelamer was added and
titrated up fortnightly to achieve phosphorus
control. Previous phosphate binders were
decreased, whenever possible. The period
of the study was 6 months. Results: Thirteen
patients (38%) dropped out because of side
effects, mainly related to the gastro-

intestinal tract. The efficacy analysis disclosed that the phosphorus concentration decreased from 2.39 +/- 0.48 to 1.84 +/-

0.48 mmol/l (p < 0.001). The mean dose of sevelamer was stabilised at 3.4 +/- 1.8

g/day. The amount of calcium- and


aluminium-based phosphate binders could
be decreased from 5.1 +/- 3.5 to 3.1 +/- 2.7
g/day (38% decrease) and from 2.4 +/- 1.5
to 1.5 +/- 1.7 g/day (36% decrease),
respectively. The calcium-phosphate
product was significantly decreased from

5.83 +/- 1.19 to 4.36 +/- 1.12 mmol/l2 (p <

0.001). The total cholesterol concentration decreased from 4.34 +/- 0.9 to 3.98 +/- 0.9 mmol/l (p < 0.01) and the low-density

lipoprotein cholesterol level from 2.61 +/-

0.98 to 2.20 +/- 0.77 mmol/l (p < 0.03).
Conclusions: Sevelamer is an effective

phosphate binder that allows a better serum phosphorus control, while allowing a

decrease in the dose of calcium- and
aluminium-based phosphate binders in

these difficult patients. The drawbacks are


the high intolerance rate and the price of the
product.
Braun J, Asmus H-G, Holzer H, et al.
Long-term comparison of a calcium-

free phosphate binder and calcium carbonate - Phosphorus metabolism and cardiovascular calcification.

Clinical Nephrology. Vol. 62(2)(pp 104-115), 2004.

114 adult hemodialysis patients were


randomly assigned to open label sevelamer
or CaCO3 for 52 weeks. Study efficacy
endpoints included changes in serum
phosphorus, calcium, calcium-phosphate
product, and lipids. In addition, initial and
sequential electron beam computerized
tomography scans were performed to
assess cardiovascular calcification status and change during follow-up. Safety

endpoints were serum biochemistry, blood


cell counts and adverse events. Results:
Patients receiving sevelamer had a similar
reduction in serum phosphorus as patients
receiving CaCO3 (sevelamer -0.58 +/- 0.68
mmol/l, CaCO3 -0.52 +/- 0.50 mmol/l; p =

0.62). Reductions in calcium-phosphate


product were not significantly different

(sevelamer -1.4 +/- 1.7 mmol2 /12 , CaCO3

-0.9 +/- 1.2 mmol2 /12 ; p = 0.12). CaCO3
produced significantly more hypercalcemia
(> 2.8 mmol/l in 0% sevelamer and 19%
CaCO3 patients, p < 0.01) and suppressed
intact PTH below 150 pg/ml in the majority

of patients. Sevelamer patients experienced


significant (p < 0.01) reductions in total (-1.2
+/- 0.9 mmol/1, -24%) and LDL cholesterol (-

1.2 +/- 0.9 mmol/1, -30%). CaCO3 patients had significant increases in coronary artery (median +34%, p < 0.01) and aortic

calcification (median +32%, p < 0.01) that
were not observed in sevelamer-treated
patients. Patients on sevelamer required
more grams of binder (sevelamer 5.9 g vs.
CaCO3 3.9 g) and experienced more

dyspepsia than patients on calcium


carbonate. Conclusions: Sevelamer is an effective phosphate binder that unlike
calcium carbonate is not associated with progressive cardiovascular calcification in hemodialysis patients.
Burke SK, Dillon MA, Hemken DE, et al.
Meta-analysis of the effect of

sevelamer on phosphorus, calcium, PTH, and serum lipids in dialysis patients. Advances in Renal

Replacement Therapy. Vol. 10(2)(pp 133-145), 2003.

We conducted a meta-analysis on the


effects of sevelamer hydrochloride on

parameters of mineral metabolism (serum phosphorous, calcium, calcium-phosphate product, and iPTH) and the lipid profile

(total, LDL, HDL, and non-HDL cholesterol,
and triglycerides) in dialysis patients. After
application of inclusion/exclusion criteria, 17
core studies were statistically analyzed to
determine the sevelamer treatment effect on
the study parameters as demonstrated by
simple, n-weighted, and inverse variance-
weighted mean changes. Analysis of inverse
variance-weighted mean changes indicated
that sevelamer treatment was associated






with a 2.14 mg/dL drop in serum phosphorus (P < .001), no significant overall effect on

calcium (0.09 mg/dL, P = .364), significant decline in calcium-phosphate product

product (15.91 mg2/dL2, P < .001), 35.99 pg/mL reduction in iPTH (P = .026),

significant reduction in total cholesterol
(30.58 mg/dL, P < .001), 31.38 mg/dL drop
in LDL cholesterol (P < .001), significant
increase in HDL cholesterol (4.09 mg/dL, P
= .008), and a significant reduction in
triglycerides (22.04 mg/dL, P < .001). This
meta-analysis suggests that sevelamer
offers a dual therapeutic benefit in dialysis
patients - a population at high risk for
cardiovascular disease - by improving
phosphorus control and the lipid profile,
without altering serum calcium.
McIntyre CW, Patel V, Taylor GS, et al.
A prospective study of combination

therapy for hyperphosphataemia with calcium-containing phosphate binders and sevelamer in

hypercalcaemic haemodialysis
patients. Nephrology Dialysis

Transplantation. Vol. 17(9)(pp 1643-


1648), 2002.

We report on a strategy of partial


replacement of calcium with sevelamer for
the management of hyperphosphataemia in
hypercalcaemic chronic HD patients.
Methods. We identified 23 HD patients with
serum calcium > 2.6 mmol/1. Dietary
phosphate and calcium intake were
assessed and baseline serum calcium,
phosphate and 1a calcidol and elemental
calcium dose recorded. Fifty per cent of this
initial calcium dose was exchanged for
sevelamer. Vitamin D doses were left
unchanged. If serum calcium was still > 2.6
mmol/1 after 4 weeks a further 50% of
calcium was exchanged. If serum phosphate
was >2 mmol/1 the sevelamer dose was
increased by 25%. The patients were
followed up for a further 4 weeks. Results.
Seven patients complained of

gastrointestinal intolerance of sevelamer. Serum calcium fell from a mean value of 2.8 +/- 0.04 (2.64-3.54) mmol/1 to 2.56 +/- 0.03 (2.4-2.9) mmol/1, P < 0.0005. The

hypercalcaemic percentage of patients fell
from 100 to 26%. Mean serum phosphate
was not significantly changed, 1.59 +/- 0.1
(0.57-2.6) mmol/1 to 1.63 +/- 0.11 (0.55-

2.68) mmol/1, 17-22% of patients having


serum phosphate > 2 mmol/1. Serum intact PTH increased from 166 +/- 47 (12-933) ng/l to 276 +/- 104 (20-1013) ng/1, P=0.02.

Mean sevelamer dose was 2.77 +/- 0.36 (0-

5.6) g per day. Elemental calcium dose fell from 2.05 +/- 0.23 (0.5-4.5) g to 1.03 +/- 0.1 (0. 5-2.5) g, P < 0. 0001. Conclusion. A

regimen based on the combination of


sevelamer and calcium is capable of

effectively managing hyperphosphataemia, without hypercalcaemia, in the majority of hypercalcaemic HD patients. Such a

minimally calcaemic approach might reduce
the financial burden of sevelamer therapy,
and enable a wider range of patients to be
treated.
Gallieni M, Cozzolino M, Carpani P, et al.
Sevelamer reduces calcium load

and maintains a low calcium-


phosphorus ion product in dialysis patients. Journal of Nephrology. Vol. 14(3) (pp 176-183), 2001.

This single-center, open-label, dose titration


study assessed the efficacy of sevelamer in
a cohort of European hemodialysis patients
with different dietary habits, in particular with
lower phosphate intake. The aim of the

study was to obtain a calcium-phosphate


product lower than 60 mg2/dL2 in all patients.
Methods. Administration of calcium- or
aluminum-based phosphate binders was
discontinued during a two-week washout
period. Nineteen patients whose serum
phosphate level at the end of washout was
greater than 5.5 mg/dL (1.78 mmol/L)
qualified to receive sevelamer for six weeks.
Based on the degree of hyperphosphatemia
during washout, patients were started on
403 mg sevelamer capsules with a dose
schedule different from previous studies.
Only one capsule was administered at
breakfast, and the rest of the phosphate
binder was divided equally at the two main
meals. Sevelamer could be increased by
two capsules per day every two weeks, if
necessary. A second two-week washout
period followed. Results. Mean serum
phosphorus rose from a baseline of 5.3+/-

1.0 to 7.4+/-1.4 mg/dL at the end of


washout, then declined to 5.4+/-0.8 mg/dL
(p < 0.001) by the end of the six-week
treatment period and rebounded significantly
to 7.1+/-1.1 mg/dL after the second two-
week washout. calcium-phosphate product
showed a similar pattern, decreasing



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