kinetic manuscript

Abstract

27Phosphorus (P) is present in diets either as naturally occurring P from raw materials or added 28 as an inorganic salt, however little is known about postprandial kinetics of P absorption in cats. 29Here we describe several studies quantifying postprandial kinetics following the ingestion of 30 diets of varying composition. Briefly, cats were fed a meal consisting of 50% of their metabolic 31 energy requirement in a randomized crossover design. A pre-meal baseline blood sample was 32 taken via cephalic catheter and repeated measurements taken regularly up to 6h post meal to 33 assess whole blood ionized calcium, plasma P and parathyroid hormone (PTH) concentrations. 34A diet containing total P 4.8g/1000kcal, sodium dihydrogen phosphate (SDHP, NaH2PO4) 35 3.5g/1000kcal, Ca:P 0.54 caused a marked increase in plasma P from baseline to a peak of 36 1.976 mmol/L with 95% confidence interval (1.724, 2.266), p<0.001, whereas a diet containing 37 total P 3.38g/1000kcal, no added inorganic P, Ca:P 1.55 resulted in a postprandial decrease in 38 plasma P (p=0.008). Subsequent data indicate that added inorganic P in the diet (above 39 0.5g/1000kcal) causes an increase in plasma P in cats while diets with low added inorganic P

Towards establishing no observed adverse effect levels (NOAEL) for different sources of dietary phosphorus in feline adult diets: results from a 7-month feeding study

“…This would largely corroborate the current understanding of regulatory mechanisms involved in P homeostasis (43) . PTH responses in cats do appear to be more rapid than FGF-23, as indicated by post-prandial profiles observed following acute feeding studies (7) , Feeding the control diet prior to baseline sampling decreased total serum Ca significantly compared to screening values (by ~ 0.2mmol.L), it is not known whether there was a concomitant decrease in iCa as it was not measured at screening. However, all diet groups subsequently increased in Ca concentration during the test period, returning to screening levels.…”

“…In mice, it was found that administration of 5µg of purified human full length FGF-23 reduced serum phosphate, PTH and calcitriol at various timepoints during the 24 hour sampling period (43) . Previous work investigating the acute responses of a high oral dose of highly soluble dietary P in cats, found that FGF-23 didn't change over a 6 hour sampling period, whereas PTH and plasma P did (7) . This could indicate that, although the timeframes are not the same, the broad mechanisms by which FGF-23 plays a role in the regulation of P may be similar, as serum P and calcitriol were found to be reduced in cats fed the moderate test diet from week 12 onwards.…”

“…This led to structural and functional changes in the kidneys as indicated by reduced GFR and proteinuria, compatible with early stage CKD. (2) This may have been due to the high postprandial serum phosphate levels induced by the test diet (7) . In a subsequent 28-week study, exposure to a more moderate level of SDHP, providing 1.5g/1000kcal (4184kJ) P (total P 3.6g/1000kcal; Ca:P 0.9) resulted in the development of renoliths and/or structural changes in the kidneys (2) .…”

“…Dietary P from organic raw materials, such as meat and bone meals or plant-based ingredients, has been shown to be less bioavailable than from soluble P salts (6; 10) . Recent studies in healthy adult cats investigating post-prandial responses following single meal exposure indicate that soluble P salts, but not organic P sources, induce Accepted manuscript rapid, dose-dependent increases in serum phosphate and parathyroid hormone (PTH), a key regulator of mineral homeostasis (7) .…”

Dietary calcium to phosphorus ratio affects postprandial phosphorus concentrations in feline plasma

“…Dietary phosphorus (P) concentrations have received increased focus as a contributing factor in accelerating kidney disease (2; 3) . Studies in cats investigating postprandial appearance of P in plasma showed that diets incorporating highly soluble forms of P induced dose-dependent increases in P concentration as well as the calcium (Ca) and P regulatory parathyroid hormone (PTH) (4) . At the highest inclusion of highly soluble P tested, there was also a significant reduction in whole blood ionized calcium (iCa) (4) .…”