The Devil’s in the “P”

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Progression of chronic kidney disease in cats is influenced by the interaction of the “devilish two Ps”: phosphate (chemical symbol “P”) and, opposing it, parathyroid hormone.

Excessive blood phosphate (hyperphosphataemia) can be an independent risk factor for chronic kidney disease progression. Due to the reduced kidney function associated with CKD, less phosphorus is excreted than usual. As meat is rich in phosphorus, even if meat is reduced in the diet, more phosphate may remain in the blood and its level may rise. This is usually only evident in advanced CKD stages. The problem is that cats are strict carnivores, and their diet, therefore, needs to be high in protein. Inorganic phosphate is also generally metabolically important. Elevated phosphorus blood levels are counteracted by the action of another substance: parathyroid hormone.

Counteraction by parathyroid hormone is persistent

Parathyroid hormone (PTH) is released from the parathyroid glands and has the following roles. Firstly, PTH increases phosphate excretion via the kidneys. It therefore counteracts increased phosphate blood levels. PTH regulation of phosphate blood levels in the remaining nephrons can increase phosphorus excretion to such an extent that raised phosphate blood levels may only manifest in later CKD stages. Remarkably, hyperphosphataemia does not become apparent in the blood until kidney function (as measured by the “glomerular filtration rate” (GFR)) has been reduced to below 20%. This represents a relatively late stage. Until then, PTH is capable of sustaining normal phosphate levels.

But, to do this, the parathyroid gland needs to be synthesising and secreting high levels of PTH. Such increased release of PTH can lead to a complication that causes further progression secondary hyperparathyroidism.

Inhibition of PTH synthesis disabled 

Phosphate metabolism is influenced not only by PTH, but also by the hormone calcitriol, the active form of vitamin D, which is produced in the kidneys. The action of both of these hormones finely regulates the phosphate-calcium balance. Calcitriol promotes the absorption of calcium and phosphate from the intestines and stimulates their release from the bones. PTH  works in unison with calcitriol in both roles. As a third role, it also increases excretion of phosphate in the kidneys. Calcitriol also inhibits PTH synthesis. As CKD progresses, not only is less phosphate excreted, and thus more retained, but calcitriol is no longer formed to keep PTH secretion in check. The consequence is that, with diminishing kidney function, phosphate levels rise (hyperphosphataemia), which in turn indirectly stimulates the release of PTH. Due to the kidney injury, calcitriol can no longer inhibit PTH synthesis and more is secreted.

At the same time, the lack of calcitriol means that less calcium is absorbed from the intestines. A reduction in blood calcium (hypocalcaemia) in turn promotes PTH. PTH triggers the release of calcium and phosphorus from the bones, which exacerbates hyperphosphataemia and, as a result, PTH secretion. The calcium released from the bone de-mineralises the bones, making them soft. In addition, the excess calcium and phosphate is deposited in various organs and can harm the heart, vessels and especially the kidneys. Calcification of the kidneys results in their further destruction. In conclusion – even less phosphate is excreted – hyperphosphataemia worsens – even more PTH is secreted – the bones further soften due to resorption of calcium and phosphate from them, and – calcification of the kidney leads to further renal injury.

Note: In CKD, phosphate levels in the blood can initially seem to be normal, masking the fact that PTH release has already risen. Therefore, control of blood phosphate in CKD cats needs to be started at an early stage.

Everything under control

Controlling your cat’s phosphate levels is vital in CKD. You can do this by giving your cat a kidney-friendly diet, which contains reduced protein (to prevent uraemia) and, most importantly, reduced phosphate. However, cats, as obligatory carnivores, are dependent on protein and phosphate-rich food, so there are limits on how much phosphate can be reduced from their diet. Another strategy is to administer phosphate binders. A wide variety of phosphate binders are available; these absorb phosphate from food in the intestines and eliminate it with the faeces. It can’t be taken up into the body. A combination of both approaches is also possible. Since phosphate binders bind the phosphate in the cat’s food, they will need to be incorporated into every portion of its food.

A new player on the pitch: FGF-23

Phosphate metabolism is also regulated by another player: fibroblast growth factor-23 (FGF-23). It is synthesised by bone cells that maintain bone matrix and increases phosphate excretion. FGF-23 is released due to increased phosphate levels, but also due to increased levels of calcitriol and PTH.

Read my article on FGF-23 for more information

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Bibliography:

  • Demmel, A. (2011): Der Einfluss der alimentären Phosphorversorgung auf ausgewählte Nierenfunktionsparameter bei Katzen [The influence of dietary phosphorus supply on selected kidney function parameters in cats]. Dissertation, LMU Munich: Faculty of Veterinary Medicine, https://edoc.ub.uni-muenchen.de/13433/
  • Moritz, A. (2013): Klinische Labordiagnostik in der Tiermedizin [Clinical laboratory diagnostics in veterinary medicine], 7th edition, Schattauer Verlag Stuttgart
  • Rade, C. (2016): Diätetik bei chronischer Nierenerkrankung von Hund und Katze – wichtigste Option in der Therapie [Dietetics in chronic kidney disease in dogs and cats – the most important therapeutic strategy], in: Kleintiermedizin (3) 2016, pp. 128–133.
  • Schmidt, V. / Horzinek, M. C./ Lutz, H. / Kohn, B. / Forterre, F. (2015): Krankheiten der Katze [Diseases of the cat], 5th fully revised and extended edition, Enge Verlag, Stuttgart.
  • Vetline: Phosphat als Kernproblem bei Katzen mit CNI [Phosphate as a core issue in cats with CKD], https://vetline.de/phosphat-als-kernproblem-bei-katzen-mit-cni/150/3252/67496/
  • , https://feline-nutrition.org/health/phosphorus-can-be-key-for-kidneys
  • Die Chronische Niereninsuffizienz der Katze was leisten die verschiedenen Phosphatbinder? [What do the different phosphate binders do in feline chronic renal insufficiency?], http://www.medscript.de/texte/phosphatbinder.pdf