Investigating the effect of paricalcitol on serum FGF23 in vitamin D deficient rats

Investigating the effect of paricalcitol on serum FGF23 in vitamin D deficient rats | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Investigating the effect of paricalcitol on serum FGF23 in vitamin D deficient rats Forough Saki, Gholamhossein Ranjbar Omrani, Farhad Koohpeyma This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.2.18457/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: We conducted this study to discover changes of serum FGF23 in non-uremic rat model of vitamin D deficiency without secondary hyperparathyroidism using paricalcitol. Methods: 30 adult male rats weighting 300±20 grams were enrolled. They were divided into three groups of 10 rats including Control, Vitamin D deficient(VDD), and Vitamin D deficient diet treated with paricalcitol(VDD+P). Serum biochemical were checked twice, at baseline and after the 22nd day of study. Results: There was no significant difference in baseline laboratory data between groups. At the end of the study, 1,25(OH)D3 was reduced in VDD (P = 0.019) and VDD+P (P < 0.001) with a more significant decline in VDD+P group. Serum level of FGF23 was reduced in VDD+P group compared to the control group (P = 0.011) and VDD group (P = 0.021). serum PTH in VDD group was higher than the control and VDD+P group (P = 0.036 and P = 0.038, respectively). Conclusion: The present study showed that paricalcitol could reduce FGF23 in vitamin D deficient rats without any changes in serum calcium, phosphorous and fractional excretion of phosphorous, which might be due to low PTH and 1,25(OH)2 D3. Urology & Nephrology Endocrinology & Metabolism FGF23 vitamin D deficiency paricalcitol Figures Figure 1 Figure 2 Figure 3 Background Fibroblast growth factor (FGF23) is a bone-derived hormone, which plays an important role in mineral metabolism (1). The main function of serum FGF23 is to suppress phosphate reabsorption and vitamin D activation in kidneys (2). However, several new klotho-dependent and klotho-independent roles including blood pressure regulation, bone mineralization and affecting innate immune system have been uncovered for FGF23 (3). Although recent studies have revealed major new functions of FGF23, it rises many new questions regarding its details (2). One of these debates has considered the effect of paricalcitol on serum FGF23 (4). Paricalcitol is a selective vitamin D receptor (VDR) activator, which has been approved since 1998 for the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) (5). Paricalcitol was introduced due to the need for a treatment that could inhibit high serum PTH in patients with SHPT, with a minimal effect on calcium-phosphorous product (Ca × P) in CKD patients, without renal toxicity (6). Nowadays, it is being considered as an anti-parathyroid agent rather than vitamin D analogue (7). Previous studies evaluated the effect of paricalcitol on serum FGF23 in SHPT patients with CKD (4,8). Some revealed that paricalcitol could increase serum FGF23 in hemodialysis patients through an increase in serum phosphate and calcium (4,8); however, others revealed that in non-uremic vitamin D deficient rats, paricalcitol could induce vitamin D deficiency state with unchanged PTH, Ca, and phosphate level (9). In addition, it is well known that serum FGF23 rises progressively as kidney function declines due to some known and unknown mechanisms (10,11), which consequently influences the conclusion regarding the exact effect of paricalcitol on serum FGF23 in non-uremic patients. Hence, we conducted this study to discover changes of serum FGF23 in non-uremic rat model of vitamin D deficiency without secondary hyperparathyroidism using paricalcitol. Furthermore, we compared the serum minerals and hormones between vitamin D deficient rats (vitamin D deficiency + SHPT) and vitamin D deficient rats using paricalcitol (vitamin D deficiency without SHPT). Methods A total of 30 adult male spargue-dawley rats (10 weeks old), weighting 300±20 grams were purchased from the animal laboratory center of Shiraz University of Medical Sciences. Subjects underwent one-week acclimatization to the animal laboratory facilities before the study. They were housed in standard cages, five per cage, with 12:12 hours light-dark cycles at temperature of 23±2°c. All rats were randomly divided into three groups of 10 rats as below: A: Control group(C): received normal standard rodent chow diet and had free access to tap water B: Vitamin D deficient group (VDD group): received standard vitamin D deficient diet (TD.87095 Brown C. C. vitamin D deficient diet, containing 20% lactose, 2% calcium and 1.25% phosphate) C: Vitamin D deficient diet + paricalcitol (VDD+P group): received the above mentioned standard vitamin D deficient diet plus intraperitoneal injections of 32 ng of 19-nor–1,25-dihydroxy vitamin D 2 (paricalcitol; Zemplar) on days 1,3,5,8,10 and 12 of the study, according to stavenuiter protocol (F). Rats’ weight was checked on days 1,10,15 and 22 of the study. At the end of the experiment, all rats were anesthetized with ketamine 10 % (100 mg/kg, Alfasan, Netherlands) and xylazin 2 % (10 mg/kg, Alfasan, Netherlands) solution intraperitoneally and sacrificed by using thiopental (100 mg/kg). Biochemical studies: Serum calcium (Ca), phosphorous (P), Alkaline phosphatase (Alp), parathormone (PTH), 25-hydroxy vitamin D 3 (25OH2D3), 1,25-dihydroxy vitamin D 3 (1,25(OH) 2 D 3 ) and serum FGF 23 were checked for all 30 rats on 1 st and 22 nd day of the study. All blood samples were centrifuged at 3500 rpm for 12 min, the plasma was stored at–70°C till further analysis. Serum Ca (mg/dl), P(mg/dl), creatinine(mg/dl), and ALP (Iu/L), were measured by colorimetric assays with a Biosystem, SA auto-analyzer, Spain. Fractional excretion of phosphorus (FEP) was assessed using this formula: (urine P x serum creatinine) ×100/(serum P x urine creatinine). Serum 25OHD 3 (ng/ml) were checked using Electrochemolumicence method, Germany, with 2 ng/ml sensitivity, 3.3% intra assay CV and 5.1% inter-assay CV. Serum 1,25(OH) 2 D 3 (pmol/ml) were measured with ELISA method produced by Bioassay Technology laboratory, China with intra- and inter-assay CVs sensitivity of less than 8% and 10%, respectively. Serum PTH (pg/ml) was measured with ELISA kits with sandwich technology, MyBioSource, USA with intra- and inter-assay of <6% and <7%, respectively. Serum FGF 23 (pg/ml) was measured by sandwich technology of ELIZA method. The kit was produced by Bioassay Technology laboratory in China with intra- and inter-assay CVs less than 8 and 10%, respectively. Statistical analysis: Data were analyzed using SPSS, version 21. Data were presented as mean ± SD. The paired-samples t- test was used to analyze values within the same group at baseline and after 22 nd day of the study. One-way ANOVA test with Tukey post-hoc test was used to compare biochemical data between the 3 studied groups. P value less than 0.05 was considered to be statistically significance. Compliance with Ethical Standards: All authors declare that they have no conflict of interest. This study was approved by the local Ethics Committee and vice-chancellor of research at Shiraz University of Medical Sciences. The study was done in accordance with the ARRIVE (Animal Research: Reporting of in vivo Experiments) guide line (12) on the use and care of research animals and all the applicable institutional and national guidelines for care and use of animals. Results Biochemical parameters were measured in all 3 groups at beginning of the experiment, and there was no significant difference in serum 25(OH)D 3 , 1,25(OH) 2 D 3 , Ca, P, Alp, and serum FGF 23 in all the 3 groups, P<0.05. All the data are summarized in table 1. Daily food intake was about 21 grams (median; Inter Quartiles 19.8–23.3) per day in all rats, without any significant difference in the 3 groups (P = 0.394) regarding energy intake. Also, no obvious change was observed in rats’ behavior. Mean body weight was similar in all 3 groups on the first day, summarized in figure–1. However, after 22 days the body weight in VDD and VDD+P groups was less than the controls. At the end of the study, all biochemical analysis was rechecked. Data are summarized in figure 2 and 3. There was significant vitamin D deficiency in VDD and VDD+P groups (P < 0.001). Also, serum 1,25(OH)D 3 was reduced significantly in VDD group (P = 0.019) and VDD+P group (P < 0.001) with a more significant decline in VDD+P group. Serum level of FGF 23 was reduced in VDD+P group compared to the control group (P = 0.011) and VDD group (P = 0.021), figure 2. Serum Ca, P, %FEP and ALP did not show significant difference between all groups (P > 0.05), figure 3. In addition, there were no significant difference in serum PTH between VDD+P and the control group; however, serum PTH in VDD group was higher than the control and VDD+P group (P = 0.036 and P = 0.038, respectively). Discussion The present study showed that paricalcitol could lower serum FGF 23 and 1,25(OH)D 3 in vitamin D deficient rats. Recent studies revealed the beneficial effects of paricalcitol in treating secondary hyperparathyroidism in chronic kidney disease, as it can lower serum PTH with a minimal effect on serum concentrations of Ca, P and calcium-phosphorous product (Ca × P), without damaging the kidneys (6, 13). However, its effect on FGF 23 should be further investigated. Donate-Correa et al. showed that in renal transplant recipients after 3-months of therapy with oral paricalcitol, serum KLOTHO concentration and KLOTHO mRNA level was increased. Also, they observed a significant reduction in serum PTH without any significant change in serum calcium and phosphorus (4). In addition, they showed a significant increase in the serum FGF 23 after paricalcitol administration. They suggested that it might be due to the general effect of vitamin D analogs on FGF 23 induction (4); however, they did not evaluate the serum 1,25(OH)D. Finch et al. investigated the effect of paricalcitol and cinacalcent on mineral metabolism in rats with chronic kidney disease (14). They showed that paricalcitol could reduce serum 1,25(OH) 2 D 3 and PTH; however, they showed that serum FGF 23 was increased. They stated that this paradox might be due to vitamin D analogs role in activating FGF 23 release (15). In contrast, Wetmore et al. found that paricalcitol and doxercociferol did not change serum FGF 23 in end stage renal disease (16). These discrepancies might be due to differences in nature of vitamin D analogues, or might be due to some other unknown factors (8). Previous studies revealed that serum FGF 23 increases as kidney function declines (10,17), but the reason for this increase is not fully understood (18). Hence, effect of paricalcitol on FGF 23 in treating secondary hyperparathyroidism should be investigated in non-uremic states affected vitamin D deficiency. In the present study, we showed that using paricalcitol in vitamin D deficient states could reduce serum PTH and 1,25(OH) 2 D 3 compared to vitamin D deficient rats, without any significant changes in serum calcium, phosphorous and fractional excretion of phosphorous. In addition, we showed that serum FGF 23 was reduced after using paricalcitol in vitamin D deficient rats. The present study suggests that reduced FGF 23 in vitamin D deficient rats, using paricalcitol could be explained by two mechanisms. The first mechanism might be low PTH level (2), which decreases serum FGF23, since PTH stimulates FGF 23 secretion in bone (19). The second mechanism of low FGF 23 in vitamin D deficient states treated by paricalcitol might be due to decrease in 1,25(OH) 2 D 3 . Previous studies showed that 1,25(OH) 2 D 3 stimulates the expression of FGF 23 in vitro in bone-derived cell cultures (15,20,21). Hence, low 1,25(OH) 2 D 3 in paricalcitol treated patients can negatively affect FGF 23 expression from bones (15). In spite of FGF 23 reduction, we did not observe any significant change in fractional excretion of phosphorous. This might be due to low serum PTH level in this group. Clarke et al. showed that FGF 23 regulation of phosphate homeostasis depends on PTH (22). Hence, using paricalcitol to reduce PTH might influence on the phosphaturic action of FGF 23 in vitamin D deficient rats treated with paricalcitol. Therefore, the present study supports Clarke’s claim. In addition to strengths of this study, we had some limitations. We did not investigate FGF 23 gene expression and KLOTHO pathway in vitamin D deficient rats treated with paricalcitol, which should be further evaluated to find out more details about FGF 23 and paricalcitol. Conclusion The present study showed that paricalcitol could reduce PTH, 1,25(OH) 2 D3 and FGF 23 in vitamin D deficient rats without any changes in serum calcium, phosphorous and fractional excretion of phosphorous. FGF23 reduction might be due to low PTH and 1,25(OH)2 D3. In addition, it supports the previous studies that claimed FGF 23 regulation of phosphorous homeostasis depends on PTH. Further investigation evaluating the FGF 23 gene expression and KLOTHO pathway should be considered in vitamin D deficient rats treated with paricalcitol, to find out more details about FGF 23 and paricalcitol. Abbreviation Fibroblast growth factor–23 (FGF23) 25-hydroxy vitamin D3 (25OH2D3) 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) Vitamin D deficient diet (VDD) Vitamin D deficient diet+ paricalcitol(VDD+P) vitamin D receptor(VDR) secondary hyperparathyroidism(SHPT) chronic kidney disease (CKD) parathormone (PTH) Calcium(Ca) phosphorous (P) Alkaline phosphatase(ALP) Statistical Package for Social Sciences(SPSS) Standard deviation(SD) one-way analysis of variance (One-way ANOVA) Animal Research: Reporting of in vivo Experiments (ARRIVE) Fractional excretion of phosphorus (FEP) Declarations Ethics approval and consent to participate: This study was approved by the local Ethics Committee of Shiraz University of Medical Sciences (SUMS). Vice chancellor of research at SUMS approved this study with ID: 97-01-33-17348. The present study is in line with the ARRIVE (Animal Research: Reporting of in Vivo Experiments) guidelines about using and coring of research animals. Consent for publication: The present study is in line with the ARRIVE (Animal Research: Reporting of in Vivo Experiments) guidelines about using and coring of research animals. Availability of data and materials The datasets used and analyzed during the current study are available from the corresponding author on reasonable request Competing Interests: The authors, declare that they have no conflict of interest. Funding : There is no financial support. Authors contribution: FS, design, data gathering, preparing the manuscript GHRO : design, data gathering, preparing the manuscript FK : design, data gathering, preparing the manuscript and the correspondence. All authors have read and approved the manuscript Acknowledgment: The authors wish to thank Mr. H. Argasi at the Research Consultation Center (RCC) of Shiraz University of Medical Sciences for his invaluable assistance in editing this manuscript. Also, we want to thank Royan Institute, Esfahan, Iran for their help in gathering vitamin D deficient diet. References Kurosu H, Ogawa Y, Miyoshi M, Yamamoto M, Nandi A, Rosenblatt KP, et al. Regulation of fibroblast growth factor-23 signaling by klotho. J Biol Chem. 2006; 281(10):6120-3. Erben RG. Update on FGF23 and Klotho signaling. Mol Cell Endocrinol. 2016; 432:56-65. Erben RG. Pleiotropic Actions of FGF23. Toxicol Pathol. 2017;45(7):904-910. Donate-Correa J, Henríquez-Palop F, Martín-Núñez E, Pérez-Delgado N, Muros-de-Fuentes M, Mora-Fernández C, et al. Effect of Paricalcitol on FGF-23 and Klotho in Kidney Transplant Recipients. Transplantation. 2016;100(11):2432-2438. Teng M, Wolf M, Lowrie E, Ofsthun N, Lazarus JM, Thadhani R. Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med. 2003; 349:446-456. 6. Coyne D, Acharya M, Qiu P, Abboud H, Batlle D, Rosansky S. Paricalcitol Capsule for the Treatment of Secondary Hyperparathyroidism in Stages 3 and 4 CKD. Am J Kidney Dis. 2006;47(2):263-76. 7. Egido J, Martínez-Castelao A, Bover J, Praga M, Torregrosa JV, Fernández-Giráldez E, et al. The pleiotropic effects of paricalcitol: Beyond bone-mineral metabolism. Nefrologia. 2016;36(1):10-8. Hansen D, Rasmussen K, Pedersen SM, Rasmussen LM, Brandi L. Changes in fibroblast growth factor 23 during treatment of secondary hyperparathyroidism with alfacalcidol or paricalcitol. Nephrol Dial Transplant. 2012;27(6):2263-9. Stavenuiter AW, Arcidiacono MV, Ferrantelli E, Keuning ED, Vila Cuenca M, ter Wee PM, et al. A novel rat model of vitamin D deficiency: safe and rapid induction of vitamin D and calcitriol deficiency without hyperparathyroidism. Biomed Res Int. 2015;2015:604275. Larsson T, Nisbeth U, Ljunggren O, Jüppner H, Jonsson KB. Circulating concentration of FGF-23 increases as renal function declines in patients with chronic kidney disease, but does not change in response to variation in phosphate intake in healthy volunteers. Kidney Int. 2003;64(6):2272-9. Imanishi Y, Inaba M, Nakatsuka K, Nagasue K, Okuno S, Yoshihara A, et al. FGF-23 in patients with end-stage renal disease on hemodialysis. Kidney Int. 2004 ;65(5):1943-6. Karp NA, Meehan TF, Morgan H, Mason JC, Blake A, Kurbatova N, Smedley D, Jacobsen J, Mott RF, Iyer V (2015) Applying the ARRIVE guidelines to an in vivo database. PLoS Biol 13(5): e1002151 Freundlich M, Abitbol CL. Oral paricalcitol: expanding therapeutic options for pediatric chronic kidney disease patients. Pediatr Nephrol. 2017;32(7):1103-1108. Finch JL, Tokumoto M, Nakamura H, Yao W, Shahnazari M, Lane N, Slatopolsky E. Effect of paricalcitol and cinacalcet on serum phosphate, FGF-23, and bone in rats with chronic kidney disease. Am J Physiol Renal Physiol. 2010;298(6):F1315-22. Kolek OI, Hines ER, Jones MD, LeSueur LK, Lipko MA, Kiela PR, et al. 1,25-dihydroxyvitamin D3 upregulates FGF23 gene expression in bone: the final link to a renal-gastrointestinal-skeletal axis that controls phosphate transport. Am J Physiol Gastrointest Liver Physiol. 2005;289(6): G1036-42. Wetmore JB, Liu S, Krebill R, Menard R, Quarles LD. Effects of cinacalcet and concurrent low-dose vitamin D on FGF23 levels in ESRD. Clin J Am Soc Nephrol. 2010 ;5(1):110-6. Shigematsu T, Kazama JJ, Yamashita T, Fukumoto S, Hosoya T, Gejyo F,et al. Possible involvement of circulating fibroblast growth factor 23 in the development of secondary hyperparathyroidism associated with renal insufficiency. Am J Kidney Dis. 2004;44(2):250-6. Wolf M. Forging forward with 10 burning questions on FGF23 in kidney disease. J Am Soc Nephrol. 2010;21(9):1427-35. Meir T, Durlacher K, Pan Z, Amir G, Richards WG, Silver J, et al. Parathyroid hormone activates the orphan nuclear receptor Nurr1 to induce FGF23 transcription. Kidney Int. 2014;86(6):1106-15. Barthel TK, Mathern DR, Whitfield GK, Haussler CA, Hopper HA, Hsieh JC, et al. 1,25-Dihydroxyvitamin D3/VDR-mediated induction of FGF23 as well as transcriptional control of other bone anabolic and catabolic genes that orchestrate the regulation of phosphate and calcium mineral metabolism. J Steroid Biochem Mol Biol. 2007;103(3-5):381-8. Saji F, Shigematsu T, Sakaguchi T, Ohya M, Orita H, Maeda Y, et al. Fibroblast growth factor 23 production in bone is directly regulated by 1alpha,25-dihydroxyvitamin D, but not PTH. Am J Physiol Renal Physiol. 2010;299(5):F1212-7. Clarke BL. FGF23 regulation of phosphorus homeostasis is dependent on PTH. Endocrinology. 2011;152(11):4016-8. Table Table 1: It describes the serum minerals, vitamin D and FGF23 levels (Mean ± SD) in first day of study in all three groups Groups 25(OH)D3 (nmol/ml) 1,25(OH) 2 D3 (nmol/ml) Ca (mg/dl) Ph (mg/dl) ALP (IU/L) FGF23 (pg/ml) Control 89.25±3.95 a 60.76±5.90 a 9.76±0.13 a 6.10±0.18 a 482.80±31.37 a 65.90±3.20 a VDD 79.7 ±4.25 a 60.91 ±5.30 a 9.26 ±0.38 a 5.88 ±0.29 a 388.80 ±24.68 a 63.54 ±4.46 a VDD+P 80.37 ±3.95 a 61.33 ±5.00 a 9.01 ±0.56 a 6.34 ±0.51 a 410.5 ±40.66 a 62.04 ±3.78 a a There was no significant difference between the experimental groups (P<0.05) VDD: Vitamin D deficient group VDD+P: Vitamin D deficient group treated with Paricalcitol Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9077","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":241927,"identity":"5f880897-2f89-4475-9e63-d7c79064c2d1","order_by":1,"name":"Forough Saki","email":"","orcid":"","institution":"Shiraz University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Forough","middleName":"","lastName":"Saki","suffix":""},{"id":241928,"identity":"46bd424f-2c51-4352-b316-09e9e9219813","order_by":2,"name":"Gholamhossein Ranjbar Omrani","email":"","orcid":"","institution":"Shiraz University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Gholamhossein","middleName":"Ranjbar","lastName":"Omrani","suffix":""},{"id":241929,"identity":"6fcaeb2d-8370-4520-b33a-b221bb429b52","order_by":3,"name":"Farhad Koohpeyma","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA70lEQVRIiWNgGAWjYBACCQYGNiiT8eEDuHACcVqYjQ1I1mImQZTDJNubjz0uqDgczd/AzFb5s22bPQP74QcMD/fg1iLNcyzdeMaZw7kzDjCz3eZtu53YwJNmwJDwDLcWOYkcM2netsO5DQf4j91mbLsN9EUO0C8HCGn5dzh3PtCWwp9tt+0Z+N/g1yIN1tJwOHcDUAsD0GGMDRIEbJHsOZYmPeNYeu7Gw8zM0jznbie2STwzOIBPi8Tx5mPSBTXWufOONzN+/FF2256fP/nhwx94tIAAMwNDM5gEA1A0EdAAVlxHSM0oGAWjYBSMZAAAC5ZOiXuvKfAAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0001-6729-7732","institution":"Shiraz University of Medical Sciences","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Farhad","middleName":"","lastName":"Koohpeyma","suffix":""}],"badges":[],"createdAt":"2019-12-05 14:26:57","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.2.18457/v1","doiUrl":"https://doi.org/10.21203/rs.2.18457/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":237857,"identity":"d6d8a8e0-f2bd-4c5e-9b00-04d04f56f6a0","added_by":"auto","created_at":"2019-12-10 21:10:04","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":48489,"visible":true,"origin":"","legend":"Body weight of studied rats in all three groups during the study","description":"","filename":"1.PNG","url":"https://assets-eu.researchsquare.com/files/4282b921-40b2-496f-813e-c8eabc27a5a0/v1/1.PNG"},{"id":237860,"identity":"afea19a6-1aef-480a-86c6-106ab250e8e2","added_by":"auto","created_at":"2019-12-10 21:10:05","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":53247,"visible":true,"origin":"","legend":"serum 25OHD3, 1, 25(OH)2D3, PTH and FGF23 serum level in all rats at the end of the study (22nd day)","description":"","filename":"2.PNG","url":"https://assets-eu.researchsquare.com/files/4282b921-40b2-496f-813e-c8eabc27a5a0/v1/2.PNG"},{"id":237862,"identity":"a2544a98-9dbc-4cda-a5f3-f27468f8dd21","added_by":"auto","created_at":"2019-12-10 21:10:05","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":41458,"visible":true,"origin":"","legend":"serum calcium, phosphorous, alkaline phosphatase and Fractional excretion of phosphorous in all rats at the end of the study (22nd day)","description":"","filename":"3.PNG","url":"https://assets-eu.researchsquare.com/files/4282b921-40b2-496f-813e-c8eabc27a5a0/v1/3.PNG"},{"id":13481313,"identity":"0187020a-97fb-414e-9a2f-de3cb7abad1b","added_by":"auto","created_at":"2021-09-16 21:46:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":412451,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9077/v1/4d06b1a7-b073-4586-82f5-a88ba2dfd93b.pdf"}],"financialInterests":"","formattedTitle":"Investigating the effect of paricalcitol on serum FGF23 in vitamin D deficient rats","fulltext":[{"header":"Background","content":"\u003cp\u003eFibroblast growth factor (FGF23) is a bone-derived hormone, which plays an important role in mineral metabolism (1). The main function of serum FGF23 is to suppress phosphate reabsorption and vitamin D activation in kidneys (2). However, several new klotho-dependent and klotho-independent roles including blood pressure regulation, bone mineralization and affecting innate immune system have been uncovered for FGF23 (3). Although recent studies have revealed major new functions of FGF23, it rises many new questions regarding its details (2). One of these debates has considered the effect of paricalcitol on serum FGF23 (4).\u003c/p\u003e\n\u003cp\u003eParicalcitol is a selective vitamin D receptor (VDR) activator, which has been approved since 1998 for the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) (5). Paricalcitol was introduced due to the need for a treatment that could inhibit high serum PTH in patients with SHPT, with a minimal effect on calcium-phosphorous product (Ca × P) in CKD patients, without renal toxicity (6). Nowadays, it is being considered as an anti-parathyroid agent rather than vitamin D analogue (7). Previous studies evaluated the effect of paricalcitol on serum FGF23 in SHPT patients with CKD (4,8). Some revealed that paricalcitol could increase serum FGF23 in hemodialysis patients through an increase in serum phosphate and calcium (4,8); however, others revealed that in non-uremic vitamin D deficient rats, paricalcitol could induce vitamin D deficiency state with unchanged PTH, Ca, and phosphate level (9). In addition, it is well known that serum FGF23 rises progressively as kidney function declines due to some known and unknown mechanisms (10,11), which consequently influences the conclusion regarding the exact effect of paricalcitol on serum FGF23 in non-uremic patients.\u003c/p\u003e\n\u003cp\u003eHence, we conducted this study to discover changes of serum FGF23 in non-uremic rat model of vitamin D deficiency without secondary hyperparathyroidism using paricalcitol. Furthermore, we compared the serum minerals and hormones between vitamin D deficient rats (vitamin D deficiency + SHPT) and vitamin D deficient rats using paricalcitol (vitamin D deficiency without SHPT).\u003c/p\u003e\n\n\n\n"},{"header":"Methods","content":"\u003cp\u003eA total of 30 adult male spargue-dawley rats (10 weeks old), weighting 300±20 grams were purchased from the animal laboratory center of Shiraz University of Medical Sciences. Subjects underwent one-week acclimatization to the animal laboratory facilities before the study. They were housed in standard cages, five per cage, with 12:12 hours light-dark cycles at temperature of 23±2°c. All rats were randomly divided into three groups of 10 rats as below:\u003c/p\u003e\n\u003cp\u003eA: Control group(C): received normal standard rodent chow diet and had free access to tap water\u003c/p\u003e\n\u003cp\u003eB: Vitamin D deficient group (VDD group): received standard vitamin D deficient diet (TD.87095 Brown C. C. vitamin D deficient diet, containing 20% lactose, 2% calcium and 1.25% phosphate)\u003c/p\u003e\n\u003cp\u003eC: Vitamin D deficient diet + paricalcitol (VDD+P group): received the above mentioned standard vitamin D deficient diet plus intraperitoneal injections of 32 ng of 19-nor–1,25-dihydroxy vitamin D\u003csub\u003e2\u003c/sub\u003e (paricalcitol; Zemplar) on days 1,3,5,8,10 and 12 of the study, according to stavenuiter protocol (F). Rats’ weight was checked on days 1,10,15 and 22 of the study.\u003c/p\u003e\n\u003cp\u003eAt the end of the experiment, all rats were anesthetized with ketamine 10 % (100 mg/kg, Alfasan, Netherlands) and xylazin 2 % (10 mg/kg, Alfasan, Netherlands) solution intraperitoneally and sacrificed by using thiopental (100 mg/kg).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eBiochemical studies:\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eSerum calcium (Ca), phosphorous (P), Alkaline phosphatase (Alp), parathormone (PTH), 25-hydroxy vitamin D\u003csub\u003e3\u003c/sub\u003e (25OH2D3), 1,25-dihydroxy vitamin D\u003csub\u003e3\u003c/sub\u003e (1,25(OH)\u003csub\u003e2\u003c/sub\u003eD\u003csub\u003e3\u003c/sub\u003e) and serum FGF\u003csub\u003e23\u003c/sub\u003e were checked for all 30 rats on 1\u003csup\u003est\u003c/sup\u003e and 22\u003csup\u003end\u003c/sup\u003e day of the study.\u003c/p\u003e\n\u003cp\u003eAll blood samples were centrifuged at 3500 rpm for 12 min, the plasma was stored at–70°C till further analysis. Serum Ca (mg/dl), P(mg/dl), creatinine(mg/dl), and ALP (Iu/L), were measured by colorimetric assays with a Biosystem, SA auto-analyzer, Spain. Fractional excretion of phosphorus (FEP) was assessed using this formula: (urine P x serum creatinine) ×100/(serum P x urine creatinine). Serum 25OHD\u003csub\u003e3\u003c/sub\u003e (ng/ml) were checked using Electrochemolumicence method, Germany, with 2 ng/ml sensitivity, 3.3% intra assay CV and 5.1% inter-assay CV. Serum 1,25(OH)\u003csub\u003e2\u003c/sub\u003eD\u003csub\u003e3\u003c/sub\u003e (pmol/ml) were measured with ELISA method produced by Bioassay Technology laboratory, China with intra- and inter-assay CVs sensitivity of less than 8% and 10%, respectively. Serum PTH (pg/ml) was measured with ELISA kits with sandwich technology, MyBioSource, USA with intra- and inter-assay of \u0026lt;6% and \u0026lt;7%, respectively. Serum FGF\u003csub\u003e23\u003c/sub\u003e(pg/ml) was measured by sandwich technology of ELIZA method. The kit was produced by Bioassay Technology laboratory in China with intra- and inter-assay CVs less than 8 and 10%, respectively.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStatistical analysis:\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eData were analyzed using SPSS, version 21. Data were presented as mean ± SD. The paired-samples\u003cem\u003e t-\u003c/em\u003etest was used to analyze values within the same group at baseline and after 22\u003csup\u003end\u003c/sup\u003e day of the study. One-way ANOVA test with Tukey post-hoc test was used to compare biochemical data between the 3 studied groups. P value less than 0.05 was considered to be statistically significance.\u003c/p\u003e\n\n\u003cp\u003e\u003cem\u003eCompliance with Ethical Standards:\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare that they have no conflict of interest. This study was approved by the local Ethics Committee and vice-chancellor of research at Shiraz University of Medical Sciences.\u003c/p\u003e\n\u003cp\u003eThe study was done in accordance with the ARRIVE (Animal Research: Reporting of \u003cem\u003ein vivo\u003c/em\u003e Experiments) guide line (12) on the use and care of research animals and all the applicable institutional and national guidelines for care and use of animals.\u003c/p\u003e\n\n"},{"header":"Results","content":"\u003cp\u003eBiochemical parameters were measured in all 3 groups at beginning of the experiment, and there was no significant difference in serum 25(OH)D\u003csub\u003e3\u003c/sub\u003e, 1,25(OH)\u003csub\u003e2\u003c/sub\u003eD\u003csub\u003e3\u003c/sub\u003e, Ca, P, Alp, and serum FGF\u003csub\u003e23\u003c/sub\u003e in all the 3 groups, P\u0026lt;0.05. All the data are summarized in table 1.\u003c/p\u003e\n\u003cp\u003eDaily food intake was about 21 grams (median; Inter Quartiles 19.8–23.3) per day in all rats, without any significant difference in the 3 groups (P = 0.394) regarding energy intake. Also, no obvious change was observed in rats’ behavior. Mean body weight was similar in all 3 groups on the first day, summarized in figure–1. However, after 22 days the body weight in VDD and VDD+P groups was less than the controls.\u003c/p\u003e\n\u003cp\u003eAt the end of the study, all biochemical analysis was rechecked. Data are summarized in figure 2 and 3. There was significant vitamin D deficiency in VDD and VDD+P groups (P \u0026lt; 0.001). Also, serum 1,25(OH)D\u003csub\u003e3\u003c/sub\u003e was reduced significantly in VDD group (P = 0.019) and VDD+P group (P \u0026lt; 0.001) with a more significant decline in VDD+P group. Serum level of FGF\u003csub\u003e23\u003c/sub\u003e was reduced in VDD+P group compared to the control group (P = 0.011) and VDD group (P = 0.021), figure 2. Serum Ca, P, %FEP and ALP did not show significant difference between all groups (P \u0026gt; 0.05), figure 3. In addition, there were no significant difference in serum PTH between VDD+P and the control group; however, serum PTH in VDD group was higher than the control and VDD+P group (P = 0.036 and P = 0.038, respectively).\u003c/p\u003e\n"},{"header":"Discussion","content":"\u003cp\u003eThe present study showed that paricalcitol could lower serum FGF\u003csub\u003e23\u003c/sub\u003e and 1,25(OH)D\u003csub\u003e3\u003c/sub\u003e in vitamin D deficient rats. Recent studies revealed the beneficial effects of paricalcitol in treating secondary hyperparathyroidism in chronic kidney disease, as it can lower serum PTH with a minimal effect on serum concentrations of Ca, P and calcium-phosphorous product (Ca × P), without damaging the kidneys (6, 13). However, its effect on FGF\u003csub\u003e23\u003c/sub\u003e should be further investigated.\u003c/p\u003e\n\u003cp\u003eDonate-Correa et al. showed that in renal transplant recipients after 3-months of therapy with oral paricalcitol, serum KLOTHO concentration and KLOTHO mRNA level was increased. Also, they observed a significant reduction in serum PTH without any significant change in serum calcium and phosphorus (4). In addition, they showed a significant increase in the serum FGF\u003csub\u003e23\u003c/sub\u003e after paricalcitol administration. They suggested that it might be due to the general effect of vitamin D analogs on FGF\u003csub\u003e23\u003c/sub\u003e induction (4); however, they did not evaluate the serum 1,25(OH)D. Finch et al. investigated the effect of paricalcitol and cinacalcent on mineral metabolism in rats with chronic kidney disease (14). They showed that paricalcitol could reduce serum 1,25(OH)\u003csub\u003e2\u003c/sub\u003eD\u003csub\u003e3\u003c/sub\u003e and PTH; however, they showed that serum FGF\u003csub\u003e23\u003c/sub\u003e was increased. They stated that this paradox might be due to vitamin D analogs role in activating FGF\u003csub\u003e23\u003c/sub\u003e release (15). In contrast, Wetmore et al. found that paricalcitol and doxercociferol did not change serum FGF\u003csub\u003e23\u003c/sub\u003e in end stage renal disease (16). These discrepancies might be due to differences in nature of vitamin D analogues, or might be due to some other unknown factors (8). Previous studies revealed that serum FGF\u003csub\u003e23\u003c/sub\u003e increases as kidney function declines (10,17), but the reason for this increase is not fully understood (18). Hence, effect of paricalcitol on FGF\u003csub\u003e23\u003c/sub\u003e in treating secondary hyperparathyroidism should be investigated in non-uremic states affected vitamin D deficiency. In the present study, we showed that using paricalcitol in vitamin D deficient states could reduce serum PTH and 1,25(OH)\u003csub\u003e2\u003c/sub\u003eD\u003csub\u003e3\u003c/sub\u003e compared to vitamin D deficient rats, without any significant changes in serum calcium, phosphorous and fractional excretion of phosphorous. In addition, we showed that serum FGF\u003csub\u003e23\u003c/sub\u003e was reduced after using paricalcitol in vitamin D deficient rats. The present study suggests that reduced FGF\u003csub\u003e23\u003c/sub\u003e in vitamin D deficient rats, using paricalcitol could be explained by two mechanisms. The first mechanism might be low PTH level (2), which decreases serum FGF23, since PTH stimulates FGF\u003csub\u003e23\u003c/sub\u003e secretion in bone (19). The second mechanism of low FGF\u003csub\u003e23\u003c/sub\u003e in vitamin D deficient states treated by paricalcitol might be due to decrease in 1,25(OH)\u003csub\u003e2\u003c/sub\u003eD\u003csub\u003e3\u003c/sub\u003e. Previous studies showed that 1,25(OH)\u003csub\u003e2\u003c/sub\u003eD\u003csub\u003e3\u003c/sub\u003e stimulates the expression of FGF\u003csub\u003e23\u003c/sub\u003e \u003cem\u003ein vitro\u003c/em\u003e in bone-derived cell cultures (15,20,21). Hence, low 1,25(OH)\u003csub\u003e2\u003c/sub\u003eD\u003csub\u003e3\u003c/sub\u003e in paricalcitol treated patients can negatively affect FGF\u003csub\u003e23\u003c/sub\u003e expression from bones (15). In spite of FGF\u003csub\u003e23\u003c/sub\u003e reduction, we did not observe any significant change in fractional excretion of phosphorous. This might be due to low serum PTH level in this group. Clarke et al. showed that FGF\u003csub\u003e23\u003c/sub\u003e regulation of phosphate homeostasis depends on PTH (22). Hence, using paricalcitol to reduce PTH might influence on the phosphaturic action of FGF\u003csub\u003e23 \u003c/sub\u003ein vitamin D deficient rats treated with paricalcitol. Therefore, the present study supports Clarke’s claim.\u003c/p\u003e\n\u003cp\u003eIn addition to strengths of this study, we had some limitations. We did not investigate FGF\u003csub\u003e23\u003c/sub\u003e gene expression and KLOTHO pathway in vitamin D deficient rats treated with paricalcitol, which should be further evaluated to find out more details about FGF\u003csub\u003e23\u003c/sub\u003e and paricalcitol.\u003c/p\u003e\n"},{"header":"Conclusion","content":"\u003cp\u003eThe present study showed that paricalcitol could reduce PTH, 1,25(OH)\u003csub\u003e2\u003c/sub\u003e D3 and FGF\u003csub\u003e23\u003c/sub\u003e in vitamin D deficient rats without any changes in serum calcium, phosphorous and fractional excretion of phosphorous. FGF23 reduction might be due to low PTH and 1,25(OH)2 D3. In addition, it supports the previous studies that claimed FGF\u003csub\u003e23\u003c/sub\u003e regulation of phosphorous homeostasis depends on PTH. Further investigation evaluating the FGF\u003csub\u003e23\u003c/sub\u003e gene expression and KLOTHO pathway should be considered in vitamin D deficient rats treated with paricalcitol, to find out more details about FGF\u003csub\u003e23\u003c/sub\u003e and paricalcitol.\u003c/p\u003e\n\n"},{"header":"Abbreviation","content":"\u003cp\u003eFibroblast growth factor–23 (FGF23)\u003c/p\u003e\n\u003cp\u003e25-hydroxy vitamin D3 (25OH2D3)\u003c/p\u003e\n\u003cp\u003e1,25-dihydroxy vitamin D3 (1,25(OH)2D3)\u003c/p\u003e\n\u003cp\u003eVitamin D deficient diet (VDD)\u003c/p\u003e\n\u003cp\u003eVitamin D deficient diet+ paricalcitol(VDD+P)\u003c/p\u003e\n\u003cp\u003evitamin D receptor(VDR)\u003c/p\u003e\n\u003cp\u003esecondary hyperparathyroidism(SHPT)\u003c/p\u003e\n\u003cp\u003echronic kidney disease (CKD)\u003c/p\u003e\n\u003cp\u003eparathormone (PTH)\u003c/p\u003e\n\u003cp\u003eCalcium(Ca)\u003c/p\u003e\n\u003cp\u003ephosphorous (P)\u003c/p\u003e\n\u003cp\u003eAlkaline phosphatase(ALP)\u003c/p\u003e\n\u003cp\u003eStatistical Package for Social Sciences(SPSS)\u003c/p\u003e\n\u003cp\u003eStandard deviation(SD)\u003c/p\u003e\n\u003cp\u003eone-way analysis of variance (One-way ANOVA)\u003c/p\u003e\n\u003cp\u003eAnimal Research: Reporting of in vivo Experiments (ARRIVE)\u003c/p\u003e\n\u003cp\u003eFractional excretion of phosphorus (FEP)\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate: \u003c/strong\u003eThis study was approved by the local Ethics Committee of Shiraz University of Medical Sciences (SUMS). Vice chancellor of research at SUMS approved this study with ID: 97-01-33-17348. The present study is in line with the ARRIVE (Animal Research: Reporting of \u003cem\u003ein Vivo\u003c/em\u003e Experiments) guidelines about using and coring of research animals.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e The present study is in line with the ARRIVE (Animal Research: Reporting of \u003cem\u003ein Vivo\u003c/em\u003e Experiments) guidelines about using and coring of research animals.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analyzed during the current study are available from the corresponding author on reasonable request\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests:\u003c/strong\u003e The authors, declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: There is no financial support.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors contribution:\u003c/strong\u003e\u003c/p\u003e\n\u003col\u003e\n\u003cli\u003e\u003cstrong\u003eFS,\u003c/strong\u003e design, data gathering, preparing the manuscript\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eGHRO\u003c/strong\u003e: design, data gathering, preparing the manuscript\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003eFK\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e design, data gathering, preparing the manuscript and the correspondence. All authors have read and approved the manuscript\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment:\u003c/strong\u003e The authors wish to thank Mr. H. Argasi at the Research Consultation Center (RCC) of Shiraz University of Medical Sciences for his invaluable assistance in editing this manuscript.\u0026nbsp; Also, we want to thank Royan Institute, Esfahan, Iran for their help in gathering vitamin D deficient diet.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKurosu\u0026nbsp;H, Ogawa Y, Miyoshi M, Yamamoto M, Nandi A, Rosenblatt KP, et al. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/16436388\"\u003eRegulation of fibroblast growth factor-23 signaling by klotho.\u003c/a\u003e J Biol Chem. 2006; 281(10):6120-3.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003col start=\"2\"\u003e\n\u003cli\u003eErben RG. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/27178987\"\u003eUpdate on\u0026nbsp;FGF23\u0026nbsp;and Klotho signaling.\u003c/a\u003eMol Cell Endocrinol. 2016; 432:56-65.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003col start=\"3\"\u003e\n\u003cli\u003eErben\u0026nbsp;RG. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/29096595\"\u003ePleiotropic Actions of FGF23.\u003c/a\u003eToxicol Pathol. 2017;45(7):904-910.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003col start=\"4\"\u003e\n\u003cli\u003eDonate-Correa J, Henr\u0026iacute;quez-Palop F, Mart\u0026iacute;n-N\u0026uacute;\u0026ntilde;ez E, P\u0026eacute;rez-Delgado N, Muros-de-Fuentes M, Mora-Fern\u0026aacute;ndez C, et al. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/27467536\"\u003eEffect of\u0026nbsp;Paricalcitol\u0026nbsp;on\u0026nbsp;FGF-23 and Klotho in Kidney Transplant Recipients.\u003c/a\u003e Transplantation. 2016;100(11):2432-2438.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003col start=\"5\"\u003e\n\u003cli\u003eTeng M, Wolf M, Lowrie E, Ofsthun N, Lazarus JM, Thadhani R. Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med. 2003; 349:446-456.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e6.\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; \u003c/strong\u003eCoyne D, Acharya M, Qiu P, Abboud H, Batlle D, Rosansky S. Paricalcitol Capsule for the Treatment of Secondary Hyperparathyroidism in Stages 3 and 4 CKD. Am J Kidney Dis. 2006;47(2):263-76.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e7.\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; \u003c/strong\u003eEgido\u0026nbsp;J, Mart\u0026iacute;nez-Castelao A, Bover J, Praga M, Torregrosa JV, Fern\u0026aacute;ndez-Gir\u0026aacute;ldez E, et al. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/26705959\"\u003eThe pleiotropic effects of\u0026nbsp;paricalcitol: Beyond bone-mineral metabolism.\u003c/a\u003e Nefrologia. 2016;36(1):10-8.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003col start=\"8\"\u003e\n\u003cli\u003eHansen\u0026nbsp;D, Rasmussen K, Pedersen SM, Rasmussen LM, Brandi L.\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/22140123\"\u003eChanges in fibroblast growth factor 23 during treatment of secondary hyperparathyroidism with alfacalcidol or paricalcitol.\u003c/a\u003e Nephrol Dial Transplant. 2012;27(6):2263-9.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003col start=\"9\"\u003e\n\u003cli\u003eStavenuiter AW, Arcidiacono MV, Ferrantelli E, Keuning ED, Vila Cuenca M, ter Wee PM, et al. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/25815325\"\u003eA\u0026nbsp;novel\u0026nbsp;rat\u0026nbsp;model\u0026nbsp;of\u0026nbsp;vitamin D\u0026nbsp;deficiency: safe and rapid induction of\u0026nbsp;vitamin D\u0026nbsp;and\u0026nbsp;calcitriol deficiency without hyperparathyroidism.\u003c/a\u003e Biomed Res Int. 2015;2015:604275.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003col start=\"10\"\u003e\n\u003cli\u003eLarsson T, Nisbeth U, Ljunggren O, J\u0026uuml;ppner H, Jonsson KB. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/14633152\"\u003eCirculating\u0026nbsp;concentration\u0026nbsp;of\u0026nbsp;FGF-23\u0026nbsp;increases\u0026nbsp;as\u0026nbsp;renal\u0026nbsp;function\u0026nbsp;declines in patients with chronic kidney disease, but does not change in response to variation in phosphate intake in healthy volunteers.\u003c/a\u003e Kidney Int. 2003;64(6):2272-9.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003col start=\"11\"\u003e\n\u003cli\u003eImanishi\u0026nbsp;Y, Inaba M, Nakatsuka K, Nagasue K, Okuno S, Yoshihara A, et al. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/15086938\"\u003eFGF-23\u0026nbsp;in patients with end-stage\u0026nbsp;renal\u0026nbsp;disease on\u0026nbsp;hemodialysis.\u003c/a\u003e Kidney Int. 2004 ;65(5):1943-6.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003col start=\"12\"\u003e\n\u003cli\u003eKarp NA, Meehan TF, Morgan H, Mason JC, Blake A, Kurbatova N, Smedley D, Jacobsen J, Mott RF, Iyer V (2015) Applying the ARRIVE guidelines to an in vivo database. PLoS Biol 13(5): e1002151\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003col start=\"13\"\u003e\n\u003cli\u003eFreundlich\u0026nbsp;M, Abitbol CL. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/28451892\"\u003eOral\u0026nbsp;paricalcitol: expanding therapeutic options for pediatric chronic kidney disease patients.\u003c/a\u003e Pediatr Nephrol. 2017;32(7):1103-1108.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003col start=\"14\"\u003e\n\u003cli\u003eFinch\u0026nbsp;JL, Tokumoto M, Nakamura H, Yao W, Shahnazari M, Lane N, Slatopolsky E. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/20200094\"\u003eEffect of paricalcitol and cinacalcet on serum phosphate, FGF-23, and bone in rats with chronic kidney disease.\u003c/a\u003eAm J Physiol Renal Physiol. 2010;298(6):F1315-22.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003col start=\"15\"\u003e\n\u003cli\u003eKolek OI, Hines ER, Jones MD, LeSueur LK, Lipko MA, Kiela PR, et al.\u0026nbsp;1,25-dihydroxyvitamin D3 upregulates FGF23 gene expression in bone: the final link to a renal-gastrointestinal-skeletal axis that controls phosphate transport.\u0026nbsp;Am J Physiol Gastrointest Liver Physiol. 2005;289(6): G1036-42.\u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003col start=\"16\"\u003e\n\u003cli\u003eWetmore JB, Liu S, Krebill R, Menard R, Quarles LD. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/19965548\"\u003eEffects\u0026nbsp;of\u0026nbsp;cinacalcet\u0026nbsp;and concurrent low-dose\u0026nbsp;vitamin D\u0026nbsp;on\u0026nbsp;FGF23\u0026nbsp;levels\u0026nbsp;in\u0026nbsp;ESRD.\u003c/a\u003e Clin J Am Soc Nephrol. 2010 ;5(1):110-6.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003col start=\"17\"\u003e\n\u003cli\u003eShigematsu T, Kazama JJ, Yamashita T, Fukumoto S, Hosoya T, Gejyo F,et al. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/15264182\"\u003ePossible\u0026nbsp;involvement\u0026nbsp;of\u0026nbsp;circulating\u0026nbsp;fibroblast growth factor 23\u0026nbsp;in the development of secondary hyperparathyroidism associated with renal insufficiency.\u003c/a\u003e Am J Kidney Dis. 2004;44(2):250-6.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003col start=\"18\"\u003e\n\u003cli\u003eWolf M. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/20507943\"\u003eForging forward with 10 burning\u0026nbsp;questions\u0026nbsp;on\u0026nbsp;FGF23\u0026nbsp;in\u0026nbsp;kidney disease.\u003c/a\u003e J Am Soc Nephrol. 2010;21(9):1427-35.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003col start=\"19\"\u003e\n\u003cli\u003eMeir\u0026nbsp;T, Durlacher K, Pan Z, Amir G, Richards WG, Silver J, et al. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/24940803\"\u003eParathyroid hormone activates the orphan nuclear receptor Nurr1 to induce\u0026nbsp;FGF23\u0026nbsp;transcription.\u003c/a\u003e Kidney Int. 2014;86(6):1106-15.\u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003col start=\"20\"\u003e\n\u003cli\u003eBarthel TK, Mathern DR, Whitfield GK, Haussler CA, Hopper HA, Hsieh JC, et al. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/17293108\"\u003e1,25-Dihydroxyvitamin D3/VDR-mediated induction of FGF23 \u0026nbsp;as\u0026nbsp;well\u0026nbsp;as\u0026nbsp;transcriptional\u0026nbsp;control of other\u0026nbsp;bone\u0026nbsp;anabolic and catabolic\u0026nbsp;genes\u0026nbsp;that orchestrate the regulation of phosphate and calcium mineral metabolism.\u003c/a\u003e J Steroid Biochem Mol Biol. 2007;103(3-5):381-8.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003col start=\"21\"\u003e\n\u003cli\u003eSaji F, Shigematsu T, Sakaguchi T, Ohya M, Orita H, Maeda Y, et al. \u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/20739393\"\u003eFibroblast growth factor 23\u0026nbsp;production\u0026nbsp;in\u0026nbsp;bone\u0026nbsp;is\u0026nbsp;directly\u0026nbsp;regulated\u0026nbsp;by 1alpha,25-dihydroxyvitamin D, but not PTH.\u003c/a\u003e Am J Physiol Renal Physiol. 2010;299(5):F1212-7.\u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003col start=\"22\"\u003e\n\u003cli\u003eClarke\u0026nbsp;BL.\u003ca href=\"https://www.ncbi.nlm.nih.gov/pubmed/22021200\"\u003eFGF23\u0026nbsp;regulation of phosphorus homeostasis is dependent on PTH.\u003c/a\u003e Endocrinology. 2011;152(11):4016-8. \u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table","content":"\u003cp style=\"margin-bottom: 10.0pt; text-align: justify; line-height: 200%; tab-stops: 17.25pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif;\"\u003eTable 1: It describes the serum minerals, vitamin D and FGF23 levels \u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif;\"\u003e(Mean \u0026plusmn; SD)\u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif;\"\u003e in first day of study in all three groups\u0026nbsp; \u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"margin-left: -.25pt; border-collapse: collapse; border: none;\" width=\"618\"\u003e\n\u003ctbody\u003e\n\u003ctr style=\"height: 48.2pt;\"\u003e\n\u003ctd style=\"width: 79.35pt; border: solid #666666 1.0pt; border-bottom: solid #666666 1.5pt; padding: 0in 5.4pt 0in 5.4pt; height: 48.2pt;\" width=\"106\"\u003e\n\u003cp style=\"margin-bottom: 10.0pt; line-height: 115%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 115%; font-family: 'Times New Roman',serif; color: black;\"\u003eGroups\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 61.3pt; border-top: solid #666666 1.0pt; border-left: none; border-bottom: solid #666666 1.5pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 48.2pt;\" width=\"82\"\u003e\n\u003cp style=\"margin-bottom: 10.0pt; line-height: 115%; tab-stops: center 3.25in left 387.5pt right 6.5in;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 115%; font-family: 'Times New Roman',serif; color: black;\"\u003e25(OH)D3\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"margin-bottom: 10.0pt; line-height: 115%; tab-stops: center 3.25in left 387.5pt right 6.5in;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 115%; font-family: 'Times New Roman',serif; color: black;\"\u003e(nmol/ml)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 75.35pt; border-top: solid #666666 1.0pt; border-left: none; border-bottom: solid #666666 1.5pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 48.2pt;\" width=\"100\"\u003e\n\u003cp style=\"margin-bottom: 10.0pt; line-height: 115%; tab-stops: center 3.25in left 387.5pt right 6.5in;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 115%; font-family: 'Times New Roman',serif; color: black;\"\u003e1,25(OH)\u003csub\u003e2\u003c/sub\u003e D3\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"margin-bottom: 10.0pt; line-height: 115%; tab-stops: center 3.25in left 387.5pt right 6.5in;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 115%; font-family: 'Times New Roman',serif; color: black;\"\u003e(nmol/ml)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 58.1pt; border-top: solid #666666 1.0pt; border-left: none; border-bottom: solid #666666 1.5pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 48.2pt;\" width=\"77\"\u003e\n\u003cp style=\"margin-bottom: 10.0pt; line-height: 115%; tab-stops: center 3.25in left 387.5pt right 6.5in;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 115%; font-family: 'Times New Roman',serif; color: black;\"\u003eCa\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"margin-bottom: 10.0pt; line-height: 115%; tab-stops: center 3.25in left 387.5pt right 6.5in;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 115%; font-family: 'Times New Roman',serif; color: black;\"\u003e(mg/dl)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 54.4pt; border-top: solid #666666 1.0pt; border-left: none; border-bottom: solid #666666 1.5pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 48.2pt;\" width=\"73\"\u003e\n\u003cp style=\"margin-bottom: 10.0pt; line-height: 115%; tab-stops: center 3.25in left 387.5pt right 6.5in;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 115%; font-family: 'Times New Roman',serif; color: black;\"\u003ePh\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"margin-bottom: 10.0pt; line-height: 115%; tab-stops: center 3.25in left 387.5pt right 6.5in;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 115%; font-family: 'Times New Roman',serif; color: black;\"\u003e(mg/dl)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 1.0in; border-top: solid #666666 1.0pt; border-left: none; border-bottom: solid #666666 1.5pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 48.2pt;\" width=\"96\"\u003e\n\u003cp style=\"margin-bottom: 10.0pt; line-height: 115%; tab-stops: center 3.25in left 387.5pt right 6.5in;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 115%; font-family: 'Times New Roman',serif; color: black;\"\u003eALP\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"margin-bottom: 10.0pt; line-height: 115%; tab-stops: center 3.25in left 387.5pt right 6.5in;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 115%; font-family: 'Times New Roman',serif; color: black;\"\u003e(IU/L)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.0pt; border-top: solid #666666 1.0pt; border-left: none; border-bottom: solid #666666 1.5pt; border-right: solid #666666 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 48.2pt;\" width=\"84\"\u003e\n\u003cp style=\"margin-bottom: 10.0pt; line-height: 115%; tab-stops: center 3.25in left 387.5pt right 6.5in;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 115%; font-family: 'Times New Roman',serif; color: black;\"\u003eFGF23 (pg/ml)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 4.35pt;\"\u003e\n\u003ctd style=\"width: 79.35pt; border: solid #666666 1.0pt; border-top: none; background: #CCCCCC; padding: 0in 5.4pt 0in 5.4pt; height: 4.35pt;\" width=\"106\"\u003e\n\u003cp style=\"margin-bottom: 10.0pt; line-height: 150%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: black;\"\u003eControl\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 61.3pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; background: #CCCCCC; padding: 0in 5.4pt 0in 5.4pt; height: 4.35pt;\" width=\"82\"\u003e\n\u003cp style=\"margin-bottom: 10.0pt; line-height: 150%; tab-stops: center 3.25in left 387.5pt right 6.5in;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: black;\"\u003e89.25\u0026plusmn;3.95\u003c/span\u003e\u003csup\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: red;\"\u003ea\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 75.35pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; background: #CCCCCC; padding: 0in 5.4pt 0in 5.4pt; height: 4.35pt;\" width=\"100\"\u003e\n\u003cp style=\"margin-bottom: 10.0pt; line-height: 150%; tab-stops: center 3.25in left 387.5pt right 6.5in;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: black;\"\u003e60.76\u0026plusmn;5.90\u003c/span\u003e\u003csup\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: red;\"\u003ea\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 58.1pt; border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; background: #CCCCCC; padding: 0in 5.4pt 0in 5.4pt; height: 4.35pt;\" width=\"77\"\u003e\n\u003cp style=\"margin-bottom: 10.0pt; line-height: 150%; tab-stops: center 3.25in left 387.5pt right 6.5in;\"\u003e\u003cspan style=\"font-size: 10.0pt; 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border-top: none; border-left: none; border-bottom: solid #666666 1.0pt; border-right: solid #666666 1.0pt; background: #CCCCCC; padding: 0in 5.4pt 0in 5.4pt; height: 13.9pt;\" width=\"84\"\u003e\n\u003cp style=\"margin-bottom: 10.0pt; line-height: 150%; tab-stops: center 3.25in left 387.5pt right 6.5in;\"\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: black;\"\u003e62.04\u003c/span\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: black;\"\u003e\u0026plusmn;3.78\u003c/span\u003e\u003csup\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Times New Roman',serif; color: red;\"\u003ea\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: justify; line-height: normal; tab-stops: 51.0pt;\"\u003e\u003cspan style=\"color: #000000;\"\u003e\u003csup\u003e\u003cspan style=\"font-size: 12pt; font-family: 'Times New Roman', serif;\"\u003ea \u003c/span\u003e\u003c/sup\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Times New Roman',serif;\"\u003eThere was no significant difference between the experimental groups (P\u0026lt;0.05)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: justify; line-height: normal; tab-stops: 51.0pt;\"\u003e\u003cspan style=\"font-size: 12pt; font-family: 'Times New Roman', serif; color: #000000;\"\u003eVDD: Vitamin D deficient group\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin-bottom: .0001pt; text-align: justify; line-height: normal; tab-stops: 51.0pt;\"\u003e\u003cspan style=\"font-size: 12pt; font-family: 'Times New Roman', serif; color: #000000;\"\u003eVDD+P: Vitamin D deficient group treated with Paricalcitol\u003c/span\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"FGF23, vitamin D deficiency, paricalcitol","lastPublishedDoi":"10.21203/rs.2.18457/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.2.18457/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: We conducted this study to discover changes of serum FGF23 in non-uremic rat model of vitamin D deficiency without secondary hyperparathyroidism using paricalcitol. \u003c/p\u003e\u003cp\u003eMethods: 30 adult male rats weighting 300±20 grams were enrolled. They were divided into three groups of 10 rats including Control, Vitamin D deficient(VDD), and Vitamin D deficient diet treated with paricalcitol(VDD+P). Serum biochemical were checked twice, at baseline and after the 22nd day of study. \u003c/p\u003e\u003cp\u003eResults: There was no significant difference in baseline laboratory data between groups. At the end of the study, 1,25(OH)D3 was reduced in VDD (P = 0.019) and VDD+P (P \u0026lt; 0.001) with a more significant decline in VDD+P group. Serum level of FGF23 was reduced in VDD+P group compared to the control group (P = 0.011) and VDD group (P = 0.021). serum PTH in VDD group was higher than the control and VDD+P group (P = 0.036 and P = 0.038, respectively). \u003c/p\u003e\u003cp\u003eConclusion: The present study showed that paricalcitol could reduce FGF23 in vitamin D deficient rats without any changes in serum calcium, phosphorous and fractional excretion of phosphorous, which might be due to low PTH and 1,25(OH)2 D3. \u003c/p\u003e","manuscriptTitle":"Investigating the effect of paricalcitol on serum FGF23 in vitamin D deficient rats","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2019-12-10 21:10:03","doi":"10.21203/rs.2.18457/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ba98065c-c835-41a8-abcb-b4af1208a943","owner":[],"postedDate":"December 10th, 2019","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":41069,"name":"Urology \u0026 Nephrology"},{"id":41070,"name":"Endocrinology \u0026 Metabolism"}],"tags":[],"updatedAt":"","versionOfRecord":[],"versionCreatedAt":"2019-12-10 21:10:03","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9077","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"identity":"rs-9077","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}