TANYA'S

COMPREHENSIVE GUIDE TO

FELINE CHRONIC KIDNEY DISEASE

 
 

DIAGNOSIS: PHOSPHORUS, CALCIUM, PARATHYROID STIMULATING HORMONE (PTH) AND SECONDARY HYPERPARATHYROIDISM

 

ON THIS PAGE:


Phosphorus:


High Phosphorus Levels


Low Phosphorus Levels


Calcium:


High Calcium Levels


Ionised Calcium Levels


Low Calcium Levels


Parathyroid Hormone (PTH)


Secondary Hyperparathyroidism


How to Test Parathyroid Hormone and Ionised Calcium Levels


 

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Home > Diagnosis > Phosphorus, Calcium, PTH and Secondary Hyperparathyroidism

 


Overview


  • There is a balance in the body between phosphorus and calcium levels.

  • In CKD cats, imbalances are very common.

  • In the worst case, problems then also arise with a hormone called parathyroid hormone.

  • These imbalances can eventually lead to a condition called secondary hyperparathyroidism, which can have serious effects on the cat.

  • It is therefore important to monitor phosphorus, calcium and PTH levels in all CKD cats.

  • Click on the links at the top of the sidebar to the left to view the contents of this page.


Phosphorus (P or Pi)                                                                                      


 

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.

 

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 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.

 

Since phosphorus control is so important, there are separate pages all about phosphorus and phosphorus binders.

 

A phosphatonin called fibroblast growth factor 23 (FGF-23) is important for the regulation of phosphorus levels in the blood. Early Detection briefly discusses the role FGF-23 may play in the early detection of CKD.

 

Cornell University College of Veterinary Medicine has some information about high phosphorus levels.

 

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.

 

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 Focus 18(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).

 

Cornell University College of Veterinary Medicine has some information about low phosphorus levels.

Pet MD also has some information.

 


Calcium                                                                                                             


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). 

 

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.

 

High Calcium Levels (Hypercalcaemia)


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.

 

In many cases, no cause for the elevated calcium levels can be found - this is known as idiopathic hypercalcaemia. Michigan State University diagnostic Center for Population & Animal Health explains more about idiopathic hypercalcaemia. The Merck Veterinary Manual also discusses it, as does Dr ME Peterson in the article, What's causing  idiopathic hypercalcemia in cats (2012).

 

Initial Steps in Cases of High Calcium Levels


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 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).

 

Cornell University College of Veterinary Medicine has some information about high calcium levels.

Veterinary Partner has a good overview of hypercalcaemia.

Pet Place explains more about hypercalcaemia.

Guidelines for evaluating hypercalcemic cats (2008) Cook AK Veterinary Medicine explains more about diagnosing hypercalcaemia.

Clinical approach to the hypercalcemic patient (2008) Ward C Veterinary Medicine also discusses diagnosis.

Hypercalcemia - distinguishing causes and preventing complications (2008) is a paper presented by CT Mooney to the World Small Animal Veterinary Association World Congress.

Antech Diagnostics (2000) has information on hypercalcaemia by Dr D Chew.

Hypercalcaemia in cats (2001) is a paper by Dr Chew presented to the World Small Animal Veterinary Association World Congress.

Hypercalcemia in dogs and cats: etiology and diagnostic approach (2002) is a paper presented to the 27th World Small Animal Veterinary Association Congress 2002 by Richard Nelson. 

 

Ionised Calcium


lcium 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.

 

Cornell University College of Veterinary Medicine has some information about ionised calcium levels.

Michigan State University Diagnostic Center for Population & Animal Health explains more about ionised calcium, and can perform the ionised calcium test (see below for how to get this done).

 

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 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. 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.

 


Parathyroid Hormone (PTH)                                                                 


 

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.

 

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.

 

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. 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 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.

 

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 the hyperthyroid cats in the study had elevated parathyroid hormone levels, which decreased following treatment of the hyperthyroidism in cats who did not have CKD.

 

Oregon State University has a helpful diagram showing 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 (2-HPTH)                                         


 

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, 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."

 

Retrospective analysis of dietary management of hyperphosphataemia in cats with CKD (2008) Elliott J Veterinary Record 18(2) pp45-47 has photos of a cat with bone problems caused by secondary hyperparathyroidism.

 

Calcification


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.

 

Kidney Research UK discusses calcification.

 

Osteodystrophy (Rubber Jaw)


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 Agrárias 29(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.

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.

 


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 Diagnostic Center for Population & Animal Health 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 test is run five days a week (Mon-Fri), and samples received in the morning will be tested that afternoon, with results available the next day (for samples received on Fridays, results will be available on Mondays). 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 your vet with 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 (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


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.

 

Click here for treatment options for the problems outlined on this page.

 

 

 

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This page last updated: 04 March 2016

Links on this page last checked: 03 April 2012

 
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