Summarize the pros and cons of common phosphate binders overtime.
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Rania Mahmoud
Summarize the pros and cons of common phosphate binders overtime. Aluminum salts: -Introduced in the 1970s, were the first phosphate binders -Reduce phosphate availability by forming coordination compounds with phosphate ions, creating insoluble aluminum phosphate precipitates in the GI tract -Pros : effective -Cons: neurotoxicity,16 cognitive disturbances, osteomalacia, and anemia Calcium-based phosphate binders: -Pros:effective,20,21 inexpensive,22 and widely used -Cons : vascular calcification and increased arterial stiffness A combination of magnesium hydroxide and aluminum hydroxide -Pros : effective for phosphate control in the 1980s and did not cause uncontrolled hypermagnesemia Calcium acetate/magnesium carbonate was also found to effectively lower phosphorus levels and was not associated with anincreased risk of hypercalcemia calcium acetate/magnesium carbonate at doses that reduced vascular calcification did not adversely affect bone remodeling or alter bone magnesium levels. -Cons: not widely studied Sevelamer hydrochloride -Pros: decreased phosphorus concentrations without increasing calcium load. Sevelamer may lead to lower all-cause death. and induce less hypercalcemia than calciumbased binders. -Cons: no clinically significant difference for outcomes of CV death, myocardial infarction, stroke, fracture, or coronary artery calcification and worsen metabolic acidosis Lanthanum carbonate -Pros :approved in 2004,also reduces phosphorus levels without increasing calcium load,potentially decreasing the risk of treatmentrelated hypercalcemia -Cons: GI obstruction, ileus, GI perforation, and fecal impaction Iron-based binders are sucroferric hydroxide and ferric citrate: -Pros: Sucroferric hydroxide was approved in 2013.It effectively reduces phosphorus levels in patients undergoing dialysis and has a lower pill burden than sevelamer carbonate.Ferric citrate was approved in 2014. Ferric citrate use and revealed it to be effective in lowering phosphorus and phosphoruscalcium product. –Cons:The medication caused significantly higher GI side effects.
Aluminum salts, were the first phosphate binders, reduce phosphate availability by forming coordination compounds with phosphate ions, creating insoluble aluminum phosphate precipitates in the GI tract.
Pros: effective, cheap
Cons: Al toxicity, neurotoxicity,16 cognitive disturbances, osteomalacia, and anemia
Calcium-based phosphate binders
Pros: effective, inexpensive, and widely used.
Cons: potential drivers of vascular calcification and, thus, contributors to increased CV mortality.23 Increased calcium load from the use of calcium-based binders has been associated with vascular calcification and increased arterial stiffness.
A combination of magnesium hydroxide and aluminum hydroxide or Calcium acetate/magnesium carbonate
Pros: did not cause uncontrolled hypermagnesemia. effectively lower phosphorus levels. reduced serum phosphorus levels and was not associated with an increased risk of hypercalcemia, calcium acetate/magnesium carbonate at doses that reduced vascular calcification did not adversely affect bone remodeling or alter bone magnesium levels.
Cons: availability, not widely studied
Sevelamer hydrochloride
Pros: decreased phosphorus concentrations without increasing calcium load. induce less hypercalcemia than calcium based binders.
Cons: no clinically significant difference for outcomes of CV death, myocardial infarction, stroke, fracture, or coronary artery calcification.
Worsen metabolic acidosis, sevelamer carbonate was developed as an alternative. However patients treated with sevelamer hydrochloride had a greater mean decrease in serum phosphorus than those treated with sevelamer carbonate.
Lanthanum carbonate
Pros: reduces phosphorus levels without increasing calcium load,
Cons: prescribing information for lanthanum includes a precaution that serious cases of GI obstruction, ileus, GI perforation, and fecal impaction have been reported. Some cases required surgery or hospitalization. Patients are advised to chew the tablet completely to reduce the risk of these serious adverse GI events. In addition, accumulation of lanthanum carbonate in the liver has been observed in animal models, as The liver is the main route for lanthanum excretion, however no conclusive evidence of hepatotoxicity related to lanthanum Hence, preexisting liver disease is not a contraindication to prescribing lanthanum.
Sucroferric hydroxide and ferric citrate
Pros: non-calcium, iron-based binders reduce phosphorus levels in patients undergoing dialysis and have a lower pill burden than sevelamer carbonate.
Cons: the medication caused significantly higher GI side effects.
magnesium containing binders
pros effective no hypercalcemia, did not adversely affect bone remodeling or alter bone magnesium levels.
cons hypermagnesemia, diarrhia
Sevelamer hydrochloride/carbonate was approved by the US FDA in 2000.
pros effective no hypercalcemia
cons expensive, GIT upset ileus, bowel obstruction, bowel perforation
Lanthanum carbonate, approved in 2004,
pros effective no hypercalcemia
cons GIT upset ileus, bowel obstruction,fecal impaction, bowel perforation, hepatoxicity
iron-based binders started in 2013
pros effective , no hypercalcemia
cons GI side effects nausea vomitting, feacal discoloration abdominal pain cough
The pros and cons of standard phosphate binders over time.
Calcium-containing and aluminum-containing were available for many years and cheaply. Calcium-containing binders are an enticing first choice, but they accelerate hypercalcemia and vascular calcification.
aluminum-containing binders have a good capacity for phosphate binding, but there was a warning about concern aluminum intoxication.
New non-calcium-based binders are the more expensive
AL based phosphate binder: effective, cheap, but deposited (aluminum phosphate precipitates) in bone causing osteomalecia, causes dementia and anemia
Ca based phosphate binder: inexpensive, source of calcium supplement in associated hypocalcemia, but increased risk of hypercalcemia contributes to vascular calcification
Non AL non Ca (sevelamer): avoid side effects of calcium and aluminum but causes GIT symptoms nausea, vomiting, ilius, fecal impact ion, bowel obstruction and perforation
Lanthanum: avoid side effects of calcium and aluminum but causes GIT symptoms nausea, vomiting, ilius, serious cases of bowel obstruction and perforation, accumulates in the liver
Iron based: effective, lower pill burden than sevelamer, source of iron, improve iron stores in associated iron deficiency, but causes significantly higher GIT side effects which may lead to ttt discontinuation.
Mg based: source of Mg, but can cause diarrhea and hypermagnesemia
Drugs targeting phosphorus absorption:
EOS789: reduce transcellular phosphorus absorption (inhibit NaPi2b cotransporter), but larger studies are lacking to support widespread use.
tenapanor: inhibit paracellular phosphorus absorption (inhibit NHE3), low pill burden (1tab bid), generally tolerable, but causes diarrhea.
Aluminum based binders:
pros….form insoluble Al po4 compounds and decrease its absorption
cons…..neurotoxicity- osteomalacia- anemia- cognitive dse
calcium base binders:
pros….decrease po4 and increase calcium stores
cons….arterial stiffness and vascular calcification
lanthanum and sevelamer based binders:
pros….no increase in calcification
cons….GIT dse as nausea, vomiting , diarrhea , fecal impaction and bowel obstruction and perforation
Iron based binders:
pros….decrease po4 and treat anemia as well
cons….stool discoloration , constipation , GIT dse
A) Aluminum BASED BINDER:
Pros:
MOST effective, cheap .
Cons :
1- neurotoxicity, 2- cognitive dysfunction, 3- aluminum induced osteomalacia and anemia
B) Calcium based:
Pros:
1- Cheap, 2- effective, 3- correct hypocalcemia 4- reduce hypocalcemia induced hyperparathyroidism,
Cons :
1- Minimal or no effect on FGF23 level 2- soft tissue calcification 3- arterial stiffness and 4- increase cardio-vascularevents on advanced cKD patients.
C) Magnesium based binders
Pros effective,
1- Effective and cheap 2- less hypocalcemia
Cons:
1- Hypermagnesemia, 2- effect on PTH secretion and bone mineralization , 3-Diarrhea
AL -based binders : cheap effective. But.. anemia neurotoxicity adymamic bone disease Calcium-based binders: Cheap Effective But.. vascular/tissues calcification Mg-based binders: cheap ca free . but
diarrhea Sevelamer
effective Ca free but GIT upset bowel perforation costy Lanthanum Ca free effective . but .. GIT obstruction accumulated in liver cells expensive iron based binder
Aluminium salts:
Effective but cause neurotoxicity,cognitive impairment,osteomalacia and anaemia.
Calcium containing phosphate binders:
effective, cheap but increase calcium load, vascular calcification and arterial stiffness.
Magnesium based binders:
effective but may be associated with diarrhoea and hypermagnesemia.
Sevelamer hydrocholaride:
effective without increase calcium load but associated with nausea,vomiting,ileus,fecal impaction,bowel obstruction or perforation,worsen metabolic acidosis.
Lanthanum carbonate:
effective without increase calcium load but associated with ileum,fecal impaction,bowel obstruction or perforation and accumulation of lanthanum in the liver.
Iron based binders(sucroferric hydroxide and ferric citrate):
reduce phosphorus but cause GI side effects.
The first one was Aluminum Pros effective and cheap .
cons :causes neurotoxicity, cognitive dysfunction, osteomalacia and anemia
Then calcium based bindersPros:cheap, effective, Cons induce metastatic calcification, arterial stiffness and promote cardio-vascular mortality,
Then Magnesium based binders
Pros effective, not causes hypercalcimia
Cons hypermagnesemia, Mg affect bone turnover and mineralization, diarrhea
sevelamir non calcium containing phosphate binders Pros effective, not cause hypercalcimia, lower overall mortality Cons causes nausea, vomiting, ileus, fecal impaction, bowel obstruction, bowel perforation, sevelamir hydrochloride cause worsening metabolic acidosis.
lanthanum Pros effective and not cause hypercalcimia Cons ileus, fecal impaction, bowel obstruction, perforation, accumulated in the liver and no evidence of causing liver injury
iron based binders Pros effective, not cause hypercalcimia, less pill burden and protect against anemia and decrease consumption of ESA
Cons more GIT side effects nausea, vomiting, discoloration of stool, diarrhea, constipation, abdominal pain
*Aluminum salt bind to phosphorous ion and form insoluble aluminum phosphate complex in GIT.
Pros :effective cons :causes neurotoxicity, cognitive dysfunction, osteomalacia and anemia
*calcium based binders
Pros:cheap, effective and wide spread
Cons :cause vascular calcification, arterial stiffness and high cardio-vascular mortality
*Magnesium based binders
Pros :effective, not causes hypercalcimia
Cons :hypermagnesemia, Mg affect bone turnover and mineralization, diarrhea
*sevelamir non calcium containing phosphate binders
Pros :effective, not cause hypercalcimia, lower overall mortality
Cons : causes nausea, vomiting, ileus, fecal impaction, bowel obstruction, bowel perforation, sevelamir hydrochloride cause worsening metabolic acidosis.
*lanthanum
Pros :effective and not cause hypercalcimia
Cons :ileus, fecal impaction, bowel obstruction, perforation, accumulated in the liver
*iron based binders
Pros :effective, not cause hypercalcimia, less pill burden
Cons : more GIT side effects nausea, vomiting, discoloration of stool, diarrhea, constipation, abdominal pain, cough.
Aluminium hydroxide is still an effective phosphorous binder, but we use as rescue therapy for not more than a couple of weeks when we are unable to use calcium-containing binders not to increase the risk of calcification.
Still, the Ca-based binders are the main stay of therapy and the first line. Sevalemer or Lantanum are given to patients on dialysis who failed to maintain normal phosphorous levels despite effective dialysis with Ca-based treatment given for a minimum of 3 months. Despite insurance limitations, this is good for relief of the hypocalcemia dominant in end-stage kidney disease.
aluminium hydroxide is cheap but toxic, leading to cognitive problems and anaemia
Ca-based binders are cheap and help restore calcium balance but will lead to calcium overload in the long run
sevelamer is better but may lead to negative calcium balance, less potent (somehow); the burden of the high number of tablets may cause trouble
Lantanum, available in our country as a powder (500/750/1000) is very effective but gastrointestinal intolerance is a handicap. Accumulation is still something that need to be monitored afterwards. No big problem has been reported till now since Lantanum entered the markets
NOTE: Price is not an issue (ALL HD patients are covered with government insurance)
Aluminum phosphate binder has been used since 1970, it is a good phosphate binder but found to have a lot of side effects which affect its use.It is will not affect the Ca balance.
Ca phosphate binder it is expensive and affects the total Ca balance which in turn will increase the vascular stiffness.
Sevelamer and lanthanum both of them are Phosphate binders, expensive and have a lot of GIT side effects
1-Phosphate binders began with the 1970s-introduced 1-aluminum salts. In the GI tract, aluminum salts form coordination compounds with phosphate ions, yielding insoluble aluminum phosphate precipitates. Aluminum-based phosphate binders were successful, but osteomalacia and anemia caused their discontinuation.
2- Calcium-based phosphate binders were introduced in the mid-1980s to replace aluminum-based ones.
They were effective, cheap, and extensively used when first launched.
However, calcium-based binders may cause arterial calcification and increase CV mortality.
Calcium-based binders enhance vascular calcification and arterial stiffness.
3-Calcium acetate/magnesium carbonate in an animal model assessed magnesium’s potential impact on bone turnover and mineralization.
29 Calcium acetate/magnesium carbonate decreased vascular calcification without affecting bone remodeling or magnesium levels.
4- sevelamer reduced phosphorus without increasing the calcium burden.
A Cochrane systematic review of phosphate binders indicated that sevelamer may reduce all-cause mortality in dialysis patients. Sevelamer carbonate was created because sevelamer hydrochloride worsened metabolic acidosis33.
5-Lanthanum carbonate, licensed in 2004, reduces phosphorus levels without increasing calcium load. possibly reducing treatment-related hypercalcemia.
Lanthanum’s prescription instructions warn of significant GI blockage, ileus, GI perforation, and fecal impaction.
6- Ferric citrate and sucroferric hydroxide bind 6-iron. 2013 authorized sucroferric hydroxide. It lowers phosphorus levels in dialysis patients with fewer pills than sevelamer carbonate. 2014 authorized ferric citrate. A meta-analysis of 16 trials found ferric citrate to decrease phosphorus and phosphorus-calcium product better than no active treatment and equivalent to other phosphate binders. However, the drug produced more GI side effects.
Summarize the pros and cons of common phosphate binders overtimecalcium based phosphate binders:
pros:
1-effective
2-inexpensive
3-widely used
cons:
1-vascular calcification(increase calcium load)
2-increase cv mortality
3-increase arterial stifness
============
aluminum based phosphate binder:
pros:
1-effective
2-not associated with hypercalcemia
cons:
risk of aluminum toxicity
=========
sevelamer HCL:
pros:
1-decrease serum phosphorous without increase serum calcium
cons
worsen metabolic acidosis
============
lanthanum carbonate :
pros: decrease serum phosphorous without increase serum calcium cons: GI obstruction ,ileus ,perforation and faecal impaction expensive
Summarize the pros and cons of common phosphate binders overtime.
All are effective in reducing phosphate levels and associated with significant side effects, the differences comes in terms pills burden. The newer ones such as iron-based may have less pills burden
Summarize the pros and cons of common phosphate binders overtime.
Aluminum salts:
-Introduced in the 1970s, were the first phosphate binders
-Reduce phosphate availability by forming coordination compounds with phosphate ions, creating insoluble
aluminum phosphate precipitates in the GI tract
-Pros : effective
-Cons: neurotoxicity,16 cognitive disturbances, osteomalacia, and anemia
Calcium-based phosphate binders:
-Pros: effective,20,21 inexpensive,22 and widely used
-Cons : vascular calcification and increased arterial stiffness
A combination of magnesium hydroxide and aluminum hydroxide
-Pros : effective for phosphate control in the 1980s and did not cause uncontrolled hypermagnesemia
Calcium acetate/magnesium carbonate was also found to effectively lower phosphorus levels and was not associated with anincreased risk of hypercalcemia calcium acetate/magnesium carbonate at doses that reduced vascular calcification did not adversely affect bone remodeling or alter bone magnesium levels.
-Cons: not widely studied
Sevelamer hydrochloride
-Pros: decreased phosphorus concentrations without increasing calcium load. Sevelamer may lead to lower all-cause death.
and induce less hypercalcemia than calciumbased binders.
-Cons: no clinically significant difference for outcomes of CV death, myocardial infarction, stroke, fracture, or coronary artery calcification and worsen metabolic acidosis
Lanthanum carbonate
-Pros : approved in 2004, also reduces phosphorus levels without increasing calcium
load, potentially decreasing the risk of treatmentrelated hypercalcemia
-Cons: GI obstruction, ileus, GI perforation, and fecal impaction
Iron-based binders are sucroferric hydroxide and ferric citrate:
-Pros: Sucroferric hydroxide was approved in 2013. It effectively reduces phosphorus
levels in patients undergoing dialysis and has a lower pill burden than sevelamer carbonate. Ferric citrate
was approved in 2014. Ferric citrate use and revealed it to be effective in lowering phosphorus and phosphoruscalcium product.
–Cons:The medication caused significantly higher GI side effects.
Here is a suggested answer:
Aluminum salts, were the first phosphate binders, reduce phosphate availability by forming coordination compounds with phosphate ions, creating insoluble aluminum phosphate precipitates in the GI tract.
Pros: effective, cheap
Cons: Al toxicity, neurotoxicity,16 cognitive disturbances, osteomalacia, and anemia
Calcium-based phosphate binders
Pros: effective, inexpensive, and widely used.
Cons: potential drivers of vascular calcification and, thus, contributors to increased CV mortality.23 Increased calcium load from the use of calcium-based binders has been associated with vascular calcification and increased arterial stiffness.
A combination of magnesium hydroxide and aluminum hydroxide or Calcium acetate/magnesium carbonate
Pros: did not cause uncontrolled hypermagnesemia. effectively lower phosphorus levels. reduced serum phosphorus levels and was not associated with an increased risk of hypercalcemia, calcium acetate/magnesium carbonate at doses that reduced vascular calcification did not adversely affect bone remodeling or alter bone magnesium levels.
Cons: availability, not widely studied
Sevelamer hydrochloride
Pros: decreased phosphorus concentrations without increasing calcium load. induce less hypercalcemia than calcium based binders.
Cons: no clinically significant difference for outcomes of CV death, myocardial infarction, stroke, fracture, or coronary artery calcification.
Worsen metabolic acidosis, sevelamer carbonate was developed as an alternative. However patients treated with sevelamer hydrochloride had a greater mean decrease in serum phosphorus than those treated with sevelamer carbonate.
Lanthanum carbonate
Pros: reduces phosphorus levels without increasing calcium load,
Cons: prescribing information for lanthanum includes a precaution that serious cases of GI obstruction, ileus, GI perforation, and fecal impaction have been reported. Some cases required surgery or hospitalization. Patients are advised to chew the tablet completely to reduce the risk of these serious adverse GI events. In addition, accumulation of lanthanum carbonate in the liver has been observed in animal models, as The liver is the main route for lanthanum excretion, however no conclusive evidence of hepatotoxicity related to lanthanum Hence, preexisting liver disease is not a contraindication to prescribing lanthanum.
Sucroferric hydroxide and ferric citrate
Pros: non-calcium, iron-based binders reduce phosphorus levels in patients undergoing dialysis and have a lower pill burden than sevelamer carbonate.
Cons: the medication caused significantly higher GI side effects.
Aluminum salts, 1970s
pros effective
cons neurotoxicity, cognitive disturbances, osteomalacia, and anemia.
Calcium-based phosphate binders 1980s
pros effective,inexpensive,and widely used.
cons vascular calcification and, increased CV mortality. increased arterial stiffness
magnesium containing binders
pros effective no hypercalcemia, did not adversely affect bone remodeling or alter bone magnesium levels.
cons hypermagnesemia, diarrhia
Sevelamer hydrochloride/carbonate was approved by the US FDA in 2000.
pros effective no hypercalcemia
cons expensive, GIT upset ileus, bowel obstruction, bowel perforation
Lanthanum carbonate, approved in 2004,
pros effective no hypercalcemia
cons GIT upset ileus, bowel obstruction,fecal impaction, bowel perforation, hepatoxicity
iron-based binders started in 2013
pros effective , no hypercalcemia
cons GI side effects nausea vomitting, feacal discoloration abdominal pain cough
Alaminuim-based binders
Pros: effective and cheap
Cons:cognitive disorder , osteomalacia , anemia.
Magnesium-based binders
Pros: effective and cheap
Cons:hypermagnesemia ,diarrhea.
Lanthanuim- based binders
Pros: effective no hypercalcimia
Cons: illeus , GI obstruction, GI perforation, feacal impaction.
Calcium-based binders
Pros:effective and cheap
Cons:vascular calcification,arterial stiffness.
Sevelamir hydrochloride
Pros:effective no hypercalcimia
Cons:nausea,vomiting, illeus, feacal impaction , intestinal obstruction, intestinal perforation.
Iron-based binders
Pros:effective no hypercalcimia
Cons:nausea ,vomiting,cough.diarrhea,constipation,abdominal pain,discolored feases.
The pros and cons of standard phosphate binders over time.
aluminum-containing binders have a good capacity for phosphate binding, but there was a warning about concern aluminum intoxication.
phosphate binders (phosphorus chelators):
Drugs targeting phosphorus absorption:
Aluminum based binders
Pros:
effective, cheap .
Cons :
cognitive dysfunction, aluminum induced osteomalacia and anemia .
Calcium based
Pros:
Cheap, correct hypocalcemia .
Cons :
Vascular calcification, arterial stiffness .
Magnesium based binders
Pros
Effective and cheap .
Cons:
Hypermagnesemia, Diarrhea .
Sevelamer
Pros
effective, no hypercalcemia .
Cons
GIT side effects, cost .
lanthanum
Pros
effective, no hypercalcemia .
Cons
expensive, GIT side effects, accumulation in liver .
Iron based phosphate binders
Pros
effective, no hypercalcemia.
Cons
GIT disturbance .
Aluminium based binders
Cheap , effective
Osteomalacia, anemia, cognitive impairment
Mg based binders
Cheap, effective
Diarrhea, hypermagnesemia
Ca based binders
Cheap
Hypercalcaemia, calciphylaxis
Sevelamir
Effective, avoid hypercalcaemia
Expensive, GIT complications, acidosis
Lanthanum
Effective, avoid hypercalcaemia
Expensive, GIT complications, bone deposits
Iron based
Reduce pill burden, epo dose , effective
Expensive, teeth staining, constipation
Aluminum based binders:
pros….form insoluble Al po4 compounds and decrease its absorption
cons…..neurotoxicity- osteomalacia- anemia- cognitive dse
calcium base binders:
pros….decrease po4 and increase calcium stores
cons….arterial stiffness and vascular calcification
lanthanum and sevelamer based binders:
pros….no increase in calcification
cons….GIT dse as nausea, vomiting , diarrhea , fecal impaction and bowel obstruction and perforation
Iron based binders:
pros….decrease po4 and treat anemia as well
cons….stool discoloration , constipation , GIT dse
Aluminum based binders
Pros:
effective, cheap .
Cons :
cognitive dysfunction, aluminium induced osteomalacia and anemia
Calcium based
Pros:
Cheap, correct hypocalcemia
Cons :
no effect on FGF23 level, soft tissue calcification, arterial stiffness
Magnesium based binders
Pros
Effective and cheap
Cons:
Hypermagnesemia, effect on PTH secretion and bone mineralization ,Diarrhea
Sevelamer
Pros
effective, no hypercalcemia,
Cons
GIT side effects, costly
lanthanum
Pros :
effective, no hypercalcemia,
Cons
expensive, GIT side effects, accumulation in liver
Iron based phosphate binders
Pros:
effective, no hypercalcemia, improve anemia
Cons:
GIT disturbance
A) Aluminum BASED BINDER:
Pros:
MOST effective, cheap .
Cons :
1- neurotoxicity, 2- cognitive dysfunction, 3- aluminum induced osteomalacia and anemia
B) Calcium based:
Pros:
1- Cheap, 2- effective, 3- correct hypocalcemia 4- reduce hypocalcemia induced hyperparathyroidism,
Cons :
1- Minimal or no effect on FGF23 level 2- soft tissue calcification 3- arterial stiffness and 4- increase cardio-vascularevents on advanced cKD patients.
C) Magnesium based binders
Pros effective,
1- Effective and cheap 2- less hypocalcemia
Cons:
1- Hypermagnesemia, 2- effect on PTH secretion and bone mineralization , 3-Diarrhea
Non calcium containing phosphate binders:
D) Sevelamer:
Pros
1- effective, 2- no hypercalcemia,
Cons
1- Nausea, vomiting, 2- bowel obstruction, -3- sevelamer hydrochloride cause metabolic acidosis.
E) lanthanum:
Pros :
1- effective, 2- no hypercalcemia,
Cons
1- expensive 2- ileus, 3- fecal impaction, 4- bowel obstruction, 5- accumulated in the liver
F) Iron based phosphate binders:
Pros:
1- effective, 2- no hypercalcemia, 3- improve anemia
Cons:
1- GIT side effects nausea, vomiting, 2- stool discoloration 3- constipation, 4-abdominal pain
AL -based binders :
cheap
effective.
But..
anemia
neurotoxicity
adymamic bone disease
Calcium-based binders:
Cheap
Effective
But..
vascular/tissues calcification
Mg-based binders:
cheap
ca free .
but
diarrhea
Sevelamer
effective
Ca free
but
GIT upset
bowel perforation
costy
Lanthanum
Ca free
effective .
but ..
GIT obstruction
accumulated in liver cells
expensive
iron based binder
effective
but
GIT complication
Aluminium salts:
Effective but cause neurotoxicity,cognitive impairment,osteomalacia and anaemia.
Calcium containing phosphate binders:
effective, cheap but increase calcium load, vascular calcification and arterial stiffness.
Magnesium based binders:
effective but may be associated with diarrhoea and hypermagnesemia.
Sevelamer hydrocholaride:
effective without increase calcium load but associated with nausea,vomiting,ileus,fecal impaction,bowel obstruction or perforation,worsen metabolic acidosis.
Lanthanum carbonate:
effective without increase calcium load but associated with ileum,fecal impaction,bowel obstruction or perforation and accumulation of lanthanum in the liver.
Iron based binders(sucroferric hydroxide and ferric citrate):
reduce phosphorus but cause GI side effects.
The first one was Aluminum Pros effective and cheap .
cons :causes neurotoxicity, cognitive dysfunction, osteomalacia and anemia
Then calcium based bindersPros:cheap, effective, Cons induce metastatic calcification, arterial stiffness and promote cardio-vascular mortality,
Then Magnesium based binders
Pros effective, not causes hypercalcimia
Cons hypermagnesemia, Mg affect bone turnover and mineralization, diarrhea
sevelamir non calcium containing phosphate binders Pros effective, not cause hypercalcimia, lower overall mortality Cons causes nausea, vomiting, ileus, fecal impaction, bowel obstruction, bowel perforation, sevelamir hydrochloride cause worsening metabolic acidosis.
lanthanum Pros effective and not cause hypercalcimia Cons ileus, fecal impaction, bowel obstruction, perforation, accumulated in the liver and no evidence of causing liver injury
iron based binders Pros effective, not cause hypercalcimia, less pill burden and protect against anemia and decrease consumption of ESA
Cons more GIT side effects nausea, vomiting, discoloration of stool, diarrhea, constipation, abdominal pain
*Aluminum salt bind to phosphorous ion and form insoluble aluminum phosphate complex in GIT.
Pros :effective cons :causes neurotoxicity, cognitive dysfunction, osteomalacia and anemia
*calcium based binders
Pros:cheap, effective and wide spread
Cons :cause vascular calcification, arterial stiffness and high cardio-vascular mortality
*Magnesium based binders
Pros :effective, not causes hypercalcimia
Cons :hypermagnesemia, Mg affect bone turnover and mineralization, diarrhea
*sevelamir non calcium containing phosphate binders
Pros :effective, not cause hypercalcimia, lower overall mortality
Cons : causes nausea, vomiting, ileus, fecal impaction, bowel obstruction, bowel perforation, sevelamir hydrochloride cause worsening metabolic acidosis.
*lanthanum
Pros :effective and not cause hypercalcimia
Cons :ileus, fecal impaction, bowel obstruction, perforation, accumulated in the liver
*iron based binders
Pros :effective, not cause hypercalcimia, less pill burden
Cons : more GIT side effects nausea, vomiting, discoloration of stool, diarrhea, constipation, abdominal pain, cough.
Phosphate binders pros and cons
Calcium carbonate;
Pros;
Cons;
Calcium acetate;
Pros;
Cons;
Aluminum hydroxide;
Pros;
Cons;
Sevelamer-HCL;
Pros;
Cons;
Sevelamer carbonate;
Pros;
Cons;
Lanthanum carbonate;
Pros;
Cons;
Magnesium based;
Pros;
Cons;
Trivalent iron containing binder;
Pros
Cons;
AL -based binders :
pros –
cheap
effective.
cons :
anemia –neurotoxicity—MBD.
Calcium-based binders:
pros :
cheap—— effective
cons:
vascular calcification —
Mg-based binders:
pros
cheap—-ca free .
cons
diarrhea
Sevelamer
pros
effective —Ca free
Cons
GIT upset—-bowel perforation .—-expensive
Lanthanum
pros
Ca free —effective .
cons
GIT obstruction —–accumulated in liver cells .—-expensive
iron based binder
pros
effective ———-
cons
GIT complication
Aluminium hydroxide is still an effective phosphorous binder, but we use as rescue therapy for not more than a couple of weeks when we are unable to use calcium-containing binders not to increase the risk of calcification.
Still, the Ca-based binders are the main stay of therapy and the first line. Sevalemer or Lantanum are given to patients on dialysis who failed to maintain normal phosphorous levels despite effective dialysis with Ca-based treatment given for a minimum of 3 months. Despite insurance limitations, this is good for relief of the hypocalcemia dominant in end-stage kidney disease.
aluminium hydroxide is cheap but toxic, leading to cognitive problems and anaemia
Ca-based binders are cheap and help restore calcium balance but will lead to calcium overload in the long run
sevelamer is better but may lead to negative calcium balance, less potent (somehow); the burden of the high number of tablets may cause trouble
Lantanum, available in our country as a powder (500/750/1000) is very effective but gastrointestinal intolerance is a handicap. Accumulation is still something that need to be monitored afterwards. No big problem has been reported till now since Lantanum entered the markets
NOTE: Price is not an issue (ALL HD patients are covered with government insurance)
Aluminum phosphate binder has been used since 1970, it is a good phosphate binder but found to have a lot of side effects which affect its use.It is will not affect the Ca balance.
Ca phosphate binder it is expensive and affects the total Ca balance which in turn will increase the vascular stiffness.
Sevelamer and lanthanum both of them are Phosphate binders, expensive and have a lot of GIT side effects
.
Summarize the pros and cons of common phosphate binders overtime.
calcium-based phosphate binders :
1- pros : inexpensive.
2- cons : arterial stifness and vascular calcification.
Aluminum based phoshate binders
1- pros : inexpensive, no effect on calcium balance.
2- Cons : Aluminum toxicity with anaemia, dementia, CKD MBD
Sevelamer :
1- pros : no effect on calcium balance.
2- cons : expensive, unpalatable, GIT side effects, SBO GI perforation ileus fecal impaction
Lanthunum :
1- pro : no effect on calcium balance.
2- cons : expensive, GIT side effects, sbo, GI perforation, fecal impaction accumulation in liver
Why is it hard for most patients to achieve target phosphate levels?
1-Phosphate binders began with the 1970s-introduced 1-aluminum salts. In the GI tract, aluminum salts form coordination compounds with phosphate ions, yielding insoluble aluminum phosphate precipitates. Aluminum-based phosphate binders were successful, but osteomalacia and anemia caused their discontinuation.
2- Calcium-based phosphate binders were introduced in the mid-1980s to replace aluminum-based ones.
They were effective, cheap, and extensively used when first launched.
However, calcium-based binders may cause arterial calcification and increase CV mortality.
Calcium-based binders enhance vascular calcification and arterial stiffness.
3-Calcium acetate/magnesium carbonate in an animal model assessed magnesium’s potential impact on bone turnover and mineralization.
29 Calcium acetate/magnesium carbonate decreased vascular calcification without affecting bone remodeling or magnesium levels.
4- sevelamer reduced phosphorus without increasing the calcium burden.
A Cochrane systematic review of phosphate binders indicated that sevelamer may reduce all-cause mortality in dialysis patients. Sevelamer carbonate was created because sevelamer hydrochloride worsened metabolic acidosis33.
5-Lanthanum carbonate, licensed in 2004, reduces phosphorus levels without increasing calcium load. possibly reducing treatment-related hypercalcemia.
Lanthanum’s prescription instructions warn of significant GI blockage, ileus, GI perforation, and fecal impaction.
6- Ferric citrate and sucroferric hydroxide bind 6-iron. 2013 authorized sucroferric hydroxide. It lowers phosphorus levels in dialysis patients with fewer pills than sevelamer carbonate. 2014 authorized ferric citrate. A meta-analysis of 16 trials found ferric citrate to decrease phosphorus and phosphorus-calcium product better than no active treatment and equivalent to other phosphate binders. However, the drug produced more GI side effects.
Summarize the pros and cons of common phosphate binders overtimecalcium based phosphate binders:
pros:
1-effective
2-inexpensive
3-widely used
cons:
1-vascular calcification(increase calcium load)
2-increase cv mortality
3-increase arterial stifness
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aluminum based phosphate binder:
pros:
1-effective
2-not associated with hypercalcemia
cons:
risk of aluminum toxicity
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sevelamer HCL:
pros:
1-decrease serum phosphorous without increase serum calcium
cons
worsen metabolic acidosis
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lanthanum carbonate :
pros:
decrease serum phosphorous without increase serum calcium
cons:
GI obstruction ,ileus ,perforation and faecal impaction
expensive
Calcium-based binders (such as calcium acetate and calcium carbonate):
Pros:
Relatively inexpensive.
Are safe and well-tolerated.
Cons:
May increase the risk of hypercalcemia and vascular calcification, kidney stones with long-term use.
Aluminum-based binders:
Pros:
Very very effective in lowering phosphate levels. ( In my experience the most effective).
Inexpensive.
Cons:
risk of aluminum accumulation in CNS, Bone , Bone marrow.
May cause constipation.
Sevelamer ( sevelamer carbonate and sevelamer hydrochloride):
Pros:
May reduce the risk of cardiovascular events. The ost effective in decreasing fgf23 level (-30 precent).
Cons:
More expensive
Gastrointestinal side effects .
Lanthanum carbonate:
Pros:
May reduce the risk of cardiovascular events. The ost effective in decreasing fgf23 level (-30 precent).
Cons:
More expensive than calcium-based binders.
Gastrointestinal side effects like nausea, vomiting, and diarrhea.
Summarize the pros and cons of common phosphate binders overtime.
1- pros : inexpensive.
2- cons : +ve calcium balance and vascular calcification.
1- pros : inexpensive, no effect on calcium balance.
2- Cons : Aluminum toxicity with anemia, dementia, adynamic bone disease.
1- pros : no effect on calcium balance.
2- cons : expensive, unpalatable, GIT side effects
1- pro : no effect on calcium balance.
2- cons : expensive, GIT side effects, accumulate in liver
Summarize the pros and cons of common phosphate binders overtime.
All are effective in reducing phosphate levels and associated with significant side effects, the differences comes in terms pills burden. The newer ones such as iron-based may have less pills burden
1.Almnium-based binders in 1970s
2.Calcium-based binders in 1980s
3.Magnesium-based binders in1980s
4.Sevelamer hydrochloride/Carbonate in 2000
5.Lanthanum carbonate in 2004
6.Iron-based 2013/2014