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statistically significant (p<0.05) reduction
(0.8 g/dL) in serum albumin concentration,
without affecting iPTH. Taken together,

these results indicate that sevelamer


worsens metabolic acidosis, which needs to be corrected.
Katopodis KP, Andrikos EK, Gouva CD, et
al.

Sevelamer hydrochloride versus


aluminum hydroxide: Effect on
serum phosphorus and lipids in

CAPD patients. Peritoneal Dialysis International. Vol. 26(3)(pp 320-


327), 2006.

The present study was designed to evaluate the efficacy of SH in the control of

hyperphosphatemia and its effect, compared
to AH, on serum lipid parameters in patients
on CAPD. Methods: 30 stable patients on

CAPD were included in an open-label, randomized crossover study. After a 2-week phosphorus binder washout period, 15


patients (group I) were administered SH for

8 weeks and in the remaining patients


(group II), AH was introduced (phase A).

After a new 2-week washout period, patients crossed over to the alternate agent for

another 8 weeks (phase B). Results: There were similar reductions in serum

phosphorus levels over the course of the study with both agents: by 1.18 +/- 0.07 mg/dL (0.38 +/- 0.03 mmol/L) with SH and by 1.25 +/- 0.15 mg/dL (0.40 +/- 0.05

mmol/L) with AH in phase A (p = NS), and by 1.35 +/- 0.25 mg/dL (0.43 +/- 0.08

mmol/L) with AH and by 1.23 +/- 0.80 mg/dL (0.39 +/- 0.25 mmol/L) with SH in phase B (p = NS). Moreover, SH administration was

associated with a 10.5% +/- 9.4% and a

20.1% +/- 6.8% fall in total cholesterol (p <

0.05) and low-density lipoprotein cholesterol (p < 0.001) in phase A, and 11.9% +/- 7.2% (p < 0.05) and 21.5% +/- 2.4% (p < 0.001), respectively, in phase B. In both phases of the study, AH administration was not

followed by a significant change in serum lipid parameters. Conclusion: Sevelamer hydrochloride is a well-tolerated alternative to calcium- or aluminum-containing

phosphorus binder in the control of serum phosphorus in CAPD patients. Furthermore, SH improves the lipid profile in these

patients.

Daly JA, Valenzuela Mujica MP.
The safety of phosphate binders.

Expert Opinion on Drug Safety. Vol. 5(5) (pp 675-686), 2006.

Disturbances of mineral metabolism occur during the early stages of CKD. As renal function worsens, excess dietary

phosphorus accumulates and blood levels


increase, that can be clearly seen when the
glomerular filtration rate has fallen below 30
ml/min/ 1.73m2 . In patients with ESRD,

standard dialysis (three times/week) falls far short of removing adequate amounts of

absorbed phosphorus; therefore,

hyperphosphataemia is found in the majority of these patients. Hyperphosphataemia has long been associated with progression of

SHPT and renal osteodystrophy, it can also lead to soft-tissue and vascular calcification. Recent observational data have associated hyperphosphataemia with increased

cardiovascular mortality among dialysis patients. Adequate control of serum

phosphorus remains a cornerstone in the






clinical management and, despite the


growing amount of available therapeutic

options, achievement of NFK/KDOQI targets for mineral metabolism remain poor. Several reasons may explain the failure to

adequately treat hyperphosphataemia: poor compliance with diet and phosphate binder prescriptions are common causes. Also,

factors related with cost, tolerance,


palatability, safety and efficacy are

important. In this article, the authors review the advantages and drawbacks of

conventional and emerging therapies in phosphorous binding.

Finn WF.


Lanthanum carbonate versus
standard therapy for the treatment
of hyperphosphatemia: Safety and
efficacy in chronic maintenance
hemodialysis patients. Clinical
Nephrology. Vol. 65(3)(pp 191-202),
2006.

This large-scale study compares the safety of lanthanum with standard therapy (any

approved phosphate binder) in patients who were treated for up to 2 years. Efficacy,

having previously been demonstrated, was a


secondary endpoint. Materials and methods:
After washout, patients were randomized to
receive lanthanum (n = 682) or their pre-

study phosphate binder (n = 677). Over a 6-


week period, lanthanum was titrated to a

maximum daily dose of 3,000 mg elemental lanthanum (serum phosphorus target levels for titration were ≤ 5.9 mg/dl (1.90 mmol/1)). Safety assessments included adverse

events (AEs), full laboratory parameters and blood profiles. Efficacy assessments

included serum phosphorus, calcium,


calcium-phosphate product and PTH levels.
Results: Average treatment exposure was
greater in the standard therapy group (501.4
days) than in the lanthanum group (370.3
days) because standard therapy patients
who switched or combined treatments were
allowed to continue in the study. The most
common AEs were gastrointestinal. The
incidences of AEs in the lanthanum and
treatment exposure-corrected standard
therapy groups were nausea, 37 versus
29%; vomiting, 27 versus 22% and diarrhea
(24% in each group). Hypercalcemia that
was reported as an AE (lanthanum versus
treatment exposure-corrected standard
therapy) occurred in 4.3% and 8.4% of
patients, respectively. There was no
indication of liver toxicity, suppression of erythropoiesis or changes in the mini-mental state examination. Over 2 years,

phosphorus control was similar in both


groups; in the lanthanum group, however,
serum calcium was lower and serum PTH
levels were maintained in the range
recommended by the National Kidney
Foundation Kidney Disease Outcomes
Quality Initiative (K/DOQI). Conclusions: The
2-year tolerability and efficacy of lanthanum
are similar to those seen with standard
therapy, although lower serum calcium
levels and improved PTH levels were
observed in the lanthanum group. These
results support lanthanum as a viable new
option for the management of

hyperphosphatemia in ESRD.


Finn WF and Joy MS. A long-term, open-
label extension study on the safety

of treatment with lanthanum


carbonate, a new phosphate binder,
in patients receiving hemodialysis.
Curr Med Res Opin 21(5): 657-64,
2005.

A 1-year extension study to two randomized controlled studies was conducted to

evaluate the long-term safety of lanthanum carbonate in patients who received

hemodialysis. RESEARCH DESIGN AND METHODS: Patients from two previous

lanthanum carbonate studies were eligible to continue treatment in a 1-year open-label

extension. A total of 77 patients (N = 77; 11 from Study 1, 66 from Study 2) were

enrolled in this extension. The mean age of
patients was 60.9 years (SD +/- 12.5 years);
65% were male and 35% were female. All
patients received lanthanum carbonate at
the optimal dose for phosphorus control,

determined in their previous study. Safety and tolerability were assessed by monitoring adverse events, laboratory parameters, and vital signs. The number of patients who

maintained serum phosphorus levels at < or = 5.9 mg/dL (1.9 mmol/L) was recorded,

along with serum calcium, calcium-


phosphate product, and PTH levels.

RESULTS: Lanthanum carbonate was well tolerated and was associated with few

treatment-related adverse events. The most
commonly reported adverse events were
nausea (26.0%), peripheral edema (23.4%),
and myalgia (20.8%). No treatment-related






serious adverse events occurred. By Week


4, the mean serum phosphorus level had
decreased by approximately 1 mg/dL to 5.7
+/- 2.0 mg/dL (1.84 +/- 0.7 mmol/L). At the
end of the study, the mean pre-dialysis

serum phosphorus level was 5.7 +/- 1.4 mg/dL (1.84 +/- 0.5 mmol/L); 53% of

patients had controlled phosphorus levels. calcium-phosphate product decreased

during Week 1 and remained within a clinically acceptable range thereafter. There were no clinically significant changes in serum calcium, or PTH levels.

CONCLUSION: Lanthanum carbonate is well tolerated and is effective for the long-
term maintenance of serum phosphorus control in patients with ESRD.
Sonikian MA, Pani IT, Iliopoulos AN, et al.
Metabolic acidosis aggravation and

hyperkaliemia in hemodialysis


patients treated by sevelamer

hydrochloride. Renal Failure. Vol. 27(2) (pp 143-147), 2005.

In a retrospective analysis, we evaluated SH impact on metabolic acidosis and serum

potassium (K) in hemodialysis (HD) patients. Two groups of stable HD patients were

studied. Group A included 17 patients,
M/F=15/2, 64 (42-80) years old, dialyzed

since 130 (34-253) months, under SH for 24 months. Group B serving as controls was made of 7 patients, M/F=4/3, 67 (48-91)

years old, dialyzed since 67 (27-174)
months, under CaCO3 and/or Al (OH)3 as
phosphate binders also for 24 months.
Bicarbonate (BIC), K, Ca, phosphorus (P),
Ca-PP, alkaline phosphatase (ALP), and
intact PTH were recorded before (MO) and
at the end (M24) of 24-month SH or CaCO
3-Al(OH)3 treatment in group A and B
patients. In group A, BIC fell from 20.02+/-

1.43 to 17.89+/-2.30 mEq/L, P=.002; and K rose from 5.45+/-0.51 to 5.75+/-0.49 mEq/L, P=0.02. In group B, BIC (19.8+/-3.03 to

19.0+/-3.3 mEq/L) and K (5.01+/-0.8 to

4.9+/-1.1 mEq/L) had nonsignificant


changes. In group A, iPTH rose from

132.82+/- 124.08 to 326.89+/-283.91 pg/mL, P=.0008; P fell from 5.92+/-1.48 to 4.9+/-

1.01, P=.02; and Ca-PP decreased from

52.04+/-9.7 to 45.58+/- 10.42 mg2 /dL2 ,


P=.04. In group B, changes in iPTH from

240.71 +/-174.7 to 318.57+/- 260.2 pg/mL, P


from 4.9+/-0.5 to 4.8+/-1.3 mg/dL, and Ca-
PP product from 44.3+/-6.6 to 44+/-11.2 mg2
/dL2 were nonsignificant. The changes
observed in Ca and ALP in both groups

were nonsignificant. Correlations in group A between metabolic acidosis (BIC) and SH doses, or iPTH and BIC, Ca, or P changes, were also found to be nonsignificant. Long-


term use of SH, effectively controlling serum P levels and Ca-PP values, is associated with acidosis aggravation and

hyperkaliemia. Worsening of SHPT, also noted, needs to be confirmed and could be related to Ca/Al salt discontinuation and to metabolic acidosis aggravation itself.

Loghman-Adham M.

Safety of New Phosphate Binders for Chronic Renal Failure. Drug

Safety. Vol. 26(15)(pp 1093-1115),
2003.

Phosphate (Pi) retention is a common


problem in patients with CKD, particularly in
those who have reached ESRD. In addition
to causing SHPT and renal osteodystrophy,
recent evidence suggests that, in ESRD
patients, high serum phosphorus
concentration and increased calcium-
phosphate product are associated with
vascular and cardiac calcifications and
increased mortality. Dietary phosphorus
restriction and Pi removal by dialysis are not
sufficient to restore Pi homeostasis.
Reduction of intestinal Pi absorption with the
use of Pi binders is currently the primary
treatment for Pi retention in patients with
ESRD. The use of large doses of calcium-
containing Pi binders along with calcitriol
administration may contribute to over-
suppression of PTH secretion and adynamic
bone disease as well as to a high incidence
of vascular calcifications. When used in
patients with impaired renal function,
aluminium salts were found to accumulate in
bone and other tissues, resulting in
osteomalacia and encephalopathy.
Sevelamer, an aluminium- and calcium-free
Pi binder can reduce serum phosphorus
concentration and is associated with a
significantly lower incidence of

hypercalcaemia, while maintaining the ability to suppress PTH production. An additional benefit of sevelamer is its ability to lower low density lipoprotein-cholesterol and total

cholesterol levels. Sevelamer attenuates the progression of vascular calcifications in

haemodialysis patients, which may lead to


lower mortality. The use of sevelamer in






non-dialysed patients might aggravate


metabolic acidosis, common in these
patients. Several other calcium-free Pi
binders are in development. Lanthanum

carbonate has shown significant promise in


clinical trials in ESRD patients. Magnesium
salts do not offer a significant advantage

over currently available Pi binders. Their use is restricted to patients receiving dialysis

since excess magnesium must be removed by dialysis. Iron-based compounds have

shown variable efficacy in short-term clinical trials in small numbers of haemodialysis

patients. Mixed metal hydroxyl carbonate
compounds have shown efficacy in animals
but have not been studied in humans. Major

safety issues include absorption of the metal component with possible tissue

accumulation and toxicity.
Health economics, resources, risk/benefit
White CA, Jaffey J, Magner P.
Cost of applying the K/DOQI

guidelines for bone metabolism and disease to a cohort of chronic

hemodialysis patients. Kidney International. Vol. 71(4)(pp 312-
317), 2007.

Hyperphosphatemia is a common feature of advanced CKD and is treated routinely with oral calcium-based phosphate binders. In 2003, the National Kidney Foundation

Kidney Disease Outcomes and Quality Initiative (K/DOQI) published Clinical Practice Guidelines (CPGs) for the

treatment of Bone Metabolism and Disease in CKD. These advocate broad usage of expensive non-calcium-based phosphate binders such as sevelamer. This study was designed to determine the cost of

implementation of the K/DOQI CPGs as they pertain to phosphate binding in a large

Canadian hemodialysis (HD) unit.


Laboratory and medication data for all
chronic HD patients at the Ottawa Hospital
were reviewed (n=416). Patients meeting
each of the relevant K/DOQI guidelines were
identified. Where guidelines would
recommend a switch to non-calcium binders,
equivalent sevelamer doses were estimated.
The cost of implementing each guideline
was then calculated individually and an
estimate total cost of implementing all the guidelines was derived. Overall, 53% (222) patients fulfilled at least one criterion for sevelamer use. The yearly cost of

implementation of the K/DOQI guidelines at this center was estimated at $ 500 605

(American dollars). Given the significant
cost, widespread adoption of the K/DOQI
CPGs for Bone Metabolism and Disease
should await the publication of compelling
data demonstrating significant improved

outcomes in patients treated with sevelamer.


Brennan A, Akehurst R, Davis S, et al.
The cost-effectiveness of lanthanum

carbonate in the treatment of


hyperphosphatemia in patients with
end-stage renal disease. Value in
Health. Vol. 10(1)(pp 32-41), 2007.
To assess the cost-effectiveness of

lanthanum carbonate (LC) as a second-line


therapy for hyperphosphatemia in ESRD
patients not achieving target phosphorus
levels. Methods: A cohort of ESRD patients
not adequately maintained on calcium

carbonate (CaCO3) and three subgroups of


patients with baseline phosphorus levels of

5.6 to 6.5 mg/dl, 6.6 to 7.8 mg/dl, and more


than 7.9 mg/dl were modeled. The following
policy options were considered: continued
CaCO3 (Policy 1); LC trial - if successful

continue LC, if unsuccessful switch to


CaCO3 (Policy 2). The survival benefit of
using second-line LC to improve phosphorus
control has been extrapolated from the
relationship between hyperphosphatemia
and mortality. Lifetime UK National Health
Service drug and monitoring costs, expected
survival, and quality-adjusted life-years
(QALYs) were examined (discounting at

3.5% per annum). Results: Policy 2 had a cost-effectiveness ratio (cost/QALY) of

25,033 relative to Policy 1. The results show it is particularly cost-effective to treat

patients with phosphorus levels above 6.6 mg/dl. The outcomes did not vary

significantly during the one-way sensitivity
analysis carried out on important model
parameters and assumptions except when

the utility value for ESRD was decreased by more than 30%. Conclusions: Applying a

cost-effectiveness threshold of 30,000 per QALY, the model shows it is cost-effective to follow current treatment guidelines and treat all patients who are not adequately

maintained on CaCO3 (serum phosphorus








above 5.6 mg/dl) with second-line LC. This is particularly the case for patients with

serum phosphorus above 6.6 mg/dl. Our estimates are probably conservative as the possible compliance difference in favor of LC and the reduced number of

hypercalcemic events with LC relative to CaCO3 was not considered.

White A, Odedina F, Xiao H, et al.
The economic burden of end-stage

renal disease with

hyperphosphatemia: A study of Florida Medicaid. Disease

Management & Health Outcomes. Vol. 14(2)(pp 99-106), 2006.

The aims of this study were to: (i) describe the characteristics of ESRD patients with hyperphosphatemia in terms of

demographics, comorbidities, and


healthcare utilization; (ii) evaluate the
primary cost drivers in the treatment of these
patients; and (iii) assess the cost of illness
associated with treating ESRD patients with
hyperphosphatemia. Methods: This
retrospective study extracted data from the
Florida Medicaid database. Healthcare costs
were assessed from a third-party payor
perspective. The patient inclusion criteria
were current use of either sevelamer or
calcium acetate and continuous eligibility to
receive Florida Medicaid services from July
1, 1999 to December 31, 2002 with a run-in
period from July 1, 1999 to December 31,
1999 to ensure that patients had been taking
either of the two drugs for at least 6 months.
The patient exclusion criteria were
documented HIV and hemophilia. The
specific direct costs included in the study
were hospitalization costs, outpatient costs,
emergency room costs, and prescription
costs (only those for sevelamer and calcium
acetate). The price year for the cost analysis
was 2002. Results: A total of 10 058
recipients constituted the study sample, of
which 54.0% were male and 46.0% were
female. African Americans represented the
largest racial group (45.6%), followed by
Caucasians (28.6%). The most frequent
comorbidities were hypertension, anemia,
and congestive heart failure. Healthcare was
most often utilized through facility visits
(78.1%), followed by pharmacy-related
services (17.2%) and then medical services
(4.7%). Based on medical claims, the
ambulance service contributed the most to
healthcare utilization (8.7%), followed by
recipient home visits (3.3%) and inpatient
visits (2.1%). Facility claims utilization was
dominated by dialysis center visits (48.5%),
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