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Abstract

Objectives

Vitamin D deficiency accompanies chronic cholestatic liver disease (CLD) in humans. The vitamin D status of cats with CLD is unknown. The objectives of this study were to describe serum vitamin D concentrations in cats with CLD and to determine if they correlated with indices of liver disease severity.

Methods

Thirty-six cats with CLD, defined by increases in serum bilirubin and serum alanine aminotransferase, and 23 sick cats with non-hepatobiliary diseases were prospectively enrolled. Serum 25-hydroxyvitamin D (25[OH]D), parathyroid hormone (PTH) and ionized calcium were measured. Signalment, clinical signs, comorbidities, diet history, serum bilirubin, liver enzyme activity, albumin, phosphorus, white blood cell count, prothrombin time and final hepatic cytologic/histopathologic diagnosis, when available, were recorded.

Results

Median serum 25(OH)D levels were similar in cats with CLD (89.5 nmol/l; range 21–112 nmol/l) and sick cats (89.0 nmol/l; range 49–115 nmol/l). Overall 12/36 (33%) cats with CLD and 4/23 (17%) sick cats had 25(OH)D levels below the lower limit of the reference interval (<65 nmol/l). Median PTH concentrations in cats with CLD were significantly higher (0.95 pmol/l; range 0–11.3 pmol/l) than in sick cats (0.70 pmol/l; range 0.5–6 pmol/l). In cats with CLD, 6/36 (17%) had high PTH levels in contrast to only 1/23 (4%) sick cats. In cats with CLD, 25(OH)D concentrations did not correlate with serum bilirubin, albumin or serum liver enzymes but were moderately negatively correlated with white blood cell count (r = − 0.402, P = 0.013). Cats with hepatic lipidosis had the highest prevalence of 25(OH)D concentrations that fell below the reference interval.

Conclusions and relevance

Many cats with CLD have serum 25(OH)D concentrations below the lower limit of the reference interval. Further study is warranted to determine the clinical relevance and whether supplementation would provide benefits.

Keywords

25-hydroxyvitamin D parathyroid hormone hepatic lipidosis cholangitis hepatobiliary disease

Introduction

Vitamin D deficiency accompanies chronic cholestatic liver disease (CLD) in humans reflecting the liver’s central role in absorption of fat-soluble vitamin D and synthesis of the active form of vitamin D.^1–10 Cholestatic cholangiopathies are a common form of liver disease in cats.^11–17 Cats with these disorders frequently have inadequate concentrations of another fat-soluble vitamin, vitamin K.^18–20 Low vitamin D status, determined from serum 25-hydroxycholecalciferol (25[OH]D) concentrations, occurs in cats with inflammatory bowel disease (IBD), intestinal small cell lymphoma and infections.^21–24 Low serum 25(OH)D measurements also predict mortality in hospitalized cats.²⁵ The vitamin D status of cats with CLD is unknown.

In humans with liver disease, low serum 25(OH)D concentrations are associated with advanced disease, enhanced fibrogenesis and lipogenesis, poor response to therapy and increased susceptibility to infection and endotoxemia.^{3,5,6,8,26–33} Evidence suggests that vitamin D signaling represents a natural defense mechanism against hepatic fibrosis by inhibiting cytokine-induced activation of extracellular matrix-producing hepatic stellate cells.^26,27,34,35 Knockout of the vitamin D receptor and long-term vitamin D deficiency in mice are associated with development of biliary cirrhosis.^27,36 Additionally, low serum vitamin D concentrations correlate with increased hepatic fibrosis on biopsy and/or with higher clinical scores of liver disease severity in humans.^{2,3,6,8,30,32,37} In laboratory rodents, vitamin D deficiency enhances lipogenesis and reduces beta oxidation of lipids leading to hepatic fat accumulation.^38–40 Evidence is mounting that correction of vitamin D insufficiency or deficiency with supplementation may have therapeutic benefits in infectious, inflammatory and metabolic disease in humans and animal models.^{26,27,32,41–45} Considering the potential adverse effects of altered vitamin D signaling in the liver, studies that examine if vitamin D metabolism is altered in cats with hepatobiliary disease are indicated.

We hypothesized that 25(OH)D concentrations in cats with CLD would measure below the reference interval (RI), be significantly lower than 25(OH)D concentrations in sick cats with non-hepatobiliary disorders and correlate with indices of hepatic dysfunction or infection, such as serum liver enzyme elevation, albumin, bilirubin concentrations and/or white blood cell count (WBC).

Materials and methods

Study design and population

The study was observational and designed as a prospective study. Cats were recruited from animals hospitalized at the Foster Hospital for Small Animals at Cummings School of Veterinary Medicine at Tufts University from 2011 to 2014. The study population was classified into two groups: cats with CLD and cats sick without evidence of hepatobiliary disease. The study was reviewed and approved by the Clinical Studies Review Committee at Cummings Veterinary Medical Center at Tufts University. Participation was voluntary and informed consent was obtained.

The inclusion criteria for cats with CLD was increased serum bilirubin, defined as bilirubin measurement greater than the upper limit of normal (ULN) provided by the reference diagnostic laboratory (reference laboratories included the Clinical Pathology Laboratory at Cummings Veterinary Medical Center, Grafton, MA, USA; IDEXX Laboratories, Westbrook, MA, USA; and Antech Laboratories, Irvine, CA, USA), combined with an elevation in serum alanine aminotransferase (ALT) or serum alkaline phosphatase (ALP) activity greater than three times the ULN provided by the measuring diagnostic laboratory, and/or cytologic or histopathologic diagnosis of primary hepatobiliary disease. Classification of sick cats without evidence of primary hepatobiliary disease was based on the following inclusion criteria: absence of inclusion criteria for cats with hepatobiliary disease and a minimum of 1 week of clinical abnormality (eg, anorexia, vomiting, lethargy, diarrhea) based on owner-reported history. To avoid misclassifying cats with serum liver enzyme elevations associated with reactive hepatopathies, cats with a clinical, biochemical or imaging diagnosis of IBD, pancreatitis or hyperthyroidism were excluded. To avoid misclassifying cats with unrelated alterations of calcium homeostasis or bile acid metabolism, additional exclusion criteria for both groups were age <1 year, presence of hypercalcemia, chronic renal disease (elevated serum creatinine in combination with isosthenuria) and a history of corticosteroid or ursodeoxycholic acid administration in the previous 2 weeks.

Collection of additional data

A standard data collection form was completed by a veterinarian to document additional data points, including clinical signs, indoor or outdoor environment, diet over the previous 3 months, duration of decreased appetite, current medications, comorbidities, body weight, muscle condition score (MCS), body condition score (BCS), serum biochemical abnormalities (ALT, ALP), total bilirubin, WBC, albumin, phosphorus, prothrombin time (PT), activated partial thromboplastin time (aPTT), packed cell volume (PCV), and histological or cytological diagnosis, if available.

Measurement of vitamin D profile and subsequent classification

Approximately 3 ml whole blood was obtained by jugular venipuncture in each cat; serum was separated and stored at −80º C until batched and shipped on ice overnight for analysis. Previous studies have verified the stability of 25(OH)D stored in this manner.^46,47 Serum 25(OH)D, parathyroid hormone (PTH) and ionized calcium (iCa) were determined by validated assays performed at Michigan State University Veterinary Diagnostic Laboratory. Serum 25(OH)D (including both D2 and D3) was measured with a commercially available radioimmunoassay kit (vitamin D profile including PTH, iCa, 25(OH)D, Michigan State University, Veterinary Diagnostic Laboratory, Lansing, MA, USA).⁴⁸

Statistical analysis

Descriptive statistics including means or median were calculated after determining if data were normally distributed using visual inspection of histograms, as well as calculation of skew and kurtosis. When necessary, non-parametric measures were log-transformed to achieve normality for statistical evaluation. The 25(OH)D, PTH and iCa concentrations of sick cats with and without liver disease were compared with the Student’s t-test. One-way ANOVA was used to compare 25(OH)D concentrations in cats with various types of CLD. Population data (age, weight, BCS, days of hyporexia and biochemical parameters) were compared with the Student’s t-test. Correlations between 25(OH)D concentrations and blood parameters or clinical signs serum bilirubin, albumin, WBC, phosphorus, iCa, serum ALT, days of hyporexia and PT (only cats with CLD) were assessed with Pearson’s correlation coefficient. Categorical data (clinical signs, decreased muscle condition) were compared with Fisher’s exact test. A P value of <0.05 was considered significant. Online statistical software was used for analysis (http://statpages.info/anova1sm.html; https://www.danielsoper.com/statcalc/calculator.aspx?id=43; https://www.socscistatistics.com/tests/pearson/).

Results

We prospectively recruited 36 sick cats without liver disease and 40 sick cats with liver disease. At the conclusion of the enrollment, all recruited cats were validated against defined inclusion and exclusion criteria. Thirteen sick cats without liver disease and four sick cats with liver disease were excluded from the study. Thus, a total of 59 cats were enrolled in the study: 36 with CLD and 23 were sick without CLD.

The population characteristics of and clinical signs in these two groups of cats are summarized in Tables 1 and 2. The sick cats and cats with CLD had similar age, weight, BCS, MCS and clinical signs. Cats with CLD had a significantly longer owner-reported duration of decreased appetite compared with the sick cats without liver disease (P = 0.04; Table 1). Biochemically, cats with CLD had significantly higher serum ALT, ALP and bilirubin compared with sick cats without liver disease; PCV, WBC, serum albumin and serum phosphorus were similar (Table 1). PT and aPTT were determined in 18 cats with CLD that underwent hepatic tissue sampling. In these cats, 5/18 (27.8%) and 1/18 (5.6%) had prolongation in PT and aPTT, respectively. Diet histories were available for 46/59 (78.0%) cats: 28/36 (77.8%) cats with CLD and 18/23 (78%) sick cats. All cats for which complete information was obtained were fed commercial cat diets. Most cats ate dry food exclusively (13/28 CLD cats and 5/18 sick cats) or a combination of dry and canned food (14/28 of CLD and 9/18 sick cats). Four of 36 (11%) and 4/23 (17%) of cats with CLD or sick cats, respectively, were indoor/outdoor cats.

Table 1

Population characteristics of cats with cholestatic liver disease and sick cats without liver disease

	Cholestatic liver disease (n = 36)	Sick without liver disease (n = 23)	P value
Age (years)	9 (4–16)	10 (1–15)	0.84
Weight (kg)	4.9 (2.9–9.2)	5.0 (2.6–9.6)	0.51
BCS	5 (2–9)	6 (1–9)	0.66
Decreased MCS	21 (58)	9 (39)	0.68
WBC (10³/µl)	13 (4–26)	10.5 (3.6–30.7)	0.30
PCV (%)	34 (27–49)	38 (26–52)	0.18
ALT (IU/l)	522 (76–1617)	82 (19–358)	<0.001
ALP (IU/l)	385 (35–980)	30 (5–88)	<0.001
Total bilirubin (mg/dl)	6.87 (1–32)	0.2 (0.1–3.9)	<0.001
Albumin (g/dl)	3.2 (2–5)	3.3 (1.4–4.4)	0.78
Phosphorus (mg/dl)	4.1 (1.9–5.2)	4.5 (1.9–7.1)	0.56

Data are median (range) or n (%)

BCS = body condition score; MSC = muscle condition score; WBC = white blood cell count; PCV = packed cell volume; ALT = alanine aminotransferase; ALP = alkaline phosphatase

Table 2

Clinical signs in cats with cholestatic liver disease and sick cats without liver disease

Clinical sign	Cholestatic liver disease (n = 36)	Sick without liver disease (n = 23)	P value*
Decreased appetite	34 (94)	18 (78)	0.10
Duration of hyporexia (days)	7 (0–180)	2 (0–14)	0.04
Decreased activity	24 (67)	11 (48)	0.29
Weight loss	21 (58)	7 (30)	0.06
Vomiting	16 (44)	11 (48)	1.0
Polyuria/polydipsia	4 (11)	2 (9)	0.92
Diarrhea	1 (3)	2 (9)	0.91

Data are n (%) or median (range)

Fisher’s exact test

Median serum 25(OH)D concentrations were similar in sick cats (89.0 nmol/l; range 49–115 nmol/l [P = 0.015]) and cats with CLD (89.0 nmol/l; range 21–147 nmol/l [P = 0.02]). (Figure 1a). Twelve of 36 (33%) cats with CLD and 4/23 (17%) sick cats had 25(OH)D concentrations below the lower limit of the RI (<65 nmol/l). No cats had concentrations above the upper limit of the RI.

Figure 1

Serum 25-hydroxycholecalciferol (25[OH]D), parathyroid hormone (PTH) and ionized calcium (iCa) concentrations in cats with cholestatic liver disease (n = 36) and sick cats (n = 23) without liver disease: (a) 25(OH)D concentrations; (b) PTH concentrations; and (c) iCa concentrations. Dashed lines indicate the upper and lower limits of the reference interval. Box plots show the median as a line and surrounding boxes represent the upper and lower quartile. *Significantly different than value in sick cats without liver disease (P <0.05)

Median serum PTH concentrations in cats with CLD were higher than the values in sick cats (0.95 pmol/l [range 0–11.3 pmol/l] and 0.7 pmol/l [range 0.5–6.0 pmol/l], respectively). Six of 36 (17%) cats with CLD and 1/23 (4.3%) sick cats without CLD had high serum PTH concentrations (Figure 1b). Median serum iCa concentrations in cats with CLD (1.32 nmol/l; range 1.07–1.28) were higher than iCa concentrations in sick cats without CLD (1.26 nmol/l; range 1.09–1.37 nmol/l), although iCa concentrations for all cats were within the RI (Figure 1c).

There was no correlation between serum 25(OH)D concentrations in cats with CLD or sick cats and serum PTH or iCa concentrations, BCS, age, duration of hyporexia or serum biochemical values (bilirubin, ALT, albumin, prothrombin time, ALP) or coagulation testing (PT, aPTT). There was a weak negative correlation between serum 25(OH)D and WBC in both cats with CLD (r = −0.327, P = 0.007) and in sick cats (r = −0.467, P = 0.05). The correlation between 25(OH)D and WBC for all cats combined (r = −0.402, P = 0.013) is shown in Figure 2.

Figure 2

25-Hydroxyvitamin D (25[OH]D) concentrations were negatively correlated with white blood cell count (WBC). Scatter plot of 25(OH)D concentrations vs WBCs from all cats in the study (n = 59). The correlation (r = −0.402) is significant (P = 0.013)

In 27 cats with CLD, fine-needle aspirate (n = 12), hepatic biopsy (n = 12) or a combination of fine-needle aspirate and hepatic biopsy (n = 3) were obtained and were interpreted by board-certified anatomic or clinical pathologists. Hepatic biopsies were obtained by percutaneous ultrasound guidance (n = 10), surgery (n = 3) and necropsy (n = 2). Twelve cats had hepatic lipidosis (44.4%), nine had cholangitis (33.3%) and six had hepatobiliary neoplasia (22%), including adenocarcinoma (n = 3), round cell (n = 2) and neuroendocrine tumor (n = 1). There was no significant difference in median 25(OH)D in the three groups with liver disease. Five of 12 (42%) cats with hepatic lipidosis, 2/9 (22%) cats with inflammatory disease and 1/6 (17%) cats with neoplasia had 25(OH)D concentrations below the lower limit of the RI (Table 3).

Table 3

Vitamin D concentration in cats with cholestatic liver diseases

Cats with cytologic and/or histopathologic diagnosis (n = 27)		25(OH)D (nmol/l)	Cats with 25(OH)D<lower limit of RI
Hepatic lipidosis	12 (44)	71.0 (12–115)	5 (41)
Cholangitis	9 (33)	96.5 (22–112)	2 (22)
Cancer	6 (22)	96.5 (36–113)	1 (17)
RI	–	65–170	–

Data are n (%) or median (range)

25(OH)D = 25-hydroxycholecalciferol; RI = reference interval

Comorbidities in cats with CLD included asymptomatic cardiac murmur (n = 5), diabetes mellitus (n = 3), blindness (n = 1), stable hypertrophic cardiomyopathy (n = 1) and pancreatic cyst (n = 1). Sick cats had a variety of confirmed or presumptive underlying disorders, including neoplasia (n = 7), infectious disease (n = 6), neurologic disease (n = 2) and one each of intestinal foreign body, diabetes mellitus, myasthenia gravis and heart failure. Four sick cats had an open diagnosis. Sick cats with neoplasia had lymphoma (n = 2), a sublingual mass, colonic mass, colonic mass with presumptive carcinomatosis, perforated jejunal mass and a palpable abdominal mass, while sick cats with infectious disease had feline immunodeficiency virus (n = 2), urinary tract infection, otitis media, pyometra and peritonitis. The two cats with neurologic disease presented for acute blindness (n = 1) and ataxia and head bobbing (n = 1). All the sick cats with a 25(OH)D concentration below the RI had a presumptive diagnosis of cancer.

Twenty-five of 36 (69%) and 18/23 (78%) sick cats with CLD and sick cats without CLD, respectively, received no medications at the time of enrollment. In enrolled cats that received medications, sick cats with CLD received antibiotics (n = 7/36), mirtazapine (n = 5/36), S-adenosylmethionine (n = 5/36), maropitant (n = 2/36), famotidine (n = 2/36) and one cat each pyrantel pamoate, lactulose, cisapride, buprenorphine and polyethylene glycol; sick cats without CLD received antibiotics (n = 4/23), buprenorphine (n = 3/23), mirtazapine (n = 2/23) and one cat each maropitant, lactulose, insulin and famotidine.

Discussion

Although median 25(OH)D concentrations in both sick cats with and without CLD were similar, almost twice as many cats with CLD had 25(OH)D concentrations below the lower limit of the RI than sick cats without CLD. Serum 25(OH)D concentrations in sick cats with and without CLD were negatively correlated with WBCs. However, serum 25(OH)D concentrations did not correlate with age, duration of anorexia, BCS, MCS or other biochemical variables such as albumin, bilirubin, serum liver enzyme activity, PT and aPTT in either population. Cats with CLD had significantly higher mean PTH and iCa values than sick cats.

Low 25(OH)D concentrations in sick cats and cats with hepatobiliary disease could be the result of several factors. Low vitamin D concentrations could be due to decreased dietary intake. In humans, vitamin D is produced in the skin as a result of UV exposure; however, this route is negligible in the cat.⁴⁹ Instead, cats rely on vitamin D in the diet.⁵⁰ All cats in this study did have some period of anorexia or hyporexia, which may have contributed to decreased dietary intake of vitamin D. However, 25(OH)D concentrations did not correlate with duration of anorexia and storage of vitamin D in the body should allow for short periods of decreased intake. Alternatively, low 25(OH)D concentrations could have resulted from dietary deficiency of vitamin D. All cats for which complete diet histories were obtained were eating commercial cat foods that should have met nutritional recommendations for vitamin D; however, the nutritional adequacy of each diet was not verified. Decreased intestinal absorption could also cause low serum 25(OH)D concentrations. Vitamin D is a fat-soluble vitamin requiring micellar concentrations of bile acids in the intestine to facilitate absorption. Cholestatic disease can prevent achievement of these critical concentrations. Several cats with CLD in this study had cholangitis and it is known these cats often have concurrent inflammation the intestine.^11–15

In the current study, sick cats without liver disease also had low serum 25(OH)D concentrations. Several studies have demonstrated that cats with IBD, intestinal lymphoma, feline immunodeficiency virus and mycobacterial infections, as well as sick cats hospitalized for a variety of disorders can have low serum 25(OH)D concentrations.^21,22,24,50 It is likely that a variety of causes contribute to the low serum 25(OH)D concentrations. Cats with IBD or intestinal lymphoma may have compromised vitamin D absorption. Chronic inflammation/infection and its associated cytokine milieu may suppress vitamin D production in part by inhibiting PTH secretion. Other illnesses may be accompanied by decreased production of serum vitamin D binding proteins or increased urinary loss that contribute to low serum 25(OH)D concentrations.

Sick cats without CLD in the current study did not need to have a definitive diagnosis and thus the cats had a variety of presumptive disorders. Of interest, all of the sick cats with serum 25(OH)D concentration below the RI (n = 4) had a presumptive diagnosis of abdominal neoplasia. Low vitamin D levels have been linked to tumorigenesis in humans by mechanisms that are not fully understood.^51–53 Further studies to investigate a possible link between vitamin D metabolism and cancer development in cats are necessary.

In this study, serum 25(OH)D did not correlate with clinicopathologic indices of liver disease severity (serum bilirubin and liver enzyme activity). Low serum 25(OH)D concentrations commonly accompany chronic liver disease in humans and correlate more with indices of disease stage such as fibrosis on hepatic biopsy, scores on validated clinical scoring models or survival than clinicopathological data.^{3,5,6,10,29,30} Future studies on the role of vitamin D in biliary disease in cats should involve evaluation of the relationship between vitamin D concentrations and histopathologic scoring of hepatic biopsy specimens, clinical scores of disease severity and survival analysis.

Vitamin D has pleiotropic action in the liver. The Vitamin D receptor is strongly expressed on non-parenchymal cells (stellate cells, endothelial cells, Kupffer cells) and biliary epithelial cells and is upregulated on hepatocytes in inflammatory disease.^{2,3,5,10,28,30,32,33,54} Vitamin D inhibits hepatic stellate cell activation and proliferation and thus has demonstrated antifibrotic effects.^5,10,26,35 It also plays an important role in regulation and synthesis of important antimicrobial peptides by the biliary epithelium, activation of B and T lymphocytes, and production of cytokines by immune cells.^2,6 The net result of these actions is that vitamin D has been shown to modulate the liver’s susceptibility to viral and bacterial infection, fat accumulation in hepatocytes, inflammatory responses and maintenance of self-tolerance in immune hepatitis.^{1,6,28,30,32,33}

Considering the known actions of vitamin D in the liver, the discovery of vitamin D insufficiency/deficiency in cats with CLD may have implications for future therapeutic management. The disease course in cats with cholangitis is marked by the occurrence of frequent complicating biliary infections and progression to cirrhosis.^13,14,33,55 In the current study, as well as one previous investigation in cats, there was an inverse correlation between WBCs and serum 25(OH)D concentrations, suggesting a possible link between vitamin D deficiency/insufficiency and inflammation.²³ Additional studies demonstrating low vitamin D concentrations in cats with infectious disease, including mycobacterial and feline immunodeficiency virus infections,^22,24 also suggest a link between vitamin D and susceptibility to infection. Data from studies in humans show a correlation between vitamin D deficiency and infectious complications in chronic hepatopathies.^2,32,33 Supplementation with vitamin D may enhance innate and adaptive immune response to facilitate clearance of biliary infections in these cats. Studies to further characterize the nature of the inflammatory response in cats with vitamin D deficiency/insufficiency and that correlate the presence of biliary infection and response to therapy are warranted.

Current therapeutic options for treatment of cholangitis in cats are limited and focused on mitigating inflammation and slowing fibrotic progression.^14,56,57 In humans with a similar inflammatory cholangiopathy, primary biliary cholangitis, vitamin D can enhance therapeutic response to ursodeoxycholate.⁵ Also, vitamin D supplementation has been shown to enhance effects of corticosteroids in non-hepatic inflammatory diseases in humans and dogs.^6,58,59 Additionally, supplementation with vitamin D is considered an effective ancillary therapy for IBD,⁶⁰ and thus may be beneficial in cats with cholangitis, many of which have concurrent IBD and/or pancreatitis.^11–15

We saw no correlation of vitamin D with PTH or iCa in this study. This was not unexpected as the relationship between vitamin D and iCa and PTH is a complex, likely non-linear, relationship. In humans, defining a state of vitamin D deficiency is still a subject of much debate.⁶¹ One of the most well accepted definitions is the breakpoint at which vitamin D values will consistently cause a rise in PTH.^62–64 However, the concentrations of 25(OH)D that lead to a rise in serum PTH in cats are not known. In the current study, we did find that cats with CLD had significantly higher PTH concentrations than sick cats. This might reflect the fact that these cats were approaching a deficient state. However, we did not see a consistent rise in PTH with lower vitamin D concentrations. One reason for this may be suppression of the parathyroid glands by cytokines or other inflammatory mediators that inhibit PTH secretion.

This study was designed as a pilot study and has several limitations. We examined a small population of cats and thus our study might not have enough power to identify significant associations. Although diet history was obtained for most cats, these cats ate different diets; this financially precluded our ability to consider dietary vitamin D analysis. Hepatic tissue sampling was not an inclusion criterion for this study and therefore not all cats had a definitive diagnosis; this made histopathological scoring of disease severity impossible. Although cats with diseases known to affect vitamin D metabolism were excluded, the cats in the study had a variety of concurrent diseases that could have affected vitamin D metabolism. Our study was not designed to provide follow-up data on either group of cats, so we have no survival analysis. We chose to determine 25(OH)D concentrations as a surrogate marker of the amount of active vitamin D; however, a recent study found that there is a C-3 epimeric form of 25(OH)D that occurs in the blood of cats in significant amounts.⁶⁵ The biological significance of C-3 epimerization of vitamin D has yet to be determined but this should be considered in future studies.

Conclusions

The results of this prospective pilot study demonstrate that there is a population of sick cats both with and without CLD that have serum 25(OH)D concentrations below the RI. Furthermore, decreases in 25(OH)D correlate with higher WBCs in both these populations. Although limited by case numbers, the results suggest that cats with hepatic lipidosis as a cause for their CLD may be more likely to have 25(OH)D concentrations below the RI. Further studies to describe the status of vitamin D metabolism in larger populations of cats with metabolic or inflammatory disease are indicated. While vitamin D supplementation in cats with 25(OH)D levels below the lower limit of the RI may prove beneficial, there is still inadequate knowledge to suggest this as a current therapeutic strategy.

Footnotes

Accepted: 24 November 2019

Author note

The study was presented in abstract form at the ACVIM Forum 2018, Seattle, WA, USA.

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: intramural grant from the Companion Animal Health Fund at Cummings School of Veterinary Medicine at Tufts University

Ethical approval

This work involved the use of non-experimental animal(s) only (owned or unowned), and followed established internationally recognized high standards (‘best practice’) of individual veterinary clinical patient care. Ethical approval from a committee was therefore not necessarily required.

Informed consent

Informed consent (either verbal or written) was obtained from the owner or legal custodian of all animal(s) described in this work for the procedure(s) undertaken. No animals or humans are identifiable within this publication, and therefore additional informed consent for publication was not required.

ORCID iD

Lesli Kibler

Cailin R Heinze

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Serum vitamin D status in sick cats with and without cholestatic liver disease

Abstract

Objectives

Methods

Results

Conclusions and relevance

Keywords

Introduction

Materials and methods

Study design and population

Collection of additional data

Measurement of vitamin D profile and subsequent classification

Statistical analysis

Results

Discussion

Conclusions

Footnotes

Author note

Conflict of interest

Funding

Ethical approval

Informed consent

ORCID iD

References