Bisphosphonates and bone mineral density in patients with end-stage kidney disease and renal transplants: A 15-year single-centre experience.

Chronic Kidney Disease Stage 5 (CKD-5) imparts a 4-fold increase in minimal trauma fracture with a substantial increase in mortality following hip fracture. Bone disease in CKD is complex, characterised by abnormal levels of PTH, calcium, phosphate, ALP, and vitamin D, manifesting as a condition known as CKD-Mineral and Bone Disorder (CKD-MBD). While bisphosphonates (BPs) are widely used in the management of osteoporosis, their therapeutic role when end-stage renal function and bone disease co-exist remains unclear. This 15-year retrospective cohort study examines the long-term use of BPs in CKD-4 and -5 patients receiving no renal replacement therapy, haemodialysis and renal transplant in a tertiary centre in Sydney, Australia. In multivariate regression adjusting for age, baseline bone mineral density (BMD) and history of fracture, BP use was associated with net gain in lumbar spine bone density in renal transplant recipients over a mean treatment period of 3.5 years (net annual BMD gain of 0.039 g/cm2, p = 0.005). No such benefit was seen in hip BMD in CKD subjects. Regardless of transplant status, CKD patients treated with BPs had no improvement in hip BMD with a general decline in hip BMD across both groups during the study period (hip BMD: transplant recipients decline 0.024 ± 0.81 g/cm2, non-transplant CKD patients decline 0.055 ± 0.84 g/cm2). BP therapy did not result in significant changes in biochemical parameters (ALP, PTH, and phosphate) and no serious adverse effects were detected in association with BP use. In particular, kidney function was not affected by BPs post-transplant (eGFR = 43 ± 29 ml/min/1.73 m2, p = 0.80). BPs preserved lumbar spine bone density in kidney transplant recipients but did not prevent declines in hip bone mineral density in either transplant patients or those with CKD-4 and -5. Summary: There remains a lack of clarity of the risks vs. benefits of bone-sparing pharmacotherapy in chronic kidney disease Stages 4 and 5. This single-centre 15-year retrospective data analysis showed that bisphosphonates are not associated with any detectable serious adverse effects in CKD-4 and -5 and effective at mitigating lumbar spine bone loss in kidney transplant patients.

Swim performance and energy homeostasis in spottail shiner (Notropis hudsonius) collected downstream of a uranium mill.

The Key Lake uranium milling operation (Saskatchewan, Canada) releases complex effluent into the local watershed. The objective of the current study was to investigate whether fish from an effluent-receiving waterbody exhibited differences in swimming performance and energy homeostasis compared to fish from a local reference site. Juvenile spottail shiner (Notropis hudsonius) were collected from a lake downstream of the uranium mill, and compared to fish collected from a nearby reference lake. Critical swimming speed (U(crit); fatigue velocity), tail beat frequency, and tail amplitude did not differ significantly when comparing fish collected from the exposure lake and reference lake. Captured shiner used in swim tests were considered fatigued, and metabolic endpoints were compared between this group and non-fatigued fish, which were treated similarly but not subjected to swim tests. In both non-fatigued and fatigued shiner, liver glycogen was significantly greater in fish collected from the exposure lake compared to the reference lake. However, it is unclear if this effect, and others related to condition, were the result of contaminant exposure or other environmental factors. While there were no differences in plasma lactate, hematocrit or liver triglycerides in non-fatigued fish between sites, only fatigued reference fish had increased lactate and hematocrit and decreased triglycerides. In non-fatigued fish, plasma glucose did not significantly differ between sites, but significantly decreased after swimming only in fish from the exposure lake. In summary, shiner from the exposure site demonstrated similar swim endurance and possessed greater energy stores despite metabolic alterations compared to shiner from the reference site. Therefore, because fish collected downstream of the uranium mill operation had similar swimming ability as fish from the reference lake, U(crit) test results presented here may not reflect or be indicative of metabolic effects of complex effluent exposure.

Evaluating the trophic transfer of selenium in aquatic ecosystems using caged fish, X-ray absorption spectroscopy and stable isotope analysis.

This research evaluated the dominant exposure pathways with regard to the bioaccumulation and trophic transfer of selenium (Se) in caged small-bodied fish inhabiting the receiving waters of a uranium-processing mill in northern Saskatchewan, Canada. A 21-day cage study was conducted using wild naïve lake chub (Couesius plumbeus) collected from a reference lake and caged in a reference and an exposure lake downstream of the mill discharge. Caged fish were fed commercially produced Chironomus spp. diets of 1.5 (basal - commercial food) and 5.5 (lab reared in Se-spiked water) µgSe/g (dry weight) at a feeding ration of 10 percent percent body weight/day. Lake chub fed the Se-spiked diet and caged in the reference lake showed increased whole-body Se concentrations compared to chub fed the basal diet after 21 days. Lake chub caged in the exposure lake from both the elevated Se and basal diet groups had significantly greater whole-body Se concentrations compared to the reference lake, and were not significantly different from each other. The use of stable carbon (C), nitrogen (N), and sulphur (S) isotope analyses indicated that alternate benthic food sources native to the exposure lake were likely consumed in conjunction with the controlled diets. Stable isotope analysis of both wild and caged lake chub indicated that the N and S isotopic signatures decreased with increasing Se exposure, which was reflective of the differences in isotopic signatures of the food sources. Dose-dependent substitution of Se for S in methionine as a consequence of dietary Se exposure was illustrated by a decreasing whole-body S isotope signature and an increasing proportion of selenomethionine-like compounds (as measured by synchrotron-based X-ray absorption spectroscopy) with increasing Se exposure. Speciation results from caged lake chub indicated that Se substituted for S in methionine was the dominant Se species found in caged lake chub exposed to dietary sources of Se.

Selenium uptake and speciation in wild and caged fish downstream of a metal mining and milling discharge.

The aim of this research was to evaluate the dominance of the feeding pathway with respect to selenium (Se) uptake and speciation in fish inhabiting the receiving waters downstream of a uranium processing mill in northern Saskatchewan, Canada. The experimental design included analysis of Se in the predominant fish species located in the study area, a caging validation study using wild, naïve (i.e., collected from a reference lake) lake chub (Couesius plumbeus) and spottail shiner (Notropis hudsonius), and a 21-day feeding cage study using wild naïve lake chub. Three exposure lakes located downstream of the uranium mill and one reference lake situated in an adjacent watershed were studied to investigate a gradient of Se exposure. Lake chub were identified as more suitable candidates for caging due to higher survival and condition factor at the completion of the 21-day trial. Analytical results indicated that lake chub caged in the exposure lakes had significantly greater whole-body Se concentrations after 21 days compared to fish caged in the reference lake. Selenium speciation results (obtained using X-ray absorption spectroscopy) from wild and caged lake chub indicated that organic Se modeled as selenomethionine was the dominant form of Se found in both wild and caged lake chub from the exposure lakes, and that selenomethionine (R-Se-R) acts as a marker of bioavailable Se exposure.

The phytopathogenic fungus Alternaria brassicicola: phytotoxin production and phytoalexin elicitation.

The metabolites and phytotoxins produced by the phytopathogenic fungus Alternaria brassicicola (Schwein.) Wiltshire, as well as the phytoalexins induced in host plants, were investigated. Brassicicolin A emerged as the most selective phytotoxic metabolite produced in liquid cultures of A. brassicicola and spirobrassinin as the major phytoalexin produced in infected leaves of Brassica juncea (whole plants). In detached infected leaves of B. juncea, the main component was N'-acetyl-3-indolylmethanamine, the product of detoxification of the phytoalexin brassinin by A. brassicicola. In addition, the structure elucidation of three hitherto unknown metabolites having a fusicoccane skeleton was carried out and the antifungal activity of several plant defenses against A. brassicicola was determined.