Effects of 1-year treatment with canagliflozin on body composition and total body water in patients with type 2 diabetes.

AIM: To characterize the long-term changes in body composition associated with sodium-glucose cotransporter-2 (SGLT2) inhibitors. MATERIALS AND METHODS: In this multicentre, single-arm, open-label study, 107 patients with type 2 diabetes were treated with canagliflozin 100 mg, as add-on therapy, for 12 months. Body composition was measured with a body composition analyser (T-SCAN PLUS) using the impedance method to prospectively analyse changes in body components, including percentage of body fat, body fat mass, total body water, muscle mass and mineral mass. Estimated plasma volume (PV) was calculated using the Kaplan formula. RESULTS: Body weight showed a significant decrease from 1 month to 12 months of treatment with canagliflozin, with a higher rate of decrease in body fat in body composition. A significant decrease in mineral mass was also observed, but its rate was low. Following treatment with canagliflozin, changes in total body water did not affect intracellular water, and a significant decrease in extracellular water, including plasma components, was observed early and was sustained up to 12 months. Protein mass, a component of muscle mass, was not affected, with only a slight decrease in water volume observed. CONCLUSIONS: Canagliflozin decreased extracellular fluid and PV in addition to decreasing fat in the body via calorie loss resulting from urinary glucose excretion. This study suggested that SGLT2 inhibitors might reduce body weight by regulating fat mass or water distribution in the body and might have cardiac and renal protective effects by resetting the homeostasis of fluid balance.

Renal effects of sodium glucose co-transporter 2 inhibitors in Japanese type 2 diabetes mellitus patients with home blood pressure monitoring.

Decrease in blood pressure contributes to the reno-protective effects of sodium-glucose cotransporter 2 inhibitors; however, its relationship with home monitoring of blood pressure is unclear. We retrospectively analyzed 101 visiting members of the Kanagawa Physicians Association with type 2 diabetes mellitus and chronic kidney disease who were taking sodium-glucose cotransporter 2 inhibitors and who monitored blood pressure at home for a median treatment period of 14 months. At baseline, the mean value of HbA1c was 59.3 mmol/mol (7.6%) and the median value of albumin-creatinine ratio was 30.9 mg/gCr that was evaluated in 88 patients. The mean blood pressure both at office and home significantly decreased, and there was a significant positive correlation between the change in albumin-creatinine ratio and both blood pressures. Controlled hypertension, masked hypertension, white coat hypertension, and sustained hypertension were observed in 10.9%, 13.9%, 12.9%, and 62.4% of patients at the initiation of therapy, which changed to 10.9%, 16.8%, 17.8%, and 54.5% at the time of the survey, respectively. In conclusion, management of blood pressure both at office and home was found to be important for the reno-protective effects of sodium-glucose cotransporter 2 inhibitors along with strict blood pressure management.

A questionnaire survey of general practitioners in Japan's Kanagawa Prefecture for the Japanese Society of Hypertension Guidelines for the Management of Hypertension 2014.

To evaluate the Japanese Society of Hypertension Guidelines for the Management of Hypertension 2014 (JSH2014) among Japanese general practitioners (GPs), we used a questionnaire survey with 209 GPs from the Kanagawa Physicians Society. Overall, 93.6% of GPs felt that the contents of the JSH2014 were useful. Based on the results showing that 81.8% of GPs instructed the measurement of blood pressure (BP) in the early morning at home to most patients, GP's acceptance of home BP methods and their penetration among patients with hypertension were considerably high. Regarding the number of home BP measurements, percentages for "one time," "two times," "three times," and "as many times as the patient decides," were 20.2%, 44.9%, 12.2%, and 22.9%, respectively; as such, no consensus was reached. Overall, 80.6% of GPs instructed most patients on sodium restriction; however, the content and method of restriction varied. Furthermore, 14.7% collected spot urine to assess salt intake. Many GPs respected the JSH2014 and faithfully adopted the guidelines during medical care. However, GPs did not necessarily agree with all guidelines. GPs sometimes selected the appropriate method for the individual patients and careful observations of how the guidelines affect actual clinical practice may lead to better medical care.

Implementation of a Community-Based Triage for Patients with Suspected Transient Ischemic Attack or Minor Stroke Study: A Prospective Multicenter Observational Study.

BACKGROUND: Japan has the highest number of magnetic resonance imaging units in the world, and citizens can freely choose medical care at any hospital or clinic. We aimed to investigate the triage of patients with suspected transient ischemic attack (TIA) or minor stroke in this unique Japanese healthcare system. METHODS: In this cohort study, patients with suspected TIA or minor stroke (National Institutes of Health Stroke Scale score <4) within 7 days after onset were prospectively enrolled and followed for 1 year. The high-risk group was defined as having at least one of the following 5 items at the initial visit: (1) atrial fibrillation, (2) carotid stenosis, (3) crescendo TIA, (4) definite focal brain symptoms, or (5) ABCD2 score of 4 or higher. After the initial assessment, the patients were diagnosed as having acute ischemic cerebrovascular syndrome (AICS) or stroke mimic. AICS was classified into 3 categories including definite, probable, and possible AICS, based on evidence of neurological deficits and brain infarction on the imaging study. RESULTS: A total of 353 patients were enrolled and 89.8% of the patients were examined by diffusion-weighted imaging at the initial visit. Kaplan-Meier analyses demonstrated a statistically significant difference in subsequent stroke risk when the patients were triaged by the ABCD2 score (P = .031), 5-item high-risk categorization (P = .032), or AICS classification (P = .001). CONCLUSIONS: This study demonstrates that hospitals and clinics with imaging facilities play a major role in triage and that the ABCD2 score, 5-item high-risk categorization, and AICS classification are useful as triage tools for patients with suspected TIA or minor stroke.

Validity of salt intake assessment system based on a 24-h dietary recall method using a touch panel computer.

BACKGROUND: An electronic system for salt intake assessment using a 24-h dietary recall method has been developed in Japan. We evaluated the validity of this salt intake system for assessing salt intake. METHODS: We prospectively obtained data on estimated salt intake using 24-hour urinary sodium excretion (24-hUNaCl) and salt intake by the salt intake assessment system from 203 consecutive outpatients with essential hypertension (age: 67.8 ± 10.7 years; 53.7% men). RESULTS: Mean values were 9.7 ± 2.9 g/day for 24-hUNaCl and 9.1 ± 2.9 g/day for the salt intake assessment system before corrections. The salt intake estimated by the present system was significantly correlated with 24-hUNaCl (r = 0.66, p < 0.0001). After corrections for habitual use of discretionary seasonings, habitual intake of salty foods, and physical activity, correlation coefficients between salt intake and 24-hUNaCl increased from 0.60 to 0.66 in men <65 years, from 0.80 to 0.81 in men ≥ 65 years, from 0.64 to 0.75 in women <65 years, and from 0.52 to 0.59 in women ≥ 65 years. After further correction for regional differences in average salt intake, the correlation coefficient reached 0.72 in all patients. CONCLUSION: After correction for dietary habits, lifestyle factors, and differences in average salt intake by region, this system may be a useful tool in Japan to encourage salt restriction in the clinical treatment of hypertension and improve public health in terms of salt restriction overall.

Pretreatment body mass index affects achievement of target blood pressure with sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus and chronic kidney disease.

Sodium-glucose cotransporter 2 inhibitor (SGLT2-I) shows excellent antihypertensive effects in addition to its hypoglycemic effects. However, whether body mass index (BMI) affects the antihypertensive effect of SGLT2-I remains unknown. We investigated the impact of baseline BMI on the achievement of target blood pressure (BP) with SGLT2-I treatment in Japanese patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). We retrospectively evaluated 447 Japanese patients with T2DM and CKD treated with SGLT2-I for at least 1 year. The primary outcome was achieving the target BP (<130/80 mmHg) after SGLT2-I treatment. Patients were divided into two groups according to a baseline BMI of 29.1 determined by receiver operating characteristic analysis and analyzed in a cohort model with propensity score matching. In each group, 130 patients were compared by propensity score matching. The target BP achievement rate was significantly higher in the BMI < 29.1 group than in the BMI ≥ 29.1 group (34% and 21%, respectively, p = 0.03). The odds ratio for achieving the target BP in the BMI ≥ 29.1 group was 0.50 (95% confidence interval, 0.28-0.90, p = 0.02). The BMI < 29.1 group had significantly lower systolic and diastolic BPs after SGLT2-I treatment than the BMI ≥ 29.1 group. Only the BMI < 29.1 group was showed a significant decrease in the logarithmic albumin-to-creatinine ratio from baseline after SGLT2-I treatment. In patients with T2DM and CKD, baseline BMI was associated with the antihypertensive effects of SGLT2-I. Patients in the lower baseline BMI group were more likely to achieve the target BP after SGLT2-I treatment. Pretreatment BMI affects the antihypertensice effect of SGLT2 inhibirors in patients with T2DM and CKD.

Cross-sectional survey of hypertension management in clinical practice in Japan: the Kanagawa Hypertension Study 2021 conducted in collaboration with Japan Medical Association Database of Clinical Medicine.

We aim to assess the data of patients with hypertension in Kanagawa Prefecture, Japan, collected in 2021 that were provided by the Japan Medical Association Database of Clinical Medicine. Data collected in 2011 and 2014 by the Kanagawa Physicians Association were used for comparative analysis. The target blood pressure (BP) achievement rates for patients whose target office and home BP were <140/90 mmHg and <135/85 mmHg, respectively, were 72.5% and 75.8% in 2011, 66.0% and 68.5% in 2014, and 46.7% and 83.3% in 2021, respectively. The target office BP achievement rate in 2021 was significantly lower than those in 2011 and 2014 (p ≤ 0.009). In contrast, there was no significant difference and improvement of the achievement rates for patients whose target office and home BP were <130/80 mmHg and <125/75 mmHg, respectively, among the three surveys. After the Japanese Society of Hypertension 2019 Guidelines were released, the achievement rates for patients whose target BP was tightened were significantly lower than those for patients with unchanged target BP (office/home, p < 0.001/0.04). The proportion of the patients who achieved their office and home target BP using more than three drugs was 38.5% and 20.0%, respectively. In the present analysis, we unveiled the current problems encountered in the clinical management of hypertension in Japan. In particular, efforts should be focused on the management of patients that require strict BP control.

The concomitant use of sodium-glucose co-transporter 2 inhibitors improved the renal outcome of Japanese patients with type 2 diabetes treated with glucagon-like peptide 1 receptor agonists.

Aims: This study aimed to clarify the renal influence of glucagon-like peptide 1 receptor agonists (GLP1Ras) with or without sodium-glucose co-transporter 2 inhibitors (SGLT2is) on Japanese patients with type 2 diabetes mellitus (T2DM). Methods: We retrospectively extracted 547 patients with T2DM who visited the clinics of members of Kanagawa Physicians Association. The progression of albuminuria status and/or a ≥ 15% decrease in the estimated glomerular filtration rate (eGFR) per year was set as the renal composite outcome. Propensity score matching was performed to compare GLP1Ra-treated patients with and without SGLT2i. Results: After matching, 186 patients in each group were compared. There was no significant difference of the incidence of the renal composite outcomes (17% vs. 20%, P = 0.50); however, the annual decrease in the eGFR was significantly smaller and the decrease in the urine albumin-to-creatinine ratio was larger in GLP1Ra-treated patients with the concomitant use of SGLT2is than in those without it (-1.1 ±â€…5.0 vs. -2.8 ±â€…5.1 mL/min/1.73 m2, P = 0.001; and -0.08 ±â€…0.61 vs. 0.05 ±â€…0.52, P = 0.03, respectively). Conclusion: The concomitant use of SGLT2i with GLP1Ra improved the annual decrease in the eGFR and the urine albumin-to-creatinine ratio in Japanese patients with T2DM.

Concomitant treatment with insulin and sodium-glucose cotransporter 2 inhibitors was associated with the renal composite outcome in Japanese patients with type 2 diabetes and chronic kidney disease: A propensity score-matched analysis.

AIMS/INTRODUCTION: We previously reported that sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment was associated with an improvement of the albumin-to-creatinine ratio in Japanese patients with type 2 diabetes mellitus and chronic kidney disease. The present study clarified how concomitant insulin treatment (IT) with SGLT2i therapy influences the renal composite outcome (RCO). MATERIALS AND METHODS: We retrospectively evaluated 624 Japanese patients with type 2 diabetes mellitus and chronic kidney disease who underwent SGLT2i treatment. The renal composite outcome was set as progression of the stage of albuminuria or a ≥15% decrease in the estimated glomerular filtration rate per year. We developed a cohort model of patients managed with and without IT (Ins [+], Ins [-]) using propensity score matching methods. Furthermore, all patients in our study population were stratified into quintiles according to their propensity score. RESULTS: The incidence of the RCO was in Ins (+) patients significantly higher than that in Ins (-) (P = 0.033). The estimated hazard ratio for the RCO was 1.55 (P = 0.035) in Ins (+) patients. The change in the estimated glomerular filtration rate and albumin-to-creatinine ratio in the groups was not statistically significant. The analysis, which was based on the quintiles, showed a statistically significant difference between the Ins (+) and Ins (-) groups (P = 0.01); the odds ratio for the RCO in patients managed with IT was 2.20 (P = 0.01). CONCLUSIONS: Concomitant administration of IT with SGLT2is influenced the RCO in Japanese patients with type 2 diabetes mellitus and chronic kidney disease. We might need to consider the influence of concomitant agents on the renoprotective effects of SGLT2i therapy.

Polypharmacy influences the renal composite outcome in patients treated with sodium-glucose cotransporter 2 inhibitors.

Polypharmacy is a serious concern in general practice, especially among elder patients; however, the evidence showing significantly poor renal outcomes is not sufficient. This survey was performed to evaluate the effect of polypharmacy on the incidence of the renal composite outcome among a sample of patients with sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment. We assessed 624 Japanese patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease who received SGLT2i treatment for greater than 1 year. The patients were classified as those with concomitant treatment, that was limited to the medications for hypertension, T2DM, and dyslipidemia, with greater than or equal to seven medications (n = 110) and those with less than seven medications (n = 514). Evaluation of the renal composite outcome was performed by propensity score matching and stratification into quintiles. A subgroup analysis of patients of greater than or equal to 62 years of age and less than 62 years of age was also performed. The incidence of the renal composite outcome was larger in patients with greater than or equal to seven medications than in those with less than seven medications in the propensity score-matched cohort model (6% vs. 17%, respectively, p = 0.007) and also in the quintile-stratified analysis (odds ratio [OR], 2.23, 95% confidence interval [CI, 1.21-4.12, p = 0.01). The quintile-stratified analysis of patients of less than 62 years of age-but not those of greater than or equal to 62 years of age-also showed a significant difference (OR, 3.29, 95% CI, 1.41-7.69, p = 0.006). Polypharmacy appears to be associated to the incidence of the renal composite outcome, especially in young patients.

Direct comparison of the reproducibility of in-office and self-measured home blood pressures.

OBJECTIVE: The aim was to compare short-term and long-term reproducibilities of in-office unattended blood pressure (BP), namely automated office blood pressure (AOBP), conventionally measured attended office BP, and self-measured home BP. METHODS: A multicentre, clinical study was conducted in Japan, and 287 Japanese outpatients on antihypertensive drug medication were followed-up for 1 year. RESULTS: The intensity of drug treatment was sustained consistently throughout the study period (defined daily doses, 1.62-1.68; P = 0.12). The mean SBP differences between baseline and 1 month later, as well as baseline and 1 year later, were less than 1.5 mmHg, whereas the standard deviations of the differences for home, AOBP, and attended office measurements for the 1-year interval were 7.7, 14.5, and 15.3 mmHg, respectively. The coefficients of variation were significantly smaller for home BP than for AOBP among all patients at both 1-month and 1-year intervals (P < 0.0001). In the 1-month interval, partial correlation coefficients of home BP (r, 0.73/0.88 for systolic/diastolic measures) were significantly higher than of conventional BP (r, 0.47/0.69). However, the correlations converged to the modest level regardless of BP information (r, 0.49-0.54/0.63-0.73) when the 1-year interval was assessed. Results were confirmatory when patients on the same drug regimen (n = 167) were analysed. CONCLUSION: A higher reproducibility of home BP was demonstrated compared with in-office BP, including AOBP. However, the modest correlations for the 1-year interval support the importance of regular assessment of BP, regardless of in-office or home measurements for treatment of hypertension.

The Proportion of Long-term Response to Anti-N IgG Antibody after 12 Months for COVID-19 Subclinical Infections and a Longitudinal Survey for COVID-19 Subclinical Infections in 2021.

Objective To examine the continuation of antibody prevalence status after 12 months and background factors in antibody-positive subjects following asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods We initially determined the SARS-CoV-2 anti-nucleocapsid protein immunoglobulin G (anti-N IgG) antibody prevalence in 1,603 patients, doctors, and nurses at 65 medical institutions in Kanagawa Prefecture, Japan. We then obtained consent from 33 of the 39 subjects who tested positive and performed follow-up for 12 months. Results Follow-up for up to 12 months showed that a long-term response of the anti-N IgG antibody could be detected in 6 of the 33 participants (18.2%). The proportions with hypertension, using an angiotensin-receptor blocker, and without a drinking habit were higher among the participants with a long-term anti-N IgG antibody response for up to 12 months than among those without a long-term antibody response. Conclusions The proportion of individuals with subclinical COVID-19 who continuously had a positive result for the anti-N IgG antibody at 12 months was low.

Persistence of Robust Humoral Immune Response in Coronavirus Disease 2019 Convalescent Individuals Over 12 Months After Infection.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits varying degrees of protective immunity conferred by neutralizing antibodies (nAbs). In this study, we report the persistence of nAb responses over 12 months after infection despite their decreasing trend noticed from 6 months. METHODS: The study included sera from 497 individuals who had been infected with SARS-CoV-2 between January and August 2020. Samples were collected at 6 and 12 months after onset. The titers of immunoglobulin (Ig)G to the viral nucleocapsid protein (NP) and receptor-binding domain (RBD) of the spike protein were measured by chemiluminescence enzyme immunoassay. The nAb titer was determined using lentivirus-based pseudovirus or authentic virus. RESULTS: Antibody titers of NP-IgG, RBD-IgG, and nAbs were higher in severe and moderate cases than in mild cases at 12 months after onset. Although the nAb levels were likely to confer adequate protection against wild-type viral infection, the neutralization activity to recently circulating variants in some of the mild cases (~30%) was undermined, implying the susceptibility to reinfection with the variants of concerns (VOCs). CONCLUSIONS: Coronavirus disease 2019 convalescent individuals have robust humoral immunity even at 12 months after infection albeit that the medical history and background of patients could affect the function and dynamics of antibody response to the VOCs.

Comparison of renal outcomes between sodium glucose co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists.

AIMS: This study aimed to clarify the differences in how sodium glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1Ra) influence kidney function in Japanese patients with type 2 diabetes mellitus (T2DM). METHODS: We retrospectively built two databases of patients with T2DM who visited the clinics of members of Kanagawa Physicians Association. We defined the renal composite outcome as either progression of albuminuria status and/or > 15% deterioration in estimated glomerular filtration rate (eGFR) per year. We used propensity score matching to compare patient outcomes after SGLT2i and GLP1Ra treatments. RESULTS: The incidence of renal composite outcomes was significantly lower in SGLT2i-treated patients than in GLP1Ra-treated patients (n = 15[11%] and n = 27[20%], respectively, P = 0.001). Annual eGFR changes (mL/min/1.73 m2/year) between the two groups differed significantly (-1.8 [95 %CI, -2.7, -0.9] in SGLT2i-treated patients and - 3.4 [95 %CI, -4.6, -2.2] in GLP1Ra-treated patients, P = 0.0049). The urine albumin-to-creatinine ratio changed owing to a significant interaction between the presence or absence of a decrease in systolic blood pressure and the difference in treatments (P < 0.04). CONCLUSION: Renal composite outcome incidence was lower in SGLT2i-treated patients than in GLP1Ra-treated patients.

The Comparison of the Kidney Effects of Dipeptidyl Peptidase 4 Inhibitors and Glucagon-Like Peptide 1 Agonist-Administered Concomitant with Sodium-Glucose Cotransporter 2 Inhibitors in Japanese Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease.

METHODS: We retrospectively constructed database of 763 Japanese patients with T2DM and CKD who received sSGLT2is for more than 1 year. Among these SGLT2i-treated patients, 338 were receiving concomitant DPP4i (DPP4i group), and 99 were receiving concomitant GLP1Ra (GLP1Ra group). The two groups were compared using the propensity score matching method. RESULTS: In the matched model including 86 cases per group, the decrease in the logarithmic value of the ACR and rate of reduction in the estimated glomerular filtration rate (eGFR; mL/min/1.73 m2) of the GLP1Ra group showed no significant difference from those in the DPP4i group (-0.12 ± 0.48 vs. -0.13 ± 0.45 and -2.3 ± 18.5 vs. -6.2 ± 13.8, respectively, P = 0.10). However, the incidence of a >6.4% decrease in the eGFR was significantly lower in the GLP1Ra group than in the DPP4i group (35% vs. 52%, respectively, P = 0.03). The level of hemoglobin A1c (mmol/mol) after SGLT2i treatment was significantly lower in the DPP4i group than in the GLP1Ra group in the matched model (58.3 ± 11.8 and 62.7 ± 14.8, respectively, P = 0.02). CONCLUSION: Among the SGLT2i-treated patients with T2DM and CKD, concomitant treatment with GLP1Ra has a marked improving effect on the change in the eGFR.

The evaluation of noninferiority for renal composite outcomes between sodium-glucose cotransporter inhibitors in Japan.

BACKGROUND: In Japan, six types of sodium-glucose cotransporter inhibitors (SGLT2Is) are currently in use. Here, we evaluated differences in renal composite outcomes between SGLT2Is with or without evidence of cardio vascular outcome trials (CVOTs). METHODS: We retrospectively surveyed 536 Japanese patients with type 2 diabetes mellitus with chronic kidney disease who received SGLT2Is for more than 1 year. Patients were classified as having received empagliflozin, canagliflozin, or dapagliflozin (n = 270, Evidence (+) group) or as having received ipragliflozin, tofogliflozin, or luseogliflozin (n = 266, Evidence (-) group). The propensity score matching method was performed. RESULT: On matched cohort model including 205 cases in each group, there were no significant differences in the incidence of renal composite outcomes (n = 28 [14%] in the Evidence (+) group, n = 21 [10%] in the Evidence (-) group for the matched model; p = 0.29) between groups. Cox hazard analyses in the matched cohort model showed that the risk ratio for renal composite outcomes in the Evidence (-) group was 0.73 (95% confidence interval: 0.40-1.32), which was greater than the noninferiority margin of 1.22. CONCLUSION: Three SGLT2Is with no CVOT's evidence did not show noninferiority compared with other SGLT2Is with evidences.

Sodium-glucose cotransporter 2 inhibitor-induced reduction in the mean arterial pressure improved renal composite outcomes in type 2 diabetes mellitus patients with chronic kidney disease: A propensity score-matched model analysis in Japan.

AIMS/INTRODUCTION: Large-scale clinical trials have reported that, in patients with type 2 diabetes mellitus, sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment affords favorable renal outcomes; the underlying mechanisms, however, remain unclear. Thus, this study investigated how SGLT2 inhibitor-induced changes in the mean arterial pressure (MAP; denoted as ΔMAP) are associated with renal outcomes in type 2 diabetes mellitus patients with chronic kidney disease (CKD). MATERIALS AND METHODS: We retrospectively assessed the data of 624 Japanese type 2 diabetes mellitus patients with CKD who had been using SGLT2 inhibitors for >1 year. For propensity score matching (1:1 nearest neighbor match, with caliper value = 0.053, no replacement), patients were categorized into two groups based on the ΔMAP (>-4 mmHg [n = 329] and ≤-4.0 mmHg [n = 295]). Composite albuminuria progression or a ≥15% annual reduction in the estimated glomerular filtration rate was regarded as the end-point. RESULTS: Per group, 173 propensity-matched patients were compared. Patients with ΔMAP ≤-4 mmHg had a significantly lower incidence of composite renal outcomes than those with ΔMAP ≥-4 mmHg (5.8% [n = 10] vs 15.6% [n = 27], P = 0.003). Although the between-group differences in the estimated glomerular filtration rates were non-significant, patients with a ΔMAP ≤-4 mmHg had significantly larger reductions in the logarithmic urine albumin-to-creatinine ratio (P = 0.005). CONCLUSIONS: The degree of blood pressure reduction after SGLT2 inhibitor treatment influenced renal composite outcomes in Japanese type 2 diabetes mellitus patients with CKD, confirming the importance of blood pressure management in type 2 diabetes mellitus patients with CKD, even when they are under SGLT2 inhibitor treatment.

Comparison of questionnaire responses regarding awareness of Japanese Society of Hypertension guidelines for the management of hypertension between 2014 and 2019 in primary care.

In 2019, the Japanese Society of Hypertension guidelines for the management of hypertension (JSH) were revised. We previously reported the awareness of JSH among general practitioners in 2014, and in the current study, the same questionnaire was administered to determine their awareness of JSH 2019, and their responses were compared. We also sought to identify effective strategies to raise awareness of hypertension. The questionnaires included the same 12 questions as in 2014 and were mailed to members of two professional organizations from October to November 2019. Responses from 256 general practitioners in 2019 and 209 in 2014 were compared using the propensity score matching method to align the responders' backgrounds. Component analysis was performed to classify responders into appropriate clusters. The matched cohort of all 202 responders was analyzed. In both 2014 and 2019, >80% of responders instructed patients to perform home blood pressure monitoring (JSH 2014: 81.7% and JSH 2019: 84.6% in the matched cohort), and >70% instructed patients with hypertension to restrict their salt intake (JSH 2014: 79.7% and JSH 2019: 74.7% in the matched cohort). Regarding the clinical blood pressure measurement method, more responders answered "one time outside the consulting room" in the JSH 2019 group (p = 0.042). Fewer general practitioners responded that differential diagnosis for primary aldosteronism was performed in the JSH 2019 group (p = 0.032); however, the frequency of checking the aldosterone-renin ratio increased in the JSH 2019 group (p = 0.055). We confirmed the change in general practitioners' awareness of hypertension management. The categorized clusters may be useful for the development of effective strategies for higher-quality hypertension management in clinical practice.

Sustained Neutralizing Antibodies 6 Months Following Infection in 376 Japanese COVID-19 Survivors.

Objective: There is scarce evidence regarding the long-term persistence of neutralizing antibodies among coronavirus disease 2019 (COVID-19) survivors. This study determined neutralizing antibody titers (NT50) and antibodies against spike protein (SP) or nucleocapsid protein (NP) antigens approximately 6 months after the diagnosis of COVID-19. Methods: COVID-19 survivors in Japan were recruited. Serum samples and data related to patients' characteristics and COVID-19 history were collected. NT50 and titers of antibodies against NP and SP antigens were measured at 20-32 weeks after the first positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results. Factors associated with NT50 were identified using the multivariable linear regression and the correlations among NT50 and titers of immunoglobulin G (IgG) and total immunoglobulins (Igs) against NP and SP were assessed by Spearman's correlation. Results: Among 376 participants (median [range] days after testing positive for SARS-CoV-2, 180 (147-224); median [range] years of age, 50 (20-78); 188 [50%] male), most tested positive for NT50 (n = 367, 98%), SP-IgG (n = 344, 91%), SP-total Ig (n = 369, 98%), NP-IgG (n = 314, 84%), and NP-total Ig (n = 365, 97%). Regression analysis indicated that higher BMI, fever, and the requirement of mechanical ventilation or extracorporeal membrane oxygenation were significantly associated with higher NT50. Anti-SP antibodies correlated moderately with NT50 (Spearman's correlation: 0.63 for SP IgG; 0.57 for SP-total Ig), while the correlation was weak for anti-NP antibodies (0.37 for NP IgG; 0.32 for NP-total Ig). Conclusions: Most COVID-19 survivors had sustained neutralizing antibodies and tested positive for SP-total Ig and NP-total Ig approximately 6 months after infection.

Retrospective Analysis of the Renoprotective Effects of Long-Term Use of Six Types of Sodium-Glucose Cotransporter 2 Inhibitors in Japanese Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease.

Aim: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) provide renal protection in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to elucidate the renal effects of long-term use of six types of SGLT2is in Japanese patients with T2DM and chronic kidney disease (CKD). Materials and Methods: The Kanagawa Physicians Association maintains a registry of patients who visit their 31 clinics. We retrieved clinical data of patients with T2DM and CKD who were prescribed with SGLT2is for >1 year. Results: A total of 763 patients with a median treatment duration of 33 months were included. The logarithmic value of urine albumin-creatinine ratio (LNACR) decreased significantly from 1.60 ± 0.65 to 1.51 ± 0.67. The multiple linear regression analysis revealed that the LNACR at the initiation of treatment, change in (Δ) diastolic blood pressure, and Δ hemoglobin A1c were independently correlated with ΔLNACR (P < 0.001). The decrease in the LNACR was significantly smaller in the patients with estimated glomerular filtration rate (eGFR) [mL/(min ·1.73 m2)] of <60 (P < 0.05). The eGFR decreased from 77.4 ± 22.3 to 72.7 ± 22.5 mL/(min ·1.73 m2) (P < 0.001). The multiple linear regression analysis showed that the LNACR at the initiation of treatment, Δbody weight at the previous survey, ΔeGFR at the previous survey, and the eGFR at the initiation of treatment correlated independently with ΔeGFR during the maintenance period (P < 0.001). Greater changes in the eGFR during the maintenance period were observed in the patients with macroalbuminuria or eGFR of <60 (P < 0.01). Conclusions: The study confirmed that the long-term use of six types of SGLT2i improved the albumin-creatinine ratio (ACR), although the eGFR gradually decreased during the treatment. The change in the ACR was significantly smaller in the patients with eGFR of <60 mL/(min ·1.73 m2) than in those with eGFR of >60 mL/(min ·1.73 m2). However, this was a retrospective observational study; further studies are needed to formulate final conclusions.