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      Association of Vitamin D Metabolites with Parathyroid Hormone, Fibroblast Growth Factor‐23, Calcium, and Phosphorus in Dogs with Various Stages of Chronic Kidney Disease

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          Abstract

          Background

          Hypovitaminosis D is associated with progression of renal disease, development of renal secondary hyperparathyroidism (RHPT), chronic kidney disease‐mineral bone disorder (CKD‐MBD), and increased mortality in people with CKD. Despite what is known regarding vitamin D dysregulation in humans with CKD, little is known about vitamin D metabolism in dogs with CKD.

          Objectives

          The purpose of our study was to further elucidate vitamin D status in dogs with different stages of CKD and to relate it to factors that affect the development of CKD‐MBD, including parathyroid hormone (PTH), fibroblast growth factor‐23 (FGF‐23), calcium, and phosphorus concentrations.

          Methods

          Thirty‐seven dogs with naturally occurring CKD were compared to 10 healthy dogs. Serum 25‐hydroxyvitamin D [25(OH)D], 1,25‐dihydroxyvitamin D [1,25(OH) 2D], and 24,25‐dihydroxyvitamin D [24,25(OH) 2D], and PTH and FGF‐23 concentrations were measured. Their association with serum calcium and phosphorus concentrations and IRIS stage was determined.

          Results

          Compared to healthy dogs, all vitamin D metabolite concentrations were significantly lower in dogs with International Renal Interest Society (IRIS) stages 3 and 4 CKD ( r [creatinine]: −0.49 to −0.60; P < .05) but not different in dogs with stages 1 and 2 CKD. All vitamin D metabolites were negatively correlated with PTH, FGF‐23, and phosphorus concentrations ( r: −0.39 to −0.64; P < .01).

          Conclusions and Clinical Importance

          CKD in dogs is associated with decreases in all vitamin D metabolites evaluated suggesting that multiple mechanisms, in addition to decreased renal mass, affect their metabolism. This information could have prognostic and therapeutic implications.

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          Health status and population characteristics of dogs and cats examined at private veterinary practices in the United States.

          Doug Armstrong, Stacey L. Kolar, M. A. Kirk … (1999)
          To determine age, breed, sex, body condition score, and diet of dogs and cats examined at private veterinary practices in the United States during 1995, and estimate prevalences of the most common disorders for these animals. Cross-sectional study. 31,484 dogs and 15,226 cats examined by veterinary practitioners at 52 private veterinary practices. Information on age, breed, sex, body condition score, diet, and assigned diagnostic codes were collected electronically from participating practices and transferred to a relational database. Prevalence estimates and frequencies for population description were generated using statistical software. Dental calculus and gingivitis were the most commonly reported disorders. About 7% of dogs and 10% of cats examined by practitioners during the study were considered healthy. Many conditions were common to both species (e.g., flea infestation, conjunctivitis, diarrhea, vomiting). Dogs were likely to be examined because of lameness, disk disease, lipoma, and allergic dermatitis. Cats were likely to be examined because of renal disease, cystitis, feline urologic syndrome, and inappetence. Results can be used by veterinary practitioners to better understand and anticipate health problems of importance in cats and dogs they examine and to better communicate with clients regarding the most prevalent disorders in cats and dogs.
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            UPDATE ON FIBROBLAST GROWTH FACTOR 23 IN CHRONIC KIDNEY DISEASE

            Myles Wolf (2012)
            Chronic kidney disease (CKD) is a public health epidemic that affects millions of people worldwide. Presence of CKD predisposes individuals to high risks of end-stage renal disease, cardiovascular disease and premature death. Disordered phosphate homeostasis with elevated circulating levels of fibroblast growth factor 23 (FGF23) is an early and pervasive complication of CKD. CKD is likely the most common cause of chronically elevated FGF23 levels, and the clinical condition in which levels are most markedly elevated. Although increases in FGF23 levels help maintain serum phosphate in the normal range in CKD, prospective studies in populations of pre-dialysis CKD, incident and prevalent end-stage renal disease, and kidney transplant recipients demonstrate that elevated FGF23 levels are independently associated with progression of CKD and development of cardiovascular events and mortality. It was originally thought that these observations were driven by elevated FGF23 acting as a highly sensitive biomarker of toxicity due to phosphate. However, FGF23 itself has now been shown to mediate “off-target,” direct, end-organ toxicity in the heart, which suggests that elevated FGF23 may be a novel mechanism of adverse outcomes in CKD. This report reviews recent advances in FGF23 biology relevant to CKD, the classical effects of FGF23 on mineral homeostasis, and the studies that established FGF23 excess as a biomarker and novel mechanism of cardiovascular disease. The report concludes with a critical review of the effects of different therapeutic strategies targeting FGF23 reduction and how these might be leveraged in a future randomized trial aimed at improving outcomes in CKD.
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              Vitamin D levels and patient outcome in chronic kidney disease.

              Patrizia Pizzini, Giovanni Tripepi, Pietro Ravani … (2008)
              Vitamin D deficiency has been linked to cardiovascular disease and early mortality in patients on hemodialysis; however, it is not known if the same association exists at earlier stages of chronic kidney disease. To determine this we enrolled 168 consecutive new referrals to a chronic kidney disease clinic over a 2 year period and followed them for up to 6 years. All patients were clinically stable and had an estimated glomerular filtration rate (eGFR) at stage 2 or less and were without an imminent need for dialysis. Baseline 25-hydroxyvitamin D levels directly and significantly correlated with eGFR. After an average follow-up of 48 months, 48 patients started dialysis and 78 had died. In crude analyses, 25-hydroxyvitamin D predicted both time to death and end-stage renal disease. A dual-event Cox's model confirmed 25-hydroxyvitamin D as an independent predictor of study outcomes when adjusted for age, heart failure, smoking, C-reactive protein, albumin, phosphate, use of converting enzyme inhibitors or angiotensin receptor blockers, and eGFR. Our study shows that plasma 25-hydroxyvitamin D is an independent inverse predictor of disease progression and death in patients with stage 2-5 chronic kidney disease.
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                Author and article information

                Contributors
                V.J. Parker: parker.888@osu.edu
                Journal
                Journal ID (nlm-ta): J Vet Intern Med
                Journal ID (iso-abbrev): J. Vet. Intern. Med
                Journal ID (doi): 10.1111/(ISSN)1939-1676
                Journal ID (publisher-id): JVIM
                Title: Journal of Veterinary Internal Medicine
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Print): 0891-6640
                ISSN (Electronic): 1939-1676
                Publication date (Electronic): 10 February 2017
                Publication date (Print): May-Jun 2017
                Volume: 31
                Issue: 3 ( doiID: 10.1111/jvim.2017.31.issue-3 )
                Pages: 791-798
                Affiliations
                [ 1 ] Veterinary Clinical SciencesThe Ohio State University Columbus OH
                [ 2 ] Center for BiostatisticsThe Ohio State University Columbus OH
                Author notes
                [*] [* ]Corresponding author: V.J. Parker, DVM, DACVIM, DACVN, The Ohio State University College of Veterinary Medicine, 601 Vernon L. Tharp St., Columbus, OH 43210; e‐mail: parker.888@ 123456osu.edu .
                Article
                Publisher ID: JVIM14653
                DOI: 10.1111/jvim.14653
                PMC ID: 5435068
                PubMed ID: 28186657
                SO-VID: 093152b5-3f12-4892-addf-4872907ebe34
                Copyright © Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
                License:

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                Date received : 16 May 2016
                Date revision received : 28 October 2016
                Date accepted : 06 December 2016
                Page count
                Figures: 4, Tables: 2, Pages: 8, Words: 7006
                Funding
                Funded by: College of Veterinary Medicine at The Ohio State University
                Funded by: National Center for Advancing Translational Sciences
                Award ID: UL1TR001070
                Categories
                Subject: Standard Article
                Subject: SMALL ANIMAL
                Subject: Standard Articles
                Subject: Nephrology/Urology
                Custom metadata
                source-schema-version-number 2.0
                component-id jvim14653
                cover-date May/June 2017
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:5.0.9 mode:remove_FC converted:17.05.2017

                ScienceOpen disciplines: Veterinary medicine
                Keywords: calcitriol,diet,international renal interest society,renal secondary hyperparathyroidism
                Data availability:
                ScienceOpen disciplines: Veterinary medicine
                Keywords: calcitriol, diet, international renal interest society, renal secondary hyperparathyroidism

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