Imbalances of phosphorus and calcium levels within the body are very
common in CKD cats.
Eventually these imbalances can lead to a serious condition known as secondary
hyperparathyroidism.
This page discusses the control of phosphorus and calcium levels in order
to reduce the risk of secondary hyperparathyroidism.
It also discusses treatments which may be used if secondary
hyperparathyroidism is present.
Please see
Diagnosis for more information on these issues.
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 which you are
giving. If you think there is a different cause, speak to you vet.
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
6mg/dl (USA) or 1.9 mmol/L (international),
it is too high and you need to get it under control.
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 BriefJun 2014 pp77-80
has more information about how to handle calcium imbalances.
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, 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.
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. This increases
the risk of
calcification, so you should ask your vet about trying to control
total calcium levels. (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).
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.
Metabolic
acidosis 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 ΅mo/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, if your cat's phosphorus level is over 6
mg/dl or
1.9 mmol/L, you need to take steps to control it, see All About Phosphorus.
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.
Nevertheless,
Hypercalcemia in chronic kidney disease
(2018) 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), though 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.
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 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 Medicine30(5)
pp15641574 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 Science22(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.
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.
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 (and only
if) ionised calcium levels are at least 25% above the normal upper limit,
you could ask your vet about 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.
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 Medicine29(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.
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
& Surgery13(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.
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.
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
MedicineMay 2007 discusses possible treatment
options in this situation (many of which are the same as those discussed above).
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 Practice41(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.
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,
Sayνn M,
Taşdemir I,
Yasavul U,
Turgan C,
Caglar SNephron59(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.
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 ACVC 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."
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).
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.
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
Medicine20(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 Care23(2) pp 134162
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 Surgery17(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 tend to perch rather uncomfortably on the fence. Controlling
secondary hyperparathyroidism is certainly important. Calcitriol may help with secondary hyperparathyroidism,
and it does seem to help some cats feel better generally. I do not think
using it is a bad idea if you follow the dosage and monitoring guidelines
(see below)
and stop it promptly if high calcium levels do result.
On the other hand, its advocates recommend starting it really early in order to
prevent secondary hyperparathyroidism and I am not aware
of any evidence for this being effective.
Treatment recommendations for CKD in cats
(2019) International Renal Interest Society
state that calcitriol might be helpful for dogs in IRIS Stage 3 but that
"beneficial effects of ultra low dose calcitriol have
not yet been established in cats."
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."
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.
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
Phosphorus 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.
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 (see
Diagnosis), and since calcitriol may
raise 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.
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.
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).
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.
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.
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 Care23(2) pp 134162
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 I would not check immediately after eating 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.
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 Care23(2) pp 134162
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 Sources
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:
Therefore 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 10% discount on orders over US$100.
In Seattle is
used by some people, though I understand they do not ship to California.
From what I hear, their prices are quite reasonable, but they merged with
Axis Pharmacy in July 2018, so I do not know if that is still the case.
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.
Took over the business
of Francks Pharmacy, which closed in July 2012 following problems with
quality control. Available strengths include 256ng/ml and 320ng/ml. Some
people use Wells and are happy but I have heard that Wells are now only
prepared to ship 7ml at a time (with a shelf life of 120 days) and that
the price has increased in recent years.
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
will 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.
Calcitriol
Groups
You can discuss the use of calcitriol on Tanya's CKD Support Group, though
not too many members use it. There are also a group dedicated to its use,
though as you might expect, this focuses on the positive aspects of
using calcitriol.
Calcitriol
Group
is a group devoted to discussing the use of calcitriol in cats and dogs,
though it is very small and inactive.
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)
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 Proceedings18(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 ACVC 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.
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.
TREATING YOUR CAT WITHOUT VETERINARY ADVICE CAN BE
EXTREMELY DANGEROUS.
I have
tried very hard to ensure that the information provided in this website is
accurate, but I am NOT a vet, just an ordinary person who has lived
through CKD with three cats. This website is for educational purposes
only, and is not intended to be used to diagnose or treat any cat. Before
trying any of the treatments described herein, you MUST consult a
qualified veterinarian and obtain professional advice on the correct
regimen for your cat and his or her particular requirements; and you
should only use any treatments described here with the full knowledge and
approval of your vet. No responsibility can be accepted.
If your cat
appears to be in pain or distress, do not waste time on the internet,
contact your vet immediately.
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