Nsw therapeutic Advisory Group Level 5, 376 Victoria Street po box 766

Дата канвертавання24.04.2016
Памер0.84 Mb.
1   ...   5   6   7   8   9   10   11   12   13

resulted in more rapid progression of coronary calcification than did use of sevelamer hydrochloride.
Iwasaki Y, Takami H, Tani M, et al.
Efficacy of combined sevelamer and

calcium carbonate therapy for

hyperphosphatemia in Japanese

hemodialysis patients. Therapeutic Apheresis & Dialysis. Vol. 9(4)(pp 347-351), 2005.

We prospectively evaluated the clinical efficacy of the combination of sevelamer hydrochloride and calcium carbonate

(CaCO3) for hyperphosphatemia. The study

group comprised 65 HD patients who had
been administered CaCO3 (≥1500 mg/ day)
for hyperphosphatemia [≥6.0 mg/dL (≥1.94
mmol/L)]. At the beginning of the study the
dose of CaCO3 was reduced by 1500

mg/day and the patients divided into two

groups according to the dose of additional
sevelamer hydrochloride: group A 2250

mg/day; group B 3000 mg/ day. Oral active vitamin D therapy was unchanged. Fourteen patients (21.5%) dropped out because of

adverse effects and of the 51 remaining patients 35 (53.8%) suffered from

gastrointestinal problems. Serum phosphate

concentration decreased significantly [from

7.5 +/- 0.8 mg/ dL (2.42 +/- 0.26 mmol/L) to

6.6 +/- 1.3 mg/dL (2.13 +/- 0.42 mmol/L), P < 0.01] in group B only after the 8 weeks of combination therapy. The calcium-

phosphate product also decreased in group

B only [from 74.4 +/- 13.4 mg2 /dL2 (5.99 +/-

1.07 mmol2/l2) to 63.7 +/- 15.8 mg2 /dL2

(5.13 +/- 1.27 mmol2/l2), P < 0.001]. The

combination of sevelamer hydrochloride and CaCO3 is a suitable regimen for

hyperphosphatemia treatment in HD
patients because it avoids both the

hypercalcemia of CaCO3 and the adverse effects of sevelamer hydrochloride when each is used as single-drug therapy. The ability of sevelamer hydrochloride to

decrease the serum phosphate

concentration is 2/3 (2250/1500 mg) that of CaCO3.

Koiwa FN, Onoda N, et al. Prospective
randomized multicenter trial of

sevelamer hydrochloride and calcium carbonate for the treatment of hyperphosphatemia in

hemodialysis patients in Japan.
Ther Apher Dial 9(4): 340-6, 2005.

A prospective, randomized open-label trial of sevelamer hydrochloride with or without

calcium carbonate (CaCO3) involved 86

hemodialysis patients in Japan. The dosage of CaCO3 was fixed at 3.0 g/day for the 12-

week study. After the first 4 weeks all

subjects were changed from CaCO3 to

sevelamer 3.0 g/day for another 4 weeks,

then allocated randomly to three groups for

the final 4 weeks: group A, sevelamer 6.0
g/day; group B, sevelamer 3.0 g/day and
CaCO3 3.0 g/day; group C, CaCO3 3.0

g/day. The target serum phosphorous

concentration (P)=5.5 mg/dL and the

corrected calcium concentration (Ca) was

9.0-10.0 mg/dL. Of the 86 patients, 62
finished the study without a change of

dosage and their data were analyzed (group A, N=16; group B, N=26; group C, N=20). At week 8 compared with week 4, the

concentration of P increased from 5.7+/-1.4 to 6.4+/-1.7 mg/dL in group A, and

decreased significantly in groups B and C, and in group B compared with groups A and C; groups A and C had similar

concentrations at week 8. The Ca
concentration decreased significantly from

9.7+/-1.0 to 9.1+/-0.7 mg/dL after the

change to sevelamer. At week 8 Ca was not
significantly changed in group A, whereas a
significant increase occurred in groups B
and C. Side-effects with sevelamer
administration occurred in 34 of the 86
patients and 24 dropped out of the study,
with a high frequency in group A (13/29;

44.8%). In conclusion, there was an additive effect of sevelamer for the treatment of

hyperphosphatemia with CaCO3. The
combination therapy was better tolerated

and showed higher patient compliance than CaCO3 or sevelamer monotherapy.

Ferramosca E, Burke S, Chasan-Taber S, et

Potential antiatherogenic and anti-

inflammatory properties of

sevelamer in maintenance

hemodialysis patients. American Heart Journal. Vol. 149(5)(pp 820-
825), 2005.

One hundred eight patients undergoing

maintenance hemodialysis were randomized
to sevelamer or calcium acetate as
treatment for hyperphosphatemia. A
coronary artery calcium score, as a measure
of plaque burden, was calculated at baseline
and 1 year, along with serial measurements
of serum lipoproteins, beta2- microglobulin,
and high-sensitivity C-reactive protein (hs-
CRP). At 1 year, coronary artery calcium
score progressed significantly from baseline
in calcium acetate-treated subjects (P <
.001) but not in sevelamer-treated patients
(P = NS). Total cholesterol (P < .0001), low-
density lipoprotein cholesterol (P < .0001),
apolipoprotein B (P < .0001), beta2-
microglobulin (P = .018), and hs-CRP (P <
.002) decreased, and high-density
lipoprotein increased significantly (P = .036)
from baseline in the sevelamer-treated
subjects but not in subjects treated with
calcium acetate despite the more frequent
use of statins in the latter group (46% vs
22%, P < .05). The changes in total and low-
density lipoprotein cholesterol,

apolipoprotein B, and hs-CRP were

significantly different between treatment
groups (all P < .01). Conclusions:
Sevelamer leads to favorable changes in lipids and inflammatory markers with
potentially useful antiatherogenic effects in hemodialysis patients

Garg JP, Chasan-Taber S, Blair A, et al.

Effects of sevelamer and calcium-

based phosphate binders on uric acid concentrations in patients undergoing hemodialysis: A

randomized clinical trial. Arthritis & Rheumatism. Vol. 52(1)(pp 290-
295), 2005.

Two hundred subjects undergoing

maintenance hemodialysis were randomly
assigned to receive either sevelamer or
calcium-based phosphorus binders in an
international, multicenter, clinical trial. Data
on baseline and end-of-study uric acid
concentrations were available in 169
subjects (85%); the change in uric acid
concentration from baseline to the end of the
study was the outcome of interest. Results.
Baseline clinical characteristics, including
mean uric acid concentrations, were similar
in subjects randomly assigned to receive
sevelamer and calcium-based phosphate
binders. The mean change in uric acid
concentration (from baseline to the end of
the study) was significantly larger in
sevelamer-treated subjects (-0.64 mg/dl
versus -0.26 mg/dl; P = 0.03). The adjusted
mean change in uric acid concentration was
more pronounced when the effects of age,
sex, diabetes, vintage (time since initiation
of dialysis), dialysis dose, and changes in
blood urea nitrogen and bicarbonate

concentrations were considered (-0.72 mg/dl versus -0.15 mg/dl; P = 0.001). Twenty-

three percent of sevelamer-treated subjects
experienced a study-related reduction in the
concentration of uric acid equal to -1.5 mg/dl
or more, compared with 10% of calcium-

treated subjects (P = 0.02). Conclusion. In a randomized clinical trial comparing

sevelamer and calcium-based phosphate binders, treatment with sevelamer was associated with a significant reduction in serum uric acid concentrations.
Qunibi WY, Hootkins RE, et al. Treatment of
hyperphosphatemia in hemodialysis

patients: The Calcium Acetate

Renagel Evaluation (CARE Study).
Kidney Int 65(5): 1914-26, 2004.
To determine whether calcium acetate or

sevelamer hydrochloride best achieves

recently recommended treatment goals of
phosphorus phosphate product conducted an 8-week randomized, double-

blind study in 100 hemodialysis patients.
RESULTS: Comparisons of time-averaged

concentrations (weeks 1 to 8) demonstrated

that calcium acetate recipients had lower
serum phosphorus (1.08 mg/dL difference,
P= 0.0006), higher serum calcium (0.63

mg/dL difference, P < 0.0001), and lower Ca

x P (6.1 mg(2)/dL(2) difference, P= 0.022)
than sevelamer recipients. At each week,

calcium acetate recipients were 20% to 24% more likely to attain goal phosphorus [odds ratio (OR) 2.37, 95% CI 1.28-4.37, P=

0.0058], and 15% to 20% more likely to
attain goal Ca x P (OR 2.16, 95% CI 1.20-

3.86, P= 0.0097). Transient hypercalcemia occurred in 8 of 48 (16.7%) calcium acetate recipients, all of whom received concomitant intravenous vitamin D. By regression

analysis hypercalcemia was more likely with calcium acetate (OR 6.1, 95% CI 2.8-13.3, P < 0.0001). Week 8 intact PTH levels were not significantly different. Serum bicarbonate levels were significantly lower with

sevelamer hydrochloride treatment (P <

0.0001). CONCLUSION: Calcium acetate
controls serum phosphorus and calcium-
phosphate product more effectively than
sevelamer hydrochloride. Cost-benefit

analysis indicates that in the absence of hypercalcemia, calcium acetate should remain the treatment of choice for

hyperphosphatemia in hemodialysis patients.

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.
Sadek TH, Mazouz H, et al. Sevelamer
hydrochloride with or without

alphacalcidol or higher dialysate

calcium vs calcium carbonate in

dialysis patients: an open-label,

randomized study. Nephrol Dial
18(3): 582-8, 2003.

We compared for 5 months two strategies for controlling moderate

hyperparathyroidism: CaCO(3) alone vs sevelamer in conjunction with measures to increase calcium balance. METHODS:

Forty-two patients were randomized: 21 continued their treatment with 4.8 g/day CaCO(3) and 21 were switched to

sevelamer (initial dose: 2.4 g/day, increased to 4.4 g/day). Each month, when serum-

corrected calcium decreased below 2.30

mmol/l, dialysate calcium was increased or
alphacalcidol was given at each dialysis
session, according to serum PO(4) levels.
The following parameters were monitored:
serum Ca, PO(4), bicarbonate and protein,
weekly; and serum PTH, 25-OH vitamin D

and total, LDL and HDL cholesterol monthly. RESULTS: Except for higher serum

phosphate at month 1, lower serum
bicarbonate at month 2 and lower LDL

cholesterol at month 5 in the sevelamer

group, no difference was found between the
two groups. Compared with baseline levels,
PTH increased and 25-OH vitamin D
decreased significantly in both groups, these
two parameters being inversely correlated.
CONCLUSIONS: Given comparable control
of plasma calcium, phosphate and 25-OH
vitamin D, PTH control is comparable in both
strategies. Sevelamer does not induce
greater vitamin D depletion than CaCO(3).
The transient decrease of serum

bicarbonate after discontinuation of

CaCO(3) in the sevelamer group suggests a
less optimal prevention of acidosis. The
sevelamer-induced decrease in LDL
cholesterol gives this drug a potential
advantage in cardiovascular prevention.

Chertow GM, Raggi P, McCarthy JT, et al.

The effects of sevelamer and

calcium acetate on proxies of

atherosclerotic and arteriosclerotic
vascular disease in hemodialysis
patients. American Journal of
Nephrology. Vol. 23(5)(pp 307-314),

To determine whether treatment with

calcium acetate was specifically associated
with hypercalcemia and progressive
vascular calcification, we conducted an
analysis restricted to 108 hemodialysis
patients randomized to calcium acetate or sevelamer and followed for one year.

Results: The reduction in serum phosphorus was roughly equivalent with both agents

(calcium acetate -2.5 +/- 1.8 mg/dl vs.
sevelamer -2.8 +/- 2.0 mg/dl, p = 0.53).

Subjects given calcium acetate were more

likely to develop hypercalcemia (defined as
an albumin-corrected serum calcium ≥ 10.5
mg/dl) (36 vs. 13%, p = 0.015). Treatment
with calcium acetate (mean 4.6 +/- 2.1 g/day

- equivalent to 1.2 +/- 0.5 g of elemental

calcium) led to a significant increase in EBT-
determined calcification of the coronary
arteries (mean change 182 +/- 350, median
change +20, p = 0.002) and aorta (mean
change 181 +/- 855, median change +73, p
< 0.0001). These changes were similar in
magnitude to those seen with calcium
carbonate. There were no significant
changes in calcification among sevelamer-
treated subjects. Conclusion: Despite
purported differences in safety and efficacy
relative to calcium carbonate, calcium
acetate led to hypercalcemia and

progressive vascular calcification in hemodialysis patients.

Chertow GM, Burke SK, et al. Sevelamer
attenuates the progression of

coronary and aortic calcification in hemodialysis patients. Kidney Int 62(1): 245-52, 2002.

We conducted a randomized clinical trial
comparing sevelamer, a non-absorbed
polymer, with calcium-based phosphate

binders in 200 hemodialysis patients. Study outcomes included the targeted

concentrations of serum phosphorus,
calcium, and intact PTH, and calcification of
the coronary arteries and thoracic aorta
using a calcification score derived from
electron beam tomography. RESULTS:
Sevelamer and calcium provided equivalent
control of serum phosphorus (end-of-study
values 5.1 +/- 1.2 and 5.1 +/- 1.4 mg/dL,
respectively, P = 0.33). Serum calcium
concentration was significantly higher in the
calcium-treated group (P = 0.002), and
hypercalcemia was more common (16% vs.
5% with sevelamer, P = 0.04). More
subjects in the calcium group had end-of-
study intact PTH below the target of 150 to
300 pg/mL (57% vs. 30%, P = 0.001). At
study completion, the median absolute
calcium score in the coronary arteries and

aorta increased significantly in the calcium

treated subjects but not in the sevelamer-
treated subjects (coronary arteries 36.6 vs.
0, P = 0.03 and aorta 75.1 vs. 0, P = 0.01,
respectively). The median percent change in
coronary artery (25% vs. 6%, P = 0.02) and
aortic (28% vs. 5%, P = 0.02) calcium score
also was significantly greater with calcium
than with sevelamer. CONCLUSIONS:

Compared with calcium-based phosphate

binders, sevelamer is less likely to cause
hypercalcemia, low levels of PTH, and

progressive coronary and aortic calcification in hemodialysis patients

Chertow GM, Burke SK, et al. (1997).
Poly[allylamine hydrochloride]

(RenaGel): a noncalcemic

phosphate binder for the treatment
of hyperphosphatemia in chronic
renal failure. Am J Kidney Dis 29(1):
66-71, 1997.

We evaluated the efficacy of cross-linked

poly[allylamine hydrochloride] (RenaGel;
Geltex Pharmaceuticals, Waltham, MA), a
nonabsorbable calcium- and aluminum-free

phosphate binder, in a randomized, placebo-

controlled, double-blind trial of 36

maintenance hemodialysis patients followed over an 8-week period. RenaGel was found to be as effective as calcium carbonate or acetate as a phosphate binder. The

reduction in serum phosphorus was
significantly greater after 2 weeks of

treatment with RenaGel (6.6 +/- 2.1 mg/dL

to 5.4 +/- 1.5 mg/dL) compared with placebo
(7.0 +/- 2.1 mg/dL to 7.2 +/- 2.4 mg/dL; P =

0.037). There was no significant change in serum calcium concentration in either

treatment group. The total serum cholesterol and low-density lipoprotein cholesterol

fraction were significantly reduced in

RenaGel-treated patients compared with
placebo-treated patients (P = 0.013 and P =

0.003, respectively) without a concomitant reduction in high-density lipoprotein

cholesterol (P = 0.93). There was no
difference among recipients of RenaGel and placebo in terms of adverse events.
RenaGel is a safe and effective alternative to oral calcium for the management of
hyperphosphatemia in ESRD.
Bleyer AJ, Burke SK, Dillon M, et al.
A comparison of the calcium-free
phosphate binder sevelamer
hydrochloride with calcium acetate in the treatment of

hyperphosphatemia in hemodialysis patients. American Journal of

Kidney Diseases. Vol. 33(4)(pp 694-
701), 1999.

This investigation describes the use of a

calcium- and aluminum-free phosphate-
binding polymer in hemodialysis patients
and compares it with a standard calcium-
based phosphate binder. An open-label,

randomized, crossover 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 administered either sevelamer
or calcium acetate, and the dosages were
titrated upward to achieve improved

1   ...   5   6   7   8   9   10   11   12   13

База данных защищена авторским правом ©shkola.of.by 2016
звярнуцца да адміністрацыі

    Галоўная старонка