Phosphorus is
a mineral which is essential for bodily function. Most of the body's
phosphorus is contained in bone. Phosphorus is important for energy
production, acid base balance (imbalances in this area can lead to a
condition known as
metabolic
acidosis) and for delivering oxygen to the body's
cells.
Virtually every CKD cat will eventually develop high phosphorus
levels (hyperphosphataemia). This happens
because the damaged kidneys can no
longer excrete excess phosphorus properly.
There is a balance in the body between phosphorus and calcium. Thus
elevated phosphorus levels can adversely affect calcium levels, with
potentially serious consequences, and can generally make the
CKD progress faster. They also make the cat feel very unwell.
Symptoms include nausea, weakness and loss of appetite.
Because of
these risks, having a phosphorus level within the normal range is not
sufficient for a CKD cat. If your cat's phosphorus level is over 6
mg/dl (USA) or
1.9 mmol/L (international), you need to take
steps to control it.
Low phosphorus levels are extremely rare in CKD cats, but may occasionally
arise. In most cases they tend to happen if you are over zealous with
phosphorus binders used to control high phosphorus levels, but may also be
seen in cats with diabetes controlled by insulin. Certain types of cancer may
cause low phosphorus levels, as may feeding a cat following a period of
prolonged starvation.
Low phosphorus levels are usually not a problem, although they may sometimes
cause lethargy, and if the level falls really low, seizures might occur.
Nutritional management of feline chronic kidney
disease (2008) Elliott J, Elliott D
Veterinary Focus18(2) pp39-44 recommends that cats in Stage 2
of CKD should not have a level below 2.5 mg/dl (0.8 mmol/L international). I would aim for
a level of around 4 mg/dl US (1.3 mmol/L international), but no lower than 3
mg/dl US (1.0
mmol/L international).
Calcium is a mineral which is also found primarily in bone. It is
important for nerve function, muscle contraction, blood
clotting, and the skeleton. CKD cats can have elevated calcium
levels (hypercalcaemia) or reduced calcium levels (hypocalcaemia).
Elevated
calcium levels are relatively common in CKD cats. In
Hypercalcemia in cats (2001)
Presentation to the World Small Animal Veterinary Association World
Congress, Dr D Chew states that 38% of hypercalcaemic cats in one
study had CKD.
The range for
calcium varies from laboratory to laboratory, but generally speaking, a
level over 11 mg/dl US (2.75 mmol/L international) is considered to be hypercalcaemia,
though you may not see any symptoms until it is higher than this. If
calcium goes above 15 mg/dl US (3.75 mmol/L international), a cat may have constipation, little appetite and sleep a
lot; if levels approach 20 mg/dl US (5.0 mmol/L international), the cat may go into a coma and
die. Fortunately, such extremely high levels are very rare so in practice
you are unlikely to see them.
Causes of High Calcium Levels
The normal
level of calcium in the blood is in ratio to the phosphorus level -
calcium levels are usually at an approximate level of 100 - 200% of
phosphorus levels. Since phosphorus levels are often high in CKD cats, calcium levels may
also rise in an attempt to maintain the ratio. Conversely, if elevated
phosphorus levels are reduced, often the calcium levels will also reduce to a
satisfactory level.
Other causes of
hypercalcaemia include metabolic acidosis
(since acid in the blood leads to
the release of calcium from proteins or from bone) or, rarely,
cancer. In
rare cases, excess Vitamin D in the diet causes hypercalcaemia - in 2006,
Royal Canin had to recall some foods to which too much Vitamin D had been
added by mistake, causing hypercalcaemia in four cats.
Around 15% of cats with hypercalcaemia
have calcium oxalate stones in the urine, though it isn't clear which
comes first. Hyperthyroidism may be another
factor.
A type of
fibre
called fructooligosaccharides (FOS), often contained in probiotics, may
cause elevated calcium levels.
Some people have
found that using
lactulose to control constipation has led to hypercalcaemia in their cats. This might just be coincidence, but you may wish to avoid
lactulose if your cat already has hypercalcaemia, and consider alternative
constipation treatments if your cat develops hypercalcaemia while using lactulose.
The first thing
to do is to run the calcium test again.
Hypercalcemia in dogs and cats: etiology and diagnostic approach
(2002) Nelson R Presentation to the27th World Small Animal Veterinary
Association Congress 2002 states "Hypercalcemia
should always be reconfirmed, preferably from a nonlipemic blood sample
obtained from the dog or cat following a 12 hour fast, before embarking on
an extensive diagnostic evaluation."
If the second
test also indicates hypercalcaemia, for which no obvious cause can be
found, the next step is to run a specialised test called the
ionised calcium test. If this is normal, there is no need to worry about the
hypercalcaemia per se. However, you do need to consider the product of
total calcium multiplied by phosphorus (see
below).
Calcium exists in three different forms in the body, but the measurement
which is important in CKD cats is ionised calcium, which forms about 50% of total
calcium. Ionised calcium is the amount of free calcium, i.e. metabolically active
calcium.
If your cat has high
calcium levels for which no obvious cause can be found, ask your vet to check ionised calcium (although not all laboratories can do this).
If ionised calcium levels are normal (or even low, which is not unusual in
CKD cats), there is no need to
treat for hypercalcaemia in a CKD cat. If ionised levels are elevated, you
do need to take action because if this is the case for any length of
time, it may contribute to CKD.
Calcitriol (1,25 dihydroxycholecalciferol) is the active form of Vitamin
D3, which, despite its name, is actually a hormone. It facilitates the
absorption of calcium from the gastro-intestinal tract and the release of
calcium from the bones where it is stored. Cats have
to make calcitriol from Vitamin D before they are able to use it, and the
final step of this process is performed by the kidneys.
Because of their failing kidneys, CKD cats may no longer be able to
convert Vitamin D into calcitriol, so they absorb less calcium from the
gastro-intestinal tract and release less from the bones, and thus levels
of calcium in the body may fall.
Excess phosphorus levels may also reduce
calcium levels by suppressing the production of calcitriol.
Up to 50% of cats with
pancreatitis have hypocalcaemia.
Phosphorus and calcium levels in the body are controlled by glands called the parathyroid glands,
which adjust phosphorus and/or calcium levels as appropriate via two
hormones called parathyroid hormone (also known as PTH) and calcitriol.
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.
Many cats who
are only in
IRIS Stage 2 will have normal phosphorus levels but will still
have elevated PTH levels, which can still lead to secondary
hyperparathyroidism. Generally
speaking, problems tend to arise when PTH is around three times the level
of the top of the normal range.
Michigan State University states that the
reference range for PTH is 0.4 - 2.5 pmol/L, so toxicity can be expected
when PTH is 7.5 pmol/L or over. However, if it is at all elevated, it is best to
take action to reduce it as soon as possible, so as to avoid secondary
hyperparathyroidism.
Parathyroid hormone, a uremic toxin
(2009) Rodriguez M & Lorenzo V Seminars in Dialysis22(4)
pp363-8 mentions that PTH can be elevated in human patients and can have a
variety of effects.
Secondary
hyperparathyroidism is not the same as
hyperthyroidism, but rather is
caused by part of the body's mechanism for controlling phosphorus and
calcium levels effectively going into overdrive, as explained
above. One study,
Feline chronic renal failure: calcium homeostasis in 80 cases diagnosed
between 1992 and 1995 (1998) Barber PJ, Elliott J
Journal of Small Animal Practice 39 pp108-116),
found that 84% of the cats in the study eventually developed this problem,
so it is important to be aware of the possibility.
As the
problems with the regulation of calcitriol and parathyroid stimulating
hormone (PTH) progress, levels of PTH will continue to
rise and eventually secondary hyperparathyroidism results. Blood calcium levels may appear
to be normal or low but over time various symptoms may appear, including lack of
appetite (blood
glucose levels rise which
stop the cat feeling hungry), anaemia, reduced immunity to infection and
muscle weakness.
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 that it is possible for a CKD
cat to develop secondary hyperparathyroidism even if phosphorus levels and
ionised calcium levels are normal. He explains "In the early stages of
chronic kidney disease increased levels of parathyroid hormone (PTH) keep
serum phosphorous within the normal range by increasing phosphate
excretion into urine. This allows for normalization of serum phosphorous
at the expense of hyperparathyroidism."
As secondary
hyperparathyroidism progresses, the cat is at risk of tissue calcification, which
means that normally soft tissue in the body goes hard, which is very
painful and can adversely affect proper function. If calcification occurs
in the kidneys, kidney function is further worsened and a vicious circle
results.
As a rough guide, if phosphorus multiplied by total calcium is
higher than around 60 in US values or 5 in international values, your cat is at
risk of calcification, though it is less likely to be a problem if the
product is above this level because of a higher calcium level rather than
a higher phosphorus level. Alternatively, you can multiply phosphorus by ionised calcium, and if the level is higher than 8.75
in US values or 35 in international values, there is a risk of calcification.
Cats with
secondary hyperparathyroidism can also develop problems with their jaw
whereby the jawbone softens. This is known as osteodystrophy or colloquially as "rubber jaw."
Oral lesions associated with renal secondary
hyperparathyroidism in an English bulldog (2008) Headley SA, Veltrini
VC, Fuck EJ, Fuck ET, Curti CE, Bettini CM, Bracarense APFRL, dos Reis ACF
Presentation to the Semina Cięncias Agrárias29(n2)
pp407-412 has x-rays and photos of a dog with this problem, although the
large lesions seen in this poor dog are unusual.
Veterinary Partner explains more about
secondary hyperparathyroidism in easy to understand language.
Pet Education has helpful information about
this disease.
Medicine Net has an article about renal
osteodystrophy in humans.
Endocrine Web - a human site but has a lot of information.
Michigan
State University Diagnostic Center for Population & Animal Health
is the best place to have PTH and ionised calcium levels checked in the
USA. Although other US laboratories do offer these tests, they often
send them to MSU anyway, so it takes longer and you will pay more. If your
vet does not already have an account with MSU, s/he can create one
here.
The test is
only run twice a week (on Mondays and Thursdays), and your sample
should arrive there the day before testing day. it needs to be sent
overnight as a chilled sample. There is more information
here.
Your cat should
fast for eight hours before the test in order to avoid
lipaemia which
may adversely affect the results. The blood can be taken by your own vet
(who will of course charge for his/her time and work), who can then send
the sample direct to MSU for analysis, using this
test form, which also includes guidelines
for how to take and send the sample.
As at April
2012, MSU charged US$34 to run both tests, but you can check the current
price
here (look under Endocrinology, no.
20033). For people within the USA, MSU can also provide an insulated prepaid Fedex overnight mailing
envelope which costs US$16 using this
order form (no. 99220). You or your vet
will need to provide cold packs to place around the sample, but overall
this usually works out cheaper than paying for chilled overnight shipping
yourself.
UK
Cambridge Specialist Laboratory Services
can measure PTH and ionised calcium in the UK. I don't know anybody who
has used them yet. I have heard of British vets submitting samples to MSU,
I'm not quite sure how they keep the samples cool long enough.
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here
for treatment options for the problems outlined on this page.
