Impact of chronic potassium binder treatment on the clinical outcomes in patients with hyperkalemia: Results of a nationwide hospital-based cohort study

Introduction: Hyperkalemia (HK) is a common disorder in patients with heart failure or chronic kidney disease, and potassium binders (PBs) are recommended to control serum potassium (S-K) levels. Although HK is often a chronic condition, short-term and intermittent PBs treatment has been largely applied to control S-K levels, and little is known about the impact of long-term and chronic PBs treatment on clinical outcomes.Method: This retrospective cohort study was conducted using a Japanese claims database (April 2008–September 2018). HK was defined as at least two S-K ≥5.1 mmol/L within a 12-month(M) interval. The index date was defined as the initial PB prescription date, and the S-K values were examined at 3M, 6M, and 12M after the index. The medication possession ratio (MPR) was used to evaluate the length of the prescribed period of PB, as prescription refill was not allowed in Japan. Clinical outcomes were analyzed by comparing MPR <80% to MPR ≥80% using Cox proportional hazards regression.Results: We found 4,321 patients with HK and were on initial PB treatments, and 993 and 3,328 patients were categorized in the MPR <80% and MPR ≥80% groups, respectively. The mean prescription days ±SD in the MPR <80% and MPR ≥80% groups were 114.7 ± 9.1 and 1151.2 ± 22.5, respectively. S-K value with adjustment by covariates in MPR <80% and MPR ≥80% groups were 5.62 (95% CI: 5.57–5.68) and 5.72 (95% CI: 5.68–5.76) at index followed by 4.65 (95% CI: 4.58–4.71) and 4.57 (95% CI: 4.51–4.62) at 3M, respectively. The hazard ratios of incidence rates in hospitalization was 1.41 (p < 0.001), introduction of renal replacement therapy was 1.25 (p < 0.003), recurrent HK was 1.67 (p < 0.001), and decreased eGFR was 1.41 (p < 0.001), respectively.Conclusion: These results indicate a higher risk of adverse outcomes when PBs were not prescribed chronically, whereas S-K levels were similarly controlled. Chronic control with continued PBs rather than temporary treatment may be associated with the reduction of adverse clinical outcomes in patients with HK

Subclinical Hearing Loss, Longer Sleep Duration, and Cardiometabolic Risk Factors in Japanese General Population

Hearing loss leads to impaired social functioning and quality of life. Hearing loss is also associated with sleeping disorders and cardiometabolic risk factors. Here, we determined whether subclinical hearing loss is associated with sleep duration and cardiometabolic risk factors in a cross-sectional and longitudinal study of healthy Japanese general population. 48,091 men and women aged 20–79 years who underwent medical checkups were included in a cross-sectional study, and 6,674 were included in an 8-year longitudinal study. The prevalence of audiometrically determined hearing loss (>25 dB) at 4000 and 1000 Hz increased significantly with increasing sleep duration in any age strata. Logistic regression analysis showed that compared with reference sleep duration (6 h) longer sleep duration (≥8 h) was significantly associated with hearing loss, even after adjusting for potential confounding factors. Simultaneously, hearing loss was significantly associated with male sex, diabetes, and no habitual exercise. In the longitudinal study, the risk of longer sleep duration (≥8 h) after 8 years was significantly greater in subjects with hearing loss at 4000 Hz at baseline. In conclusion, current results suggest a potential association of subclinical hearing loss with longer sleep duration and cardiometabolic risk factors in a Japanese general population

ダパグリフロジン投与における肥満２型糖尿病患者の治療満足度への影響：a patient reported outcome study (PRO study).

Background: The benefits of sodium glucose cotransporters 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus include plasma glucose control, reduction in body weight and blood pressure, and low risk of hypoglycemia, although they may also cause genitourinary infections, polyuria, or volume depletion. It is not clear whether dapagliflozin, an SGLT2 inhibitor, improves treatment satisfaction among patients in a comprehensive way despite the negative side effects. This study assessed the effect of dapagliflozin on glycosylated hemoglobin (HbA1c), body weight, and treatment satisfaction in overweight patients with type 2 diabetes mellitus treated with oral hypoglycemic agents. Methods: This multicenter, open-label, single-arm observational study included patients with type 2 diabetes mellitus administering dapagliflozin 5 or 10 mg per day for 14 weeks. Changes in treatment satisfaction were evaluated using a new version of the Oral Hypoglycemic Agent-Questionnaire (OHA-Q ver. 2) consisting of 23 items. Correlation between treatment satisfaction and HbA1c levels and body weight were analyzed using the Spearman's rank-correlation coefficient. Results: Of the 221 patients enrolled, 188 completed the study. Mean HbA1c decreased from 7.8 ± 0.7% (62.1 ± 7.5 mmol/mol) to 7.3 ± 0.8% (55.9 ± 8.7 mmol/mol) (change - 0.6 ± 0.7%, P < 0.001) and body weight decreased from 82.5 ± 14.6 to 80.7 ± 14.8 kg (change - 2.3 ± 2.8 kg, P < 0.001). OHA-Q ver. 2 was validated as well, the mean OHA-Q ver. 2 total score increased from 44.3 ± 9.4 to 46.6 ± 9.8 (best score 69, worst score 0; change 2.3 ± 6.6, P < 0.001). The change in body weight significantly correlated with the OHA-Q ver. 2 total score (Spearman's ρ = - 0.17, P = 0.035). The change in HbA1c levels significantly correlated with the satisfaction subscale score (Spearman's ρ = - 0.19, P = 0.011). Conclusions: Dapagliflozin significantly improved treatment satisfaction among patients with type 2 diabetes mellitus for 14 weeks. Body weight loss significantly correlated with treatment satisfaction.Trial registration UMIN-CTR: UMIN000016304.博士（医学）・甲第694号・平成31年3月15日© The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

Glucose-lowering treatment pathways of individuals with chronic kidney disease and type 2 diabetes according to the Kidney Disease: Improving Global Outcomes 2012 risk classification

Aims: To describe treatment pathways for key glucose-lowering therapies in individuals with chronic kidney disease (CKD) and type 2 diabetes (T2D) using retrospective data from DISCOVER CKD (NCT04034992). // Methods: Data were extracted from the UK Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics data (2008–2020) and the US integrated Limited Claims and Electronic Health Records Database (LCED; 2012–2019). Eligible individuals were aged ≥18 years with CKD, identified by two consecutive estimated glomerular filtration rate (eGFR) measures (15–<75 mL/min/1.73 m2; 90–730 days apart; index date was the second measurement) and T2D. Chronological treatment pathways for glucose-lowering therapies prescribed on or after CKD index to end of follow-up were computed. Median time and proportion of overall follow-up time on treatment were described for each therapy by database and by eGFR and urinary albumin-to-creatinine ratio (UACR) categories. // Results: Of 36,951 and 4339 eligible individuals in the CPRD and LCED, respectively, median baseline eGFR was 67.8 and 64.9 mL/min/1.73 m2; 64.2 and 63.9% received metformin prior to index; and median (interquartile range) time on metformin during follow-up was 917 (390–1671) and 454 (192–850) days (accounting for ~75% of follow-up time in both databases). The frequency of combination treatment increased over time. There were trends towards decreased metformin prescriptions with decreasing eGFR and increasing UACR within each eGFR category. // Conclusions: Individuals with CKD and T2D had many combinations of therapies and substantial follow-up time on therapy. These results highlight opportunities for improved CKD management

Reciprocal interaction with G-actin and tropomyosin is essential for aquaporin-2 trafficking

Trafficking of water channel aquaporin-2 (AQP2) to the apical membrane and its vasopressin and protein kinase A (PKA)–dependent regulation in renal collecting ducts is critical for body water homeostasis. We previously identified an AQP2 binding protein complex including actin and tropomyosin-5b (TM5b). We show that dynamic interactions between AQP2 and the actin cytoskeleton are critical for initiating AQP2 apical targeting. Specific binding of AQP2 to G-actin in reconstituted liposomes is negatively regulated by PKA phosphorylation. Dual color fluorescence cross-correlation spectroscopy reveals local AQP2 interaction with G-actin in live epithelial cells at single-molecule resolution. Cyclic adenosine monophosphate signaling and AQP2 phosphorylation release AQP2 from G-actin. In turn, AQP2 phosphorylation increases its affinity to TM5b, resulting in reduction of TM5b bound to F-actin, subsequently inducing F-actin destabilization. RNA interference–mediated knockdown and overexpression of TM5b confirm its inhibitory role in apical trafficking of AQP2. These findings indicate a novel mechanism of channel protein trafficking, in which the channel protein itself critically regulates local actin reorganization to initiate its movement

Prevalence of anemia in patients with chronic kidney disease in Japan: A nationwide, cross-sectional cohort study using data from the Japan Chronic Kidney Disease Database (J-CKD-DB)

Background: The Japan Chronic Kidney Disease Database (J-CKD-DB) is a nationwide clinical database of patients with chronic kidney disease (CKD) based on electronic health records. The objective of this study was to assess the prevalence of anemia and the utilization rate of erythropoiesis-stimulating agents (ESAs) in Japanese patients with CKD. Methods: In total, 31, 082 adult outpatients with estimated glomerular filtration rates of 5–60 ml/min/1.73 m2 in seven university hospitals were included this analysis. The proportions of patients with CKD stages G3b, G4, and G5 were 23.5%, 7.6%, and 3.1%, respectively. Results: The mean (standard deviation) hemoglobin level of male patients was 13.6 (1.9) g/dl, which was significantly higher than the mean hemoglobin level of female patients (12.4 (1.6) g/dl). The mean (standard deviation) hemoglobin levels were 11.4 (2.1) g/dl in patients with CKD stage G4 and 11.2 (1.8) g/dl in patients with CKD stage G5. The prevalences of anemia were 40.1% in patients with CKD stage G4 and 60.3% in patients with CKD stage G5. Logistic regression analysis showed that diagnoses of CKD stage G3b (adjusted odds ratio [95% confidence interval]: 2.32 [2.09–2.58]), G4 (5.50 [4.80–6.31]), and G5 (9.75 [8.13–11.7]) were associated with increased prevalence of anemia. The utilization rates of ESAs were 7.9% in patients with CKD stage G4 and 22.4% in patients with CKD stage G5. Conclusions: We determined the prevalence of anemia and utilization rate of ESAs in Japanese patients with CKD using data from a nationwide cohort study

Applicability of fibroblast growth factor 23 for evaluation of risk of vertebral fracture and chronic kidney disease-mineral bone disease in elderly chronic kidney disease patients

Abstract Background Elderly patients with chronic kidney disease (CKD) are usually at a high risk of fractures due to both osteoporosis and CKD-mineral bone disease (MBD). A new marker is needed to prevent fractures and control CKD-MBD from the early to advanced stages of CKD. In the early stage of CKD, fibroblast growth factor 23 (FGF23) level increases before parathyroid hormone (PTH) and phosphate levels increase, and steadily increases with the progression of kidney disease. It has been reported that FGF23 is related to the overall fracture risk. We investigated the usefulness of FGF23 as a marker for evaluating the risk of vertebral fracture and CKD-MBD in elderly CKD patients. Methods One hundred and five elderly predialysis CKD patients who had never been treated for osteoporosis and had never used calcium supplements, vitamin D supplements, or phosphate binders were enrolled in this cross-sectional study in Tokyo, Japan. We investigated the prevalence of vertebral fracture and measured serum calcium, phosphate, 1,25(OH)2 vitamin D [1,25(OH)2D], intact PTH, FGF23, alkaline phosphatase, and urinary N-terminal telopeptide levels. Then, we examined the relationship between the level of FGF23 and those of bone-metabolism-related markers and identified markers associated with vertebral fractures in elderly CKD patients. Results The background features of the patients were as follows: female, 32.4%; diabetes mellitus, 39.0%; average age (standard deviation), 73.2 (7.7) years; and estimated glomerular filtration rate (eGFR), 45.7 (24.1) ml/min/1.73 m2. Adjusted multivariate regression analysis showed that the natural logarithm value of FGF23 level [ln(FGF23)] was positively associated with body mass index (p = 0.002), serum phosphate level (p = 0.0001), and negatively with eGFR (p = 0.0006). Multivariate logistic regression analysis showed that vertebral fracture was independently associated with ln(FGF23) (adjusted odds ratio, 4.44; 95% confidence interval, 1.13-17.46). A receiver-operating-characteristic curve of ln(FGF23) showed that the optimal cutoff level of FGF23 indicative of vertebral fracture was 56.8 pg/ml (sensitivity, 0.82; specificity, 0.63). Conclusions FGF23 level was independently associated with the levels of bone-metabolism-related markers and vertebral fracture. FGF23 is a new candidate marker for detecting abnormalities of bone metabolism and vertebral fracture in elderly CKD patients.</p

Methods and Nutritional Interventions to Improve the Nutritional Status of Dialysis Patients in JAPAN—A Narrative Review

Patients receiving dialysis therapy often have frailty, protein energy wasting, and sarcopenia. However, medical staff in Japan, except for registered dietitians, do not receive training in nutritional management at school or on the job. Moreover, registered dietitians work separately from patients and medical staff even inside a hospital, and there are many medical institutions that do not have registered dietitians. In such institutions, medical staff are required to manage patients’ nutritional disorders without assistance from a specialist. Recent studies have shown that salt intake should not be restricted under conditions of low nutrition in frail subjects or those undergoing dialysis, and protein consumption should be targeted at 0.9 to 1.2 g/kg/day. The Japanese Society of Dialysis Therapy suggests that the Nutritional Risk Index-Japanese Hemodialysis (NRI-JH) is a useful tool to screen for older patients with malnutrition