The <scp>FGF</scp>‐23/klotho axis and its relationship with phosphorus, calcium, vitamin D, <scp>PTH</scp>, aldosterone, severity of disease, and outcome in hospitalised foals

Kamr, Ahmed; Dembek, Katarzyna; Hildreth, Blake E.; Morresey, Peter R.; Rathgeber, Rhonda A.; Burns, T.A.; Zaghawa, Ahmed; Toribio, Ramiro E.

doi:10.1111/evj.12946

Cited by 9 publications

(6 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…P in serum has been considered a marker of disease severity and likelihood of mortality in hospitalised foals [41]. Although in this study P in saliva did not correlate with P in plasma, it correlated in saliva with the SIRS score.…”

Section: Discussioncontrasting

confidence: 70%

Changes in saliva analytes in equine acute abdominal disease: a sialochemistry approach

et al. 2019

View full text Add to dashboard Cite

Background The biochemical components of saliva can change in certain pathologies in horses, for example in acute abdominal disease. The aim of this study was (1) to evaluate if a panel of biochemical analytes usually used in serum can be measured in saliva of horses and (2) to study the possible changes of these biochemical analytes in saliva of horses affected by acute abdominal disease. A panel of 23 analytes was analytically validated in saliva of horses and possible changes in these analytes in a pilot study with six healthy horses and six horses with acute abdominal disease were evaluated. The analytes with significant changes were then evaluated in a larger population of 20 healthy and 37 diseased horses. Results Seven analytes showed significant increases in the pilot study which were confirmed in the larger population. The analytes which showed significant changes, and their median fold increase and significance shown in the larger population were salivary γ-glutamyl transferase (gGT, 2.3 fold, P = 0.001), creatine kinase (CK, 6.2 fold, P < 0.001), urea (2.3 fold, P = 0.001), total bilirubin (2.6 fold, P < 0.001), total proteins (3.2 fold, P < 0.001), phosphorus (P, 4.5 fold, P < 0.001) and alpha-amylase (sAA, 8.5 fold, P < 0.001). Total proteins, P and sAA showed sensitivities higher than 70% at their optimal cut-off points and a specificity of 100% in differentiating between healthy horses and those with acute abdominal disease. Conclusions A panel of 23 biochemical analytes can be measured in saliva of horses, where gGT, CK, urea, total bilirubin, total protein, P and sAA levels are raised in horses with acute abdominal disease. Electronic supplementary material The online version of this article (10.1186/s12917-019-1933-6) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussioncontrasting

confidence: 70%

Changes in saliva analytes in equine acute abdominal disease: a sialochemistry approach

et al. 2019

View full text Add to dashboard Cite

show abstract

“…However, CLP was associated with increased serum creatinine, reflecting the CLP-induced decline in kidney function. FGF23 signaling requires the presence of the co-receptor Klotho [ 25 , 30 – 32 ] and there is convincing evidence that renal Klotho protein expression is reduced in septic patients with AKI [ 101 ], in septic foals [ 102 ], and in experimental sepsis models [ 101 , 103 – 106 ]. Similarly, we found diminished renal Klotho expression in female CLP mice.…”

Section: Discussionmentioning

confidence: 99%

The bone is the major source of high circulating intact fibroblast growth factor-23 in acute murine polymicrobial sepsis induced by cecum ligation puncture

et al. 2021

View full text Add to dashboard Cite

Fibroblast growth factor-23 (FGF23), a bone-produced hormone, plays a critical role in mineral homeostasis. Human diseases associated with excessive intact circulating FGF23 (iFGF23) result in hypophosphatemia and low vitamin D hormone in patients with normal kidney function. In addition, there is accumulating evidence linking FGF23 with inflammation. Based on these studies and the frequent observation of hypophosphatemia among septic patients, we sought to elucidate further the relationship between FGF23 and mineral homeostasis in a clinically relevant murine polymicrobial sepsis model. Medium-severity sepsis was induced by cecum ligation puncture (CLP) in adult CD-1 mice of both sexes. Healthy CD-1 mice (without CLP) were used as controls. Forty-eight hours post-CLP, spontaneous urine was collected, and serum, organs and bones were sampled at necropsy. Serum iFGF23 increased ~20-fold in CLP compared to control mice. FGF23 protein concentration was increased in the bones, but not in spleen or liver of CLP mice. Despite the ~20-fold iFGF23 increase, we did not observe any significant changes in mineral homeostasis or parathyroid hormone levels in the blood of CLP animals. Urinary excretion of phosphate, calcium, and sodium remained unchanged in male CLP mice, whereas female CLP mice exhibited lower urinary calcium excretion, relative to healthy controls. In line with renal FGF23 resistance, expression of phosphate-, calcium- and sodium-transporting proteins did not show consistent changes in the kidneys of male and female CLP mice. Renal expression of the co-receptor αKlotho was downregulated in female, but not in male CLP mice. In conclusion, our data demonstrate that the dramatic, sex-independent rise in serum iFGF23 post-CLP was mainly caused by an upregulation of FGF23 secretion in the bone. Surprisingly, the upsurge in circulating iFGF23 did not alter humoral mineral homeostasis in the acutely septic mice. Hence, the biological function of elevated FGF23 in sepsis remains unclear and warrants further studies.

show abstract

“…The authors observed that vitamin D deficiency combined with hypocalcemia, hyperphosphatemia, and high PTH concentrations in septic foals may point to PTH resistance being associated with the development of these abnormalities [129]. The group goes on further to identify FGF23/klotho imbalances as contributors to disease progression in the equine neonate [130].…”

Section: Horsesmentioning

confidence: 99%

Vitamin D Metabolism and Profiling in Veterinary Species

2020

View full text Add to dashboard Cite

The demand for vitamin D analysis in veterinary species is increasing with the growing knowledge of the extra-skeletal role vitamin D plays in health and disease. The circulating 25-hydroxyvitamin-D (25(OH)D) metabolite is used to assess vitamin D status, and the benefits of analysing other metabolites in the complex vitamin D pathway are being discovered in humans. Profiling of the vitamin D pathway by liquid chromatography tandem mass spectrometry (LC-MS/MS) facilitates simultaneous analysis of multiple metabolites in a single sample and over wide dynamic ranges, and this method is now considered the gold-standard for quantifying vitamin D metabolites. However, very few studies report using LC-MS/MS for the analysis of vitamin D metabolites in veterinary species. Given the complexity of the vitamin D pathway and the similarities in the roles of vitamin D in health and disease between humans and companion animals, there is a clear need to establish a comprehensive, reliable method for veterinary analysis that is comparable to that used in human clinical practice. In this review, we highlight the differences in vitamin D metabolism between veterinary species and the benefits of measuring vitamin D metabolites beyond 25(OH)D. Finally, we discuss the analytical challenges in profiling vitamin D in veterinary species with a focus on LC-MS/MS methods.

show abstract

The FGF‐23/klotho axis and its relationship with phosphorus, calcium, vitamin D, PTH, aldosterone, severity of disease, and outcome in hospitalised foals

Cited by 9 publications

References 44 publications

Changes in saliva analytes in equine acute abdominal disease: a sialochemistry approach

Changes in saliva analytes in equine acute abdominal disease: a sialochemistry approach

The bone is the major source of high circulating intact fibroblast growth factor-23 in acute murine polymicrobial sepsis induced by cecum ligation puncture

Vitamin D Metabolism and Profiling in Veterinary Species

Contact Info

Product

Resources

About