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.

Trends in Lifestyle-related Diseases and Their Risk Factors After the Fukushima Daiichi Nuclear Power Plant Accident: Results of the Comprehensive Health Check in the Fukushima Health Management Survey.

Residents were forced to evacuate owing to the radiation released after the Fukushima Nuclear Power Plant (NPP) accident following the Great East Japan Earthquake on 11/03/2021; thus, their lifestyles drastically changed. The Comprehensive Health Check (CHC) of the Fukushima Health Management Survey (FHMS) was performed to evaluate health statuses and prevent lifestyle-related diseases in evacuation area residents. The first part of the CHC survey is a retrospective analysis of pre- and post-disaster data on health check-ups of evacuation area residents. The second part is a cross-sectional, prospective analysis of post-disaster (fiscal year (FY) 2011-2017) data on health check-ups. Subjects were men and women living in 13 municipalities in areas surrounding the NPP in Fukushima Prefecture. Post-disaster (FY 2011-2012) overweight, hypertension, dyslipidemia, diabetes mellitus, metabolic syndrome, liver dysfunction, hyperuricemia, polycythemia and atrial fibrillation cases increased from the pre-disaster (FY 2008-2010) levels. This tendency was strongest among residents who were forced to evacuate. Proportion of overweight people remained unchanged, the prevalence of liver dysfunction decreased and the proportion of people with treated hypertension and dyslipidemia increased during FY 2011-2017. Meanwhile, the prevalence of diabetes mellitus and mean levels of HbA1c increased. Furthermore, Evacuees showed higher risks of diabetes mellitus, dyslipidemia, chronic kidney diseases and liver dysfunction than non-evacuees. Therefore, residents in the evacuation area, especially evacuees, are at high risk of developing lifestyle-related diseases, especially cardiovascular diseases; therefore, it is necessary to observe health statuses and implement measures to prevent lifestyle-related diseases.

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.

Japan Endocrine Society clinical practice guideline for the diagnosis and management of primary aldosteronism 2021.

Primary aldosteronism (PA) is associated with higher cardiovascular morbidity and mortality rates than essential hypertension. The Japan Endocrine Society (JES) has developed an updated guideline for PA, based on the evidence, especially from Japan. We should preferentially screen hypertensive patients with a high prevalence of PA with aldosterone to renin ratio ≥200 and plasma aldosterone concentrations (PAC) ≥60 pg/mL as a cut-off of positive results. While we should confirm excess aldosterone secretion by one positive confirmatory test, we could bypass patients with typical PA findings. Since PAC became lower due to a change in assay methods from radioimmunoassay to chemiluminescent enzyme immunoassay, borderline ranges were set for screening and confirmatory tests and provisionally designated as positive. We recommend individualized medicine for those in the borderline range for the next step. We recommend evaluating cortisol co-secretion in patients with adrenal macroadenomas. Although we recommend adrenal venous sampling for lateralization before adrenalectomy, we should carefully select patients rather than all patients, and we suggest bypassing in young patients with typical PA findings. A selectivity index ≥5 and a lateralization index >4 after adrenocorticotropic hormone stimulation defines successful catheterization and unilateral subtype diagnosis. We recommend adrenalectomy for unilateral PA and mineralocorticoid receptor antagonists for bilateral PA. Systematic as well as individualized clinical practice is always warranted. This JES guideline 2021 provides updated rational evidence and recommendations for the clinical practice of PA, leading to improved quality of the clinical practice of hypertension.

Evacuation after the Great East Japan Earthquake is an independent factor associated with hyperuricemia: The Fukushima Health Management Survey.

BACKGROUND AND AIMS: On March 11, 2011, the Great East Japan Earthquake occurred in Japan, with a nuclear accident subsequently occurring at the Fukushima Daiichi Nuclear Power Plant. The disaster forced many evacuees to change particular aspects of their lifestyles. This study assessed the association between evacuation and hyperuricemia based on the Fukushima Health Management Survey from a lifestyle and socio-psychological perspective. METHODS AND RESULTS: This cross-sectional study included 22,812 residents (9391 men and 13,297 women) who underwent both the Comprehensive Health Check and the Mental Health and Lifestyle Survey in fiscal year 2011. Associations between hyperuricemia and lifestyle- and disaster-related factors including evacuation were estimated using a logistic and liner regression analysis. With hyperuricemia defined as uric acid levels >7.0 mg/dL for men and >6.0 mg/dL for women, significant associations were observed between evacuation and hyperuricemia in men (the multivariate-adjusted odds ratio 1.20, 95% confidence interval, 1.05-1.36, p = 0.005), but not in women. In the multivariate-adjusted multiple liner regression analysis, evacuation had significant and positive associations with uric acid levels both in men (ß = 0.084, p = 0.002) and women (ß = 0.060, p < 0.001). CONCLUSION: Evacuation after a natural disaster is an independent factor associated with hyperuricemia.

Influence of post-disaster evacuation on incidence of hyperuricemia in residents of Fukushima Prefecture: the Fukushima Health Management Survey.

AIM: After the Great East Japan Earthquake, over 160,000 residents in Fukushima Prefecture were forced to evacuate the area around the Fukushima Daiichi power plant following nuclear accident there. Health problems in these evacuees have since become a major issue. We have examined the association between evacuation and incidence of hyperuricemia among residents in Fukushima. METHODS: We conducted a cohort study of residents aged 40-90 years without hyperuricemia at the time of the Fukushima disaster. Among 8173 residents who met the inclusion criteria before the disaster, 4789 residents (men: 1971, women: 2818; follow-up duration: 1.38 years; and follow-up rate: 58.6%) remained available for follow-up examinations at the end of March 2013. The main endpoint was incidence of hyperuricemia, defined by the Japanese committee guidelines, using local health data from before and after the disaster. We divided participants by evacuation status and compared outcomes between groups. Using a logistic regression model, we estimated the odds ratio for incidence of hyperuricemia, adjusting for potential confounders, age, gender, waist circumference, physical activity, and alcohol consumption. RESULTS: Incidence of hyperuricemia was higher in evacuees (men 10.1%; women 1.1%) than in non-evacuees (men 7.4%, women 1.0%). Evacuees had higher body mass index, waist circumference, triglycerides, LDL-cholesterol, fasting plasma glucose, HbA1c, and lower HDL-cholesterol after the disaster than non-evacuees. We found that evacuation was associated with incidence of hyperuricemia (adjusted odds ratio: 1.38; 95% confidence interval: 1.03-1.86). CONCLUSION: This is the first study to demonstrate an association between evacuation after a disaster and increased incidence of hyperuricemia.

Effect of evacuation on liver function after the Fukushima Daiichi Nuclear Power Plant accident: The Fukushima Health Management Survey.

BACKGROUND: The Great East Japan Earthquake and subsequent Fukushima Daiichi Nuclear Power Plant accident caused residents to switch from their normal lives to lives focused on evacuation. We evaluated liver function before and after this disaster to elucidate the effects of evacuation on liver function. METHODS: This study was a longitudinal survey of 26,006 Japanese men and women living near the Fukushima Daiichi Nuclear Power Plant. This study was undertaken using data from annual health checkups conducted for persons aged 40-90 years between 2008 and 2010. Follow-up examinations were conducted from June 2011 to the end of March 2013, with a mean follow up of 1.6 years. Changes in liver function before and after the disaster were compared among evacuees and non-evacuees. We also assessed groups according to alcohol drinking status. RESULTS: The prevalence of liver dysfunction significantly increased in all participants from 16.4% before to 19.2% after the disaster. The incidence of liver dysfunction was significantly higher in evacuees than in non-evacuees. Multivariate logistic regression analysis showed that evacuation was significantly associated with liver dysfunction among residents. CONCLUSIONS: This is the first study to show that evacuation due to the Fukushima Daiichi nuclear power plant disaster was associated with an increase in liver dysfunction.

The impact of evacuation on the incidence of chronic kidney disease after the Great East Japan Earthquake: The Fukushima Health Management Survey.

BACKGROUND: About 146,000 people were forced into long-term evacuation due to the nuclear power plant accident caused by the Great East Japan Earthquake in 2011. Disaster is known to induce hypertension in survivors for a certain period, but it is unclear whether prolonged disaster stress influences chronic kidney disease (CKD). We conducted an observational cohort study to elucidate the effects of evacuation stress on CKD incidence. METHODS: Participants were individuals living in communities near the Fukushima nuclear power plant, aged 40-74 years without CKD as of their 2011 general health checkup (non-evacuees: n = 9780, evacuees: n = 4712). We followed new-onset CKD [estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or proteinuria] using general annual health checkup data from 2012 to 2014. Association between evacuation and CKD incidence was analyzed using the Cox proportional hazard model. RESULTS: Mean age of the participants at baseline was 65 years, 46.7% were men, and baseline eGFR was 75.7 ml/min/1.73 m2. During the mean follow-up period of 2.46 years, CKD incidence rate was 80.8/1000 and 100.2/1000 person-years in non-evacuees and evacuees, respectively. Evacuation was a significant risk factor of CKD incidence after adjusting for age, gender, obesity, hypertension, diabetes, dyslipidemia, smoking, and baseline eGFR [hazard ratio (HR): 1.45; 95% confidence interval (CI) 1.35-1.56]. Evacuation was significantly associated with the incidence of eGFR <60 ml/min/1.73 m2 (HR: 1.48; 95% CI 1.37-1.60), but not with the incidence of proteinuria (HR: 1.21; 95% CI 0.93-1.56). CONCLUSION: Evacuation was a risk factor associated with CKD incidence after the disaster.

[The Unit Use Situation and Problems of the Examination of Blood Count in Fukushima].

In comprehensive health check performed in Japan, many errors have been found that were caused by man- ually transcribing family doctor's reports or commissioned health check company's reports to Medical Examina- tion Record and Results Report. Since those errors included unit's error of blood tests that caused digits differ- ences, we hereby present the result of an investigation on current situation of blood test reporting units in Japan. Results showed that, in prefectural medical institutions, only a few facilities used international units in reporting units of blood tests. However, most of the domestic or overseas quality control programs used in- ternational units, except for that conducted by the Japan Medical Association. We consider that it might be possible to prevent medical malpractices caused by erroneous judgment on health check results, by unifying the blood test reporting units upon sharing patients' information among medical facilities. [Letter].

Effects of metformin on endocrine, metabolic milieus and endometrial expression of androgen receptor in patients with polycystic ovary syndrome.

OBJECTIVE: To evaluate effects of metformin on endocrine, metabolic parameters and endometrial androgen receptor (AR) expression in polycystic ovary syndrome (PCOS). DESIGN: Prospective observational study. METHODS: We analyzed blood samples from 10 PCOS patients, of whom endometrium was also analyzed in five patients. Before and after three months of metformin treatment, endocrine, glucose metabolic parameters and the endometrial AR expressions were assessed. The relative expression levels of AR were examined by immunohistochemistry. MAIN OUTCOME MEASURES: The group post-treatment mean of homeostasis model assessment insulin resistance (HOMA-IR) for all patients was significantly lower than the pretreatment. Ovulation was restored in five out of 10 patients. The group post-treatment means of luteinizing hormone (LH) and HOMA-IR for the five ovulatory patients were significantly lower. The relative expression levels of endometrial AR were decreased in four out of the five patients as compared with pretreatment. In the four patients, one or more of the parameters, HOMA-IR, LH or free testosterone, decreased compared with pretreatment. CONCLUSION: Metformin was effective in decreasing HOMA-IR, LH, free testosterone and the relative expression levels of AR. Furthermore, metformin might improve the systemic and local environment of the uterus caused by hyperandrogenemia in PCOS patients with insulin resistance.

Chronic kidney disease score for predicting postoperative masked renal insufficiency in patients with primary aldosteronism.

CONTEXT: Chronic kidney disease (CKD) is sometimes unmasked after unilateral adrenalectomy in patients with primary aldosteronism (PA) without expectation. OBJECTIVE: Our study aim was to elucidate factors responsible for developing postoperative CKD and to provide a simple scoring system to predict postoperative CKD in PA. DESIGN AND PATIENTS: Forty-five patients with PA treated with unilateral adrenalectomy and followed for at least 1 month postsurgery were studied. Thirty-one patients with non-PA adrenal disease who underwent unilateral adrenalectomy were also studied as control. Patients with pre-operative estimated glomerular filtration rate (eGFR) < 60 ml/min/1·73 m(2) were excluded from both groups. RESULTS: A statistically significant (P < 0·001) decrease in eGFR was observed in PA group within 1 month of surgery, then stabilized. Of the 45 patients with PA, 17 (37·8%) developed CKD after surgery. None of the non-PA group developed CKD after surgery. Of the pre-operative variables, logistic regression analysis showed that lower eGFR and higher aldosterone-to-renin ratios (ARR) were the independent predictors for postoperative CKD in PA. Optimal cut-off values of the two variables analysed with ROC curves were as follows: eGFR ≤ 76·9 ml/min/1·73 m(2) and ARR ≥ 305. Using these data, we created a CKD score as a tool for predicting postoperative CKD, with an AUC for the score of 0·8866. CONCLUSION: The pre-operative eGFR and ARR were the significant contributing factors for postoperative CKD in PA. By combining these independent factors, we created a CKD score which provides useful information before surgery about the risk for development of postoperative CKD.

Relationship between evacuation after the Great East Japan Earthquake and new-onset hyperuricemia: A 7-year prospective longitudinal study of the Fukushima Health Management Survey.

INTRODUCTION: On March 11, 2011, the Great East Japan Earthquake occurred in Japan, with a nuclear accident subsequently occurring at the Fukushima Daiichi Nuclear Power Plant. The disaster forced many evacuees to change particular aspects of their lifestyles. However, the effect of evacuation on the new-onset of hyperuricemia have not been sufficiently elucidated. This study assessed the association between evacuation and new-onset hyperuricemia after the earthquake based on the Fukushima Health Management Survey from a lifestyle and socio-psychological perspective. MATERIALS AND METHODS: This is a 7-year prospective longitudinal study included 18,140 residents (6,961 men and 11,179 women) with non-hyperuricemia who underwent both the Comprehensive Health Check and the Mental Health and Lifestyle Survey in fiscal year 2011. Associations between new-onset hyperuricemia and lifestyle- and disaster-related factors, including evacuation, were estimated using a Cox proportional hazards regression model analysis. Hyperuricemia was defined as uric acid levels > 7.0 mg/dL for men and > 6.0 mg/dL for women. RESULTS: During a median follow-up of 4.3 years, 2,996 participants (1,608 men, 23.1%, 1,388 women, 12.4%) newly developed hyperuricemia. Significant associations were observed between evacuation and onset of hyperuricemia in women (adjusted hazard ratio 1.18, 95% confidence interval, 1.05-1.32, p = 0.007), but not in men (adjusted hazard ratio 1.11, 95% confidence interval, 0.99-1.24, p = 0.067). DISCUSSION: Evacuation after a natural disaster is an independent risk factor for the new-onset of hyperuricemia in women. The possibility of hyperuricemia developing in response to natural disasters should be considered.

Relationship between physical activity/exercise habits and the frequency of new onset of lifestyle-related diseases after the Great East Japan Earthquake among residents in Fukushima: the Fukushima Health Management Survey.

The effect of exercise habits on the increased incidence of lifestyle-related diseases among residents of the evacuation area in Fukushima Prefecture after the Great East Japan Earthquake is not well characterized. This study examined the influence of exercise habits on the frequency of new onset of lifestyle-related diseases in the aftermath of the earthquake using data from the Fukushima Health Management Survey (FHMS). Of the 32 289 individuals (14 004 men and 18 285 women) aged 40-90 years who underwent one or more health examinations in both 2011-12 and 2014-15, those who knew whether they had any lifestyle diseases and who responded to a questionnaire about their exercise and physical activity habits were included (dyslipidemia, 8017; hypertension, 7173; and diabetes mellitus, 13140 individuals). The association between the frequency of new onset of lifestyle-related diseases in 2014-15 and the presence or absence of persistent exercise and physical activity habits (active lifestyle) was examined using the FHMS data. The frequency of new onset of dyslipidemia was significantly lower in the active lifestyle group than in the sedentary lifestyle group (P = 0.008). On univariate and multivariate logistic regression analyses, the presence of active lifestyle, obesity and the experience of evacuation showed a significant association with new onset of dyslipidemia, independent of age, sex or follow-up period. Thus maintaining physical activity and exercise habits may help prevent the new onset of dyslipidemia among residents of the evacuation area in the Fukushima Prefecture after the earthquake.

Effects of Psychological and Lifestyle Factors on Metabolic Syndrome Following the Fukushima Daiichi Nuclear Power Plant Accident: The Fukushima Health Management Survey.

AIM: The Fukushima Daiichi Nuclear Power Plant accident dramatically changed the lifestyle of residents who lived near the plant. We evaluated the association of metabolic syndrome (MetS) with specific lifestyle- and disaster-related factors in residents following the accident. METHODS: This cross-sectional study included 20,920 residents who underwent both the Comprehensive Health Check and the Mental Health and Lifestyle Survey from June 2011 to March 2012. Associations between MetS and lifestyle- and disaster-related factors, including psychological distress (post-traumatic stress disorder [PTSD]), were estimated using logistic regression analysis, adjusted for demographic and lifestyle factors, in 2019. RESULTS: MetS was present in 30.4% of men and 11.5% of women. There were significant differences in smoking, drinking status, and PTSD prevalence between subjects with and without MetS. Multivariable logistic regression analysis showed that age, quitting smoking, and low physical activity were significantly associated with MetS. Moreover, PTSD and light to moderate drinking were also significantly associated with MetS in women. CONCLUSIONS: Lifestyle- and disaster-related factors, including PTSD, were associated with MetS among subjects who lived near the Fukushima Daiichi Nuclear Power Plant accident.

Relationship between the prevalence of polycythemia and factors observed in the mental health and lifestyle survey after the Great East Japan Earthquake.

We have been examining the Comprehensive Health Check of the Fukushima Health Management Survey of residents of 13 municipalities who were forced by the government to evacuate due to the 2011 Great East Japan Earthquake (GEJE). Our findings showed that evacuation is a risk factor for polycythemia and suggested that experiencing an unprecedented disaster and exposure to chronic stress due to evacuation might be a cause of polycythemia.We analyzed the relationship between the prevalence of polycythemia and the following factors observed in the Mental Health and Lifestyle Survey in an observational study with a cross-sectional design: traumatic symptoms, depression status, socioeconomic factors such as residential environment, and working situation after the GEJE. Target population of the survey included men and women who were at least 15 years of age and who lived in the evacuation zones specified by the government. Participants analyzed consisted of 29,474 persons (12,379 men and 16,888 women) who had participated in both the 2011 Comprehensive Health Check and Mental Health and Lifestyle Survey from June 2011 through March 2012.The prevalence of polycythemia was not associated with mental states associated with traumatic symptoms (Post-Traumatic Stress Disorder Checklist Scale ≥ 44) and depression status (Kessler 6-item Scale ≥ 13). Furthermore, multivariate analysis showed that there was a tendency for males to develop polycythemia, with characteristics such as being aged 65 years and older, highly educated, obese (body mass index ≥ 25), hypertensive, diabetic, having liver dysfunction, and a smoker being significantly related to the prevalence of polycythemia.Our findings conclusively demonstrated that polycythemia was not significantly related to psychological factors, but was significantly related to the onset of lifestyle-related disease after the GEJE.

Characteristics of awareness and behavior of medical staff for prevention of falling accidents among inpatients.

The purpose of this study is to clarify the characteristics of awareness and behavior for falling accident prevention according to medical profession. We used a questionnaire called "Self-Evaluation of Awareness and Behavior for Falling Accident Prevention," which was originally designed for nurses. In October and November 2016, the questionnaire was administered to 1,670 medical staff (nurses, doctors, lab technicians, nursing assistants, radiological technicians, pharmacists, physical therapists, nutritionists, and occupational therapists, among others) at a hospital in Japan, using a 5-step scale and a not applicable (N/A) option. Valid responses were obtained from 923 (55.3%) participants, and all seven factors extracted by factor analysis had Cronbach's α coefficients of greater than 0.9. Using cluster analysis based on principal component analysis, four categories were identified. According to the results of the N/A χ2 (chi-square) test question item and occupation, nurses answered N/A the least, followed by doctors, physical therapists, and occupational therapists. Nursing assistants' awareness and behavior were both low, suggesting the necessity of education on preventing falling accidents. By applying the "Self-Evaluation of Awareness and Behavior for Falling Accident Prevention" to all medical staff, we succeeded in clarifying their characteristics of awareness and behavior for falling accident prevention.

Latent Autonomous Cortisol Secretion From Apparently Nonfunctioning Adrenal Tumor in Nonlateralized Hyperaldosteronism.

CONTEXT: Adrenal tumors (ATs), even those diagnosed as nonfunctioning, may cause metabolic disorders. Some primary aldosteronism (PA) patients with ATs are diagnosed with bilateral PA based on adrenal venous sampling (AVS), and their ATs are apparently nonfunctioning. OBJECTIVE: To clarify the influence of apparently nonfunctioning ATs, we compared hormone levels and clinical complications between bilateral PA cases with and without ATs. DESIGN, SETTING, AND PARTICIPANTS: After retrospectively assessing 2814 patients with PA in the multicenter Japan PA study, bilateral PA cases on AVS were divided into cases with and without ATs by computed tomography findings. Importantly, patients with cortisol levels >1.8 µg/dL after the 1-mg dexamethasone suppression test (DST) were excluded. Clinical characteristics and biochemical data were compared between them. The correlation between AT size and hormone levels was also analyzed. MAIN OUTCOME MEASURES: Analyzed were 196 bilateral PA patients with ATs and 331 those without ATs. Although basal cortisol and aldosterone levels were similar between them, cortisol levels after the 1-mg DST and the prevalences of diabetes mellitus and proteinuria were significantly higher and ACTH levels and plasma renin activity were significantly lower in cases with ATs than in those without. After adjusting for patients' backgrounds, cortisol levels after the 1-mg DST and plasma renin activity remained significantly different between them. Moreover, cortisol levels after the 1-mg DST and ACTH levels correlated with AT size. CONCLUSIONS: Apparently nonfunctioning ATs in bilateral PA cases may cause latent autonomous cortisol secretion, inducing diabetes and proteinuria.

Renal impairment is closely associated with plasma aldosterone concentration in patients with primary aldosteronism.

OBJECTIVE: Several clinical studies have reported that renal impairments are sometimes observed in patients with primary aldosteronism (PA). We analyzed the prevalence of renal impairments in PA patients and identified parameters that increase the risk for them. DESIGN: This is a retrospective cross-sectional study. We assessed the PA database established by the multicenter Japan PA study (JPAS). Data were also collected from patients with essential hypertension (EHT). METHODS: We compared the prevalences of proteinuria and lowered estimated glomerular filtration rate (eGFR) between patients with PA and age, sex, blood pressure and duration of hypertension-matched patients with EHT. We also performed logistic regression analysis to identify parameters that increase the risk for these renal impairments. RESULTS: Among 2366 PA patients, the prevalences of proteinuria and lowered eGFR were 10.3 and 11.6%, respectively. The prevalence of proteinuria was significantly higher in PA patients than matched-EHT patients (16.8 vs 4.4%), whereas there was no significant difference in the prevalence of lowered eGFR (17.2 vs 15.0%). The logistic regression analysis also showed that the plasma aldosterone concentration (PAC) significantly increases the risk of proteinuria and lowered eGFR, independent of other known risk factors. CONCLUSION: Plasma aldosterone levels are closely associated with renal impairment in patients with PA. This is contrast to our earlier finding that the PAC was not itself linearly associated with cardiovascular events such as stroke or ischemic heart disease. The mechanism underlying the kidney damage in patients with PA may differ from that affecting the cardiovascular system.

High Prevalence of Diabetes in Patients With Primary Aldosteronism (PA) Associated With Subclinical Hypercortisolism and Prediabetes More Prevalent in Bilateral Than Unilateral PA: A Large, Multicenter Cohort Study in Japan.

OBJECTIVE: To investigate the prevalence and causes of diabetes in patients with primary aldosteronism (PA) in a multi-institutional cohort study in Japan. RESEARCH DESIGN AND METHODS: The prevalence of diabetes was determined in 2,210 patients with PA (diagnosed or glycated hemoglobin [HbA1c] ≥6.5% [≥48 mmol/mol]; NGSP) and compared with that of the Japanese general population according to age and sex. In 1,386 patients with PA and clear laterality (unilateral or bilateral), the effects of plasma aldosterone concentration (PAC), hypokalemia (<3.5 mEq/L), suspected subclinical hypercortisolism (SH; serum cortisol ≥1.8 µg/dL after 1-mg dexamethasone suppression test), and PA laterality on the prevalence of diabetes or prediabetes (5.7% ≤ HbA1c <6.5% [39 mmol/mol ≤ HbA1c <48 mmol/mol]) were examined. RESULTS: Of the 2,210 patients with PA, 477 (21.6%) had diabetes. This prevalence is higher than that in the general population (12.1%) or in 10-year cohorts aged 30-69 years. Logistic regression or χ2 test revealed a significant contribution of suspected SH to diabetes. Despite more active PA profiles (e.g., higher PAC and lower potassium concentrations) in unilateral than bilateral PA, BMI and HbA1c values were significantly higher in bilateral PA. PA laterality had no effect on the prevalence of diabetes; however, the prevalence of prediabetes was significantly higher in bilateral than unilateral PA. CONCLUSIONS: Individuals with PA have a high prevalence of diabetes, which is associated mainly with SH. The prevalence of prediabetes is greater for bilateral than unilateral PA, suggesting a unique metabolic cause of bilateral PA.

Effects of decreased renal cortical expression of G protein-coupled receptor kinase 4 and angiotensin type 1 receptors in rats.

Abnormalities in renal angiotensin type 1 receptor (AT1R), D1 dopamine receptor (D1R) and G protein-coupled receptor kinase 4 (GRK4) are present in polygenic hypertension. Selective renal reduction of AT1R expression by intrarenal cortical infusion of antisense oligodeoxynucleotides (As-Odns) in conscious, uninephrectomized, sodium-loaded rats decreases proteinuria, normalizes the glomerular sclerosis index (GSI), increases the sodium excretion (UNaV), and modestly increases blood pressure (BP) in spontaneously hypertensive rats (SHR) but not in normotensive Wistar-Kyoto rats (WKY). In contrast, selective renal reduction of GRK4 expression by infusion of GRK4 As-Odns increases UnaV, attenuates the increase in arterial BP with age, and modestly decreases protein excretion in SHR, but not in WKY. In this study, we report that intrarenal cortical infusion of both GRK4 and AT1R As-Odns decreased BP and increased UNaV in SHR; these effects were also noted in WKY to a lesser extent. Infusion of SHR with this combination of As-Odns resulted in a decrease in proteinuria and improvement of GSI similar to those by AT1R As-Odn only. In contrast to the increased circulating angiotensin II and aldosterone levels induced by AT1R As-Odn alone, the combination of As-Odns decreased both, contributing to greater natriuresis and amelioration of hypertension than by GRK4 or AT1R As-Odn only. Our results indicate an interaction between GRK4-regulated receptors and the renin-angiotensin system in the regulation of renal function and BP.