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

BACKGROUND: Fibroblast growth factor-23 (FGF-23) and klotho are key regulators of vitamin D and parathyroid hormone (PTH) synthesis as well as phosphorus and calcium homeostasis; however, information on the FGF-23/klotho axis in healthy and hospitalised foals is lacking. OBJECTIVES: The aims of this study were to measure serum FGF-23 and klotho concentrations and determine their association with serum phosphorus, total calcium (TCa), vitamin D metabolite [25(OH)D, 1,25(OH)2 D], PTH, and aldosterone concentrations, disease severity, and mortality in hospitalised foals. STUDY DESIGN: Prospective, multicentre, cross-sectional study. METHODS: A total of 91 foals ≤72 h old were classified as hospitalised (n = 81; 58 septic; 23 sick non-septic [SNS]) and healthy (n = 10). Blood samples were collected on admission. Hormone concentrations were determined by immunoassays. RESULTS: Serum FGF-23, PTH, phosphorus, and aldosterone concentrations were higher while klotho, 25(OH)D, 1,25(OH)2 D, and TCa concentrations were lower in septic and SNS compared to healthy foals (P<0.05). In hospitalised and septic foals, increased FGF-23 and aldosterone concentrations were associated with high phosphorus and PTH but not with TCa and vitamin D metabolite concentrations. Hospitalised foals with the highest FGF-23 and lowest klotho concentrations were more likely to die (odds ratio (OR): 3.3; 95% confidence interval (CI): 1.1-10.3 and OR: 3.1; CI: 1.1-8.0, respectively). MAIN LIMITATIONS: Blood gas, ionised calcium, blood culture information not being available for many foals, and use of the sepsis score to classify hospitalised foals. CONCLUSIONS: Imbalances in the FGF-23/klotho axis may contribute to mineral dyshomeostasis and disease progression in critically ill foals. Elevated FGF-23 and reduced klotho, together with high phosphorus and PTH concentrations suggests FGF-23 resistance. FGF-23 and klotho are good markers of disease severity and likelihood of mortality in hospitalised foals. Aldosterone may influence phosphorus and PTH dynamics in hospitalised foals. Routine measurement of phosphorus concentrations in sick foals is recommended.

Presumptive nonthyroidal illness syndrome in critically ill foals.

REASONS FOR PERFORMING THE STUDY: Hypothalamic-pituitary-thyroid (HPT) axis dysfunction is associated with morbidity and mortality in critically ill people. To date, investigations of HPT axis in critically ill foals are limited. OBJECTIVES: To document the occurrence of low thyroid hormone concentrations (presumptive nonthyroidal illness syndrome; NTIS) in critically ill newborn foals and investigate whether NTIS is associated with severity of disease and outcome. HYPOTHESIS: NTIS occurs frequently in foals with sepsis and is associated with sepsis score and outcome. Reverse T3 (rT3) concentrations will be increased in septic foals and highest in nonsurvivors. METHODS: Thyroid hormones (total and free thyroxine [TT4 and fT4], total and free tri-iodothyronine [TT3 and fT3], reverse T3 [rT3]) were prospectively measured in healthy, sick nonseptic and septic foals. Clinical and laboratory information was retrieved from the medical records. Hormones were measured by validated radioimmunoassays. RESULTS: Concentrations of all thyroid hormones except rT3 (P = 0.69) were decreased in septic and sick nonseptic foals (P < 0.01). Reductions in hormone concentrations were associated with an increased sepsis score (P < 0.01). Nonsurviving septic foals had lower TT4, fT4, TT3 and fT3 concentrations than surviving septic foals (P < 0.01). rT3 concentrations were higher in nonsurviving septic prematurefoals than surviving septic premature foals (P < 0.05). CONCLUSIONS: NTIS (euthyroid sick syndrome) is frequently observed in critically ill and premature foals, and associated with severity of disease and mortality. POTENTIAL RELEVANCE: More research is needed to better understand the mechanism of this finding and determine whether manipulation of the HPT axis or thyroid replacement therapy could be beneficial.

Parasite field study in central Kentucky on thoroughbred foals (born in 2004) treated with pyrantel tartrate daily and other parasiticides periodically.

Foals (79), born in 2004 on three thoroughbred horse farms (C, M, and S) in central Kentucky, were fed pyrantel tartrate daily, beginning at about 3 months of age. In addition, other parasiticides [fenbendazole (FBZ), ivermectin (IVM) alone or with praziquantel (PRAZ), oxibendazole (OBZ), pyrantel pamoate (PRT), and moxidectin (MOX)] were given periodically. All treatments were administered by farm personnel. Over a 14-month period, from May 2004 to July 2005, collections (n=989) of feces were made from the foals for determination of presence of internal parasite eggs/oocysts by qualitative and/or quantitative methods. Conclusions on drug activity are based necessarily on considering the combined effect of pyrantel tartrate and the other compounds. For small strongyles, this was related to which specific additional compound was given. Based on the percentage of foals with strongyle-egg-positive feces and/or the level of eggs per gram of feces (EPG) counts for the foals after treatment, drug activity on small strongyles was highest to lowest for MOX, IVM and IVM/PRAZ, FBZ, OBZ, PRT, and FBZ (2x for 5 days). The macrocyclic lactones (MOX and IVM) were highly superior to the other compounds. Some of the strongyle counts were high (over 2,000), especially on one farm (S), during periods when foals received only pyrantel tartrate, but a few days after administration of therapeutic dose rates of the drugs IVM or MOX, they were negative or very low. Ascarid eggs were present in feces of three foals after treatment with a combination of IVM and PRAZ. The qualitative method was more efficient than the quantitative method in detection of ascarid and strongyle eggs in the feces. Prevalence of eggs of ascarids (Parascaris equorum) was low (0, 4, and 31%), of strongyles high (80, 100, and 100%), of Strongyloides westeri very low (only one infected foal), and oocysts of Eimeria leuckarti medium to high (36, 41, and 85%) for the three farms, C, M, and S, respectively. It is uncertain whether the low ascarid prevalence was from activity of pyrantel tartrate and/or the other drugs or to a limited source of infective eggs.