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. 2021 Jan;35(1):321-332.
doi: 10.1111/jvim.15996. Epub 2020 Dec 24.

Risk factors associated with disturbances of calcium homeostasis after initiation of a phosphate-restricted diet in cats with chronic kidney disease

Pak-Kan Tang  1 , Rebecca F Geddes  2 , Yu-Mei Chang  3 , Rosanne E Jepson  2 , Esther Bijsmans  4 , Jonathan Elliott  1
Affiliations

Risk factors associated with disturbances of calcium homeostasis after initiation of a phosphate-restricted diet in cats with chronic kidney disease

Pak-Kan Tang et al. J Vet Intern Med. 2021 Jan.

Abstract

Background: Dietary phosphate restriction improves survival in cats with chronic kidney disease (CKD). However, feeding a phosphate-restricted diet may disrupt calcium homeostasis leading to hypercalcemia in some cats.

Objectives: To identify risk factors associated with increasing plasma total calcium (tCa) concentration after transition to a phosphate-restricted diet and to explore its role in CKD-mineral and bone disorder (CKD-MBD) in cats.

Animals: Seventy-one geriatric (≥9 years) euthyroid client-owned cats with International Renal Interest Society (IRIS) stage 2 to 3 azotemic CKD.

Methods: Retrospective cross-sectional cohort study. Changes in plasma tCa concentration in the first 200 days of diet transition were assessed using linear regression. Binary logistic regressions were performed to identify risk factors for increasing calcium concentration. Changes in clinicopathological variables associated with CKD-MBD over time were explored using linear mixed model and generalized linear mixed model analyses.

Results: Lower baseline plasma potassium (odds ratio [OR] = 1.19 per 0.1 mmol/L decrease; P = .003) and phosphate (OR = 1.15 per 0.1 mmol/L decrease; P = .01) concentrations remained independent risk factors for increasing plasma tCa concentration. Plasma creatinine (β = .069 ± .029 mg/dL; P = .02), symmetric dimethylarginine (β = .64 ± .29 μg/dL; P = .03), phosphate (β = .129 ± .062 mg/dL; P = .04), and ln[FGF23] (β = .103 ± .035 pg/mL; P = .004) concentrations had significantly increased rates of change in cats with increasing plasma tCa concentration over time.

Conclusion and clinical importance: Lower plasma potassium or phosphate concentrations or both at the time of transition of cats with CKD to a phosphate-restricted diet are independently associated with increased risk of an increase in plasma tCa concentration. Increasing plasma tCa concentration is associated with progression of CKD.

Keywords: CKD-MBD; FGF23; feline; hypercalcemia; progression; renal diet.

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Conflict of interest statement

P.‐K. T. received a PhD studentship funded by Royal Canin SAS. R. F. G. received funding from Petplan and an RVC Internal Grant; has a consultancy agreement with Boehringer Ingelheim; speaking honoraria from Boehringer Ingelheim. Y.‐M. C. declared no conflicts of interest. R. E. J. received funding from PetPlan, Feline Foundation for Renal Research, RVC Internal Grant, PetSavers, and consultancy agreements: Boehringer Ingelheim, CEVA. Speaking honoraria: Boehringer Ingelheim, Hills Pet Nutrition, CEVA. E. B. is employed by Royal Canin SAS. J. E. received funding from Consultancies: Elanco Ltd, CEVA Animal Health Ltd, Boehringer Ingelheim Ltd, Orion Incorp, Idexx Ltd, Nextvet Ltd, Waltham Petcare Science Institute, Kindred Biosciences Inc, Invetx Inc; grant funding from Elanco Ltd, Waltham Petcare Science Institute, Royal Canin SAS, Idexx Ltd, Zoetis Ltd, CEVA Animal Health, Member of the International Renal Interest Society which receives a grant from Elanco Ltd.

Figures

FIGURE 1
FIGURE 1
Receiver operating characteristic curve illustrating the performance of the final multivariable model in predicting an “uptrend” calcium status after transition to a phosphate‐restricted diet in CKD cats. AUC, area under curve; CKD, chronic kidney disease
FIGURE 2
FIGURE 2
Scatter plots illustrating the linear change of, A, total calcium; B, ionized calcium; C, creatinine; D, symmetric dimethylarginine (SDMA); E, phosphate; F, log‐transformed PTH (ln[PTH]); and, G, log‐transformed fibroblast growth factor 23 (ln[FGF23]) in CKD cats grouped according to the trend of plasma total calcium concentration (“uptrend” vs “nonuptrend”) during the first 200 days after transition to a phosphate‐restricted diet. The solid lines represent the regression lines and the shaded areas represent 95% confidence interval (95% Cl) for the fitted linear regression. Outliers have been omitted from the graph for creatinine, SDMA, and phosphate. The P values shown are the interactions between groups and the rate of change for these analyses within groups are presented in Table S1. CKD, chronic kidney disease; PTH, parathyroid hormone
FIGURE 3
FIGURE 3
Boxplots illustration the fractional excretion of, A, phosphate and, B, calcium between groups of cats according to the trend of plasma total calcium concentration after transition to a phosphate‐restricted diet (“nonuptrend” [n = 13] vs “uptrend” [n = 17]) at baseline visit (termed prediet) and postdiet visit (termed postdiet). Asterisk indicates significant difference (P < .05) was observed, either between groups or between visits
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