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DIAGNOSIS: PHOSPHORUS, CALCIUM, PARATHYROID STIMULATING

 

HORMONE (PTH) AND SECONDARY HYPERPARATHYROIDISM

 

ON THIS PAGE:


Phosphorus


Calcium


Phosphorus Multiplied by Total Calcium


Parathyroid Hormone (PTH) and Calcitriol


Secondary Hyperparathyroidism


Chronic Kidney Disease-Mineral and Bone Disorder (MBD): Calcification and Osteodystrophy


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 levels and calcium levels.

  • In CKD cats, imbalances are very common.

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

  • 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 to the left to view the contents of this page.


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.

  • 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.

  • Your aim is to reduce your cat's phosphorus to a level of below 4.6 mg/dl (1.5 mmol/L international).

  • You may not be able to get it this low if your cat is in IRIS Stage 3 or 4, but aim never to let it go above 6 mg/dl (1.9 mmol/L international).

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:

  • If it goes below around 1.5 mg/dl (0.5 mmol/L international), it is potentially life threatening.

  • I would aim for a level no lower than 3 mg/dl US (1.0 mmol/L international).

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:

  • 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. 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).

  • Michigan State University Veterinary Diagnostic Laboratory gives a reference range for ionised calcium of 1.0-1.4 mmol/l.

  • 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 (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:

  • parathyroid hormone (PTH)

  • calcitriol

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..

 

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

 

 

Back to Page 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

 

   

  *****

 

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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