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.
Low phosphorus levels (below 3 US or 1.0 international)
are extremely uncommon in CKD cats, though are occasionally seen in
diabetic cats on insulin. 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.
As the
Diagnosis section
explains, high calcium levels in CKD cats are not
normally a problem unless ionised calcium levels are also high. However,
there is an exception to this rule. If calcium multiplied by phosphorus is
higher than 60-70 in US values or 5 in international values, it increases
the risk of
calcification, in which case you should ask your vet about trying to control
total calcium levels.
If
ionised
calcium levels are high, you definitely need to take action.
Metabolic
acidosis can contribute to hypercalcaemia, so if your cat has metabolic
acidosis, treating it can help reduce calcium levels.
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 below ineffective, it is worth asking your vet to
test for cancer.
Antech Diagnostics (2000) has information on hypercalcaemia
and how to treat it from Dr D
Chew.
These
treatments are simple in that you will probably be using them for other
reasons anyway, or they do not require much effort to implement.
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 (300 international) 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.
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.
Phosphorus Binders
Since
phosphorus and calcium levels within the body are closely related,
reducing elevated phosphorus levels may also help reduce calcium levels.
If your cat's phosphorus level is over 6
mg/dl (USA) or
1.9 mmol/L/l (international), you need to take
steps to control it, see All About Phosphorus.
If you are using phosphorus binders, never use calcium-based
phosphorus binders in a cat with elevated calcium levels.
Limiting
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,
e.g.
Hi-Vites.
Also ensure that you are not feeding a food high in Vitamin D.
Dietary
Changes
It is worth
checking which 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. Normal commercial diets tend to have a ratio of
around 1.2:1 (calcium to phosphorus). However, prescription kidney diets
tend to contain more calcium 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.
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
prescription kidney diet. Cats in these stages do not normally need a low
protein diet, see
Nutritional Requirements, though it must not be
forgotten that a prescription kidney diet has many features other than
merely low protein, see
Which Foods. Your vet can help you decide what to focus on. If your cat does require a prescription 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.
Fibre
Increased fibre in the diet may help to reduce calcium levels by binding
with the calcium. One food that may help with this is Hill's w/d, since it has added fibre.
The canned version of this food would be suitable for most CKD cats, with
a phosphorus level of 0.68% and a protein level of 39.60%. The phosphorus
level in the dry food is a little high at 0.89%, with a protein level of
38.60%, but this might still be acceptable if your cat's phosphorus levels
are under control.
You need to be
careful when choosing a fibre. One type of fibre
called fructooligosaccharides (FOS), often contained in
probiotics,
may actually cause elevated calcium levels. See
Nutritional Requirements for more information on fibre.
Advanced Treatments
These
treatments have pros and cons, and some of the cons are potentially
serious. These treatments may nevertheless be necessary in a small number
of cases. Discuss with your vet.
Corticosteroids
Corticosteroids
such as prednisolone may sometimes be used to control high calcium levels.
Using steroids can have certain undesirable side effects, see
steroids.
The Merck Veterinary Manual
has more
information about using steroids for this purpose.
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
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.
Lasix (furosemide)
is a loop
diuretic which reduces calcium levels because it increases the
excretion of calcium via the kidneys. Diuretics are commonly used in heart
disease but they are hard on the kidneys, and therefore not ideal for a
CKD cat, so I would not use Lasix unless you absolutely had to.
Bisphosphonate Drugs
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.
One drug in this family is called alendronate (Fosamax). It is commonly
used to treat humans with osteoporosis, and may be recommended for CKD
cats for similar reasons i.e. so the bones absorb calcium, which then
reduces calcium levels in the blood.
This is a last resort treatment -
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." The
usual starting dose is 10mg for cats. This is only given once a week but 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. If you
are using
ranitidine (Zantac 75) intravenously for
excess stomach acid (highly unlikely outside a hospital setting), be aware
that it doubled the effect of alendronate in one human study. Ionised calcium levels should be checked regularly,
starting four weeks after the first dose, and the dose should be
adjusted if necessary .
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
Medicine19(1) pp29-33 found
it appeared to be safe and effective. However, pamidronate has to be given
intravenously and may cause electrolyte imbalances, plus it may be
contraindicated for CKD cats.
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.
Low Calcium Levels
Low calcium levels are sometimes seen in CKD cats. The simplest treatment is a calcium supplement such as calcium
carbonate (Tums). If this type of treatment is used, calcium blood
levels should be checked regularly because the opposite problem of high
calcium may result.
Calcitriol (see below) is also used in some cases because it tends to
raise calcium levels.
Untreated
elevated parathyroid hormone (PTH) levels may eventually lead to a
condition called
secondary hyperparathyroidism.
These are the treatments which may be used:
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 -
in one study,
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, a low phosphorus diet, with added binders where
necessary, prevented the rise in
parathyroid hormone
levels seen in the control cats who were not restricted as regards
phosphorus. 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.
I would not use famotidine to treat elevated PTH levels only, but if you
are using it anyway to control excess stomach acid, you may possibly see a
reduction in PTH levels as well.
Calcitriol, or
1,25 dihydroxycholecalciferol, is
Vitamin D3, the active form of Vitamin D. Despite its confusing name, it is
not the same thing as Vitamin D, and is actually a hormone. It
plays an important part in regulating phosphorus and calcium levels in the
body.
Calcitriol production tends to fall in CKD, which is a factor in the
development of
secondary hyperparathyroidism, so human patients with
secondary hyperparathyroidism are sometimes given additional calcitriol,
and some people do the same for their CKD cats.
Why the Use of Calcitriol in Cats is
Controversial
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 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. Vets in the opposing camp
believe that you can control PTH levels and prevent or postpone the
development of secondary hyperparathyroidism by controlling phosphorus
levels. They also are concerned about the potential for calcitriol
supplementation to cause elevated calcium levels.
In
Renal disease (2006) Dr D Polzin
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.
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 don't think
using it is a bad idea if you follow the dosage and monitoring guidelines
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'm not aware
of any evidence for this being effective.
The International Renal Interest Society
states that calcitriol might be helpful
for dogs in IRIS Stage 3 but that "the beneficial effects of ultra low dose calcitriol have
not been established in cats."
Overall, I would be happy to consider using calcitriol, but I do not consider it
essential. If you can find it, and can afford it and the accompanying
testing schedule, and your cat seems to tolerate it, then you could give
it a go. If you do want to try it, Dr Larry Nagode of Ohio State
University College of Veterinary Medicine advises starting it when
creatinine reaches 2 US mg/dl or 175 mmol/L international, assuming
pre- and post-renal causes of the elevated creatinine have been ruled
out. However, 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.
Calcitriol will not work for cats whose phosphorus levels are already
above US: 8 mg/dl (international
2.6 mmol/L), and is of limited value for cats with phosphorus
levels above US: 6 mg/dl (1.9 mmol/L). On the other hand, it can still
cause ionised calcium levels to increase.
Prolonging life and kidney function
(2007) a paper presented to the 32nd World Small Animal
Veterinary Association World Congress by Dr D Chew,explains more
about these issues. Therefore, if your cat's phosphorus levels are above 6
(US) or 1.9 (international),
you must first take all possible steps to control phosphorus
levels (see
Phosphorus for
information on how to do this).
You also need
to consider your cat's 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.
In
Chronic kidney disease in dogs and cats: the pivotal
role of phosphorus control (2011) A Presentation to the 63rd
CVMA Convention, Dr D Chew 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." Dr Chew also mentions that calcitriol will be
less effective if your cat's ionised calcium level is low.
Dosage
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. This is a tiny amount, so in practice you must
use compounded calcitriol in order to obtain cat-sized doses (see below
for sources).
most people
these days use an intermittent dosing schedule, giving calcitriol every
3.5 days, in which case the dose is 8.75 - 12.25 ng twice a week. Dosing
in this way is not only as effective as daily dosing, it can also work out
cheaper, and may reduce the risk of hypercalcaemia. This 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).
A kg is 2.2
lbs, so if your cat weighs 10lb, 10lbs divided by 2.2 is 4.55kg. If you
are giving the 2.5 ng starting dosage of calcitriol to this cat, you would
therefore give 11.4 ng a day. If you are giving it every 3.5 days, you
would give 38.8 ng (rounded up to 39 ng).
Calcitriol is
given on an empty stomach, in either oil-filled capsules or oily liquid
form. The amounts needed are tiny, so the treatment has to be compounded
to the correct dosage for a cat.
If you are using a liquid formulation, be sure
to give it into the side of the mouth, not into the front.
You should avoid giving any supplements etc. containing calcium on the
days when you give calcitriol. Do not store calcitriol in the fridge.
It is usual to
start with the lowest dose, and to check PTH, calcium and phosphorus
levels after 10-14 days. You should check at least 24 hours after giving a
dose of calcitriol. 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.
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.
In
Renal disease (2006) Dr D Polzin 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."
Calcitriol Group - a group devoted to discussing the use of calcitriol
in cats and dogs.
Interactions and Side
Effects
The US National Library of Medicine National
Institutes of Health
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 somewhat. Keep an eye
on this, and increase your phosphorus binder dose as necessary.
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.
Since cats need only tiny doses of calcitriol, you usually have to have it
compounded. It 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.
USA
Calcitriol is
not too expensive in the USA. If you buy six months supply at a time, it
works out at about US$10 a month. If you do buy six months' supply at a
time, make sure its shelf life is for six months or longer.
You do need an experienced compounder, because the doses are so tiny that
mistakes may happen. These compounded pharmacies are often recommended in
the USA:
Wells Pharmacy Network. Apparently Wells took over the business
of Francks Pharmacy, which closed in July 2012 following problems with
quality control. I do not know anyone who has used them yet, though most
people were very satisfied with the calcitriol they got from Francks.
Thriving Pets
If you enter the word "tanya" (without the ") in the promotional code box,
you will receive a 10% discount on orders over US$55.
The use of
calcitriol is difficult in the UK, because it is very hard to find a
pharmacy which is authorised to compound medications for veterinary use into cat-sized dosages.
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 enter the word "tanya" (without the ") in the promotional code box,
you will receive a 10% discount on orders over US$55.
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.
Cinacalcet (Sensipar)
Sensipar
(cinacalcet HCl) belongs to a family of drugs known as calcimimetics and was approved by the USA Food and Drug Administration in
March 2004 for the treatment of secondary hyperparathyroidism in humans.
It is also used to treat hypercalcaemia caused by
parathyroid cancer.
Sensipar 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..
