The rate of blood pressure control among hypertensive patients is poor and the reasons for poor control of blood pressure remain poorly understood globally.To assess the rate of blood pressure control among adult hypertensive patients at Jimma University Specialized Hospital.We conducted a hospital based cross sectional study among adult hypertensive patients at Jimma University Specialized Hospital hypertension clinic from March 4, 2015 to April 3, 2015. Data on sociodemographic characteristics of the participants and adherence to antihypertensive medication(s) were collected from patients by face to face interview using a pretested structured questionnaire. Comorbidities, antihypertensive medication(s) and blood pressure measurements were collected retrospectively from medical records. Medication adherence was assessed using Morisky’s Medication Adherence Scale-8 score. We did the statistical analysis using chi-square test and binary logistic regression with level of α set at 0.05. Statistical significance was considered for variables with p<0.05.Out of 311 participants, 286 patients were eligible and were studied. More than half, 154 (53.8%), of the participants were males. The mean age of the participants was 54.8± 12.6 years (range 26 to 94). The majority, 196 (68.53%), of the participants were taking more than one antihypertensive medication. More than one third (39.5%) of the participants were non adherent to their medication(s). The rate of blood pressure control was 50.3%. In a univariate logistic regression analyses, age ≥65 years old (P = 0.008), physical inactivity (p<0.001), chat chewing (P<0.001), adding salt to food (P<0.001), and coffee use (P<0.001) are significantly associated with uncontrolled blood pressureAlmost half of the hypertensive patients on follow up had uncontrolled blood pressure. We recommend better health education and care of patients to improve the rate of blood pressure control at the hospital. Hypertension is one of the most significant risk factors for cardiovascular diseases (CVDs). Its global burden increasing , 2. It iThe burden of hypertension and other cardiovascular diseases is increasing in developing countries , 6–8. InThe majority of patients’ blood pressure remains uncontrolled in all societies , 13, 14 Despite the availability of effective medical therapy, more than half of hypertensive patients on treatment have blood pressures above 140/90 mm Hg threshold , 16. In Uncontrolled hypertension can lead to increased incidence of complications including coronary heart disease, acute myocardial infarction, peripheral vascular disease, stroke, congestive heart failure and renal failure , 20. A lRecent evidence indicates that hypertension and elevated BP are increasing partly because of the increase in risk factors including smoking, obesity, harmful use of alcohol and lack of exercise , 23, 24.There are a limited number of researches on BP control status of hypertensive in Ethiopia. The lack of adequate studies on hypertension significantly affects hypertension management and care of hypertensive patients in the country. Thus, this study aimed to assess BP control status among adult hypertensive patients at Jimma University Specialized Hospital (JUSH).We conducted a hospital based cross sectional study among adult hypertensive patients at Jimma University Specialized Hospital (JUSH) hypertension clinic from March 4, 2015 to April 3, 2015. Jimma University Specialized Hospital (JUSH) is both a referral and teaching hospital with 523 beds serving for, approximately, 20,000 admissions and 140, 000 outpatient visits a year. It serves for a catchment population of about 15 million people. Hypertensive patients get follow up care and antihypertensive medications at hypertension clinic every month. The clinic provides service for 1694 ambulatory hypertensive patients.The study was approved by Jimma University Collage of Public Health and Medical Sciences Ethical Review Committee. Prior to data collection on sociodemographic characteristics and adherence of participants to antihypertensive medication(s), each participant signed a written informed consent. We conducted a face to face interview with a pretested structured questionnaire. The participants had a right to withdraw from participation. Comorbidities, antihypertensive medication(s) and blood pressure measurements were collected from medical records of patients using a pretested data abstraction format.To maintain the validity of the data collection tool, a structured questionnaire was developed and translated to local languages (Amharic and Afan Oromo) and back translated to English. We used Morisky’s Medication Adherence Scale (MMAS-8) to assess the participants’ medication adherence.Physical activity was assessed by asking each participant the number of minutes per day and the number of days per week a patient spent doing physical activity. The participants were classified into physically active if they reported that they were farmer or if they reported that they exercise greater than 30 minutes for greater than 5 days of the week otherwise they were classified as physically inactive. Body weight was measured to the nearest 0.1kg using a digital scale and height was measured to the nearest 0.1cm in the standing position using a portable height board. Body mass index was calculated as weight in kilogram divided by squared height (meter square).Participants included in the study were all hypertensive patients getting follow up at JUSH hypertension clinic. Participants ≥18 years old who were on follow up for at least 12 months and whose medical records contained complete pertinent data and who were willing to participate were included. Seriously ill patients not able to complete the interview and patients with incomplete medical records such as demographics and BP were excluded. The data were collected by six clinical nurses working at Jimma University Specialized Hospital (JUSH).Data extracted included sociodemographic characteristics, co-morbidities, adherence status of patients to antihypertensive medication(s), type of antihypertensive medication(s), duration of hypertension, and one year blood pressure measurements. The main outcome of the study was blood pressure control status.We analyzed the data using SPSS Version 20.0 . We conducted a univariate logistic regression analyses to identify factors that are associated with uncontrolled blood pressure. Variables with P<0.05 were considered statistically significant.Hypertension was defined as a sustained high blood pressure (SBP≥140 or DBP ≥90mmHg) or reported regular use of anti-hypertensive medication(s) . ControlIn this study, a total of 311 participants were interviewed and 286 of them were eligible and studied. The response rate was 92%. As shown in The majority, 160 (55.9%), of the participants have been taking salt with food. More than half, 158 (55.2%) of the participants were physically inactive. Nine participants (3.11%) were cigarette smokers, 48 (16.8%) were alcohol drinkers and 122 (42.7%) were chat chewers. The majority, 167 (58.4%), of the participants have been drinking coffee . The majThe majority, 167 (58.4%), of the participants had at least one co-morbidity. Seventy eight (27.2%) of the participants had diabetes, 66 (23.1%) had peripheral neuropathy, 32 (11.2%) had dyspepsia and 14 (4.9%) had hypertensive heart disease (HHD). The remaining 43 (15%) had other comorbidities .Out of the 286 participants, 196 (68.53%) were prescribed with more than one antihypertensive medication. The majority, (52.1%), were on two medications and 84 (29.4%) were on mono-therapy. Seventy seven (27%) of the participants on two medications had uncontrolled BP. Fifty three (18.6%) of the participants on monotherapy had controlled blood pressure. Forty six (16.1%) participants were prescribed with triple antihypertensive medications and only one participant was on four antihypertensive medications. The number of antihypertensive medications prescribed was not associated with blood pressure control status (P = 0.094). Ninety two (32.2%) of the participants have been getting their medication for free. Dietary approach to stop hypertension (DASH) therapy was practiced by 6 (2.4%) of the participants.Angiotensin converting enzyme inhibitors (ACEIs) and diuretics were the most commonly prescribed combination antihypertensive medication(s), 88 (30.8%). More than two third, 206 (72.0%), of the participants were prescribed with ACEIs  and 182 (34.7%) were prescribed with thiazide diuretics (hydrochlorothiazide) .According to MMAS-8 score, 173(60.5%) of the participants were adherent to their antihypertensive medications . The MMAThe rate of blood pressure control in this study was 50.3%. The mean SBP was 132.13 ± 20.30 mmHg and mean DBP was 81.5±12.1 mmHg. We performed univariate analyses to identify factors associated with uncontrolled hypertension . Age ≥65In this study about half, (49.7%), of the participants had uncontrolled blood pressure. More than half, 60.5%, of the participants were adherent to their antihypertensive medications. Diabetes mellitus and peripheral neuropathy were the commonly encountered co-morbidities among hypertensive patients.In our study more than half, 60.5%, of the study subjects were adherent to their antihypertensive medication(s). In United Arab Emirates , adherenThe level of adherence in our finding is similar to the findings in Gondar, Northwest Ethiopia (64.6%) and Adama, Southeast Ethiopia (59.5%) , 37. ThiWe found that 27.2% of the participants had diabetes mellitus co-morbidity. This finding is in line with the finding from Brazil (29.8%), but lower than the finding from Bahrain (55.8%) . This maThe rate of BP control in our study was 50.3%. This is lower than the findings reported from Bahrain (66.3%) and USA (69.7%) ,38. The The rate of blood pressure control is better than the findings reported by Goverwa et al (32.8%) from Zimbabwe, Lulebo et al (15.6%) from Congo, and Adebolu et al (42%) from South Africa ,34,39. TIn Kenya, 64.7% of the renal transplant recipients attending nephrology clinics had uncontrolled hypertension (BP≥130/80 mmHg)  which isThe rate of BP control was relatively similar to the study in Addis Ababa, Ethiopia (40.1%) and Gondar, Ethiopia (46.6%) , 41. ThiLiteratures showed that age is strongly related to systolic blood pressure and isolated systolic hypertension accounts for the majority of cases with uncontrolled BP in individuals greater than 60 years of age . HoweverFor many hypertensive patients, combination therapy is believed to achieve better BP control than monotherapy . In our In a univariate logistic regression analyses, age ≥65 years old (P = 0.008), physical inactivity (p<0.001), chat chewing (P<0.001), adding salt to food (P<0.001), and coffee use (P<0.001) are significantly associated with uncontrolled BP.Our study revealed that almost half of the participants had uncontrolled BP. More than half of the participants were adherent to their antihypertensive medications. Diabetes mellitus and peripheral neuropathy were the most commonly encountered comorbidities associated with hypertension. Age ≥65 years old (P = 0.008), physical inactivity (p<0.001), chat chewing (P<0.001), adding salt to food (P<0.001), and coffee use (P<0.001) are significantly associated with uncontrolled BP In a univariate logistic regression analyses. Based on our finding, we recommend Jimma University Specialized Hospital and Federal Ministry of Health of Ethiopia to devise strategies to provide education to hypertensive patients on dietary approach to stop hypertension (DASH) and medication adherence, develop hypertension management clinical practice guidelines and involve dedicated senior physicians and clinical pharmacists at hypertension clinic for better treatment and care of hypertensive patients.S1 Fig(TIFF)Click here for additional data file.S2 Fig(TIFF)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S4 Table(DOCX)Click here for additional data file.


Objective: The aim of this study was to evaluate the effect of Premenstrual Syndrome (PMS) treatment with selective serotonin reuptake inhibitor (SSRI) on treatment response of refractory hypertension of the patients.Method: This was a triple-blind randomized clinical trial conducted on female patients suffering from refractory hypertension and PMS at the same time. We obtained informed consent from 40 patients who had inclusion criteria and selected 20 patients for the intervention  and 20 for the control groups. The study period was five weeks. The mean of systolic and diastolic blood pressure before and after intervention was measured separately for each individual in each group and the mean of blood pressure of the members of the two groups were compared with each other.Results: The mean age of the participants was 43.60 ± 4.57. In this study, systolic and diastolic blood pressure of both groups reduced after intervention. The mean of systolic blood pressure was reduced by 40.86 mmHg in the intervention group and this reduction was 16 mm Hg in control group after intervention (P<0.001). Comparing this reduction between the two groups, we found that reduction rate in systolic blood pressure of the two groups did not have a significant statistical difference before and after the intervention (P = 0.11). Mean of diastolic blood pressure also showed reduction of 9.17 mm Hg and that of control group showed 6.7-mmHg reduction. Reduction rate of diastolic blood pressure in the intervention group had a statistically significant difference with that of the control group (P<0.017).Conclusion: Administration of sertraline is more effective in controlling diastolic blood pressure in women suffering from refractory hypertension and comorbid PMS. Clinical disorders related to mood and behavior in premenstrual phase have been the focus of attention since the past . PremensWhile PMS could affect 80% of women in childbearing age, PMDD incidence is about 5% . If sympSome randomized control trial studies on women suffering from PMDD have shown that selective serotonin reuptake inhibitors (SSRIs) have suitable effects with least side effects -9. A sysStudies have shown that in women with PMS, activity of the sympathetic nervous system increases in final stages of luteal phase and inversely activity of parasympathetic nervous system decreases in this stage , 14. In The primary objective of treating those suffering from hypertension, is reaching minimum cardiovascular disorders, which is possible through reduction of blood pressure and reversible risk factors . No compThe aim of this study was to evaluate the effect of PMS treatment with sertraline to control refractory hypertension in women with premenstrual syndrome.This was a triple- blinded randomized controlled study performed from June 2010 to June 2012. In this study, 100 female patients with the age range of 15 to 49 who suffered from refractory hypertension  and referred to the cardiology clinic of Tabriz University of Medical Sciences, the main referral center in Northwest of Iran, were selected.Among these 100 refractory hypertension patients, 40 who were also suffering from premenstrual syndrome based on test of Daily Record of Severity of Problems (DRSP) were selected after providing written informed consent. DSRP is a method used for diagnosis and evaluation of DSM-IV Premenstrual Dysphoric Disorder .Using Randlist software  patients were divided into two groups randomly: one group received 50 mg sertraline daily and the other received placebo. Inclusion criteria were being female, having refractory hypertension, having criteria for premenstrual dysphoric disorder, age between 15 and 49, and providing written informed consent. Exclusion criteria were history of allergy or complication to sertraline, bipolar mood disorders, depressive disorders and anxiety, psychosis, mental retardation, breastfeeding and pregnancy, acute coronary syndrome and heart failure. Patients with psychiatric disorders were excluded from the study, using a structured routine psychiatric interview.In this study, the physicians, patients and statisticians were not aware of type of consumed drug (medication or placebo). This was a triple- blinded study. Patients used their anti-hypertension medications as usual after joining the study, and no change was made in anti-hypertension drug regimen of the patients. Patients in the intervention group received 50 mg sertraline daily  for five weeks. Patients in the control group underwent treatment by placebo with a similar duration. The two groups were studied for five weeks, and between weeks 2 and 3, the patients of both groups were controlled in terms of medication side effects (using a related checklist) in person or by phone; and the checklist of side effects of SSRIs was completed for all patients. In addition, both groups were studied in terms of symptoms of sudden increase or decrease in blood pressure by history taking. TONOPORTAll participants signed a written consent, and the Ethics Committee of Tabriz University of Medical Sciences (TUMS) approved the study protocol, which was in compliance with Helsinki Declaration. The registration code of this study in Iranian Registry of Clinical Trials (IRCT) web site is IRCT138904092181N4.At the beginning of study and at the end of the fifth week, blood pressure of both groups were controlled again by 24-hour TONOPORT  , which is a portable patient monitor for ambulatory blood pressure measurement. The mean of blood pressure, minimum and maximum BP and even blood pressure of the patient in nighttime was obtained and all were compared with pre-study blood pressure. Obtained data have been represented as Mean ± Standard deviation (Mean ± SD), and also distribution and percentage. SPSSTM Version 15  was used for statistical analysis. Independent t-test and chi square test were used to analyze the data. P value less than 0.05 was considered as statistically significant.Forty patients participated in this study, and the mean age of the intervention group was 43.60 ± 4.57 years. The minimum age among the patients in the intervention group was 32 years and that of the control group was 33 years. The maximum age in the both groups was 49 years. No significant difference was found between the two groups in terms of age .During the study period, three patients (from intervention group) were excluded from the study due to experiencing medication side effects, and three persons from the control group due to dissuasion and lack of consent for continuing the study.In this study, the mean of systolic and diastolic blood pressures was not significantly different between the two groups based on the results of the t- test  and .At the end of the study, systolic and diastolic blood pressures of both groups were decreased.The mean of systolic blood pressure of the intervention group had a reduction of 40.86 mm Hg and that of the control group a reduction of 16 mm Hg. The mean of diastolic blood pressure of the intervention group had a reduction of 17.9 mm Hg and that of the control group a reduction of 6.7 mm Hg . Blood pressure of both groups at the start and at the end of the study is demonstrated in The reduction of systolic and diastolic blood pressure was statistically significant after prescribing medication in the intervention group (P<0.001 for both). In addition, reduction in systolic and diastolic blood pressure was statistically significant at the end of study in the control group . The reduction rate of systolic blood pressure was not significantly different between the two groups before and after the intervention .The reduction rate of diastolic blood pressure was statistically significant between the two groups before and after the intervention, and reduction of diastolic blood pressure was more in the intervention group . . Effect Placebo, compared to sertraline, had a lower effect on diastolic blood pressure of the patients  In this study, the observed side effects in prescribing five-week sertraline with dose of 50 mg daily, which were clinically important for patients were nausea (45%), stomach ache (25%), drowsiness (20%), increase or decrease of appetite (20%), vomiting (15%) and feelings of inner tension (15%). No side effects were reported in placebo group.Attention should be paid to the point that a major part of these side effects is almost clinically negligible and is seen in prescribing placebo. Since blood pressures of both groups were controlled by sphygmomanometer at a cardiology clinic, perhaps stress and anxiety resulted by measuring blood pressure on patient is more on systolic blood pressure rather than diastolic one. After the intervention, the systolic blood pressure reduced in the control group and it might have masked the probable effect of medication on systolic blood pressure.In addition, in this study, basic blood pressure of both groups was measured by normal barometer, but blood pressure was registered and controlled by a 24-hour monitoring after the intervention. However, checking blood pressure at clinics could lead to momentary hypertension in some people .In a case report study, hypertension in two women with recurrent hypertension after both were diagnosed with PMS, after treatment PMS problems with 25 mg amitriptyline and 1/5 mg Bromazepam daily during luteal phases per cycle in one case, and 50 mg sertraline daily and 1/5 mg Bromazepam twice a day, in the other one besides of antihypertensive drugs, blood pressure was well controlled. The authors suggested that in women with refractory hypertension who are not yet in menopause, PMS and the treatment beside of antihypertensive treatment should be considered .In a study conducted on women with PMS, it was found that diastolic blood pressure (DBP), heart rate (HR) and (SBP) systolic blood pressure in women with PMS were higher in healthy subjects and the difference was statistically significant .Considering that reduction in diastolic blood pressure in the group receiving PMS treatment (intervention group) was significantly different compared with that of the control group, it may be possible that accompaniment of PMS and HTN has higher effect on DBP rather than SBP. This issue should be investigated more in further studies.In a study, plasma aldosterone level was higher in women with PMS during luteal phase compared with that of the control group.Water and salt retention during luteal phase takes place in women with PMS ; and oneSome studies have shown that norepinephrine concentration in luteal phase in considerably higher in that in follicular phase , 22. IncSome studies showed that activity of sympathetic nervous system (SNS) during luteal phase is more compared to during follicular phase -26.Increase in the activity of SNS and decrease in the activity of parasympathetic nervous system during luteal phase could justify hypertension in people with PMS .According to the findings of this study, it is suggested that in women with refractory hypertension who are not in their menopausal period, diagnosis and treatment of PMS be considered as a comorbid disease for a better control of their diastolic hypertension.In terms of side effects of sertraline during the five weeks of prescription, some side effects of this study were more than those of the others; for instance, in this study nausea was reported to be 45%, which was 27% in another study . In thisOn the other hand, some of the reported side effects of this study were less than those of other studies. For example, in this study, significant sexual side effects were not reported. It should be mentioned that due to small sample size, low treatment period and type of consumed medication, generalization of medication side effects of this study or comparing them with the results of other studies is not possible.In this study, recovery or failure in recovery in PMS symptoms of patients were not controlled, and the only criterion was prescription of medication. It is recommended to consider the control or lack of control of PMS symptoms and their effects on controlling patients’ blood pressure in the future studies.According to the findings of this study, prescribing 50 mg sertraline daily for women with refractory hypertension and comorbid PMS is more effective as an anti-hypertension medication and a better control of DBP than placebo and it is not due to its effect on anxiety conditions, since people with anxiety disorder were excluded of this study. This effect does not have a statistically significant difference with the effect of placebo about systolic blood pressure. Thus, further studies should be designed with higher populations or different subtypes of patients. It is suggested that further studies with larger sample size and with other common treatments of PMS be conducted in this field. In this study, considering the fact that sertraline was started for the trial group with a high dose, this may be the reason for high side effects reported in this study compared with other studies.


This study was aimed to explore the molecular mechanisms of hypertensive nephropathy (HTN).Gene expression profile of GSE37460, which based on 27 healthy living donor samples (HTN group) and 15 hypertensive nephropathy samples (control group), were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between two groups were identified. STRING database was used to reveal protein-protein interaction (PPI) network of DEGs, followed by the functional enrichment analysis of the PPI network. Additionally, miRNA-DEG regulatory network was constructed to reveal the validated miRNAs targeting the DEGs.CYP3A4) and angiotensin II receptor type 1 (AGTR1) had a higher degree, and CYP3A4 interacted with CYP4A11. The DEGs in the network were significantly enriched in drug metabolism, focal adhesion and arachidonic acid metabolism. Furthermore, in the miRNA-DEG regulatory network, hsa-miR-335-5p and hsa-miR-26b-5p were the two most outstanding miRNAs. AGTR1, CYP3A4 and CYP4A11 were predicted to be regulated by hsa-miR-26b-5p.In total, 51 up-regulated genes and 140 down-regulated genes were obtained. In the PPI network, cytochrome P450 3A4 (AGTR1, CYP3A4 and CYP4A11 may play critical roles in the development of HTN likely via the regulation by hsa-miR-26b-5p and taking part in some pathways.The DEGs, such as  Hypertensive nephropathy (HTN) is a kind of the kidney injury due to chronic high blood pressure . Hyperte. have shown a major change in transcriptional control by hepatocyte nuclear factor 1 that affects pathways like redox and other genes, which further lead to the hypertensive renal injury  were listed in Table With the combined score > 0.9, a total of 1220 nodes  were included in the PPI network , alpha polypeptide (ADH1A)], focal adhesion [e.g. collagen type IV alpha 1 (COL4A1)], and arachidonic acid metabolism [e.g. cytochrome P450 family 2 subfamily B member 6 (CYP2B6) and cytochrome P450 family 4 subfamily A member 11 (CYP4A11)]  and 295 interactions were included in this network  superfamily, which is a group of heme-thiolate monooxygenases and participate in a variety of oxidation reactions [CYP3A4 is induced by glucocorticoids and involved in the metabolism of multiple drugs [CYP3A4 T16090C SNP responses to amlodipine among African-Americans with early HTN [CYP3A4 is elevated in patients with end-stage renal disease [CYP4A11, a homologue of CYP3A4, had a higher degree in the PPI network and interacted with CYP4A11. In this study, CYP4A11 was significantly enriched in the pathway of arachidonic acid metabolism. CYP P450 metabolites of arachidonic acid play an important role in the control of blood pressure, chronic kidney disease through the maintenance of the glomerular permeability barrier to albumin [CYP4A11 that produces 20-HETE have been linked to elevated blood pressure in humans [CYP4A11 in HTN. In the present study, CYP4A11 was predicted to be regulated by hsa-miR-26b-5p. An recent study has demonstrated that expression of miR-26b-5p is significantly decreased in basal serum samples from those patients with acute kidney injury, and it is a diagnostic biomarker of acute kidney injury [CYP3A4, CYP4A11 and hsa-miR-26b-5p with HTN. Given the above studies, we speculated that CYP3A4 and CYP4A11, as well as hsa-miR-26b-5p may play pivotal roles in the progress of HTN.In the present study, eactions . CYP P45eactions , which ieactions . The exple drugs . A previarly HTN . Moreove disease . CYP4A11 albumin , 28. Furn humans , 30, indy injury . CurrentAGTR1 also had a higher degree in the PPI network, and it was modulated by hsa-miR-26b-5p. AGTR1 encodes of angiotensin II type 1 receptor, which is an important effector in the control of blood pressure [AGTR1 are associated with hypertension [AGTR1 is believed to increase hypertension risk among African Americans [AGTR1 polymorphisms are believed to be associated with the renal function [. have reported that intrarenal production of angiotensin II plays an important role in mediating HTN through inducing podocyte injury and promoting the development of glomerulosclerosis [AGTR1 and HTN, we speculate that AGTR1 may exert critical functions in the progress of HTN.pressure . Previourtension , 34. Themericans . Moreovefunction , 37. Durclerosis . Furtherclerosis , which pclerosis . AlthougHowever, this study has several limitations. The major limitation is that the aforementioned results should be validated by other microarray data or experimental studies, which will be conducted and reported later. Furthermore, more patients with HTN should be included for the analysis. Additionally, the clinical data of the patients are not available, thus the patients may be heterogenous. In the further study, more samples from patients with HTN will be used for the verification experiments to confirm our results.CYP3A4, CYP4A11 and AGTR1, may be crucial in the progress of HTN, via the regulation by miRNAs (e.g. hsa-miR-26b-5p) and participation in the biological pathways (e.g. arachidonic acid metabolism). Notably, the above discussed genes and miRNA are new-found to be correlated with HTN in this study, and they are worth further investigation. These findings provide new information for further experimental studies. If these genes and miRNAs are confirmed by experiments, they will be promising to be used in the diagnosis or clinical therapy of HTN.In conclusion, 51 up-regulated DEGs and 140 down-regulated DEGs were identified in the HTN samples compared with the healthy controls. The DEGs such as


Background: Blood viscosity and aortic sclerosis (AS) are strong predictors of cardiovascular events. The effects of blood viscosity on AS have not been studied adequately. We aimed to investigate the potential connection between whole blood viscosity (WBV) and AS.Methods: AS was detected by transthoracic echocardiography. The estimation of WBV was carried out at both high shear rate (HSR) (208/s) and low shear rate (LSR) (0.5/s) by previously validated formulae using hematocrit (HcT) and total protein (TP) in g/L. WBV at HSR (208/s) is: (0.12 × HcT) + 0.17 (TP - 2.07) and WBV at LSR (0.5/s) is: (1.89 × HcT) + 3.76 (TP - 78.42). Comparisons of WBV at both HSR and LSR were made between patients with and without AS. Results: We included 94 patients with AS  and 97 control subjects without AS . Almost all of the clinical, echocardiographic, and biochemical characteristics were similar, but TP values were significantly higher in the AS group than in the control group . Hemoglobin and HcT levels were similar . In the AS group, WBV at LSR and HSR was higher than that in the control group . In multiple stepwise logistic regression analysis, WBV was an independent predictor of AS .Conclusion: We found higher WBV in patients with AS than in patients without AS at both LSR (0.5/s) and HSR (208/s). WBV at both LSR and HSR was independently associated with AS. It is not an infrequent finding with aging during cardiac imaging, and leaflet restriction is not hemodynamically significant,5 which is expressed by a maximal transvalvular velocity < 2–2.5 m/s. Aortic valve stenosis is a precursor of aortic stenosis (AS) and an important predictor of coronary artery disease.6 Although coronary artery disease and AS share histopathological and etiological similarities, medical therapies such as statins have no effect on stopping or slowing AS,5 which necessitates the identification of other potential risk factors and, thus, new therapeutic options. On the other hand, the effects of blood viscosity on AS have not been studied adequately. In this context, we aimed to investigate the potential relationship between WBV and AS.Blood viscosity is the internal dynamic resistance of blood to flow and determines the frictional force applied against the vessel walls. The determinants of blood viscosity are plasma viscosity, hematocrit (HcT), and aggregation and deformation abilities of erythrocytes, making blood a non-Newtonian fluid.We evaluated 94 patients with AS and 97 age- and gender-matched control subjects without AS selected from among individuals referred to the Echocardiography Laboratory of Ankara Numune Training and Research Hospital. Patients with AS, moderate-to-severe valvular disease, bicuspid aortic valve, history of rheumatic heart disease, left ventricular systolic dysfunction, symptomatic coronary artery disease, history of chronic kidney disease, paraproteinemia, acute blood loss or surgery, and history of hematological disease and anemia according to the patients’ self-report and medical records were excluded from the study. Hypertension was defined as blood pressure > 140/90 mmHg or use of antihypertensive drugs. Diabetes mellitus was defined as fasting blood glucose > 125 mg/dL or use of antidiabetic treatment. Hypercholesterolemia was defined as total cholesterol > 200 mg/dL or use of antilipidemic treatment. Laboratory tests for fasting blood glucose, lipid profile, creatinine levels, complete blood count, and total protein (TP) were performed with standard methods using commercially available laboratory kits.7, 8AS was detected by using a commercially available echocardiography device  with a 2.5–3.5 MHz transducer. AS was defined as focal areas of increased echogenity and thickening of the aortic trileaflet valve without valve motion restriction and left ventricular outflow tract obstruction (aortic jet velocity < 2.5 m/s with continuous wave Doppler ultrasound). The modified Simpson method was used to estimate the left ventricular ejection fraction. The diameter of the ascending aortic aorta and the presence of mitral annular calcification were also recorded. These measurements and evaluations were performed by 2 experienced cardiologists in accordance with the current recommendations of practice guidelines.2, 9, 10 which utilize HcT and total plasma protein concentration. For HSR, the WBV (208/s) formula is as follows: (0.12 × HcT) + 0.17 (TP – 2.07) and for LSR, WBV (0.5/ s) is: (1.89 × HcT) + 3.76 (TP – 78.42), where HcT is hematocrit in %, TP is total protein concentration in g/L, and WBV is whole blood viscosity in centipoise (cP).The estimation of WBV was carried out in both high shear rate (HSR = 208/s) and low shear rate (LSR = 0.5/s) via previously validated formulas,t-test or the Mann– Whitney U-test, where appropriate. The categorical variables were evaluated with the χ² test or the Fischer exact test. Factors affecting AS were determined with multiple stepwise logistic regression analysis. A p value < 0.05 was considered statistically significant.The statistical analyses were performed with IBM SPSS for Windows, version 22.0. The continuous variables are expressed as means ± SDs or medians (minimum – maximum), where appropriate, and the categorical variables are expressed in percentages. The parametric test assumptions  were tested before the groups were compared in terms of the continuous variables. The Shapiro–Wilk test was used when the continuous variables were not normally distributed. The homogeneity of the variances was tested using the Levine test. The continuous variables were tested with the The baseline clinical, echocardiographic, and biochemical characteristics of the study groups are summarized in In the multiple stepwise logistic regression analysis, AS was taken as a dependent variable. LDL, HDL, platelet count, ejection fraction, presence of mitral annular calcification, and WBV at LSR were included in Model 1 and LDL, HDL, platelet count, ejection fraction, presence of mitral annular calcification, and WBV at HSR were included in Model 2. In both models, WBV was an independent predictor of AS  .5 Although the progression rate of AS is low, studies suggest that AS is closely associated with increased cardiovascular events and mortality.11, 12 Current medical treatments like statins do not slow or stop the progression of AS.13 In our study, we did not find a statistical difference between the AS and control groups apropos medical treatment. In this regard, the potential risk factors that may play a role in AS development and progression other than conventional ones should be determined with a view to improving therapeutic options. Dyslipidemia, hypertension, smoking, inheritance, obesity, diabetes, and metabolic syndrome are well-known risk factors for vascular sclerosis. However, a substantial portion of individuals with vascular sclerosis are free from classical risk factors. In this context, about 20% of myocardial infarctions are seen in the absence of these risk factors.14 Conventional risk factors fail to adequately depict the full picture. Elevated WBV is associated with an increased risk of acute myocardial infarction and cardiovascular death.15, 16 WBV may be the neglected part of this picture.In the present study, we found that, by comparison with patients without AS, patients with AS had high WBV at both LSR (0.5/s) and HSR (208/s). WBV at both LSR and HSR was an independent determinant of AS. This result suggests that WBV may have a potential role in the development of AS. AS shows a prevalence of about 10 % and an incidence of 1.7% to 8.8%. The progression of AS to clinical AS per year is < 2%.14 In our study, the prevalence of hypertension was not different between the groups with and without AS; nonetheless, WBV was elevated in the group with AS, which also shows the significance of hyperviscosity in the absence of hypertension.The significance of acute hyperviscosity syndromes like polycythemia vera and leukemia is well known, and immediate intervention is necessary. However, lesser elevation in viscosity in a chronic manner is not appreciated adequately. Acute hyperviscosity syndromes possess analogy with hypertensive crisis; and just like chronic hypertension, chronic hyperviscosity is associated with a shorter life expectancy. Both conditions may operate in synergy. Additionally, authors have suggested that chronic hyperviscosity be treated in the same manner as chronic hypertension.17, 18 Increased viscosity is associated with increased shear stress for a given shear rate, and increased WBV may trigger valvular inflammation by increasing shear stress. In our study, the presence of mitral annular calcification in the patients was independently associated with AS. Both conditions are not simple degenerative processes and have similarities to atherosclerosis inasmuch as they share some risk factors. In a recent study, Çetin et al.19 demonstrated that WBV was an independent predictor of the presence of mitral annular calcification and limitation in annular motion. We also found that WBV was an independent predictor of AS apart from the presence of mitral annular calcification.One of the main mechanisms triggering valvular sclerosis is inflammation, which is also related with the activation of the leaflet endothelium with an increase in cell adhesion molecules and proinflammatory cytokines. Shear stress abnormalities may enhance the expression of proinflammatory genes and trigger tissue mineralization.Our study has some limitations. In our study, we did not measure WBV directly by using a viscometer. Instead, we used previously validated equations for estimating WBV. Actual measurements may differ from the estimated viscosity calculated with regression-based equations. We employed single measurements of TP and HcT to calculate WBV. However, AS is a chronic process and multiple measurements at wider time intervals may be more appropriate to show the interaction.Higher whole blood viscosity levels were independently associated with aortic sclerosis at both high shear rate and low shear rate.


Left bundle branch block (LBBB) has been proposed as a risk factor for cardiovascular morbidity and mortality. We sought to characterize the strength of these associations in a population without preexisting clinical heart disease.The association between LBBB and new-onset congestive heart failure (CHF) or death from cardiovascular diseases was examined in 1,688 participants enrolled in the SPPARCS study who were free of known CHF or previous myocardial infarction. SPPARCS is a community-based cohort study in residents of Sonoma, California that are > 55 years. Medical history and 12-lead ECGs were obtained every 2 years for up to 6 years of follow-up. LBBB at enrollment or year 2 was considered “baseline” and assessed as a predictor of CHF and cardiovascular death ascertained at years 4 and 6.The prevalence of LBBB at baseline was 2.5% (n = 42). During 6 years of follow-up, 70 (4.8%) people developed new CHF. Incidence of CHF was higher in patients with LBBB than in participants without LBBB. This association persisted after controlling for potential confounders (odds ratio (OR): 2.85; 95% confidence interval (CI): 1.01 - 8.02; P = 0.047). A higher mortality from cardiovascular diseases was also found in participants with LBBB after adjusting for potential confounders .LBBB in the absence of a clinically detectable heart disease is associated with new-onset CHF and death from cardiovascular diseases. Further study is warranted to determine if additional diagnostic testing or earlier treatment in patients with asymptomatic LBBB can decrease cardiovascular morbidity or mortality. The electrocardiogram (ECG) is one of the most commonly ordered tests in everyday clinical practice. Consequently, detecting subjects with abnormalities of the cardiac conduction system such as left bundle branch block (LBBB) in the absence of clinically detectable heart disease is relatively common , 2.It is not clear what cardiovascular morbidities to expect, if any, when asymptomatic patients develop LBBB. Previous studies investigating cardiac conduction abnormalities have focused mainly on survival of patients with LBBB in the setting of ischemic heart disease and acute coronary artery disease -7. The sWe analyzed data from the Study of Physical Performance and Age-related Changes in Sonomans (SPPARCS) Project. The project is a community based prospective longitudinal cohort study of physical activity and physical fitness in people 55 years or older that live in Sonoma, CA or in the city’s vicinity. The methods of recruitment and the representative of the sample to its target population have been described . A commuEnrolled participants underwent detailed standardized interviews and filled out standardized questionnaires. These included detailed questions about medical conditions. Identified medical conditions were ascertained by physician's diagnosis and medical treatment, 12 lead ECG testing was done at regular 2 year intervals. Patients were followed for 4 total assessments unless they died, left the study, or were lost to follow-up. The primary outcomes of the current study were incident CHF and death from cardiovascular diseases. Cardiovascular deaths were those included in International Classification of Disease 9th Revision (ICD9) codes 394 through 448. CHF and cardiovascular death were ascertained at the 3rd and 4th assessments.5, and V6, and (4) small of absent R waves in leads V1 and V2. The other predictors examined were demographic and medical characteristics including age, gender, atherosclerosis, hypertension, diabetes, kidney disease, and COPD at each time interval. Age was recorded as a continuous variable and all the other risk factors were recorded as a yes/no dichotomous variables.LBBB was defined as (1) QRS duration > 120 ms, (2) PQ interval > 120 ms, (3) predominantly upright complexes with slurred R waves in leads I, V2 test, and continuous data were compared using ANOVA. Logistic regression analyses were used to determine the relationship of LBBB with CHF and cardiovascular death in both bivariate models and multivariable analysis controlling for all potential confounders. A value of P < 0.05 was considered to be statistically significant. The study was approved by the Committee on Human Research at the University of California, San Francisco and the Committee for protection of Human Subjects at the University of California, Berkeley. Written informed consent was obtained from all subjects in the study prior to data collection. No extramural funding was used to support this work. The authors are solely responsible for the design and conduct of this study; all study analyses, the drafting and editing of the paper and its final contents.The statistical analyses were performed using SPSS version 16. Categorical data were compared using the χA total of 1,688 individuals aged 55 years or older were enrolled and followed for at least 6 years. Shown in During follow up, 70 (4.8%) people of the study population developed CHF. In bivariate analysis, baseline LBBB was associated with a 3.64 greater odds of developing CHF : 1.37, 9.71; P = 0.006). In multivariable logistic regression analysis adjusting for potential confounders, participants with baseline LBBB remained nearly three (2.85) times more likely to develop CHF . Other rOf a total of 351 (20.1%) deaths from all causes that occurred during follow-up, 133 (7.9%) were listed as cardiovascular diseases . UnadjusIndividuals with asymptomatic LBBB had an increased incidence of CHF and death from cardiovascular disease. It is unclear if LBBB is a marker of subclinical cardiac disease that manifests overtly later, or if LBBB is intrinsically deleterious, causing CHF and cardiovascular death.The association between LBBB and cardiovascular morbidity has been investigated, but given conflicting results, controversy regarding the prognosis of LBBB persists. Fahy observed a higher rate of developing overt cardiovascular disease among people with isolated LBBB . HoweverOne might speculate on a possible causal role in which LBBB may lead to CHF. It is believed that right-to left ventricle endocardial activation that occurs in LBBB results in left ventricular dyssynchrony, compromising systolic and diastolic function . This dyThe association between LBBB and mortality has been previously suggested by a few studies in the literature , 15. In In view of our findings and those of others, it appears reasonable to question whether the finding of asymptomatic LBBB should prompt further diagnostic testing or early treatment that might prevent CHF and cardiovascular morbidity. Currently, neither further testing nor treatment is recommended when asymptomatic LBBB is found. Other studies would be helpful to evaluate possible therapeutic options. The benefit of early treatment of diagnosed CHF has been previously shown by other studies in patients following myocardial infarction . Heart fSeveral limitations exist to our study. First, the assessment of medical conditions was based on interviews with the patient rather than independent adjudication. For example, participants may have been unaware of underlying CHF or may have failed to recollect the diagnosis when completing the baseline questionnaire. Second, our assessment of LBBB was based on one to two 12 lead ECGs done over 2 years. Therefore, some participants may have had intermittent LBBB that was not detected. However, this likely would have resulted in decreased power and should not have resulted in false positive associations.Our data indicate that patients with asymptomatic LBBB are at increased risk of developing CHF and of dying from cardiovascular diseases. Further study is warranted to determine if more diagnostic testing or earlier treatment in patients with asymptomatic LBBB can decrease cardiovascular morbidity or mortality.


To investigate changes in eye coats, axial length, and ocular perfusion pressure (OPP) in hemodialysis (HD) patients with chronic renal failure (CRF).  We included HD patients who were diagnosed with CRF in our hospital from January to December 2015. Fifty-two patients met the inclusion criteria; all right eyes were used for observation. Systolic and diastolic blood pressures were recorded to calculate OPP. Approximately 30 minutes before and after HD, we recorded multiple parameters, including lens thickness (LT), axial length of vitreous (VAL), axial length of eye (EAL), ciliary body thickness (CBT), choroidal thickness (CT), and retinal thickness (RT). P < 0.01, F = 7.023) and CBT became significantly thinner . CT was significantly thinner and differed among measurement locations . Further, RT thickened and differed among measurement locations , whereas LT, VAL, and EAL significantly increased after HD .  After HD, OPP significantly decreased ( HD impacts the thickness of the eye coats and VAL, particularly affecting CBT, CT, and RT. OPP transiently decreases during HD, which may contribute to an ischemic state. Chronic renal failure (CRF) is an irreversible deterioration of renal function, which is characterized by numerous disorders that involve many organs . Hemodialysis (HD) is one of the main treatment methods in patients with CRF; its main objective is to correct the excessive accumulation and abnormal distribution of body fluid. However, sometime during or after HD, patients will occasionally develop a sharp increase in intraocular pressure (IOP), followed by transient blurred vision, eye pain, headache, and other symptoms , 2. HD cThe aim of this study was to observe ocular parameters of the eyeball  and ocular perfusion pressure (OPP) changes in hemodialysis patients before and after HD, as well as to explore the possible mechanisms of these changes. Further, we attempted to provide a fundamental basis for protecting visual function during HD through stabilization of the biological structures of the eye and improvement of ocular blood supply.Fifty-two patients, who were diagnosed as CRF and underwent HD in our hospital, were enrolled in this group . General characteristics of patients are summarized in Patients who exhibited good compliance and appropriate levels of physical activity and had signed informed consents.Patients whose visual acuity was ≥0.3 on the logMAR scale.Patients whose IOP was 10–21 mmHg.Inclusion criteria were as follows:Patients with a history of glaucoma or ocular hypertension or eye surgeryPatients suffering from severe fundus lesions.Patients exhibiting media opacity that affects optical clarity.Patients diagnosed with diabetes.Exclusion criteria were as follows:Only morning session HD patients were included. All patients underwent 4 h HD sessions, 3 days per week, at a blood flow rate of 250 mL/min. Patients were treated using high-performance dialyzers: 4008S-type Fresenius HD machine (Germany) and a Campbell 8L reusable dialyzer (Sweden); patient blood was dialyzed against bicarbonate dialysate . All patients exhibited arteriovenous fistulae and used a polysulfone hollow-fiber dialyzer . The total body weight was measured before and after HD.Blood samples were obtained within 60 seconds before the start and end of HD then used to calculate plasma osmotic pressure (plasma osmotic pressure = 1.86 × Na + glucose ÷ 18 + urea nitrogen ÷ 2 + 9).IOP was measured 30 min before the start of HD, 2 h after HD, and 30 min after ending HD, using a handheld rebound tonometer. Simultaneously, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded. OPP was acquired according to the formula: OPP(mean) = ((4/9) × DBP) + ((2/9) × SBP)–IOP.All pre- and post-HD measurements were performed by the same examiner to minimize bias.CCT was measured using a corneal endothelial cell counter , 30 min before the start and end of HD; it was measured three times to determine the mean value.Patients were placed in the supine position. After administration of a topical anesthetic (0.25% oxybuprocaine eye drop), the patient was allowed to fix his or her finger to maintain vision straight ahead. Then, the central anterior chamber depth (ACD) and lens thickness (LT) were measured by A-ultrasonography, 30 min before the start and end of HD. Ten measurements were performed, and the average value was used.μm in front of the scleral spur; intersecting with the anterior surface of the iris; and measuring the thickness of the iris at this point, as shown in IT measurement: drawing a straight line perpendicular to the trabecular meshwork, 500 CBT: measuring the thickness at the posterior 1 mm of the scleral spur, as shown in Patients were placed in the supine position, with constant indoor brightness. A total of 30 min before the start and end of HD, iris thickness (IT) and ciliary body thickness (CBT) were measured by UBM at 12 o'clock, 6 o'clock, 3 o'clock, and 9 o'clock positions; the average values of the four quadrants were used. μm distance from the fovea on both nasal and temporal sides. CT was measured from the outer portion of the high reflection line, corresponding to the retinal pigment epithelium, to the inner surface of the sclera. RT was measured from the retinal inner limiting membrane to the high reflection line of the retinal pigment epithelium, as shown in A total of 30 min before the start and end of HD, choroidal thickness (CT) and retinal thickness (RT) were measured by OCT; these measurements were performed at the fovea, as well as at 1500 t-test. The Pearson coefficient test was used to determine correlations among changes in IOP and CCT, changes in eye coat thicknesses , and the total amount of HD ultrafiltration. P values of <0.05 were considered to be statistically significant.All data were analyzed using the SPSS statistical package, version 19.0. The Kolmogorov-Smirnov test was used to assess normality of the data. SBP, DBP, IOP, and OPP were compared among groups, using the repeated measures one-way analysis of variance (ANOVA). Other variance comparisons were performed utilizing the paired-sample Ethical approval was obtained from the Medical Ethics Committee of the Affiliated Hospital of Qingdao University, before the start of the study. We certify that all applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during this research.P < 0.05, t = 3.041).Plasma osmotic pressure after HD was significantly lower than plasma osmotic pressure before HD (F = 6.175) and revealed significant differences (P < 0.05). SBP decreased significantly after 2 h of HD (P < 0.05) then returned to its pre-HD levels within 30 min after HD (P > 0.05).SBP in three groups was analyzed by one-way ANOVA (F = 1.024); there were no statistical differences among the three groups (P > 0.05).DBP was analyzed by one-way ANOVA (F = 0.495) showed that there were no statistical differences among the three groups (P > 0.05).One-way ANOVA of IOP (F = 7.023) showed significant differences among the three groups (P < 0.01). Compared with pre-HD levels, OPP significantly decreased 2 h after HD (P < 0.01); after the end of HD, OPP returns to its pre-HD levels, such that there was no significant difference between the two groups (P > 0.05).One-way ANOVA of OPP . Compared with pre-HD measurements, CT was significantly thinner at all measurement points . After HD, the RT was significantly thickened at all measurement points . Although CCT and IT both decreased after HD, these changes were not statistically significant.After the end of HD, CBT became significantly thinner . VAL and EAL both significantly increased after HD, relative to their pre-HD values . ACD slightly decreased after HD, but the difference was not statistically significant.LT significantly increased after HD , as well as between the total amount of ultrafiltration and differences in CT . We did not observe a correlation between differences in IOP (before and after HD) and differences in CCT . No obvious correlations were observed between the total amount of ultrafiltration and differences in CCT , IT , or RT .There were significant correlations between the total amount of ultrafiltration and differences in CBT (As an important treatment for patients with CRF, the side effects of hemodialysis have attracted much attention from health researchers. HD can cause a series of changes in the eye, including changes in refractive status, onset of dry eye, conjunctival calcification, banded keratopathy, lens opacity, and optic neuropathy , 10. MorDuring HD, toxic substances in the blood, such as urea nitrogen and creatinine, are dispersed into the hemodialysis solution, which causes a decrease in plasma osmotic pressure. Concurrently, ultrafiltration causes gradual reduction of extracellular fluid, thereby raising the osmotic pressure of the extracellular fluid. Subsequently, intracellular fluid outflow is altered to buffer extracellular osmotic pressure, resulting in a state of relative water shortage within tissues. Because of individual differences, the time for recovery of plasma osmotic pressure is different among patients; in some patients, plasma osmotic pressure returns to its pre-HD levels shortly after completion of HD. In this study, plasma osmotic pressure was measured only 60 sec after completion of HD. Although the plasma composition was not yet stable at this early stage, plasma osmotic pressure at this stage can reflect its variation during and after HD. Because of changes in plasma osmotic pressure, as well as the use of ultrafiltration in HD, the eye coat may be thinner. In previous studies, Dinc et al.  observedDuring HD, the urea nitrogen in the lens could not decrease at the same rate as the urea nitrogen in the blood, which resulted in an imbalance of osmotic pressure between the lens and aqueous humor; thus, the lens absorbed water and expanded, resulting in an increase in LT. Post-HD VAL was significantly greater than the pre-HD VAL. Concurrently, plasma osmotic pressure decreased, along with the plasma osmotic pressure of the eye coats; subsequently, water entered the vitreous cavity, leading to an increase in the length of the vitreous axis. The effect of HD on ACD is more complex: the increase of LT and forward positioning of the lens iris diaphragm may cause a shallow anterior chamber. However, the iris root and ciliary body were both thinner, which should cause a widening of the anterior chamber. Thus, there was no significant change in ACD after HD, in our study. Because of the changes in LT and VAL, axial length of the eye noticeably increased after HD.Conflicting results have been reported concerning the effects of HD on IOP. In most studies, HD either causes increased IOP or causes no change in IOP –18; a smHD is known to cause unfavorable side effects on systemic parameters, frequently including hypotension . During OPP represents the pressure of blood flowing in ocular blood vessels and is defined as the difference between arterial pressure and IOP, which is an important factor in regulating blood flow within the eye. OPP is calculated using blood pressure and IOP . In thisIn summary, the effect of HD on ocular parameters is mainly manifested in eye coat thinning, especially in the ciliary body and choroid. The retina is a nervous system with complex self-regulatory function; however, HD can cause retinal edema, and retinal thickening caused by edema was much greater than the thinning caused by dehydration. Because the choroid is rich in blood vessels, it is the main oxygen and nutrient supply for the outer retina. Decreased choroidal thickness from HD may affect retinal metabolism. There was no significant change in the IOP in our HD patients, but the OPP of these patients transiently decreased during HD, which may contribute to an ischemic state within the eye. Therefore, HD patients should aim to minimize fluctuations in blood pressure during HD. Clinicians should work to actively improve vascular conditions within HD patients, to slow the process of vascular sclerosis and calcification and to prevent vascular sclerosis or obstruction caused by weakened automatic regulation of ocular vessels, in order to protect visual function.HD impacts the thickness of the eye coats and the vitreous axial length, including the thickness of the ciliary body, choroid, and retina, which may contribute to a decrease in ocular blood supply and retinal edema. OPP transiently decreases during HD, which contributes to an ischemic state within the eye. Thus, clinicians should work to minimize fluctuations in blood pressure during HD, in order to prevent this damage.


Obesity is associated with both obstructive sleep apnea (OSA) and obesity hypoventilation. Differences in adipose tissue distribution are thought to underlie the development of both OSA and hypoventilation. We explored the relationships between the distribution of upper airway, neck, chest, abdominal and muscle fat in very obese individuals.We conducted a cross-sectional cohort study of individuals presenting to a tertiary sleep clinic or for assessment for bariatric surgery. Individuals underwent magnetic resonance (MR) imaging of their upper airway, neck, chest, abdomen and thighs; respiratory polygraphy; 1 week of autotitrating CPAP; and morning arterial blood gas to determine carbon dioxide partial pressure and base excess.2; there were 27 males (51%). Soft palate, tongue and lateral wall volumes were significantly associated with the AHI in univariable analyses (p < 0.001). Gender was a significant confounder in these associations. No significant associations were found between MRI measures of adiposity and hypoventilation.Fifty-three individuals were included, with mean age of 51.6 ± 8.4 years and mean BMI of 44.3 ± 7.9 kg/mIn very obese individuals, our results indicate that increased volumes of upper airway structures are associated with increased severity of OSA, as previously reported in less obese individuals. Increasingly large upper airway structures that reduce pharyngeal lumen size are likely to lead to OSA by increasing the collapsibility of the upper airway. However, we did not show any significant association between regional fat distribution and propensity for hypoventilation, in this population.The online version of this article (10.1007/s11325-017-1599-x) contains supplementary material, which is available to authorized users. Obesity is associated with significant comorbidities, including obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS). These conditions coexist in only some obese individuals, whereas others develop only one of the complications or do not develop either. The individual distribution of adiposity may be crucial in determining which patients develop OHS, OSA or both.Obesity may cause OSA by different mechanisms. Increased neck circumference may cause increased external loading pressure on the airway leading to OSA –3. The mCRIT.The apnea hypopnea index (AHI) is the most common measure of OSA severity. The AHI is influenced by the anatomic susceptibility of the upper airway to collapse along with dilator muscle responsiveness and other factors . AutotitThe underlying mechanisms of OHS are not fully understood, but regional variations in fat distribution are believed to play a role. Abdominal adiposity is known to be associated with decreased lung volumes and hypoventilation . In addi2), obesity, and no other aetiology present to explain the ventilatory failure. Arterial base excess represents renal compensation via increased bicarbonate levels in response to periods of hypercapnia. Our group has previously published data from this cohort showing that an intermediate group of patients, with an elevated bicarbonate level, but with a normal daytime PaCO2, is likely to represent early OHS [OHS diagnostic criteria include elevated daytime arterial carbon dioxide partial pressure . The study was approved by local research ethics committee (Oxfordshire REC B 11/H0605/9) and conducted in accordance to the Declaration of Helsinki. All participants included in the study gave written informed consent.This was a prospective observational study conducted in a single tertiary care hospital of individuals presenting to sleep clinic or for bariatric surgery. We have utilised unreported MR imaging (MRI) data from a previously published obesity and ventilatory failure trial . Thus, t2 and base excess (BE). Individuals taking diuretics, theophylline, respiratory stimulants or respiratory depressants were excluded. Full details of the subjects included, and blood gas analysis can be found in the Individuals underwent magnetic resonance (MR) imaging of their upper airway, neck, chest, abdomen and thighs; overnight in-lab polygraphy; 1 week of autotitrating CPAP; and early morning arterial blood gas to determine PaCOMRI of the upper airways, neck, chest and abdomen was performed. Details of MRI acquisition can be found in the All images were manually examined using Amira image analysis software . Upper airway structures were segmented individually between the posterior nasal spine and the level of the hyoid. This allows calculation of the volumes of different upper airway structures, as we have performed in other studies , 15, 16.3) were calculated of the following upper airway structures: the soft palate, the tongue, the parapharyngeal fat pads and the airway lateral walls. Neck and chest fat analysis extended from the inion to the C7-T1 intervertebral space and from the C7-T1 level to the diaphragm, respectively. The abdominal fat analysis used the L2–L3 and L3–L4 landmark slice visceral fat measurements, as these have been shown to be predictive of total visceral adipose tissue [Using the Amira image software, volumes  was performed. This included nasal pressure via nasal cannula, oximetry, pulse rate and respiratory effort via thoracic and abdominal bands. Body movements , heart rate and pulse transit time changes were also routinely recorded as markers of arousal from sleep. Apnea was defined as ≥ 10 s with < 10% airflow, and hypopnea as ≥ 10 s with 50% reduction in nasal airflow  with > 4% oxygen desaturation. The apnea hypopnea index (AHI) was defined as the number of apneas and hypopneas per hour of sleep. ODI was calculated as the number of oxygen desaturations > 4% per hour of sleep.Regardless of AHI, all patients tried autoCPAP . Only individuals using CPAP for at least seven nights and with an average usage of greater than 4 h per night had CPAP their 95th centile autoCPAP setting recorded.t tests.Detailed statistical methods can be found in the 2) and MRI variables were explored using univariable linear regression.The relationships between sleep parameters (autoCPAP and AHI) and MRI variables were explored using univariable linear regression. Log and square root transformations were performed where necessary. Similarly, the relationships between hypoventilation measures .The relationships between potential confounding variables  and MRI variables, OSA measurements and hypoventilation measurements were explored using univariable and multivariable linear regression. As a further analysis, multivariable associations between MR imaging variables and AHI/autoCPAP/BE/PCOAs this is considered an exploratory, hypothesis-generating analysis, no correction for multiple comparisons or sample size/power analysis has been performed.2 > 6.0 kPa) and 53% (27 of 51) met our previously described criteria for early OHS (BE ≥ 2 mmol/l) [Seventy-two patients were recruited to the study, of whom 53 (74%) underwent MR imaging of the upper airway; thus, only these 53 patients were included in this analysis. Baseline characteristics are shown in Table  mmol/l) .Table 1BAll 53 patients had satisfactory upper airway MR imaging, 50 had satisfactory neck and chest MR imaging and 52 had satisfactory thigh muscle MR imaging. Only 31 (59%) patients had satisfactory abdominal MR imaging, with 15 scans not containing the area of interest, 5 affected by motion artefact and 2 being unable to appropriately landmark. MRI variable measurements are shown in Table AHI was not normally distributed, and therefore, the AHI was square root transformed to give an approximately normal distribution. The univariable associations between MR imaging variables and OSA measurements (square root of the AHI and AutoCPAP setting) are displayed in Table p = 0.05) association with higher BE.The univariable associations between MR imaging variables and hypoventilation measurements are displayed in Table e-Table The univariable and multivariable associations between the potential confounders of age, gender and height, and the MRI variables, OSA measures and hypoventilation measures were assessed and the results are shown in the online supplement e-Table p = 0.004), tongue volume (p < 0.001), and lateral walls (p < 0.001) and a decreased intramuscular fat/muscle ratio (p = 0.003); taller height was associated with increased neck (p = 0.01) and chest (p = 0.01) visceral fat volumes; both male gender (p = 0.02) and taller height (p = 0.001) were associated with increased submental fat volumes; there were trends towards significant associations between both age (p = 0.08) and height (p = 0.09) with L2–L3 visceral fat; there was a trend towards a significant association between age (p = 0.05) and L3–L4 visceral fat.After adjusting for other potential confounders in multivariable analysis, male gender was associated with increased volumes of the soft palate , with gender as a covariate. There was a trend towards increasing volume of the tongue and increasing square root transformed AHI , with gender as a covariate. There was no significant association between the volume of the lateral walls  and the square root transformed AHI, with gender as a covariate. There were no significant associations between the neck visceral fat volumes  or L2–L3 visceral fat area  and the square root transformed AHI, with height as a covariate.There remained a significant association between increasing volume of the soft palate and increasing square root transformed AHI , with gender as a covariate. There was no association between the volume of the tongue  or the intramuscular fat:muscle ratio  and the autoCPAP setting, with gender as a covariate.There was a trend towards increasing volumes of the soft palate being associated with increasing autoCPAP settings , with height as a covariate.There was a trend towards increasing chest visceral fat volumes being associated with an increased base excess  and those without OSA (108.3 ± 17.5 cm3), when compared with previous studies examining both OSA patients (101.2 ± 17.7 cm3) and controls (85.5 ± 13.8 cm3) [An anatomical susceptibility of the upper airway to collapse is associated with an elevated AHI . Althoug3.8 cm3) . The finCRIT) as a measure of the collapsibility of the upper airway. PCRIT is concerned with the pharynx at its point of collapse, and the autoCPAP setting describes the pressure needed to hold open the airway to the point of minimal flow limitation, making it a reasonable proxy measure [AutoCPAP was considered as a potential alternative to the critical closing pressure of the pharynx  assessments of abdominal visceral adiposity were correlated with BE . It was 2 > 7 kPa, and therefore, we cannot make conclusions about the relationship between MRI measurements of adiposity and more severe hypoventilation. In addition patients included were all obese and as a result had significant abdominal and thoracic adiposity. Therefore, there may be a relationship between visceral adiposity and hypoventilation over wider range obesity. However, this study does raise the hypothesis that over a certain threshold of visceral obesity other non-anatomical factors, such as physiological ventilatory responses, may determine the risk of hypoventilation.The sample size is an important limitation of this study, particularly for abdominal MR imaging, where only 31 patients had adequate imaging. It is possible that a modest association between abdominal visceral adiposity and hypoventilation may have been missed. A limitation of this current study is that only a small proportion of patients met criteria for established hypoventilation (18%), though 27 (53%) had a raised BE. In this study, no patients had a daytime PaCOThe AHI, which was derived by polygraphy, and the autoset CPAP setting were not adjusted for sleep stage or position. As full polysomnography was not recorded, the AHI was not recorded by sleep stage or sleep position. As the autoset CPAP setting was derived from 1 week of therapy, it is unlikely to have been influenced by sleep stage. Therefore, it is possible that the time in different sleep stages or positions varied between individuals and may have biased the relationship between MRI measurements and the AHI or the autoset CPAP setting.MR images were recorded during wakefulness. Rostro-caudal fluid shifts that occur at night are likely to further increase the volume of the upper airway soft tissue and further reduce cross-sectional area. However, as patients with congestive cardiac failure and other significant comorbidities were excluded, it is unlikely that rostro-caudal fluid shifts will have significantly influenced our results.We found significant confounding relationships between gender and the volume of soft palate, tongue, lateral upper airway walls, neck visceral fat, estimates of abdominal visceral fat and the thigh intramuscular fat/muscle ratio.Gender differences in the anatomy of the upper airway may well be an important determinant of the differences in collapsibility of the male and female upper airway. These results could be due to smaller tongue and soft palate sizes, as we have shown that the volume of these structures is associated with sleep apnea severity. Others have shown that females have smaller tongues, soft palate size and shorter airway length, and this was associated with a less collapsible upper airway . Airway Differing cut-offs in measurements of visceral adiposity for predicting the metabolic syndrome have been described in the literature for pre-menopausal women compared to post-menopausal women and men . Most stWe found significant associations between height, gender and MRI measurements of adiposity. Male gender and not taller height mediated increasing volumes of upper airway structures, whereas taller height and not male gender mediated increased chest and neck fat volumes. The relationship between height and volume of major visceral adipose tissue is well established, as it is with the common measurement of BMI , where wVisceral abdominal tissue is known to increase with age and this has been linked with the metabolic syndrome . Hormona2. This disparity warrants further investigation into the role of abdominal fat in the genesis of obesity hypoventilation syndrome.In these very obese individuals, we have shown that increased tongue and soft palate volumes are associated with increased severity of OSA. Increasingly large upper airway structures are likely to lead to OSA by increasing the collapsibility of the upper airway. Many associations were confounded by covariates of age, gender and height. Contrary to findings relating to measurements of OSA, we did not show any association between regional fat distribution and propensity for hypoventilation in this population. This contrasts with our previous finding in a different subset of very obese individuals, where visceral adiposity measured on DEXA scanning was predictive of hypoventilation in individuals with a BMI < 40 kg/mESM 1(DOCX 24 kb)


It is not uncommon for patients without preceding history of kidney disease to present to the Emergency department with renal failure. The absence of prior medical records or renal imaging presents a diagnostic challenge. Elevated parathyroid hormone levels or echogenic contracted kidneys on ultrasound are known to point to a diagnosis of chronic kidney disease. The literature in this regard is surprisingly limited. The objective of this study is to assess the role of intact parathyroid (iPTH) blood level and bedside ultrasound in differentiating acute kidney injury from chronic kidney disease. A systematic review which included a literature search of 3 databases, PubMed, Embase, and Cinahl (R) as also secondary sources, was done. The inclusion criteria evaluated studies which evaluated iPTH or bedside ultrasound in differentiating acute kidney injury from chronic kidney disease. We excluded studies which used other laboratory biomarkers like neutrophil gelatin associated lipocalin (NGAL) or carbamylated haemoglobin. A total of 2256 articles were identified. After screening, the relevant articles were reviewed, and an assessment of their methodological quality was made based on the CASP: Critical Appraisals Skill Programme. Of the 2256 articles identified, after screening, only 5 were identified as relevant. An elevated parathyroid hormone level and echogenic contracted kidneys on bedside ultrasound in the Emergency department can help differentiate acute kidney injury from chronic kidney disease. This differentiation helps decide need for admission as well as further management. Although iPTH level may also rise in acute kidney injury, the value  can discriminate it from chronic kidney disease. In the Emergency department, it is increasingly common to find patients presenting for the first time with raised creatinine and no antecedent blood reports which could help differentiate acute kidney injury (AKI) from chronic kidney disease (CKD). This is specially a problem for patients who are temporary immigrants or tourists where previous medical records are unavailable. The differentiation of AKI from CKD is of paramount importance as it influences management, clinical course, prognosis, and disposition of the patient. AKI is a medical emergency and appropriate initial treatment can prevent complications and subsequent need for long-term renal replacement therapy , 2.Often in these situations, it is unclear whether a patient has AKI or CKD or an AKI on the background of CKD. This can be a diagnostic dilemma for Emergency care team and also causes great apprehension for patients and their families. Current estimates suggest 8-16% of the world population has CKD. The supply of nephrologists is outstripped by this burgeoning demand. Emergency care physicians and internists will have to be conversant in this area.The objective of our study is to assess the role of intact parathyroid (iPTH) blood level and bedside ultrasound in the Emergency room to differentiate acute kidney injury from chronic kidney disease based on a systemic review of literature.st January 2018. The search terms used and applied are described in the Appendix.To identify relevant studies, a literature search was conducted from 1966 up to 1Ethics committee approval was not required as study did not involve human subjects or medical records. Literature search was limited to human studies in English language literature. Reference list of identified articles were manually searched for additional literature.The search strategy was applied to the following:st January 2018MEDLINE (PUBMED): 1966 – 1EMBASE; 1966- 1st January 2018CINAHL (R): 1984 - 1st January 2018.Additional sources included in the secondary search strategy werereferences from relevant articlesWeb-based resources:http:///www.bestbets.orghttp://www.clinicaltrials.govhttps://scholar.google.com.sgAll articles using intact parathyroid hormone level iPTH or ultrasound to differentiate AKI from CKD were included.Trails using other laboratory parameters like (NGAL) or carbamylated haemoglobin to differentiate AKI and CKD were excluded. Records identified through EMBASE, MEDLINE, and CINAHL were identified for duplicates and excluded. Detailed search strategies for these 3 major database search engines are given in the Appendix. A uniform filter strategy was applied to all the major database engines.The studies were initially screened to check against all titles and abstracts with regard to the eligibility criteria at Level I screening. Those publications not excluded in Level 1 screening were reviewed by 2 reviewers to confirm all eligibility criteria were met and no exclusions were applicable (Level 2).There is a paucity of articles on this subject and hence all the articles which compared ultrasound and/or intact parathyroid hormone assay to differentiate AKI from CKD were included. Total 2256 articles were found but only 5 were relevant .The relevant articles were reviewed, and an assessment of their methodological quality was made based on the CASP: Critical Appraisals Skill Programme diagnostic tool questionnaire was used . AssessmThe review of literature supports use of kidney ultrasound and/or measurement of serum iPTH levels in differentiating AKI from CKD in patients with deranged kidney function with no available prior serum creatinine values. However, there is paucity of literature in this area. The identified relevant studies were appraised and presented as per the guidelines for systematic reviews.Factors which may help to differentiate AKI from CKD were identified. A history of nocturia and pruritus along with clinical features like anaemia, sallow skin, hypertension, or peripheral neuropathy would suggest CKD. A history of oliguria or anuria after a renal insult and normal sized kidneys on ultrasound with prior renal function suggesting a normal serum creatinine would suggest AKI. Unfortunately, in a large number of patients, the history is not available and other features have poor predictive value .For the purposes of this study, AKI was defined as an increase of serum creatinine by at least one and a half times baseline as per the RIFLE criteria . CKD wasOzmen et al.  prospectThe authors concluded that renal length in patients with CKD was significantly shorter 90±15 mm, than those with AKI, 112±14 mm (p<0.001). When compared to healthy adult volunteers (N=33), renal length was (107±6 mm) almost similar to those in AKI group.The ROC analysis curve for renal length cut off to differentiate AKI from CKD was 0.865.A small kidney with highly echogenic parenchyma on ultrasound is characteristic of chronic renal failure/or chronic kidney disease . Normal In patients with AKI, grade 1 echogenicity of the cortex was present in 33/62 (53%) patients. Of 65 patients with CKD, Grade 2 and grade 3 patients' echogenicity was seen in 34 (52%). Therefore, although the increase in echogenicity has less value as compared to renal length in differentiating AKI from CKD, hyperechogenic (Grade 3) kidneys were only seen in CKD .Bennidor and Israelit  in a revPoint of care ultrasound (POCUS) is widely used in the Emergency department. In fact, comprehensive training in POCUS is an integral part of Emergency medicine (EM) training in North America. When compared to standard consultative ultrasound, POCUS performed by the EM physician who knows the clinical history and examination can rapidly integrate ultrasound findings to better arrive at a management plan. EM physicians are already routinely performing renal ultrasound on patients with AKI, urinary tract infection, and nephrolithiasis . A recenLaboratory tests like carbamylated haemoglobin and serum 1,5-anhydroglucitol have been utilized to differentiate AKI from CKD , 13. TheOzmen et al.  prospectCavayero et al.  describeZhang et al. in their systemic review and meta-analysis concluded that serum Cystatin C (Cys C) appears to be a good biomarker in the prediction of AKI while urinary Cys C excretion had only moderate diagnostic value .Physicians working in acute care, Emergency medicine, or primary care frequently encounter patients with undifferentiated renal failure and no prior medical records. Early differentiation between AKI and CKD can benefit the management of this group of patients. Available literature supports the use of kidney ultrasound and serum iPTH assays. The strength of evidence is moderate. Further studies are required based in the Emergency department which would validate whether point of care ultrasound is useful in the above scenario.It is important to remember that iPTH level may rise in acute kidney injury; however, a cut-off value set at 170ng/ml is an excellent discriminator from chronic kidney disease.


The renoprotective effect of sodium-glucose cotransporter 2 inhibitors is thought to be due, at least in part, to a decrease in blood pressure. The aim of this study was to determine the renal effects of these inhibitors in low blood pressure patients and the dependence of such effect on blood pressure management status.  The subjects of this retrospective study were 740 patients with type 2 diabetes mellitus and chronic kidney disease who had been managed at the clinical facilities of the Kanagawa Physicians Association. Data on blood pressure management status and urinary albumin-creatinine ratio were analyzed before and after treatment. n = 537) and those with ≥102 mmHg (n = 203) at the time of the survey were −0.25 ± 1.02 and −0.03 ± 0.97, respectively, and the difference was significant in analysis of covariance models even after adjustment for the logarithmic value of urinary albumin-creatinine ratio at initiation of treatment (p < 0.001).  Changes in the logarithmic value of urinary albumin-creatinine ratio in 327 patients with blood pressure < 130/80 mmHg at the initiation of treatment and in 413 patients with BP above 130/80 mmHg were −0.13 ± 1.05 and −0.24 ± 0.97, respectively. However, there was no significant difference between the two groups by analysis of covariance models after adjustment of the logarithmic value of urinary albumin-creatinine ratio at initiation of treatment. Changes in the logarithmic value of urinary albumin-creatinine ratio in patients with mean blood pressure of <102 mmHg ( Our results confirmed that blood pressure management status after treatment with SGLT2 inhibitors influences the extent of change in urinary albumin-creatinine ratio. Stricter blood pressure management is needed to allow the renoprotective effects of sodium-glucose cotransporter 2 inhibitors. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are new oral glucose-lowering agents, which act by increasing urine glucose excretion through inhibition of SGLT2 present in the renal proximal tubules. The associated loss of calories through the huge amount of urinary glucose excretion leads to body weight (BW) loss. In addition to their direct effects on blood glucose level, SGLT2i have other indirect beneficial effects, such as lowering blood pressure (BP) and improving dyslipidemia and liver dysfunction. These pleiotropic effects have attracted attention and wide use of SGLT2i in the treatment of type 2 diabetes mellitus (T2DM), especially in obese patients.The results of several large-scale cardiovascular outcome clinical trials on SGLT2i, such as the EMPA-REG OUTCOME trial  and CANV2). The following patients were excluded: (1) type 1 DM, (2) on chronic dialysis, (3) had severe liver dysfunction, severe heart failure, or severe infection, (4) malignancy on terminal stage, (5) pregnant women, (6) irregular use of SGLT2i during the study period based on information included in the medical records, and (7) individuals who indicated intention of opt-out at the time of the survey. The following parameters were recorded both at the time of initiation of SGLT2i treatment and at the time of the survey: age, sex, BW, BP (both systolic (SBP) and diastolic (DBP)), serum Cr, hemoglobin A1c (HbA1c), ACR (mg/gCr), and proteinuria . Based on the above criteria, 67 patients were excluded from the study. Thus, the study included 740 patients who were treated with SGLT2i for a median duration of 15.9 months . We collected data based on the observations of the GPs. BP measurements at office were performed at each participating medical office using their own validated cuff oscillometric devices. According to the JSH 2014 guidelines [2) = 194 × age−0.287 × serum creatinine−1.094 × [0.739 for women]) [The study was approved by the Human Ethics Committee of Kanagawa Medical Association . The study subjects included all 935 T2DM patients who were registered and visited the clinics of medical facilities of the Kanagawa Physicians Association between November 2016 and March 2017. The inclusion criteria of this study were as follows: T2DM patients (1) aged more than 20 years, (2) who commenced treatment with SGLT2i for the first time at least 4 months before the current study, and (3) who had CKD as defined by the K/DOQI clinical practice guidelines for CKD [The study patients were divided into two groups based on BP management status: the “poorly controlled” group, which included 413 patients whose SBP or DBP at the initiation of SGLT2i treatment was over 130 mmHg or 80 mmHg, respectively, and the “well-controlled” group that comprised 327 patients with BP at the initiation of SGLT2i of less than 130/80 mmHg.n = 537) and ≥102 mmHg group (n = 203).Based on the receiver operating characteristic (ROC) analysis shown in ΔLNACR) at the end of the treatment period was analyzed retrospectively.The change in the logarithmic value of ACR . Differences between before and after treatment data of the two groups were analyzed by the paired Analysis of covariance (ANCOVA) was performed with LNACR at the initiation of SGLT2i as the covariate and LNACR at the time of the survey as the dependent variable, taking into consideration BP management at the initiation of SGLT2i treatment (well-controlled versus poorly controlled groups) and the MAP at the time of the survey (<102 versus ≥102 groups).ROC curve was used to test the overall prediction accuracy of the MAP at the survey and the improvement or lack of improvement in ACR in patients treated with SGLT2i, and the results were reported as the area under the curve (AUC). The IBM SPSS Statistics 25.0 software program  was used in all statistical analyses.Supplementary p < 0.0001)  in ACR of 102 mmHg, with sensitivity of 30% and specificity of 23%, with an AUC of 0.52  of 0.48-0.56,  0.0001) .p < 0.001, p < 0.001, p < 0.001, p = 0.002, p < 0.001, and p < 0.001, respectively). Patients of the poorly controlled group were significantly younger than those of the well-controlled group (p < 0.001).p < 0.001, p < 0.001, p < 0.001, p = 0.018, p < 0.001, and p = 0.023, respectively). The MAP ≥ 102 group included significantly higher proportion of young males compared with the MAP < 102 group .1c, and BP at office were significantly larger in patients of the poorly controlled group . However, there was no significant difference in the changes in LNACR between these two groups.p = 0.004 and p < 0.001, respectively). There was a significant difference in changes in LNACR between these two groups.p < 0.001, estimated difference (95% CI) was -0.28 (-0.43 to 0.12)).1c relative to the placebo group, but the appropriate treatment was used in both groups of patients for the management of complications, such as hypertension, <130/80 mmHg, and/or lipid disorders.Several cardiovascular outcome clinical trials (CVOCT) of new glucose-lowering agents have been performed to determine their effects on cardiovascular events. The EMPA-REG OUTCOME trial  and CANVWhat are the mechanisms of the organ protective effects of SGLT2i? Several studies hinted to a multitude of factors, such as body weight loss, improvement of glucose control, correction of dyslipidemia, and lowering of BP. Terami et al.  reportedWe reported recently the renoprotective effect of SGLT2i in Japanese T2DM patients with CKD . The mulOn the other hand, our study showed no significant improvement in ACR in patients of the MAP ≥ 102 group (patients with SBP/DBP of 135/85 mmHg) after treatment with SGLT2i. The pathogenesis of diabetic nephropathy is suggested to involve glomerular hyperfiltration . Hyperfip < 0.05, each) [The control of BP is an important aspect of the overall management of DM, especially in CKD patients . In most5, each) . A simil5, each) ). SGLT2iThe above findings highlight the advantage of using SGLT2i in the dual management of T2DM and BP. It should be noted, however, that our study showed that SGLT2i treatment did not significantly improve ACR in patients with poor BP control. It is possible, however, for patients with poor BP control during treatment with SGLT2i to exhibit improvement in ACR than patients on placebo. Based on the renal data of the EMPA-REG OUTCOME trial , ACR decThe present study was a retrospective observational study. The use of other glucose-lowering and antihypertensive agents was only investigated at the survey. Patients of the adequate BP group might include those who discontinued antihypertensive agents after the initiation of SGLT2i therapy. Further, our study is only a single-arm study that did not include patients treated with placebo. Although these clinical and methodological limitations do not allow firm conclusions, the large number of patients included in this study provides clear evidence for the benefits of SGLT2i in hypertensive T2DM patients.Our results confirmed that blood pressure management status after SGLT2i administration influences the extent of change in urinary albumin-creatinine ratio. Stricter BP management might be needed in general practice to demonstrate the renoprotective effects of SGLT2i in Japanese T2DM patients with CKD.