We aimed to determine the feasibility and effectiveness of an intervention anchored on mHealth and task sharing strategy of involving non-physician health workers (NPHW) on population level detection, treatment and control of hypertension and diabetes in India.Non-physician health workers (NPHWs) equipped with tablet computers that were linked with point-of-care devices for blood pressure (BP) and blood sugar measurements visited households, screened adult individuals for hypertension and diabetes from two randomly selected villages in the Medchal district, Telangana, India. Further, they digitally connected those individuals with hypertension and diabetes to a study physician via Skype, and handed over a printed e-prescription. Medication adherence checks, BP and fasting blood sugar measurements were done once a month and doctor consultations once in three months during follow-up.Among 2456 eligible individuals, 1751 and 1686 individuals were screened for hypertension and diabetes, respectively. Prevalence of hypertension was 23·6% (95% CI 21·6%-25·6%) and among them 38.9% were newly detected. Prevalence of diabetes was 11·2% (9·7%-12·7%) and 28.6% of them were newly detected. After 24 months of intervention, control of BP and blood sugar was achieved in 54.0% and 34·1% of individuals with hypertension and diabetes, respectively. Blood pressure control rate improved by 12% (7.9%-16.0%) in known hypertensive individuals over the intervention period.This research demonstrates the feasibility and local acceptability of a mHealth intervention strategy anchored on NPHWs guided by physicians for detection, treatment and regular follow-up of individuals with hypertension and diabetes in a community setting in India. Currently, 28% of all deaths in India are attributable to cardiovascular diseases (CVD). HyperteHypertension and diabetes awareness, treatment and control are abysmally poor in India–7. AchieThe Medchal district in Telangana, India has 40 villages and 10,176 households with a total population of 49,617. SHARE  INDIA developed a GPS  mapped database called the REACH database, with a listing of each resident in all the households in the Medchal district by name, date of birth, and gender [Adult male and female participants aged 20 years and above residing in the selected two villages were identified from the REACH database. We approached all the eligible adults residing in the selected two villages for participation in the study. Individuals who were not reachable, not willing to provide consent for participation, pregnant and lactating women were excluded. The study started in July, 2015 and completed in August, 2017.task sharing and mHealth. The NPHW worked under the supervision of a physician, and connected to him through a tele-medicine platform as part of the digital health tool .The key strategies of the intervention were We engaged Accredited Social Health Activist (ASHA) as NPHW in the study and trained them in using a customised mHealth tool to identify and manage hypertension and diabetes in community settings. The ASHAs cater to a population of approximately 1000 individuals and are the first point of contact for healthcare needs of the community. They work closely with the Auxiliary Nurse Midwife (ANM) at the health sub-center . The ANMs are a pivotal workforce at the sub-centre level facilitating access to and providing care for maternal and child health services especially those related to antenatal care, immunization, acute respiratory tract infections and diarrhoeal illnesses.We deployed three ASHAs—two in one and one in the other village proportional to the size of population and designated them as study NPHWs. Additionally, we deployed two ANMs -one in each village. The ASHAs networked with the ANMs to get blood samples drawn from eligible participants as per the study protocol. The services of the ANMs were required only for 4 months spread over a year. The ANMs deployed in this project had formal training and certification from an accredited institution as per the guidelines of the regulatory authority for nursing education in India.All NPHWs engaged in the study were provided with intensive in-office training for one week and subsequently for twelve weeks in the field. The training curriculum included the process of household data collection, use of tablet computer, sphygmomanometer, glucometer, printer and arranging Skype interview between the participant and the physician. The NPHWs performed various study related tasks including, questionnaire administration, BP measurement, fasting blood sugar measurement using capillary blood, uploading data on tablet PC, and networking with the study physician on Skype under direct supervision of specially trained supervisors during the twelve weeks field training period. In order to compensate for the time of each NPHW, we paid an honorarium of Rs.3000 per month .The study physician was a medical doctor with MBBS degree and attended telemedicine calls between 7:30 am and 12:30 pm, six days a week. Additionally, two supervisors-one per village were engaged to train the NPHWs in the field and also to monitor the activities of NPHWs. The supervisors were trained medical social workers with prior community based experience in managing health problems.A project manager with primary training in computers and electronics handled technological troubleshoot requests received from the NPHW and the doctor. The project manager also supervised the work of the supervisors and the NPHW on a day-to-day basis.The NPHWs guided by a supervisor visited each household and identified eligible individuals’ for screening. The NPHWs collected information related to medical history, obtained readings of BP and fasting blood sugar. The screening data of all participants were linked to the REACH project database. A structured study questionnaire was administered to gather information on general medical condition, past and present illnesses in local language and responses were noted in a tablet computer. The questionnaire also included sections on self-reported use of tobacco and alcohol, history of medical conditions such as hypertension, diabetes, bronchial asthma, thyroid disease, kidney disease, cardiovascular disease, and neurological diseases. Additionally, name, dose and duration since use of current medications were recorded.We developed an in-house mHealth application on Windows. The mHealth application was installed on the assigned tablet computers given to the NPHW. The application facilitated easy access to the screening tool, and all the study questionnaires. The mHealth application also generated a daily list of the participants due for follow-up visits and provided alerts to the NPHW to schedule Skype calls with the physician when required. Additionally, it created an electronic health record (EHR) for all study participants. Internet access in all the given tablets enabled the NPHW to synchronize the EHR with a cloud server. The study physician reviewed the EHR directly on his computer dashboard. The study physician also received a real-time alert on his mobile phone for an immediate tele-appointment. The NPHW with the help of the mHealth application facilitated a video Skype call between the study participant and the physician. Based on the tele-medicine consultation with the participant and the details available in the EHR, the study physician recommended appropriate management . The treBlood pressure measurement and diagnosis of hypertensionWe used Rossmax (model MJ701f) automated sphygmomanometer for BP measurements. The automated sphygmomanometer was interfaced with the tablet computer for automated input of measurements, which were subsequently uploaded on to a secure cloud system via internet. All the BP measurements were integrated with the individual’s medical history, other clinical parameters, and maintained as part of an electronic health record (EHR). The calibration protocol for the automated sphygmomanometer was followed as per the manufactures instruction manual. In addition, the automated BP sphygmomanometers were cross checked once a month with a manual mercury sphygmomanometer by a trained professional. In case there was a difference of more than 10 mm Hg in systolic or 5 mm Hg in diastolic between the two devices, the automated sphygmomanometer was discontinued from use and sent for calibration.Three BP readings were obtained from all study participants on the right arm using an appropriate sized cuff, with the patient comfortably seated, and arm at the level of the heart. All readings were obtained with at least one minute gap between two consecutive readings. The first systolic and diastolic BP readings were ignored, and an average of the second and third readings was considered as the systolic and diastolic BP for that occasion. The first blood pressure reading was disregarded to improve the accuracy of BP readings based on the theoretical possibility that the first reading of blood pressure may be elevated as compared to the subsequent measurements.nd and 3rd systolic BP measurements across the three visits was ≥140 mm Hg or the average of 2nd and 3rd diastolic BP across the three visits was ≥90 mmHg. All those who were on anti-hypertensive drugs were included in the hypertension category irrespective of their BP levels.Hypertension was diagnosed if the first visit systolic BP was ≥180 or diastolic BP ≥110 mm Hg in those without past medical history of hypertension. Among others without a past medical history of hypertension, follow up measurements of two more sets of three BP measurements were obtained on two different days within the first week of recruitment. Hypertension was diagnosed if the average of 2Blood sugar measurement and diagnosis of diabetes mellitusCapillary Blood sugar was measured with Codefree glucometer. The glucometer was interfaced with the tablet computer and the data were automatically gathered as part of EHR. Diabetes mellitus was suspected if fasting blood sugar (FBS) was ≥126 mg/dl. Among individuals with suspected diabetes, venous blood was drawn by the study ANM at the participant’s household and was transported to an accredited central laboratory. Glycated haemoglobin (HbA1c) test was performed by high performance liquid chromatography. An individual with FBS ≥ 126mg/dland HbA1c ≥ 6.5% was diagnosed to have diabetes. All those on anti-diabetic drugs were also included in the diabetes category irrespective of their blood sugar levels.Serum creatinineSerum creatinine estimation was done for all the subjects diagnosed with hypertension and /or diabetes. Serum creatinine estimation was done by Jaffe’s Kinetic method. The HbA1c and serum creatinine results were directly integrated with the EHR system from the laboratory itself. Serum creatinine was used by the study physician for decision making while prescribing metformin and antihypertensive drugs.Blood pressure and blood sugar control definitionsThe intended duration of follow-up was two years. Assessment of blood sugar was done monthly during the follow-up and HbA1c at endline. Blood sugar control was defined as HbA1c<7% or FBS<126mg/dl and analysis presented according to both criteria. Blood pressure control was defined as systolic BP<140 mm Hg and diastolic BP <90 mmHg.Data were summarised as mean± SD for continuous variables and proportions for categorical variables. Comparison of paired proportions (before and after the intervention) was done by McNemar’s chi-square test. As post-hoc analyses, a new variable on overall control status was defined that summarised the control status at all follow-up visits. Adequate control of blood sugar and BP during follow-up visits was defined as achievement of fasting blood sugar <126 mg/dl and BP <140/90 mm Hg respectively in more than 60% of the follow-up visits. Additionally, mean levels of BP, blood sugar and HbA1c (paired comparisons between baseline and endline) were compared using paired t test.As an indicator for operational feasibility and the performance of NPHW, the percentage of individuals with hypertension and/or diabetes successfully followed-up from the listing of those due for monthly and quarterly follow-up was assessed. The data were analysed using STATA version 13.We explained the objectives, methods, benefits, and risk of our study to the participants and took written informed consent. We used unique identification numbers for each participant to mask their identity and maintain confidentiality. Institutional Review Board of MediCiti Institute of Medical Sciences, Hyderabad, India approved the study. Confidentiality of EHR was ensured by providing passcode-protected access only to authorized study personnel.The total population in the study villages was 3684 with an eligible population (aged≥20 years) of 2456. Among the eligible individuals, 122 could not be contacted and 499 refused to participate. The demographic characteristics of the non-participants and participants were not largely different except that relatively higher proportion of males refused to participate in the study . The study questionnaire was administered to the remaining 1835 (76.3%) individuals . The popBlood pressure was measured in 1751 individuals . PrevaleOverall, 54% of the individuals with hypertension achieved BP control status based on the end of study visit measurements. Among those with a past medical history of hypertension the control rate was 59%, while it was 46% in the newly screen detected individuals with hypertension. Among those with a past medical history of hypertension the BP control rate improved from 47·0% at baseline to 59·0% at endline (McNemar’s chi square p <0.0001). Further, 31·2% of all individuals with hypertension achieved BP control status for at least 60% of the cumulative follow-up visits. Among individuals with a past medical history of hypertension at baseline, the pre-post mean differences in SBP and DBP were 6·5 mmHg and 5·9 mmHg, respectively . SimilarScreening for diabetes mellitus was done in 1686 individuals. The total number of individuals with diabetes was 189  Past medical history of diabetes was present in 135 individuals ; of them 128 were currently on medication and seven were not. Diabetes was confirmed in all seven of those who were not on any medications. Screening contributed to detecting diabetes in 54 additional individuals  .Among individuals with a past medical history of diabetes, 32·0% had their blood sugar under control at baseline as measured by their HbA1c. Based on the end of study visit HbA1c measurements, blood sugar was controlled in 34·0% of all individuals with diabetes; 34·4% in those with a past medical history and 33·3% in those newly detected. Further, 15·4% of all individuals with diabetes achieved fasting blood sugar <126 mg/dl in at least 60% of the cumulative follow-up visits.Among individuals with a past medical history of diabetes, the mean fasting blood sugar did not change much from baseline to endline ; but the mean HbA1c decreased from 8·3% at baseline to 8·0% (p = 0·03) at endline . Among nMonthly follow-up visits were duly completed in 88·8% and 90·8% of individuals diagnosed with hypertension and diabetes, respectively; and quarterly follow-up visits including Skype consultations were completed in 79% of those due for follow-up.Our study demonstrates the feasibility of implementing a novel model in detection and management of hypertension and diabetes in resource poor settings. The intervention model is unique due to the following reasons; a) employs a combination of task-sharing and mHealth strategies, b) incorporates technological capabilities of integrating both screening and evaluation tools in one single mHealth application, c) facilitates direct entry of all objective measurements into the EHR, d) enables electronic consultation between the patient and the study physician that permits real time prescription of appropriate medicines for the control of BP and blood sugar. The technology enabled and trained NPHW shared the responsibility of screening, risk management, and maintenance of the electronic health records of hypertension and diabetes patients. The implementation study highlights the acceptability of the intervention model in community settings, and shows improvement in clinical outcomes in terms of BP and blood sugar control at the community level.The relatively high participation rate in screening and follow-up demonstrate the acceptability of the intervention strategy at the community level. Identification of NPHWs from the study villages itself may have improved the acceptability of the intervention. However, the study NPHWs were above average in their capabilities, motivation and performance in the field. Additionally, the intensive in-office and long duration of on-field supervised training are quite demanding for an average ASHA. It is therefore, a challenge to maintain the same quality and standard in scale-up operations of the developed intervention strategy. Involving higher cadres of NPHW in implementation with better education and skills may help to improve the performance indicators of the intervention strategy.The digital health application developed as part of the mHealth strategy integrated a structured framework for screening and follow-up. With the help of internet, it facilitated electronic video consultations with the study physician. In India, NPHWs are not allowed to prescribe medicines for management of hypertension and diabetes. The electronic consultation and two-way real-time access to EHR both by the physician and NPHW resolved this issue and helped us to provide on-time treatment. The timely treatment may have improved the confidence of the patients in the intervention model and resulted in better clinical outcomes. We had involved ANMs, another cadre of NPHW other than ASHAs, in drawing venous blood from the selected participants for HbA1c assessment. However, it is possible to integrate a point of care (POC) HbA1c measurement device with the mhealth application. Several POC devices are available now in the market and they often require a small sample of blood (5μl) from a finger prick for running on-site HbA1c assay. Even lay people with minimal training can run the test and the results will be available in about five minutes,13. AlthAbout one fifth of the population in our study had hypertension, which is similar to the observed prevalence of hypertension in other studies from rural south India ,14. DiabIn our study population, nearly half and one third of individuals with past medical history of hypertension and diabetes had their BP and blood sugar under control, respectively. The BP control rate in our study population at baseline is much higher than that reported in a systematic review of rural Indian data IrrespecBeing a demonstration project on a small scale without a comparison group, our results have limited generalizability. Therefore, large implementation studies of our intervention strategy of combining both mHealth and task-sharing strategies are required for scale-up.Our study demonstrates the feasibility, and local acceptability of implementing a mHealth and task-sharing intervention model for hypertension and diabetes detection and control in community settings in India. Our strategy holds promise to facilitate delivery of care on a continuum for hypertension and diabetes in resource poor settings.S1 File(XLSX)Click here for additional data file.


Most prior studies characterizing post-transplantation diabetes mellitus (PTDM) have been limited to single-cohort, single-organ studies. This retrospective study determined PTDM across organs by comparing incidence and risk factors among 346 liver and 407 kidney transplant recipients from a single center.Univariate and multivariate regression-based analyses were conducted to determine association of various risk factors and PTDM in the two cohorts, as well as differences in glucometrics and insulin use across time points.There was a higher incidence of PTDM among liver versus kidney transplant recipients (30% vs. 19%) at 1-year post-transplant. Liver transplant recipients demonstrated a 337% higher odds association to PTDM , p<0.01). 1-month FBG was higher in kidney patients , while 1-month insulin use was higher in liver patients . Age, BMI, insulin use, and inpatient FBG were also significantly associated with differential PTDM risk.Kidney and liver transplant patients have different PTDM risk profiles, both in terms of absolute PTDM risk as well as time course of risk. Management of this population should better reflect risk heterogeneity to short-term need for insulin therapy and potentially long-term outcomes. Health care providers face an important tradeoff in managing patients who have undergone solid organ transplantation. Corticosteroids and immunosuppressive agents such as tacrolimus and sirolimus prevent graft rejection. However, these medications bring significantly increased risk for development of impaired glucose tolerance and post-transplantation diabetes mellitus (PTDM), also known as new onset diabetes after transplant (NODAT). PTDM is a potentially serious complication of solid organ transplantation affecting patients without a prior history of a diabetes diagnosis, leading to decreased graft function and survival, increased risk of cardiovascular disease, and increased healthcare costs , 2.Most clinical recommendations on PTDM emphasize the need for prevention of organ rejection while maintaining standards of care for those who develop concurrent PTDM , 4. HoweIn recent years, availability of transplant patient data has allowed for analyses to better understand the pre-transplant risk factors for PTDM –21. HoweWe introduce a dataset of liver transplantation patients to complement a dataset of kidney transplantation patients previously used in published analyses by Boloori et al. . TogetheThis was a retrospective study of a dataset compiled through a de-identified chart review with IRB (Mayo Clinic IRB) approval (Continuing Review #: PR16-008236-03). One dataset consisted of 346 patients who underwent first time liver-only transplant between 2007 and 2012. Information collected on each patient included demographic data and medical history, as well HbA1c, fasting blood glucose (FBG), and diabetes mellitus (DM) status pre-transplant and at 1-, 4-, and 12-months post-transplant. In addition, we collected type of hypoglycemic medication administered to each patient, type of immunosuppressant used, corticosteroid use, and trough level of immunosuppressive agent at each time point post-transplant. We also utilized a previously published data set of 407 kidney transplant patients who underwent transplant between 1999 and 2006 at the same institution . This daIn renal transplants, the standard immunosuppression protocol is induction therapy with either rabbit anti-thymocyte, immumoglobulin, or basiliximab. All patients typically receive a 5-day tapering course of glucocorticoids. Subsequently, most receive a steroid-free maintenance immunosuppression using mycophenolate mofetil, and tacrolimus is instituted. For patients undergoing a liver transplant, an immunosuppression protocol of intravenous corticosteroids, tacrolimus, and mycophenolate mofetil is used postoperatively. Corticosteroid administration follows the regimen of 500 mg intravenous methylprednisolone preoperatively, 50 mg twice daily on postoperative day 0; and 25 mg twice daily on postoperative day 1, then progressively tapered to a treatment stop by 4 months, but may continue in certain patients with autoimmune hepatitis. Mycophenolate mofetil stops at four months unless the patient has renal impairment.Data were reviewed to remove significant outliers that indicated human error in data collection , with only a minimal number (less than 1%) of observations removed from the dataset. In concordance with previous literature , 22, we We report means and standard deviations for available variables of interest determined as those found in previous literature to be predictive of PTDM risk . DiffereA substantial percentage of both renal and liver transplant patients without preexisting DM develop hyperglycemia while still hospitalized. Consequently, insulin is often required at discharge. For example, 87% of renal transplant patients included in this analysis without pre-existing DM exhibited hyperglycemia while hospitalized, and 66% were discharged on insulin . Additioall 3 follow-ups, compared to 8.1% of renal patients. Transient hyperglycemia, that is hyperglycemia which only occurs in the immediate post-transplant period (1-month) followed by remission, accounted for a large percentage of the difference, with 17.5% of liver patients meeting the criteria only in month 1 compared to 6.2% in the kidney group. However, if transient hyperglycemia is not included in the analysis as suggested by the 2014 International Consensus Meeting [Fasting glucose and HbA1c values for patients who did not develop PTDM and those who did are shown in Fasting blood glucose values of patients who did develop PTDM increased over the follow-up period in the liver group, but did not change significantly in the kidney transplant cohort . The 1 mAmong patients who did not develop PTDM , more liLiver transplantation protocols called for tapering off of steroids by 4 months. While 93.6% of liver patients were on steroids at 1 month, this percentage dropped to just 14% at 4 months and 3.6% at 1 year. This contrasts steroid use in the kidney group in which steroid use was relatively stable at all 3 follow-ups . Among patients on steroids, the percentage with hyperglycemia decreased in the kidney cohort , while hyperglycemia in liver transplant steroid users increased over from 1 month to 1 year .Finally, an adjusted analysis was conducted  to deterAll patients undergoing solid organ transplant without a prior history of DM are at risk of developing PTDM. This risk results from a combination of traditional factors  and immunosuppressant medications known to affect glucose metabolism , 28. OncMost studies of PTDM in kidney and liver transplant patients have typically involved analyses of the single organ. To the authors’ knowledge, a comparative study of liver and kidney transplants with regards to PTDM has not been undertaken. The time course for development of PTDM may not be identical between the two, and insulin needs may differ over the short term (1-year) follow-up. Understanding any potential differences can shed insight into how to modify treatment and follow-up algorithms according to the transplant type. Prior analysis by Boloori at al.  demonstrThe analyses demonstrated significant differences in PTDM risk between the two transplant populations. Liver transplant recipients had a 337% greater odds of developing PTDM compared to kidney recipients. There are multiple possible reasons for the differential risk between kidney and liver transplantations that warrant further investigation. First, steroid protocols differ for liver transplant patients compared to renal patients which may impact hyperglycemic effects. Secondly, there may be inherent differences in glucose metabolism between kidney and liver transplant recipients which are not accounted for in this analysis. Finally, lifestyle differences may exist between these populations as a result of different recovery times from transplant allowing for modifications in diet/exercise.Different patterns of hyperglycemia were also noted. Glucose levels were highest at 1 month in the kidney transplant group, and then declined thereafter. In the liver cohort, glucose values did not change over the follow-up time period. These differences in glucose between the two transplant cohorts may well have been due to their respective immunosuppression protocols. We also demonstrated large differences in the time course and remitting/relapsing nature of hyperglycemia between kidney and liver transplant patients. This analysis illustrates further the complex nature of post-transplant hyperglycemic and the need to better understand how the diabetogenic effects of immunosuppressive drugs impact short terms changes in glycemic control.In the adjusted analysis, insulin use at 1 month was predictive of PTDM risk. The proportion of patients on insulin differed between the kidney and liver transplant patients. Among patients who did not develop PTDM, both renal and liver cohorts were able to discontinue insulin after 1 month post-transplant. A similar percentage of renal transplant patients who did have PTDM remained on insulin therapy across the three follow-up periods, while the proportioned declined in liver patients. The reason underlying these different proportions of insulin use cannot be ascertained from this analysis. In addition to HbA1c and blood glucose values, insulin therapy in the outpatient setting is driven by results and patterns of SMBG, which are not available here. It should be noted, however, that both groups had around 30% of recipients on insulin therapy at 1-year, meaning a majority of recipients had their PTDM adequately managed without antidiabetic agents, potentially through diet and exercise.In 2014, the International Consensus Meeting on Post-transplantation Diabetes Mellitus published recommendations and future direction on dealing with PTDM in the medical community . Among tThere are limitations of this study that should be noted. First, the sample size of patients who developed PTDM may be underpowered to detect some of the significant differences in outcomes in the time points where no significant difference was detected. Previous analysis by Boloori et al. , which aThese results provide the first evidence to support differential guideline-making and management between kidney and liver transplant patients to reflect differences in both the risk factors and timeline at which patients may be at risk to develop PTDM. Furthermore, these findings highlight the need for further investigation of PTDM features and outcomes across other transplanted organs, as well as novel strategies to manage PTDM risk. In addition, potential effectiveness of screening strategies to better diagnose and monitor glucose intolerance in this population should be explored. It is likely that hospitals across the United States would benefit from standardization of protocols that optimize PTDM risk management in this patient population to minimize likelihood of poor diabetes outcomes while maximizing the health of the transplanted organ.


In parallel, 55 healthy subjects and 21 patients with severe coronary artery disease were studied as controls. We evaluated anthropometric parameters, peripheral blood pressure, biochemical and serum analysis at the enrollment and at twelve months after surgery. Plasmatic levels of MPO-DNA complexes were assessed by ELISA. NETs levels were higher in obese than in control group (p < 0.001) and correlated with the main anthropometric variable , glyco-metabolic variables and systolic blood pressure. NETs trend after intervention was uneven. The reduction of NETs correlated with the entity of reduction of BMI , visceral fat area , and glycemia . In medical history of patients in whom NETs increased, we observed a higher number of thromboembolic events. Our observations indicate that severe obesity is associated with increased generation of NETs, which in turn could influence the patients’ systemic inflammatory state. Weight loss and in particular, loss of adipose tissue after bariatric surgery does not in itself correct NET’s dysregulated production. Finally, patients in whom NETs accumulation persists after surgery are probably those at the highest risk of cardiovascular events.Neutrophil extracellular traps (NETs) are DNAs products involved in immune process. Obesity through a low-grade chronic inflammation determines neutrophil activation, but it is still unclear its role in NETs formation. Here we analyzed the NETs levels in healthy and morbid obese, their association with anthropometric and glyco-metabolic parameters and their changes after bariatric surgery. For this study, we enrolled 73 patients with morbid obesity (BMI ≥40 kg/m NETs are DNA filaments decorated with proteases and citrullinated histones, endowed with a bactericidal action, which is played either directly or via activation of the complement and the coagulation systems2. Thus NETs influence dramatically the extracellular environment and they contribute to systemic inflammation, persistent autoimmune diseases and thromboembolic events6.Generation of neutrophil extracellular traps (NETs) contributes to the effector function of neutrophils7 as well as rheumatic diseases8. Currently the extent of the generation of NETs and their role in experimental models of obesity and in obese patients is controversial11. As far as we know, only few studies have analyzed this topic. Braster et al.9 investigated the effect of NETs (by release inhibition or not) on the development of insulin resistance in a high fat diet mouse model; there was no difference in insulin resistance between treatment groups.Obesity increases cardiovascular risk even in the absence of other risk factors such as diabetes, dyslipidaemia, hypertensionet al.11 observed an effect of NETs on endothelial function  in a mouse model.On the contrary, Wang et al.10 studied a human obese patients before and after gastric band surgery observing a reduction in pro-inflammatory state and NETs production.Finally, Roberts 12, although, as in other interventions, post-procedural weight gain is described13.Bariatric surgery (metabolic surgery) has become a relevant therapeutic tool in obesity, particularly effective on obesity-associated comorbidities such as glycol-metabolic and cardiovascular dysfunctionsHere we have investigated whether byproducts of NETs generation/catabolism accumulate in the plasma of morbid obese patients, whether they correlate with the anthropometric and glyco-metabolic parameters of the patients. We have also compared NETs byproducts before and 12 months after bariatric surgery to verify whether the relative depletion of the adipose mass impacts on neutrophil function.2) eligible for sleeve gastrectomy were recruited. Patients with severe obesity were studied immediately before and one year after sleeve gastrectomy.The study group consisted of 73 patients  with morbid obesity  and age between 20 and 65 years.Inclusion criteriaa) all indicated for sleeve gastrectomy– liver, renal and heart failure, secondary causes of obesity , and severe psychiatric diseases ; and (b) patients with autoimmune , infectious disease or neoplasia emerging before or after surgery19.The exclusion criteria were  : nine with previous acute myocardial infarction, and twelve that required angioplasty and stent implantation after coronary angiography . All patients and controls gave their written informed consent to participate to the study.2) was measured at the end of a normal exhalation by ultrasonography (using a 3.5 MHz convex array probe) according to the Hirooka formula20. Three different distances were measured in order to apply the above-mentioned formula, as follows: VFA = −9.008 + 1.191 × [distance between the internal surface of the abdominal muscle and the splenic vein (mm)] + 0.978 [distance between the internal surface of the abdominal muscle and the posterior wall of the aorta at the umbilicus (mm)] + 3.644 [thickness of the fat layer of the posterior right renal wall (mm)]. The distance between the internal surface of abdominal muscles and the splenic vein was scanned transversely in the midline. None of the patients had dorsal or lumbar spine deformity, nor abdominal aortic aneurysm. Subcutaneous fat thickness  refers to the thickness of subcutaneous fat layer as measured by ultrasonography using a 7.5-MHz linear array probe and performing a longitudinal scan 1 cm below xiphoid apophysis. Subcutaneous fat thickness was defined as the distance between the skin and external face of the rectus abdominal muscle. Bioimpedentiometry , with electrodes applied on the plantar surface of both feet, was used to determine fat mass and free fat mass as a percentage of body weight.The weight and height were measured and used to calculate body mass index (BMI). Waist and hip circumferences were measured and used to calculate the waist-hip ratio. Peripheral blood pressure was assessed with the patients in supine position by a validated device in the non-dominant arm, after 10 minutes of rest in a quiet environment. Insulin-resistance was determined using the homeostasis model assessment-insulin resistance (HOMA-IR). Visceral fat area  in vacutainers containing clot activator (to prepare serum samples) and containing EDTA (to prepare platelet free plasma). Serum and plasma were retrieved after centrifugation (3000 rpm for 10 minutes). To prepare platelet- free plasma, a second centrifugation of the obtained plasma was performed at 13,000 × g, 5 minutes at 4 °C. Platelet-free plasma retrieved were aliquoted and stored at −80 °C until quantification of NETs.Blood sample was drawn in the morning after a 13-hour fast. Routine auto-analyzers were used to assess hematological parameters and blood chemistry including glycemia, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), triglycerides (TG), apolipoprotein-A1 and –B and insulinemia. Low-density lipoprotein cholesterol (LDL-c) was calculated by Friedewald formula. Serum levels of hs-CRP were measured by colorimetric enzyme-linked immunosorbent assay (ELISA) following the manufacturer’s instructions .21. Briefly, multiwell plates were coated with anti-human MPO mAb (capture) overnight at 4 °C, washed and blocked with BSA. After washing, human platelet-free plasma samples were placed in the coated wells with peroxidase-conjugated anti-DNA antibodies  following the kit instructions. Results are expressed as arbitrary units of optical density (OD).Plasmatic levels of MPO-DNA complexes (a bona fide marker of NET formation/catabolism) were identified using a capture ELISA as previously described±standard deviation). Kolgomorov-Smirnov test was used to determine the normal distribution of the variables. Mann-Whitney U test was used to compare the means of two unmatched groups variables . Differences between two paired groups before and after surgery were calculated by Wilcoxon signed-rank test. Variations of the concentration of plasmatic MPO-DNA complexes were analyzed by Mann-Whitney test and the trend in each patient recorded. Chi-Square test statistics was performed to determine if there was a significant relationship between two nominal  variables. Kruskal-Wallis test was used to compare the values of more than two different groups. Correlation coefficients were calculated with Spearman correlation rank tests, as appropriate. Eta squared analysis was used to study correlations between interval and nominal variables. The difference of different variables at time 0 and after intervention was calculated .Analyses were performed using SPSS software for Windows , with significance set at a 2-sided P < 0.05. Values are expressed as mean .A significantly higher accumulation of DNA fragments associated to MPO was observed in patients with severe obesity than in healthy controls . Conversely an increase in HDL-c (p < 0.05) was observed. In 73 patients, the plasmatic concentration of MPO-DNA complexes was determined before and after one year of sleeve gastrectomy , of BMI , of VFA , and of glycemia   and reduction of weight . It is tempting to speculate that neutrophils infiltrating the adipose visceral tissues are the main source of NETs in these subjects (correlations). Conversely, a distinct group of patients fail to respond in terms on NET accumulation to surgery, and this group comprises subjects with an higher incidence of cardiovascular events. The possible role of non-fat associated stimuli supporting neutrophil activation and in particular of the reciprocal activation of neutrophils, platelets and endothelial cellsAnthropometric characteristics, general blood values and NETs non obese patients with severe coronary artery disease


De novo Donor Specific Antibodies (DSA) are considered as a risk factor for the kidney allograft outcomes in recipients after simultaneous liver–kidney transplantation (SLKT). We hypothesized that length of hospital stay (LOS) might be associated with de novo DSA development of due to the increased likelihood of receiving blood transfusions with reduced immunosuppressive regimens.de novo DSA and LOS was assessed by logistic regression models adjusted for PS.This study is a single-center, retrospective cohort study consisting of 85 recipients who underwent SLKT from 2009 to 2018 in our hospital. We divided the patients into two groups according to LOS [long hospital stay (L) group (LOS >14 days) and short hospital stay (S) group (LOS ≤14 days)]. Propensity score (PS) has been created using logistic regression to predict LOS greater than median of 14 days. The association between the presence of de novo DSA after SLKT (9.4%), all of them were in (L) group. Longer LOS was significantly associated with higher risk of development of de novo DSA in unadjusted  and PS adjusted  analysis.The mean age at transplantation of the entire cohort was 55.5 ± 10.1 years. Sixty percent of the recipients were male and Caucasian. Median LOS in (L) group was three-fold longer than (S) group . Eight patients developed de novo DSA in SLKT.Longer hospitalization is significantly associated with the development of  For the sensitivity analysis, the threshold of long LOS was replaced with 28 days, which was two-times longer compared to the main analysis and based on the previous literature ,30.We extracted data about recipients’ baseline characteristics including age, gender, race, body mass index (BMI), marital status, insurance, cause of end-stage liver disease (ESLD), cause of chronic kidney disease (CKD)/end stage renal disease (ESRD), pre-SLKT dialysis information including length and type , comorbid conditions (diabetes: DM and hypertension: HTN), the Model for End-stage Liver Disease (MELD) score at SLKT, the number of Human Leucocyte Antigen (HLA) mismatches, calculated panel reactive antibody (cPRA), and cold-ischemic time (CIT) of donated kidney from the above mentioned sources. As post-SLKT information, first discharge destination, delayed allograft kidney function (DGF), primary non-function (PNF) on allograft kidney, death following transplant hospitalization. DGF was defined as needs of dialysis within one-week post SLKT  and PNF de novo DSA after SLKT. Furthermore, prevalence of post-transplant DSA (persistent or de novo DSA), was also assessed as secondary outcome. Persistent DSA was defined as DSA detected before and after SLKT, while de novo DSA was defined as newly developed DSA following SLKT. We assessed the incidence of persistent DSA or de novo DSA or in each patient after SLKT. HLA specificities were identified using a solid phase single antigen bead platform  combined with Luminex xMAP technology . Patients with any observed class DSA were categorized as de novo DSA (+), while those negative for identified de novo DSA were classified de novo DSA (−). We defined post-DSA that has a mean fluorescence intensity (MFI) value that is elevated compared to pre-transplant levels or has an MFI of greater than 1000. The median days of measurement of DSA from SLKT in both any post-transplant DSA and de novo DSA were also calculated as sum of days. The DSA measurements were performed as per clinical indication. The methodology of detecting DSA including the decision of measurements, technical issues, and thresholds of DSA was not changed during the study period.Primary outcome was incidence of development of T-test or Mann-Whitney test for continuous variables and chi-square-test (or Fisher’s exact test) for categorical variables.Baseline characteristics were described for the entire cohort and for groups categorized based on the LOS and presented as mean ± standard deviation (SD) or median and interquartile range (IQR) for continuous variables and percent for categorical variables as appropriate. Differences between groups were assessed by student Table S1, Supplementary material), including all available covariates without missing values for LOS, including age, gender, race, marital status, insurance, cause of ESLD, diabetes, hypertension, BMI, blood type, MELD score, first discharge destination, and DGF. The purpose of this step was to be able to adjust for co-variates which showed association with LOS. Because only 8 patients developed de novo DSA, we were able to adjust for only one variable in our adjusted logistic regression analysis used for assessing association between LOS (as exposure) and development of de novo DSA or any post-transplant DSA (as outcomes). We then assessed logistic regression analysis, unadjusted and PS score adjusted, to calculate the relative risk (odds ratio) for newly developing de novo DSA or any post-transplant DSA.We calculated the propensity score (PS) for probability of long hospital stay in the main analysis (LOS >14 days versus ≤14 days) and in the sensitivity analysis (LOS >28 days versus ≤28 days) using logistic regression model .p < .001], respectively. In (L) group, incidence of returning to home as first discharge destination was significantly lower than in (S) group . No PNF was observed; however, DGF of the allograft kidney was significantly higher in (L) group. Incidence of death during SLKT hospitalization was higher in (L) group compared to (S) group.de novo DSA (9.4%) and 12 patients were identified with any post-transplant DSA consisted of both persistent and de novo DSA (14.1%) after SLKT (de novo DSA and 11 out of 12 patients with any post-transplant DSA were in (L) group. The median days from SLKT was 22.0 days (IQR: 8.0–280.5 days) for measurement of any post-transplant DSA and 53.0 days was (IQR: 14.0–280.5 days) for measurement of de novo DSA  and PS adjusted  analysis  and PS adjusted  analysis .Longer LOS defined as >28 days was significantly associated with higher risk of development of de novo DSA development after SLKT. In addition, our study indicates that longer LOS occurred more frequently in SLKT patients with higher MELD scores and higher incidence of DGF in allograft kidney. Furthermore, 30% of the patients in (L) group, compared to exact percentage in (S) group, were discharged to their home after SLKT. All of those who developed de novo DSA had longer hospitalizations. Our study implies that LOS might be a useful surrogate marker of a higher probability for persistent DSA and de novo DSA development. Patients, if not all, with longer hospitalization should be routinely screened for DSA after SLKT. We believe this is the first report to evaluate an association between the length of hospitalization and post-transplant DSA development in SLKT.In this single center, retrospective study, we found significant associations between longer hospitalization and higher probability of both persistent post-transplant DSA and de novo ClassII DSA, has been thought to be a significant risk factor for patient-, allograft liver-, and allograft kidney outcome [de novo DSA in SLKT, although the potential for exposure to sensitizing events might be expected to be higher in SLKT than liver or kidney transplantation alone (LTA and KTA). Although LTA patients typically do not undergo maintenance dialysis therapy before LTA, 30–50% of SLKT candidates undergo dialysis therapy immediately prior to SLKT [Sensitized status in SLKT has tended to be neglected due to the absorptive capacity by allograft liver . In fact outcome . No prev to SLKT ,36. We o to SLKT . Higher  to SLKT , which lde novo DSA. The relationship between assumptive exposures,  and EAD and LOS has already been reported in other patient cohorts [de novo DSA development. Our preliminary findings suggest LOS might be a consequence of DGF on allograft kidney secondary to persistent DSA or de novo DSA development or other potential intermediated mediators (indicator). Although we could not identify the exposure in each patient, a relationship between presumptive exposures and de novo DSA development could exist in accordance with this conceptual model.We constructed a conceptual model of the assessed relationship between LOS and DSA. We identified an association between longer LOS and developing  cohorts ,15 as we cohorts ,23. We wde novo post-transplant DSA. In our cohort, 4 patients had persistent DSA; 2 patients had both persistent and de novo DSA after SLKT  group. Furthermore, DSA measurement was indication based and not routine, which might have caused observational bias. In this study, we were not able to assess the pathophysiological role of Class I and II DSA separately, as almost all of the patients with post-transplant DSA had at least Class II DSA (N = 11/12)  . Finallyde novo DSA development in SLKT. Our results support the conclusion that DSA monitoring can be implemented into clinical practice for SLKT patients.Despite some limitations, our study has confirmed several previous findings. LOS has been shown to be predicted by factors such as ethnicity, discharge destination, and type of insurance . In our de novo DSA development after SLKT. Although longer hospitalization could be an indicator and not a direct cause for de novo DSA development, DSA monitoring after LOS might be able to help providers improve outcomes after SLKT. Additional prospective and larger studies are highly warranted to identify more modifiable and non-modifiable predictors for persistent and de novo DSA development following SLKT.In conclusion, longer hospitalization was significantly associated with higher probability of persistent DSA and Click here for additional data file.


The Y-AIDA study was designed to investigate the renal- and home blood pressure (BP)-modulating effects of add-on dapagliflozin treatment in Japanese individuals with type 2 diabetes mellitus (T2DM) and albuminuria.2, and urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g creatinine (gCr) were enrolled, and 85 of these patients were administered add-on dapagliflozin for 24 weeks. The primary and key secondary endpoints were change from baseline in the natural logarithm of UACR over 24 weeks and change in home BP profile at week 24.We conducted a prospective, multicenter, single-arm study. Eighty-six patients with T2DM, HbA1c 7.0–10.0%, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 mP < 0.001). In addition, changes in morning, evening, and nocturnal home BP from baseline were as follows: morning systolic/diastolic BP − 8.32 ± 11.42/− 4.18 ± 5.91 mmHg (both P < 0.001), evening systolic/diastolic BP − 9.57 ± 12.08/− 4.48 ± 6.45 mmHg (both P < 0.001), and nocturnal systolic/diastolic BP − 2.38 ± 7.82/− 1.17 ± 5.39 mmHg . Furthermore, the reduction in UACR after 24 weeks significantly correlated with an improvement in home BP profile, but not with changes in other variables, including office BP. Multivariate linear regression analysis also revealed that the change in morning home systolic BP was a significant contributor to the change in log-UACR.Baseline median UACR was 181.5 mg/gCr . Baseline morning, evening, and nocturnal home systolic/diastolic BP was 137.6/82.7 mmHg, 136.1/79.3 mmHg, and 125.4/74.1 mmHg, respectively. After 24 weeks, the logarithm of UACR decreased by 0.37 ± 0.73 . The study was conducted from July 1, 2015 to August 1, 2018.The online version of this article (10.1186/s12933-019-0912-3) contains supplementary material, which is available to authorized users. The number of patients with type 2 diabetes mellitus (T2DM) is increasing, and renal and cardiovascular complications often provoke serious conditions in diabetic patients –3. AlbumDapagliflozin is a sodium–glucose cotransporter-2 (SGLT2) inhibitor that primarily acts by increasing the excretion of glucose in urine to decrease the blood glucose level. Several large randomized trials have demonstrated that SGLT2 inhibitors reduce the occurrence of CVD and have renal protective effects in T2DM patients –13. FurtCompared with office BP, out-of-office BP, such as home BP measurements and ambulatory BP monitoring (ABPM), is a better predictor of CVD events, exacerbation of chronic kidney disease (CKD), transition to end-stage renal disease (ESRD), and mortality –19. In tIn the present study, we investigated the renal effects of 24-week add-on dapagliflozin treatment on urinary albumin excretion in Japanese patients with T2DM and DN. We also examined the effects of dapagliflozin on home BP profiles, including average home BP levels and home BP variability.http://www.umin.ac.jp/ctr/index-j.htm). All patients provided written informed consent prior to participation. Registration and collected data were audited by an independent data management center.This study complied with the ethical principles of the Declaration of Helsinki, and was approved by the institutional ethics committee at each participating hospital. The study is registered at the UMIN Clinical Trials Registry  and estimated glomerular filtration (eGFR) ≥ 45 mL/min/1.73 mpulation . To meetAfter the run-in period, eligible individuals were initially given dapagliflozin 5 mg as add-on to existing therapy in the morning (visit of 0 weeks), and the dose of dapagliflozin could be titrated up to 10 mg daily 8 weeks or 16 weeks after treatment initiation to achieve the HbA1c target (< 7.0%) if necessary. In the study period, anti-diabetic, anti-hypertensive, and anti-dyslipidemia medication regimens were not modified in principle.Body weight, body mass index (BMI), office BP, and pulse rate (PR) were measured at baseline (0 weeks) and after a period of 8 weeks, 16 weeks, and 24 weeks of treatment.All participants took home BP readings using a validated and internet-interfaced BP monitor  using a mobile telecommunication system , which enabled automatic transmission of all home BP readings to a server for data recording after each measurement to allow accurate analysis of the home BP profile , 25. ThrThe HEM-7252G-HP monitor can record BP readings at fixed times, and was preset to record nocturnal home BP measurements at 2:00, 3:00, 4:00, and 5:00 a.m. (4 time points). Participants were instructed to measure their nocturnal home BP for a 7-day study period before the 0- and 24-week visits. Mean nocturnal home BP was defined as the average nighttime BP for the 7-day study period, which represented the mean of 4 readings each night. Nocturnal home BP variability was defined as the SD of mean nocturnal home BP each day for the 7-day study period.Based on home BP measurements, circadian BP patterns were classified as follows: non-dipper, dipper, extreme-dipper, or riser pattern. The nocturnal BP decline was defined by calculating the percentage of the decline in the systolic BP during the nighttime. Non-dippers were defined as having nocturnal declines that were 0–10% of the daytime systolic BP. Dippers were defined as having nocturnal declines that were 10–20% of the daytime systolic BP. Extreme-dippers were defined as having nocturnal declines that were > 20% of the daytime systolic BP. Risers were defined as having nocturnal declines that were < 0% of the daytime systolic BP . DaytimeBlood and urine sampling was performed in a fasted state at baseline (0 weeks) and after 8 weeks, 16 weeks, and 24 weeks of treatment. Urinalysis was performed in spot urine samples at the applicable visits. Measurement methods were as follows. UACR were determined using a turbidimetric immunoassay . Insurance-uncovered laboratory parameters -to-creatinine ratio, urine type IV collagen-to-creatinine ratio, urine 8-hydroxy-2′-deoxyguanosine (8-OHdG)-to-creatinine ratio, low-density lipoprotein (LDL)-cholesterol, pentosidine) were also measured by SRL Inc.  as described previously –30. We pThe primary endpoint was the change in the natural logarithm of the UACR (log-UACR) of the spot urine sample from baseline to 24 weeks. Subgroup analysis was also conducted to determine the change from baseline in the log-UACR at week 24 using angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) at baseline. Additionally, to interpret the extent of changes in albuminuria for their clinical relevance, the change in the non-logarithmic UACR values were analyzed. Changes from baseline in other measurements, including home BP parameters, were secondary endpoints. Based on home BP measurements, circadian BP patterns were classified at baseline and week 24. Safety and tolerability were assessed based on adverse event (AE) reported throughout the study period. In addition, drug adherence was assessed by the proportion of patients taking dapagliflozin on the visit day during the study period.The primary analysis was the estimation of changes in the natural logarithm of the UACR after per-protocol dapagliflozin treatment for 24 weeks in a single arm using a one-sided paired t-test. Based on a previous study of dapagliflozin , we assut-test. Associations between the primary endpoint and other variables were assessed using Pearson’s correlation coefficients. Multivariate linear regression analyses were performed to identify the factors affecting the change in log-UACR. The independent variables entered into the model for multivariate regression analysis were as follows: diabetes duration, baseline values of fasting blood sugar (FBS), glycated hemoglobin (HbA1c), and white blood cell (WBC) levels, and changes from baseline in the morning home systolic BP, office systolic BP, HbA1c, body weight, and diacron-reactive oxygen metabolites (d-ROMs) at week 24, which were significantly different or showed a decreasing tendency, after 24 weeks of dapagliflozin treatment. Frequency differences in the circadian BP patterns between baseline and week 24 were assessed using the Chi-squared test. Statistical analysis was performed using SAS version 9.4 (SAS Institute Japan) at the department of biostatistics and epidemiology in Yokohama city university graduate school of medicine, and a value of P < 0.05 was considered statistically significant.Data in the text and tables are presented as the mean, mean ± SD, percentage, or median (interquartile range). Data in the figures are presented as the mean ± standard error (SE). For the statistical analysis of the difference from baseline to each visit, the change in each parameter after add-on dapagliflozin therapy for 8, 16, or 24 weeks was analyzed using a one-sided paired 2. The median UACR was 181.5 mg/gCr  with mean eGFR 67.34 mL/min/1.73 m2. Most participants had hypertension (89.2%), and mean office systolic/diastolic BP was 142.2/79.0 mmHg; 68.2% of patients were taking angiotensin II receptor blockers (ARBs) and 4.7% were taking angiotensin-converting enzyme (ACE) inhibitors  received study medication. One participant withdrew consent to participate before receiving study medication. Table P = 0.0026)    and in patients who were not receiving ARBs/ACE inhibitors . On the other hand, although treatment with add-on dapagliflozin initially decreased eGFR at week 8 , continuous treatment with dapagliflozin resulted in a gradual recovery of eGFR afterwards and change in eGFR from baseline to week 24 was not statistically significant   from baseline was noted, with a difference from baseline of 0.23 ± 0.72 (26) Fig. a. Log-UAP = 0.0163) (Table P = 0.0354) at week 24. Add-on dapagliflozin therapy for 24 weeks did not change the pulse rate, but significantly reduced body weight and BMI throughout the treatment period.From baseline to week 8, add-on dapagliflozin therapy significantly decreased office systolic BP  Table . This deP = 0.0284) and week 16 , but not at week 24  (Table P = 0.0332) at week 16 and 2.995 ± 11.988 mmHg (P = 0.0168) at week 24. Furthermore, double product declined by 425.5 ± 1836.5 (P = 0.0321) at week 8, and the improvement in double product was maintained at week 16 and week 24.Pulse pressure (PP: difference between systolic BP and diastolic BP), mean arterial pressure (MAP: 2/3 diastolic BP + 1/3 systolic BP), and double product (heart rate × systolic BP) are markers of arterial stiffness that have been linked to cardiovascular outcomes , 35. AddTreatment with add-on dapagliflozin resulted in a significant decrease in fasting blood sugar (FBS) and HbA1c at 8 weeks, and this improvement in glucose metabolism was maintained throughout the study period Table . SimilarSub-clinical inflammation was reported to be involved in the pathogenesis of endothelial dysfunction, which leads to vascular complications including nephropathy in diabetic patients . HoweverP < 0.001), evening systolic/diastolic BP − 9.57 ± 12.08/− 4.48 ± 6.45 mmHg (both P < 0.001), and nocturnal systolic/diastolic BP − 2.38 ± 7.82/− 1.17 ± 5.39 mmHg  without an evident increase in PR .Based on home BP measurements, circadian BP patterns were classified at baseline and week 24. The results of home BP measurement revealed that 33.8% of patients had the dipper pattern, 15.6% of patients had the extreme-dipper pattern, 29.9% of patients had the non-dipper pattern, and 20.8% of patients had the riser pattern at baseline  and diacron-reactive oxygen metabolites (d-ROMs)  at week 24 -to-creatinine ratio   Fig. . HoweverEight subjects 9.5%) experienced mild or moderate episodes of hypoglycemia (Table % experie2 and UACR ≥ 30 mg/gCr), concomitant with improvement in home BP profile. Three new findings were obtained in this study: (i) dapagliflozin decreased out-of-office BP, which contributed to the ameliorating effects of dapagliflozin on albuminuria; (ii) dapagliflozin improved BP variability, which is an indicator of BP quality control; and (iii) Japanese patients with T2DM and DN, who have high salt sensitivity genetically and high dietary salt intake, were enrolled as the study population [The main finding of this prospective, multicenter, interventional, single-arm study was that add-on dapagliflozin therapy for 24 weeks reduced albuminuria without decreasing eGFR in Japanese patients with T2DM and early-stage DN  to evaluate the effects of dapagliflozin on out-of-office BP . SGLT2 iG-HP to eAsian patients genetically have a high salt sensitivity and a high dietary salt intake , 38, andThe current study also showed that add-on dapagliflozin therapy improved the day-by-day variability of home BP, an indicator of quality of BP control, in addition to mean office and home BP levels. Recent studies indicate that the measurement of day-by-day variability of home BP provides a clinically useful distinction between high- and low-CVD risk groups in hypertensive patients . With reIn the present study, we evaluated urinary biomarkers and oxidative stress markers to explore the mechanism by which dapagliflozin reduces albuminuria in T2DM patients with DN. A decreasing trend was observed for dROMs, an oxidative stress marker, although the change was not statistically significant. Dapagliflozin has been shown to suppress inflammation and oxidative stress in the kidneys of a mouse model of T2DM . In anotThe limitations of the present study were as follows. First, the trial design included a single arm, meaning that bias and placebo effects could not be excluded. Second, albuminuria was evaluated through single-spot urine sampling, which may have contributed to large variations in the data. Methods such as 24-h urine collection or multiple spot sampling may provide a more accurate evaluation of albuminuria. Third, this study may be underpowered to estimate the association between the log-UACR decrease and changes in other cardiometabolic parameters because the sample size calculation was based on the expected changes in log-UACR. Fourth, post-prandial glucose levels and continuous glucose monitoring were not measured in this study. It was unknown whether dapagliflozin treatment improved glucose variability, and whether the change in glucose variability affected an improvement in log-UACR.Add-on dapagliflozin therapy for 24 weeks improved albuminuria levels as well as out-of-office BP parameters including morning, evening, and nocturnal home BP levels and day-by-day variability of home BP in Japanese patients with T2DM and DN. Additionally, improved morning home systolic BP with dapagliflozin was independently associated with amelioration in albuminuria in this population.Additional file 1: Figure S1. Univariate correlation analysis between the decreases in body weight, body mass index (BMI), fasting blood sugar (FBS), glycated hemoglobin (HbA1c), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GTP), white blood cells (WBC), and platelets (Plt), and the decrease in urine albumin-to-creatinine ratio (UACR).


Hypertension and diabetes mellitus are often jointly present, especially in early onset cases of either disease. We investigated clinical characteristics of hypertensive patients with newly diagnosed diabetes and diabetic patients with newly diagnosed hypertension.Our study subjects were recruited in a China nationwide multicenter registry of hypertension and diabetes (n = 2510). We performed logistic regression to compare patients seen for hypertension in cardiology, with newly diagnosed diabetes (n = 137) and patients seen for diabetes mellitus in endocrinology, with newly diagnosed hypertension (n = 155). Albuminuria was defined as a urinary albumin-to-creatinine ratio of ≥ 30 mg/g, and left ventricular hypertrophy according to the Cornell product index.P ≥ 0.06). However, hypertensive patients with newly diagnosed diabetes, compared to diabetic patients with newly diagnosed hypertension, had a significantly greater body mass index  and slower heart rate . In logistic regression analyses adjusted for sex (48.3% women) and age (mean 60.0 ± 11.5 years), the odds ratio for newly diagnosed diabetes mellitus versus newly diagnosed hypertension was 1.27 (95% CI 1.03–1.56) and 0.80 (95% CI 0.66–0.96) for body mass index (+ 3 kg/m2) and heart rate (+ 10 beat/min), respectively. Hypertensive patients with newly diagnosed diabetes also had a lower prevalence of albuminuria  and slightly and non-significantly higher prevalence of left ventricular hypertrophy  than diabetic patients with newly diagnosed hypertension.These two groups of patients with both hypertension and diabetes mellitus were similar in most of the characteristics (Earlier or later onset of hypertension than diabetes mellitus may have different risk factors and organ damage. Hypertension and diabetes mellitus are closely related . These tOur China nationwide registry in the settings of cardiology and endocrinology offers a unique opportunity to investigate the newly diagnosed hypertension in diabetes and the newly diagnosed diabetes mellitus in hypertension . In the Our study participants were recruited from the abovementioned China multicentre registry, which was a cross-sectional study carried out in the departments of cardiovascular and endocrine medicine of hospitals from June 2011 to March 2012 . The stuTo be eligible for inclusion, a patient had to be at least 20 years old, and was able to attend two clinic visits 2 to 5 days apart. At the first clinic visit, physicians administered a standardized questionnaire to collect information on medical history, lifestyle, and use of medications. Blood pressure and anthropometry were measured. At the second clinic visit, blood pressure was measured for the second time. Venous blood samples were drawn after overnight fasting for measurements of plasma glucose, glycosylated haemoglobin A1 (HbA1c) and serum lipids. Morning void urine samples were collected for urinary measurements. Oral glucose tolerance test (OGTT) was performed in the hypertensive patients without known diabetes mellitus [A total of 2510 patients were registered from 20 departments of cardiology (n = 1330) and 20 departments of endocrinology (n = 1180) of 25 hospitals [Blood pressure was measured using the validated Omron HEM-7201 automated oscillometric blood pressure monitor  at the first and second clinic visits. On each of the two occasions, three consecutive blood pressure readings were obtained in the seated position after the subjects had rested for at least 5 min. These six readings on two clinic visits were averaged for statistical analysis in all subjects and for the diagnosis of hypertension in patients seen in endocrinology without known hypertension. The newly diagnosed hypertension was defined as a blood pressure of at least 140 mmHg systolic or 90 mmHg diastolic.In patients seen in cardiology without previously diagnosed diabetes mellitus, OGTT was performed for the diagnosis of diabetes mellitus, which was defined as a plasma glucose concentration of at least 7.0 mmol/L at fasting or 11.1 mmol/L 2 h after ingestion of 75 g of glucose dissolved in water.Standard 12-lead electrocardiogram (ECG) was recorded in all subjects. ECG left ventricular hypertrophy was defined according to the Cornell product index as (RaVL + SV3) × QRS duration > 244 mV·ms .https://www.cap.org). In the absence of apparent urological infections on urine samples, albuminuria was defined as a urinary albumin-to-creatinine ratio more than 30 mg/g. Albuminuria included both microalbuminuria (30–299 mg/g) and macroalbuminuria (≥ 300 mg/g).Urinary routine test was performed on fresh urine samples at the laboratory of each participating hospitals. Urinary albumin and creatinine excretions were measured using the immunochemical method in a core laboratory certified by the College of American Pathologists  cholesterol concentration of 3.37 mmol/L or higher, or a serum high-density lipoprotein (HDL) cholesterol concentration of 1.04 mmol/L or lower, or as the use of statin or other lipid lowering agents .Ischaemic heart disease included myocardial infarction and angina. Ischaemic heart disease and stroke were self-reported.For database management and statistical analysis, we used SAS software . Means and proportions were compared by the Student t-test and Fisher’s exact test, respectively. Continuous measurements with a skewed distribution were normalized by logarithmic transformation and represented by geometric mean and 95% confidence interval. Logistic regression analyses were performed to study the associations of interest.P ≤ 0.03) lower proportion of women (40.9% vs 54.8%) and were slightly older (2.4 ± 0.7 years).Table P ≤ 0.0001) lower plasma fasting glucose and HbA1c. However, they had similar systolic and diastolic blood pressure (P ≥ 0.47). Among the other clinical characteristics, statistical significance (P ≤ 0.03) was observed for body mass index and heart rate.Hypertensive patients with newly diagnosed diabetes mellitus, compared to diabetic patients with newly diagnosed hypertension, had significantly (P for trend was 0.02) and decreased from 55.9% in patients with a heart rate below 60 beats/min to 47.6% and 38.0% in patients with a heart rate of 60–89 beats/min and ≥ 90 beat/min, respectively (P for trend was 0.10).Further categorical analyses Fig.  accordin2 greater body mass index  and 0.80 for 10 beats/min faster heart rate , higher prevalence of ischaemic heart disease  and slightly and non-significantly higher prevalence of ECG-left ventricular hypertrophy  for ECG left ventricular hypertrophy, 3.03  for ischaemic heart disease and 0.53  for albuminuria.After adjustment for sex, age, body height and body weight, current smoking and alcohol intake, mean arterial pressure, plasma glucose and serum triglycerides and total to HDL cholesterol ratio, the odds ratio in newly diagnosed diabetes mellitus versus newly diagnosed hypertension was 2.02 (95% CI 0.46–8.77, Our finding was that hypertensive patients with newly diagnosed diabetes mellitus had a greater body mass index and higher prevalence of left ventricular hypertrophy and ischaemic heart disease and a slower resting heart rate and lower prevalence of albuminuria than diabetic patients with newly diagnosed hypertension. Because the joint presence of these two clinical entities confers an even higher cardiovascular risk than either one alone, –4 our fiOur observation on the risk of diabetes mellitus associated with a greater body mass index in patients with previously diagnosed hypertension is in keeping with the results of several previous prospective studies –14. In 1Our observation on the risk of newly diagnosed hypertension associated with a faster heart rate in patients with an established diagnosis of diabetes mellitus is also in line with the concept that resting heart rate is a marker of cardiovascular risk, as demonstrated in numerous observational studies –19. RestOur explanation on the higher prevalence of left ventricular hypertrophy in hypertensive patients with a newly diagnosed diabetes mellitus and higher prevalence of albuminuria in diabetic patients with a newly diagnosed hypertension can be straight forward. Left ventricular hypertrophy is a major cardiac structural complication of hypertension . PatientOur study should be interpreted within the context of its limitations. First, our study had a cross-section design and does not allow any causal inference. Although our patients had newly diagnosed hypertension or diabetes, our study was still different from a prospective observational one. Second, our study had a relatively small sample size with few measurements of biological markers. Third, albuminuria was evaluated on a single spot urine sampling. However, albuminuria and creatinine were measured in a core laboratory. A stringent quality assurance programme was implemented, including the exclusion of patients with suspected urinary tract infections. Fourth, we did not collect information on the frequency of patients’ clinic visit. Hypertensive and diabetic patients in China are usually followed up on a monthly basis for drug prescriptions. However, it is still possible that the time interval varied between patients, which might influence the between-group comparisons.In conclusion, earlier or later onset of hypertension than diabetes mellitus may have different risk predictors and organ damages. Our finding should be tested in prospective intervention studies on the possible pathophysiological pathways behind obesity and tachycardia.Additional file 1: Appendix 1. Participating hospitals of the China ATTEND Registry.


Iodinated contrast agent (ICA)-induced acute kidney injury (AKI) following acute coronary syndrome (ACS) is a frequent complication, which may lead to chronic kidney disease and increased mortality. Optical coherence tomography angiography (OCT-A) of the retina is new tool delivering a rapid and noninvasive assessment of systemic microvascularization, which is potentially involved in the occurrence of ICA-induced AKI. Between October 2016 and March 2017, 452 ACS patients were admitted to our cardiac intensive care unit. OCT-A was performed within 48 h after the ICA injection. Patients with a history of retinal disease were excluded. The patients included were divided into two groups depending on whether or not AKI occurred after injection of ICA, according to KDIGO criteria. Of the 216 patients included, 21 (10%) presented AKI. AKI was significantly associated with age, Mehran score, GRACE score, and NT-proBNP. AKI patients had significantly lower retinal vascular density (RVD)) and had more frequent low RVD . Adding low RVD to the Mehran score and the NT-proBNP, or to the GRACE score and the NT-proBNP, significantly improved their predictive values, suggesting that systemic microvascular involvement remains incompletely addressed by either standard risk scores or factors known to be associated with ICA-induced AKI. The incidence of contrast-induced AKI ranges from 10 to 20% of patients who undergo procedures for ACS2. AKI is directly correlated with short-term patient prognosis, with a fivefold increase of intrahospital mortality, as well an increased risk of end-stage renal failure in the long term6. Several studies have made it possible to specify the main determinants of contrast-induced AKI, some of which establish risk scores, such as the Mehran score7. Some new risk markers for AKI have recently been identified in ST elevation myocardial infarction (STEMI) patients, such as the severity of coronary artery disease, characterized by a SYNTAX score >108, a GRACE score >1609 and a high level of NT-proBNP at admission10. The observed actions of ICAs reported so far associate hypoxia-inducing renal medullary vasoconstriction with acute tubular necrosis secondary to endothelin and adenosine release, and direct tubular toxicity13. Based on the microvascular hypothesis, derived from experimental models of hypertension and diabetes16, studies analyzing retinal vascularization in patients with chronic kidney disease have demonstrated an independent association between microvascular retinopathy and chronic kidney disease (CKD)21. While the link between retinal vascular damage and CKD is well documented, no data are available on the relationship between AKI and retinal microvascular dysfunction. However, given the multiple evidence of combined retinal and systemic damage , and given the microcirculatory involvement in AKI, retinal abnormalities may be associated with the occurrence of AKI after coronary angiography in patients at high cardiovascular risk.At a time when revascularization by angioplasty has taken a predominant place in the management of acute coronary syndrome (ACS), resulting in a pronounced improvement in patient symptoms and prognosis26. The contrast between static retinal cells and erythrocyte movement provides a model of retinal vascularization27. Furthermore, this technique’s software provides automatic quantitative evaluation of retinal vascular parameters such as vascular density. The EYE-MI study, recently conducted in our center, identified an independent association between low retinal vascular density (RVD) with impaired left ventricular ejection fraction (LVEF) and high cardiovascular risk in patients with ACS using OCT-A to analyze retinal vascular density28. Based on these observations, we studied the potential value of measuring retinal vascular density in OCT-A as a marker of microvascular dysfunction related to the occurrence of AKI after coronary angiography for ACS.Optical coherence tomography angiography (OCT-A) is a new noninvasive technique based on blood flow imaging. It allows a reproducible study of retinal vascularization through the analysis of erythrocyte movement without fluorescent dye injectionThis study was based on the prospective follow-up of a cohort of patients hospitalized for ACS in our Cardiology Intensive Care Unit. All patients treated for ACS  between 01 September 2016 and 05 March 2017 and who underwent coronary angiography while they were hospitalized were eligible for an OCT-A within the first 48 h after admission. The exclusion criteria were a history of an eye disease , patients on dialysis, patients not affiliated to national health insurance, patients under legal protection, minors, or those who refused to participate.The study complied with the tenets of the Declaration of Helsinki, the locally appointed ethics committee (Comité de Protection des Personnes (CPP) Est I, Dijon, France) approved the research protocol and written informed consent was obtained from the patient or his/her legal representative. During the OCT-A exams, a cardiologist monitored the patients’ heart rhythm and hemodynamic status.29. The SYNTAX score, an anatomical-based risk score for coronary lesions  was determined for all patients who received a coronary angiography and for whom the initial SYNTAX score was evaluable30. The GRACE admission score assessing the patient’s individual ischemic risk and prognosis with calculation of the probability of in-hospital and 6-month mortality was also calculated31.Patients’ medical records were collected from the obseRvatoire des Infarctus de Côte d’Or (RICO). This regional survey, set up in 2001, collects clinical and biological data from patients hospitalized for ACS, with written consent, in all Cardiology Intensive Care departments in the Côte d’Or region of France. From these data, we selected information pertaining to cardiovascular risk factors, cardiovascular history, history of chronic renal failure, treatments including beta-blockers, angiotensin-converting enzyme (ACE) inhibitors and angiotensin 2 receptor blockers (ARBs) grouped into renin-angiotensin-aldosterone system inhibitors, diuretic treatments and vasopressors, systolic and diastolic blood pressure (BP), and Killip stage. Biological data were also collected: NT-proBNP , troponin peak, creatinine and creatinine clearance (according to CKD-EPI and modified MDRD), and anemia (according to the WHO definition). Anemia was defined according Mehran score definition .Angiographic data such as the type of angioplasty, the decision to perform coronary artery bypass surgery, the placement of an intra-aortic balloon pump (IABP) and the volume of ICA injected were retained for analysis. The left ventricular ejection fraction (LVEF) was measured with Simpson’s biplane method of discs within the 24 h following admission32. OCT-A is a rapid noninvasive examination (less than 30 s), and feasible in 82–86% of patients. It is performed by nurses and the acquisition time is about 2 min for each patient. Retinal vascular density and the foveal avascular zone were measured using software for automatic quantitative analysis (Angioplex software v10.0). OCT-A showed substantial reproducibility . Retinal vascular density is the average density of the superficial capillary plexus in the four sectors  initially analyzed separately  represents the total length of perfused vasculature per unit area in a region of measurement.The study was conducted on 3 × 3-mm angiograms with CIRRUS™ HD-OCT Model 5000 ; its technical aspects have been recently described33, only one eye was retained for analysis: the right eye for the first patient and then the left eye for the second patient for images of equivalent quality and so on for subsequent patients. If the patient was single-eyed, the image was taken from the functional eye. If one of the two images was uninterpretable, the other eye was used. Only images collected with a signal strength >7/10 were retained. Given the absence of vascular density standards or cutoffs on the retinal OCT-A, we determined a threshold value after analysis of the ROC curves for the prediction of AKI, allowing us to define two groups: the first group had a low vascular density while the second had a high vascular density  corresponds to the retinal zone of high cone density and low capillary vessel count, delineated by the perifoveal anastomotic arcade. Given the good correlation between the vascular characteristics of the two eyes demonstrated in several studies on retinal OCT-A34. The occurrence of AKI defined the “AKI” group, while its absence determined the “non-AKI” group.Acute renal failure after injection of iodinated contrast agent was defined according to the KDIGO criteria, with an increase in serum creatinine (ΔCr) of at least 26.5 µmol/L at 48 h of injection or >50% compared to the initial dosage within 7 days after injection of ICA7, which includes eight weighted variables  and has been proved to have good predictive performance on the onset of AKI linked to the injection of ICA.We also calculated the Mehran scoreContinuous variables are presented as means (±SD) and medians (interquartile ranges). The dichotomous variables are expressed as numbers (percentages). For continuous variables, normality was verified with a Kolmogorov test. The characteristics of the AKI and non-AKI groups were compared using the Mann-Whitney test for continuous variables and the chi-square or Fisher exact test for categorical variables. All tests were bilateral, and significance was set at P < 0.05.35. The areas under the ROC curve (AUC) were compared using the method described by DeLong36. All analyses were performed using the SPSS 22.0 0 software .For multivariate models, factors associated with AKI were assessed using a stepwise backward multivariate regression analysis with an inclusion and exclusion threshold value of 5%. Before the multivariate models were constructed, collinearity between the variables was excluded. The correlation matrix of the multivariate model shows that the correlation between variables (r-coefficient) did not exceed a positive or negative value of 0.25. Since the NT-proBNP values do not follow a normal distribution, a logarithmic transformation was performed. Chi-square improvements and maximum log likelihood stepwise methods, including the Hosmer-Lemeshow goodness-of-fit test, were used to evaluate the regression model. All multivariate models were tested for multicollinearity and were stable: tolerance ranged from 0.69 for the GRACE score to 0.88 for retinal vascular density. The inflation variation factor ranged from 1.14 for retinal vascular density to 1.44 for the Mehran score. To evaluate the discrimination capacity of the different variables on the occurrence of AKI, we constructed ROC curves for the Mehran score, GRACE score, NT-proBNP and perifoveolar vascular density. The best sensitivity and specificity thresholds were determined using the Youden methodDuring the study period, 275 patients hospitalized for ACS in our unit had a coronary angiography and an OCT-A. Finally, 216 patients were included; 21 patients (10%) developed AKI, while the remaining 195 (90%) did not meet the KDIGO criteria , with a mean age of 62.6 years. Patients with AKI were significantly older than those who did not develop AKI , had a history of atrial fibrillation  and chronic kidney disease   .−1 in the AKI group compared with 19.3 mm−1 in the non-AKI group (P = 0.001) (Table −1 with a sensitivity (Se) of 81% and a specificity (Sp) of 60%. Analysis of the ROC curves determined the best threshold values of 5 for the Mehran score , 142 for the GRACE score  and 512 pg/mL for the NT-proBNP .The mean perifoveolar vascular density (inner vessel) was 17.5 mm1) Table  showed n−1) and NT-proBNP . We therefore established two multivariate models including, first, the Mehran score, NT-proBNP and low vascular density (model 1), and second, the GRACE score, NT-proBNP and low vascular density (model 2). In addition to the statistically significant incremental value added by NT-proBNP to these two scores, the addition of the low vascular density evaluated by OCT-A further improved the performance of the AKI model for model 1  as well as for model 2  , comparing the improvement in the performance of these scores by the consecutive addition of two variables strongly associated with univariate AKI analysis but that do not figure in the scores and are not collinear: low vascular density defined from the threshold value on the ROC curve  is a biomarker for onset of acute kidney injury with iodinated contrast media.−1 is an independent predictor of contrast-induced AKI, and retinal vascular density has a predictive performance equivalent to the Mehran score.LRVD defined as less than 19.7 mmThe sequential addition of NT-proBNP and low vascular density to the GRACE or Mehran scores significantly improves the ability of these scores to predict AKI.To our knowledge, this study is the first to show an association between retinal vascular density and the occurrence of acute kidney injury following the injection of contrast agents. The main results of this study are as follows:This prospective observational study shows for the first time that low retinal vascular density assessed by OCT-A is associated with acute kidney injury.et al.21 demonstrated an association, independent of classic cardiovascular risk factors, between changes in glomerular filtration rate (GFR) and retinal abnormalities  (P = 0.008). In a case–control study conducted by Sng et al.37, the fractal dimension was associated with chronic renal failure after adjustment for cardiovascular risk factors . On the other hand, from a cohort of 3199 patients followed for 15 years, the “Beaver Dam CKD” study demonstrated the absence of a causal link between worsening of GFR and retinal vascular abnormalities after adjustment (P = 0.3)38. The authors highlighted a parallel injury through shared pathophysiology between retinal and renal disease. These observations were more recently confirmed by Yip et al., who analyzed the occurrence of terminal CKD in 5763 patients with an average follow-up of 4.3 years39. Thus, retinal OCT-A, which is a noninvasive, rapid, reproducible examination that can be done by paramedical personnel, and whose analysis is automated and instantaneous, appears to be a relevant tool for the evaluation of systemic microvascular involvement.Since the mechanisms of contrast-induced nephropathy are mainly related to microvascular and endothelial dysfunction, the analysis of the potential relationship with OCT-A measurement of retinal vascular density is therefore relevant. Indeed, in a study of more than 3000 patients, Lim 40. We used the Mehran score, validated in the ACS population, for its comprehensive multiparametric approach . Several studies underlined similar Mehran scores regardless of the AKI definition. In the analysis of the ROC curves, Liu et al. reported an AUC at 0.776 (P = 0.219) for an AKI defined by an ΔCr ≥ 0.3 mg/dL , and an AUC at 0.840 (P = 0.247) for a ΔCr ≥ 0.5 mg/dL9. Although some of the score parameters in the present study were not independently associated with AKI (notably the volume of injected ICA), the results are consistent with other studies published on the topic.The incidence of AKI was 10% in our population, which is comparable to the literature9. In our series, the threshold value was 142 , which is in agreement with the threshold of 140 traditionally used to define the population at a high risk of cardiovascular events31. These results are explained by the fact that multiple hemodynamic and renal parameters, directly involved in the occurrence of AKI, were taken into account in this model. The ability of the Mehran and GRACE scores to similarly predict the occurrence of AKI as well as major cardiovascular events41 indicates that ICA-induced nephropathy may be a marker of events in high cardiovascular risk patients.In our analysis, the GRACE score had a performance close to the Mehran score. Another team previously demonstrated that a GRACE score ≥160 allows AKI to be predicted independently in multivariate analysis , with a predictive ability similar to the Mehran score (AUC 0.723)et al. showed that in a STEMI population, with 10.4% evolving toward AKI, NT-proBNP predicted the occurrence of contrast-induced nephropathy significantly in multivariate analysis10. Our current study is in agreement with Goussot et al.’s work, since NT-proBNP is strongly associated with ICA-induced AKI. In our analysis, the threshold value of 512 pg/mL  was very close to the data in the literature43. This biomarker is usually increased in cases of myocardial injury44. Hemodynamic renal impairment in the context of ACS is also a factor involved in the increase of this peptide, partly by decreasing its clearance46. Finally, other factors associated with the increase in NT-proBNP  are also predictive factors for contrast-induced AKI. However, NT-proBNP retains an incremental value in the prediction of AKI when coupled with the Mehran and GRACE scores, which in turn directly take into account the patient’s age, kidney function, presence of diabetes, and hemodynamic status.Previous work carried out in our team by Goussot 47, is associated with an increased risk of acute renal failure49. All these data suggest a microvascular alteration common to all these organs, leading to their respective dysfunctions. Microvascular abnormalities and endothelial dysfunction  appear to be imperfectly addressed by standard scores and biomarkers , which may explain the increased value of low retinal vascular density in predicting AKI risk.Low retinal vascular density was strongly associated with AKI in bivariate analysis, and in addition, provided an incremental value for the prediction of AKI when added to the Mehran score (or the GRACE score) and NT-proBNP. It is also known that no-reflow, involving endothelial dysfunctionThese results support the hypothesis that microvascular dysfunction, characterized by low retinal vascular density, could play a role in the occurrence of contrast-induced AKI after coronary angiography in the context of ACS.50.There are some limitations to the study. The first is the relatively small number of patients included compared to other studies on AKI with postcoronary angiography ICAs. On the other hand, only patients who could benefit from the ophthalmological examination were included, automatically excluding the most severe patients who could not be moved to the examination room. Third, the “low vascular density” threshold value found is close to the population’s median vascular density, suggesting that this measurement alone cannot be used to stratify the risk of AKI, but instead should be considered in combination with other variables or integrated into a score as suggested here. Quantitative data concerning vascular density should be taken with caution as they were not validated with a gold standard measurement of vessel density in histologyAKI was strongly and independently associated with low retinal vascular density. OCT-A evaluation of retinal vascular density offers a noninvasive, reliable and rapid result supporting the hypothesis of systemic microvascular involvement directly contributing to the occurrence of contrast-induced AKI. The presence of a low retinal vascular density even seems to predict AKI with diagnostic performance close to standard prediction scores, and the incremental value of this new biomarker suggests that microcirculatory damage has not been taken into account in determining AKI risk until now. While prevention methods are still limited, identifying the mechanisms and establishing strong predictive factors are key steps towards the prevention of contrast-induced nephropathy after myocardial infarction.Supplementary figures and table