In previous work, we reported the HR for the risk (95% CI) of the secondary kidney composite endpoint  with ertugliflozin compared with placebo as 0.81 . The effect of ertugliflozin on exploratory kidney-related outcomes was evaluated using data from the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes (VERTIS CV) trial (NCT01986881).Individuals with type 2 diabetes mellitus and established atherosclerotic CVD were randomised to receive ertugliflozin 5 mg or 15 mg (observations from both doses were pooled), or matching placebo, added on to existing treatment. The kidney composite outcome in VERTIS CV (reported previously) was time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death. The pre-specified exploratory composite outcome replaced doubling of serum creatinine with sustained 40% decrease from baseline in eGFR. In addition, the impact of ertugliflozin on urinary albumin/creatinine ratio (UACR) and eGFR over time was assessed.−1 [1.73 m]−2 , respectively. Ertugliflozin was associated with a consistent decrease in UACR and attenuation of eGFR decline across subgroups, with a suggested larger effect observed in the macroalbuminuria and Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease (KDIGO CKD) high/very high-risk subgroups.A total of 8246 individuals were randomised and followed for a mean of 3.5 years. The exploratory kidney composite outcome of sustained 40% reduction from baseline in eGFR, chronic kidney dialysis/transplant or renal death occurred at a lower event rate (events per 1000 person-years) in the ertugliflozin group than with the placebo group (6.0 vs 9.0); the HR (95% CI) was 0.66 . At 60 months, in the ertugliflozin group, placebo-corrected changes from baseline (95% CIs) in UACR and eGFR were −16.2%  and 2.6 ml minAmong individuals with type 2 diabetes and atherosclerotic CVD, ertugliflozin reduced the risk for the pre-specified exploratory composite renal endpoint and was associated with preservation of eGFR and reduced UACR.ClinicalTrials.gov NCT01986881The online version contains peer-reviewed but unedited supplementary material available at 10.1007/s00125-021-05407-5. The trial was conducted in accordance with the principles of Good Clinical Practice and was approved by the appropriate institutional review boards and regulatory agencies, with all participants providing written informed consent.The full details of trial eligibility criteria have been previously described , 12. The−1 [1.73 m]−2, ≥60 ml min−1 [1.73 m]−2 and <90 or <60 ml min−1 [1.73 m]−2, respectively. For the classification by baseline UACR, participants were classified into normoalbuminuria, microalbuminuria or macroalbuminuria categories if UACR (mg/mmol [mg/g]) was <3.39 (<30), ≥3.39 and ≤33.9 (≥30 and ≤300) or >33.9 (>300), respectively. The KDIGO CKD risk category  was based on the prognosis of CKD by eGFR  and albuminuria categories heat map  eGFR; (2) UACR; and (3) the Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease (KDIGO CKD) risk categories, which combine eGFR and UACR. For the eGFR category, baseline eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) study equation ; partici eGFR; (2−1 [1.73 m]−2 and eGFR ≥60 ml min−1 [1.73 m]−2).All analyses reported here were pre-specified, either in the statistical analysis plan of the trial or in a separate analysis plan completed prior to database lock and unblinding . Briefly, results are reported for the hierarchically tested secondary composite kidney outcome , as well as the individual components of the composite, and a sensitivity analysis based on sustained doubling of serum creatinine , chronic kidney dialysis/transplant or renal death. As a sustained 40% decline from baseline in eGFR is an appropriate surrogate endpoint for kidney failure that allows for the accrual of more events in a shorter period of time , we carrThe analyses of kidney composite endpoints and each individual component were performed on the intention-to-treat population . The analyses of eGFR and UACR endpoints were carried out on the full analysis set . The analyses of eGFR and UACR endpoints were performed on the pooled ertugliflozin population and by ertugliflozin dose (5 mg and 15 mg). Data after the initiation of glycaemic rescue therapy were included; however, data obtained more than 2 days after the last dose of study medication were excluded from the change-from-baseline analyses of the eGFR and UACR endpoints. The analyses of the adverse event of acute kidney failure were carried out on the safety population (randomised participants who took one or more doses of study medication); adverse events occurring up to 30 days after the final dose of study medication were included.p value of the interaction term is presented for subgroup analyses. Time-to-event endpoints, if no event had occurred, were censored at the time of the last follow-up visit.The time-to-event endpoints were analysed using a stratified Cox proportional hazards model, including treatment group as a covariate with cohort as a stratification factor . For baseline subgroup analyses, the models included terms for treatment, subgroup  and treatment-by-subgroup interaction. The baseline subgroups were evaluated by eGFR category, KDIGO CKD risk categories and UACR category. The 1c and baseline systolic BP (SBP) if the analysis model converged. Owing to the non-normal distribution of UACR, UACR data were log-transformed prior to analysis. The geometric means and adjusted mean percentage change (derived from exponentiation of adjusted estimates from the cLDA model) with 95% CIs are presented by treatment and timepoint. The difference between ertugliflozin treatment and placebo in mean percentage change in UACR from baseline was estimated and presented. For subgroup analyses of eGFR and UACR, a repeated measures ANCOVA (RMANCOVA) method was used. The RMANCOVA model adjusted for baseline of response variable, baseline HbA1c, treatment, time, subgroup, treatment-by-subgroup interaction and treatment-by-subgroup-by-time interaction. For subgroup analyses based on factors that were already in the main model, the respective term appeared in the model only once. In both cLDA and RMANCOVA models, time was treated as a categorical variable. An unstructured covariance matrix was used to model the correlation among repeated measurements. When the covariance structure did not converge, a Toeplitz covariance structure was used. Summary statistics are provided for baseline demographic and disease characteristics. In this exploratory kidney outcomes analysis, type 1 error of 5% was not controlled for multiple testing. The nominal p values are reported. All statistical analyses were performed using SAS Version 9.4 .Mean changes from baseline in eGFR and UACR endpoints over time were estimated using the constrained longitudinal data analysis (cLDA) model for the overall population. The model contained the fixed effects for treatment, time, treatment-by-time interaction, baseline HbA1c was 66.5 mmol/mol (8.2%) and mean SBP was 133.3 mmHg.A total of 8246 individuals were randomised and followed for a mean (SD) of 3.5 1.2) years. Of these, 2747 received placebo and 5499 received ertugliflozin (5 mg or 15 mg doses). Details of participant disposition and study conduct have been reported . Of the .2 years.−1 [1.73 m]−2 and the median for UACR was 2.1 mg/mmol (19.0 mg/g) in the overall cohort. Baseline characteristics in the pooled ertugliflozin population were similar to those of the individual ertugliflozin 5 mg and 15 mg groups  occurred at an event rate (events per 1000 person-years) of 9.3 and 11.5 in the ertugliflozin and placebo groups, respectively, with a HR (95% CI) of 0.81 0.63, 1.04)  in the ertugliflozin group than with placebo (6.0 vs 9.0), with a HR (95% CI) of 0.66  Figs . Similarp values for interaction by baseline kidney function categories were non-significant.The risk reduction for the pre-specified exploratory kidney composite endpoint with ertugliflozin compared with placebo is presented in ESM Table In the overall population, ertugliflozin was associated with a reduced risk of progression to microalbuminuria  or macroalbuminuria  compared with placebo Fig. . Event rp value for interaction was 0.04  or normoalbuminuria  compared with placebo. The event rate for regression of microalbuminuria and macroalbuminuria per 1000 person-years was 87.7 and 72.3 in the ertugliflozin and placebo group, respectively, with a HR (95% CI) of 1.23 . While beneficial effects on regression of albuminuria were observed consistently among all subgroups, a larger effect is suggested in the subgroup with greater baseline elevation of albuminuria, as the In the overall cohort, ertugliflozin was associated with a reduction in UACR compared with placebo, and this persisted for the duration of the study Fig. . Placebo−1 [1.73 m]−2  and −0.5 ml min−1 [1.73 m]−2  in the ertugliflozin and placebo groups, respectively  (p < 0.01). Values of eGFR over time using the MDRD equation were similar when compared with calculations using the CKD-EPI equation  was 2.06 , 2.59  and 5.80  in participants treated with ertugliflozin who had normoalbuminuria, microalbuminuria and macroalbuminuria at baseline, respectively.In the overall cohort, least squares mean change 95% CI) in eGFR from baseline to week 6 was −3.0 ml min−1 1.3 m−2 . In the subgroup with baseline eGFR ≥60 ml min−1 [1.73 m]−2, the proportion of participants with one or more kidney-related adverse events was similar in the ertugliflozin and placebo groups .In the overall population, the proportion of participants with one or more kidney-related adverse events (utilising the SMQ) did not differ between the ertugliflozin and placebo groups . The event rates per 1000 person-years were 14.5 (ertugliflozin group) and 16.9 (placebo group), with a HR (95% CI) of 0.87 . The most frequent preferred term from the SMQ was acute kidney injury (AKI), the frequency of which was 2.2% and 1.8% for the placebo and ertugliflozin groups, respectively. These kidney-related safety findings were similar in participants with baseline eGFR <60 and ≥60 ml minVERTIS CV is the fourth SGLT2 inhibitor CVOT to evaluate kidney outcomes –9. These−1 [1.73 m]−2 [−1 [1.73 m]−2, as was used in EMPA-REG OUTCOME) and the requirement for sustainability of the decline. Consistent with previous CVOTs −2 . In the .73 m]−2 . A possius CVOTs , 18, ertThe effect of SGLT2 inhibitors on UACR lowering has been consistently demonstrated, occurring in individuals with type 2 diabetes with preserved and impaired kidney function , 19, andSGLT2 inhibitors have characteristic effects on kidney function. In human mechanistic studies, empagliflozin reduced inulin-based GFR and renal blood flow in individuals with type 1 diabetes , in conjReports from the US Food and Drug Administration’s adverse event reporting system suggested higher AKI risk with SGLT2 inhibitors. In individual CVOTs, AKI risk was either neutral or reduced with SGLT2 inhibitors, and in meta-analyses involving cardiorenal outcome studies, AKI risk was reduced by approximately 25% , 17, 18.Our analysis does have limitations. We recognise that although observations from this analysis are generally consistent with renal-related effects in other trials with SGLT2 inhibitors, findings from this cohort with type 2 diabetes and established atherosclerotic CVD may not be generalisable to other groups of individuals. We used pre-specified exploratory endpoints and did not control for type 1 error. The protocol amendment at the end of 2015 resulted in two cohorts with different durations of follow-up. A subgroup analysis of the interaction of the secondary kidney outcome by cohort was found to be non-significant. As reported in previous event-driven trials, the number of participants decreased through the observation period, limiting the interpretability of the results for eGFR and UACR over time. Although valuable as a measure of long-term kidney risk, UACR does have inherent limitations due, in part, to variability of single UACR measures. Nevertheless, the VERTIS CV trial included a large sample size, which mitigated some of the inherent limitations around the use of single UACR measurements at each time point. Furthermore, the use of single measurements and related variability would have biased our analysis towards null. Hence, the effects of ertugliflozin may be underestimated. Early and late haemodynamic effects of the SGLT2 inhibitor class of medications may limit the interpretability of the UACR results. The assessment of acute renal failure was based on adverse event reporting by investigators; however, a blinded external independent panel adjudicated all important renal events for assessment of causality with study medication. Finally, we recognise that the endpoints were exploratory in nature; however, the use of sustained 40% decline in eGFR rather than doubling of serum creatinine is widely recognised as being clinically relevant and has been used in other kidney protection studies , 31.In conclusion, when used in addition to standard of care medications, ertugliflozin was associated with a decrease in the risk of a sustained 40% decline in eGFR, with less albuminuria and with preservation of eGFR over time in individuals with type 2 diabetes and established atherosclerotic CVD. Observations from the VERTIS CV study suggest that the effects of ertugliflozin on the kidneys are generally consistent with the known benefits of SGLT2 inhibitors.ESM Statistical Analysis Plan(PDF 399 kb)ESM Tables and Figures(PDF 899 kb)


The authors aimed to investigate the ideal achieved BP in ESRD patients with CAD after coronary intervention. Five hundred and seventy‐five ESRD patients who had undergone percutaneous coronary interventions (PCIs) were enrolled and their clinical outcomes were analyzed according to the category of systolic BP (SBP) and diastolic BP (DBP) achieved. The clinical outcomes included major cardiovascular events (MACE) and MACE plus hospitalization for congestive heart failure  event).The mean systolic BP was 135.0 ± 24.7 mm Hg and the mean diastolic BP was 70.7 ± 13.1 mm Hg. Systolic BP 140–149 mm Hg and diastolic BP 80–89 mm Hg had the lowest MACE  and total CV event . Patients with systolic BP < 120 mm Hg had a higher risk of MACE  than those with systolic BP 140–149 mm Hg. Patients with systolic BP ≥ 160 mm Hg  and diastolic blood BP ≥ 90 mm Hg  had a higher risk of total CV event rate when compared to those with systolic BP 140–149 mm Hg and diastolic BP 80–89 mm Hg. A J‐shaped association between systolic (140–149 mm Hg) and diastolic (80–89 mm Hg) BP and decreased cardiovascular events for CAD was found in patients with ESRD after undergoing PCI in non‐Western population.Hypertension is a frequent manifestation of chronic kidney disease but the ideal blood pressure (BP) target in patients with coronary artery disease (CAD) with end‐stage renal disease (ESRD) (eGFR < 15 ml/min/1.73m Although most clinical trials did not enroll patients with poor renal function, current guidelines still suggest that patients with CKD should be considered a high‐risk group and that aggressive BP control is recommended to reduce future risk.2This larger retrospective, single‐center observational study included participants with symptomatic CAD who received a PCI between July 2006 and December 2015 at the Taipei Veteran General Hospital, Taiwan. In brief, CAD diagnosis included positive results on the stress test, a history of angina with ECG ischemic changes, myocardial infarction, or angina symptoms with a significant stenosis lesion on coronary computed tomography angiography (CCTA). All patients who received PCI either with coronary stenting or balloon angioplasty were screened.2,Patients with CKD stage V, defined as an eGFR < 15 ml/min/1.73mAfter enrollment, PCI procedures and treatment strategies were recorded. Baseline characteristics, including sex, age, history of hypertension, diabetes, hyperlipidemia, smoking, family history of premature CAD, and cerebral vascular disease, were collected from every patient. Furthermore, biochemical data describing renal function, lipid profiles, and medications were also collected by trained study nurses and qualified cardiologists. Blood pressure was measured by a well‐trained nurse with an electronic BP monitor according to the ACC/AHA Guideline suggestion for recording BP in adultsDuring follow‐up, the primary outcome, major adverse cardiovascular events (MACE), which included cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke, was recorded. The secondary outcome was the total cardiovascular event , which was a composite of the MACE plus hospitalization for congestive heart failure. Myocardial infarction was confirmed in patients presenting with ischemic symptoms with elevated serum cardiac enzyme levels and/or characteristic ECG changes. Ischemic stroke was confirmed as an obstruction within a brain blood vessel with imaging evidence by either MRI or CT scan and a new neurological deficit lasting for at least 24 h. The protocol for CV event follow‐up was performed as previously described.p‐values < .05 were considered significant. In addition to crude hazard ratios (HRs), adjusted HRs were estimated after adjustment for potential confounding factors, including age, sex, history of hypertension, diabetes, and smoking habit. All analyses were performed using the statistical package SPSS for Windows Categorical and continuous variables were expressed as the mean ± standard deviation or frequency (percentage). Between various BP groups, the chi‐square test or Fisher's exact test was used for comparing the continuous data and the categorical variables were analyzed by one‐way analysis of variance (ANOVA). The clinical outcomes were presented as overall percentages and expressed as proportions with a 95% confidence interval (CI). The prognostic difference and event‐free survival rate between groups of patients with various maintained BP levels were analyzed using the Kaplan–Meier method based on the log‐rank test. Hazard ratios (HRs) from the Cox regression model were used to analyze each outcome. 3Tables A total of 575 patients  with ESRD who underwent successful coronary intervention were enrolled. The baseline characteristics of the participants according to the achieved SBP and DBP categories are presented in Figure Figure A). Regarding the CHF hospitalization incidence, there was a linear association between SBP values and the incidence of hospitalization for heart failure.Clinical follow‐up was carried out with all patients for a mean period of 65.6 months. During this time, there were 66 cardiovascular deaths, 175 cardiac nonfatal myocardial infarctions, 64 nonfatal strokes, and 287 hospitalizations for heart failure. Figure B) than patients in the other diastolic BP groups. Kaplan–Meier curves were used to assess the occurrence of future adverse events according to the categories of SBP and DBP maintained in the ESRD patients who underwent coronary PCI  amid various SBP and DBP categories and in the total CV event  among the DBP groups (p < .05).In the diastolic BP categories, patients who maintained a diastolic BP of approximately 80–89 mm Hg had a lower incidence of MACE (13.3%), total CV event (21.1%), cardiac death (2.6%), nonfatal stroke (0%), and HF hospitalization (10.5%) Figure 1B thanTable Figure ). The same phenomenon appears in different age groups (age < 70 years and ≥ 70 years). In both groups, diastolic BP found similar U‐shape result was found in MACE and total CV event. For those > 70 years, U‐shape was still found in total CV event, but not so significant for the MACE  association between BP and the incidence of hospitalization for heart failure. This was reasonable because all dialysis patients needed dialysis to maintain output balance. Higher BP may represent unstable sodium‐fluid homeostasis. Volume overload, excess sodium, and a decompensated state that could deteriorate heart function, further leading to acute decompensated heart failure.n < 3) and it was difficult to make a conclusion based on limited cases. However, we still can found that patients whose SBP between 140 and 149 plus DBP between 80 and 89 had the lowest incidence of future MACE and total CV events. Therefore, a larger‐scale population is needed to verify the current study findings. Second, we used in‐hospital and outpatient clinic visit BP recordings, not home BP measurements. The bias between hospital‐visit BP measurements and home BP measurements cannot be excluded. Third, our study was from a single‐center observational registry. Patients were enrolled and followed up regularly for clinical events in the outpatient clinics of the medical centers or teaching hospitals, which could not reflect the referral nature of the practice at this tertiary referral medical center in Taiwan. Finally, cancer survivors had a higher risk of cardiovascular diseases such as deep vein thrombosis, heart failure, arrhythmia, pericarditis, and usually had poor outcome. In our study, there were 15 CAD patients with cancer history enrolled in our study, and no cardiac death was found among these patients. Because few cancer patients enrolled in our current study and limited events were identified, the cancer effect cannot be evaluated. We provide evidence of a J‐curve association between SBP and DBP and adverse cardiovascular events in CAD patients who underwent dialysis after PCI. The SBP and DBP associated with the lowest future MACE were 140–149 mm Hg and 80–90 mm Hg, respectively. For the relationship between heart failure incidence and BP values, no J‐curve association was observed. A larger‐scale population‐based study is needed to confirm our observations.This study has limitations that should be mentioned. First, we have ever grouped those CAD patients according to six SBP and four DBP categories. Some BP groups have few cases (The Author(s) declare(s) that there is no conflict of interest.A consortium has been organized to conduct this study. H.‐B. Leu, and Y.‐L. Yang, contributed to the study design. Y.‐L. Yang contributed to infrastructure design and technician training for this project. All investigators of this study  are in charge of collecting clinical informatics and tissue sample in hospital. H.‐B. Leu, S.‐C. Chen, Y.‐L. Yang contributed to data analysis and data interpretation. H.‐B. Leu, and Y.‐L. Yang contributed to paper writing. All the investigators approved the paper.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.


With respect to medicine accessibility, 98.8% (n = 338) and 42.9% (n = 61) received at least one medication from the hospital pharmacy of KATH and UHS, respectively. Using MARS-10, 49.2% (n = 70) and 52.9% (n = 181) were nonadherent in UHS and KATH, respectively. There was a significant association between adherence and BP control at both UHS (p=0.038) and KATH (p=0.043). At UHS, there was a significant association between accessibility to medicines at the hospital and BP control (p=0.031), whilst at KATH, no significant association was observed (p=0.198). Supply chain practices and delays in payment by the NHIA affected accessibility to antihypertensive medications. Blood pressure control was inadequate among participants in both facilities. Accessibility to medicines was better at the tertiary facility compared to the secondary facility. Increased accessibility and adherence to antihypertensives were related to blood pressure control in both facilities. Good supply chain practices and prompt payment by the National Health Insurance Authority would enhance accessibility to antihypertensive medications.Hypertension is the second leading cause of death in Ghana, partly accounting for two-thirds of all medical admissions and more than 50% of deaths. This study aimed to comparatively evaluate adherence and accessibility to antihypertensive medications at two different levels of healthcare facilities in Kumasi, Ghana, and determine factors associated with medicine accessibility and adherence. A cross-sectional study involving outpatient department (OPD) hypertensive patients, 143 at KNUST Hospital (UHS) and 342 at Komfo Anokye Teaching Hospital (KATH), was conducted using a semistructured questionnaire. Correlations were drawn to evaluate the effect of accessibility and adherence on blood pressure control. A face-to-face interview was also conducted with relevant stakeholders involved in procurement of medicines. Blood pressure was uncontrolled in 50.4% ( The incidence of hypertension and its prevalence and death due to complications have increased globally. The prevalence of hypertension in sub-Saharan Africa is estimated to be 38% in some communities with an expected rise in numbers by 2025 . PopulatPoor adherence is the most important cause of uncontrolled BP. Research has shown that an estimate of about 50–70% of hypertensive patients do not adhere to their antihypertensive therapy as prescribed . This reThe Ghana National Health Insurance Scheme (NHIS) was instituted as a social intervention to reduce cost and to increase accessibility to healthcare. However, due to setbacks resulting from delays in payment of service providers and lack of financial sustainability, supply of medicines to public health facilities has been a challenge. In addition, uncoordinated care, inadequate funds, shortage of healthcare professionals, and low health insurance coverage contribute to the weak healthcare system in Ghana . Even thThis study therefore sought to investigate and compare the accessibility of antihypertensive medication and its effect on adherence and blood pressure control at two different levels of healthcare facilities. Komfo Anokye Teaching Hospital (KATH) is a 1200-bed tertiary and referral hospital easily accessible to people in the Kumasi and the northern sector of Ghana . The divData from this study will enable relevant stakeholders of healthcare appreciate the factors that affect accessibility to medicines and its effect on adherence and blood pressure control in order to institute measures to achieve holistic outcome-oriented patient care.A hospital-based cross-sectional study was carried out during the hypertensive clinic days at University Health Services (UHS) and Komfo Anokye Teaching Hospital (KATH) in Kumasi.Z2PQ) ÷ E2, where Z is the confidence interval, P is the prevalence rate, Q = (1 − P), and E is the desired level of precision. The confidence interval was set at 95% with a precision of ±5. The power of the study was estimated to be 91.5% using SPSS version 25. A sample size of 408 was obtained. To accommodate a 10% margin of error, a stronger statistical power, and effect size, a total of 485 participants were interviewed for the study, 342 from KATH and 143 from UHS, in proportion to estimated daily visits at these healthcare facilities. We also interviewed five pharmacists: the director of pharmacy (DP), deputy director (DDPS), two clinical pharmacists (CP), and head of the medical store (MS). These individuals were directly responsible for the acquisition and supply of medicines in both facilities.Participants enrolled for the study were hypertensive patients aged between 25 and 80 years visiting UHS or KATH for review. Their oral consent was sought prior to the study. In estimating the minimum sample size, Glenn's formula was used  version 25 tool for data and multinomial logistics regression (MLRM) using R packages. Normality was tested using Shapiro–Wilk test. Significant association between variables was assessed with the chi-square test. Statistical significance was set at All procedures were in compliance with ethical standards obtained from the Committee for Human Research Publication of KNUST (CHRPE/AP/410/18), and informed consent was sought from all participants. The study was reported in accordance with the preferred standard in reporting observational studies in epidemiology (STROBE) .n = 94)) than males. At KATH, the mean age was 60.16 ± 11.50 with a slight majority falling between the ages of 61 and 70 years, representing 54.4% (n = 186). Similar to UHS, more females (72.5% (n = 248)) than males were enrolled. Diabetes mellitus was the commonest comorbid condition at UHS with stroke being the commonest at KATH. There was a normal distribution which was seen for all variables ) and KATH (76.2% (n = 245)) was public transport. There was a statistically significant association between time taken to access facility and adherence in both UHS (p=0.033) and KATH (p=0.006) A negatively skewed distribution was observed for time taken to reach the facility and mode of transport  were covered by the NHIS, whilst 86.5% (n = 296) were covered at KATH. A representation of 8.4% (n = 12) and 0.3% (n = 1) utilized private insurance companies at UHS and KATH, respectively. A negatively skewed distribution was seen for insurance coverage  were given a combination of calcium channel blocker with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and diuretics, while at KATH, the commonest combination was calcium channel blocker with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and diuretics, representing 38.2% (n = 131). Other common antihypertensives administered in addition to the combinations included methyldopa, hydralazine, and beta blockers  could not recall precautionary measures and counselling given; 49.2% (n = 70) were nonadherent. At KATH, 72.5% (n = 248) could not recall precautionary measures; 52.9% (n = 181) were nonadherent. There was a statistically significant association between awareness of precautionary measures and counselling and BP control at both UHS (p=0.023) and KATH (p < 0.001) as well as adherence and BP control at UHS (p=0.038) and KATH (p = 0.043)  .n = 73) received 70% and above of their prescribed antihypertensives from the hospital pharmacy, whilst that of KATH was 35.1% (n = 120) out of 342 participants. There was a significant association between accessibility to medicines at UHS and BP control (p=0.031). There was no significant relationship between accessibility of antihypertensives and BP control at KATH (p=0.198)  .From the interview, it was deduced that availability of medicines was dependent on the Drug and Therapeutics Committee who were tasked with the development of hospital formularies, preparation of treatment guidelines, and ensuring the sustained availability of medicines in the healthcare facilities. The interviews sought to identify the role of supply chain and NHIS processes as determinants of accessibility to medicines.I will say geographical location of the suppliers. If the headquarters is not in Kumasi, there is a delay in supply. And sometimes the quantities the suppliers have might not be enough, so these are some of the issues we face” (MS).“Medicines are supplied to both hospitals via a tender system. Suppliers who win the bids may have some difficulties that cause a delay in the delivery of the ordered medications.Every morning we check the drugs we have so the ones where the quantities are down, we order (CP).”“Essentially, in a functional system, measures should be put in place to ensure continuity of supply through the setting of minimum ordering points, maximum ordering points, and emergency ordering points to guide ordering of medicines. There were means of getting around ordering challenges even though the process was not standardized.I will rate the difficulty at 5 and this depends on the product (DDPS).”“We send list to prescribers telling them the drugs and when they will expire and sometimes, we call other hospitals and swap (CP).”“Expiration of medicines seemed to be a problem for all stakeholders who gave the problem a 5 rating. They all had measures put in place to curb expiries.More training will help from time to time so we learn new ways to do the job (MS).”“Stakeholders emphasized the need for refresher courses on supply chain to help them remember what they had previously learnt and be abreast with new trends that are emerging.They write the drugs on NHIS prescription form, stamped, signed by the prescriber and given to the clients to obtain the drugs from NHIS-accredited pharmacies outside the facility (DDPS).”“Patients on the NHIS can obtain covered medicines from both hospitals. Additionally, KATH offers alternative measures for its clients if they are unable to supply their clients' prescribed drugs. They reportedUnavailability of drugs to clients resulting in the worsening of the disease condition of clients (MS).”“There is also 10% deduction in the total amount owed KATH by NHIA to defray errors that occur in the NHIS claims forms which are not refunded to the facility when no errors are detected (DP).”“The reimbursement of the facilities by the NHIA for their supplied drug is mostly delayed, hence making availability of drugs at the facility irregular or reduced. It was also realized that the NHIS medicine list does not cover all antihypertensive medications; hence, clients are made to pay for those drugs. The delay in reimbursement of KATH by the NHIA poses a lot of challenges to the facility such asFrom our study, the majority of participants were aged over 50 years, and this is to be expected as the prevalence of hypertension is associated with increasing age; often, due to the development of arterial stiffness, a decrease in sensitivity to the baroreceptors as well as changes in the renal system results in alteration of sodium metabolism . There wJNC 7 and 8 recommend the use of a calcium channel blocker or a diuretic as the first line in the management of hypertension in blacks . The datA section of the participants had in addition to their regimen a beta blocker, hydralazine, or methyldopa which could partly be a result of the existence of resistant hypertension where BP is still greater than 140/90 even after the patient is given three or more antihypertensive drugs . StatinsComparatively, a higher section of the participants at KATH could not recall information on their medications. This could partly be as a result of the number of antihypertensives given or inadequate education from health workers. Patients may receive inadequate information on their medicines due to the high workload in these hospitals. The former is in line with previous studies which have closely related forgetfulness to nonadherence and subsequent poor BP control . There wAt both sites, blood pressure was uncontrolled in more than half of participants; however, control was poorer at KATH than at UHS. Uncontrolled blood pressure increases the likelihood of occurrence of cardiovascular-related morbidity and mortality. Therefore, as expected, some of the participants from both study sites presented with comorbidities such as diabetes, stroke, and chronic kidney diseases. This was in line with previous studies from sub-Saharan Africa which further recommended the need for BP control to prevent morbidity and mortality with resultant improvement in patients' quality of life .From our study, the majority of patients from both facilities were not adherent to medications with UHS, reporting a comparatively better adherence rate than KATH. There was also a significant association between adherence and BP control. A rise in systolic BP of 20 mmHg and diastolic BP by 10 mmHg above 115/75 mmHg doubles the risk of the incidence of cardiovascular diseases, hence the urgency to maintain optimal BP levels . HyperteRegarding accessibility to the healthcare facility, time taken to access UHS was relatively shorter as compared to KATH. This is because UHS provides primary healthcare mainly to the university community and surrounding suburbs, whilst KATH, a tertiary hospital, is the main referral hospital in the Ashanti Region. Regardless, the majority of participants reported that transportation was affordable. This implies that though the distances required to travel to the healthcare facilities vary, both facilities are relatively accessible to patients. From our study, there was a significant association between time taken to access the facility and adherence in both hospitals, and this has been previously shown by research to be significantly associated with blood pressure control , 37 as eAccessibility to antihypertensive agents has been shown to be several times associated with good BP control , 39, andGhana is endowed with more than 5,000 community pharmacies, and for most Ghanaians, the community pharmacy is their first port of call to meet their health needs. Recently, the Pharmacy Council of Ghana abolished the 400-meter rule which only allowed pharmacies to be situated 400 meters apart. The sole aim of this decision was to enhance accessibility to pharmaceutical services. It is therefore not surprising that alternative sources of obtaining antihypertensive medicines by participants were the community pharmacies . It was In recent times, supply chain management has been an area of focus, especially in the public sectors. Even though the relevance of efficient logistics systems in achieving positive outcomes in healthcare has been widely discussed, several studies have reported high stockout rates of essential medicine, rendering medicines inaccessible in developing countries. Our study identified lapses in logistics management on the part of stakeholders mostly in forecasting, ordering, and losses to expiry. Stakeholders reported a need for constant training of the aforementioned areas as part of an interventional measure in their bid to enhance accessibility, and this has been proven to be effective by several authors . LogistiWe studied the impact of accessibility to antihypertensives and adherence on blood pressure control as well as the role of the supply chain and NHIS in making medicines accessible. Comparatively, BP control was poorer at KATH than at UHS. Antihypertensives were more accessible at UHS than at KATH, and there was a significant correlation between accessibility and BP control. We found out that accessibility is largely driven by good supply chain practices and prompt payment of claims by the NHIA. Knowledge on medications was significantly higher at UHS than at KATH with a significant correlation to BP control. Adherence was significantly associated with BP control with participants at UHS being comparatively adherent than at KATH. It is imperative that antihypertensives are made accessible, and more education is given on the management of hypertension to improve adherence and BP control. Other factors affecting accessibility as well as other methods to improve adherence amongst hypertensives such as follow-ups and phone reminders can be studied in Ghana.


Hypertension and type 2 diabetes are associated with each other, and their coexistence is linked to diabetes-related complications such as stroke, coronary artery disease, kidney disease, retinopathy and diabetic foot. This study aimed to determine the prevalence, awareness and control of hypertension and factors associated with hypertension among people with type 2 diabetes mellitus (T2DM) in Bangladesh.A cross-sectional and retrospective study was conducted in 2017, and data from 1252 adults with T2DM were collected from six hospitals that specialise in diabetes care. These hospitals provide primary, secondary and tertiary healthcare and cover the rural and urban populations of Bangladesh. Cross-sectional data were collected from patients via face-to-face interviews, and retrospective data were collected from patients’ past medical records , locally known as the patients’ guidebook or record book. The associations between hypertension and its related factors were examined using the bootstrapping method with multiple logistic regression to adjust for potential confounders.The mean age of participants was 55.14 (± 12.51) years. Hypertension was found to be present among 67.2% of participants, and 95.8% were aware that they had it. Of these, 79.5% attained the blood pressure control. The mean duration of diabetes was 10.86 (± 7.73) years. The variables that were found to be related to hypertension include an age of above 60 years, physical inactivity, being overweight or obese, a longer duration of diabetes and chronic kidney disease.The prevalence of hypertension as well as its awareness and control were very high among people with known type 2 diabetes. As there is a strong relationship between hypertension and diabetes, patients with diabetes should have their blood pressure regularly monitored to prevent major diabetes-related complications. Hypertension is a major non-communicable disease and is identified as a global disease burden that is ranked as the third-largest cause of disability-adjusted life years . GloballDiabetes mellitus and hypertension are inter-related diseases that strongly promote the spread of atherosclerotic cardiovascular disease within populations . HyperteThe population of Asian, especially South Asia, is facing an increasing burden from hypertension  has led to an increase in hypertension among people with T2DM in Bangladesh. Thus, it is essential that patients and healthcare workers are aware of the co-existence of hypertension and T2DM to ensure that there is tight monitoring of blood pressure (BP) and blood sugar levels. To ensure good regulation, it is quintessential that an updated prevalence of hypertension, it’s awareness and control, and the factors associated with hypertension in patients with T2DM is available. Thus, this study aimed to determine the prevalence of hypertension and its associated factors among people with T2DM in Bangladesh.A cross-sectional and retrospective study was conducted in 2017 in Bangladesh. Data were collected from outpatient department of six selected hospitals across the country that are under the umbrella of the Diabetic Association of Bangladesh (BADAS). All hospitals under BADAS are locally known as diabetes hospitals, as their primary focus is to treat patients with diabetes and its related complications. These hospitals are operated privately, but they provide healthcare services on a not-for-profit basis . These hospitals are located both outside and inside metropolitan areas across the country. The hospitals outside the metropolitan areas provide primary and secondary level healthcare services. However, within the metropolitan areas, the selected hospitals are the central hospitals that deliver primary, secondary and tertiary healthcare. The selection of the specific hospitals in this study made it possible to recruit a heterogeneous sample in terms of participants’ residential areas and socio-economic status.BADAS has created a sustainable model of health care for people with diabetes and the general population. Most of the diabetic patients in Bangladesh prefer to visit hospitals under BADAS because of the availability of endocrinologists and diabetes-centred care and because the quality of facilities is higher than those in public hospitals. Thus, despite the fact that the participants in our study do not represent all people with T2DM in Bangladesh, they represent the majority of them. Hospitals under BADAS were purposively selected for data collection, as all patients are provided a record book or medical passport, which keeps patients’ records of laboratory test results, medications, complications and comorbidities.It was calculated that a sample size of 1252 participants would be required to ensure accurate results. The primary outcome of this study was to determine haemoglobin A1c (HbA1c) levels and diabetes control , and theDuring each day of data collection, around 10 patients were recruited from each hospital’s general outpatient department. The data collectors started the day by randomly selecting a patient from the first K patients attending the hospital and invited them to participate. The value of K was determined by dividing the total estimated hospital outdoor attendance each day by 10. After that, every Kth patient was approached. If this patient declined to participate in the study or did not have T2DM, the next patient was invited. The recruitment continued for 6 months, from Saturday to Thursday each week. The inclusion criteria were as follows: patients were over 18 years of age, were registered with BADAS and had had T2DM for over 1 year. The study excluded people suffering from other types of diabetes.. A PhD research student and two data collectors were recruited and trained for data collection.A structured questionnaire was developed based on published literature and different standardised questionnaires –23. The Data on sociodemographic characteristics, mental health (anxiety and depression), diabetes-related medical history and lifestyle behaviours were collected. The Global Physical Activity Questionnaire (GPAQ) was used to assess physical activity level . The PatThe following variables were extracted from medical passports or clinical records: most recent HbA1c level, lipid profiles, most recent estimated glomerular filtration rate (GFR), diagnosis of hypertension, medications used, and history of macro-vascular (coronary artery disease (CAD), stroke and diabetic foot) and micro-vascular  complications. For CAD and retinopathy, patients’ past medical records, past documented diagnoses, medications or past procedures were used to extract the data. Research Electronic Data Capture (REDCap) was used to collect and manage the data .2 = underweight; 18.50 to 22.99 kg/m2 = normal; 23.00 to 27.49 kg/m2 = overweight and ≥ 27.5 = obese [2 and/or a documented diagnosis [Participants’ household income was categorised as follows: up to 20,000 Bangladeshi Taka (BDT), 21,000 to 60,000 BDT and over 60,000 BDT . The mon = obese . High wa = obese . Hyperte = obese . Based oiagnosis .This study has been approved by the Monash University Human Research Ethics Committee (ID: 1469), the Ethical Review Committee of the Bangladesh University of Health Sciences and the Ethical Review Committee of BADAS.p-value of less than 0.15 from the univariate analysis [n = 108), waist–hip ratio  and glycaemic control .Stata/SE version 15.0 was used for the data analysis. Data were summarised and presented as means (± standard deviation) for numerical data and relative percentages for categorical data. Chi-square tests and univariate logistic regression analysis were used to examine associations between hypertension and its associated factors. Potential variables were then identified using a clinical assessment, literature review and the variables with a analysis . Of thesn = 1253) were drawn from each of the five imputed samples. This created 25,000 samples. A multiple logistic regression analysis was then performed for each of the 25,000 samples where all potential variables were added into the model, and the variables that appeared as significant were recorded. The percentage of the time that each variable was selected as significant  was calculated and variables were ranked from the highest to the lowest percentage. A multiple logistic regression model was then run using the variables that were selected in at least 40% of the bootstrap samples, which adjusted the effect of each variable with potential confounders.Missing data were imputed five times using the chained equation method, creating five imputed samples , 34. TheA total of 1404 people with diabetes were approached, but 89 of them had type 1 or gestational diabetes, and 63 of them declined to participate  were unaware that they had it, but upon measuring their blood pressure during this present study it was found to be classified as being high. Furthermore, of those who were previously aware that they had hypertension, 79.5% (n = 642/807) had controlled hypertension, when measured for the present study. However, using a more aggressive BP cut point of 130/80 mmHg, as recommended for patients with diabetes, hypertension prevalence, awareness and control were 72.5% (n = 909/1252), 88.8% (807/909), and 60.2% (n = 486/807) respectively . The prevalence of hypertension awareness for male and female was 95.3 and 96.4%  respectively for BP cut point of 140/90 mmHg, and that was 88.1 and 89.6%  for BP cut point of 130/80 mmHg respectively  of the participants in this study had hypertension. Of those with hypertension, 95.8% (807/842) were aware that they had hypertension (informed either by a doctor or nurse on previous occasions). The remaining 4.2% n = 5/842 werp-value < 0.001). Hypertension prevalence was similar between male and female . The prevalence of hypertension was also significantly higher among people who resided in urban areas, were physically inactive, were obese or had a high waist–hip ratio . The presence of hypertension was also significantly higher among people who never smoked (66.1%) compared to those who smoke presently (48.9%) and did in the past (63.9%), with a p-value of 0.004  as compared to patients 60 years and below (57.8%) (p < 0.001). Also, the presence of hypertension was higher among people who had depression, anxiety or micro- and macro-vascular complications (p < 0.001)  or have a history of chronic kidney diseases showed an increased prevalence of hypertension , overweight , obese  or physically inactive  increased the odds of hypertension. Furthermore, higher odds were observed among patients with chronic kidney disease  and who had diabetes for over 10 years    or otherThe prevalence of hypertension awareness among hypertensive T2DM in this study was 95.8%, and among them 79.5% had it controlled. The data on hypertension awareness and its control among T2DM patients is scarce in the South Asian countries. However, a multi-country study conducted from 2003 to 2009 on the general population in India, Pakistan and Bangladesh showed that 40.4% of the hypertensive patients were aware of it and 12.9% had it controlled . In compThe multivariable analysis in the current study showed that older age, physical inactivity, being overweight or obese, longer duration of diabetes and chronic kidney disease are related to hypertension among people with T2DM. As previous evidence suggests, our study demonstrated that being physically inactive was associated with an increased prevalence of hypertension , 44 and This study has strengths and limitations. First, it used a relatively large sample that came from six diabetes hospitals that provide primary, secondary and tertiary healthcare and cover rural and urban populations. Second, in addition to a large sample size, this study used validated questionnaires, which provides a valuable repository of data that merits dissemination. Third, the investigation of various demographic, behavioural and clinical factors added strength to the study. A limitation of this study was that it was cross-sectional and retrospective in its design, which only allows for the implication of association, rather than causation. The unavailability of data on the treatment of hypertension among hypertensive T2DM patients was another limitation. Finally, a major limitation is that the findings of this study are not generalizable to diabetes patients not receiving care at BADAS hospitals.Considering the high proportion of hypertension among patients with diabetes and the close pathophysiological association between T2DM and hypertension, patients with T2DM should have regular monitoring of blood pressure to diagnose and control hypertension. The factors related to hypertension among patients with T2DM are the same as those found in other studies, and this study highlights the need for lifestyle interventions to decrease obesity levels and increase physical activity. The BADAS hospitals’ policy of mandatory blood pressure monitoring in each diabetes check-up visit and a full or partial fee waiver for investigation and treatment for financially disadvantaged patients may be a key factor for high levels of hypertension awareness and controls among T2DM patients. This study suggests and highlights the successful policy implementation of hypertension management at hospitals in Bangladesh and other similarly positioned countries in accordance with international guidelines .


In 2017, the American College of Cardiology/American Heart Association revised guidelines for diagnosis and management of hypertension in adults. The regional impact of the updated guidelines on the prevalence of hypertension in India is unknown.Data from nationally representative Indian households were analyzed to estimate the regional prevalence of hypertension according to the old and the new guidelines in men (age 18–54 years) and women (age 18–49 years). The old guidelines defined hypertension as a systolic blood pressure of ≥140 mmHg or diastolic blood pressure of ≥90 mmHg or treatment. The new guidelines define hypertension as a systolic blood pressure of ≥130 mmHg or diastolic blood pressure of ≥80 mmHg or treatment. We calculated the increase in the prevalence of hypertension among the states and union territories of India (hereafter “states”).Among 679,712 participants (85.6% women), the median age was 31 years  and was comparable among men and women . The overall weighted prevalence according to old and new guidelines was 18.5%  and 43.0% , respectively. There was a significant increase in hypertension prevalence, both among men and women, and across all regions. The northeast region of the country had the highest prevalence.The overall prevalence of hypertension significantly increases with the new compared to the old guidelines, however, the regional heterogeneity of prevalence of hypertension is maintained. Promotion of a healthy lifestyle and sustained blood pressure control from an early age can have huge cost-effect benefits, especially for a low- and middle-income country such as India.2The study was conducted following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines (Supplement Table 1).We analyzed data from the 2015–2016 National Family Health Survey-4 (NFHS-4).All participants gave written, informed consent before participation in the survey. We used publicly available de-identified data and approval from the Institutional Review Board was not required.All fieldworkers collecting data were trained to accurately measure blood pressure. The field manual and data collection questionnaire is available online.We excluded participants aged <18 years and those with pregnancy at the time of BP measurement. We excluded participants with systolic blood pressure less than or equal to diastolic blood pressure. We also excluded participants with systolic blood pressure <60 mmHg or >250 mmHg or diastolic blood pressure <30 mmHg or >250 mmHg due to biological implausibility. There were no exclusion criteria based on treatment for hypertension.2.1The Eighth Joint National Committee (JNC8) guidelines (hereafter “old guidelines”) define hypertension as either a systolic blood pressure ≥140 mmHg or diastolic blood pressure of ≥90 mmHg or treatment with antihypertensive medications.2.2The main outcome of the study was to assess the national and regional impact of the 2017 ACC/AHA guidelines on the prevalence of hypertension in India.2.3In this survey, 2-stage cluster sampling was used. The primary sampling unit was a village for a rural area or a census enumeration block in an urban area. This sampling was done using probability proportion to population, with the 2011 census population of India as the reference. Next, systematic random sampling was used to select households within each sampling unit. Data from men aged 15–54 years were collected from 15% of randomly selected households.Systolic and diastolic blood pressure was defined as the average of the 2nd and the 3rd blood pressure reading. In patients with only 2 blood pressure readings, the average of the first 2 readings was taken. Household sampling weights were used for calculating the overall prevalence. Strata with singleton primary sampling units were treated as certainty units and contributed nothing to the standard error around the overall weighted prevalence.Continuous variables were reported as medians with interquartile ranges (IQRs) and categorical variables were represented as counts with proportions. Chi-squared tests were used to identify the differences in hypertension prevalence with new guidelines and across different states. All statistical analyses were conducted in Stata version 14.2 .3Data from 679,712 participants were available for analysis . The median age of the study population was 31 years ; 85.5% were women. Three readings of systolic blood pressure and diastolic blood pressure were available in 97.7% of the study participants. Mean systolic blood pressure among men and women was 121 mmHg  and 114 mmHg , respectively. Mean diastolic blood pressure among men and women was 80 mmHg  and 77 mmHg , respectively.The overall weighted prevalence according to the old guidelines was 18.5% . The overall weighted prevalence according to the new guidelines was 43.0% . There was significant heterogeneity in the overall prevalence across the region: the prevalence according to the new guideline ranged from 39.9%  in the central region to 51.8%  in the northeastern region (Supplement Table 2). The prevalence according to the old guidelines in the central and the northeastern region was 14.6%  and 23.1% , respectively.The overall weighted prevalence according to old and new guidelines among men was 21.2%  and 52.3% , respectively A and B. The distribution of BP categories across the four new stages of hypertension among participants not on any anti-hypertension medications (96.7% of the study population), is given in 4In this analysis of a survey population of Indian adults aged 18–54 years for men and 18–49 years for women, the overall prevalence of hypertension increased by 2.3 times from 18.5% to 43% with the new guidelines. Overall, less than 50% of men and less than 60% of women had normal blood pressure according to the new guidelines.,,Large randomized control trials have suggested an incremental benefit of intensive blood pressure control to prevent adverse cardiovascular events.,,An analysis from the Global Burden of Disease Study in 2016 showed a wide regional variation in the burden of cardiovascular diseases in India.,National Health Policy of India in 2017 aims to reduce premature deaths due to cardiovascular causes by 25% and treating ≥80% of patients with hypertension by 2025 (NHP). Understanding regional heterogeneity in cardiovascular risk factors might help direct targeted and cost-effective interventions. Similar to previous studies, our study suggests a disproportionately high prevalence in the Northeast region.Besides conventional risk factors such as obesity, and smoking, high ambient air pollution, and dietary salt consumption are of special importance in India.At a national level, the government should invest in population screening and promotion of a healthy lifestyle, including but not limited to a low salt diet and regular physical exercise. At a local level, the primary health care centers and sub-centers can serve as valuable tools to deliver preventive health care and blood pressure management. Strategies for hypertension management can also help manage other cardiovascular risk factors such as dyslipidemia, diabetes mellitus, and obesity. It is important to note that the current Indian Guidelines for Hypertension-IV, published in 2019, do not endorse the lowered cut-off.There are several limitations to our study. As discussed previously, there was oversampling of women and a relatively young age group. The results do not apply to the entire adult population. We aimed to assess the regional impact on the prevalence and did not analyze urban-rural differences. Current guidelines recommend taking 3 blood pressure readings on 2 different occasions.Currently, there is no longitudinal data from India to understand the benefit of more stringent blood pressure control. However, it is unlikely that the cardiovascular benefit would differ from the large, randomized control trials in other countries.5In this analysis of a cross-sectional survey from India, we found a significant increase in the national and regional prevalence of hypertension according to the 2017 ACC/AHA guidelines. There is regional heterogeneity in the prevalence of hypertension.None.10.13039/501100002973Daiichi-Sankyo, 10.13039/100000968American Heart Association, and fees for educational activities from the 10.13039/100005485American College of Cardiology, Society for Vascular Medicine, Society for Cardiovascular Angiography and Interventions, Janssen and Janssen, 10.13039/100004319Pfizer, Medscape, and Clinical Exercise Physiology Association. The other authors have no conflict of interest related to this work.Dr. Qamar reports receiving institutional grant support from


This study aims to explain the correlation among non-alcoholic fatty liver disease (NAFLD), hyperuricemia, and thyroid function and to find independent risk factors for each other.Data were obtained from subjects who underwent health examination in the Health Promotion Centre of Sir Run Run Shaw Hospital of Zhejiang University from January 2017 to February 2019. The diagnosis of NAFLD was according to the clinical diagnosis of the guidelines. Serum uric acid (SUA) > 360 μmol/L  and SUA > 420 μmol/L  were enrolled in the hyperuricemia group. R software was used for statistical analysis.N=19004), and 65.73% of patients were classified as non-NAFLD group (N=36445). The levels of gender ratio, age, BMI, waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), HbA1c, triglyceride (TG), high-density lipoprotein (HDLC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN), creatinine (CR), FT3, FT4, and TSH were significantly different between the non-NAFLD group and NAFLD group. Age, BMI, waist circumference, DBP, fFBG, HbA1c, total cholesterol (TC), low-density lipoprotein (LDLC), AST, and UA were all independent risk factors for NAFLD. In the normal uric acid group, variables other than SBP and TSH were independent factors of NAFLD. In the hyperuricemia group, all variables except SBP, FT4, and TSH were independent factors of NAFLD.55,449 subjects were included in the analysis. 34.27% of patients were classified as NAFLD group (The level of uric acid is related to the occurrence of NAFLD. Hyperuricemia is one of the independent risk factors of NAFLD. TSH level is not related to the occurrence of NAFLD, while FT3 and FT4 may be related to NAFLD. Nonalcoholic fatty liver disease (NAFLD) is a common chronic disease characterized by the accumulation of fat in the liver, which can be associated with obesity, and can progress to fibrosis, cirrhosis, and even liver cancer . NAFLD iUric acid is mostly metabolized by the kidneys and is a product of purine metabolism in the human body. Hyperuricemia is a common manifestation in patients with chronic kidney disease, which is believed to be related to vascular smooth muscle proliferation, endothelial dysfunction, and interstitial inflammatory infiltration . StudiesThyroid hormones T3 and T4 are synthesized in the thyroid gland and are associated with thyroglobulin . Some reData were obtained from subjects who underwent health examination in the Health Promotion Centre of Sir Run Run Shaw Hospital of Zhejiang University from January 2017 to February 2019. The diagnosis of NAFLD is based on the following three criteria: nonalcoholic, fatty degeneration detected by imaging or histological examination, and other liver diseases excluded . ExclusiNAFLD was consistent with no history of alcohol consumption or alcohol consumption equivalent to ethanol < 140 g/week , ethanol < 70 g/week , except for viral hepatitis, drug-induced liver disease, total parenteral nutrition, hepatolenticular degeneration, autoimmune liver disease, and other specific diseases that can lead to fatty liver disease. According to the diagnostic criteria and exclusion criteria of NAFLD, we divided the samples into NAFLD group and non-NAFLD group.The results were grouped according to serum uric acid levels. Serum uric acid (SUA) > 360 mmol/L  and SUA> 420 mmol/L  were enrolled in the hyperuricemia group, while the rest were enrolled in the non-hyperuricemia group.t test, and P < 0.05 was considered statistically significant. Classification data were compared by chi-square test, and the difference was statistically significant by P < 0.001. The measurement data of non-normal distribution were expressed by the median (interquartile distance), the Mann-Whitney U rank sum test was used for pantwise comparison, and the multivariate logistic regression analysis was used for risk factor analysis.R software was used for statistical analysis. The measurement data conforming to the normal distribution were expressed as the mean ± standard deviation (‾X ± SD). The comparison between the two groups was conducted by N=19004), and 65.73% of patients were classified as non-NAFLD group (N=36445). Gender ratio, age, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, HbA1c, triglyceride, high-density lipoprotein, glutamate transaminase, glutamate transaminase, urea nitrogen, creatinine, FT3, FT4, and TSH were significantly different between the two groups (P < 0.05) . In the multivariate logistic regression model, age, BMI, waist circumference, diastolic blood pressure, rapid blood glucose, HbA1c, total cholesterol, low-density lipoprotein, AST, and uric acid were all independent risk factors for NAFLD (OR > 1). Systolic blood pressure and TSH are independent factors (see Table N = 39183), the NAFLD group (N = 10615) compared with the non-NAFLD group (N = 28568), sex, age, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, triglyceride, total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), ALT, AST, FT3, FT4, etc., all have significant difference and with no difference of TSH in the two groups (p = 0.309). In subjects with the hyperuricemia (N = 16266), the fatty liver group (N = 8389) compared with the non-NAFLD group (N = 7877), sex ratio, age, BMI, waist circumference, systolic pressure, diastolic blood pressure, triglyceride, total cholesterol, HDL-c, LDL-c, ALT, AST, FT3, etc., all have significant difference and with no difference of TSH (p = 0.784) and FT4 (p = 0.173) in the two groups . Male, total cholesterol, high-density lipoprotein, AST, FT3, and FT4 were protective factors (OR < 1). At the same time, we divided the NAFLD group and the control group according to the uric acid level. In the normal uric acid group, variables other than systolic blood pressure and TSH were independent factors of NAFLD. In the hyperuricemia group, all variables except systolic blood pressure, FT4, and TSH were independent factors of NAFLD.We found that FT3 and FT4 were considered as protective factors of NAFLD. After secondary grouping, FT3 and FT4 were protective factors for NAFLD under normal uric acid conditions. In the case of increased uric acid, only FT4 was a protective factor for NAFLD. Thyroid hormone has a metabolic effect on protein, carbohydrate, and fat. The decrease of thyroid level is related to the low metabolism, which can be manifested as weight gain, increased blood lipid, and increased blood sugar . StudiesSince our study found that there was no correlation between TSH and NAFLD, which was inconsistent with other studies, we hoped to look for common clues. We found that after adjusting for age and gender, TSH was associated with NAFLD when other variables were adjusted separately; when TSH was adjusted together with BMI, waist circumference, and TG, TSH was not associated with NAFLD. Therefore, we hypothesized that the correlation between TSH and NAFLD may be affected by body weight and blood lipids, which needs to be further confirmed by further studies. In summary, NAFLD, hyperuricemia, and thyroid dysfunction are all related to components of metabolic syndrome, and hyperuricemia is a risk factor for the increased incidence of NAFLD. Whether uric acid level is normal or not, TSH is not related to NAFLD, while FT3 and FT4 are related to NAFLD, but whether they are the factors of NAFLD remains to be confirmed.The level of uric acid is related to the occurrence of NAFLD. Hyperuricemia is one of the independent risk factors of NAFLD. TSH level is not related to the occurrence of NAFLD, while FT3 and FT4 may be related to NAFLD.


Measuring blood pressure in patients with obesity is challenging. The ClearSight™ finger cuff (FC) uses the vascular unloading technique to provide continuous non-invasive blood pressure measurements. We aimed to test the agreement of the FC with invasive radial arterial monitoring (INV) in patients with obesity.2 and underwent laparoscopic bariatric surgery. FC and INV measurements were obtained simultaneously every 5 min on each patient, following induction of anesthesia. Agreement over time was assessed using modified Bland-Altman plots and error grid analysis permitted clinical interpretation of the results. Four-quadrant plots allowed assessment of concordance in blood pressure changes.Participants had a body mass index (BMI) ≥45 kg/m2 (IQR 48.3–55.3). The observed bias  for systolic blood pressure (SBP) was 14.3 mmHg , 5.2 mmHg  for mean arterial pressure (MAP) and 2.6 mmHg  for diastolic blood pressure (DBP). Error grid analysis showed that the proportion of readings in risk zones A-E were 90.8, 6.5, 2.7, 0 and 0% for SBP and 91.4, 4.3, 4.3, 0 and 0% for MAP, respectively. Discordance occurred in ≤8% of pairs for consecutive change in SBP, MAP and DBP.The 30 participants had a median (IQR) BMI of 50.2 kg/m2.The vascular unloading technique was not adequately in agreement with radial arterial monitoring. Evaluation in a larger sample is required before recommending this technique for intraoperative monitoring of patients with BMI ≥45 kg/m Accurate non-invasive blood pressure (NIBP) measurement is an important component of perioperative care. This measurement is known to be difficult patients with Class III obesity . Traditi2 undergoing cardiothoracic surgery, Martina and colleagues found that the FC met Association for the Advancement of Medical Instrumentation (AAMI) criteria for validation [The ClearSight™ EV1000 Clinical Platform   provideslidation . Howeverlidation .The evaluation of ClearSight™ in patients with obesity was limited until recently, when Rogge et al. evaluated ClearSight™  and SchuDevices utilising FCs rather than oscillometric NIBP cuffs have potential benefits by avoiding the variation in arm shape that is observed in patients with obesity . Accurat2. The primary aim was to assess the agreement of the FC with INV measurements over time, including systolic blood pressure (SBP), mean arterial pressure (MAP) and diastolic blood pressure (DBP). An error grid analysis was undertaken to permit clinical interpretation of our results. We performed a four-quadrant plot, reporting on concordance, to evaluate the ability of the FC to track changes in blood pressure. In addition, we sought to describe the arm morphology of our participants in terms of mid-arm circumference and conicity index.We aimed to compare the accuracy of the continuous NIBP measurements obtained via a FC with the gold standard, invasive radial arterial blood pressure monitoring (INV), in patients with BMI ≥45 kg/m2. A BMI > 40 kg/m2 is considered Class III obesity. We excluded participants if they had a known cardiac arrhythmia, were American Society of Anesthesiologists physical status [This prospective methods comparison study was approved by the Human Research Ethics Committee of The Royal Brisbane and Women’s Hospital, Brisbane, Australia,  and participants provided written informed consent. This manuscript adheres to the STROBE guideline. We included participants if they were scheduled for elective laparoscopic bariatric surgery, were aged ≥18 years and had a BMI ≥45 kg/ml status  ≥ 4, hadMeasurements were obtained from both upper limbs according to standard anthropometric procedures , by two Prior to induction, we inserted a radial arterial catheter. We placed the FC on the same side as the arterial line, on the middle phalanx of the middle finger using the appropriately-sized cuff and zeroed using the heart reference sensor. The cuff was selected using the finger-sizing guide provided by the manufacturer . Where tGeneral anesthesia was induced and maintained according to the preference of the specialist anaesthetist. No blood pressure targets were specified. It is our institutional practice to use vasopressor (metaraminol or phenylephrine) to maintain blood pressure during laparoscopic bariatric surgery and we documented the details of vasopressor use. Following standard positioning of the patient  the first blood pressure measurements were obtained (T0). These included the SBP, DBP and MAP from the FC and INV measurement devices. Pressures were recorded digitally at 5 min intervals for each patient up to 1 hour, or until completion of anesthesia and stored for analysis.The primary outcome was the agreement of the FC with INV measurements  at 5 min intervals during general anesthesia. Secondary outcomes included: a clinical interpretation of the data using an error grid analysis and a concordance analysis using four-quadrant plots to evaluate the ability of the FC to track arterial pressure changes.Participant characteristics were summarised using descriptive statistics; mean and standard deviation (SD) for continuous normally distributed variables, median and interquartile range (IQR) for non-normally distributed variables and frequency and percent for categorical variables.The data structure over time consisted of paired INV and FC measurements of MAP, SBP and DBP taken at 5-min intervals for each patient from commencement of anesthesia for 60 min or completion of general anesthesia, whichever occurred first. Agreement between INV and FC for MAP, SBP and DBP over the time points was assessed using the modified true value varies method of the Bland-Altman analysis for multiple observations per participant , 16. TheA.No risk B.Low risk C.Moderate risk D.Significant risk E.Dangerous risk An error grid analysis was undertaken, based on the work of Saugel et al. . This meWe calculated the percentage of blood pressure readings corresponding to the risk levels A-E and the actual values were represented visually as five zones on the error grid. Clinically acceptable targets were considered to be less than 5% of readings in Zone B, 4% in Zone C and 2% in Zone D .Changes in blood pressure between consecutive time points  for FC and INV methods were plotted against each other in four-quadrant plots, reporting on concordance. An exclusion zone of +/− 5 mmHg was set, indicating only small changes in blood pressure with random noise. R  was used for all analyses.2 , 26 (87%) were female and 4 (13%) were male. Table Thirty participants were eligible and completed the protocol between September 2018 and November 2019. Figure The total number of individual blood pressure measurements across MAP, SBP and DBP for both INV and FC was 2229. All patients had complete blood pressure measurements up to 15 min, after which the number of measurements per method ranged between 26 and 30, due to variations in the duration of surgery.Table The results of the error grid analysis are shown in Fig. The four-quadrant plots for SBP, MAP and DBP are shown in Fig. 2, the vascular unloading technique did not provide blood pressure measurements in agreement with those provided by the gold standard radial arterial monitoring. When measurements were assessed over time, we concluded that the FC could not be used interchangeably with radial arterial monitoring. The error grid analysis demonstrated that 97.3 and 95.7% of SBP and MAP readings were within the no- or low-risk zones (no or benign treatment). For MAP, the percentage of readings meeting the criteria for category C fell just outside that suggested as acceptable by Saugel et al. (4%) [2. The proportion of discordant pairs of readings for SBP, DBP and MAP were similar to those reported by Rogge et al. [When used intraoperatively in patients with BMI ≥45 kg/mal. (4%)  and these et al. . Based o2, Rogge et al. showed that the mean difference between these techniques was greater for the SBP, followed by the MAP and the DBP  [2) the bias was greater for all three . The limits of agreement calculated from the Rogge data are consistent with ours. Schumann et al. evaluated the finger cuff in 90 patients with a mean (SD) BMI of 48 (7) kg/m2. Their results, in patients with a mean (SD) mid-arm circumference of 43 (5) cm were more favourable towards the finger cuff [This pattern was also observed in the study by Rogge et al. . In 35 pctively) . In our ger cuff . Our resger cuff  and Schuger cuff , in whicger cuff . HoweverPre-operatively, the detection of hypertension in patients with obesity warrants investigation and optimisation . In thisBased on their arm morphology, our cohort is representative of patients likely to have erroneous NIBP readings and for whom an accurate alternative is required , 4. ThrePouwel and colleagues failed to validate Nexfin™ in patients with obesity when compared to auscultatory sphygmomanometry . A limitOur study adds to the currently limited understanding of the clinical performance of the vascular unloading technique, compared with invasive techniques, in patients who are very obese. Until recently, there were no studies evaluating the utility of this technique in this specific population. Our 30 participants were larger than the 35 evaluated by Rogge et al.  and larg2 are required.Our study has limitations. Female participants were over-represented in our group, reflecting our national bariatric registry sex differential and this has been previously noted locally . Our resThis study also raises known difficulties in validating non-invasive continuous blood pressure monitoring devices, particularly in patients with obesity . Current2. In this pilot study, the vascular unloading technique did not provide accurate blood pressure measurements when assessed over time, with the FC tending to provide lower values. The clinical consequences of these errors would have led to inappropriate interventions of moderate risk in a small but arguably significant fraction of readings, in this population with a high burden of comorbidities. Equipment suitable for patients with obesity is required for all perioperative phases and when invasive monitoring is not appropriate. Further evaluation of this device is required in larger numbers of patients with obesity.An increasing body of work is emerging regarding alternatives to oscillometric NIBP cuff measurements of blood pressure in patients with BMI ≥45 kg/m


Background: Cardiovascular complications are the leading cause of morbidity and mortality at any stage of chronic kidney disease (CKD). Moreover, the high rate of cardiovascular mortality observed in these patients is associated with an accelerated atherosclerosis process that likely starts at the early stages of CKD. Thus, traditional and non-traditional or uremic-related factors represent a link between CKD and cardiovascular risk. Among non-conventional risk factors, particular focus has been placed on anaemia, mineral and bone disorders, inflammation, malnutrition and oxidative stress and, in this regard, connections have been reported between oxidative stress and cardiovascular disease in dialysis patients. Methods: We evaluated the oxidation process in different molecular lines  in 155 non-dialysis patients at different stages of CKD and 45 healthy controls. To assess oxidative stress status, we analyzed oxidized glutathione (GSSG), reduced glutathione (GSH) and the oxidized/reduced glutathione ratio (GSSG/GSH) and other oxidation indicators, including malondialdehyde (MDA) and 8-oxo-2’-deoxyguanosine (8-oxo-dG). Results: An active grade of oxidative stress was found from the early stages of CKD onwards, which affected all of the molecular lines studied. We observed a heightened oxidative state (indicated by a higher level of oxidized molecules together with decreased levels of antioxidant molecules) as kidney function declined. Furthermore, oxidative stress-related alterations were significantly greater in CKD patients than in the control group. Conclusions: CKD patients exhibit significantly higher oxidative stress than healthy individuals, and these alterations intensify as eGFR declines, showing significant differences between CKD stages. Thus, future research is warranted to provide clearer results in this area. Patients affected by renal disease are extremely vulnerable to cardiovascular disease (CVD). Indeed, cardiovascular complications are the leading cause of morbidity and mortality at any stage of chronic kidney disease (CKD), with annual mortality rates 10–20-fold higher than in the general population even after adjusting for age, sex, ethnicity and presence of diabetes mellitus ,4.Among these non-traditional risk factors, there has been a particular focus on anaemia, mineral and bone disorders, insulin resistance, inflammation, malnutrition and oxidative stress ,5,6. AmoThere is experimental evidence that implicates reactive oxygen species (ROS) as primary mediators in the pathogenesis of kidney damage caused by ischemic, toxic processes and antibody–antigen reactions at the glomerular and tubular level. Oxidative stress also generates subclinical inflammation which induces endothelial dysfunction and vascular aging, reducing the availability of nitric oxide ,8. This In this regard, connections have been reported between oxidative stress and CVD in dialysis patients ,14,15, wThis cross-sectional study was conducted over 30 months in 155 CKD non-dialysis-dependent (CKD-NDD) patients from the outpatient clinic of the nephrology department at the Hospital Clínico Universitario of Valencia. The study was approved by the research ethics committee of the hospital, and all patients signed consent forms in accordance with the Declaration of Helsinki.Patients aged between 18-80 years, with previous CKD diagnosis at least 12 months before study initiation and clinical stability during the last 6 months were included.Patients with active neoplasia or inflammatory, present or recurrent infectious disease, having received intravenous iron in the last six months or blood transfusion in the 15 days prior to blood sample extraction were excluded.Of the 157 patients screened, two were excluded due to active infection. Finally, 155 CKD-NDD patients at stages 3–5 were included in the study, along with a control group of 45 healthy subjects with similar demographic data.All patients attended our outpatient clinic at baseline and we reviewed the medical records of these patients, recording their demographic data and clinical characteristics: etiology of kidney disease, history of smoking, hypertension, dyslipidemia, diabetes mellitus, ischemic heart disease , arrhythmia, heart failure, stroke, or peripheral arterial disease.Blood samples were collected after 12 h of fasting, for haematology and biochemical screening, including urea, creatinine, lipid and protein panel, albumin and phospho-calcium metabolism. Renal function was measured by the estimated glomerular filtration rate (eGFR) using the CKD-EPI formula, and patients were classified according to CKD stage following KDIGO guidelines .To determine oxidative stress parameters in each patient, 14 mL of blood was withdrawn in a tube with EDTA as an anticoagulant. These samples were immediately centrifuged to separate plasma. Mononuclear cells were isolated by Ficoll–Hypaque centrifugation, followed by three saline washes. Mononuclear cells were resuspended in RPMI 1460 medium (Sigma) and lysed with RNA/DNA stabilization Reagent for Blood/Bone marrow mar lysis buffer (Roche) for DNA extraction were then stored at −80 °C until use. Nuclear DNA was isolated following the Gupta method, with the modification described by Muniz et al.  in which260 nm: wavelength of peak nucleic acid absorption.280 nm: wavelength of maximum protein absorption.The DNA obtained was quantified by spectrophotometry, diluting the sample 1/100 in TE buffer  and measuring the absorbance of the dilution at two different wavelengths:The relationship between the readings at 260 nm and at 280 nm helps us determine the purity of the extraction. If this ratio is greater than 1.8, the DNA purity is considered acceptable; if not, the sample is discarded.To study lipid peroxidation, malondialdehyde (MDA) was determined in isolated mononuclear cells by high resolution liquid chromatography, and the protein concentration in each sample was measured by Lowry’s method to reference these parameters .Pro-oxidation analysis was studied by determining oxidized glutathione (GSSG), reduced glutathione (GSH) and the relationship between GSSG/GSH by high-performance liquid chromatography in mononuclear cells following the methods described by Ursini and Navarro .Lastly, isolation and the analysis of the modified base 8-oxo 2′-deoxyguanosine (8-oxo-dG) was performed by HPLC-EC in previously isolated and digested nuclear DNA following the conditions described by Frenkel et al. .p ≤ 0.05.Variables were expressed as mean ± standard deviation and as median and interquartile range for variables with non-normal distribution (Shapiro–Wilk test). Next, logarithmic transformation was performed. For comparison of two independent variables, T student with Levene test was used for equality of variances. To compare qualitative variables, chi square with the Yates correction was performed; and in case of less than five observations we used Fischer’s test. To study different correlations between variables, Pearson’s bivariate correlation was performed. There were no missing data among the included patients and significance was set at One-way ANOVA was performed for comparison analysis between the five groups of all the oxidative stress parameters studied. The percentiles of the oxidative stress parameters in the control group were also calculated. The 90th percentile of the oxidized variables was considered the upper level of normality and lower level of normality was the 10th percentile of antioxidant variables. MedCalc version 15.4 and SPSS for Windows version 19 were used for statistical analysis.The final sample of the study consisted of 155 CKD-NDD patients at different stages of CKD, 51.6% of whom were women with an average age of 68.64 years; 48.4% were men with an average age of 68.09 years. The baseline characteristics of these patients, demographic data and primary cause of kidney disease are summarized in The prevalence of cardiovascular risk factors observed in the study are shown in p < 0.05). The prevalence of CVD distributed by CKD stage is described in Most patients showed a high percentage of conventional cardiovascular risk factors across the different stages of CKD. Moreover, hypertension and dyslipidemia were present in more than 90% of patients, even in earlier stages of CKD. Notably, no significant differences were found between CKD groups, except for homocysteine between G3A and all remaining groups (p = 0.04). No other significant between-group differences were detected in the remaining comorbidities . When comparing the means obtained from controls against renal-affected patients, we found a statistically significant difference (p < 0.001) in all oxidative stress parameters studied.Oxidative stress analysis results in CKD-NDD patients and controls are shown in p < 0.001) between all groups except between CKD G4 and G5-NDD (p = 1000) (p < 0.001) between all stages of CKD (p = 0.080). (c) Statistically significant variations (p < 0.001) in levels of 8-oxo-dG—a molecule derived from oxidative damage of nuclear genetic material—were identified between all stages of CKD, although no association was observed between CKD G4 and G5-NDD (p = 1.000) (p < 0.001), compared to other stages   revealed the following: (a) At lipid peroxidation level (MDA) differences were statistically significant ( = 1000) . (b) Amos of CKD ; however= 1.000) . (d) Reg G5-NDD) .The highest mean values of all oxidative parameters were observed in CKD stage G5. Of note, CKD stages G4 and G5 showed no statistically significant differences in oxidative stress levels. Nonetheless, for oxidative parameters, the mean values in patients with CKD were higher than the 90th percentile of the control group. Whether the CKD group was considered as a whole or separately across CKD stages was observed. In contrast, mean levels of antioxidant parameters were lower in the CKD population than in the control group. On stratifying CKD groups by stages, the mean values of all oxidative parameters were above the 90th percentile of the control group at all stages. The same occurred with the oxidative stress parameters, with the exception of CKD G3A, whose mean value was higher than the 10th percentile of the control group.6 dG of 8-oxo-dG increased across stages: 62.1% in G3A, 78.3% in G3B, 87.24% in G4 and 91.67% in G5 ; except for one patient in G3A, 99% of patients had higher GSSG values at 0.646 U/mg protein; 100% of GSSG/GSH ratios in all study groups were above 2.218; the percentage of patients with measurements higher than 4.19 U/107% in G5 ; finallyp < 0.001) was found. Analysis of the correlation between oxidative parameters showed a positive correlation between all the oxidizing molecules ; however, a negative correlation with antioxidant molecule (GSH) (p < 0.001), revealing a negative relationship with all the oxidizing molecules (R between −0.684 and −0.653) and a positive one with the antioxidant (R = 0.441) parameters.We evaluated a possible relationship between eGFR and different oxidative stress parameters. All oxidative stress parameters were correlated with eGFR (CKD-EPI formula) levels (p = 0.056–0.147).Interestingly, we found no statistical differences between diabetic kidney disease-affected patients and those without this condition. A total of 74 diabetic patients were compared to 81 non-diabetic patients and none of the mean oxidative stress parameters showed significant differences ; moreover, we observed that MDA levels increased at worse stages of CKD. Furthermore, all patients presented higher levels of MDA than the 90th percentile of the control group.Our results are in agreement with previously published studies . At lipi2) and chronic haemodialysis [Given the paucity of studies in the dialysis population analyzing the oxidative damage of genetic material in patients with renal disease, we explored this issue using the molecule 8-oxo-2′-deoxyguanosine (8-oxo-dG) in CKD-NDD patients ,37. Tarndialysis ,38. Rangdialysis . They coThe generation and accumulation of uremic toxins favors free radical production and, therefore, molecular oxidation with the increase of oxidized substances, which has an impact on erythropoiesis. Hence, reduced mitochondrial DNA copy number, reduced energy production, and higher levels of stress markers contribute to this condition in CKD. Moreover, the decrease in the ability to synthesize erythropoietin due to kidney disfunction causes the appearance of anemia . On the Protein oxidation is assessed by measuring oxidized glutathione (GSSG: glutathione disulfide) and the ratio of oxidized glutathione to reduced glutathione (GSSG/GSH), an indicator of oxidative status of the cell and cellular toxicity . We alsoThe decrease in antioxidant systems, together with an increase in oxidative stress markers that accompany the pathogenesis of different diseases, has led to speculation, not yet fully substantiated, about the effectiveness of administrating exogenous antioxidants.In some clinical trials, antioxidants showed either no or even a negative effect in terms of increased mortality, with conflicting data. Various aspects and mechanisms may contribute to the failure of antioxidant use as therapeutic agents. These were recently reviewed by Schmidt, HH et al. . ApproprIn conclusion, CKD patients show significantly higher oxidative stress levels than healthy individuals, and these changes are intensified as eGFR declines, showing marked differences between CKD stages. Moreover, differences in oxidative stress parameters affected the three molecular lines studied equally. The process begins in the early stages of renal disease and increases along the course of deterioration, while antioxidant capacity decreases. Although future research is warranted to provide clearer results in this area, our findings are important, particularly in the pre-dialysis population, in whom current therapies are unsuccessful in slowing down CKD progression and reducing cardiovascular risk.