In malalignment syndrome, the spino-pelvic alignment correction with foot orthotics can be applied only to a standing position in the coronal plane. Considering the fact that the average time Koreans spend sitting in a chair is 7.5 hours per day, studies on spino-pelvic correction in sitting position is needed. The purpose of this study is to investigate the pressure changes and radiographic assessment of spino-pelvic alignment using a chair equipped with a height-adjustable seat-plate. This study was conducted on 30 participants with spinopelvic malalignment. All participants were subjected to measure buttocks interface pressure while seated using a smart chair in three consecutive steps:1.on initial seated,2.on balancing seated, and then3.on 1 hour balancing seated.t test. The pressure discrepancy improvement between buttocks from 36.4 ± 32.3 mm on initial seated to 15.7 ± 20.3 mm on balancing, 12.7 ± 10.9 mm on 1hr balancing seated . The radiographic results of pelvic imbalance compensation during seated show a statistical improvement of average SHD  and average ICHD . For a standing posture after use of smart chair, average SHD value , ICHD , and average LLD value  were statistically significant improved.Radiographically, the five spino-pelvic parameters such as shoulder height differences (SHD), iliac crest height differences (ICHD), leg length discrepancy (LLD), pelvic oblique angle (POA), and coronal imbalance were analyzed to investigate the effect of pelvic imbalance compensation on spino-pelvic alignment. Statistical analysis was performed using ANOVA and paired Spine-pelvic malalignment can be improved by individually customized pelvic compensation using balanced seat plate height adjustments under the real-time pressure sensing and monitoring on the buttocks while seated. Pelvic alignment influences spinal posture and stability, and pelvic malalignment is a common cause of lower back, hip, and leg pain. The symptoms and signs of malalignment syndrome include persistent foot, leg, or low back pain, change of the spine curvature, asymmetrical muscle bulk, or strength or inability to turn the body as much in a particular direction. Malalignment syndrome is commonly treated using biomechanical foot orthosis (BFO). It is the only form of therapy that addresses the correction of biomechanical malalignments in the lower extremity kinetic chain. The goal of treatment is the restoration of normal structure and function of the spine and pelvis; therefore, the devices used are designed to realign the body. However, the biomechanical effects of the orthoses used for the clinical treatment of malalignment syndrome are not completely understood. Previous studies have focused primarily on the effects of orthotic devices on foot structure rather than on the pelvis or spine in correction of malalignment syndrome. This study investigated the effect of IoT-based smart chair equipped with adjustable seat plate, pressure sensing and monitoring on spino-pelvic alignment and posture balance in the malalignment syndrome while seated.Malalignment syndrome was defined by Wolf Schamberger, as follows: malalignment associated biomechanical changes, especially a shift in weight bearing and asymmetries of muscle tension and strength, and joint ranges of motion affecting soft tissues, joints, and organ systems throughout the body.22.1 All patients provided informed consent, and the protocols involving baseline measures and contact for re-measurement were approved by the institutional review board (No 2017-07-010-006). The inclusion criteria were as follows: The participants of nonstructural malignment syndrome with shoulder height differences (SHD) or iliac crest height differences (ICHD) >5 mm in radiographic images excluding participants with structural deformity. The participants within a normal range with SHD or ICHD of <5 mm are excluded for the qualitative level of the study in considering measuring errors. The exclusion criteria were as follows: patients with structural spinal deformity or who require surgery or had surgery on spine, pelvis, or hip joint, and children or elderly persons. All patients with eligible inclusion criteria were measured for baseline value. This number of patients exceeds the minimum number of cases per variable (of at least two) for five independent variables in our linear regression models. The 30 participants consist of 21 females and 9 males. In the 21 female participants, the average age was 27 ± 7 years old (19 old to 58 years old), the average height was 161.9 ± 5.6 cm (150–173 cm), and the average weight was 55 ± 9.5 kg (42–75 kg). In the 9 male participants, the average age was 36 ± 12.1 old (19–50 years old), the average height was 173 ± 4.8 cm (167–182 cm), and the average weight was 70 ± 14.4 kg (50–98 kg). A research flow chart for this study of spino-pelvic compensation using IoT-based real-time ischial pressure adjustment is shown in Figure From august 2017 to September 2017, a total of 30 patients with malalignment syndrome were consecutively recruited at the single institute. Diagnostic criteria of malalignment syndrome is defined as biomechanical changes, signs and symptoms  consistently seen in association with 2 of these indications: rotational malalignment, upslip of the sacroiliac joint, and inflare/outflare.1.on initial seated,2.on balancing seated, and3.on 1-hour balancing seated were compared.Changes in radiographic vertebrae parameters in sitting and standing positions were also compared statistically on initial unbalanced seating and an hour-balancing seated.2.2 ICHD and LLD values were defined as the vertical distance between 2 lines when the horizontal line is drawn from the superior aspect of the iliac crest and femoral head to the plumb line with the right angle in the anterior-posterior radiograph of the pelvis. POA was defined as the angle between first line  and second line . Coronal imbalance was defined as a >20 mm distance between the C7 plumb line and central sacral vertical line (CSVL). It was defined as positive imbalance when the C7 plumb line passes 2 cm or more to the right side of CSVL, and negative imbalance when C7 plumb line passes 2 cm or more to the left.The anteroposterior x-ray images were obtained in the sitting and standing positions. The five spino-pelvic parameters for evaluation of smart chair were as follows: SHD, ICHD, leg length discrepancy (LLD), pelvic oblique angle (POA), and coronal imbalance Fig. . SHD was2.3Smart chair  was used to measure the pressure of the buttocks in the patient's sitting position, and to balance both buttocks’ pressures by the left seat plate equipped with adjustable height motor Fig. . We anal1.on initial seated,2.on balancing seated, and3.on 1hr balancing seated.The pressure sensors that installed on each seat plates measure the seat-interface pressure applied to both the buttocks while sitting on smart chair. Then, the measured results are displayed on a mobile internet of things (IOT) device's user experience/user interface (UX/UI). Balance adjustment was performed by adjusting the height of the left seat plate; When left pressure was large, height of the left seat plate was increased . When right pressure was large, height of the left seat was lower . When adjusting the height of the left seat plate to balance both pressures, the seat-interface pressures were measured. After 1hr balancing seated, the pressure was measured again.2.4The research was conducted on 30 research participants diagnosed with malalignment syndrome, as previously defined by the Patients section. The seat-interface pressure measurements and radiographic assessments of all participants are as follows Fig. .1.In radiographic images of all participants at the sitting and standing positions, the radiographic assessments were investigated.2.Smart chair measured seat-interface pressure by both ischium on the parallel seat plates. The height of the left seat is adjusted to balance the left and right pressures, and then seat-interface pressures were obtained again.3.The seat-interface pressure values of all participants were obtained after 1hr balancing seated. The radiographic assessments using x-ray images at the sitting and standing positions are measured and analyzed.2.5t test. All analyses were conducted using Prism version 7 .The values measured by 2 observers with more than 5 years of experience in the spine field were independently used. Intra-examiner reproducibility and inter-examiner reliability were examined using the intra- and inter-class correlation coefficients. Unbalance and balanced pressure measurements were analyzed using ANOVA test and paired 33.1We analyzed difference values of seat-interface pressure between left and right buttock for three steps:1.initial seated,2.on balancing seated, and3.on 1hr balancing seated Fig. .P = .003) on balancing seated. The average difference values after 1 hour balancing seated was 12.7 ± 10.9 Ω . These results show that the pressure difference measured after an hour was improved by 65.1%.For the initial unbalanced seating, the average pressure difference value was 36.4 ± 32.3 Ω (7.0–153.1 Ω). The average height of left seat was changed by 3.7 ± 1.7 mm (1–8 mm) to balance left and right pressure, and the average pressure difference was 15.7 ± 20.3 Ω , and was statistically significant. In standing position, average values of SHD value , ICHD , and LLD  improved. Figure The improvement of all the above measurements was statistically significant Fig. . In sitt4 Abnormal loading to pelvis that exceed this normal displacement in any direction can cause the adjoining SI joint surfaces to end up in an aberrant position so that the surfaces no longer match and stay compressed in some areas, separated in others, affecting normal movement. If the surfaces of SI joint become fixed or locked in an abnormal position, major consequences include dysfunction of SI joint mobility, a disturbance of the lumbo–pelvic–hip complex and its ability to transfer weight and absorb shock, and an alteration of gait. Deformation and degenerative changes in spinal posture cause changes in the coronal and sagittal plane arrangement and make the changes in the whole spine alignment and deformation.,11,12 The arrangement of the coronal and sagittal plane involves compensatory mechanism using the change of the lower limbs and the balance of the spine-pelvis.,14 Change of the spinal-pelvic balance is the starting point for inducing a compensatory response that accounts for the entire spinal imbalance.,15 Therefore, the compensatory response of the pelvis occurs simultaneously with the change of the legs as the imbalance increases. The effect of compensatory mechanism is appeared more prevalent in the pelvis and lower extremities, and the adaptive response in the thoracic alignment is less.,16 However, this compensatory mechanism is also related age. In the course of “natural cascade of degeneration,” the elderly secures the stability of the spine by restabilization process including facet joint hypertrophy, bony overgrowth, and ossification of the anterior and posterior longitudinal ligament. Therefore, the older the age, it is harder to correct the spinal-pelvic imbalance by this compensatory mechanism. The younger the age, the faster correction of spinal pelvic imbalance is needed.The term “malalignment syndrome” is considered to be a biomechanical change accompanied by signs associated with rotational malalignment of pelvis, upslip of the sacroiliac joint, and inflare/outflare of pelvis surfaces. Orthotics increase sensory input from the sole surface, and the stimulation of proprioceptive receptors has been shown to help control pain. A reduced perception of pain may also elicit reflex relaxation of muscles, which may help to reduce muscle tension asymmetry.,18 Orthotic intervention is believed to influence the pattern of lower extremity movement through a combination of mechanical control and biofeedback.,19 Kim et al found that BFO reduce pelvic-tilt sidedness, and pelvic rotation angle asymmetry was significantly decreased in the BFO condition, compared to the barefoot and shoes conditions, which implies that BFO contributes to the correction of pelvic rotational asymmetry. However, this study participant had moderate to severe pelvic asymmetry, and it remains undetermined whether BFO is effective for patients with mild pelvic asymmetry.Malalignment syndrome is commonly treated using BFO treatment, the only therapy that corrects biomechanical malalignments in the lower extremity kinetic chain. The goal of this method is to restore normal structure and function of the spine and pelvis; therefore, the devices used are designed to realign the body. These orthotics increase foot stability by providing contact for weight bearing across a larger part of the sole and decrease the tendency of the feet to roll inwards or outwards after alignment has been achieved, and may decrease torque forces on legs.The starting point of the compensatory mechanism of spinal imbalance is the change of pelvis and leg position. The foot orthosis can correct the pelvis asymmetry by change the leg position. However, there is no way to correct the pelvis asymmetry by acting directly on the pelvis. Therefore, we developed a smart chair that could directly correct the imbalance of the pelvis by directly affecting the pelvic and evaluated its effectiveness. The present study described the immediate influence of smart chair on malalignment syndrome, especially with respect to change in pelvic asymmetry. This study found that pelvic asymmetry was significant decreased in the smart chair condition, which implies that smart chair contributes to the correction of pelvic asymmetry. reported the result of improved pelvic tilt of 0.92 ± 0.42 using biomechanical foot orthosis (BFO) and shoes (Table ,19 we obtained an improved discrepancy reduction using our IoT-based real-time pressure sensing and monitoring on the buttocks with a smart chair.Kim et alThe shortcomings of this study are as follows. First, there is limited number of enrolled cases in this study. The main reason for this small number of registrations is that the awareness of spino-pelvic imbalance in the coronary plane was ambiguous, although it is well recognized that the functional imbalance of the spine progresses and eventually fixes to structural deformation. Thus, in order to determine the inclusion criteria, clear exclusion criteria were first established, such as structurally fixed spinal deformity patients. Relatively younger groups were registered in this study whilst the elderly groups with structural changes in the natural aging process were excluded. The elderly patient with severe or irreversible degenerative structural change is more likely to be unresponsive to the alignment correction using the smart chair. Second, only coronal radiographic parameters measured is available at the sitting position in this study. Generally, most of the radiographic parameters are evaluated in sagittal plan and or standing position. Lastly, the appropriate time of the intervention applying the smart chair was not established yet. Therefore, additional studies are needed to confirm whether 1 hour apply is really effective in correcting the alignment. The study of the degree of effect of applying over time is essential later. Despite these limitations, the importance of this study was conducted to understand the effect of intervening in functional changes in daily life so that functional spinal deformation does not progress to structural deformation.5Spine-pelvic malalignment can be improved by individually customized pelvic compensation using balanced seat plate height adjustments under the IoT-based real-time pressure sensing and monitoring on the buttocks while seated.M-J. S. conceived of the presented idea and supervised the project. H-W. K., K. H. K., S-W. Y carried out the experiment. H. L. performed the analytic calculation. M-J. S. took the lead in writing the manuscript. H-W. K., K. H. K., and S-W. Y contributed to the interpretation of the results. M-J. S. and H. L. contributed to the final version of the manuscript. All authors provided critical feedback and helped shape the research, analysis and manuscript.Data curation: Haenghwa Lee.Investigation: Byung-Jou Lee, Hae-Won Koo, Kwang Hyeon Kim, Sang-Won Yoon.Methodology: Hae-Won Koo, Kwang Hyeon Kim, Sang-Won Yoon.Project administration: Moon-Jun Sohn, Byung-Jou Lee.Supervision: Moon-Jun Sohn.Validation: Hae-Won Koo, Kwang Hyeon Kim, Sang-Won Yoon.Writing – original draft: Moon-Jun Sohn, Byung-Jou Lee.Writing – review & editing: Moon-Jun Sohn, Haenghwa Lee.


Deficiency or excess exposure to manganese (Mn), an essential mineral, may have potentially adverse health effects. The kidneys are a major organ of Mn site-specific toxicity because of their unique role in filtration, metabolism, and excretion of xenobiotics. We hypothesized that Mn concentrations were associated with poorer blood pressure (BP) and kidney parameters such as estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), and albumin creatinine ratio (ACR). We conducted a cross-sectional analysis of 1931 healthy U.S. adolescents aged 12–19 years participating in National Health and Nutrition Examination Survey cycles 2013–2014, 2015–2016, and 2017–2018. Blood and urine Mn concentrations were measured using inductively coupled plasma mass spectrometry. Systolic and diastolic BP were calculated as the average of available readings. eGFR was calculated from serum creatinine using the Bedside Schwartz equation. We performed multiple linear regression, adjusting for age, sex, body mass index, race/ethnicity, and poverty income ratio. We observed null relationships between blood Mn concentrations with eGFR, ACR, BUN, and BP. In a subset of 691 participants, we observed that a 10-fold increase in urine Mn was associated with a 16.4 mL/min higher eGFR . These exploratory findings should be interpreted cautiously and warrant investigation in longitudinal studies. Manganese (Mn) is an essential nutrient required for normal human development, with critical roles in energy metabolism, protection against oxidative stress, immunological system function, and nervous system function ,2. ChangWhile evidence supports Mn nephrotoxicity at high doses ,5, low-dAlthough limited by study design and challenges in exposure assessment, the evidence of adverse effects of Mn exposure on United States (U.S.) adolescents is compelling enough to warrant further research. This study aimed to investigate the potential relationship between blood and urine Mn concentrations and blood pressure and kidney parameters including estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), and albumin creatinine ratio (ACR). The study expands upon prior research by examining the U.S. adolescent population and testing for evidence of effect modification by race/ethnicity and sex.n = 664), missing values for blood Mn measurements (n = 1147), blood Mn measurements outliers (n = 1), missing values for poverty income ratio (n = 195), and those who took BP medication (n = 4). The final analytic sample consisted of 1931 participants with available blood Mn measurements , a cross-sectional survey that is nationally representative of the noninstitutionalized U.S. population. The survey procedures were approved by the National Center for Health Statistics Internal Review Board, and all participants gave informed consent. This study was exempt from review by the Icahn School of Medicine at Mount Sinai’s (ISMMS) Institutional Review Board . We obtained publicly available data collected through household interviews and physical and laboratory examinations from NHANES 2013–2014, 2015–2016, and 2017–2018 for adolescents aged 12 to 19 years, for a total of 3942 participants. We excluded participants who had missing values for eGFR  readings were obtained after the participant rested quietly in a seated position for 5 min and once the participant’s maximum inflation level was determined; a fourth attempt was made if a BP measurement was interrupted or incomplete. An average value for both systolic (SBP) and diastolic BP (DBP) was calculated using the second and third BP readings. If one or both of the second and third BP readings were missing or had zero values, then averages of two of the available readings were used. We used the single BP reading for those participants who only had one BP reading available.BUN was analyzed on a Beckman UniCel DxC800 Synchron  by Collaborative Laboratory Services, LLC., to determine the concentration in serum or plasma by means of the enzymatic conductivity rate method. The lower limit of detection (LLOD) was 1.00 mg/dL for BUN. Detailed information on specimen collection and processing is available in the NHANES laboratory procedures manual .Urinary albumin concentrations were measured by solid-phase fluorescent immunoassay . UrinaryWhole-blood Mn concentrations were measured by quadrupole inductively coupled plasma mass spectrometry . Partici2) at or above the sex-specific 95th percentile of the U.S. Centers for Disease Control and Prevention BMI-for-age growth charts and classified into 4 categories: underweight (z-score < −2), normal (−2 ≤ z-score < 1), overweight (1 ≤ z-score < 2), and obese (z-score ≥ 2). Covariates were chosen a priori, according to prior literature.Demographic characteristics were taken from the questionnaire data and included age and sex. Race/ethnicity was categorized as Mexican American, other Hispanic, Non-Hispanic White, Non-Hispanic Black, Non-Hispanic Asian, and Other (including multi-race). Family poverty-income ratio (PIR) values were categorized into two groups: low income (PIR < 1) and high income (PIR ≥ 1). Body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared  estimate and the corresponding 95% confidence intervals (CI). We also conducted sex- and race/ethnicity-stratified analyses to examine the association between blood Mn and BP and kidney parameters. In secondary analyses, we used weighted multivariable linear regression models using NHANES urine metal sampling weights to calculate the beta estimate and the corresponding 95% CI for the association between creatinine-adjusted urine Mn and BP and kidney parameters adjusted for age, gender, BMI z-score, race/ethnicity, and PIR. Sensitivity analyses using age- and sex-specific blood Mn z-scores were conducted to calculate the beta estimate and corresponding 95% CIs [Descriptive statistics of participant characteristics, Mn concentrations, and BP and kidney parameters were calculated. Blood and urine Mn concentrations, as well as ACR, were log 95% CIs . AdditioAfter exclusions, our final study population consisted of 1931 adolescents. 2. Fourteen participants had an eGFR less than 60 mL/min/1.73 m2. The mean SBP was 109 mmHg, while the mean DBP was 61 mmHg. Adolescent hypertension is defined as BP of 130/80 mmHg or higher. Based on this definition, one participant could be putatively classified as having hypertension.The mean eGFR was 100.4 mL/min/1.73 mThe associations of blood Mn with BP and kidney parameters are shown in 10-unit increase in blood Mn (µg/L) was only moderately (p = 0.1) associated with a 5.8 mL/min higher eGFR  after covariate adjustment. We conducted additional analyses to examine the effect of each individual covariate on the association and observed that sex had the greatest influence on the results. When stratified by sex, we observed null associations between blood Mn levels and eGFR, SBP, DBP, BUN, and ACR . Thus, our findings may have enhanced generalizability to the U.S. adolescent population, an improvement over studies of adolescents in smaller, regional areas. This study provides an important foundation from which to design prospective studies investigating the relationship of developmental Mn exposure, BP, and renal health in other studies and populations.In conclusion, this cross-sectional study using NHANES data identified no relationships between blood Mn concentrations in healthy U.S. adolescents and BP or kidney parameters. We observed a putative positive relationship between urine Mn and eGFR. Longitudinal studies are needed to further examine these exploratory findings of the complex relationships between Mn in kidney parameters and BP regulation, including race/ethnicity- and sex-related differences.


Hypertension is the most frequent chronic and non-communicable disease all over the world, with about 1.5 billion affected individuals worldwide. Its impact is currently growing, particularly in low-income countries. Even in high-income countries, hypertension remains largely underdiagnosed and undertreated, with consequent low rates of blood pressure (BP) control. Notwithstanding the large number of clinical observational studies and randomized trials over the past four decades, it is sad to note that in the last few years there has been an impressive paucity of innovative studies. Research focused on BP mechanisms and novel antihypertensive drugs is slowing dramatically. The present review discusses some advances in the management of hypertensive patients, and could play a clinical role in the years to come. First, digital/health technology is expected to be increasingly used, although some crucial points remain . Second, several areas should be better outlined with regard to BP diagnosis and treatment targets. Third, from a therapeutic standpoint, existing antihypertensive drugs, which are generally effective and well tolerated, should be better used by exploiting available and novel free and fixed combinations. In particular, spironolactone and other mineral-corticoid receptor antagonists should be used more frequently to improve BP control. In particular, some drugs initially developed for conditions different from hypertension including heart failure and diabetes have demonstrated to lower BP significantly and should therefore be considered. Finally, renal artery denervation is another procedure that has proven effective in the management of hypertension. Because of its high prevalence and important clinical impact, hypertension remains a leading contributor to the risk of cardiovascular disease and death ,2,3,4. IDespite such impressive growth, the proportion of treated hypertensive subjects with normal BP (‘controlled hypertension’) remains very low worldwide. It has been estimated that such a proportion approaches 23% in women and 18% in men . NotablyThus, a first basic consideration is that, although the prevalence and clinical impact of arterial hypertension is consistently growing worldwide, its control remains disappointing, particularly in low-income countries.A second consideration is that, despite the huge number of observational studies and randomized controlled trials completed over the past four decades, the last few years have been characterized by an impressive paucity of innovative studies. In a comprehensive review, Dzau noted that research on new antihypertensive drugs and therapeutic targets is slowing dramatically . In addiThe current review aims to discuss the main trends and perspectives related to the clinical diagnosis and treatment of hypertension over a foreseeable future. More specifically, our review describes the use of new blood-pressure lowering drugs and device-based approaches to achieve better blood pressure control rates and improve cardiovascular outcomes in patients with hypertension are also reviewed. In other words, we offer clinicians some answers to the following question: “what will the management of hypertensive patients be like in 2030?”Owing to the refinement of digital/health technology, the marketing of electronic devices for remote BP measurement and transmission is growing. Theoretically, these devices have the potential to improve the diagnosis of hypertension and the achievement of an adequate BP control at the population level. Just to create a parallel with diabetes, Dzau noted in his review that the number of apps for diabetes management was about 1800 in 2016, with an impressive increase in digital diabetes marketing . There iThe system should be easily wearable, cheap, and non-intrusive. Systems included in normal smartwatches would be ideal;The system should be validated for accuracy at independent academic or hospital centers. It should allow continuous or almost-continuous BP detection over prolonged periods of time of months or even years;The system should be connectable to an easy-to-use protected digital repository, with software allowing easy BP retrieval over variable periods of time for calculation of appropriate statistical measures  and attached graphics;The system should be easily accessible to doctors, thereby enabling rapid check and response for patients and the suggestion of changes in drug treatment or other measures;Clinical research should urgently identify BP measures retrievable from the system which are more appropriate for the prediction of organ damage and, hopefully, prognosis. In other words, research should identify which BP measurements obtained by the system are more important for clinical decisions.Unfortunately, not all BP measurement devices on the market have been appropriately validated according to existing guidelines ,18 and sIt is hoped that the application of artificial intelligence to these databases, which are expected to include many different types of biological data for each patient, may help doctors and patients in identifying better strategies for hypertension control, possibly in combination with strategies promoting a healthier diet, better physical activity, and a more intelligent use of drugs. The growing use of ‘tele-medicine’ during the current COVID pandemic should be extended to the management of hypertension. However, there still a long way to go.Whereas the European Society of Cardiology and the European Society of Hypertension (ESC/ESH) define hypertension by office BP levels ≥140 mmHg systolic or 90 mmHg diastolic,  the AmerOf note, the more aggressive diagnostic targets endorsed by the US guidelines  do no im(a)Patients with office BP ≥ 160/100 mmHg regardless of other considerations ,23,24;(b)Patients with BP ≥ 140/90 mmHg in the presence of ischemic heart disease, cerebrovascular disease, or heart failure ,23,24.Notably, all guidelines share the recommendation that drug treatment should be started immediately for:All guidelines suggest that drug treatment should be initiated, regardless of other considerations, in patients with BP persistently ≥ 140/90 mmHg in case of inefficacy of life-style measures ,23,24.In the case of a BP between 130/80 and 140/90 mmHg, the AHA/AHA guidelines recommend drug treatment in patients with overt cardiovascular disease , as well as in patients without overt cardiovascular disease  if their 10-year risk of cardiovascular disease is ≥10% according to the ASCVD calculator .Available guidelines provide different recommendations in terms of BP targets and definitions of BP control. The ISH and the ESC/ESH guidelines recommend a uniform BP target (<140/90 mmHg), and individualized targets based on age, tolerability, and comorbidities. Conversely, the AHA/ACC guidelines recommend an identical BP target (<130/80 mmHg) in all patients, regardless of age and comorbidities. The potential advantages and disadvantages of these different approaches have been discussed in detail ,26,27.Interestingly, the recent 2021 ESC Guidelines on Cardiovascular Prevention  introducIn summary, hypertension guidelines seem to be oriented towards individualized BP targets according to the general principle that the lowest well-tolerated BP target should be a reasonable target, with the main goal to prevent the most closely BP-related adverse complication of hypertension, which include stroke and heart failure .Although frequently not utilized by many patients, life-style measures play a pivotal role in BP control. These measures include weight reduction for overweight or obese subjects, a low sodium diet, smoking cessation, alcohol and caffeine limitations, and regular physical activity ,23. We sMany studies conducted at independent centers have demonstrated beyond any reasonable doubt the overwhelming prognostic impact of nighttime BP ,31,32. O2 of body surface area) and uncontrolled hypertension were randomized to chlorthalidone or placebo, with the randomization stratified by prior use of loop diuretics. After 12 weeks of treatment, average 24-h systolic BP was 10.5 mmHg lower in the chlorthalidone group than in the placebo group (p < 0.001) [For the time being, it seems reasonable to advise combining morning and evening administration of antihypertensive drugs in selected patients with severe or resistant hypertension, as well as in those with particularly high nighttime BP. Preference should be given to antihypertensive drugs with a long duration of action, capable of covering the entire 24-h period. For example, when choosing among different diuretics, chlorthalidone appears to be the agent of first choice in patients without severe renal failure ,41. In a< 0.001) .In a double-blind, placebo-controlled, within-patient trial (PATHWAY-2) , 335 patIn a run-out sub-study of PATWAY-2, amiloride, a distal tubular diuretic that inhibits the epithelial sodium channel sensitive to spironolactone, exerted an antihypertensive effect similar to that of spironolactone and was superior to placebo, doxazosin, and bisoprolol . NotablyEplerenone seems to possess a better safety profile than spironolactone and, thus, it might be an alternative to the latter ,46. HoweAnti-aldosterone drugs are currently recommended in patients with resistant hypertension ,23,47. IEndothelin regulates vascular tone and BP, producing a powerful vasoconstrictor effect and contributing to the pathogenesis of hypertension ,49. It cFurthermore, endothelin-1  is an endothelial cell-derived peptide with a wide variety of developmental and physiological functions, which include embryogenesis and nociception ,51. MoreInterestingly, aging affects the shift in balance of release and/or activity of endothelium-derived substances, including increased expression, release, and activity of ET-1 ,52. The Based on evidence that endothelin is a very potent endogenous vasoconstrictor , some trDevelopment of darusentan, and endothelin-A blocker, was stopped for safety concerns.A trial with atrasentan in patients with diabetic nephropathy, was stopped for reasons related to low recruitment, and apparently different from safety.Aprocinentan, a blocker of both endothelin-A and endothelin-B receptors with a very long pharmacological half-life (about 44 h), proved more effective than placebo and lisinopril . InteresThe heart produces different natriuretic peptides which include the atrial natriuretic peptide, the B-type natriuretic peptide and the C-type natriuretic peptide . These pNeprilysin, a zinc endopeptidase, inactivates, not only the cardiac natriuretic peptides, but also bradykinin , therebyOmepatrilat was the first-in-class combination of naprilysin with an angiotensin-converting-enzyme inhibitor, but its development was abandoned because of occurrence of severe angioedema . In contIt is reasonable to foresee that LCZ696 will be increasingly used in the future not only in heart failure, but also for improving BP control, particularly in patients with resistant hypertension. Various reasons are currently favoring a preferential development of this drug in patients with heart failure, but the stage is set for a growing role of this drug in the treatment of hypertension ,64.Angiotensin II induces vasoconstriction by stimulating the angiotensin 1 receptors, and vasodilatation by stimulating the angiotensin 2 receptors. In experimental and clinical settings, stimulation of angiotensin 2 receptors inhibits fibrosis  and induAbout 97% of glucose secreted at glomerular level is reabsorbed in the proximal renal tubule through the sodium-glucose cotrasporter-2 receptors (SGLT2) . The remIn pivotal phase III clinical trials, selective SGLT2 receptor inhibitors empagliflozin, canagliflozin, dapagliflozin and ertugliflozin modestly reduced systolic and diastolic BP through various mechanisms which may include natriuresis, osmotic diuresis and reduction of the sympathetic tone . These dIn the EMPA-REG BP trial, empagliflozin 10 mg and 25 mg reduced 24-h ambulatory BP by 3.44/4.16 mmHg more than placebo and the degree of antihypertensive effect was comparable in the presence of none, one or more than one antihypertensive drug .According to available meta-analyses , the degAlthough these drugs are generally well tolerated, concerns have been raised about volume depletion, acute kidney injury, and genital infections as potential adverse effects. The SGLT2 receptor inhibitors have been recently suggested by guidelines as first-line antidiabetic drugs in patients with diabetes at high or very high cardiovascular risk due to organ damage or concomitant risk factors . In the Renal sympathetic overactivity contributes to the development and progression of hypertension ,82,83. RSome clinical trials published over the past 15 years generated many expectations on the clinical utility of renal denervation . UnfortuRenal artery denervation has a strong pathophysiological rationale to justify a significant BP lowering effect .It is well known that sympathetic firing originating from the ganglia located in the central nervous system induces a variety of effects at cardiac, renal, vascular, and muscular levels that ultimately trigger BP elevation. Several mechanistic studies have demonstrated that ablation of efferent and afferent renal nerves is followed by a reduction of the neural ‘bursts’ of sympathetic activity, detectable by neurography, with parallel reduction in BP . Furtherp = 0.03) [In the DENERHTN trial , 106 pat = 0.03) .p < 0.05) [p < 0.05) [p < 0.05) [In the SPYRAL HTN-ON MED trial , 80 pati < 0.05) . In the  < 0.05) . Finally < 0.05) . OverallConcerns remain about the persistence of the antihypertensive effect over the long term. However, encouraging results came from the open and not comparative Global SIMPLICITY Registry , which fA clinical trial compared different techniques of denervation and concluded that the ultrasound technique targeted on both main renal artery and its bifurcations was superior to the radiofrequency technique targeted on the main renal artery alone .In conclusion, renal artery denervation has the potential to be furtherly adopted in clinical practice over the next few years. The main contraindication remains renal artery stenosis, which is rare in unselected patients, but relatively higher, up to 30%, in those with more severe or resistant hypertension . ProceduOngoing studies should lead to identification of patients more likely to benefit from renal denervation in terms of BP lowering effect. According to a position paper of the Italian Society of Hypertension , some clOf note, patients with moderate to severe chronic kidney disease were excluded from large international trials, and smaller studies suggest limited utility in this population .Despite the evidence that renal denervation is associated with a low incidence, of mostly, minor complications ,95,97, aThus, when considering renal nerve ablation, arteries with visible stenosis, with calcification or atheromatous plaques, represent relative contraindications ,78,80.Finally, available data argue in favor of an incomplete and insufficient ablation of renal sympathetic nerves as a major cause of inadequate BP responses to catheter-based interventions. Indeed, it is not entirely clear whether catheter design and energy delivery may influence the variability of the response to renal nerve ablation and the risk of the development of renal artery stenosis ,104.BP is a very potent risk factor. Unfortunately, at variance with other risk factors, such as serum cholesterol, glucose or creatinine, or even body weight or cigarette smoking, BP is extremely variable over time and this may leave uncertainty or even frustration on the real value of what we are measuring. BP recording remains generally intrusive and the precise rules for a correct BP measurement in the clinical practice are scarcely known. Many patients still do not realize that is perfectly normal to find out BP values of 125/70 and 145/85 mmHg at distance of few minutes. Clearly, such imprecision in diagnosis does not help to achieve BP control when needed.It is hoped that the future will lead to development of accurate and non-intrusive devices for BP measurement in the long-term. From a therapeutic standpoint, we currently dispose of many effective and well tolerated antihypertensive drugs, but a long way is still to do for an optimal use of these drugs, alone or in combination. Unfortunately, research on new antihypertensive drugs dramatically slowed over the past few years. We agree with Bhudia that the future in the management of hypertensive patients remains uncertain . However


In multivariate analysis, CCB (odds ratio (OR) = 2.68, p < 0.0001) and age  were independently associated with clinically important nocturia. Conclusion: CCB was associated with nocturia, while AHTs other than CCBs and elevated blood pressure were not.Background: The associations of nocturia with hypertension and anti-hypertensive agents (AHTs) remain to be validated. Methods: This cross-sectional study examined whether blood pressure and/or frequently used classes of AHTs had consistent associations with nocturia. Methods: A total of 418 male patients aged ≥ 40 years were retrospectively assessed in terms of the International Prostate Symptom Score (IPSS), prescription medications, and blood pressure. Nocturia was evaluated using item 7 of the IPSS, and two or more episodes of nocturia per night was considered to indicate clinically important nocturia. Results: Patients taking calcium channel blockers (CCBs), but not other AHTs, experienced more episodes of nocturia than patients not taking AHTs (1.77 ± 1.07, 1.90 ± 1.19, and 1.48 ± 0.98 in CCBs alone, CCBs + other AHTs, and other AHTs alone, vs. 1.35 ± 1.08 in not taking AHTs;  The International Continence Society defines nocturia as the number of times an individual passes urine during their main sleep period, from the time they have fallen asleep up to the intention to rise from that period ,2. NoctuThe cause of nocturia is often multifactorial; however, distinct pathophysiological mechanisms have been delineated, including global polyuria, nocturnal polyuria, diminished bladder capacity, and primary or secondary sleep disorders. The etiology of nocturia frequently does not occur in isolation, and patients often present with many medical comorbidities, complicating both diagnosis and therapeutic management . MedicalEpidemiological studies demonstrated a significant relationship between hypertension and nocturia ,14,15,16This cross-sectional study of men aged 40 years or older examined whether blood pressure (BP) and/or frequently used classes of AHTs had consistent associations with nocturia.n = 35), bladder CIS or muscle-invasive bladder tumor (n = 19), hemodialysis (n = 9), history of prostate surgery within 6 months before study entry (n = 5), and symptomatic cystitis (n = 1). A total of 418 cases were analyzed.This retrospective cross-sectional observational study was approved by the institutional review board at Jichi Medical University Saitama Medical Center . Data from male patients aged 40 years or older, who were hospitalized in the Department of Urology, Jichi Medical University Saitama Medical Center from January 2018 to December 2019 and completed the International Prostate Symptom Score (IPSS) questionnaire , were coAll patients in this study completed the IPSS questionnaire on referral to the Department of Urology. Clinically important nocturia was defined as two or more episodes per night, according to item 7 of the IPSS. The overactive bladder symptom score (OABSS) questionnaire  was alsoUse of prescription medications was captured by self-reporting and direct observation of medication labels by pharmacists in our institute. We recorded use of the six classes of AHTs most commonly prescribed in our population: CCBs (dihydropyridine type), angiotensin receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACE-Is), β-blockers, α-blockers, and thiazide diuretics.Elevated BP was defined as systolic blood pressure (SBP) >140 mmHg or diastolic blood pressure (DBP) >90 mmHg in the daytime. Daytime BP was measured between 10:00 and 14:00 on the first day of hospitalization (the day before surgery), and morning BP was measured between 06:00 and 07:00 the following day (the day of surgery).Diabetes mellitus (DM) was defined as glycated hemoglobin >6.2% or taking hypoglycemic agents. The sum of the scores on IPSS items 1–6 was used to define LUTS other than nocturia. Other covariates included age, body mass index (BMI), and the estimated glomerular filtration ratio (eGFR). Glycated hemoglobin and eGFR were assessed within 4 months before admission.The primary endpoint was whether AHTs and/or elevated BP were associated with nocturia. The secondary endpoint was which types of AHTs were associated with nocturia.All data are shown as the mean and ± standard deviation (SD) unless otherwise indicated. Variables were compared using the Mann–Whitney U test and Fisher’s exact test, as appropriate. Comparisons among three or more groups were performed using the Kruskal–Wallis test with Dunn’s multiple comparison test. Spearman’s rank correlation coefficient was used to calculate correlations. Binary logistic regression analysis was performed to identify factors independently associated with clinically important nocturia. Statistical analyses were performed using GraphPad Prism  and SPSS Statistics for Windows software .p < 0.05 was taken to indicate statistical significance.In all analyses, n = 250, 60%), prostate biopsy for suspected prostate cancer , partial or radical nephrectomy for kidney cancer , nephroureterectomy for renal pelvic/ureteral cancer , and others   .n = 170, 71%), ARBs , ACE-Is , β-blockers , α-blockers , and thiazide diuretics . The 107, 94, and 39 patients were taking single, dual, and more than three types of AHTs, respectively. Daytime BP was elevated in 113 patients (27%). A total of 100 patients (24%) were classified as having DM, 61 of whom were taking hypoglycemic agents.The mean duration from reporting IPSS questionnaire to assessing medications and BP was 2.71 ± 1.60 months. A total of 240 patients (57%) were taking AHTs, including CCBs  were 8.23 ± 6.88 and 1.58 ± 1.11, respectively. The mean score on item 7 increased with age  .p = 0.14, , while the difference in number of nocturia episodes did not differ between patients taking AHTs other than CCB and those not taking AHTs , although a difference was still evident in older patients ≥ 76 years)   C. The tip = 0.02 and p = 0.06, respectively) (p = 0.05 and p = 0.005). The OABSS questionnaire was available in 388 patients (93%). The scores for nighttime frequency, urgency, and urgency incontinence were higher in patients taking CCB alone or CCB plus other AHTs compared to in those not taking AHT in OABSS   . The scoctively) .r = 0.27, p < 0.0001) and the sum of the scores on IPSS items 1–6 , and a very weak correlation between the number of nocturia episodes and the glycated hemoglobin level . In contrast, no correlation was detected between nocturia and BMI (p = 0.60) or eGFR (p = 0.15) (There were positive correlations between the number of nocturia episodes and age ( = 0.15) . The pre = 0.15) .p < 0.0001), age , and the sum score for IPSS items 1–6  were independently associated with clinically important nocturia.A total of 190 patients exhibited clinically important nocturia, while 227 patients did not. In univariate analysis, age, eGFR, the sum of the scores on IPSS items 1–6, CCBs, and β-blockers were associated with clinically important nocturia, while BMI, elevated daytime and morning BP, glycated hemoglobin level, ARBs, ACE-Is, α-blockers, and thiazide diuretics were not . In multIn the present study, we assessed the association of nocturia with frequently used classes of AHTs and other covariates, including BP, in more than 400 patients, demonstrating that CCB use, but not use of AHTs other than CCB nor BP elevation itself, was associated with nocturia.Although nocturia has often been treated with agents targeting benign prostatic hyperplasia and/or overactive bladder, such treatment has been shown to be beneficial only in certain patients ; recentlRecently, associations of hypertension and AHTs with nocturia were demonstrated ,22,23,24Yokoyama et al. demonstrated an association between nocturnal polyuria and untreated hypertension in women . MeanwhiThis study had some limitations. In particular, the retrospective design may have led to selection bias. The number of patients was relatively small in some groups, especially the number of patients taking ACE-Is, β-blockers, α-blockers, and thiazide diuretics. Also, most patients had urological cancers, which may have affected the LUTS, including nocturia. BP measurements were obtained in the hospital and there were 2.7 months of lags from reporting IPSS questionnaire to assessing medications or BP, which might affect results in the present study. Finally, nocturia episodes were determined based on the IPSS questionnaire in the present study, although a frequency volume chart is more reliable for determining nocturia .In conclusion, CCBs were the only AHTs associated with nocturia in this study, especially in the younger patients, while BP elevation itself showed no such association. CCBs were also associated with storage symptoms. Urologists and physicians should take the association between CCB and nocturia into consideration when starting or adding AHTs and evaluating or treating nocturia.


Methods: Retrospective clinical and laboratory data from 489 overweight and obese children and adolescents were reviewed. Children were classified according to the 2004 and 2017 AAP guidelines for systolic and diastolic blood pressure. Lipid profile and glucose metabolism data were recorded; triglyceride/HDL ratio (TG/HDL) was calculated as an index of endothelial dysfunction. Hepatic steatosis was detected using the ultrasonographic steatosis score. Results: Children with elevated blood pressure increased from 12.5% with the 2004 AAP to 23.1% with the 2017 AAP criteria (p < 0.001). There was a statistically significant increase in children with high blood pressure in all age groups according to the new cut-off values. Notably, the diagnosis of hypertension according to 2017 AAP criteria had a greater positive association with Hepatic Steatosis  and TG/HDL ratio . Conclusions: The 2017 AAP tables offer the opportunity to better identify overweight and obese children at risk for organ damage, allowing an earlier and more impactful prevention strategy to be designed.The prevalence of primary hypertension in pediatric patients is increasing, especially as a result of the increased prevalence of obesity in children. New diagnostic guidelines for blood pressure were published by the American Academy of Pediatrics (AAP) in 2017 to better define classes of hypertension in children. The aim of our study is to evaluate the impact of new guidelines on diagnosis of hypertension in pediatrics and their capacity to identify the presence of cardiovascular and metabolic risk.  Over the last years, there has been increasing interest in childhood hypertension and greater recognition that many adult cardiovascular diseases have their origin in childhood. The childhood obesity epidemic had led to an increase in the prevalence of hypertension and its consequences in the young . A recenPediatric hypertensive patients are usually asymptomatic, making this condition frequently misdiagnosed, but may present early manifestations of organ damage: 40% of patients among hypertensive children suffer from left ventricular hypertrophy and increased carotid intima-media thickness, an early marker of atherosclerosis . ChildreAt the time, given the lack of outcome data, the current definition of hypertension in children and adolescents is based on the normative distribution of BP in healthy children. The lack of reliable data on the long-term consequences represents the major limitation of all attempts to define arterial hypertension in the pediatric age. Although it may seem intuitive that a non-physiological situation can lead to long-term damage and the more and more evidence is supported by the literature, it is important to design specific studies in pediatric populations to answer the question. The American Academy of Pediatrics (AAP) revised and published in 2017 new guidelines for the diagnosis of hypertension in children and adolescents, replacing the previous reference values published in 2004 ,6. New cThe aim of our study is to evaluate the impact of new guidelines on diagnosis of hypertension in pediatrics and their capacity to identify the presence of cardiovascular and metabolic risk.We retrospectively analyzed the data of 489 children and adolescents, all Caucasian, admitted to Pediatric Outpatient Clinic of University of Foggia  for overweight including obesity, in the period between February 2008 and December 2013. Overweight was defined as body mass index (BMI) ≥ 85° and <95° percentile and obesity as a BMI ≥ 95° percentile for age and sex, according to the growth curves of the Center for Disease Control .The presence of secondary forms of excess weight or other chronic diseases has been considered a criterion for exclusion. Anamnestic information, auxological data  were collected for all subjects according to standard procedures .Since BMI is gender- and age-dependent, the z-score BMI was calculated for all analyzed subjects, which is a measure completely independent from these variables. According to CDC 2000 standards, the LMS method was used  . The waiSystolic and diastolic blood pressure was obtained for each child. The blood pressure measurement was performed in a seated patient, after at least five minutes of rest, with differential cuffed aneroid sphygmomanometer (auscultatory method) according to the age and constitution of the child. Three blood pressure measurements were taken for each patient and the average value recorded for the analysis ,11.In a first time, absolute values were converted to age-, gender-, and height-specific percentiles, using tables provided by the 2004 National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (2004 AAP) and based on these data, we calculated the blood pressure z-score . The samFor children with abnormal values of blood pressure, second-level clinical-laboratory and instrumental investigations were carried out to exclude secondary hypertension. Only data of children without evidence of secondary hypertension were included into the study. The study was approved by the Ethics Committee of the University Hospital of Foggia.Venous blood samples from each subject were taken in the morning, after at least 10 h of fasting. Blood glucose was determined using the gluco-oxidase method.Total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides were determined using automated enzymatic methods . Insulin was measured by the ELISA method . The HOMA index (Homeostasis Model Assessment) was calculated as an insulin resistance index .The triglycerides/HDL ratio was also calculated as a marker of endothelial dysfunction ,14.® 7, GE Medical Systems, Milwaukee, WI, USA). The level of liver echogenicity was graded according to the ultrasonographic steatosis score [All subjects underwent liver ultrasound examination after a minimum of 10 h of fasting, using a high-resolution ultrasound system  with 95% confidence interval for continuous variables, as percentages for categorical and discrete variables. For the non-Gaussian distribution parameters, instead, the median and the interquartile range were used. The Kolmogorov–Smirnov test was applied to test the hypothesis of normality of the data. The data were analyzed by t-Student test, Mann–Whitney U test, χp = 0.668). Their mean BMI z-score was 2.3 ± 0.49 (range 1.64–5.62), in particular 2.4 ± 0.6 for boys and 2.2 ± 0.3 for girls (p = 0.001).The study population consisted of 489 children, mean age 9.4 ± 2.5 years (range 3–15.8 years): 270 boys  and 219 girls . The diastolic pressure z-score was 0.4 ± 0.79 in the total population: 0.4 ± 0.8 in males and 0.38 ± 0.78 in females (p = 0.531).The median value of systolic pressure z-score in the total population was 0.33 (IQR −0.19–0.89): in male subjects 0.38 (IQR −1.45–1), in female subjects 0.35 : 71.2% values showed normal systolic blood pressure, 13.5% were in the range of higher systolic blood pressure, 12.5% of hypertensive Stage 1, 2.9% of hypertensive Stage 2. Regarding diastolic pressure: normal diastolic values were found in 78.9% 9.2% were in high diastolic range, 10.6% in Stage 1, and 1.2% in Stage 2. In particular: 76.9% systodiastolic values were in normal range 11% were in hypertensive range only for systolic, 7% only for diastolic and 5.1% for both.p < 0.001), in particular from 6.1% to 11% for systolic blood pressure only, from 3.3 to 7% for diastolic blood pressure only, from 3.1 to 5.1% for systodiastolic hypertension range.Then there was a shift from 12.5% to 23.1% of total hypertensive values from the old to the new classification : 28 values reclassified as systolic arterial hypertension, 20 values as diastolic hypertension and 4 as systodiastolic hypertensive state.p = 0.489). With the 2017 AAP classification, instead, 22.3% in I, 20.3% in II, 22.8% in III, 27% in IV (p = 0.647).In particular, by analyzing the population according to quartiles by age, listed in p = 0.009). Of the 52 with abnormal values with new classification, 17.3% suffered from hepatic steatosis. Children with ultrasonographic signs of hepatic steatosis are listed in The subjects recognized has having high blood pressure according to AAP 2017 but classified has normotensive in AAP 2004 were 7/121 in the I quartile (5.8%), 11/123 in II (8.9%), 15/123 in III (12.2%), 19/122 in IV (15.6%). The increase in the percentage of subjects carrying abnormal values according to the quartile by age, was statistically significant at the trend test (p = 0.001), with liver steatosis , but not with HOMA index (p = 0.181) nor with TG/HDL ratio (p = 0.153).Values falling in the hypertensive range according to 2004 AAP showed positive and statistically significant correlation with WtHR , with HOMA index , with liver steatosis  and with TG/HDL ratio . Data on clinical and metabolic parameters of children divided according to AAP 2004 and AAP 2017 blood pressure values are expressed in Values falling in the hypertensive range according to 2017 AAP had positive and statistically significant correlation with WtHR  and, in particular, had a statistically significant association with HOMA index, an insulin resistance parameter, and with the TG/HDL ratio, an indirect endothelial dysfunction index within the same population of overweight or obese children . This asOur data show that even in younger children, those of I quartile with age <7.75 years, we found a percentage of more than 20% of subjects harboring abnormal values, while the percentage was even close to 27% in IV quartile subjects. Since the most frequent form of hypertension in pediatrics is the secondary one, especially in younger children, it is suggestive to imagine that the increase of hypertensive values found in in our population is not only related to the increased sensitivity of the new diagnostic guidelines, but also to the spread of the epidemic of obesity with a consequent change in the epidemiology of hypertension in pediatric age . The useThe strengths of the study were to investigate the correlation of BP values with objective markers of metabolic or vascular dysfunction , not limiting the study to a retrospective observation according to new criteria. Furthermore, the population was ethnical homogenous, allowing to avoid any confusion factor belonging to different prevalence in non-European populations.The major limit is the single evaluation of BP. In effect, a correct diagnosis of BP state  need at least three consecutive evaluations to classify the subject . The ret


Objective: Due to ongoing technical progress, the ultrasonic measurement of blood pressure (BP) as an alternative to oscillometric measurement (NIBP) or the continuous non-invasive arterial pressure method (CNAP) moves further into focus. The US method offers several advantages over NIBP and CNAP, such as deep tissue penetration and the utilization of different arterial locations. Approach: Ten healthy subjects  volunteered in our investigation. In the ultrasonic BP measurement, we differentiated between the directly measured (pulsatile diastolic and systolic vessel diameter) and indirectly calculated variables at three different artery locations on both arms, with two different ultrasound devices in the transversal and longitudinal directions of the transducer. Simultaneously, NIBP monitoring served as reference BP, while CNAP monitored the steady state condition of the arm under investigation. The Moens–Korteweg algorithm (MKE) and the algorithm of the working group of San Diego (SanD) were selected for the indirectly calculated ultrasonic BP data. Main results: With US, we were able to measure the BP at each selected arterial position. Due to the investigation setup, we found small but significant interactions of the main effects. Bland and Altman analysis revealed that US-BP measurement was similar to NIBP, with superior accuracy when compared to the established CNAP method. In addition, US-BP measurement showed that the measurement accuracy of both arms can be regarded as identical. In a detailed comparison of the selected arterial vascular sections, systematic discrepancies between the right and left arm could be observed. Conclusion: In our pilot study, we measured BP effectively and accurately by US using two different devices. Our findings suggest that ultrasonic BP measurement is an adequate alternative for live and continuous hemodynamic monitoring. Ultrasonic blood pressure (BP) measurement has become a major focus in the noninvasive assessment of BP ,12,13,14The physical and physiological approaches for assessing arterial BP using ultrasound have been theoretically evaluated elsewhere. Since the physical principle of the ultrasound method cannot measure blood pressure directly, the data for blood pressure can be calculated based on algorithms. In addition to the established methods according to the Moens–Korteweg equation (MKE) ,17,18,19Ultrasonic transducers display information on the local position. The simplicity of handling ultrasound enables rapid changes in transducer position. Alternatively, several flexible transducers can be positioned over relevant vascular sections. Both principles enable the generation of relevant information on local hemodynamics.TM system also allowed for controlling of a hemodynamic steady state condition along the arm under investigation.The main objective of this study was the extraction of noninvasive information from arterial vessels for the determination of BP at three positions on the left and right arm with ultrasound using two different ultrasound devices. To clarify the universal application, we introduced two ultrasound devices in combination with vessel imaging in the longitudinal and transverse directions. Based on the broad range of algorithms, the MKE ,13 and tThe investigation was conducted in accordance with the Declaration of Helsinki Ethical Principles and Good Clinical Practices, and was approved by the local ethics committee of the University of Lübeck (19-364A). After informed consent was obtained, ten healthy, non-smoking volunteers  were investigated in a relaxed and horizontal supine position on a stretcher under standardized conditions with sufficient access to both arms and without spontaneous movements by the volunteer. The volunteers were asked to abstain from alcohol, caffeine, and taurine as well as intense physical activity for 4 h prior the experiments.TM  were placed on the first arm  BP measurements with the cuffs at the UA and as well at the finger site. After removing the CNAP cuff at the UA, the examiner turned the arm a little outwards and started the examination with the ultrasound devices, in each case with the transducer in the longitudinal and transversal directions, and at the three designated positions. At the end of the examination on the first arm, BP was measured three times again via NIBP, controlling the steady state conditions, and data were stored with the Dräger Infinity Monitor. The same examination was repeated on the contralateral arm.ECG, pulse oximeter and CNAPThe test systems involved two ultrasound devices: a Philips iU22, Transducer L17-5 (17 MHz linear)  with software package 6.3.7.745, and a Siemens Acuson S2000, Transducer 14L5 (14 MHz linear)  with the software package 400.1.031; both had a frame rate of approximately 30 Hz when using B-mode. The ultrasonic assessment was carried out by a single experienced examiner in order to reduce examination-related errors. Data were stored in a video format, followed by further offline processing.The noninvasive reference measurements for BP were discontinuously performed with a calibrated oscillometric device and manual data acquisition.TM SmartPod®, and additionally with digital data recordings in near-real time using data software . The beginning and end of the ultrasonic examination phases were marked accordingly. This enabled an almost simultaneous evaluation of the recorded (with CNAP) and generated (with US devices) curves.The control for steady state conditions during the examination of one arm included visual and continuous monitoring via Dräger Infinity and CNAPCNAP is a method for noninvasive and continuous BP measurement. For this purpose, two finger cuffs are connected to an optical unit. The inflowing blood volume to the finger is kept constant by the cuff and only the pressure pulse is assessed photoplethysmographically. Calibration is performed on the ipsilateral UA using the oscillometric method. The time frame for recalibration can be modified to a maximum of up to 30 min. A calibration can be initiated autonomously by the device during use if a systematic difference is measured between both finger cuffs. This function was switched off for our experiments, in order to have the maximum time frame available. The main advantage of CNAP is the visualization and recording of the arterial BP curve.The test and reference systems NIBP and CNAP are approved medical products and have a CE mark.Ultimately, the acquisition of 24 data points per test subject resulted in a total of 240 data points for all ten volunteers. At each data point at least 10 to 12 s by ultrasound were recorded in parallel by CNAP and evaluated offline. During the measurement phases on one arm, a prerequisite was that the BP remain nearly constant.Ultrasound data acquisition depends on the examiner and the procedure. Timepoints for each measurement were recorded in the reference system (CNAP). The BP (NIBP) was oscillometrically measured three times at the beginning and at the end of each examination, first on the left arm and then on the right arm. Times and measured values were then logged.® SPSS® Statistics, Version 27 for Windows, Munich, Germany). This also included estimates for the variance between subjects and residual variance within a subject when the experimental conditions were all the same. The normal distribution was tested with the Q-Q plots of the residuals.We worked with a complete factorial examination plan on ten subjects, with the following fixed factors or levels: manufacturer (Siemens | Phillips), arm (left | right), alignment of the transducer , position of the vessel section (AA | AB | AR). For the subjects, random effects came into the model according to the assumption that individual expected values follow a normal distribution. We estimated the expected values under the various test conditions, their differences, and the 95% confidence intervals from all measurements simultaneously using the mixed model for the analysis of variance By inserting the Young’s modulus of elasticity , as well as the vessel expansion (Δr):The By adding the diastolic BP value from the reference NIBP, the BP can be calculated according to:The derivatives of the formulas are essentially taken from the works of ,13,20,21The algorithm of the working group of San Diego extracts the values for the BP calculation by measuring the change of the cross-section and, assuming a rotationally symmetrical vessel, thereby derives the change in vessel diameter. Further assumptions are that the vessel is elastic or only slightly changed atherosclerotically, and that the blood viscosity is almost constant. The systolic blood pressure is calculated with:In this algorithm, α is described as a rigidity coefficient:SP and DP are added from the NIBP reference.Algorithm  is derivThe basis for the evaluation were video segments of approximately 10 – 12 s in length and with 30 frames per second .Investigating the US devices, we differentiate between the directly measured and the indirectly calculated variables. The first focus was the directly measured variables as an indicator of the displayed precision and thus of the downstream accuracy of the calculated data. The most sensitive parameter to be emphasized is the change in diameter, d (mm), between systole and diastole . However, regardless of these findings, a difference in hemodynamics between the left and right arm is visible at position AB and AR, as these are captured both by the alignment and the US systems.Comprehensive and systematic deviations between the examinations with both US devices and the alignment of the transducers in the longitudinal and transversal directions, both for the right and for the left arm and in relation to the selected positions, can be ruled out. There are minor but systematic differences in both the alignment of the transducer and in the US systems, which are most evident in the differences in the diameter  and the algorithm of the working group of San Diego (SanD) were selected as representative.The main results of the present study are that both US systems with transducer alignment in longitudinal and transversal directions generated similar information to NIBP. Furthermore, the ultrasonic method can be applied at three different positions on both arms with congruent results. Both algorithms used to determine BP, MKE and SanD, provide reproducible data with an accuracy that is superior to the validated CNAP method when compared to NIBP.S-D of the right arm shows a different course in contrast to the left arm . A parallel image recording of B-mode and PW-Doppler has not yet been implemented by default in the software of the US device manufacturers, as favored by Rabben [PWV in the present study has been calculated by further application of the MKE and the oscillometrically measured BP. If the parallel recording becomes routinely available, the PWV calculation can be implemented directly in the ultrasonic measurement of BP. In addition, it is possible to obtain information about blood flow using specific spatial dimensions, which provides the possibility of further measurement by US.Simultaneously, PW Doppler analysis can be used to measure flow velocity and to determine the local pulse wave velocity  is possible. These downsides of rigid handheld US transducers have led to the development of flat, flexible, and stick-on US pads . US padsThe aforementioned disadvantages and possible sources of errors cannot be entirely ruled out by an experienced investigator, but were largely avoided. Since even slight exertions of pressure by the transducer can lead to changes in the pulse curve, we continuously monitored acute BP alterations with the CNAP system. The simultaneous CNAP measurement showed no acute ipsilateral reduction in the target variable BP due to arterial compression by the US transducer throughout the experiments.The wide range of US-based methods for BP measurement can be divided into four groups:PWV, which depends on the blood pressure and blood volume flow, as well as the elasticity of the examined vessel and the viscosity of the blood.The first group works according to the physiological principles of Moens  and KortBy simplification of some assumptions and paradigms of the first group , the second group calculates BP through variables which can be measured directly in B-mode . The proThe algorithms of both groups require external calibration by at least one systolic and/or diastolic blood pressure value.β. Supposing that the stiffness index β is constant in the early systolic period, several variables can be extracted, ultimately resulting in the “level of diastolic blood pressure” value. The working group of Zakrzewski [The third group contains the next level of simplification, measurement without an external calibration value. Nabeel  uses twokrzewski  applied As a fourth group, one might consider continuous measurement via flexible sensors in several positions ,9,12.PWV. The fact that PWV is not measured directly but rather indirectly through repeated application of MKE, and thus calculated from the NIBP, shows a clear limitation of our study. The main reason for this limitation can be found in the US devices used in our experiments. Parallel measurement of the local PWV by US (B-mode plus Doppler-mode) offers a promising approach and has already been confirmed experimentally [PWV via plethysmography in parallel to US and integrated this data in an algorithm derived from the Bramwell–Hill model.The MKE and SanD algorithms require calibration through a direct measuring method. For investigation on healthy volunteers, noninvasive, oscillometrical BP measurement is the method of choice, and was therefore used as reference in the present study. The NIBP defines the limits of the US-based BP measurement. While the values of the directly measured BP are included in the SanD algorithm, the application of MKE requires additional integration of the mentally , but is mentally , who meaNothing is as divergent as the definition of BP on the one hand and the methods for BP measurement in different areas of application on the other hand ,34.The physiological derivation on which BP values are measured is controversially discussed. The systolic BP is subject to modulation by the cardiac stroke volume and elastic properties of the vessel . The MAPThere are three possible clinical scenarios for BP measurement: First, the hypertensive patient with associated cardiovascular diseases; second, the normotensive patient; and third, the hypotensive patient, which further includes patients who are undergoing operations with general anesthesia. The detection of BP drops and the duration of hypotonic phases is essential to sufficiently avoid organ damage in anesthetized patients. Quick adaptation to the patient’s individual BP during anesthesia reduces the risk of organ dysfunction . Hence, The CNAP system provides BP data with “acceptable” ,40, “comCNAP is a noninvasive and continuous measuring device, and currently fills the gap in BP monitoring. Due to the above-mentioned limitations, it might support the perioperative BP management for anesthetized and hemodynamically stable patients, and can potentially reduce severe periods of hypotension. The CNAP monitor provides a BP curve in near real time and therefore allows the assessment of beat-to-beat performance.During our experiments, the BP curve of the CNAP system was visually checked for consistency. In addition, continuous recordings of the CNAP data were checked offline and evaluated to the corresponding data points. In this signal analysis, sudden alterations  of the CNAP system occurred in 21 of the 240 measuring points. To ensure a balanced analysis, these data points were excluded from analysis. Despite this adjustment, CNAP differed from NIBP on a larger scale see also , i.e., CBP monitoring during anesthesia is essentially based on NIBP ,47,48,49In the present study, the oscillometric BP measurement on the upper arm was chosen as a reference. To improve the accuracy of NIBP, the measurement was repeated three times and the mean value was regarded as the reference value. This further allows a statement about the consistency during the ultrasonic examination, given that the measurement is repeated on the same arm after the examination and the patient is in a steady position.With this set up, we did not choose the “gold standard” , but ratThe use of NIBP to estimate intra-arterial pressure is controversial. Invasive intra-arterial pressure measurement represents the reference method for critically ill patients, since it provides a continuous BP monitoring . HoweverThe main point of criticism is the variability of measurement accuracy. However, this applies equally to other BP measuring methods, intra-arterial measurement as well as auscultatory and oscillometrical measurement. This variability in measurement accuracy has been the subject of review articles . It shouOur results suggest that US-based methods are applicable for BP measurement in healthy subjects. Further clinical studies are needed in order to confirm our findings.For our study we examined discontinuous BP measured via ultrasound, and used NIPB as a reference. Since we used CNAP as a continuous reference in measurement along the investigated arm, we encountered minor protocol violations due to CNAP calibration. This ultimately led to the loss of 21 of 240 data points, which were excluded from analysis.The behavior of CNAP in this regard is known. Particularly in critical BP changes or differences between both finger cuffs, the system usually starts a complex and long-lasting oscillometric calibration with the upper arm cuff, and thus interferes with simultaneous BP assessment. The measurement accuracy of this method is somewhat reduced compared to the discontinuous NIBP measurement.PWV for calculating the BP with MKE, a second approach by MKE with NIBP was required. This would certainly have a systematic error as a consequence. However, the data presented suggests that our approach is applicable. For future clinical experiments, it should be considered that direct measurement of the local PWV might show more stable results.Since we needed the The limitations in the use of NIBP as a noninvasive reference for BP will continue to be a focus of discussion in future studies. Both NIBP as well as the intra-arterial and invasive BP measurement have pros and cons. In order to solve the discussion, US-based methods could bring more information.A small cohort of ten subjects undergoing the examination has several statistical limitations.The first limitation is the assumption of a random distribution of the effects through the selection of the subjects. Secondly, the high number of data points, which is responsible for a quickly visible significance in the presence of only minor clinical differences or abnormalities.Finally, the Bland and Altman analysis as a recognized method for comparing measurement accuracy between two methods is limited if clear trends can be found. We introduced an extended analysis at this point, which also allows a direct assessment through the visual graphical representation of all data points.Two disadvantages of the US and the algorithms we used are the exclusion of elasticity of the vascular wall and the viscoelasticity of the blood. The assumption is that the change in the elasticity of the vascular wall in advancing arteriosclerosis as well as the variable of the viscoelasticity of the flowing blood are only rudimentarily considered in the algorithms. In modern patient BP management prior to and during operations and interventions, certain changes in viscoelasticity in case of blood loss with therapeutic volume application and significantly reduced number of erythrocytes and hemoglobin concentration may occur.It can be assumed that in future clinical investigations and based on further technical or software developments data from US imaging, both for measurements in B-mode and for Doppler signals, could also be extracted and incorporated into the resulting analysis in a modulating way.The following results were obtained from this study on healthy volunteers without known cardiovascular diseases.The determination of BP with ultrasound is successful regardless of the US system used and the alignment of the ultrasonic probe. The CNAP device is a general reference method for measuring continuous BP in both arms.The algorithms MKE and SanD are calibrated with the NIBP values. These form a kind of framework and define the limits. It is therefore understandable that the data according to MKE and SanD are within these limits. In this study setup they overestimate the diastolic and underestimate the systolic BP.The CNAP calibration with the upper arm cuff requires a maximum 30 min interval. A shorter calibration time could not be set up due to the course of the investigation. This may generate a systematic error by using the upper arm cuff, both per se as well as through the long calibration interval.PWV, which can be found squared in MKE. This point is clinically relevant when BP drops significantly. In this area of a hypotonic circulatory reaction, the local PWV, if measured directly, can then be used as a further variable, and additionally provide a reliable quantification of the hypotension.A relevant difference between MKE and SanD is the variable of the Relevant variables generally find entrance in these algorithms regarding the vascular dimensions, blood flow and pulse waves, and associated velocities. The flow characteristics of the blood in connection with the blood cells in it and the associated flow profiles are also relevant, but are often neglected in the analysis.In addition to a continuous measurement that can only be obtained on a calm level, information about the “dynamic cardiovascular status” will be necessary in the future. This means the application at a reference level to the standard approach (upper axillary fold) and under the conditions of movement and physical exertion. This is a challenge for the measurement process with regard to artifact reduction and signal quality. At the same time, however, the clinical aspect of measuring BP in the event of a significant reduction in BP (severe hypotension) and its use in young and youngest patients must also be taken into account.An increasing subject of clinical considerations is the complexity of the status of central and peripheral vessels, to be emphasized as a mismatch of stiffness, elasticity and increasing resistance . Since uUltrasonic transducers only display information on the local position. The simplicity of handling ultrasound transducers means that rapid changes in position can be set up, or alternatively, that several flexible transducers can be positioned over the relevant vascular sections. Both considerations have in common that the possibility is shown here to generate relevant information on local hemodynamics.PWV and intravascular blood flow in the vessel at the measurement site can provide clinically relevant information. Only if this can be achieved can the recommendation be made to use US-based methods for BP determination. The advantages far outweigh the previous disadvantages. These disadvantages can be transformed into clinically applicable advantages through technical and methodological advancements.The value of US-based methods and of the algorithms becomes relevant when data can be measured in patients during the onset of severe hypotonic phases with and without intravascular volume depletion. It is during these phases that measurement of local This pilot study of BP measurement with ultrasound delivers insight into several selected methods: two clinical standard devices, alignment of the transducer, and the two algorithms used. Due to the large amount of data in ten subjects, we found small systematic differences with slight confidence intervals. Both US-based methods show value in the range of the NIBP and CNAP system, with superior accuracy compared to CNAP. Having in mind the perspective of making ultrasound BP measurements at selected, hemodynamically relevant sites, it seems to be a possibility in the future to enable continuous and noninvasive monitoring of essential hemodynamic parameters.


Diabetic kidney disease (DKD) is a major long-term complication of diabetes mellitus (DM). Given the paucity of data on DKD in Jordan, we aimed to evaluate the prevalence, characteristics and correlates of DKD in Jordanian patients with type 2 DM.This cross-sectional study included 1398 adult patients with type 2 DM who sought medical advice in the endocrinology clinic between March and September 2019. Demographic, clinical and laboratory data were reviewed. DKD was defined as reduced eGFR, and/or albuminuria. Three regression models were constructed to identify factors associated with CKD stages, albuminuria and DKD.p < 0.01; OR: 1.1, 95% CI: 1.01–1.2; and OR: 0.98, 95% CI: 0.97–0.99, p < 0.01 respectively). Metformin and renin-angiotensin system blockers were negatively associated with albuminuria and chronic kidney disease stages (p < 0.01).Overall, 701 (50.14%) patients had DKD, with a median age of 59.71 ± 11.36  years. Older age, high triglycerides, and low high-density lipoprotein were associated with DKD (multivariable odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01–1.03, Our study demonstrated that approximately one half of patients with type 2 DM had DKD. Further studies are necessary to understand this high prevalence and the underlying factors. Future research are needed to assess implementing targeted community-based intervention. Worldwide, diabetes mellitus (DM) is a growing healthcare challenge and imposes a heavy burden on public health . DM typeDiabetic kidney disease (DKD) is a major long-term complication of DM type 2 and is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) worldwide . AlthougThere are marked racial differences in the epidemiology of DKD, which could be partially explained by the differences in health care services and environmental factors such as dietary intake and smoking . StudyinAlthough the prevalence of DM type 2 in Jordan has been shown to be on the rise [This cross-sectional study aimed to assess the prevalence of DKD among patients aged >18 years who were diagnosed with type 2 diabetes and sought medical advice at the University of Jordan Hospital, Endocrinology clinic, between March and September 2019. We excluded patients with missing data , ESKD on dialysis, and other possible causes of CKD or proteinuria. Informed consent was obtained from all participants. This study was approved by the University of Jordan Institutional Review Board and followed the institutional and/or national research committee’s ethical standards and the principles of the World Medical Association Declaration of Helsinki.Patients diagnosed with DM type 2 were identified according to patients’ medical records and verified during their clinic visits by an assigned research assistant. The following data were collected via face-to-face interviews and referral to medical charts by a trained research assistant: medical history including hypertension, myocardial infarction, coronary artery disease, heart failure, stroke, and the onset of diabetes; current diabetes status with complications such as retinopathy, peripheral neuropathy, and cardiovascular disease as reported during the interview; data on glycemic control, i.e., latest values of fasting blood glucose and hemoglobin A1c (HbA1c); and smoking status. Current medication usage, such as antidiabetics, antihypertensives, lipid-lowering agents, and other medications, taken by the patients was also reviewed. A trained research assistant performed the following measurements in the office: blood pressure  and we considered abnormal blood pressure reading >140 mmHg systolic and >90 mmHg diastolic, height, weight, and waist circumference. We also collected data on HbA1c, fasting blood sugar, fasting lipid profile (if available) as we considered abnormal results as following: High density lipoprotein (HDL <38 mg/dl in men and <50 mg/dl in women) and high triglyceride >160 mg/dl and Low density lipoprotein (LDL) >100 mg/dl, and serum albumin levels up to 3–6 months from the clinic visit using the latest blood test results when available. We assessed the kidney function using serum creatinine and urinary albumin excretion measurements on two occasions at least 3 months apart. We excluded patients who did not have 2 readings of any of the kidney function assessment within 6 months of the assigned clinic visit.The estimated glomerular filtration rate (eGFR) was determined for each patient using a standardized serum creatinine level and the Chronic Kidney Disease Epidemiology Collaboration formula. Increased urinary albumin excretion was diagnosed as 1) microalbuminuria, if the urinary albumin to creatinine ratio (ACR) was ≥30 and ≤300 mg/g or the protein to creatinine ratio (PCR) was >0.150 and <0.500 g/g or 2) macroalbuminuria, if the ACR was ≥300 mg/g or the PCR was >0.500 g/g, and 3) albuminuria indicated patients with either micro- or macroalbuminuria , 8. Urin2, and/or increased urinary albumin excretion, ≥30 mg/g creatinine that persisted for ≥3 months in the presence of longstanding diabetes and exclusion of other causes of CKD.DKD was defined as a reduced eGFR, <60 mL/min/1.73 mAll analyses were performed using STATA . Categorical variables are presented as percentages, while continuous variables are presented as the mean ± standard deviation.p-values of ≤0.05 were considered to indicate statistical significance.Differences in sociodemographic characteristics, past medical history, comorbidities, and medications among patients with or without evidence of DKD were assessed using the chi-square test for categorical variables and Student’s t-test continuous variables. Three regression models were constructed: (i) to identify variables associated with CKD stages, a multistage ordinal logistic regression analysis was used, (ii) to assess variables associated with the degree of albuminuria, a multistage ordinal logistic regression analysis was used, and (iii) finally, a binary logistic regression was used to assess the variables associated with an increased risk of DKD. The confidence interval was set at 95%, and Among 1652 patients, 1398 patients met our inclusion criteria. The median age was 59.71 ± 11.36 years, there were 573 men (40.99%) and 825 women (59.01%), and the median duration of DM type 2 was 10.42 ± 7.99 years. Further, 970 (69.38%) patients in our study population were hypertensive with a mean systolic blood pressure of 135.53 ± 21.37 mmHg, and the mean diastolic blood pressure was 77.72 ± 13.61 mmHg. A body mass index (BMI) of >30 was identified in 66% of the population. The mean HbA1c level was 7.71% ± 1.60%. Retinopathy was documented in 477 patients (34.12%). These baseline characteristics of our study population are summarized in Table 2.We found that 701 (50.14%) patients had DKD, 625 (44.7%) had albuminuria, and 268 (19.17%) had CKD with an eGFR of <60 mL/min/1.73 mp < 0.001) . We also found that patients with DKD were more likely to have had used insulin, metformin, and renin-angiotensin system (RAAS) blockers (p < 0.01) than were those without DKD (p < 0.05) p < 0.001p < 0.0001). DKD was also associated retinopathy and neuropathy (p < 0.01).On univariate analysis comparing patients with DKD to those without DKD, we found age >60 years, longer duration of diabetes, higher HbA1c of >7%, and hypertension were correlated to DKD (p < 0.01). Retinopathy, neuropathy, high triglyceride levels, and low high-density lipoprotein (HDL) levels were also correlated with DKD . Metformin was negatively correlated with DKD . The use of insulin, beta blockers, calcium channel blockers, and diuretics was also significantly associated with DKD  . It was also strongly associated with the use of beta-blockers, diuretics, and calcium channel blockers . We observed that RAAS blocker and metformin use were negatively associated with advanced CKD stage  . Hypertension and high triglyceride levels were associated with higher albuminuria levels . The use of Metformin and RAAS blocker was negatively associated with the presence of albuminuria . The serum albumin level was associated with the degree of albuminuria  (p < 0.01) , diabetic microvascular and macrovascular complications, and dyslipidemia. Metformin and RAAS blockers were associated with a lower degree of albuminuria and less advanced CKD.Our results were in line with the reported prevalence of DKD in the Middle East (33–54.1%) , 11. TheThe prevalence of DKD increases with age and is more evident by a low eGFR than by albuminuria. This can be explained by the physiological decline in renal function with age, which is associated with a gradual decline in eGFR . This obOur results showed that patients who reported using metformin or RAAS blocker had a lower risk of developing DKD and proteinuria. Metformin is the preferred treatment option for DM type 2 and we found that metformin was negatively associated with DKD, albuminuria, and advanced CKD, consistent with most of the observational studies reporting that metformin is associated with reduced progression to ESKD in type 2 diabetes patients with DKD. However, the reason for these observations remains unknown . In mostClinical trials have also demonstrated the beneficial effects of RAAS blockers in delaying the progression of DKD. Two large randomized long-term trials, the Angiotensin Antagonist Losartan study  and the 2 without evidence of albuminuria.Albuminuria is considered the first clinical symptom of DKD and is traditionally used as a screening test for DKD. However, mounting evidence suggests that the traditional concept of the natural history of DKD has changed, and a considerable proportion of adult diabetics are normoalbuminuric despite having a low eGFR . The preThe association between hypertension and albuminuria is well established but the mechanism is still controversial. It is thought to be an endothelial dysfunction, which is strongly associated with increased cardiovascular risk, and causes renal manifestation. Hypertension is reported in approximately 70–80% of DM type 2 at the time of diagnosis and known to exacerbate diabetic nephropathy . Our stuThe association between dyslipidemia and the development of DKD was investigated in several studies, and many epidemiological studies demonstrated an association between diabetic dyslipidemia and DKD . Post-hoThere were several limitations to this study. First, the retrospective and the cross-sectional study design introduced recall bias and precluded temporal evaluation of risk factors and outcomes of interest. Therefore, a cause-effect relationship cannot be concluded. However, the data obtained by personal interviews and referring to medical charts minimized the recall bias and improved the data quality.Second, our study was performed in a tertiary medical center and might not reflect the status-quo of diabetes in Jordan. Nevertheless, this tertiary center provides service to a wide range of patients with different socio-economic backgrounds all over Jordan. Additionally, given the Jordanian population’s unique composition, our findings can be generalized to the middle East. Third, this study had a small sample size for a common disease and did not examine the onset and the course of DKD in the population as the baseline readings of albuminuria and renal function at the time of diagnosis were not available.We found that more than half of the patients with DM type 2 had DKD with approximately one-third were at moderate risk of major adverse events. DKD was correlated to older age, longer duration of diabetes, the presence of diabetic complications, and dyslipidemia. In addition, patients who were using metformin or RAAS blocker had a lower risk of DKD and proteinuria. Albuminuria adds valuable information regarding the prevalence, epidemiological characteristics, and risk factors of DKD. Prospective studies with long follow-up duration are needed to understand the natural course of DKD and future research should also focus on the effect of raising awareness about DKD in patients with DM type 2 to aid in implementing a more targeted community-based intervention.