Geriatric Nutritional Risk Index is associated with adverse outcomes in patients with hypertension: the Fukushima Cohort study.

Malnutrition is reportedly associated with adverse clinical outcomes in various populations. However, associations between nutritional status and adverse outcomes in patients with hypertension have not been sufficiently elucidated. We therefore aimed to investigate the impact of nutritional status as evaluated by the Geriatric Nutritional Risk Index (GNRI) on adverse outcomes in patients with hypertension. We conducted a retrospective cohort study of 1588 hypertensive patients enrolled in the Fukushima Cohort Study. Participants were categorized into tertiles (T1-T3) according to GNRI at baseline. The primary endpoint of the present study was a kidney event, defined as a combination of a 50% decline in eGFR from baseline and end-stage kidney disease requiring kidney replacement therapy. Associations between GNRI and kidney events were assessed using Kaplan-Meier curves and multivariate Cox regression analyses. Median age was 64 years, 55% were men, median eGFR was 63.1 mL/min/1.73 m2, and median GNRI was 101.3. The lower GNRI group (T1) showed an increased incidence of kidney events in the Kaplan-Meier curve analysis. Compared to the highest GNRI group (T3), lower GNRI carried a higher risk of kidney events for both T2 (hazard ratio [HR] 1.38, 95% confidence interval [CI] 0.71-2.68) and T1 (HR 3.59, 95%CI 1.96-6.63). Similar relationships were observed for risks of all-cause death and cardiovascular events. Lower GNRI was associated with kidney events, all-cause death, and cardiovascular events in patients with hypertension. Nutritional status as evaluated by GNRI could offer a simple and useful predictor of adverse outcomes in this population.

Effectiveness of calcimimetics on fractures in dialysis patients with secondary hyperparathyroidism: meta-analysis of randomized trials.

INTRODUCTION: This study aimed to assess the effectiveness of calcimimetics in reducing the risk of fractures in dialysis patients with secondary hyperparathyroidism (SHPT). MATERIAL AND METHODS: A comprehensive literature search was conducted using PubMed, Embase, and Cochrane Library for articles published through December 9, 2023. The quality of each trial was evaluated using the Cochrane Collaboration tool. Meta-analysis was performed using a random-effects model, and effect measures across studies were synthesized. The risk ratio (RR) and 95% confidence interval (CI) were used to quantify the risk of fracture. RESULTS: We identified seven studies involving 6481 dialysis patients with SHPT. The administration of calcimimetics reduced fracture incidence compared to placebo or conventional treatment (RR: 0.50, 95% CI 0.29-0.88, p = 0.02). Calcimimetics demonstrated a low number needed to treat (NNT) to prevent an incident fracture (NNT: 47). CONCLUSION: The use of calcimimetics offers a significant benefit in reducing the risk of fractures in patients undergoing dialysis with SHPT.

Blood data trends of children in Fukushima after the Great East Japan Earthquake: Fukushima health management survey.

BACKGROUND: After the Great East Japan Earthquake on March 11, 2011 and the subsequent accident at the Tokyo Electric Power Company-operated Daiichi Nuclear Power Plant, the Fukushima Prefecture government initiated the Fukushima Health Management Survey (FHMS) to assess the long-term health effects of the disaster on Fukushima residents. The blood tests of children aged ≤15 years between 2011 and 2012 did not reveal any changes regarding peripheral blood data; however, long-term monitoring is still necessary. Therefore, this study aimed to investigate the long-term health status of children aged ≤15 years who had evacuated the Fukushima Prefecture. METHODS: From 2011 to 2018, 71,250 evacuees aged 15 years or younger participated in the FMHS and were subjected to blood tests. By analyzing the data of the comprehensive health check survey managed by the FHMS, we examined the changes in hemoglobin (Hb) levels, white blood cell (WBC) counts, including fractions, and platelet (PLT) counts among children from 2011 to 2018. RESULTS: Minor fluctuations in Hb levels, PLT counts, and WBC counts were observed during the study period, but the central 95% intervals of distribution of the laboratory values were generally within previously reported reference intervals. In particular, there was no increase in the proportions of patients with anemia, polycythemia, or deviating WBC counts. CONCLUSION: From 2011 to 2018, there was no increase in the percentages of children with anemia, polycythemia, or deviating WBC counts among the Fukushima Prefecture evacuees.

Impact of red blood cell distribution width-albumin ratio on prognosis of patients with CKD.

The red blood cell distribution width-albumin ratio (RAR) is a prognostic factor for adverse outcomes in various populations. However, whether RAR is associated with renal outcomes remains unclear. Therefore, we aimed to investigate the impact of RAR on the prognosis in patients with chronic kidney disease (CKD). We conducted a retrospective cohort study using 997 CKD patients who were enrolled in the Fukushima Cohort Study. Patients were categorized into tertiles (T1-3) according to the baseline RAR. The associations of RAR with end-stage kidney disease (ESKD) were assessed using Kaplan-Meier curves and multivariable cox regression analyses. Receiver operating characteristic (ROC) curves were performed to test whether significant differences were present between red cell distribution width (RDW) and RAR. The median age was 66, 57% were men, the median eGFR was 47.8 ml/min/1.73 m2, and the median value of RAR was 3.5. The higher RAR group showed an increased risk for ESKD in the Kaplan-Meier curve analysis. Compared to the lowest RAR group, higher RAR groups had a higher risk of ESKD (hazard ratio [HR] 1.37, 95% CI 0.68-2.78 and 2.92, 95% CI 1.44-5.94) for T2 and T3 groups, respectively. ROC curve analysis proved that the discriminating ability of RAR for ESKD was superior to RDW. A higher RAR value was associated with worse renal outcomes in patients with CKD. RAR could be a convenient and useful prognostic marker for renal prognosis.

Changes in Metabolomic Profiles Induced by Switching from an Erythropoiesis-Stimulating Agent to a Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor in Hemodialysis Patients: A Pilot Study.

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are a new class of medications for managing renal anemia in patients with chronic kidney disease (CKD). In addition to their erythropoietic activity, HIF-PHIs exhibit multifaceted effects on iron and glucose metabolism, mitochondrial metabolism, and angiogenesis through the regulation of a wide range of HIF-responsive gene expressions. However, the systemic biological effects of HIF-PHIs in CKD patients have not been fully explored. In this prospective, single-center study, we comprehensively investigated changes in plasma metabolomic profiles following the switch from an erythropoiesis-stimulating agent (ESA) to an HIF-PHI, daprodustat, in 10 maintenance hemodialysis patients. Plasma metabolites were measured before and three months after the switch from an ESA to an HIF-PHI. Among 106 individual markers detected in plasma, significant changes were found in four compounds (erythrulose, n-butyrylglycine, threonine, and leucine), and notable but non-significant changes were found in another five compounds (inositol, phosphoric acid, lyxose, arabinose, and hydroxylamine). Pathway analysis indicated decreased levels of plasma metabolites, particularly those involved in phosphatidylinositol signaling, ascorbate and aldarate metabolism, and inositol phosphate metabolism. Our results provide detailed insights into the systemic biological effects of HIF-PHIs in hemodialysis patients and are expected to contribute to an evaluation of the potential side effects that may result from long-term use of this class of drugs.

Risks of femoral localized periosteal thickening in patients with autoimmune inflammatory rheumatic diseases.

OBJECTIVES: The incidence of femoral localized periosteal thickening (LPT), which can precede atypical femoral fracture (AFF), is not low (1-10%) in Japanese patients with autoimmune inflammatory rheumatic diseases (AIRDs). We explored the associations between underlying AIRDs and the prevalence of LPT. METHODS: We conducted post hoc analyses of two cohorts that included a total of 280 Japanese women, 105 of whom had AIRDs and had been taking bisphosphonate (BP) and prednisolone (PSL) and 175 of whom had rheumatoid arthritis (RA). RESULTS: LPT was detected in a total of 18 patients (6.4%) and 3 (1.1%) developed AFFs. RA was negatively correlated with LPT. A disease other than RA requiring glucocorticoid treatment, BP use ≥5 years, PSL use ≥7 years, and a PSL dose ≥5.5 mg/day were positively correlated with LPT. After adjusting for age, diabetes mellitus, and BP duration or daily PSL dose, RA was no longer associated with LPT. CONCLUSIONS: LPT in Japanese patients with AIRDs was associated with BP and glucocorticoid treatment rather than underlying AIRDs. When PSL dose ≥5.5 mg/day is required long-term [typically combined with long-term BP treatment (≥5 years)], clinicians need to pay particular attention in cases LPT and AFF as well as glucocorticoid-induced osteoporosis.

Long-term effectiveness of a primary care practice facilitation program for chronic kidney disease management: an extended follow-up of a cluster-randomized FROM-J study.

BACKGROUND: Practice facilitation program by multidisciplinary care for primary care physicians (PCPs) is expected to improve chronic kidney disease (CKD) outcomes, but there is no clear evidence of its long-term effectiveness. We have previously performed a cluster-randomized controlled trial for 3.5 years (the Frontier of Renal Outcome Modifications in Japan (FROM-J) study) with two arms-group A without the program and group B with the program. We aimed to assess the long-term effectiveness of the practice facilitation program on CKD outcomes via an extended 10-year follow-up of the FROM-J study. METHODS: We enrolled patients who were in the FROM-J study. The primary composite endpoint comprised cardiovascular disease (CVD), renal replacement therapy initiation and a 50% decrease in the estimated glomerular filtration rate (eGFR). The secondary endpoints were survival rate, eGFR decline rate and collaboration rate between PCPs and nephrologists. RESULTS: The occurrence of the primary composite endpoint tended to be lower in group B (group A: 27.1% versus group B: 22.1%, P = 0.051). Furthermore, CVD incidence was remarkably lower in group B (group A: 10.5% versus group B: 6.4%, P = 0.001). Although both mortality and the rate of eGFR decline were identical between both groups, the eGFR decline rate was significantly better in group B than in group A only in patients with stage G3a at enrollment (group A: 2.35 ± 3.87 mL/min/1.73 m2/year versus group B: 1.68 ± 2.98 mL/min/1.73 m2/year, P = 0.02). The collaboration rate was higher in group B. CONCLUSIONS: The CKD practice facilitation program for PCPs reliably decreases CVD events and may reduce the progression of cases to end-stage kidney disease.

Association of polypharmacy with incidence of CKD: a retrospective cohort study.

BACKGROUND: Polypharmacy is common in patients with chronic kidney disease (CKD) and is associated with a decline in kidney function. However, its impact on patients without CKD has not been adequately elucidated. Therefore, we aimed to investigate the association between polypharmacy and the incidence of CKD. METHODS: We conducted retrospective cohort study using 1221 participants who were enrolled in the Fukushima Cohort Study with one or more risk factors of CKD, an estimated glomerular filtration rate (eGFR) of ≥ 60 mL/min/1.73 m2, and without proteinuria. Participants were categorized into three groups based on the number of medications: non-polypharmacy, 0-4 medications; polypharmacy, 5-9 medications; and hyper-polypharmacy, ≥ 10 medications. RESULTS: The median age was 62 years, 49% were men, the median eGFR was 75.4 ml/min/1.73 m2, and the median number of medications was 5. Polypharmacy and hyper-polypharmacy were noted in 506 (41%) and 250 (20%) participants, respectively. During follow-up, 288 participants developed CKD and 67 cardiovascular events were observed. Compared to the non-polypharmacy group, the hyper-polypharmacy group had a higher risk of CKD and cardiovascular events. The adjusted hazard ratios were 1.41 (95% CI1.01-1.99) and 2.24 (95% CI1.05-4.78) for the incidence of CKD and cardiovascular events, respectively. Sensitivity analyses yielded similar findings for the restricted cubic spline function models. CONCLUSIONS: Hyper-polypharmacy is associated with a higher risk of CKD and cardiovascular events.

Association between Dietary Diversity and Sociopsychological Factors and the Onset of Dyslipidemia after the Great East Japan Earthquake: Fukushima Health Management Survey.

This study aimed to clarify the relationship between the onset of low-density lipoprotein hypercholesterolemia (hyper-LDLemia), high-density lipoprotein hypocholesterolemia (hypo-HDLemia), and hyper-triglyceridemia (hyper-TGemia) and lifestyle/socio-psychological factors among Fukushima evacuation area residents after the Great East Japan Earthquake. Participants included 11,274 non-hyper-LDLemia, 16,581 non-hypo-HDLemia, and 12,653 non-hyper-TGemia cases in the Fiscal Year (FY) 2011. In FY2011, these participants underwent a health checkup and responded to a mental health and lifestyle survey. The onset of each disease was followed through FY2017. The evacuation experience was positively associated with the risk of hyper-LDLemia, hypo-HDLemia, or hyper-TGemia. Conversely, the middle high dietary diversity score was negatively associated with the onset of hyper-TGemia. Moreover, low sleep satisfaction was positively associated with hypo-HDLemia and hyper-TGemia. The "almost never" exercise habit was positively associated with hypo-HDLemia. Current smoking and audible nuclear power plant explosions were positively associated with the risk of hyper-TGemia. Drinking habits exhibited a negative association with the onset of hyper-LDLemia, hypo-HDLemia, and hyper-TGemia. The results of this study indicate the need for continuous improvement in lifestyle, as well as efforts to eliminate the impact of disasters to prevent the onset of dyslipidemia among disaster evacuees.

Impact of lifestyle and psychosocial factors on the onset of hypertension after the Great East Japan earthquake: a 7-year follow-up of the Fukushima Health Management Survey.

Natural disasters force many evacuees to change several aspects of their lifestyles. This longitudinal study aimed to investigate whether factors such as living environment and lifestyle factors were related to new-onset hypertension in survivors of the Great East Japan Earthquake over a long-term follow-up of up to 7 years after the earthquake. The present study examined data collected from 29,025 Japanese participants aged 39-89 years, sourced from general health checkups and the Fukushima Mental Health and Lifestyle Survey, which was conducted in 13 communities between 2011 and 2018. A total of 10,861 participants received follow-up examinations. During a median follow-up of 4.3 years, 3744 participants (1588 men, 41.4%; 2,156 women, 30.7%) had newly developed hypertension. Heavy drinking (adjusted hazard ratio 1.38, 95% confidence interval 1.21-1.57, p < 0.001) and obesity (adjusted hazard ratio 1.27, 95% confidence interval 1.19-1.37, p < 0.001) were significantly associated with new-onset hypertension after the disaster in multivariate-adjusted analysis. Furthermore, experiencing evacuation after the disaster was also significantly associated with the risk of new-onset hypertension in men (adjusted hazard ratio 1.14, 95% confidence interval 1.02-1.27, p = 0.016). The present study indicated that lifestyle factors, such as drinking and obesity, and evacuation experience in men had significant effects on the risk of new-onset hypertension in the long term after the earthquake.

First-in-Patient Phase I/II Study of Upacicalcet in Japanese Patients with Secondary Hyperparathyroidism Undergoing Hemodialysis: Pharmacokinetic and Pharmacodynamic Properties.

OBJECTIVE: Upacicalcet is a new renally excreted and injectable calcimimetic agent. We evaluated the pharmacokinetics, pharmacodynamics, safety, and tolerability of single and multiple intravenous administration of upacicalcet in patients with secondary hyperparathyroidism undergoing hemodialysis. METHODS: This study was a multicenter, randomized, placebo-controlled, double-blinded, dose-escalation study consisting of a single-dose study and a multiple-dose study. The single-dose study consisted of seven dose steps from 0.025 to 0.8 mg. For each step, six patients were randomly assigned 2:1 to receive upacicalcet or a placebo. The multiple-dose study occurred over 3 weeks in three-dose steps from 0.05 to 0.2 mg. For each step, 12 patients were randomly assigned 3:1 to receive upacicalcet or a placebo. RESULTS: The plasma concentration of upacicalcet increased in a dose-dependent manner and was maintained for the next dialysis. Upacicalcet was approximately 80% removed by a single dialysis and did not increase in the plasma concentration with repeated administration. Serum intact parathyroid hormone and corrected calcium (Ca2+) levels tended to decrease in response to the plasma concentration of upacicalcet. In the single-dose study, upper gastrointestinal symptoms were observed as a non-serious and mild adverse drug reaction in the groups receiving upacicalcet ≥ 0.4 mg. In the multiple-dose study, abdominal discomfort occurred in each patient in the 0.1 mg and 0.2 mg groups. CONCLUSIONS: Upacicalcet for patients with secondary hyperparathyroidism undergoing hemodialysis could be a calcimimetic agent that acts in a dose-dependent manner and persistently until the next dialysis session. No safety or tolerability issues specific to upacicalcet were found.

Relationship Between Risk of Hyper-Low-density Lipoprotein Cholesterolemia and Evacuation After the Great East Japan Earthquake.

BACKGROUND: The Great East Japan Earthquake and the Fukushima Daiichi nuclear disaster forced the evacuation of residents and led to many changes in lifestyle for the evacuees. The Comprehensive Health Check was implemented to support the prevention of lifestyle-related disease and we analyzed the effect of prolonged evacuation (average of 3.0 years) on the new onset of hyper-LDL cholesterolemia. METHODS: The study participants were Japanese adults living near the Fukushima Daiichi nuclear power plant in Fukushima Prefecture. Annual health checkups focusing on metabolic syndromes were conducted for persons ≥40 years by the Specific Health Checkup. Based on data from annual checkups from 2011 or 2012, we followed 18,670 participants without hyper-LDL cholesterolemia who underwent at least one other annual checkup during 2013-2015. RESULTS: We found that the new onset of hyper-LDL cholesterolemia was 31% higher in evacuees than in non-evacuees. Evacuees had a significantly higher prevalence of obesity, hypertension, and diabetes, and higher frequency of weight change. Furthermore, logistic regression model analysis showed that the evacuation was significantly associated with the new onset of hyper-LDL cholesterolemia after adjusting age, gender, body mass index, smoking habit, alcohol consumption, diabetes, weight change, sleep deprivation, and exercise. CONCLUSION: The findings of the present study suggest that prolonged evacuation after a disaster is a risk factor for the new onset of hyper-LDL cholesterolemia, and lead to an increase in cardiovascular disease. It is therefore important to follow-up evacuees and recommend lifestyle changes where necessary.

Association between Serum Inorganic Phosphorus Levels and Adverse Outcomes in Chronic Kidney Disease: The Fukushima CKD Cohort Study.

Objective Although an association between serum inorganic phosphorus levels and a poor prognosis has been noted in dialysis patients, these associations have been insufficiently reported in non-dialysis-dependent chronic kidney disease (NDD-CKD) patients. This study attempted to determine the association between serum inorganic phosphorus levels and adverse outcomes in Japanese NDD-CKD patients. Methods We investigated the relationships between serum inorganic phosphorus levels and adverse outcomes, such as kidney events, cardiovascular events, and all-cause death, in Japanese NDD-CKD patients using longitudinal data from the Fukushima CKD Cohort Study with a median follow-up period of 2.8 years. The study evaluated 822 patients with NDD-CKD enrolled between June 2012 and July 2014. A kidney event was defined as a combination of doubling of the baseline serum creatinine or end-stage renal disease. Cox regression was performed to analyze the relationships of the quartile of the serum inorganic phosphorus with kidney events, cardiovascular events, and all-cause death. Results The frequency of kidney events per 1,000 person-years exhibited a U-shaped distribution based on serum inorganic phosphorus levels, with these levels not significantly associated with an increased risk of cardiovascular events and all-cause death. A multivariable Cox regression analysis showed an increased risk of kidney events for the highest quartile of the serum inorganic phosphorus levels (≥3.7 mg/dL) versus the second quartile (2.9-3.2 mg/dL, hazard ratio, 3.30; 95% confidence interval, 1.50-7.28; p=0.003). There were no significant associations between the serum calcium levels and adverse outcomes. Conclusion Serum inorganic phosphorus levels were associated with an increased risk of CKD progression in Japanese NDD-CKD patients.

Smoking and risk of fractures requiring hospitalization in haemodialysis patients: a nationwide cohort study in Japan.

BACKGROUND: Smoking is a well-established lifestyle risk factor for fractures in the general population, but evidence specific to haemodialysis populations is lacking. This nationwide cohort study used data from the Japanese Society for Dialysis Therapy Renal Data Registry to examine the association between smoking status and fractures. METHODS: A total of 154 077 patients (64.2% men; mean age 68 years) aged ≥20 years undergoing maintenance haemodialysis thrice weekly at the end of 2016 were followed for 1 year. Among these, 19 004 (12.3%) patients were current smokers. Standardized incidence rate ratios of hospitalization due to any fracture were calculated and analysed by multivariable logistic regression analysis, controlling for potential confounders. Propensity score (PS) matching and subgroup analyses were also performed as sensitivity analyses. RESULTS: During the 1-year follow-up period, 3337 fractures requiring hospitalization (1201 hip, 479 vertebral and 1657 other fractures) occurred in 3291 patients. The age- and sex-standardized incidence ratio for current smokers was 1.24 (95% confidence interval 1.12-1.39) relative to non-smokers. Standardized incidence ratios were similar after stratification by age group and sex. Multivariable logistic regression analysis revealed a 1.25-fold higher risk of any fracture requiring hospitalization (95% confidence interval 1.10-1.42) in current smokers relative to non-smokers in a fully adjusted model. PS matching showed similar results (odds ratio 1.25; 95% confidence interval 1.05-1.48). Subgroup analyses for baseline covariates revealed no significant interactions. CONCLUSIONS: Smoking is a significant risk factor for any fracture requiring hospitalization in haemodialysis patients.

Association of Polypharmacy with Kidney Disease Progression in Adults with CKD.

BACKGROUND AND OBJECTIVE: Polypharmacy is common in patients with CKD and reportedly associated with adverse outcomes. However, its effect on kidney outcomes among patients with CKD has not been adequately elucidated. Hence, this investigation was aimed at exploring the association between polypharmacy and kidney failure requiring KRT. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We retrospectively examined 1117 participants (median age, 66 years; 56% male; median eGFR, 48 ml/min per 1.73 m2) enrolled in the Fukushima CKD Cohort Study to investigate the association between the number of prescribed medications and adverse outcomes such as kidney failure, all-cause mortality, and cardiovascular events in Japanese patients with nondialysis-dependent CKD. Polypharmacy and hyperpolypharmacy were defined as the regular use of 5-9 and ≥10 medications per day, respectively. RESULTS: The median number of medications was eight; the prevalence of polypharmacy and hyperpolypharmacy was each 38%. During the observation period (median, 4.8 years), 120 developed kidney failure, 153 developed cardiovascular events, and 109 died. Compared with the use of fewer than five medications, adjusted hazard ratios (95% confidence intervals) associated with polypharmacy and hyperpolypharmacy were 2.28 (1.00 to 5.21) and 2.83 (1.21 to 6.66) for kidney failure, 1.60 (0.85 to 3.04) and 3.02 (1.59 to 5.74) for cardiovascular events, and 1.25 (0.62 to 2.53) and 2.80 (1.41 to 5.54) for all-cause mortality. CONCLUSIONS: The use of a high number of medications was associated with a high risk of kidney failure, cardiovascular events, and all-cause mortality in Japanese patients with nondialysis-dependent CKD under nephrology care.

Suboptimal diabetic control and psychological burden after the triple disaster in Japan: the Fukushima Health Management Survey.

INTRODUCTION: A triple disaster struck eastern Japan in March 2011. We investigated the psychological distress and post-traumatic stress disorder (PTSD) symptoms caused by the disaster in people without or with diabetes mellitus. RESEARCH DESIGN AND METHODS: This cross-sectional analysis examined the 16 097 evacuees (1820 (11.3%) with and 14 277 (88.7%) without diabetes mellitus) included in the Fukushima Health Management Survey. Non-specific mental health distress was assessed using the Kessler-6 Scale, and traumatic symptoms were evaluated using the PTSD Checklist. Logistic regression analyses were used to estimate the OR and 95% CI associated with symptoms, adjusted for diabetes-related and disaster-related factors. RESULTS: In the age-adjusted and sex-adjusted logistic models, suboptimal diabetic control (hemoglobin A1c (HbA1c) ≥7%) was associated with both psychological distress and possible PTSD. In the same models, current smoking, evacuation, and sleep dissatisfaction were associated with psychological distress and possible PTSD. In the multivariate-adjusted logistic models, HbA1c ≥7% was associated with psychological distress, independent of job change, evacuation, or sleep dissatisfaction. CONCLUSION: After the triple disaster, non-specific mental health distress was associated with suboptimal diabetic control. Thus, patients with diabetes, especially those with suboptimal diabetic control, may be vulnerable to postdisaster psychological burden.

Lower trabecular bone score is associated with an increased incidence of localized femoral periosteal thickening.

INTRODUCTION: Femoral localized periosteal thickening (LPT, also termed "beaking") of the lateral cortex often precedes an atypical femoral fracture (AFF). Bisphosphonate (BP) use, glucocorticoid use, and Asian race are major risk factors for developing such fractures. The aim of this study was to determine whether the trabecular bone score (TBS) reflecting the lumbar trabecular microarchitecture was related to LPT in glucocorticoid-treated Japanese patients with autoimmune diseases. MATERIALS AND METHODS: We retrospectively investigated 111 women with autoimmune diseases treated with prednisolone (PSL) who had undergone both femoral X-ray and dual-energy X-ray absorptiometry of the L1 - L4 lumbar vertebrae and for whom TBS could be evaluated for two or more of these. RESULTS: Femoral LPT was evident in the X-rays of 18 of 111 patients (16.2%). Higher body mass index (BMI), longer duration of PSL use and longer duration of BP use were significant in patients with LPT compared to those without. The TBS was significantly lower in patients with LPT than in those without (1.314 ± 0.092 vs. 1.365 ± 0.100, p = 0.044); however, the lumbar bone mineral density did not differ significantly (0.892 ± 0.141 vs. 0.897 ± 0.154 g/cm2, p = 0.897). TBS was significantly associated with LPT (odds ratio, 0.004; 95% CI, 0 - 0.96; p = 0.048), but not in the multivariate analysis including BMI, duration of PSL use and duration of BP use. CONCLUSIONS: The TBS was lower in glucocorticoid-treated Japanese women with autoimmune diseases with LPT than in those without LPT, and deteriorated trabecular microarchitecture influenced by longer use of BP and glucocorticoid might be associated with the development of LPT.

Xanthine oxidase inhibitors are associated with reduced risk of cardiovascular disease.

As previous studies have reported finding an association between hyperuricemia and the development of cardiovascular and chronic kidney disease, hyperuricemia is thought to be an independent risk factor for hypertension and diabetic mellitus. However, we have not been able to determine whether the use of xanthine oxidase inhibitors can reduce cardiovascular disease. The present study used the longitudinal data of the Fukushima Cohort Study to investigate the relationship between the use of xanthine oxidase inhibitors and cardiovascular events in patients with cardiovascular risks. During the 3-year period between 2012 and 2014, a total of 2724 subjects were enrolled in the study and followed. A total of 2501 subjects had hypertension, diabetic mellitus, dyslipidemia, or chronic kidney disease, and were identified as having cardiovascular risks. The effects of xanthine oxidase inhibitor use on the development of cardiovascular events was evaluated in these patients using a time to event analysis. During the observational periods (median 2.7 years), the incidence of cardiovascular events was 20.7 in subjects with xanthine oxidase inhibitor and 11.2 (/1000 person-years, respectively) in those without. Although a univariate Cox regression analysis showed that the risk of cardiovascular events was significantly higher in subjects administered xanthine oxidase inhibitors (HR = 1.87, 95% CI 1.19-2.94, p = 0.007), the risk was significantly lower in subjects administered a xanthine oxidase inhibitor after adjustment for covariates (HR = 0.48, 95% CI 0.26-0.91; p = 0.024) compared to those without. Xanthine oxidase inhibitor use was associated with reduced risk of cardiovascular disease in patients with cardiovascular risk factors.

Burden of Undiagnosed Type 2 Diabetes in Diabetic Kidney Disease: A Japanese Retrospective Cohort Study.

The risk of developing diabetic kidney disease (DKD) in patients with undiagnosed diabetes mellitus (UD) has never been evaluated. We studied the burden of UD on the risk of developing DKD in the Japanese population in a single-center retrospective cohort study. The patients with type 2 diabetes mellitus, but without DKD (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or proteinuria), were recruited from January 2018 to January 2019; medical records were scrutinized retrospectively from January 2003 until May 2019. The individuals, with diabetes that could not be denied based on past and current records, comprised the undiagnosed diabetes (UD) group whereas those with confirmed diagnosis comprised the diagnosed diabetes (DD) group. The group differences were tested using a Kaplan-Meier curve and Cox proportional hazards model. Among the 408 participants, 164 (40.2%) and 244 (59.8%) comprised the DD and UD groups, respectively. The baseline parameters, including age, male gender, and BMI were comparable between the groups, but the plasma glucose, HbA1c levels, and diabetic retinopathy prevalence were higher in the UD group. The risk of developing DKD (log rank test, p < 0.001), an eGFR of < 60 mL/min/1.73 m2 (p = 0.001) and proteinuria (p = 0.007) were also higher in the UD group. The unadjusted and adjusted hazard ratios for DKD were 1.760 ((95% CI: 1.323-2.341), p < 0.001) and 1.566 ((95% CI: 1.159-2.115), p = 0.003), respectively, for the UD group. In conclusion, this is the first report showing that UD is a strong risk factor for DKD. The notion that a longer duration of untreated diabetes mellitus is involved strongly in the risk of developing DKD warrants the need for the identification and monitoring of UD patients.