Attenuation of Bone Mineral Density Decline During Anemia Treatment With Methenolone Acetate in Myelodysplastic Syndrome.

In an aging society, addressing the risks and management of osteoporotic fractures is critical to reduce mortality. Similarly, the morbidity of chronic kidney disease and myelodysplastic syndrome increases with aging. The association between chronic kidney disease and fractures is well understood; however, recent reports have indicated an increased risk of incident osteoporosis in patients with prevalent myelodysplastic syndrome. In this case report, we present an older man with stage 4 chronic kidney disease complicated by myelodysplastic syndrome and progressive decline in bone mineral density. He was treated with methenolone acetate and darbepoetin for anemia caused by myelodysplastic syndrome. During anemia treatment, the decline in bone mineral density was attenuated overtime. The case findings suggest the potential association between the use of methenolone acetate as a synthetic anabolic steroid and attenuated decline in bone mineral density.

Romosozumab improves low bone mineral density in a postmenopausal woman undergoing chronic hemodialysis and treated with a calcium-sensing receptor agonist.

Preventing osteoporotic fractures is an issue requiring urgent attention to reduce mortality. However, unlike chronic kidney disease-mineral and bone disorder (CKD-MBD), osteoporosis is inadequately addressed in patients undergoing chronic dialysis. In fact, little is known about the proper use of anti-osteoporotic drugs for patients with CKD-MBD. A recent study showed that romosozumab, an anti-osteoporotic drug, increased bone mineral density in osteoporotic patients on hemodialysis without clinically significant adverse events. However, the efficacy and safety of coadministering romosozumab with a calcium-sensing receptor (CaSR) agonist, a pivotal drug used in the management of CKD-MBD, remain unclear. Here, we report the case of a postmenopausal woman undergoing chronic hemodialysis and treated with add-on romosozumab for osteoporosis to CaSR agonist for secondary hyperparathyroidism. After 1 year of treatment, her bone mineral density increased; however, hypocalcemia occurred during the treatment. These results suggest that the concomitant use of romosozumab with CaSR agonist may be a possible treatment option for severe osteoporosis in postmenopausal women receiving chronic hemodialysis with a high fracture risk, but serum calcium levels should be monitored closely and those at risk of ectopic calcification might not be ideal candidates for such treatment.

Central volume shift in acute heart failure revealed by blood volume monitoring during haemodialysis.

Central volume shift is one of the major pathophysiological mechanisms of acute pulmonary oedema in acute heart failure (AHF). Pathological vasoconstriction results in central volume shift; however, its onset and course have been rarely detected or recorded in clinical practice. We report an exceptional case of AHF developing during haemodialysis, with marked blood pressure (BP) elevation and paradoxical repeated reduction in blood volume (BV) detected by real-time BV monitoring, accompanied by worsening dyspnoea. This inverse correlation of BV and BP during haemodialysis indicates that the theoretical central volume shift was captured in real-world AHF.

Physical Exercise Improves Cognitive Function in Older Adults with Stage 3-4 Chronic Kidney Disease: A Randomized Controlled Trial.

INTRODUCTION: Patients with chronic kidney disease (CKD) exhibit a higher probability of having cognitive impairment or dementia than those without CKD. The beneficial effects of physical exercise on cognitive function are known in the general older population, but more research is required in older adults with CKD. METHODS: Eighty-one outpatients (aged ≥65 years) with CKD stage G3-G4 were assessed for eligibility. Among them, 60 were randomized (single-center, unblinded, and stratified) and 53 received the allocated intervention (exercise n = 27, control n = 26). Patients in the exercise group undertook group-exercise training at our facility once weekly and independent exercises at home twice weekly or more, for 24 weeks. Patients in the control group received general care. General and specific cognitive functions (memory, attention, executive, and verbal) were measured, and differences in their scores at baseline and at the 24-week follow-up visit were assessed between the 2 groups. RESULTS: Forty-four patients completed the follow-up at 24 weeks (exercise n = 23, control n = 21). Patients in the exercise group showed significantly greater changes in Wechsler Memory Scale-Revised Logical Memory delayed recall (exercise effect: 2.82, 95% CI: 0.46-5.19, p = 0.03), and immediate and delayed recall (exercise effect: 5.97, 95% CI: 1.13-10.81, p = 0.02) scores than those in the control group. CONCLUSIONS: The 24-week exercise intervention significantly improved the memory function in older adults with pre-dialysis CKD. This randomized controlled trial suggests that physical exercise is a useful nonpharmacological strategy for preventing cognitive decline in these patients.

Welfare receipt and the risk of vitamin D deficiency in Japanese patients on maintenance hemodialysis: a cross-sectional, retrospective study.

BACKGROUND: Vitamin D deficiency is often observed in patients undergoing maintenance hemodialysis and is associated with significantly increased risk of overall mortality. Despite reports of poor nutrition/intake, vitamin D status among patients on maintenance hemodialysis receiving welfare remains unknown. This study investigated the vitamin D status in welfare recipients undergoing maintenance hemodialysis. METHODS: This cross-sectional study investigated vitamin D status among 106 outpatients undergoing maintenance hemodialysis at two medical facilities in Japan. Patients were divided into welfare and non-welfare groups based on their status as of September 2018. Patients were divided into two categories: serum vitamin D deficiency, defined as serum 25(OH)D concentrations < 12 ng/mL, or non-deficiency. Vitamin D deficiency was used as a dependent variable, while welfare receipt was used as the main predictor variable. RESULTS: Mean [± standard deviation] patient age, median [interquartile range] body mass index, and hemodialysis duration were 66.9 [± 10.8] years, 21.5 [19.6, 24.3] kg/m2, and 7.9 [2.9, 12.3] years, respectively. Among 106 patients, 45 were women (42.5%) and 16 (15.1%) were receiving welfare. The welfare group had a higher diabetes prevalence (P = 0.003) and significantly lower median serum 25-hydroxyvitamin D concentrations (11.5 [8.7, 14.0] vs. 14.8 [11.2, 19.9] ng/mL, P = 0.005). Multiple logistic regression analysis revealed that welfare receipt was a significant risk factor for vitamin D deficiency (odds ratio [95% confidence interval], 4.41 [1.08, 18.07]). CONCLUSIONS: Welfare recipients undergoing maintenance hemodialysis are at significantly increased risks of vitamin D deficiency compared with patients not receiving welfare.

Bone responsiveness to parathyroid hormone is negatively associated with parathyroid hormone-lowering drug use in patients undergoing hemodialysis: a cross-sectional study.

BACKGROUND: Parathyroid hormone (PTH) acts on bone to indirectly increase the number and activity of osteoclasts. Thus, PTH has a stimulatory effect on bone resorption and upregulates bone turnover. However, the responsiveness of bone to PTH varies widely among patients receiving dialysis. In fact, relative to the serum PTH level, the level of serum tartrate-resistant acid phosphatase-5b (TRACP-5b), a bone resorption marker derived from osteoclasts, varies as well. This study aimed to examine factors related to bone responsiveness to PTH in patients undergoing chronic hemodialysis (HD). METHODS: This study included patients receiving chronic HD in Kawasaki Municipal Tama Hospital (Kanagawa, Japan) and Yonaha Medical Clinic (Okinawa, Japan) and excluded patients who received HD for less than 6 months, those who received a combination of HD and peritoneal dialysis, and those who had cancer bone metastases or myeloma. The TRACP-5b/intact PTH (iPTH) ratio was created as an index of bone responsiveness to PTH, categorized into tertiles (low, medium, and high), and a cross-sectional study was conducted. P < 0.05 indicated statistically significant differences. RESULTS: One hundred and six patients were analyzed. Age (P = 0.010), body mass index (BMI) (P = 0.003), use of calcium-sensing receptor (CaSR) agonists (P = 0.008), use of vitamin D receptor activators (VDRAs) (P = 0.012), plasma iPTH level (P < 0.001), serum 1,25(OH)2D level (P = 0.003), and serum TRACP-5b level (P < 0.001) were significantly different among the three categories. In the single linear regression analysis, age (P = 0.016), corrected serum calcium level (P = 0.007), and ln [1,25(OH)2D] (P = 0.044) showed a significant positive correlation with ln [TRACP-5b/iPTH], whereas BMI (P = 0.026), use of CaSR agonists (P = 0.001), use of VDRAs (P = 0.009), and serum phosphorus level (P = 0.018) showed a significant negative correlation. Upon conducting multiple linear regression analysis incorporating significant variables in the single linear regression analysis, a significant negative correlation was observed between the TRACP-5b/iPTH ratio and intravenous administration of a CaSR agonist (etelcalcetide) and/or a VDRA (calcitriol or maxacalcitol) in all the adjusted models. CONCLUSIONS: Bone responsiveness to PTH is negatively correlated with the intravenous administration of a CaSR agonist and/or a VDRA in patients undergoing chronic HD.

Calcium-Alkali Syndrome Associated with Hypoparathyroidism Following Total Thyroidectomy.

BACKGROUND: Patients with permanent postsurgical hypoparathyroidism, a complication of total thyroidectomy, often require high calcium supplementation with vitamin D to maintain serum calcium levels. The epidemiology of calcium-alkali syndrome (CAS) in patients with hypoparathyroidism after total thyroidectomy remains unclear. This study aimed to investigate the incidence of hypercalcemia, renal impairment, metabolic alkalosis, and CAS in patients treated for presumed hypoparathyroidism after total thyroidectomy. METHODS: Twenty-seven patients with neck cancers who underwent total thyroidectomy without parathyroid autotransplantation between January 2010 and October 2013 at our hospital were consecutively included. All patients received calcium lactate and alfacalcidol for postsurgical hypocalcemia. We defined hypercalcemia as a corrected serum calcium level (cCa) ≥10.5 mg/dL, metabolic alkalosis as a difference in serum sodium and serum chloride ([sNa-sCl]) ≥39 mEq/L, and renal impairment as a ≥50% increase in serum creatine and/or ≥35% decrease in estimated glomerular filtration rate (eGFR) compared to baseline. RESULTS: cCa peaked (11.1 ± 1.5 mg/dL) at a median of 326 days (interquartile range 78-869) after surgery. At peak cCa, [sNa-sCl] was significantly higher (p < 0.01), and eGFR was significantly lower (p < 0.01) than that at baseline. Fifteen patients (55.6%) had hypercalcemia, 19 (70.3%) had alkalosis, 12 (44.4%) had renal impairment, and 9 (33.3%) had CAS. Patients with CAS (mean age 67.1 ± 10.8 years) were older than those without CAS (56.7 ± 13.6 years, p = 0.06). The mean dose of alfacalcidol in the CAS group (3.1 ± 1.2 µg/day) was significantly larger than that in the non-CAS group (2.1 ± 1.0 µg/day, p = 0.03). CONCLUSIONS: This retrospective study reveals the high incidence of CAS in patients with hypoparathyroidism after total thyroidectomy. Furthermore, these findings suggest that the serum calcium level, acid-base balance, and renal function should be closely monitored in patients with postsurgical hypoparathyroidism who receive large doses of active vitamin D.

Hexavacant γ-Dawson-type phosphotungstates supporting an edge-sharing bis(square-pyramidal) {O2M(µ3-O)2(µ-OAc)MO2} core (M = Mn2+, Co2+, Ni2+, Cu2+, or Zn2+).

In aqueous media, the introduction of additional metal species into polyoxometalates (POMs) with multiple vacant sites, such as a hexavacant Dawson-type phosphotungstate, which is of interest for the synthesis of novel metal oxide clusters, is generally difficult because they easily undergo self-condensation and/or structural decomposition. In this study, we succeeded in developing a novel synthetic method to obtain metal-substituted γ-Dawson-type phosphotungstate monomers by introducing metal species into an organic solvent-soluble lacunary phosphotungstate, TBA4H10[α-P2W12O48] (I) (TBA = tetra-n-butylammonium), in organic media. The reaction of I, which possessed two types of vacant sites, i.e. middle and edge sites, with divalent metal species such as Mn2+, Co2+, Ni2+, Cu2+, or Zn2+ in acetonitrile afforded a series of isostructural POMs M2 (TBA5[γ-P2W12O44M2(OAc)(CH3CONH)2]·nH2O·mCH3CN; M = Mn2+, Co2+, Ni2+, Cu2+, or Zn2+; OAc = acetate) with an edge-sharing bis(square-pyramidal) {O2M(µ3-O)2(µ-OAc)MO2} core. The bis(square-pyramidal) core was selectively placed at the middle site of the hexavacant lacunary phosphotungstate, and the two metals in the core were bridged by two phosphate units and one acetate species. Meanwhile, the edge sites were capped by acetimidate ligands, which protect the reactive lacunary POM from self-condensation. To the best of our knowledge, this is the first report describing the synthesis and characterization of metal-substituted hexavacant γ-Dawson-type POM monomers.