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Re: High phosphorus levels
From: FiOS-Dave@fakeaddress.zz (FiOS-Dave)
"mainframetech" <mainframetech@yahoo.com> wrote in message news:a2f52f74-7e79-40a7-ada7-ec36b2ba3fc9@f20g2000vbp.googlegroups.com...
On Apr 4, 5:28 pm, Ja...@nospam.com (Jason) wrote:
I found this info. in another newsgroup.
Hyperphosphatemia in End-Stage Renal Disease
Renagel and OtherTreatment Modalities
BY FRANK MOORE, RPA-C
Dialysis has become a way of life for many renal failure patients. In
the United States, there are an estimated 250,000 dialysis patients,
with an estimated growth rate of 7% to 10% per year.1 One of the most
commonly encountered challenges in the management of patients with end-
stage renal disease (ESRD) is the increasing levels of serum
phosphorus secondary to a decrease in the glomerular filtration rate
(GFR less than 25%).
Hyperphosphatemia, which has an estimated prevalence rate of
approximately 50% in this population, contributes significantly to
their morbidity and mortality.1 Hyperphosphatemia is considered a
potent contributing stimulus for the development of secondary
hyperparathyroidism, metastatic calcifications and renal
osteodystrophy.2 Managing dialysis patients' serum phosphate levels is
a multi-interrelated task, involving the patients' serum calcium,
parathyroid hormone (PTH), vitamin D and dietary intake of phosphate.
In the dialysis patient, unlike the non-dialysis-dependent patient,
interventions to control phosphate imbalance often result in unwanted
consequences.
Throughout the years, hemodialysis has proven limited in its ability
to effectively control serum phosphorus levels.3 This is true even in
instances involving a restricted dietary intake of phosphate.3 The
explanation offered for the poor removal of phosphate by dialysis is
the slow efflux of phosphate from the intracellular space and/or bone
to the extracellular space.4 Current management modalities for
hyperphosphatemia in chronic renal failure patients include dietary
regulation of phosphate intake and the pharmacologic approach using
oral phosphate binders. The most commonly used phosphate binders are
either calcium- or aluminum-containing, which are often limited by
their undesirable adverse side effects and toxicity.
Here is an overview of the consequences of hyperphosphatemia in ESRD
and a discussion of the strengths and limitations of the current
pharmacologic options, including the most recently approved calcium-
free, aluminum-free phosphate binder known as Renagel (sevelamer HCl),
by Genzyme Corp.
Pathophysiology
PTH and calcitriol, the active metabolite of vitamin D, regulate the
control of serum phosphorus and calcium accumulation in people with
normal renal function. When serum calcium is decreased, a reciprocal
increase in PTH directly stimulates bone dissolution, increases kidney
reabsorption of calcium and decreases the renal reabsorption of
phosphorus.1
Moreover, a high PTH increases the intestinal absorption of calcium
secondary to its effects on calcitriol. This is often sufficient to
restore serum calcium and maintain appropriate serum phosphate levels.
The main function of calcitriol is the regulation of intestinal
calcium absorption and, to a lesser extent, intestinal phosphorus
absorption.5
Calcitriol directly suppress PTH synthesis and release.5 Patients with
chronic renal failure are unable to produce sufficient quantities of
calcitriol to maintain normal serum calcium, which leads to an
increased secretion of PTH. The decrease in calcitriol production is
thought to be secondary to a reduction in renal tissue mass and an
inhibition of 1-alpha-hydroxylase activity, which is responsible for
the conversion of 25-hydroxyvitamin D to its active form (1,25-
dihydroxyvitamin D).6 Furthermore, serum calcium levels are affected
by calcium-phosphate precipitation into soft tissues (metastatic
calcifications) and poor dietary intake.
Despite variations in individual dietary phosphate intake, the
estimated average phosphate intake is 1,000 mg to 1,800 mg (32 to 58
mmol/dL) per 24 hours.7 Approximately 30% of this ingested phosphorus
load is excreted via the gastrointestinal tract, and the remainder is
excreted via the kidneys.8 Therefore, significant decreases in renal
function (GFR less than 25%) will result in major homeostatic
complications. In advanced renal failure, the compensatory mechanisms
responsible for decreasing the rate of renal tubular reabsorption of
phosphorus are not effective and therefore result in dangerously
elevated serum phosphorus levels.9 Maintaining a relatively normal
plasma concentration of phosphorus is perhaps the most potent
regulator in preventing secondary hyperparathyroidism, renal
osteodystrophy and metastatic soft-tissue calcifications.9
Secondary Hyperparathyroidism
Hyperphosphatemia is believed to be a significant factor in the
development of secondary hyperparathyroidism. The diagnosis is made by
obtaining an elevated serum intact PTH level. Secondary
hyperparathyroidism can be differentiated from primary
hyperparathyroidism by the coexistence of chronic renal failure (CRF)
and the absence of hypercalcemia.
One proposed explanation for the development of secondary
hyperparathyroidism in CRF is known as the "trade-off" mechanism,
first described by Bricker in a 1972 article in the New England
Journal of Medicine.10 Dr. Bricker explained that as renal failure
progresses, the number of renal excretory units decreases, and thus
the surviving nephrons must make an increasing contribution to
maintain homeostasis. The maintenance of phosphorus balance requires
that excretion be equal to intake. To accomplish this, the residual
nephrons are stimulated by an increased PTH level, which induces a
phosphaturic effect. This compensatory workload of the parathyroid
glands results in hyperplasia of the chief cells in the glands. In
other words, for an increase in phosphate excretion per residual
nephrons, the cost is the development of secondary
hyperparathyroidism.
Patients with chronic renal failure are constantly being stimulated to
secrete PTH in response to their reduced glomerular filtration rate,
hyperphosphatemia, hypocalcemia and decreased calcitriol production.
The outcome of this vicious cycle is often hypertrophy of the
parathyroid glands.11
Secondary hyperparathyroidism in turn increases mobilization of
calcium, magnesium and phosphorus from bones, predisposing to the
development of soft-tissue calcifications and bone demineralization.12
Therefore, adequate and early control of serum phosphate levels in a
patient with chronic renal failure is critical in preventing and
treating secondary hyperparathyroidism.13
Metastatic Calcifications
Calcifications could affect any part of the body and most often
involve the arterial vasculature, ocular and periarticular tissue,
cutaneous and subcutaneous tissue and the visceral organs.10 Kuzela
and colleagues, in the American Journal of Pathology in 1977, assessed
the accuracy of claims that an elevated phosphorus level can induce
metastatic soft-tissue calcifications. They reviewed autopsy protocols
and microscopic slides of 56 dialyzed patients and 18 nondialyzed
chronically uremic patients. They identified calcifications in
approximately 80% of the dialysis patients and 44% of the nondialysis
patients. The visceral calcifications, when present, most frequently
affected the heart, lung, stomach and kidneys.14 The calcifications
were severe in 36% of the dialysis patients and, if located in the
myocardium, were often life-threatening.
Other proposed factors contributing to the development of soft-tissue
calcifications include an elevated PTH level, calcitriol
supplementation, local tissue pH and the critical calcium-phosphate
product (greater than 70 mg/dL).15 Calcifications affecting the joints
could precipitate arthritic attacks and limit patients' range of
motion. Periarticular calcifications are usually visible on X-rays--
unlike those affecting the viscera, which are more insidious in onset
and contribute significantly to the mortality rate of the dialysis
population.14
Renal Osteodystrophy
The increased secretion of PTH in renal failure stimulates increased
osteoblastic and osteoclastic bone activity, leading to osteitis
fibrosa cystica (high-turnover bone disease).16 Osteitis fibrosa
cystica is a presentation of renal osteodystrophy commonly seen in the
ESRD population.
Other presentations of this syndrome include osteomalacia and adynamic/
aplastic bone disease (low-turnover bone disease).16 The objective of
medical management using calcium and calcitriol supplementation in
osteitis fibrosa cystica is lowering the PTH level. This approach may
result in the development of hypercalcemia, which forces
discontinuation of both medications.
Adynamic/aplastic bone disease is thought to occur secondary to a
decrease in PTH level, which is seen with advanced age, diabetes
mellitus and oversuppression of the parathyroid glands.17
Treatment Modalities
The management approach to hyperphosphatemia in ESRD must be
considered in the context of patients' nutritional intake, serum
calcium, PTH level and vitamin D supplementation.5 No form of dialytic
therapy alone effectively maintains normal serum phosphorus levels.
Dietary phosphate restriction is often the first and most benign
approach to controlling serum phosphorus. Phosphate restriction may be
effective in the early stages of chronic renal failure, but as the GFR
continues to decline, it becomes less effective. Therefore, oral
phosphorus binding agents must be relied on to control the serum
phosphorus.
Dietary Phosphorus Restriction
Phosphorus restriction is limited in its ability to effectively
regulate the serum phosphorus levels in ESRD. Of utmost concern with
phosphorus restriction is that food products high in phosphorus are
often the best source of protein.18 Restricting these food products
places constraints on the patients' protein intake and predisposes
them to malnourishment.19 Malnutrition is estimated to exist in
approximately 50% of the ESRD population and is a major contributing
factor to their increased morbidity and mortality rates.20 The current
recommendation is that a dietary protein intake of 1.0g/kg/day be
ingested to maintain a neutral nitrogen balance.18 Yet in light of
this limited protein intake, the dialysis patient is still apt to
develop hyperphosphatemia. Confronted with such limitations, oral
phosphorus binders are often implemented to help control serum
phosphorus.
Phosphorus-Binding Agents
Binders often are implemented as a result of either inadequate
dialysis removal of phosphorus or an unfavorable outcome of dietary
phosphate restriction. Phosphorus-binding agents include aluminum
gels, calcium-containing salts, magnesium-based compounds and the most
recently approved aluminum-free, calcium-free nonabsorbable phosphorus
binder, Renagel.
Aluminum-Containing Binders
Historically, aluminum-containing binders were considered the premier
phosphate-binding agents in the ESRD population. However, throughout
the years their use has continually declined. Much of the decline is
related to the fact that during the earlier years of aluminum-
containing binder use, many dialysis units reported epidemic outbreaks
of aluminum-associated encephalopathy, osteomalacia, myopathy and
anemia.21 It is now widely known that ESRD patients receiving aluminum-
containing phosphate binders are at an increased risk of developing
aluminum toxicity. The recommendations are that these binders be used
only in instances where calcium-containing binders have proven
inadequate or have resulted in hypercalcemia.22 Chronic administration
of aluminum-containing binders should be avoided.
Calcium-Containing Binders
In light of the adverse effects associated with aluminum-containing
binders, calcium-containing binders have become the premier phosphate-
binding therapy in the last decade. These include calcium carbonate,
calcium acetate, calcium citrate and calcium alginate. Of these, the
most commonly used are calcium carbonate and calcium acetate. The dose
of calcium-containing phosphate binder prescribed varies significantly
and depends largely on the individuals phosphorus intake.
Hypercalcemia is the most frequently encountered complication
associated with the use of calcium-containing phosphate binders. This
is most likely to occur in patients with a low bone-turnover rate or
in patients receiving vitamin D supplementation.23
An alternative to calcium carbonate is calcium acetate (Phoslo), which
is thought to be twice as effective in lowering serum phosphorus
levels. Sheikh and colleagues evaluated the accuracy of this claim by
using a gastrointestinal washout method to compare the effectiveness
of calcium carbonate vs. calcium acetate.24 Subjects were given a meal
containing 11.1 mmol of phosphorus and divided into two groups. One
group received 25 mmol of elemental calcium from calcium carbonate.
The other group received an equivalent dose of calcium from calcium
acetate. The carbonate group decreased their absorbed phosphate load
from 8.5 mmol to 4.9 mmol, and the acetate group decreased their
phosphate load to an astonishing 2.9 mmol on average.
Calcium citrate is infrequently used, because it is thought to enhance
gastrointestinal aluminum absorption by opening cellular tight
junctions in the small intestines.25 The other calcium-containing
binders are considered relatively expensive and are generally avoided.
Magnesium-Containing Binders
Magnesium-containing binders are considered effective in controlling
serum phosphorus levels in ESRD patients. Reluctance to their use may
be due to concerns for the development of hypermagnesemia and its
associated complications (e.g., cardiac arrhythmia, seizures,
diarrhea).12
I have read a few posts here from a few people that are in dialysis
and say that they take very few prescribed medications. If so, I
would think they would be the ones to talk to. Any effort you make to
avoid medications that are unneeded is a benefit to my view. There
are so many side effects these days with all the drugs they're putting
out, that it's hard to determine which of them are causing or fixing a
problem.
Good Luck,
Chris
I have been on dialysis now for eight weeks. My Nephrologist started me
on Renagel two weeks ago. It appears to be causing severe constipation,
so he has now switched me over to Phoslo. He says that they both can
have side effects and that each patient is different.
There is also a cost consideration, since these pills can run as much as $1.25 each.
At 3-4 pills per day, or in some cases, 6-8 per day, this can be quite expensive.
For those individuals that have been told that they are going to be on a binder,
please review ALL the above information!
FiOS-Dave
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 Re: High phosphorus levels | |
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