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Phosphorus Imbalances
Calcium Imbalances
Secondary Hyperparathyroidism, Including Calcitriol and Cinacalcet (Sensipar)
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Phosphorus, Calcium and Secondary Hyperparathyroidism
Overview
Phosphorus
Imbalances
Low Phosphorus
Levels (Hypophosphataemia)
Low phosphorus levels (below 3 mg/dl or
1.0 mmol/L) are extremely uncommon in CKD cats, though are
occasionally seen in diabetic cats on insulin, or in cats with
certain kinds of cancer. They may also be seen in a cat who is
being fed following a prolonged period of starvation.
If the phosphorus level is too low as a
result of using phosphorus binders, you can reduce the dose of
binder that you are using. Talk to your vet about the best
approach.
See Diagnosis for
more information on low phosphorus levels.
High Phosphorus Levels (Hyperphosphataemia)
In most cases, CKD cats have high phosphorus levels. High
phosphorus levels can make the cat feel bad and may make the CKD
progress faster. For a CKD cat, being within the normal range is
not sufficient.
If your cat's phosphorus level
is over 6 mg/dl
(USA) or 1.9 mmol/L (international),
it is too high and you need to get it under control.
This important topic has its own page here.
Calcium Imbalances
Since phosphorus and calcium work together in the body, calcium
imbalances are also relatively common in CKD cats. High calcium
levels (hypercalcaemia) are more common in CKD cats, but some
cats have low calcium levels (hypocalcaemia).
Managing calcium disorders (2014)
Odunayo A Clinician's Brief Jun 2014 pp77-80 has
more information about how to handle calcium imbalances.
Low Calcium Levels (Hypocalcaemia)
Although high calcium levels are more common in CKD cats, low
calcium levels are occasionally seen.
The simplest treatment is a calcium supplement such as calcium
carbonate (e.g. Tums, or an over the counter calcium carbonate
product). If this type of treatment is used, calcium blood
levels should be checked regularly because the opposite problem
of high calcium may result.
Calcitriol is a hormone produced by the kidneys which helps to
regulate parathyroid
hormone (PTH), so some people use calcitriol as a supplement
to try to control secondary
hyperparathyroidism. Since calcitriol tends to increase
calcium levels, occasionally it is also used for cats with low
calcium levels. In such cases, it would normally be dosed twice
daily in extremely tiny doses. See below for
more information on calcitriol.
Dr Larry Nagode (formerly of Ohio State University College
of Veterinary Medicine, now deceased) has stated that niacin
and niacinamide (vitamin B3), which some people are now
using as phosphorus
binders, may increase calcium levels and therefore might be
a suitable supplement for cats with low calcium levels. I do not
know what might be an acceptable dose when used for this
purpose.
In really severe cases, intravenous calcium may be necessary at
the vet's office, though fortunately this is rare. Parenteral
calcium for hypocalcemia: different salts, different dosages (2015)
Plumb DC Plumb's Therapeutic Brief Sept 2015 has
more information about this.
High Calcium Levels (Hypercalcaemia)
High calcium levels are more common in CKD cats than low calcium
levels, but it is not always essential to treat hypercalcaemia.
See Diagnosis for
more information about hypercalcaemia
High Calcium
Levels: When to Treat
High calcium levels are not normally a problem unless:
-
if ionised
calcium levels are also high, you definitely need to
take action; or
-
if calcium multiplied by phosphorus is higher than 60-70 in
US values or 5 in international values; or if you multiply
phosphorus by ionised calcium, and the level is higher than
8.75 in US values or 35 in international values. Either of
these situations increases the risk of calcification,
so you should ask your vet about trying to control total
calcium levels.
High Calcium
Levels: Treatments
High Calcium Levels: Simple
Treatments
These treatments are simple in that you will probably be using
them to help with other problems anyway, or they do not require
much effort to implement. You may well find that you need to use
more than one treatment.
See below for
more advanced treatments.'
High Calcium Levels: Metabolic
Acidosis
Metabolic acidosis (disturbance of the acid-base in the
body) can contribute to hypercalcaemia, so if your cat has
metabolic acidosis, treating it can help reduce calcium levels.
High Calcium Levels: Subcutaneous
Fluids (Sub-Qs)
Keeping your cat properly hydrated is one of the main goals of
CKD treatment, so most cats with creatinine over 3.5 mg/dl or
300 µmol/L will be receiving sub-Qs for this reason. As it
happens, giving sub-Qs may also reduce calcium levels, though it
is not usually recommended to use sub-Qs solely in order to
control calcium levels.
Pitfalls in the management of idiopathic
hypercalcemia in cats (2013)
Peterson ME Proceedings of the 2013 American College of
Veterinary Internal Medicine (ACVIM) Forum pp538-540 says
"Fluid therapy is used as an adjunct treatment in cats with
idiopathic hypercalcemia, especially those that have developed
renal failure. The administration of subcutaneous fluids on a
daily or every other day basis may help expand the extracellular
fluid, and promote calciuresis.”
Normally cats on sub-Qs with high calcium levels are given saline
solution rather than lactated
ringers solution (LRS). This is for two reasons: firstly,
saline solution has no added calcium, and secondly, saline
solution promotes calcium excretion in the urine.
Alternatively, Normosol-R might
be suitable. If you are using LRS, discuss switching with your
vet.
High Calcium Levels: Phosphorus
Binders
Since phosphorus and calcium levels within the body are closely
related, reducing elevated phosphorus levels may also help
reduce calcium levels.
Even if your cat's calcium levels are normal,
you need to take steps to control
your cat's phosphorus level if it is over 6 mg/dl or 1.9
mmol/L, see The
Importance of Phosphorus Control.
Never use calcium-based
phosphorus binders in a cat with elevated calcium levels.
High Calcium Levels: Limit
Treatments Containing Calcium or Vitamin D
Slippery elm bark contains calcium, so it is probably safer
not to use it if your cat has hypercalcaemia.
Some people have found that using lactulose to
control constipation has led to hypercalcaemia in their cats.
This may be coincidence, since hypercalcaemia is not uncommon in
CKD cats, but you may wish to avoid lactulose if your cat
already has hypercalcaemia, and consider alternative treatments
if your cat has developed hypercalcaemia since beginning
lactulose. See All
About Constipation for more information and alternative
treatments for constipation.
Also check for any supplements containing vitamin
D, and ensure that you are not feeding a food high in
vitamin D.
High Calcium Levels: Dietary
Changes
It is worth looking at the food you are feeding because some
contain more calcium than others.
The body needs a balance between phosphorus and calcium, so
foods usually have a particular ratio of calcium to phosphorus.
The minimum is 1:1, though for healthy cats a higher ratio of
calcium to phosphorus is not normally a problem. Standard
commercial diets tend to have a ratio of around 1.2:1 (calcium
to phosphorus).
Therapeutic kidney diets tend to contain more calcium in ratio
terms because they are usually focused on keeping phosphorus
levels low:
-
Hill's k/d has a level of 1.7:1 canned and 1.43 dry;
-
Purina NF is 1.68:1 for the dry and 1.36:1 for the canned;
-
Royal Canin has much higher levels, at around 2:1;
but the overall amount of calcium is still usually low.
Hypercalcemia in chronic kidney disease
(2024) van den Broek H International Renal Interest
Society states "A diet change is the first step advised for
management of cats with mild hypercalcemia. When persistent
hypercalcemia occurs or is worsening in a cat fed a renal diet,
and no other underlying cause has been identified, it is
advisable to discontinue feeding 100% renal diet. Either the
proportion of renal diet fed on a daily basis could be reduced,
or renal diet could be stopped completely. A dietary transition
could then be made to a diet less stringently phosphate
restricted, such as a senior diet, or to a calcium oxalate
prevention diet, which is restricted in calcium."
If your cat is hypercalcaemic and in IRIS stages 1 and 2,
discuss with your vet whether to feed a normal commercial diet
with a lower calcium content rather than a therapeutic kidney
diet. Cats in these stages do not normally need a reduced
protein diet (see Nutritional
Requirements), and in fact low protein and low phosphorus
diets may not be the best choice, according to
Clinical progression of cats with early-stage
chronic kidney disease fed diets with varying
protein and phosphorus contents and calcium to
phosphorus ratios (2021) Schauf S, Coltherd JC,
Atwal J, Gilham M, Carvell-Miller LJ, Renfrew H,
Elliott J, Elliott D, Bijsmans ES, Biourge VC,
Watson P & Bakke AM Journal of Veterinary
Internal Medicine 35(6) pp2797-2811. In
this study, cats in IRIS stages 1 or 2 were fed a low
protein, low phosphorus diet, followed by a moderate protein,
moderate phosphorus diet. The study concludes "Cats with
early CKD developed hypercalcemia after long-term feeding of a
highly P-restricted diet. Increasing dietary P and reducing Ca :
P ratio maintained renal markers, while improving Ca-P balance.
Cats with early CKD could benefit from moderately protein- and
P-restricted diets."
However, it must not be forgotten that a therapeutic kidney diet
has many features other than reduced protein levels (see Which
Foods). Your vet can help you decide what to focus on.
If your cat does require a therapeutic kidney diet, I would
check the calcium:phosphorus ratio carefully and aim for a food
with a lower calcium:phosphorus ratio, assuming your cat will
eat it. You might wish to add a food to it which is relatively
low in calcium, in order to adjust the calcium:phosphorus ratio.
You should also avoid feeding acidified
diets.
Nutritional management of idiopathic
hypercalcaemia in cats (2012) Peterson ME Insights
into Veterinary Endocrinology discusses ways to treat
idiopathic hypercalcaemia (idiopathic means no obvious cause can
be found) through diet.
In Pitfalls
in the management of idiopathic hypercalcemia in cats (2013)
Peterson ME Proceedings of the 2013 American College of
Veterinary Internal Medicine (ACVIM) Forum pp538-540, Dr
Peterson also says "Unfortunately, in most cats with idiopathic
hypercalcemia, dietary therapy will be of minimal long-term
benefit, but this management is very unlikely to be harmful. In
addition, because many cats with idiopathic hypercalcemia do not
show clinical signs for months to years, it is appropriate to
try dietary therapy as the first line of therapy at least in
cats with mild ionized hypercalcemia."
High Calcium Levels: Fibre
Increased fibre in the diet may help to reduce calcium levels by
binding with the calcium and thus reducing the amount of calcium
that can be absorbed into the body through the gastrointestinal
tract.
ACVIM small animal consensus
recommendations on the treatment and prevention of uroliths in
dogs and cats (2016) Lulich JP, Berent AC,
Adams LG, Westropp JL, Bartges JW & Osborne CA Journal of
Veterinary Internal Medicine 30(5) pp1564–1574 states
that "In dogs and cats with hypercalcemia, correcting or
controlling hypercalcemia aids in preventing calcium oxalate
urolith recurrence. Doing so is difficult in cats with
idiopathic hypercalcemia and no single treatment has been shown
to be effective, including glucocorticoids, bisphosphonate
administration, or dietary modification using a high-fiber diet
with potassium citrate administration, but 5 cats with
idiopathic hypercalcemia had normalization of blood calcium
concentrations when treated with a high-fiber diet."
However, you do need to be careful when choosing a fibre. One
type of fibre called fructooligosaccharides (FOS) may actually
cause elevated calcium levels. See Nutritional
Requirements for more information on fibre.
One food to discuss with your vet is Hill's w/d, which has added
fibre. The canned version of this food would be suitable for
most CKD cats, with a phosphorus level of 0.67% and a protein
level of 39.60%. The phosphorus level in the dry food is a
little higher at 0.84%, with a protein level of 40.80%, but this
might still be acceptable if your cat's phosphorus levels are
under control.
High Calcium Levels: Chia
Seeds
One form of fibre to consider is chia seeds, which also contain omega
3 fatty acids. Managing
feline idiopathic hypercalcemia with chia seeds (Salvia
hispanica L.): s case series (2020)
Fantinati M & Priymenko N Frontiers in Veterinary Science 22(7) p421
found that giving chia seeds (2g per day) normalised ionised
calcium levels in three cats with idiopathic hypercalcaemia
after four weeks. The cats in this study only had slightly
elevated calcium levels, and it is not clear whether dietary
changes alone might have sufficed.
A couple of Tanya's CKD Support Group members have successfully
used chia seeds in their cats with hypercalcaemia. They used the
2g per day suggested in the above study, and mixed the seeds
with a little water, then let it stand for about twenty minutes
before adding part of the mixture to each of the cat's canned
foods over the day. It is probably best to keep the mixture in
the fridge between feedings.
High Calcium
Levels: Advanced
Treatments
These treatments may be necessary if the simple treatments
described above do not resolve the problem. They all have pros
and cons, and some of the cons are potentially serious. Discuss
with your vet.
High Calcium Levels: Corticosteroids
Corticosteroids such as prednisolone may sometimes be used to
control high calcium levels. Hypercalcemia
in dogs and cats (2016)
Peterson ME Merck Veterinary Manual says "Administration
of prednisone results
in longterm decreases in ionized and total calcium
concentrations in some cats." In Pitfalls
in the management of idiopathic hypercalcemia in cats (2013)
Peterson ME Proceedings of the 2013 American College of
Veterinary Internal Medicine (ACVIM) Forum pp538-540, Dr
Peterson states "If normocalcemia has not been restored after a
dietary feeding trial of 6 to 8 weeks, treatment with
glucocorticosteroids should be considered...Approximately 50% of
cats with idiopathic hypercalcemia become normocalcemic with 5
or 10 mg prednisone/day."
Using steroids can have certain undesirable side effects. Pitfalls
in the management of idiopathic hypercalcemia in cats (2013)
Peterson ME Proceedings of the 2013 American College of
Veterinary Internal Medicine (ACVIM) Forum pp538-540 says
"approximately a third of cats will develop secondary diabetes,
especially with long-term, high-dose steroid therapy." See steroids for
more information about possible problems with steroids..
High Calcium
Levels: Loop Diuretics Such As Furosemide
(Lasix))
Furosemide (Lasix) is a loop diuretic.
Diuretics are commonly used in heart disease, but may
occasionally be used to help reduce high calcium levels, which
they do by increasing the excretion of calcium via the kidneys.
Diuretics are not usually appropriate for CKD cats because they
may increase the risk of dehydration, but be guided by your vet.
High Calcium Levels: Bisphosphonate
Drugs: Alendronate or Pamidronate
If ionised calcium levels remain high despite trying the above
treatments, you may have to consider using bisphosphonate drugs.
These medications are commonly used to treat humans with
osteoporosis, and are occasionally used in hypercalcaemic cats.
They help by encouraging the bones to absorb calcium, which then
reduces calcium levels in the blood.
Hypercalcemia in chronic kidney disease
(2024) van den Broek H International Renal Interest
Society states "If serum ionized calcium concentration has
not improved 6 weeks after diet change, treatment with specific
calcium lowering medications such as bisphosphonates (PO
alendronate, IV pamidronate) or prednisolone could be
instigated. Bisphosphonates as a treatment option for
hypercalcemia have only been examined in few animals, but appear
safe and reasonably effective in lowering serum calcium
concentrations, although hypercalcemia may reoccur after
treatment is stopped."
Alendronate (Fosamax)
One drug in this family is called alendronate (Fosamax). This
may be administered intravenously in a hospital setting, though
it may also be given orally at home once a week. Treatment
of ionized hypercalcemia in 12 cats (2006-2008) using
PO-administered alendronate (2015)
Hardy BT, de Brito Galvao JF, Green TA, Braudaway SR, DiBartola
SP, Lord L & Chew DJ Journal of Veterinary Internal Medicine 29(1) pp200-6
looked at the use of alendronate in cats with idiopathic
hypercalcaemia. The cats were given a dose of 5-20 mg orally
every seven days. The study reduced calcium levels in all the
cats with no major side effects and concludes "Alendronate was
well tolerated and decreased iCa in most cats for the 6-month
period of observation."
Pitfalls in the management of idiopathic
hypercalcemia in cats (2013)
Peterson ME Proceedings of the 2013 American College of
Veterinary Internal Medicine (ACVIM) Forum pp538-540
"Recently, I have been bypassing prednisolone completely and
going right to oral alendronate, starting at 10 mg orally per
week...Compared to glucocorticoids, alendronate is more
successful in lowering calcium concentration without the
diabetogenic effects."
The usual starting dose is 10mg for cats, given orally only once
a week, and many people opt for a twelve hour fast beforehand.
The cat must stay upright for at least 15 minutes after taking
it so as to avoid oesophageal damage. Always follow the
treatment with a water
chaser. Plumb's suggests buttering the cat's lips to
encourage swallowing. Alendronate
dosing protocol for cats with idiopathic hypercalcaemia (2014)
Peterson ME Insights into Veterinary Endocrinology discusses dosing.
Ionised calcium levels should be checked regularly, starting
four weeks after the first dose, and the dose should be adjusted
if necessary .
If you are using ranitidine (Zantac
75) intravenously for gastric hyperacidity (highly unlikely
outside a hospital setting), be aware that it doubled the effect
of alendronate in one human study.
There is some concern about using bisphosphonates in CKD
patients. Plumb's Veterinary Drug Handbook states
that "because of a lack of experience, the drug is not
recommended for use in human patients with severe renal
dysfunction."
Drugs lists
possible side effects of alendronate in humans.
Pamidronate
Another bisphosphonate is pamidronate. Uses
and effectiveness of pamidronate disodium for treatment of dogs
and cats with hypercalcemia (2005)
Hostutler RA, Chew DJ, Jaeger JQ, Klein S, Henderson D,
DiBartola SP Journal of Veterinary Internal Medicine 19(1) pp29-33
found it appeared to be safe and effective.
Use of bisphosphonates to treat severe
idiopathic hypercalcaemia in a young Ragdoll cat (2011)
Whitney JL, Barrs VR, Wilkinson MR, Briscoe KA & Beatty JA Journal
of Feline Medicine & Surgery 13(2) pp129-34 discusses
the case of a young cat with idiopathic hypercalcaemia who
became clinically normal following the use of bisphosphonate
drugs. Idiopathic means no obvious cause could be found.
However, pamidronate has to be given intravenously and may cause
electrolyte imbalances. Like alendronate, it may be
contraindicated for CKD cats.
High Calcium Levels: Calcitriol
Calcitriol is a hormone produced by the kidneys which helps to
regulate parathyroid
hormone (PTH). Some people use calcitriol as a supplement to
try to control secondary
hyperparathyroidism.
Although calcitriol may cause calcium levels to rise, in some
cases it may actually be used to try to reduce calcium levels.
However, this should only be attempted if ionised calcium is
above midrange (or even at the top of the normal range), and an
intermittent dosing schedule should be used. The
causes and consequences of feline hypercalcemia (2009)
Cook AK Presentation to the ACVIM Forum explains more
about treatments for hypercalcaemia and mentions the use of
calcitriol in CKD cats who have both elevated calcium and
elevated ionised calcium levels. It states that if ionised
calcium levels increase while using calcitriol for this purpose,
it must be discontinued immediately.
I would definitely try other treatment options first.
See below for more information on calcitriol.
High Calcium Levels: Cancer
Although it is fairly rare, high calcium levels may be caused by
cancer, so if the cause of your cat's hypercalcaemia is unknown,
especially if you find the treatments above ineffective, it is
worth asking your vet to test for cancer. The
causes and consequences of feline hypercalcemia (2009)
Cook AK Presentation to the ACVIM Forum explains more
about this.
Treating paraneoplastic hypercalcemia in
dogs and cats (2007) Fan
TM, de Lorimier L-P, Lucas P & Lacoste H Veterinary Medicine May
2007 discusses possible treatment options in this situation
(many of which are the same as those discussed above).
Elevated PTH and Secondary
Hyperparathyroidism
Untreated elevated parathyroid
hormone (PTH) levels may eventually lead to a condition
called secondary
hyperparathyroidism.
These are the treatments which may be used:
Secondary Hyperparathyroidism:
Phosphorus Control
The first line of attack to reduce the risks of secondary
hyperparathyroidism is to feed your CKD cat a diet low in
phosphorus. If this is not sufficient, you should also use
phosphorus binders.
For many cats, phosphorus control will be enough to avoid secondary
hyperparathyroidism. Survival
of cats with naturally occurring chronic renal failure: effect
of dietary management (2000) Elliott J, Rawlings JM,
Markwell PJ, Barber PJ Journal of Small Animal Practice 41(6) pp235-242
found that a low phosphorus diet, with added binders where
necessary, prevented the rise in parathyroid
hormone levels seen in the control cats whose
phosphorus levels were not restricted. In fact, the cats who ate
reduced phosphorus food or food with added phosphorus binders
lived more than twice as long as those who did not.
Phosphorus control is such an important topic for CKD cats that
there is a page devoted to the subject here,
and a page devoted to phosphorus binders (which are used when
dietary restriction of phosphorus is not sufficient to control
phosphorus levels) here.
Magnesium Supplements
If your cat also has low magnesium levels in the blood, a magnesium
supplement might be helpful.
Dietary magnesium supplementation in cats with chronic kidney disease: a
prospective double-blind randomised controlled trial (2024) Tang
P-K, van den Broek DHN, Jepson RE, Geddes RF, Chang Y-M, Lötter N,
Moniot D, Biourge V & Elliott J Journal of Veterinary Internal
Medicine 38(4) pp2180-2195 states that CKD cats with low
magnesium levels tend to have a shorter survival time. The study
concludes "Magnesium-enriched PRD [phosphate-restricted diet] is a novel
therapeutic strategy for managing feline CKD-MBD in cats, further
stabilizing plasma FGF23 and preventing hypercalcemia."
There is more information about magnesium and supplements
here.
Secondary Hyperparathyroidism: Famotidine
Famotidine (Pepcid AC) is commonly used in CKD cats to block
the production of gastric
hyperacidity.
As a side effect it may reduce PTH levels in CKD patients. Famotidine
reduces serum parathyroid hormone levels in uremic patients (1991)
Arik N, Arinsoy T, Sayín
M, Taşdemir
I, Yasavul
U, Turgan
C, Caglar
S Nephron 59(2) p333 explains more
about this, but I am not aware of any detailed, controlled
studies into this. Therefore I would not use famotidine to treat
elevated PTH levels only, but if you are using it anyway to
control gastric hyperacidity, you may possibly see a reduction
in PTH levels as well.
Secondary Hyperparathyroidism:
Calcitriol
Calcitriol: What is It?
Calcitriol is the active form of vitamin D. Despite its
name, it is not the same as the vitamin D we eat or obtain from
sunlight or supplements. Calcitriol is actually a hormone, and
it plays an important part in regulating phosphorus and calcium
levels in the body.
Here is how calcitriol is produced in the body:
-
Vitamin D2 (ergocalciferol) is found in some plant-based
foods.
-
Vitamin D3 (cholecalciferol) is produced in the skin when
the skin is exposed to sunlight (which is a poor mechanism
in cats, probably because of their fur coats), but may also
be found in certain foods such as eggs.
-
Supplements containing vitamin D2 and vitamin D3 are also
widely available (but not normally required in cats).
-
Vitamin D (whether D2 or D3) is converted in the liver into
calcidiol (25-hydroxyvitamin D [25(OH)D], or
25-hydroxycholecalciferol).
-
Calcidiol is then converted in the kidneys into the
biologically active form known as calcitriol
(1,25-dihydroxyvitamin D [1,25(OH)2D], or 1,25
dihydroxycholecalciferol.
Calcitriol: What Does It
Do?
Calcitriol facilitates the absorption of calcium from the
gastointestinal tract and the release of calcium from the bones
where it is stored.
In healthy cats, if phosphorus levels are too high, or if
calcium levels are too low, the levels of ionised
calcium in the body fall. The parathyroid glands are then
stimulated to produce more parathyroid
hormone, which tries to adjust the levels of calcium and
phosphorus to their correct levels, partly by taking calcium
from the bone and partly by increasing the excretion of
phosphorus in the urine. Parathyroid hormone also stimulates the
kidneys to produce calcitriol, which helps to increase the
levels of ionised calcium in the blood.
Once ionised calcium has been restored to the correct level,
this process should cease because normally calcitriol can stop
the secretion of PTH. Unfortunately, as kidney function reduces
and calcitriol is not produced in adequate amounts, this
mechanism may no longer work properly. Therefore, phosphorus
levels may continue to rise and may also block calcitriol
synthesis. A vicious circle then results, and eventually a
condition called secondary
hyperparathyroidism may develop.
Human patients with secondary hyperparathyroidism are therefore
sometimes given additional calcitriol, and some people do the
same for their CKD cats. The
role of phosphorus in feline chronic renal disease (2010) Chew
D & Kidder A CVC in
San Diego Proceedings states "In
some instances, PTH cannot be controlled despite dietary
intervention and use of intestinal phosphate binders. Other
treatments with calcitriol and calcimimetics may be indicated in
these cases."
Mar Vista Vet has more
information on calcitriol.
Calcitriol Debate
The use of calcitriol in cats is somewhat controversial, in part
because no studies clearly show that it is effective for cats
(although it does appear to be effective for dogs). In fact,
Announcement of changes to IRIS guidelines (2023) International
Renal Interest Society mentions one of the changes to be
"The removal of the mention of calcitriol treatment for cats in
the management of Stage 3 and 4 CKD due to lack of any evidence
of a beneficial effect."
The willingness or otherwise of US vets to use calcitriol may
depend in part upon which vet school they attended. Initial
studies at Cornell University College of Veterinary Medicine and
later studies at the University of Georgia College of Veterinary
Medicine found that using calcitriol caused calcium levels to
rise. However, Ohio State University College of Veterinary
Medicine has also conducted research into the use of calcitriol
in CKD cats, and it believes that the risk of hypercalcaemia is
dosage dependent and that the risk can be managed.
Calcitriol: Pro
Calcitriol advocates believe that it is possible to have normal
phosphorus levels and still have secondary hyperparathyroidism.
They believe not only that the use of calcitriol is therefore
essential, but also that calcitriol may help control uraemia and
even slow the progression of CKD.
Benefits of calcitriol therapy and serum
phosphorus control in cats and dogs with chronic renal failure.
Both are essential to prevent or suppress toxic
hyperparathyroidism (1996)
Nagode LA, Chew DJ, Podell M Veterinary Clinics of North
American Small Animal Practice 26 pp1293-1330
discusses the importance of controlling secondary
hyperparathyroidism in cats and the role of calcitriol in doing
so.
However, Comparison
of the effects of daily and intermittent-dose calcitriol on
serum parathyroid hormone and ionized calcium concentrations in
normal cats and cats with chronic kidney failure (2006)
Hostutler RA, DiBartola SP, Chew DJ, Nagode LA, Schenck PA,
Rajala-Schultz PJ, Drost WT Journal of Veterinary Internal
Medicine 20(6) pp1307-13 found "At the dosages used,
calcitriol treatment did not result in significant differences
in serum parathyroid hormone concentrations before and after
treatment in both normal cats and cats with chronic renal
failure. With these dosages, adverse affects of calcitriol
administration were not seen. Potential reasons for lack of
apparent effect include small sample size, insufficient duration
of study, insufficient dosage of calcitriol, problems with
formulation or administration of calcitriol, and variable
gastrointestinal absorption of calcitriol.”
Calcitriol, calcidiol, parathyroid
hormone, and fibroblast growth factor-23 interactions in chronic
kidney disease (2013) de Brito Galvao JF, Nagode LA, Schenck
PA & Chew DJ Journal of Veterinary Emergency and Critical
Care 23(2) pp 134–162 is a more recent paper which
discusses calcitriol and its
effectiveness and renoprotective qualities for dogs and humans,
but which concludes "Long-enough trials to determine any
benefits for CKD cats treated with calcitriol have yet to be
conducted."
Calcitriol: Con
There is evidence that you can control PTH levels and prevent,
reverse or at least postpone the development of secondary
hyperparathyroidism simply by controlling phosphorus levels. Feline
hyperparathyroidism: pathophysiology, diagnosis and treatment of
primary and secondary disease (2015)
Parker VJ, Gilor C & Chew DJ Journal of Feline Medicine and
Surgery 17(5) pp427-439 says “Treatment of RSHP
includes controlling serum phosphorus concentrations by feeding
a reduced phosphorus diet ± administration of a dietary
phosphorus binder.” See above for
information on how to do this.
Chronic kidney disease (CKD) in dogs and cats — staging and
management strategies (2015) Chew
D Presentation to the Virginia Veterinary Medical Association
2015 Virginia Veterinary Conference says "Early
phosphorus restriction in CRF has been shown in dogs and cats to
blunt or reverse renal secondary hyperparathyroidism. In a study
of cats with naturally-occurring CRF, renal secondary
hyperparathyroidism was successfully managed by dietary
restriction of phosphorus; one-third of the cats also required
treatment with phosphorus binders.”
There is also some concern about the potential for calcitriol
supplementation to cause both elevated phosphorus levels and
elevated calcium levels. Renal
Disease (2006) Polzin
DJ Delaware
Valley Academy of Veterinary Medicine states "the
decision to use calcitriol must be made with caution because
hypercalcemia is a potentially serious complication. Sustained
calcitriol-induced hypercalcemia will likely result in
reversible or irreversible reduction in GFR." GFR is
a measure of kidney function.
Renal Disease (2006) Polzin
DJ Delaware
Valley Academy of Veterinary Medicine states "Nagode
and colleagues have suggested that normalization of PTH levels
using calcitriol therapy may provide clinical benefits that
cannot be achieved by phosphorus restriction alone including
amelioration of many clinical signs associated with CKD. We have
been unable to completely substantiate these claims, but did
find that calcitriol therapy significantly prolonged survival in
dogs with stages 3 and 4 CKD." He further states "A
recommendation for or against routine use of calcitriol awaits
results of properly designed controlled clinical trials."
What do I think? I've been running this website for 25 years and
I have seen very few cats use calcitriol during that time.
People who have given it to their cats seem overall to be happy
with it, but there is no evidence of its effectiveness in CKD
cats, and it is tricky to obtain in cat-sized dosages.
Personally, I would save my money and efforts and focus on more
proven treatments.
Calcitriol:
Considerations Before Starting
Calcitriol will not work for cats whose phosphorus levels are
already above 8 mg/dl or 2.6 mmol/L, and is of limited value for
cats with phosphorus levels above 6 mg/dl or 1.9 mmol/L.
Calcitriol, calcidiol, parathyroid
hormone, and fibroblast growth factor-23 interactions in chronic
kidney disease (2013) de Brito Galvao JF, Nagode LA, Schenck
PA & Chew DJ Journal of Veterinary Emergency and Critical
Care 23(2) pp 134–162 says “Serum phosphorus should
be less than 1.9 mmol/L [<6.0 mg/dL] before starting calcitriol
treatment and thereafter to ensure calcitriol efficacy in PTH
suppression."
Therefore, if your cat's phosphorus levels are above 6 mg/dl or
1.9 mmol/L, you must take all possible steps to control
phosphorus levels (see The
Importance of Phosphorus Control for information on how to
do this) before using calcitriol.
Calcitriol may cause ionised calcium levels to increase. Prolonging
life and kidney function (2007)
Chew D Presentation to the 32nd World Small Animal Veterinary
Association World Congress explains more about this.
On the other hand, Chronic
kidney disease (CKD) in dogs and cats — staging and management
strategies (2015) Chew D Presentation
to the Virginia Veterinary Medical Association 2015 Virginia
Veterinary Conference mentions that calcitriol will
be less effective if your cat's ionised calcium level is low.
You also need to consider your cat's total calcium levels. If
your cat's calcium level x phosphorus level is over 60-70 in US
values or over 5 in international values, your cat is at risk of
soft tissue mineralisation, and since calcitriol may
increase calcium levels, you should not use it until this level
has been reduced. Chronic
kidney disease (CKD) in dogs and cats — staging and management
strategies (2015) Chew D Presentation
to the Virginia Veterinary Medical Association 2015 Virginia
Veterinary Conference states: "Calcitriol should not
be administered until hyperphosphatemia has been controlled. If
the Ca X P solubility product exceeds 60-70, calcitriol should
be avoided because of the risk of soft-tissue mineralization."
This also applies if you multiply phosphorus by ionised calcium,
and the level is higher than 8.75 in US values or 35 in
international values.
Calcitriol: When to Start
As stated earlier, calcitriol is not an essential treatment, so
if you are unable to obtain it or cannot afford it, or if it
does not seem to agree with your cat, I would give it a miss.
Please also see considerations
before starting.
If you and your vet do decide to use calcitriol, and wish to
start before your cat's PTH levels
are elevated, Dr Larry Nagode, formerly of Ohio State University
College of Veterinary Medicine, now sadly deceased, advises
starting calcitriol when creatinine reaches 2 mg/dl or 175 mmol/L,
assuming pre-
and post-renal causes of the elevated creatinine have been
ruled out.
Calcitriol: Dosage
Calcitriol: Dosage Amount
The usual dose recommended for cats by Ohio State University
College of Veterinary Medicine is 2.5-3.5 ng per kg of
bodyweight orally each day. Note this is nanograms, not
milligrams. These are tiny amounts, so in practice you must use
compounded calcitriol in order to obtain cat-sized doses (see below for
sources).
Calcitriol, calcidiol, parathyroid
hormone, and fibroblast growth factor-23 interactions in chronic
kidney disease (2013) de Brito Galvao JF, Nagode LA, Schenck
PA & Chew DJ Journal of Veterinary Emergency and Critical
Care 23(2) pp 134–162 says "Doses lower than 2.5 ng/kg
are rarely used, and occasionally a dose as high as 6ng/kg/day
is used when lower doses do not succeed in lowering PTH."
Initially the dose will probably be based to a degree on your
cat's creatinine levels, So, for example, if your cat's
creatinine level is 2 mg/dl, you might start at 2.5 ng/kg, but
if your cat's creatinine level is 4 mg/dl, your vet might
suggest starting at 3.5 ng/kg. Once you know your cat's PTH levels
(you should be monitoring PTH levels once you have begun
calcitriol), your vet will probably use that as a guide when
deciding whether to adjust the dose.
Calcitriol: Dosage Frequency
Calcitriol used to be given daily, which requires really tiny
amounts. Therefore there has been research into giving it in
slightly larger amounts but less frequently, sometimes referred
to as intermittent dosing.
Comparison of the effects of daily and
intermittent-dose calcitriol on serum parathyroid hormone and
ionized calcium concentrations in normal cats and cats with
chronic kidney failure (2006)
Hostutler RA, DiBartola SP, Chew DJ, Nagode LA, Schenck PA,
Rajala-Schultz PJ, Drost WT Journal of Veterinary Internal
Medicine 20(6) pp1307-13 found that intermittent
dosing did not seem to make any difference in terms of
effectiveness. It can also work out cheaper, and may reduce the
risk of hypercalcaemia. It is recommended that intermittent
dosing be used for cats whose calcium levels are at the high end
of the normal range.
Therefore most people these days use an intermittent dosing
schedule, giving calcitriol every 3.5 days, in which case the
standard dose is 8.75 - 12.25 ng twice a week.
The timing must be exact, i.e. every 3.5 days rather than every
three days or every four days, so many people use a schedule of
giving it on Wednesday evenings and Sunday mornings, at a time
to suit (e.g. 10 a.m. Sunday and 10 p.m. Wednesday).
For a 10lb (4.55kg) cat, this works as follows:
-
If you are giving the 2.5 ng/kg starting dosage of
calcitriol to this cat, you would be giving a total of 11.4
ng a day (2.5 x 4.55).
-
If you are giving it every 3.5 days, you would give 38.8 ng
(11.4ng per day x 3.5 days).
-
This would be rounded up to 39 ng.
To work this out for your own cat, do as follows:
-
Take your cat's body weight in pounds and divide by 2.2 to
get the equivalent in kg.
-
Take your cat's body weight in kg and multiply by your daily
dose, e.g. 2.5 ng.
-
Multiply the result by 3.5 (days).
For example, let's say your cat weighs 7 lbs:
-
7.5lb divided by 2.2 = 3.41kg
-
3.41 kg x 2.5ng/kg per day = 8.53ng
-
8.53ng x 3.5 days = 29.86ng
-
Round it, so your cat's dose would be 30ng twice a week
(every 3.5 days).
In practice your vet should tell you how much to give.
Calcitriol: Pulse Dosing
Occasionally pulse dosing may be considered for cats whose PTH
levels do not reduce as expected on calcitriol. In such cases,
you give a dose of 20ng/kg twice weekly for three weeks,
followed by 10ng/kg twice weekly dosing for 2-3 weeks, after
which you test PTH levels. If the PTH level is still more than
three times the top of the normal range, you repeat the pulse
dosing. One or two sessions of pulse dosing are normally
sufficient to get PTH levels down, after which normal dosing may
continue as outlined above.
Calcitriol, calcidiol, parathyroid
hormone, and fibroblast growth factor-23 interactions in chronic
kidney disease (2013) de Brito Galvao JF, Nagode LA, Schenck
PA & Chew DJ Journal of Veterinary Emergency and Critical
Care 23(2) pp 134–162 explains more about pulse
dosing.
Calcitriol: How to Give
The amounts needed are tiny, so the treatment has to be
compounded into the correct dosage for a cat (see below for
suppliers).
Calcitriol is provided in either oil-filled capsules or oily
liquid form. If you are using a liquid formulation, be sure to
give it into the side of the mouth, not into the front.
Cats receiving calcitriol daily do not need to be fasted
beforehand unless their blood calcium levels are near the top of
the range, in which case they should be fasted for 2-4 hours
before giving the calcitriol and for 30-60 minutes afterwards.
Cats receiving calcitriol every 3.5 days should ideally be
fasted for 2-4 hours before giving the calcitriol and for an
hour afterwards. If their blood calcium levels are near the top
of the range, the fasting is very important.
You should avoid giving any supplements etc. containing calcium
on the days when you give calcitriol.
Do not store liquid calcitriol in the fridge. Do not shake it.
Calcitriol: Monitoring
With standard dosing, it is usual to start with the lowest dose.
Many people check PTH, calcium and phosphorus levels after 10-14
days, though Calcitriol,
calcidiol, parathyroid hormone, and fibroblast growth factor-23
interactions in chronic kidney disease (2013) de
Brito Galvao JF, Nagode LA, Schenck PA & Chew DJ Journal of
Veterinary Emergency and Critical Care 23(2) pp
134–162 says "After receiving the initial dose for 2 months, a
recheck of serum PTH concentration will indicate if an
incremental calcitriol dosage increase is necessary."
If you are using pulse dosing, you would normally check 5-6
weeks after starting pulse dosing.
Your goal is to reduce PTH levels, whilst keeping phosphorus
levels low and calcium levels within normal range. If the levels
are acceptable, you should check again after about a month. If
they still are out of range, adjust the dose and check again
after 10-14 days. Once you have determined the correct dose, you
should continue to check PTH, calcium and phosphorus levels
every 4-8 weeks.
You should wait at least 24 hours after giving a dose of
calcitriol before running these blood tests.
It is not normally necessary to fast your cat before testing,
but on thd other hand do not allow your cat to eat shortly
before testing. I would aim to keep food away from your cat for
about four hours before the blood is taken. Dr Nagode has stated
that waiting 1-2 hours is probably acceptable, but aim for four
hours if you can.
Calcitriol
Side Effects and interactions
MedlinePlus lists
possible side effects, including weakness, vomiting,
constipation, and increased urination, especially at night.
Some cats seem to feel a little off colour on the days when they
are given calcitriol. In such cases, the twice weekly dosing
schedule seems to work better.
Using calcitriol may increase your cat's phosphorus levels. Keep
an eye on this, and increase your phosphorus
binder dose as necessary (and do not use calcium-based
phosphorus binders). Calcitriol,
calcidiol, parathyroid hormone, and fibroblast growth factor-23
interactions in chronic kidney disease (2013) de
Brito Galvao JF, Nagode LA, Schenck PA & Chew DJ Journal of
Veterinary Emergency and Critical Care 23(2) pp
134–162 says "If hyperphosphatemia develops during calcitriol
treatment, due to further loss of renal excretory function or
less likely more intestinal absorption, it is necessary to
increase the extent of dietary phosphate restriction and/or to
increase the dose or class of intestinal phosphate binder with
use of a combination of binders (eg, aluminum, lanthanum, and
sevelamer carbonate) thus minimizing any toxic effects of each
individual class of binder.”
Calcitriol may also cause your cat's calcium levels to rise too
far. If this happens, you will probably have to stop using
calcitriol, after which calcium levels should reduce within a
few days or so.
According to Plumb's Veterinary Drug
Handbook, corticosteroids may
cancel out the effects of calcitriol. This is because calcitriol
increases calcium absorption, whereas corticosteroids
inhibit calcium absorption.
Calcitriol: Where to Buy
Since cats need only tiny doses of calcitriol, you usually have
to have it compounded. Calcitriol comes in an oily suspension,
and the compounding pharmacy normally needs to dilute this
further with more oil in order to create cat-sized doses. The
end product is supplied in either a liquid, oily form, or is
hardened and supplied in capsules.
Most compounding pharmacies should be able to do this in theory,
but you need a pharmacist who is used to producing these tiny
strengths and able to ensure that the medication is evenly
distributed throughout the end product. Below are details of
pharmacies that people have used with success.
USA
If you buy six months supply at a time, it works out at about
US$10-40 a month. If you do buy six months' supply at a time,
make sure its shelf life is for six months or longer.
These compounded pharmacies are often recommended in the USA:
Thriving Pets
Thriving Pets
Offers calcitriol in pre-set concentrations, so your vet will
need to decide which concentration to use in order to get the
dosage which you need. Thriving Pets can help you with this if
necessary, just call them.
If you enter the word "tanya" (without the ")
in the promotional code box, you should receive a US$5 discount
on orders over US$100.
Axis Pharmacy Northwest
Axis Pharmacy Northwest
In Seattle has been used by some people, though II haven't heard
from anyone who has used them for several years. I have been
told they do not ship to California.
Triad
Triad Compounding
Sell calcitriol in various strength including 196ng/ml. I have
heard that they may be relatively expensive, but do not know
their current pricing levels.
Wells
Wells
Pharmacy Network
Wedgewood Pharmacy
Wedgewood Pharmacy
One member of Tanya's CKD Support Group has used Wedgewood with
no problems. She paid US$54.50 for 20ml of the 80ng/ml strength
(March 2020).
UK
The use of calcitriol is difficult in the UK, because it is hard
to find a pharmacy which is authorised to compound medications
for veterinary use into cat-sized dosages. Your vet may know of
a veterinary compounding pharmacy that can help. Some people use
human calcitriol but I'm not too clear how they manage to obtain
cat-sized doses from it.
If you can find a vet with a US licence who can write a
prescription for calcitriol, Thriving
Pets may be able to fill it for you.
If you are unable to obtain calcitriol, please do not be too
despondent. It is not an essential treatment for most CKD cats.
If you focus on phosphorus
control, for many cats this will be sufficient to avoid
secondary hyperparathyroidism, except possibly for very end
stage cats.
Calcimimetics
Calcimimetics are a family of drugs which are used in humans to
treat secondary hyperparathyroidism and hypercalcaemia caused by
parathyroid cancer. Occasionally these medications are used to
treat severe secondary hyperparathyroidism in CKD cats.
Cinacalcet (Sensipar)
Cinacalcet (Sensipar) was approved by the US Food and Drug
Administration in March 2004 for the treatment of secondary
hyperparathyroidism in humans. Cinacalcet
hydrochloride (Sensipar) (2005)
Poon G Baylor University Medical Center Proceedings 18(2) pp182-184
gives an overview of cinacalcet.
Health Canada reports
that in 2007 the use of cinacalcet in humans was restricted to
those on dialysis because it was found that patients receiving
cinacalcet who were not on dialysis were more likely to develop
low calcium levels.
Cinacalcet is occasionally used in CKD cats for whom other
attempts to reduce parathyroid hormone levels have not worked. The
role of phosphorus in feline chronic renal disease (2010) Chew
D & Kidder A CVC in
San Diego Proceedings states "In
some instances, PTH cannot be controlled despite dietary
intervention and use of intestinal phosphate binders. Other
treatments with calcitriol and calcimimetics may be indicated in
these cases."
Cinacalcet works by lowering calcium levels, so should not be
used in patients with low calcium levels. It is very expensive.
I have only heard of a couple of people who have used it in
cats, and never heard back to see how they got on with it.
Elevated PTH levels can contribute to anaemia. Improved
parathyroid hormone control by cinacalcet is associated with
reduction on darbepoetin requirement in patients with end-stage
renal disease (2011)
Battistella M, Richardson RM, Bargman JM & Chan CT Clinical
Nephrology 76(2) pp99-103 found that cinacalcet meant
less ESA
treatment for anaemia was required in human patients. I
don't think this is unique to cinacalcet, but rather because of
the reduction in PTH levels.
Amgen — prescribing
information from the manufacturer.
MedlinePlus explains more about
cinacalcet.
Etelcalcetide
Etelcalcetide is
another member of the calcimimetic family which is marketed
under the name Parsabiv. It was approved in the USA in 2017 for
the treatment of secondary hyperparathyroidism in humans on
dialysis. I am not aware of any usage in cats to date.
Amgen - prescribing information
from the manufacturer.

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