Evolution of cooperation in multiplex networks through asymmetry between interaction and replacement.

Cooperation is the foundation of society and has been the subject of numerous studies over the past three decades. However, the mechanisms underlying the spread of cooperation within a group are not yet fully comprehended. We analyze cooperation in multiplex networks, a model that has recently gained attention for successfully capturing certain aspects of human social connections. Previous studies on the evolution of cooperation in multiplex networks have shown that cooperative behavior is promoted when the two key processes in evolution, interaction and strategy replacement, are performed with the same partner as much as possible, that is, symmetrically, in a variety of network structures. We focus on a particular type of symmetry, namely, symmetry in the scope of communication, to investigate whether cooperation is promoted or hindered when interactions and strategy replacements have different scopes. Through multiagent simulations, we found some cases where asymmetry can promote cooperation, contrasting with previous studies. These results hint toward the potential effectiveness of not only symmetrical but also asymmetrical approaches in fostering cooperation within particular groups under certain social conditions.

Serum Fibroblast Growth Factor 23 Levels are Associated with Vascular Smooth Muscle Dysfunction in Type 2 Diabetes.

AIM: Increased level of serum fibroblast growth factor 23 (FGF23) is a hallmark of abnormal phosphate metabolism in patients with chronic kidney disease (CKD) and is recently shown to be associated with the risk of cardiovascular disease even in those without CKD. This study investigated the association between serum FGF23 levels and vascular function in patients with type 2 diabetes. METHODS: This was a cross-sectional study involving 283 Japanese patients with type 2 diabetes. Flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation (NMD) of the brachial artery were measured via ultrasonography to evaluate vascular endothelial and smooth muscle functions, respectively. Serum intact FGF23 levels were determined via a sandwich enzyme-linked immunosorbent assay. RESULTS: The median values of FMD, NMD, and serum FGF23 were 6.0%, 14.0%, and 27.3 pg/mL, respectively. The serum FGF23 levels were inversely associated with NMD but not with FMD, and the association was independent of atherosclerotic risk factors, estimated glomerular filtration rate (eGFR), and serum phosphate levels. Furthermore, the relationship between serum FGF23 levels and NMD was modified by kidney function, which was pronounced in subjects with normal kidney function (eGFR ≥ 60 mL/min/1.73 m2). CONCLUSION: Serum FGF23 levels are independently and inversely associated with NMD in patients with type 2 diabetes, particularly in those with normal kidney function. Our results indicate that FGF23 is involved in vascular smooth muscle dysfunction and that increased serum levels of FGF23 may serve as a novel biomarker for vascular smooth muscle dysfunction in patients with type 2 diabetes.

Associations of time-dependent changes in phosphorus levels with cardiovascular diseases in patients undergoing hemodialysis: results from the Japan Dialysis Active Vitamin D (J-DAVID) randomized clinical trial.

Background: While the risk of exceeding the standard range of phosphorus levels has been investigated, the impact of the degree of fluctuations has not been investigated. Methods: Data were derived from the Japan Dialysis Active Vitamin D trial, a 4-year prospective, randomized study involving 976 patients without secondary hyperparathyroidism undergoing hemodialysis in Japan. Laboratory data were collected every 6 months and the primary outcome was the time to the occurrence of cardiovascular events. The effect of time-dependent changes in phosphorus levels was assessed using a time-varying Cox proportional hazards regression model. Results: The median serum phosphorus levels at baseline and at the final observation were 4.70 mg/dl [interquartile range (IQR) 3.90-5.30] and 5.00 mg/dl (IQR 4.20-5.80), respectively. Over each 6-month period, phosphorus changes ranged from -7.1 to +6.7 mg/dl, with a median value of -0.1 to +0.3 mg/dl. During follow-up, composite cardiovascular events occurred in 103 of 964 patients. Although the P-value for the interaction between serum phosphorus level fluctuations and baseline phosphorus levels was insignificant, the following trends were observed. First, patients with relatively high initial phosphorus levels over a 6-month period showed a trend towards a higher hazard, with greater changes in the phosphorus level over the 6-month period. Second, it was suggested that oral vitamin D receptor activators could contribute to the relationship between fluctuating phosphorus levels and cardiovascular events. Conclusions: Our results suggest the importance of maintaining stable phosphorus levels, not only in the normal range, but also without fluctuations, in the risk of cardiovascular events among patients without secondary hyperparathyroidism undergoing maintenance hemodialysis.

Dialysate calcium, alfacalcidol, and clinical outcomes: A post-hoc analysis of the J-DAVID trial.

The selection of dialysate calcium concentration (D-Ca) is still controversial among chronic hemodialysis (HD) regimens. We examined the trajectories of CKD MBD parameters among the J-DAVID trial participants to see the effect of D-Ca and alfacalcidol. The trial was an open-label randomized clinical trial including 976 HD patients with intact PTH of 180 pg/mL or lower which compared the users of vitamin D receptor activator (oral alfacalcidol) and non-users over a median of 4 years. The main D-Ca used at baseline were 3.0 mEq/L in 70% and 2.5 mEq/L in 25%, respectively. The primary endpoint was the composite of fatal and non-fatal cardiovascular events and the secondary endpoint was all-cause mortality. Multivariable Cox proportional hazard regression analyses in which D-Ca was included as a possible effect modifier and serum laboratory data as time-varying covariates showed no significant effect modification for composite cardiovascular events or all-cause mortality. This post hoc analysis showed that the effects of alfacalcidol on cardiovascular outcomes were not significantly modified by D-Ca.

Effects of alfacalcidol on cardiovascular outcomes according to alkaline phosphatase levels in the J-DAVID trial.

In the Japan Dialysis Active Vitamin D (J-DAVID) trial, oral alfacalcidol numerically, but not significantly, increased the risk of cardiovascular events among patients undergoing hemodialysis. Because the cardiovascular effect of alfacalcidol could be modulated by bone turnover status, this post-hoc analysis of the J-DAVID examined how alkaline phosphatase (ALP), a more precise marker of bone turnover than parathyroid hormone (PTH), modifies the impact of alfacalcidol. The J-DAVID was a 48-month, open-label, randomized controlled trial comparing oral alfacalcidol with no vitamin D receptor activators use in terms of cardiovascular events among 976 hemodialysis patients without secondary hyperparathyroidism. This post-hoc analysis included 959 patients with available data on baseline ALP. The median [25-75th percentile] baseline ALP level was 234 [183-296] U/L. In a Cox proportional hazards model, ALP did not significantly modify the effect of alfacalcidol on the rate of cardiovascular events or all-cause death (P for effect modification = 0.54 and 0.74, respectively). The effect of alfacalcidol on time-series changes in calcium, phosphate, and intact PTH were similar across ALP subgroups. In conclusion, oral alfacalcidol did not significantly affect cardiovascular outcomes irrespective of bone turnover status.

Factors associated with atrial fibrillation in Japanese patients with type 2 diabetes mellitus: a cross-sectional study.

Aims: Atrial fibrillation (AF) increases cardiovascular complications and mortality in patients with diabetes. Diabetes is a risk factor for AF; however, risk factors for AF among patients with type 2 diabetes (T2D) remain unknown, especially among Asian people. We clarified the prevalence of AF, regardless of type (i.e., paroxysmal, persistent, or permanent) in Japanese patients with T2D and clarified factors associated with AF. Methods: This cross-sectional study was conducted at Fujiidera Municipal Hospital (Osaka, Japan). Patients with T2D (n = 899: 518 men and 381 women with a mean age ± SD of 69.0 ± 12.1 years) were included. Their electrocardiographs were checked during routine examinations between January 2017 and January 2018. A diagnosis of AF was determined from single time-point standard 12-lead electrocardiographic findings. We analyzed clinical parameters (e.g., age, sex, diabetes duration, glycated hemoglobin, body mass index, estimated glomerular filtration rate, albuminuria or proteinuria, use of biguanide, and presence of hypertension) between patients with and without AF. Results: The prevalence of AF among patients with T2D was 5.9%; it became higher as age increased and tended to be higher in men than in women. The prevalence became higher as albuminuria or proteinuria progressed and as the eGFR decreased. Multiple logistic regression analyses revealed that older age, male sex, and reduced eGFR were independently and significantly associated with the coexistence of AF. However, multiple logistic regression analysis revealed no significant relationships between AF and the presence of albuminuria or proteinuria. Conclusions: Older age, male sex, and reduced eGFR were associated with AF in Japanese patients with T2D. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-021-00563-w.

Fibroblast Growth Factor 23 as Regulator of Vitamin D Metabolism.

Fibroblast growth factor 23 (FGF23) is a hormone produced by osteocytes in bone that acts on the kidneys to regulate phosphate and vitamin D metabolism.FGF23 levels were shown to be increased in the early stage of chronic kidney disease (CKD), with a slight decline in estimated glomerular filtration rate (eGFR) even when the range was restricted to above 60 mL/min/1.73 m2, indicating that subtle phosphate load is a stimulator of FGF23 in serum. FGF23 is also known to inhibit vitamin D activation from 25-hydroxyvitamin D (25-OH-D) to 1,25-dihydroxyvitamin D [1,25(OH)2D], while it stimulates its degradation from 25-OH-D to 24,25-dihydroxyvitamin D [24,25(OH)2D]. Previously, we demonstrated a significant and negative association of serum FGF23 with serum 1,25(OH)2D and 1,25(OH)2D/25-OH-D ratio, a putative parameter for CYP27B1, and confirmed the physiological effects of FGF23 on phosphate and vitamin D metabolism in non-CKD subjects. Elevated FGF23 by itself is reported to be associated with various adverse outcomes, including left ventricular hypertrophy, endothelial dysfunction, and activation of the renin-angiotensin-aldosterone system, leading to increased mortality even in non-CKD individuals. On the other hand, our previous study showed that the impaired incremental response of serum FGF23 in response to oral phosphate load in diabetic patients can help to significantly increase serum phosphate (Yoda et al., J Clin Endocrinol Metab 97:E2036-43, 2012) and thus may contribute to progression of vascular calcification in those patients (personal observation). It is suggested that increased serum FGF23 might be an important indicator of adverse outcomes in non-CKD as well as CKD patients.

Dose-Response of Tenapanor in Patients With Hyperphosphatemia Undergoing Hemodialysis in Japan-A Phase 2 Randomized Trial.

INTRODUCTION: Simplified, but effective, hyperphosphatemia treatments with novel mechanisms of action, tolerable safety profiles, and low pill burden are needed for patients undergoing hemodialysis. Tenapanor is a calcium (Ca)-free, nonmetal, nonpolymeric drug that reduces phosphate absorption by selectively inhibiting intestinal sodium-hydrogen exchanger 3. As the serum phosphorus (P) level-lowering effect of tenapanor has not been evaluated in Japanese patients with hyperphosphatemia undergoing hemodialysis, we evaluated its efficacy and safety in this population. METHODS: This was a multicenter, phase 2, double-blind, placebo-controlled, parallel-group, dose-finding study. Change in serum P level from baseline at week 6 was the primary end point. RESULTS: Overall, 207 patients were randomized to 5 groups (placebo [n = 41] and tenapanor 5-mg taken twice daily [BID] [n = 42], 10-mg BID [n = 41], 30-mg BID [n = 42], and 30-mg BID dose-titration [n = 41]) and treated for 6 weeks. Mean changes from baseline at week 6 in serum P level were 0.64, -0.93, -1.36, -1.92, and -1.99 mg/dl in the placebo and tenapanor groups, respectively. Serum P level was significantly decreased from baseline in all tenapanor groups compared with placebo (P < 0.001, for each dose). Diarrhea was the most frequent drug-related adverse event (AE) with an incidence of 9.8%, 50.0%, 65.9%, 76.2%, and 65.9% in the respective placebo and tenapanor groups. CONCLUSION: In Japanese patients undergoing hemodialysis, tenapanor was found to have a dose-responsive, serum P level-lowering effect. Diarrhea was the most frequent drug-related AE; most cases were mild and generally tolerable. Tenapanor may become a first-in-class therapeutic agent for patients with hyperphosphatemia.

Significant Association of Diabetes With Mortality of Chronic Hemodialysis Patients, Independent of the Presence of Obesity, Sarcopenia, and Sarcopenic Obesity.

OBJECTIVES: This retrospective cohort study investigated the association of diabetes with mortality in hemodialysis patients with regard to obesity, sarcopenia, and sarcopenic obesity, along with examining the prevalence of each group and diabetes. METHODS: Muscle strength, muscle mass, and fat mass were evaluated using a hand dynamometer and dual-energy X-ray absorptiometry, respectively, in 308 chronic hemodialysis patients (age 58.0 ± 11.9 years, hemodialysis duration 6.5 ± 6.0 years, males 60.1%, diabetes 32.8%). Sarcopenia was defined according to the new criteria established by the Asian Working Group on Sarcopenia 2019. Obesity was defined by percent body fat mass (males ≥25%, females ≥35%). RESULTS: The enrolled patients were divided into the normal (38.7%), obesity (18.8%), sarcopenia (26.9%), and sarcopenic obesity (15.6%) groups. The prevalence of diabetes was significantly skewed among the 4 groups (χ2 test, P = .0057), being higher in the sarcopenic obesity group (54.2%) compared to the others (25.9-33.7%). Multivariate regression analysis revealed that diabetes was significantly and independently associated with sarcopenic obesity (odds ratio 3.495, 95% confidence interval 1.683-7.255, P = .0008) after adjustments for several cofounders, but not significantly associated with sarcopenia. During the follow-up period of 76 ± 35 months, 100 patients died. Those in the sarcopenia and sarcopenic obesity groups had significantly higher rates of all-cause mortality compared to patients in the normal and obesity groups (P = .0004, log-rank test). Furthermore, multivariate Cox proportional hazards analysis revealed that presence of diabetes was significantly associated with higher all-cause mortality in all 308 patients, after adjustments for several factors, including the presence of each group in 4 models. CONCLUSION: Sarcopenic obesity is highly prevalent in chronic hemodialysis patients. Diabetes was found to be a significant and independent contributor to the presence of sarcopenic obesity. Diabetes was shown to be a significant predictor of all-cause mortality, independent of the present normal, obesity, sarcopenia, and sarcopenic obesity groups.

Role of adiponectin in the relationship between visceral adiposity and fibroblast growth factor 23 in non-diabetic men with normal kidney function.

Fibroblast growth factor 23 (FGF23) is a key regulator of phosphate metabolism. Circulating FGF23 levels are associated with obesity, metabolic syndrome, and cardiovascular disease in the general population, but the underlying mechanism remains unclear. Therefore, we aimed to determine the associations between serum FGF23 levels and visceral adiposity as well as serum adiponectin levels in 189 adults without diabetes and with normal kidney function who were selected from the MedCity21 health examination registry. The exclusion criteria included diabetes mellitus or impaired kidney function (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2). Levels of serum FGF23 and total adiponectin, and visceral fat area (VFA) on computed tomography images were measured. Serum FGF23 levels were higher and VFA was greater, whereas serum adiponectin levels were lower in men than in women. Serum FGF23 levels positively correlated with VFA in men; they remained marginally significant after adjusting for age, eGFR, and serum levels of calcium, phosphate, intact parathyroid hormone, and 1,25-dihydroxyvitamin D. Importantly, when serum adiponectin levels were included as a covariate, serum adiponectin levels comprised an independent determinant of serum FGF23 levels in men, whereas VFA did not. In conclusion, lower serum adiponectin, rather than a greater VFA, was associated with higher serum FGF23 levels in non-diabetic men with normal kidney function. These findings suggest that adiponectin plays a role in the relationship between visceral adiposity and FGF23 in men.

Bexarotene-induced central hypothyroidism assessed by TRH stimulation test in cutaneous T-cell lymphoma patients.

Bexarotene-induced central hypothyroidism (CH), for which levothyroxine (LT4) replacement is recommended, has been shown to be caused by pituitary but not hypothalamic disorder experimentally, though the underlying mechanism in humans remains unclear. Here, the pathophysiology of bexarotene-induced CH was examined using a TRH stimulation test in cutaneous T-cell lymphoma (CTCL) patients. In this retrospective longitudinal observational study, serum TSH and free T4 (F-T4) levels were measured in 10 euthyroid patients with CTCL during 24 weeks of bexarotene treatment. TRH stimulation testing was performed following CH diagnosis, with LT4 replacement dosage adjusted to maintain F-T4 at the pre-treatment level. After one week of bexarotene administration, all 10 patients developed CH, based on combined findings of low or low-normal F-T4 with low or normal TSH levels. TSH peak response after a stimulation test at one week was reached at 30 minutes. However, that was <4 µIU/mL in all patients, indicating a blunted though not exaggerated and delayed TSH response. In eight who continued bexarotene for 24 weeks, median LT4 replacement dosage was 125 (range, 75-150) µg/day. TSH level at 30 as well as 15, 60, 90, and 120 minutes after TRH stimulation was significantly correlated with LT4 replacement dosage (ρ = -0.913, p = 0.002), whereas TSH and F-T4 basal levels at one week were not. These results suggest that pituitary hypothyroidism is responsible for bexarotene-induced CH, while TSH levels after TRH stimulation precisely reflect residual pituitary-thyroid function in patients receiving bexarotene.

Associations of cardiovascular disease and blood pressure with cognition in hemodialysis patients: The Osaka Dialysis Complication Study.

BACKGROUND: Previous studies have reported mixed results regarding the contributions of cardiovascular disease (CVD) and blood pressure (BP) to cognitive impairment in chronic kidney disease. METHODS: This was a cross-sectional study in 1213 patients on maintenance hemodialysis from 17 dialysis units in Japan. The main exposures were prior CVD and BP components including systolic BP (SBP) and diastolic BP (DBP). The outcome was low cognitive function evaluated with the Modified Mini-Mental State (3MS) examination with a cut-off level of 3MS <80. RESULTS: The median age was 67 years, median duration of dialysis was 71 months, 37% were women, 39% had diabetic kidney disease and 36% had any pre-existing CVD. Median (interquartile range) of 3MS score was 91 (82-97), and 240 patients (20%) had 3MS <80. Logistic regression analysis showed that 3MS <80 was associated with the presence of any prior CVD, particularly prior stroke. 3MS <80 was associated with lower DBP but not with SBP. When patients were stratified by the presence of prior stroke, lower DBP, higher age and lower education level were factors associated with 3MS <80 in both subgroups. In the subgroup of patients without prior stroke, diabetic kidney disease was an additional factor associated with 3MS <80. CVDs other than stroke were not associated with 3MS in either subgroup. CONCLUSIONS: Prior stroke and lower DBP were associated with 3MS <80 in hemodialysis patients. These findings support the hypothesis that these vascular factors contribute to low cognitive performance in patients undergoing hemodialysis.

Micropetrosis in hemodialysis patients.

Micropetrosis develops as a result of stagnation of calcium, phosphorus and bone fluid, which appears as highly mineralized bone area in the osteocytic perilacunar/canalicular system regardless of bone turnover of the patients. And microcracks are predisposed to increase in these areas, which leads to increased bone fragility. However, micropetrosis of hemodialysis (HD) patients has not been discussed at all. Micropetrosis area per bone area (Mp.Ar/B·Ar) and osteocyte number per micropetrosis area (Ot.N/Mp.Ar) were measured in nine HD patients with renal hyperparathyroidism (Group I), twelve patients with hypoparathyroidism within 1 year after the treatment of renal hyperparathyroidism (Group II) and seven patients suffering from hypoparathyroidism for over two years (Group III). And bone mineral density (BMD) and tissue mineral density (TMD) were calculated using µCT to evaluate bone mineral content of iliac bone of the patients. These parameters were compared among the three groups. Only Mp.Ar/B·Ar was statistically greater in Group II and III compared to Group I in the parameters of bone mineral content and micropetrosis. However, the other parameters were not statistically different among the three groups. In long-term HD patients, BMD and TMD may be modified by the causes of renal insufficiency and the treatment of renal bone disease. We concluded that Mp.Ar/B·Ar was greater in patients with long-term hypoparathyroidism than both those with short-term hypoparathyroidism and with renal hyperparathyroidism. Special attention should be paid to avoid long-term hypoparathyroidism of the patients from the view point of increased fracture risk caused by increased micropetrosis area.

Association of Reduced Free T3 to Free T4 Ratio with Lower Serum Creatinine in Japanese Hemodialysis Patients.

PURPOSE: Low T3 syndrome is defined by a fall in free triiodothyronine (FT3) in spite of normal serum thyroid-stimulating hormone (TSH) and often normal free thyroxin (FT4). A low FT3/FT4 ratio, a relevant marker for low T3 syndrome, is known as a risk of mortality in hemodialysis (HD) patients, as well as low muscle mass in the general population. Because of the local activation of T4 to FT3 in muscle tissue, we examined the association of FT3/FT4 ratio with serum creatinine, a marker of muscle mass and strength in HD patients to investigate the significance of muscle tissue in the development of low T3 syndrome in HD patients. METHODS: This was a cross-sectional study derived from our prospective cohort study, named DREAM, of Japanese HD patients. After the exclusion of patients with treated and untreated thyroid dysfunction, 332 patients were analyzed in the study. RESULTS: The serum FT4 and TSH of HD patients (n = 332) were 0.9 ± 0.1 ng/dL. and 2.0 ± 0.9 µIU/mL, which were within the respective normal range, while serum FT3 was 2.2 ± 0.3 pg/mL. As many as 101 out of 332 (30.4%) HD patients exhibited a serum FT3 less than the normal lower limit of 2.2 pg/mL. The serum FT3/FT4 ratio correlated significantly positively with serum creatinine, and inversely with serum log CRP and total cholesterol, while it exhibited a tendency towards positive correlation with serum albumin. Multiple regression analysis, which included serum creatinine, albumin, and log CRP, simultaneously, in addition to sex, age, diabetic kidney disease or not, log HD duration, body mass index, systolic blood pressure, and Kt/V, as independent variables, revealed an independent and significant positive association of serum creatinine, but not serum albumin or CRP, with the serum FT3/FT4 ratio. CONCLUSIONS: The present study demonstrated an independent and positive correlation of serum creatinine with the serum FT3/FT4 ratio in HD patients. The lack of association of the serum FT3/FT4 ratio with serum albumin and CRP suggested the presence of a creatinine-specific mechanism to associate with serum FT3/FT4 ratio. Because of the local activation of T4 to T3 at muscle tissue, a lower muscle mass may be causatively associated with low T3 syndrome.

Extension of Healthy Life Span of Dialysis Patients in the Era of a 100-Year Life.

With both the elongation of hemodialysis (HD) duration resulting from the sophistication of HD technology and the increasing age at the time of HD initiation due to the aging society of Japan, the mean age of prevalent HD patients is increasing at an accelerating rate [...].

Importance of Considering Malnutrition and Sarcopenia in Order to Improve the QOL of Elderly Hemodialysis Patients in Japan in the Era of 100-Year Life.

In the current aging society of Japan, malnutrition and resultant sarcopenia have been widely identified as important symptomatic indicators of ill health and can cause impairments of longevity and quality of life in older individuals. Elderly individuals are recommended to have sufficient calorie and protein intake so as to enjoy a satisfactory quality of life, including maintaining activities of daily living in order to avoid emaciation and sarcopenia. The prevalence of emaciation and sarcopenia in elderly hemodialysis (HD) patients in Japan is higher than in non-HD elderly subjects due to the presence of malnutrition and sarcopenia associated with chronic kidney disease (CKD). Furthermore, comorbidities, such as diabetes and osteoporosis, induce malnutrition and sarcopenia in HD patients. This review presents findings regarding the mechanisms of the development of these early symptomatic conditions and their significance for impaired QOL and increased mortality in elderly HD patients.

Efficacy of romosozumab in patients with osteoporosis on maintenance hemodialysis in Japan; an observational study.

INTRODUCTION: Romosozumab reportedly increases bone mineral density (BMD) potently but might adversely affect cardiovascular disease (CVD). We evaluated the efficacy of romosozumab in osteoporotic HD patients with a high risk of fracture. MATERIALS AND METHODS: This was a single-center 1-year study in Japanese HD patients. Among 96 HD romosozumab-treated HD patients with high risk of fracture, 76 HD patients completed 1 year of subcutaneous administration of romosozumab (210 mg/4 weeks) for 1 year. Romosozumab-untreated HD patients (n = 55) were also included. Changes in BMD and serum markers, together with fracture occurrence, and CVD events, were monitored. RESULTS: During romosozumab treatment of 76 HD patients, BMD time-dependently increased significantly by 15.3% ± 12.9% at the lumbar spine (L1-4), and 7.2% ± 8.3% at the femoral neck at 1 year. Serum BAP and total P1NP increased significantly and serum TRACP-5b decreased at 4 weeks. Fragility fractures occurred in three (3.8%) patients. Hypocalcemia occurred at 4-48 weeks despite the increased dosing of active vitamin-D derivatives, but without any symptom. New CVD events occurred in 5.2% of romosozumab-treated HD patients and10.9% in romosozumab-untreated HD patients. CONCLUSIONS: BMD was increased significantly during romosozumab treatment at the lumbar spine, and the femoral neck, respectively, at 1 year in HD patients. Hypocalcemia occurred but without any intolerable event. There was no apparent increase in CVD events during 1 year of study, suggesting romosozumab as a promising agent for HD patients with severe osteoporosis.

Potassium Metabolism and Management in Patients with CKD.

Potassium (K), the main cation inside cells, plays roles in maintaining cellular osmolarity and acid-base equilibrium, as well as nerve stimulation transmission, and regulation of cardiac and muscle functions. It has also recently been shown that K has an antihypertensive effect by promoting sodium excretion, while it is also attracting attention as an important component that can suppress hypertension associated with excessive sodium intake. Since most ingested K is excreted through the kidneys, decreased renal function is a major factor in increased serum levels, and target values for its intake according to the degree of renal dysfunction have been established. In older individuals with impaired renal function, not only hyperkalemia but also hypokalemia due to anorexia, K loss by dialysis, and effects of various drugs are likely to develop. Thus, it is necessary to pay attention to K management tailored to individual conditions. Since abnormalities in K metabolism can also cause lethal arrhythmia or sudden cardiac death, it is extremely important to monitor patients with a high risk of hyper- or hypokalemia and attempt to provide early and appropriate intervention.