submitted manuscript

Abstract

To evaluate the impact of dietary phosphorus (P) intake on renal function in healthy adult cats, two independent studies were completed. Study 1: 48 cats, 1.7 - 9.1 y, were stratified into control or test diets providing 1.2 or 4.8 g/1000 kcal P (Ca:P 1.2 and 0.6) for 36 weeks. Study 2: 50 cats, 1.4 - 7.8 y, were stratified into control or test diets, providing 1.3 or 3.6 g/1000 kcal P (Ca:P 1.2 and 0.9) for 29 weeks. Health markers, glomerular filtration rate (GFR) and mineral balance were measured at regular intervals, with abdominal ultrasound at baseline and completion. Study 1; after 4 weeks the study was halted as test group GFR reduced by 0.4 (0.3, 0.4) ml/min/kg (p<0.001), serum creatinine increased by 24.9 (24.4, 25.5) mol/L (p<0.001) and renal ultrasound revealed changes in echogenicity. Study 2; at week 28, no differences in GFR were observed (p>0.05) and serum creatinine did not change from baseline in the test group (p>0.05). Ultrasound revealed new renoliths in 27% of control and 60% of test cats, with changes in renal echogenicity in 36% of test cats. Feeding a diet containing 4.8 g/1000 kcal total P; inorganic P 3.6 g/1000 kcal; Ca:P 0.6 resulted in a loss of renal function and marked changes in ultrasound suggestive of renal pathology. Intake of a diet containing 3.6 g/1000 kcal total P, Ca:P 0.9, led to more subtle structural changes in a third of test cats, however nephrolithiasis occurred in both groups complicating data interpretation

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

“…It is a progressive disease that can be triggered by a number of genetic and environmental factors (3) . Among acquired causes of the disease, dietary phosphorus (P) has been linked to its development and/or progression, not only in cats (2) , but also in humans (Reviewed in 4) .…”

“…Several studies have indicated that inclusion of high levels of soluble P salts in diets, often added for technical, palatability and nutritional reasons, can cause glucosuria and increase blood urea nitrogen content whilst decreasing creatinine clearance (5; 6) . In a recent feeding study (2) , reduced feed intake and vomiting were observed within four weeks in adult cats fed high dietary levels of sodium dihydrogen phosphate (NaH 2 PO 4 ; SDHP) providing 3.6g/1000kcal (4184kJ) P (total P 4.8g/1000kcal; calcium:phosphorus ratio [Ca:P] 0.6). This led to structural and functional changes in the kidneys as indicated by reduced GFR and proteinuria, compatible with early stage CKD.…”

“…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) .…”

“…(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) . Although biochemical markers of kidney health remained within physiological reference ranges in most of these cats, three out of 25 in the test group were removed from the study due to persistent azotaemia (2) .…”

“…Since 2018, however, The European Pet Food Industry FEDIAF, has added a precautionary footnote to maximum dietary P recommendations, suggesting that inorganic P compounds may pose a risk to feline renal function (2; 8; 9) . The studies reported by Alexander et al (2) indicate that further long term feeding trials are needed to determine safe upper limits of dietary P and particularly in the form of added soluble salts. 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) .…”