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> Phosphorus, Calcium, PTH and
Secondary Hyperparathyroidism
Overview
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There is a balance in the body between phosphorus levels and calcium levels.
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In CKD cats,
imbalances are very common.
Phosphorus (P or Pi)
Phosphorus is a mineral that 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.
The kidneys
are responsible for removing excess phosphorus from the body, but
damaged CKD kidneys find this more difficult, so phosphorus levels
within the body begin to rise. This activates a
phosphatonin called fibroblast growth factor 23 (FGF-23), which is
important for the regulation of phosphorus levels in the blood.
FGF-23 may play a role in the early detection of CKD, as discussed in
Early Detection.
If nothing is done to control phosphorus levels in the cat's bloods,
complications may arise, as discussed below
If you are
looking at your cat's blood test results, phosphorus may be abbreviated as
phos, P or Pi.
Oregon State University
provides an overview of phosphorus and its functions in the body.
Cornell University College of Veterinary Medicine
provides an overview of phosphorus.
High Phosphorus Levels (Hyperphosphataemia)
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 also adversely affect calcium levels, with
potentially serious consequences. They can also make the
CKD progress faster and 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.
Since
phosphorus control is so important, there are separate pages
All About Phosphorus
and
Phosphorus
Binders.
Low Phosphorus Levels (Hypophosphataemia)
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.
Refeeding syndrome Sumner C Angell Medical
Center explains more about this.
Hypophosphatemia
(2020)
Allen J Clinician's Brief
Jan 2020 p29 lists possible
causes of hypophosphataemia.
Low phosphorus levels are usually not a major problem. They may sometimes
cause lethargy or anaemia, and if the level falls really low, seizures might occur.
To be on the safe side, I would aim for the following:
Pet MD
has some information about low phosphorus levels.
Calcium
Calcium is a mineral that, like phosphorus, is also found primarily in bone. It is
important for nerve function, muscle contraction, blood clotting, and the
skeleton.
The kidneys excrete excess phosphorus from the body, but damaged kidneys
are less able to do this. Since there is a relationship between phosphorus
and calcium levels within the body, calcium imbalances are relatively
common in CKD cats. Some CKD cats have calcium levels that are too low
(hypocalcaemia), but elevated calcium levels (hypercalcaemia) are more
common.
A review of the role of fibroblast growth factor 23
in phosphate homeostasis and the pathophysiology of mineral bone
disorder associated with chronic kidney disease
(2023) Elliott J, Geddes R & Jepson R
International Renal
Interest Society states "It is important to assess plasma
calcium concentration (ideally ionised calcium) in all cats with CKD at
diagnosis of CKD as idiopathic hypercalcaemia has been associated with
CKD." Very few vets do check ionised calcium levels routinely.
Oregon State University
provides an overview of calcium
and its functions in the body.
Cornell University College of Veterinary Medicine
provides an overview of calcium.
Calcium Forms
Calcium exists in three different forms in the blood:
-
bound, which is bound to proteins
(around 80% to albumin
and 20% to globulins)
-
complexed, with certain anions such
as bicarbonate
-
ionised, or free
The total calcium figure on a blood
chemistry panel is the sum of all of these, with ionised calcium
comprising about 52% of the total in healthy cats (protein-bound accounts for around 40%
and complexed for around 8%). Ionised calcium is the value of main
concern for most CKD cats, because, being free (biologically active) in
the body, it is this that may cause problems.
CKD cats may have reduced calcium levels (hypocalcaemia) or elevated
calcium levels (hypercalcaemia). Whether these are a concern depends in
part upon the ionised calcium level.
Low Calcium Levels (Hypocalcaemia)
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 gastrointestinal 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
gastrointestinal tract and release less from the bones, and thus levels
of calcium in the body may fall.
Hypocalcaemia is generally considered to be present when total calcium
is below 9 mg/dl or
ionised calcium is below 1.2
mmol/L.
Excess phosphorus levels may also reduce
calcium levels by suppressing the production of calcitriol.
Up to 50% of cats with
pancreatitis have hypocalcaemia.
Serum ionised calcium as a prognostic risk factor
in the clinical course of pancreatitis in cats (2015) Dias C
& Carreira LM Journal of Feline Medicine & Surgery
17(12)
pp984-90 states "The results suggest that hypocalcaemia is common in
patients with pancreatitis and that [Ca(2+)i] may be used as a
prognostic risk factor for predicting the clinical course of the
disease, with values < 1 mmol/l corresponding to a poor prognosis."
VCA Animal Hospitals
discusses hypocalcaemia.
Colorado State University has some
information about calcitriol.
Cornell University College of Veterinary Medicine
has some information about low calcium levels (scroll down).
Michigan State University Veterinary Diagnostic
Laboratory has some information about
hypercalcaemia.
Hypocalcemia
(2020) Allen J Clinician's Brief
Mar 2020 p41 outlines
possible causes of hypocalcaemia.
High Calcium Levels (Hypercalcaemia)
What constitutes a high calcium level? The range for
calcium varies from laboratory to laboratory, but generally speaking:
-
if levels
approach 20 mg/dl US (5.0 mmol/L international), the cat may go into a
coma and die.
Hypercalcemia in dogs and cats (2016)
Peterson ME Merck Veterinary Manual says "serum
concentrations of >18 mg/dL are often associated with severe,
life-threatening signs." Fortunately, such extremely high levels
are very rare, so in practice you are unlikely to see them.
Elevated calcium levels are relatively common in CKD cats.
Hypercalcaemia in cats (2001) Chew D
Presentation to the World Small Animal Veterinary Association World
Congress states that 38% of hypercalcaemic cats in one
study had CKD.
Chronic kidney disease in cats and the risk of total
hypercalcaemia (2017) van den
Broek DHN, Chang Y-M, Elliott J & Jepson RE
Journal of Veterinary
Internal Medicine 31(2) pp465–475 found that CKD cats with
azotaemia (elevated kidney values in the blood) were four times as
likely to develop hypercalcaemia as CKD cats without azotaemia.
Even if your cat's calcium levels are not high enough to be
life threatening, they can still have adverse effects on the cat's body.
Hypercalcemia in chronic kidney disease
(2022) Van den Broek H International Renal Interest Society
states "hypercalcemia may worsen signs related to CKD as it further
reduces glomerular filtration rate (GFR) and can cause anorexia,
polyuria and polydipsia, muscle weakness, and constipation.
Hypercalcemia can furthermore contribute to urolithiasis and, especially
in combination with hyperphosphatemia, to soft tissue calcification.
Calcification of the aorta, gastric wall, kidneys, and paws has been
reported in cats with CKD."
Using urine specific gravity (2022) Watson
ADJ, Lefebvre HP & Elliott J International Renal Interest Society
mentions that cats with hypercalcaemia may also have a low
urinary
specific gravity (USG).
Even if your cat's total calcium levels are normal, make sure ionised
calcium levels are checked.
A review of the role of fibroblast growth factor 23
in phosphate homeostasis and the pathophysiology of mineral bone
disorder associated with chronic kidney disease
(2023) Elliott J, Geddes R & Jepson R
International Renal
Interest Society states "It is important to assess plasma
calcium concentration (ideally ionised calcium) in all cats with CKD at
diagnosis of CKD as idiopathic hypercalcaemia has been associated with
CKD." Very few vets do check ionised calcium levels routinely. See
below for more information.
Guidelines for evaluating hypercalcemic cats
(2008) Cook AK Veterinary Medicine explains more about
diagnosing hypercalcaemia.
Clinical approach to the hypercalcemic patient
(2008) Ward C CVC in Washington Proceedings also discusses diagnosis.
Hypercalcemia in dogs and cats: etiology and diagnostic approach
(2002) Nelson R Presentation to the 27th World Small Animal Veterinary
Association Congress 2002 explains more about hypercalcaemia.
High Calcium Levels: Causes
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.
Around 15% of cats with hypercalcaemia
have
calcium oxalate stones in the urine, though it is not clear which
came first.
Hyperthyroidism may be another
factor.
A type of
fibre
called fructooligosaccharides (FOS) may
cause elevated calcium levels.
Recent research indicates that early stage CKD cats who are fed a diet
low in phosphorus, particularly therapeutic kidney diets, may develop
hypercalcaemia, especially if they already have reasonably low blood
phosphorus levels.
Hypercalcemia in chronic kidney disease (2022) Van den Broek
International Renal Interest Society
says that the attributes "of clinical renal diets (although dependent on
the exact formulation) could theoretically all contribute to an increased
serum calcium concentration in the cat or dog with CKD."
The benefits of therapeutic diets are usually considered to outweigh the
potential risk of hypercalcaemia. However, this is another reason not to feed
these foods to early stage cats (see
Nutritional
Requirements). For cats at any stage,
Treatment recommendations for CKD in cats
(2023) International Renal Interest Society say
"Monitor serum calcium and if total calcium
exceeds 12mg/dl (3mmol/l) switch the cat to a less phosphate restricted
diet."
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.
Many commercial foods seem to contain levels in
excess of current maximum US allowances (10,000 iu/kg for adult cats).
Update on the etiology of tooth resorption in
domestic cats (2005) Reiter AM, Lewis JR & Okuda A
Veterinary Clinics Small Animal Practice
35 pp913-942 states
"results of experimental studies on cats fed diets high in vitamin D3
(15,000–33,840 IU/kg of dry matter) were contradictory, ranging from no
evidence of detrimental effects on feline health to a high prevalence of
renal dysfunction and mortality."
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.
Slippery elm bark also contains calcium, so it is probably safer not to use it
if your cat has hypercalcaemia.
Top 10 differentials for hypercalcemia in the dog
(2012) Peterson ME Insights Into Veterinary Endocrinology discusses how to
narrow down the cause in dogs using mnemonics (GOSH DARN IT and HARD IONS).
Hypercalcemia — distinguishing causes and preventing complications
(2008) Mooney CT Presentation to the
World Small
Animal Veterinary Association World Congress discusses possible causes
of hypercalcaemia.
Michigan State University Veterinary Diagnostic
Laboratory has some information about
hypercalcaemia.
High Calcium Levels:
Idiopathic Hypercalcaemia
In many cases,
no cause for the elevated calcium levels can be found. This is known as
idiopathic hypercalcaemia.
Michigan State University Veterinary Diagnostic
Laboratory explains more about idiopathic hypercalcaemia
(scroll down).
What's causing idiopathic hypercalcemia in
cats? (2012) Peterson ME Insights Into Veterinary Endocrinology discusses idiopathic hypercalcaemia.
High Calcium Levels: Initial Steps
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 the
27th 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 an
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).
Should treatment be necessary after checking ionised calcium levels,
Treatments explains more about the possible treatment options.
Ionised Calcium
Ionised calcium is the amount of free calcium, i.e. metabolically
active calcium, in the body. It forms about 52% of total calcium in
healthy cats.
Many vets simply look at the total calcium levels in blood test results,
but these are not an accurate indication of ionised calcium levels.
Prediction of serum ionized calcium
concentration by serum total calcium measurement in cats
(2010) Schenck PA & Chew D
Canadian Journal of Veterinary Research
74(3) pp209–213 states "In general, tCa concentrations cannot be
relied on to accurately assess calcium status in cats as shown by
discordance with iCa measurement. This is especially important in cats
with CRF where abnormalities in TP, albumin, and complexed calcium
fractions may be present. Due to the high number of false negatives, many
cats may appear normocalcemic when tCa is measured, but actually have a
derangement in calcium homeostasis. Ionized calcium concentration must be
directly measured to accurately assess calcium status.”
Hypercalcemia in chronic kidney disease (2022) Van den Broek
International Renal Interest Society
says "(true)
ionized hypercalcemia will be under diagnosed in cats when only total
calcium is measured. Serum ionized calcium should therefore be measured to
allow a correct diagnosis and adequate management in both cats and dogs."
Ionized hypercalcemia
in cats with azotemic chronic kidney disease (2012-2018) van
den Broek DHN, Geddes RF, Lötter NS, Chang Y-M, Elliott J & Jepson RE Journal
of Veterinary Internal Medicine 36(4)
pp1312-1321 looked at cats at the time of diagnosis of elevated kidney
values and found that 4% of the cats had elevated total calcium levels but
20% had elevated ionised calcium levels. Cats were more likely to have
ionised hypercalcaemia if they were male, or had higher potassium and total
calcium levels and lower parathyroid levels. After 140 days, 26% of the
cats whose calcium levels had initially been normal had also developed
elevated ionised calcium levels. The study concludes "CKD cats should be
monitored for the presence of, or development of, hypercalcaemia, ideally
by assessing ionised calcium."
Therefore, if your cat has high
calcium levels for which no obvious cause can be found, ask your vet to check ionised calcium,
which will almost always have to be done by an external laboratory
(although not all laboratories can do this).
-
If ionised levels are elevated (over 1.4 mmol/l or over 5.6 mg/dl), you do need to take action because if this
is the case for any length of time, it may contribute to CKD. See
Treatments for how to do this.
Cornell University College of Veterinary Medicine
has some information about ionised calcium levels.
Michigan State University Veterinary Diagnostic
Laboratory
explains more about ionised
calcium, and can
perform the ionised calcium test (see
below for more
information).
Update on feline ionized hypercalcemia
(2017) de Brito Galvão JF, Parker V,
Schenck PA & Chew DJ Veterinary Clinics of North America: Small Animal Practice
47(2):273-292
Hypercalcemia in cats — update on diagnosis and
treatment (2018) Beatty J Presentation to the
World Small Animal Veterinary Association World Congress discusses
diagnosis and treatment.
Phosphorus Multiplied by Total Calcium
Although, as
stated above, ionised calcium is usually what matters for CKD cats, you do have to
take total calcium levels into account in one main regard: you have
to consider the level of phosphorus multiplied by total calcium.
This is
because cats with a high number are at risk of a problem called
calcification.
Hypercalcaemia in cats
(2001) Chew D
Presentation to the World Small Animal Veterinary Association World
Congress
says "The degree of interaction with serum phosphorus is
important, as those with a total serum calcium times phosphorus
concentration product greater than 70 are most likely to have severe
tissue changes associated with mineralization."
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.
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.
It is less
likely to be a problem if the product is above these levels because of a
higher calcium level rather than a higher phosphorus level; but I would
still recommend trying to reduce these levels if at all possible.
Parathyroid
Hormone (PTH) and Calcitriol
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:
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 gastrointestinal 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. 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.
FGF-23 is a renal biomarker that is being investigated for its potential
role in the early detection of CKD.
A review of the role of fibroblast growth factor 23
in phosphate homeostasis and the pathophysiology of mineral bone
disorder associated with chronic kidney disease
(2023) Elliott J, Geddes R & Jepson R
International Renal
Interest Society
states "Down-regulation of
tissue klotho expression occurs in CKD (Sakan et al., 2014) secondary to
uraemic toxins (indoxyl sulphate and p-cresyl; Young & Wu, 2012) and
proteinuria (Delitsikou et al. 2020). This makes FGF23 much less able to
activate FGF-1 receptors (where klotho is needed as a co-receptor) at
which point plasma PTH concentrations start to rise (due to lack of FGF23
inhibition of PTH synthesis and secretion) and eventually plasma phosphate
concentrations start to increase and ionised calcium concentrations
decrease."
High levels of
PTH may also adversely affect the production of
erythropoietin, a hormone
which stimulates the bone marrow to make red blood cells, and may
therefore be a factor in a CKD cat developing anaemia.
Role of secondary hyperparathyroidism in
erythropoietin resistance of chronic renal failure patients
(2002) Drücke TB & Eckardt K-U Nephrology Dialysis Transplantation
17 Supp.5 pp17-21 mentions this in human patients.
Many cats who
are only in
IRIS Stage 2
will have normal phosphorus levels but may nevertheless
have elevated PTH levels, which can still lead to secondary
hyperparathyroidism.
Parathyroid hormone concentration in geriatric cats
with various degrees of renal function
(2012) Finch NC, Syme HM & Elliott J
Journal of the American
Veterinary Medical Association 241(10) pp1326-35 found that
"renal secondary hyperparathyroidism can develop prior to
azotemia in cats, even in the absence of hyperphosphatemia and
hypocalcemia."
Generally
speaking, problems tend to arise when PTH is around three times the level
of the top of the normal range.
Michigan State University Veterinary Diagnostic
Laboratory has
stated that the
reference range for PTH is 0.4 - 2.5 pmol/L. Therefore
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 in order to avoid secondary
hyperparathyroidism.
Calcium and phosphate homeostasis in hyperthyroid
cats: associations with development of azotaemia and survival time
(2012) Williams TL, Elliott J & Syme HM
Journal of Small Animal
Practice 53(10) pp561-71 found that approximately 60% of
cats in the study with
hyperthyroidism
(an overactive thyroid) had elevated parathyroid hormone levels, which decreased
following treatment of the hyperthyroidism in cats who did not have CKD.
The US food and Drug Administration
(2017) warns that in humans, taking large doses of biotin supplements
may adversely affect test results for parathyroid hormone,
T4
and
T3.
Oregon State University discusses calcium and phosphorus homeostasis.
Cornell University College of Veterinary Medicine
has some information about parathyroid hormone.
Parathyroid hormone, a uremic toxin
(2009) Rodriguez M & Lorenzo V
Seminars in Dialysis
22(4)
pp363-8 mentions that PTH can be elevated in human patients and can have a
variety of effects.
Secondary Hyperparathyroidism (RSHP,
formerly 2-HPTH)
Secondary
hyperparathyroidism is
caused by part of the body's mechanism for controlling phosphorus and
calcium levels effectively going into overdrive, as explained
above. It
is not the same as
hyperthyroidism.
As 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, anaemia, reduced immunity to infection and
muscle weakness. Other severe consequences may also result, see
below.
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 CKD cats in the study eventually developed secondary
hyperparathyroidism,
so it is important to be aware of the possibility.
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 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."
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
discusses secondary hyperparathyroidism (in very technical terms).
Veterinary Partner
explains more about
secondary hyperparathyroidism in easy to understand language.
PetCoach
has helpful information about
this disease.
Endocrine Web is a human site but has a lot of information.
The clinical consequences of secondary
hyperparathyroidism: focus on clinical outcomes
(2004) Hörl WH Nephrology Dialysis Transplantation 19 (suppl 5)
v2-v8 discusses the problems that may arise with secondary
hyperparathyroidism in humans.
Chronic Kidney
Disease-Mineral and Bone Disorder (CKD-MBD)
In cats with secondary hyperparathyroidism that goes untreated, in the
worst case, CKD-MBD may result.
CKD-MBD is an abbreviation for chronic kidney disease-mineral and bone
disorder, a syndrome wherein there are mineral disturbances (as you
might expect, the two main minerals affected are phosphorus and
calcium), bone problems and soft tissue calcification (hardening).
Chronic kidney disease in cats and the risk of total
hypercalcaemia (2017) van den
Broek DHN, Chang Y-M, Elliott J & Jepson RE
Journal of Veterinary
Internal Medicine 31(2) pp465–475 says "One syndrome with
abnormalities correlated with CKD and renal osteodystrophy is called
chronic kidney disease-mineral and bone disorders (CKD-MBD). Development
of this syndrome is a consequence of reduced glomerular filtration rate
(GFR) and associated phosphate retention."
Hypercalcemia in chronic kidney disease (2018) Van den Broek
International Renal Interest Society mentions CKD-MBD.
Calcification
As secondary hyperparathyroidism progresses, the cat is at risk of tissue
calcification, which means that normally soft tissue in the body becomes
hardened, which is very painful and can adversely affect proper function.
Hypercalcemia in chronic kidney disease
(2018) Van den Broek H International Renal Interest Society
states "Calcification of the aorta, gastric wall, kidneys, and paws has been
reported in cats with CKD."
FGF-23 is a renal biomarker that is being investigated for its potential
role in the early detection of CKD.
Recent advances in mineral bone disorders in CKD
van den Broen & Elliott J International Renal Interest Society says
"Recent advances in understanding the role of FGF23 - α-Klotho axis in the
pathophysiology of bone and mineral disorders associated with chronic
kidney disease and recognition of the way in which serum magnesium impacts
on this hormonal system and influences the propensity for vascular
calcification are important. Routine measurement of serum FGF23 and
magnesium could identify those veterinary patients that will benefit most
from effective management of these bone mineral disturbances."
Risk factors and implications associated with renal mineralization in
chronic kidney disease in cats (2022)
Tang P, Jepson RE, Chang Y, Geddes RF, Hopkinson M & Elliott J Journal
of Veterinary Internal Medicine 36(2) pp634-646 looked at
deceased cats in stages 1-3 azotaemic CKD and found that 21.6% had no
calcification. but 78.4% had mild to severe calcification (grades 1 and
2). The cats with grade 2 had significantly higher total calcium levels,
although only one cat had calcium levels outside the laboratory
reference range. Rather surprisingly, cats fed a therapeutic kidney diet
were at higher risk of calcification, but on the other hand cats whose
diet consisted of more than 50% therapeutic kidney food also survived
longer, so the study still advocates feeding this diet.
Feline chronic kidney disease
(2015) Grauer GF Today's Veterinary Practice
5(2)
pp36-41
has photos of calcification.
See
above for when
the risk of calcification becomes a concern.
Osteodystrophy (Rubber Jaw)
Cats with
secondary hyperparathyroidism can also develop problems with their jaw
whereby the jawbone softens, though this is far more common in dogs. This is known as osteodystrophy or colloquially as "rubber jaw."
Chronic kidney disease
in cats and the risk of total hypercalcaemia
(2017) van den Broek DHN, Chang Y-M, Elliott J & Jepson RE
Journal of Veterinary Internal Medicine
31(2) pp465–475 says "One syndrome with abnormalities correlated with
CKD and renal osteodystrophy is called chronic kidney disease-mineral and
bone disorders (CKD-MBD). Development of this syndrome is a consequence of
reduced glomerular filtration rate (GFR) and associated phosphate
retention."
Renal osteodystrophy due to secondary hyperparathyroidism in a cat
(2021)
Gonzalez SE, Roth IG, Schmiedt CW, Patrick MH & Meindl AG Journal of
the American Animal Hospital Association 57(4) pp179-183
reports on a six year old cat with a very high PTH reading who developed
renal osteodystrophy.
University of Georgia College of Veterinary Medicine
has a photo of a dog with osteodystrophy.
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 Ciências Agrárias
29(n2)
pp407-412 has x-rays and photos of a dog with osteodystrophy, although the
large lesions seen in this poor dog are unusual.
Testing PTH
and Ionised Calcium
Any laboratory
can measure phosphorus and total calcium levels, but it is a lot harder to
find a laboratory which can measure PTH and ionised calcium.
Michigan State University Veterinary Diagnostic
Laboratory
explains why cats with CKD should have PTH and ionised calcium checked.
USA and
Canada
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 PTH and ionised calcium test is run
four days a week (Mon-Wed and Fri), and turnaround time is 1-4 days. The sample needs to be sent
overnight as a chilled or frozen 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
2023, MSU charged US$51 to run both tests, but you can check the current
price
here (look for test number.20033).
For people within the USA, MSU can also provide your vet with an
insulated prepaid UPS
overnight mailing envelope,
which costs US$25 (number
99220). You or your vet
will need to provide cold packs to place around the sample
(though I heard from one person who said
it was included in the package they received from MSU), but overall
this usually works out cheaper than paying for chilled overnight shipping
yourself.
UK
NationWide Specialist Laboratories in
Cambridge
can measure PTH and ionised calcium in the UK. There is more information
and a price list (which doesn't seem to contain any prices)
here. 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 enough to last for the length of the
journey..
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Index
With thanks to Dr Larry Nagode, now sadly deceased,
previously of Ohio State University College of Veterinary Medicine, for
his help with this page. This page last
updated: 03 April 2023
Links on this page last
checked: 03 April 2023
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