Studies on the effect of dietary protein intake (DPI) on chronic kidney disease (CKD) progression, along with the potential hazard of protein-energy wasting (PEW), are scarce. We evaluated the association between DPI and kidney function both cross-sectionally and longitudinally, particularly emphasizing the role of PEW, in a large-scale, observational, multicenter, prospective study. We enrolled 1572 patients with non-dialysis CKD between 2011 and 2016. CKD progression was defined by a >50% estimated glomerular filtration rate (eGFR) decrease, serum creatinine doubling, or dialysis initiation. A Cox proportional hazard regression analysis was conducted. During the mean follow-up period of 41.6 months, CKD progression was observed in 296 patients. Cross-sectionally, increased DPI was significantly associated with increased eGFR. Similarly, increased DPI tertile was significantly associated with increased renal survival in a Kaplan–Meier curve analysis. In the multivariate Cox proportional hazard regression analysis, the statistical significance of the DPI tertile group in CKD progression was lost when PEW-related variables were added as covariates. In penalized spline curve analysis, the adjusted odds ratio of PEW significantly increased as DPI decreased. DPI, per se was not a major determinant of CKD progression. An intimate association between reduced DPI and PEW may be a more important predictor of CKD progression than DPI. Since most uremic toxins are waste products of protein metabolism , a low-pPatients with CKD are exposed to a high risk of developing syndromes of muscle wasting, malnutrition, and inflammation. Recently, the term protein energy wasting (PEW) was suggested to describe this syndromic uremic malnutrition . As CKD Unintentionally low DPI is a key component of PEW , suggesthttp://www.clinicaltrials.gov) [The KNOW-CKD is a multicenter prospective cohort study in Korea that enrolled 2238 patients with non-dialysis CKD stages 1–5 between February 2011 and January 2016. The detailed design and methods of the KNOW-CKD were published previously  . The proals.gov) . CKD andals.gov) .Of the 2238 patients, 319 were excluded; these included 247 with missing 24-h urine creatinine (Cr), 55 with missing 24-h urine urea, 3 with missing data to calculate the Cr index (CRI), 10 with missing serum albumin, and 4 with missing cholesterol. Of the 1919 eligible patients, 347 were further excluded because of incomplete 24-h urine collection. Therefore, 1572 patients were included in the final analysis.2). Serum Cr levels were measured at a central laboratory . Completeness of 24-h urine collection was ascertained by CRI ≥ 0.7 [2 as the optimal value [Clinical data, including detailed demographic information and baseline laboratory results, were extracted from the electronic data management system (PhactaX). Body mass index (BMI) was calculated as weight (kg) per square of height .Hypertension was determined by physician diagnosis, systolic blood pressure (BP) ≥ 140 mm Hg or diastolic BP ≥ 90 mmHg, or treatment with antihypertensive drugs. Diabetes was determined by physician diagnosis, fasting glucose ≥ 126 mg/dL, or treatment with insulin or oral antidiabetic drugs. Alcohol drinking was defined as drinking alcoholic beverages more than once a month. PEW components were created based on the International Society of Renal Nutrition and Metabolism diagnostic criteria . An expeTertiles of DPI were <0.93 g/kg/day in the first tertile, 0.93–1.16 g/kg/day in the second tertile, and ≥1.16 g/kg/day in the third tertile, respectively. The main outcome was the development of renal events, which were defined by a decrease in eGFR of >50% from the baseline values, doubling of serum Cr, or dialysis initiation, and these were detected annually.The following were the variables with missing values: current smoking , alcohol drinking , hypertension , diabetes , causes of CKD , bilirubin , fasting plasma glucose , hemoglobin , urine protein-to-Cr ratio , and high sensitivity C-reactive protein .p-trends were analyzed for normally distributed continuous variables using a linear-term of the one-way analysis of variance (ANOVA); for non-normally distributed continuous variables, Jonckheere–Terpstra tests were used; and for categorical variables, a linear-by-linear association was used. Differences were analyzed using a Bonferroni post hoc analysis of one-way ANOVA for normally distributed continuous variables, Mann–Whitney U tests for non-normally distributed continuous variables, and chi-square tests for categorical variables. Death before renal events was treated as a censored observation. For the survival analysis, the Kaplan–Meier curve was employed, and the statistical significance was calculated using the log-rank test. The hazard ratio (HR) and its 95% confidence interval (CI) for renal events was assessed using the Cox proportional hazard regression analysis. The assumption of proportional hazard was tested by log minus log plot for categorical variables and interaction analysis with time covariate using time-dependent Cox regression for continuous variables. Since DPI, blood urea nitrogen (BUN), eGFR, bilirubin, serum albumin, and hemoglobin did not meet the proportion hazard assumption, categorical versions of these variables  were used instead for the Cox proportional hazard regression analysis. Odds ratios (OR) and 95% CI were calculated using the logistic regression analysis. In multivariate analyses, covariates were chosen based on their clinical and statistical relevance: age, sex, current smoking, alcohol drinking, hypertension, diabetes, causes of CKD, UPCR, BUN, eGFR, bilirubin, hemoglobin, and hsCRP. The multivariate generalized additive model (GAM) for Gaussian distribution [p value of < 0.05 was considered statistically significant. All analyses, unless otherwise specified, were performed using SPSS version 22 .The distributions of continuous variables were evaluated using histograms and Q-Q plots. Two variables, hsCRP and UPCR, were not normally distributed. Normally distributed continuous variables are expressed as mean ± standard deviation, non-normally distributed continuous variables as median (interquartile range), and categorical variables as percentages. ribution  was adap2, and the median UPCR was 0.47 g/g Cr. The stages of CKD were 17.0% in stage 1, 20.2% in stage 2, 16.3% in stage 3a, 21.5% in stage 3b, 19.8% in stage 4, and 5.2% in stage 5. The mean DPI of the patients was 1.1 g/kg/day. The mean values of BMI, estimated SMM, serum albumin, and cholesterol were 24.5 kg/m2, 28.3 kg, 42.1 g/L, and 4.5 mmol/L, respectively. The overall prevalence of PEW was 6.8%. During the mean follow-up period of 41.6 months, 296 patients (18.8%) experienced renal events, 172 patients (10.9%) had >50% eGFR decline or serum Cr doubling, and 235 patients (14.9%) had dialysis initiation , hypertensive nephropathy (20.7%), glomerulonephritis (32.9%), and other causes (23.3%). The mean eGFR was 54.6 mL/min/1.73 mitiation . The perThe baseline characteristics of the DPI tertile group were compared . As the p < 0.001). This was confirmed in multivariate Cox proportional hazard regression analysis (p = 0.02). However, the statistical significance of the DPI tertile group on renal event development was lost when variables related to PEW were added as covariates (Model 2). In the sensitivity analysis according to the various PEW conditions , whereas DPI was not directly associated with serum albumin and cholesterol. These results suggest several clinical meanings. First, in an ordinary outpatient clinic, decreased DPI may not be a sign of good LPD; rather it may be a red flag of the beginning of PEW in patients with CKD, which finally can deteriorate kidney function. Second, to build up patients’ body mass, increased DPI may be a good treatment option without fear of CKD deterioration, at least in Korean patients with CKD. Finally, increased DPI only may not be effective to increase serum levels of albumin and cholesterol, suggesting a much more complex pathogenesis in the derangement of biochemical parameters.This study has several limitations. First, the choice and definition of PEW components in this study did not strictly follow the International Society of Renal Nutrition and Metabolism diagnostic criteria . HoweverIn conclusion, DPI per se was not shown to be a major determinant of future development of renal events. Instead, PEW was associated more with CKD progression. Therefore, clinicians should cautiously interpret the meaning of reduced DPI because this can be the red flag of PEW, particularly when patients are not on well-organized LPD programs. Future studies are necessary to confirm our study results.


The Constant score (CS) is one of the most frequently applied tools for the assessment of the shoulder joint. However, evaluation of strength is not standardized leading to potential bias when comparing different studies.Seventy-six patients with fractures of the proximal humerus undergoing open reduction and internal fixation (ORIF) were assessed using standardized CS strength measurements at the deltoid muscle insertion and at the wrist in three different arm positions. Variation coefficients were evaluated for each patient and position.Forty women (57%) and 36 men (43%) were examined 96 months in mean after ORIF. We could state a maximum of 105.3 N difference if measurements were performed at the wrist or the insertion of the deltoid muscle in 90° forward flexion on the injured arm . The lowest variation coefficient of the three performed measurements could be stated at the deltoid muscle insertion in a 90° abduction position in the scapula plane (6.94 ± 5.5).Following our study results, different positions of force measurement can change the total CS by a whole category (e.g. “very good” to “good”). We recommend performing the measurement at the insertion of the deltoid muscle in a 90° abduction position in the scapula plane. Otherwise, even in the non-injured, it is hard to reach a “normal” shoulder function, based on the CS. When using the CS as outcome parameter, authors must give detailed information about the force measuring and use an exact measuring device. Rehabilitation of shoulder function after conservative or operative therapy is essential for patients and the preservation of individual independence. For that reason, numerous scores are used to evaluate post-interventional results. These scores often refer to both, objective measurements and subjective patient perception. Accordingly, one of the most commonly used scores is the Constant Score (CS) –3.The CS was originally designed to assess shoulder disorders in general by combining subjective and objective measurements such as pain 15 points), activities of daily living (20 points), strength (25 points) and the range of motion 40 points) [0 points  points, The primary aim of this study was to evaluate results of the different arm positions for the force measurements mentioned in several standardized CS protocols , 10, 14.The study includes data of 191 adult (age > 18) patients who underwent surgical treatment of proximal humeral fractures using fixed angle plate osteosynthesis at the BG Trauma Center - University Hospital Tübingen, Germany. Seventy-six patients were re-examined after surgery and demonstrated bony union (lost to follow up 60.51%). Exclusion criteria for this study were the change of therapeutic concept of an anatomical reconstruction of the humeral head during the follow-up period (e.g. revision surgery with arthroplasty), additional injuries of the shoulder/upper extremity of the ipsi- or contralateral arm, non–shoulder-related severe comorbidities (e.g. dementia) and loss of contact due to death or relocation. All follow-up patients could at least abduct the arm in a 90° position. These results were published by Bahrs et al. in 2015 [The CS is a multi-item 0- to 100-point score (high scores indicate a high level of function) with 10 items, which are half subjectively measured (0 to 35 points) and the other half objectively (0 to 65 points) .A score between 86 and 100 points is a “very good” result. A “good” result is considered as a score between 71 and 85 points. Between 56 to 70 points, patients reach a “fair” result and under 56 points the outcome is considered as “poor” . The objMeasuring points were the distal humeral insertion of the deltoid muscle and the wrist. The different measuring positions were 90° abduction, followed by 90° abduction / 30° anteversion (scapula plane) and 90° forward flexion of the arm. The elbow was fully extended and the hand in pronated position. Force was measured in Newton (N). Patients had to hold the respective arm over a period of 5 seconds. Testing was performed by a doctoral candidate under supervision of a specialist in orthopedic surgery. Mean values were calculated from three measurements with maximal force and a recovery time of 3 min in between.In order to elucidate the best measuring arrangement, we calculated variation coefficients for various possible arm positions and measuring points of the non-injured side of each individual patient in any position. The measuring arrangement with the smallest averaged variation coefficient promises the most reproducible measurements and should therefore preferably be used.p < .05.Statistical analysis was performed using JMP 10.0.0 . Differences between two groups (e.g. men and women) were calculated with the t-test after stating that the data showed normal distribution. The level of significance in the evaluation of the results was recorded with a value of The group included 76 patients, 40 women (53%) and 36 men (47%). Patients were examined at a mean of 96 months (range 74 to 133 months) postoperatively. Mean age was 62 years (range 26 to 90 years) at the time of final follow-up. According to the Neer classification, most of the patients showed 3-part fractures . In 43 patients (57%), plate removal was performed after union at a mean of 11 months after surgery (range 4 to 26 months) (Table p = <.0001). Results of force measurements didn’t show a significant difference regarding the impact of the dominant hand. If the injured arm was the dominant arm, patients could reach a force of 83.4 N (SD ± 42.9 N) in 90 ° abduction in the scapula plane at the wrist. If the non-injured arm was the dominant arm, patients showed a force of 82.5 N (SD ± 34.3 N) in mean (p = .93).Force measurements were performed in all patients of the follow-up group. Patients of the follow –up group could perform a force of 63.8 N SD ± 31.2 N) on average in 90 ° abduction in the scapula plane, measured at the wrist on the operated side. This represented 82.3% of the strength of the non-injured arm on average . Taking the measurement in the same position but at the insertion of the deltoid muscle we could measure 161.8 N (SD ± 83.5 N) at the injured side (Table  N on aveDifferent positions of measuring the force showed very similar results as we compared the reproducibility of three measurements for each position. There was no position with a particularly low variation coefficient Table .Table 3The effect of different arm positions and measuring points on the CS itself showed a wide variation starting from 63.77 N (± 31.4) to 164.81 N (± 79.5) resulting in a big influence on the score ), the difference within the score between each measurement couldn’t be bigger. The fictional calculated maximum difference would have been 44 points in 90° abduction at the deltoid insertion compared to the wrist as measuring point.On average, patients showed 79.0 points  on the operated side based on the CS. Thirty-six patients (46.8%) achieved a “very good” result (86-100Points), 24 patients (31.2%) a “good” (71–85 points), seven patients (9.1%) showed a “fair” (56–70 points) and ten (13.0%) showed a “poor” result (< 56 points). At the non-injured side an average of 89.6 points  was stated. Fifty-eight patients (75.3%) showed a “very good”, 15 a “good” (19. 5%), three a “fair” (3.9%) and only one patient (1.3%) a “poor” result.The aim of our study was to evaluate different results of arm positions and measuring points for force measurements mentioned in several descriptions and publications of the CS. We examined 76 patients with humeral fracture undergoing ORIF. The analyzed data showed a wide range of variation coefficients for the different positions. The achieved force was mainly dependent on whether the measurements were performed at the wrist or the insertion of the deltoid muscle.The investigation technique for the CS was not exactly defined in the original paper. This could be one reason why there are still numerous problems when different studies are compared . In partVariation coefficients for measurement results were, however, very similar for all positions and measuring points and rather high so that no measuring arrangement could be stated as superior in reproducibility and could therefore be particularly recommended.There is also different information about the measuring point. Constant and Murray et al. favored a measurement at the deltoid muscle insertion , 19, wheBalcess-Diaz et al. recently stated, that statistically differences in the CS occur because of age and gender specific differences . Our datBased on our study results, we recommend performing the measurement at the insertion of the deltoid muscle in a 90° abduction position in the scapula plane. It is obvious that even for non-injured people, it is hard to reach a “normal” shoulder function, following the CS. When using the CS as outcome parameter, authors must give detailed information about the force measuring and use an exact measuring device.


Reduced kidney volume (KV) following prematurity is a proxy for reduced nephron number and is associated with the development of hypertension and end-stage renal disease in adults. We investigated whether extreme prematurity affects KV, function, and blood pressure in school-aged children and if nephrocalcinosis (NC) developed during the neonatal period had additional effects.We investigated 60 children at a mean age of 7.7 years: 20 born extremely preterm ), 20 born EPT without NC (NC−), and 19 born as full-term infants (control). We measured KV by ultrasound, collected blood and urine samples to evaluate renal function, and measured office and 24-h ambulatory blood pressure (ABPM).p = 0.018) and lower but normal cystatin C–based glomerular filtration rate compared with control , p = 0.035). KV and function were not different between NC+ and NC− groups. Change in KV in relation to BSA (KV/BSA) from the neonatal period to school age showed significantly more EPT children with neonatal NC having a negative evolution of KV (p = 0.01). Blood pressure was normal and not different between the 3 groups. Fifty percent of EPT had a less than 10% day-to-night decline in ABPM.Children born EPT had significantly smaller kidneys (EPT (NC+ NC−) vs control , Kidney growth and volume is affected by EPT birth with NC being a potential aggravating factor. Circadian blood pressure regulation seems abnormal in EPT-born children. Extreme prematurity interferes with nephrogenesis, leaving each individual with a finite number of nephrons which might increase the risk for reduced functional capacity and the later development of impaired renal function and hypertension –3. SinceNC is defined as the pathological deposition of calcium crystals in the renal parenchyma. The incidence of neonatal NC varies between 7 and 64% depending on ultrasonographic criteria and is highest in the most premature infants . UltrasoNutrition is suspected to have an important impact on early postnatal kidney development and health. Recent research suggests that high protein intake, advocated for better growth velocity for extremely preterm (EPT) infants, might have a disadvantageous effect on the kidney. It has been suspected that this high-risk group could have difficulties in metabolizing the amount of protein given, leading to mild metabolic acidosis and possibly to hypercalciuria . Also, tThe current evidence indicates that neonatal-acquired NC resolves by 50% during the first year of life and to 75% by school age without having an impact on kidney function , 16. HowIn this study, we investigate whether NC developed during the neonatal period in children born EPT has an impact on kidney volume and function at school age. Eventual effects on blood pressure are evaluated by 24-h blood pressure monitoring (ABPM).The study was approved 5by the Ethical Committee at Karolinska University Hospital. Written and oral consent was obtained from all parents and children.We identified 213 infants born before 28 weeks gestational age (GA) between 2008 and 2011 at the Karolinska University Hospital, Stockholm, Sweden , bronchopulmonary dysplasia (BPD) as defined by NIH, acute kidney injury (AKI) defined and staged by the KDIGO guidelines, patent ductus arteriosus (PDA) requiring treatment, sepsis episodes , necrotizing enterocolitis (NEC) Bell stage II or more, surgical interventions for NEC, retinopathy of the premature (ROP) grade III or higher (and or any plus disease), and intraventricular hemorrhage (IVH) or parenchymal hemorrhage as defined by Papile were documented. Small for gestational age (SGA) was defined as a birth weight < − 2 standard deviations (SD) according to Swedish reference data for normal fetal growth .2), body surface area (BSA = 0.007184 × Height0.725 × Weight0.425) [At the visit, patient and parental medical histories, as well as maternal and paternal height and weight, were registered. The same research nurse performed all anthropometric measurements for weight, height, head circumference, and waist circumference on the children, who were wearing light indoor clothing. Height was measured using a wall-mounted stadiometer. Waist circumference was measured midway between the lower rib margin and the iliac crest using a normal measuring tape. Body mass index (kg/mht0.425)  and waisSystolic or BPDiastolic < 10% relative to the diurnal mean value [Office blood pressure was measured in all patients using an automated oscillometric device . After a 30-min rest, three consecutive measurements were taken on the child’s non-dominant arm with an appropriate cuff size (bladder width that was at least 40% of the arm circumference ). We usean value . Hypertean value .Morning urine samples were collected from all study participants and analyzed for sodium, potassium, creatinine, albumin, calcium, phosphate, magnesium and protein HC (α-1-microglobulin) and immunoglobulin G. Sodium and potassium were measured using potentiometry with ion-selective electrodes . Urine phosphate, calcium, and magnesium were measured using photometric technique , and urine albumin was measured using immunochemical and turbodimetric method . Protein HC and immunoglobulin G were measured by immunochemical and nephelometric method .k = 36) as well as the cystatin C–based CAPA formula [Blood samples were taken in 55 patients  after placing a local application of a topical anesthetic cream containing 2.5% lidocaine and 2.5% prilocaine . Blood samples were investigated for plasma sodium and potassium using potentiometry with ion-selective electrodes ; calcium, phosphate, alkaline phosphatase, creatinine, and urea using photometric technique; and cystatin C using immunochemical and turbidometric method . For the estimation of GFR, we used the simplified Schwartz formula  was performed by pediatric radiologists using a Siemens S 2000 with a 6C2 curved transducer  at an average age of 36 weeks postmenstrual age following local guidelines. All images from the neonatal period for the 41 included children were reviewed by a senior pediatric radiologist in 2018. Diagnosis of NC was confirmed in 39 of the 41 cases. In each group (NC+/NC−), one patient was misdiagnosed and moved to the opposite group. Kidney volume for the neonatal period was calculated in 36 out of the 41 patients using the equation for an ellipsoid described elsewhere  and exprUltrasound of the kidneys at school age visits was performed by a single experienced user. All investigations were performed with a Philips EPIQ 7G with SW1.5.2 software  using a C9-2 curved transducer. Multiple (at least two) measurements of kidney length, width, and depth were performed. An average of these measurements was entered in the equation for an ellipsoid, and KV was calculated . Results2 was used to compare the precision of different models. Non-normal continuous variables were analyzed with Kruskal-Wallis test. Dichotomous variables were analyzed with cross tables and Pearson’s chi-square test. As additional analyses, the kidney volume was analyzed with a mixed effects model including right and left volume in the same analysis. A hierarchical model with the child as the main unit was set up, taking into consideration the correlation between right and left side, with the covariance structure unstructured (UN). In all statistical analyses, the relevant assumptions were checked. The significance level alpha was set to 0.05.For descriptive statistics, continuous variables were presented with mean and standard deviation (SD). Continuous variables, approximately normally distributed, were analyzed with respect to the three defined groups, using analysis of variance (ANOVA). In order to adjust for continuous prognostic variables, covariance analysis was used (ANCOVA). Stepwise regression analysis was used to examine the impact of a set of prognostic variables. The coefficient of determination, RThe neonatal characteristics and morbidities did not differ significantly between the NC+ and NC− groups; however, the NC+ group tended to be younger, smaller, and with more vancomycin, less prenatal steroid use, and more frequent IVH for all grades Table . Childrep = 0.0004, ANOVA, Fig. p = 0.056) (Table p = 0.016). The effects of the following factors on total KV by using stepwise linear regression were also tested: age at visit, AKI, PDA, NEC, BPD, sepsis, and treatment with furosemide (days) and antenatal steroids. None of the tested confounding factors seemed to have the potential to explain a difference in total KV between the two preterm groups. Total KV calculated as the ratio of KV and BSA (KV/BSA) [p = 0.016), but not reaching significance for the NC− group (p = 0.08) . The KV/BSA ratio from the neonatal period compared with the measurements at school age showed that children who had suffered from NC (NC+) during the neonatal period had significantly lower KV/BSA ratios than those without NC (NC−) . Among NC+ children, only 2 of 18 (11%) had a rise in KV/BSA ratio from neonatal to school age, while 9 of 18 (50%) in the NC− group showed a rise in KV/BSA ratio (p = 0.01).Unadjusted total kidney volumes (KV) were significantly lower for both preterm groups in comparison with controls   was sign8) Table . Both pr2, p = 0.012, 0.035 respectively). The difference between the NC+ and NC− groups was not significant (p = 0.11).All groups had normal estimated glomerular filtration rate (eGFR) calculated by the cystatin C–based CAPA formula but showed lower values for the NC− group compared with controls as well as for both preterm groups taken together  . Although entirely normal, plasma creatinine was significantly higher in controls compared with both groups of preterm-born children (NC+ 38.5 (5.9); NC− 40.1 (7.9); control 46.2 μmol/l (8.6), p = 0.011). Urinary proteins and electrolytes were not significantly different between the three groups (data on request).There was no difference between the groups when using the simplified Schwartz formula (eGFRcreatinine with p = 0.58). Four of the preterm-born children had high office blood pressure measurements: 3 had both systolic and diastolic, and 1 had isolated diastolic blood pressure above the 90th percentile. One child in the control group had isolated high diastolic blood pressure measurements above the 90th percentile.Office blood pressure and systolic and diastolic standard deviation score (SDS) were not different between the three groups (mean (SD); NC+, 0.18 (0.94); NC−, − 0.07 (0.72); control, − 0.005 (0.72), ABPM readings were successful in 34 of the 41 EPT-born children. Neurodevelopmental disorders of autism spectrum disorders and/or ADHD were present in 16 children born EPT (12/20 NC+ (60%); 4 of 21 NC− (19%)). In seven of these children, ABPM measurements were not possible due to compliance problems or had to be discarded because of low quality. However, none of the investigated children with ADHD or autism spectrum diseases was on medical treatment at the time of investigation. The results of ABPM in the 34 performed were in the normal range for all preterm-born children. ABPM could verify the high office blood pressure measurements in only one of the five patients mentioned above. The majority of the children had systolic values below or at the 50th percentile  [2, which can be defined as mild renal insufficiency [Kidney function was, by definition, normal among all three groups. Cystatin C–based eGFR, which has been advocated to be more appropriate for the age group investigated here, was lower in the group of children born prematurely in comparison with the control group = 0.036) . Using t . Using ficiency . Giaprosficiency . Follow-Early elevated blood pressure in children born very preterm, and even hypertension, has been reported in previous studies , 38. It The results of the ambulatory blood pressure measurements were within the normal limits for systolic and diastolic age and height related percentiles (< 90th) . HoweverAmong the scarce evidence available for preterm-born children, a study in 41 preterm-born children (26–36 weeks GA) examined at the age of 7 years found in comparison with 27 healthy controls insufficient night dipping in 73% of the preterm group compared with 41% in the control group . It is rThe variation of blood pressure over 24 h is regulated by the autonomic nervous system (ANS) via the hypothalamo-pituitary-adrenal axis . It has A general weakness of this study is the size, as the numbers in all three groups are limited. We regard it as a strength that we have analyzed KV with different methods and have thoroughly tested adjusting for different variables. Our investigation and analysis allowed us to make clear differentiations for gender as well as for right and left kidney sides. It was also beneficial that all study subjects were recruited from the same hospital which minimized confounding effects by different practices and that all histories and ultrasound examinations were performed by the same investigator, as well as all anthropometric measurements being taken by the same research nurse. ABPM were only taken in the EPT group and thus correlated to population blood pressure references which is another weakness.In this study, we showed that children at the age of 6–10 years born EPT have significantly smaller kidney volume and lower cystatin C–based GFR, but within normal limits. Our results do not entirely support our hypothesis that NC which developed during the neonatal period has a significant impact on reduced kidney volume at school age. However, the NC+ group of EPT-born children had significantly lower renal growth. Kidney function at school age has not been affected by NC. The high number of non-dippers in preterm-born children at school age is a new observation and has potential implications for the development of hypertension. However, the clinical significance of this finding needs to be studied further. It is important to know when early morphological changes such as the reduced nephron endowment lead to clinical findings in children born prematurely. As more EPT infants are surviving, research describing the consequences is essential in order to be prepared for adequate support and to organize early preventive efforts for this high-risk group.


However, it was not associated with blood pressure change over time  and 0.01 mmHg , respectively). We found no significant link between vegetable intake and blood pressure, neither cross-sectionally nor longitudinally. In addition to the association with diet, we observed increasing SBP and mostly steady DBP over age, with deceleration and downward turn after the ages of 55–59 years. On the whole, this analysis found no consistent association between F&V intake and trajectories of blood pressure in older age.Diet rich in fruits and vegetables (F&V) is an established protective factor for hypertension, but the available evidence regarding the impact of F&V consumption on age-related blood pressure change is limited. We examined whether systolic (SBP) and diastolic (DBP) blood pressure trajectories are influenced by F&V intakes in an ageing Russian cohort. Dietary data was available for 8997 men and women in the Health, Alcohol and Psychosocial Factors in Eastern Europe prospective cohort study. Blood pressure measurements were taken at three time-points over 12 years of follow-up, during which time the mean age of the sample changed from 58 to 69 years. The relationships between F&V intake and SBP and DBP were assessed using mixed-effect multilevel models. In the multivariable adjusted models, fruit intake was inversely related to both systolic and diastolic blood pressure at baseline (mean SBP and DBP was 3.5 mmHg and 1.4 mm Hg lower in the highest compared to the lowest intake tertiles, respectively (both  Blood pressure changes with age. It gradually increases during most part of the adulthood, reaching the highest values around the mid-60 s or early 70 s; after this age, as most studies suggest, it stays steady or turns into slow decline –4. AlthoStrong evidence, supported by large observational and experimental studies, indicate that fruit and vegetable (F&V) consumption is inversely related to blood pressure –7. In faCardiovascular morbidity and mortality rates in Eastern European countries have been historically high, and hypertension among adults is also more prevalent here than in most Western European states –13. ThisUsing longitudinal data from the Russian arm of the Health, Alcohol and Psychosocial Factors in Eastern Europe (HAPIEE) study, the main aim of this analysis was to examine whether systolic and diastolic blood pressure trajectories are influenced by fruit or vegetable intakes in adult and elderly individuals over a follow-up of 12 years.HAPIEE study is a multi-centre prospective cohort which was established to investigate non-communicable chronic diseases, primarily CVD, and their risk factors in four Eastern European countries . The RusAll participants signed informed consent and study protocols were approved by ethical committees at University College London and Institute of Internal and Preventive Medicine in Novosibirsk.r = 0.26), similarly to many other large-scale studies [Nutritional data collection procedures in the HAPIEE study have been described previously in details , 18. Bri studies , which sSystolic (SBP) and diastolic blood pressure (DBP) measurements were taken in all three waves of the study by trained nurses following a standard protocol using an Omron M5-I digital sphygmomanometer. Subjects were in a sitting position after 5 min of quiet rest. The measurements were taken on the right arm which was bent in 45-degree at the elbow and supported by a flat surface (table). Three measurements were taken with 2 min intervals between them. The means of the second and third measurement of systolic and diastolic blood pressure values were used in the analyses.Baseline measurements of self-reported smoking , frequency of alcohol consumption , leisure time physical activity , marital status , education  and energy intake (from FFQ) were used as covariates in the statistical analyses. Information on antihypertensive medication use  was assessed at all three data collection waves.In line with recommendations for nutritional epidemiological analyses , we excln = 1756) and losses of follow-up for other reasons (n = 3574). Compared to those who remained in the study, individuals lost to follow-up were older, more likely to be males, smokers and with lower levels of education. Their SBP and DBP were also higher at baseline  and interaction terms between each covariate and time.without interaction with time provided information on their cross-sectional relationship with blood pressure (intercept), whereas the coefficients with interaction between F&V intake and time indicated the respective longitudinal association (change in SBP or DBP per one year of follow-up time) (slope).The obtained coefficients for F&V intake tertiles Models were first adjusted for sex, age (centered at 58 years), antihypertensive medication use (as time-varying covariate) and energy intake (centered at 10.6 MJ/day), corresponding to model 1. In model 2, they were further adjusted for education, marital status, smoking, alcohol intake, leisure time physical activity and fruit or vegetable intake.In order to ease interpretation of the results, fully adjusted blood pressure trajectories in the different fruit or vegetable intake tertiles were also plotted separately by 5-year birth cohorts using the ‘margins’ command in Stata .Statistical analyses were carried out using the MLwiN v3.01 software which was accessed through Stata v13.1 with the help of the ‘runmlwin’ command .Availability of data from the HAPIEE study is restricted due to legal reasons. Further information and access, including on availability of statistical codes, can be requested by contacting the principle investigator, Professor Martin Bobak (m.bobak@ucl.ac.uk) who will seek approval by the HAPIEE Study Steering Committee and the Research Ethics Committee at UCL and participating centres.Table p < 0.001). However, the cross-sectional associations with vegetable intake were not statistically significant (p = 0.204 for SBP and p = 743 for DBP). Longitudinally, the coefficients indicated mostly non-significant associations and inconsistent trends across the tertiles for both fruit and vegetable intakes.Cross-sectional (intercept) and longitudinal (slope) associations between fruit and vegetable intakes and SBP and DBP are presented in Table Multivariable adjusted (model 2) trajectories, separately by 5-year birth cohorts, are shown in Figs. Although multilevel modelling can adequately deal with missing data under the missing at random assumption , 24, we In further sensitivity analyses, we assessed the associations only among those participants who took no antihypertensive medications  are particularly popular in Russia. This is mainly due to the climatic conditions as these are the fruits which can grow relatively well in continental and subarctic climates typical to large part of the country, including the Novosibirsk region in Western Siberia. There is some evidence which suggest that berries may be less effective in the prevention of CHD and stroke than many other types of fruit . TherefoThere are a number of potential explanations for the lack of clear association between F&V intake and longitudinal blood pressure change. Firstly, it is possible that measurement error of dietary intakes reduced the capacity of the data to identify actually existing associations. However, the adequate validity of the FFQ in relation to biomarkers , the facThe inverse relationship with fruit intake at baseline together with the parallel blood pressure trends across intake groups over time also mean that the beneficial effects of fruit consumption were maintained during the observational period. This suggests that eating adequate amount of fruits throughout the lifecourse do have an impact on blood pressure in older age even if its effect on the age-related change itself is limited.Previous analyses suggest a constant increase in blood pressure from early to late adulthood with the steepest rise between 40 and 55 years , 4. AfteIn addition to the potential impacts of measurement bias and residual confounding on the results, which were mentioned above, we also acknowledge the fact that, due to the moderate response rate and restrictions during sampling , our sample is not fully representative to the Russian population as a whole. It is likely that the current cohort is healthier than the general population . HoweverOn the other hand, our study has important strengths as well. This is one of the first longitudinal analyses which examined the impact of dietary factors on blood pressure trajectories in adult/elderly individuals over more than ten years of follow-up. In addition, we carried out the analysis using data from an Eastern European cohort, representing a population which often lacks good quality epidemiological data.High blood pressure is one of the most important modifiable risk factors for CVD and overall mortality. Investigating the lifestyle habits which can influence its trajectories in older age has a clear practical importance. Despite our inconsistent findings, F&V intake remains a prime behaviour to reduce blood pressure and further research in this topic is strongly warranted.Systolic and diastolic blood pressure changes with age with a mostly increasing trend in mid and late adulthood.High fruit and vegetable intake is an established protective factor for hypertension.Using data from a Russian population sample, this study confirms that blood pressure increases during older age, but the trend changes in the 60 s, after which age it stays steady or potentially turns into a decline.Fruit intake is inversely associated with systolic and diastolic blood pressure, but the impact of fruit or vegetable intake on age-related blood pressure change remains unclear.Supplemental material


The objective of this study was to determine the effects of strict volume control and nondipper situation on cardiovascular disease in chronic hemodialysis patients. This study is an observational and cross-sectional study including 62 patients with normotensive chronic hemodialysis using no antihypertensive drugs. A series of measurements including ambulatory blood pressure monitoring, left ventricular mass index by echocardiography, common carotid artery intima-media thickness by ultrasound, and body fluids by bioimpedance analysis were conducted for all subjects. The patients were divided into two groups as dippers and nondippers according to their ambulatory blood pressure monitoring results. Average 48 h systolic, diastolic, and mean arterial blood pressure and nocturnal systolic, diastolic, and mean arterial blood pressure were significantly different between the dipper and nondipper groups (p<0.05). Before and after dialysis, extracellular fluid/intracellular fluid and extracellular fluid/dry body weight ratios were significantly higher in the nondipper group. Left ventricle mass index and interventricular septum thickness were significantly higher in the nondipper group (p<0.05). Left ventricle ejection fraction was significantly lower and common carotid artery intima-media thickness was higher in the nondipper group with a statistical significance (p<0.05). A two-predictor logistic model was fitted to the data to predict the comparability of dippers and nondippers. According to logistic regression analysis, the odds ratio for daytime diastolic blood pressure indicates that nondippers are 0.45 times more likely to have high blood pressure than dippers in daytime. But in night time, nondippers are about 2.55 times more likely to have high blood pressure comparing to dippers. An important finding of this study is that nondipping pattern is associated with cardiac hypertrophy and lower left ventricle ejection fraction in dialysis of patients with no hypertension. The results also suggest that applying strict volume control to achieve a normal blood pressure alone is not sufficient to reduce the risk of cardiovascular morbidity and mortality if the patients do not have a dipper status of nocturnal blood pressure. Most patients receiving hemodialysis (HD) therapy due to end stage renal disease (ESRD) usually develop hypertension (HT) which is mainly systolic . When HDAmbulatory blood pressure monitoring (ABPM) is an automated technique that measures blood pressure at regular intervals over a period of 24 hours to 48 hours without interfering with the patient's normal daily activities. The multiple values obtained by ABPM without “alarm reactions” yield excellent measurement results . Wide vaAssessment of body composition by bioimpedance analysis (BIA) provides easy, noninvasive, safe, quick, inexpensive, and detailed information about the fluid overload in patients with HD. This technology, based on transmission of current in the human body, consists of two components: resistance induced by water and ions and reactance induced by the capacitor characteristics of the cell membranes. BIA is a useful technique for determining dry body weight in patients with HD , 10.Today we know that atherosclerosis is an inflammatory disease that plays a significant role in cardiovascular disease-related morbidity and mortality in patients with chronic HD , 12. TheThis study was conducted between May 2005 and May 2008. The study included 62 patients receiving chronic HD treatment at the HD unit of Fırat University Medical Faculty Hospital for at least 3 months. Their blood pressure levels were regulated through strict volume control, they had adopted and maintained a lifestyle with serious restriction of salt (<4-5 gr/day) to successfully allow strict volume control, and they did not receive any antihypertensive therapy. This is an observational and cross-sectional study involving HD patients, and all patients with HD were randomly selected. None of the patients had residual renal function and urine output. All patients received erythropoietin alpha treatment at a dose of 75-150 U/kg/week.The exclusion criteria were as follows: significant heart disease, arrhythmia, cardiac pacing, presence of prosthesis, clinical manifestations of carotid artery stenosis, being hospitalized recently, and hypertension. In addition, patients with uncontrolled diabetes, obesity, sleep apnea, chronic lung disease, and pulmonary hypertension were excluded from the study. A patient was accepted to have a hypertension if his/her arterial blood pressure was measured as ≥140/90 mmHg based on at least two measurements with 5 minutes intervals while the patient was on a seated position. All the patients included in the study were weighed with the same scale before and after dialysis to calculate their intradialytic weight gain. The study protocol and the procedures were approved by Fırat University Local Ethical Committee and fully complied with the Declaration of Helsinki, and all subjects were recruited upon obtaining their informed consents.Sympathetic activity is assessed in many studies by noninvasive techniques. Heart rate variability, BP variability, and baroreceptor sensitivity are the most frequently used methods to assess autonomic nervous system function and cardiovascular variability, a measure of the integrated control mechanisms of circulation . In thishttp://www.HDCN.com.Patients received HD three times weekly on volumetric dialysis devices using a synthetic polysulfone membrane  and bicarbonate-based dialysate delivery system. In the standard 4-hour HD sessions three times weekly, we applied a blood flow rate of 250-350 mL/min and a dialysate flow rate of 500 mL/min. Dialysate sodium, potassium, and calcium concentrations were 133 mmol/L, 0-3.0 mmol/L, and 1.25 mmol/L, respectively. The vascular access was in the form of arteriovenous fistula in all patients. It was used with biocompatible dialyzers. All of the patients had the same temperature prescription. The ultrafiltrations of the patients were determined according to their dry weight. At the end of the dialysis session, the patients were reduced to their designated dry weight. The calculations of dialysis adequacy (Kt/Vurea) and body surface areas (BSA) were performed online by submitting the patient data, dialysis technique, and the test results on The 48-hour ABPM measurements were conducted with an oscillometric ABPM device . The monitor was applied to the patients' nonfistula arms immediately after the dialysis when the patients were in dry weight status with their heights and weights recorded. The monitors recorded readings every 30 minutes from 08:00 to 22:00 and every 60 minutes from 22.00 to 08.00 in the next morning. To obtain valid and acceptable results, we had to perform a minimum of 36-hour monitoring with readings recorded at least once an hour. Sleep-wake cycles were evaluated based on the information obtained from the patients. Intradialytic hypotension is defined as a systolic blood pressure of less than 100 mmHg or a systolic blood pressure decrease of greater than 10 mmHg or a mean arterial pressure decrease of greater than 30 mmHg with or without symptoms. Patients with intradialytic hypotension were recorded. We agreed that the finding of a nocturnal blood pressure fall of more than 10% of daytime values (night-to-day blood pressure ratio <0.9) can be accepted as an arbitrary cutoff to define patients as ‘dippers' .μA and 50 kHz alternating sinusoidal current, RJL/Akern System, Florence, Italy) while BIA electrodes were placed on the body side not used for dialysis tubing in standard conditions. BIA was conducted twice a week, immediately before the last HD session of the week and 30 minutes after the session. The procedure was performed after at least 30 minutes of rest in the supine position and in a quiet environment where the temperature was between 22°C and 24°C. At each measurement, the electrodes remained attached to the device and the patient from the predialysis period until the end of the postdialysis period. Based on a fluid model using these resistances, extracellular fluid (ECF), intracellular fluid (ICF), and total-body fluid (TBF) are calculated. These volumes then are used to determine the amount of fluid state. All calculations are performed automatically by the software of the Body Composition Monitor [Bioimpedance analysis is a useful technique for determining dry body weight in patients with HD. The same operator took the measurements using BIA 101-S plethysmograph (injecting 800  Monitor .2 –D (d)2]/{4[P(s)—P(d)]}/ 7,6 (mm2/kPa). .The same cardiologist conducted the carotid Doppler and echocardiographic examination of the patients at the beginning of each HD session in the midday of the short interdialytic days. The teleradiographic images were taken before dialysis on the day of the examination. Arterial compliance was calculated by the formula (AC) = Π[D (s)The predialysis and postdialysis blood samples were taken after the short interdialytic day. The samples were analyzed on the same day by our hospital's central laboratory without delay. During the study, we conducted routine hematology, biochemistry, coagulation, and immunology tests, as well as parathyroid hormone and hs-CRP tests. t-test was used to compare the data between groups. The correlation between some parameters in patients was analyzed by Pearson's correlation test. To explain which independent variable (among the given variables) correctly predicts the dependent variables of dippers and nondippers, the logistic regression was employed. Logistic regression is used to predict the outcome based on values of a set of predictor variables. It is similar to a linear regression model but is suited to models where the dependent variable is dichotomous. Logistic regression coefficients can be used to estimate odds ratios for each of the independent variables in the model . For all tests, a p value of ≤ 0.05 was considered statistically significant.The research data obtained from the groups were analyzed using SPSS 21.0 for Windows . The data were checked with the Shapiro-Wilk test, where normal distribution was not observed, and it was accepted that if p>0.05 the data were not normal, while if p<0.05 the data were considered normal. The data obtained during the study were presented as mean ± standard deviation. SimpleA total of 62 patients were included in this study. Of these 62 patients, 19 had secondary chronic pyelonephritis/urinary system infection, 18 had glomerulopathy, 15 had secondary kidney stone, and the remaining 10 had other diseases. Sleep apnea and pulmonary hypertension were not present in any of our patients. Two years after completion of our study, none of our patients had died from cardiovascular events, and only 1 out of 62 patients died from infection. The patients were divided into two groups as dippers and nondippers according to their ABPM results. Basic patient demographic characteristics and laboratory data are shown in Ambulatory blood pressure monitoring results of the dipper and nondipper patients are shown in The results of BIA are shown in The results of echocardiography and carotid artery Doppler examination are shown in χ2  (2) =55.15; p<0.05). The correlation between some important parameters is shown in The most important finding of this study is that nondipping pattern is associated with cardiac hypertrophy and lower LVEF in dialysis of patients with no HT. The findings also suggest that a salt-restricted diet and a strict volume control are very effective to control the blood pressure of chronic HD patients. According to our results, a normal blood pressure (normotensive) of a patient is not enough to reduce the risks of cardiovascular diseases, but a dipper nocturnal blood pressure profile is also needed. The present study was set up to use an established method for determining body composition, hydration, and blood pressure status in chronic HD patients. Demographic data of patients and some laboratory findings are shown in While the centers using antihypertensive medication for HT during the treatment of chronic renal failure have reported failure in 75% of the patients despite using triple or quadruple drug combinations, the centers implementing the method of strict salt and volume control have reported achieving and maintaining normal blood pressure in over 90% of the patients , 4. It iNumerous studies on chronic renal patients have examined the association between HT and fluid/salt loading by BIA method . In the M-mode echocardiography is a precise diagnostic tool for predicting left ventricular hypertrophy, dilatation, and systolic and diastolic dysfunction . LVMI, lUltrasound measurements of common carotid artery (CCA) IMT are considered a reliable approach that can be used in the studies aiming to identify cardiovascular risk factors . London We also examined the correlation between some parameters in all patients, including both patient groups . NegativIn conclusion, we emphasize in this study that the tight volumetric control is effective. The findings of this study suggest that nondipping pattern may generate cardiac hypertrophy and a lower LVEF in dialysis of patients even if they do not have HT. The findings of the current study are in accordance with earlier observations in the literature suggesting that a salt-restricted diet not restricting water intake and strict volume control are essential for controlling the blood pressure in patients with chronic HD. However, we also observed that having normal blood pressure through strict volume control is not sufficient to reduce cardiovascular mortality and morbidity in these patients; they should also have a dipper nocturnal blood pressure profile in addition to being normotensive. Hence, our findings clearly suggest that HD patients should be strictly checked for this hidden blood pressure to avoid cardiovascular mortality and morbidity risks.Although we had some limitations including medications, genetic background, and nutrition interaction of the patients, the results of the current study have also produced other important questions that remain unanswered to date: Do the elevated hsCRP levels in nondipper patients with HD result from the excess ECF volume? Is the microinflammation detected by hsCRP measurements an underlying cause of nondipper status? Is it reasonable to suggest that chronic microinflammation can be prevented by implementing strict volume control and that patients with ESRD can avoid cardiovascular events by applying this method? Further studies are required to address these questions.


P < .001) than the nonleft ventricular hypertrophy group.Recent studies have shown that hypertension is poorly controlled in many populations worldwide. Electrocardiographic left ventricular hypertrophy is a common manifestation of preclinical cardiovascular disease that strongly predicts cardiovascular disease morbidity and mortality. However, little information is available regarding the role of left ventricular hypertrophy in blood pressure (BP) control. We aimed to assess the relationship between electrocardiographic left ventricular hypertrophy and BP control in the China Stroke Primary Prevention Trial. The study population included 17,312 hypertensive patients who were selected from a group of 20,702 adults who had participated in the China Stroke Primary Prevention Trial and had undergone electrocardiography at baseline visit. Multivariate analysis identified left ventricular hypertrophy as a predictor of unsatisfactory BP control. The results revealed that 8.1% of hypertensive adults exhibit left ventricular hypertrophy and that the disease is more prevalent in males (12.8%) than in females. Multivariate regression analysis showed that the electrocardiographic left ventricular hypertrophy group had a significantly higher rate of unsatisfactory BP control [odds ratio (OR) 1.42, 95% confidence interval (95% CI) 1.26–1.61, P < .001) and females  and especially among patients with comorbid diabetes . In conclusion, the results of this study indicate that electrocardiographic left ventricular hypertrophy appears to be an independent predictive factor for poor BP control, especially in females and patients with comorbid diabetes.Notable differences in BP control were also observed among males (OR 1.37, 95% CI 1.17–1.60,  A 2013 to 2014 nationally representative survey indicated that the prevalence of hypertension in China was 27.8%. Of those with hypertension, 31.9% were previously diagnosed; of those diagnosed, 82.9% were treated, and of those treated, only 34.6% achieved proper blood pressure (BP) control (<140/90 mm Hg); the overall control rate was only 9.7% among those with hypertension.  Several studies have established electrocardiographic (ECG LVH) as an independent predictor of cardiovascular morbidity and mortality.–6 However, few studies have focused on the relationship between LVH and the achievement rates of target BP levels in patients with hypertension, as defined by the 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults (JNC8 2014).Electrocardiography is a routine, accessible, cost-effective, and recommended diagnostic tool for the initial evaluation and follow-up of hypertensive patients. It is widely available, inexpensive, and carries prognostic value independent of other left ventricular hypertrophy (LVH) detection techniques .The present study assessed whether LVH voltage criteria were associated with higher rates of lack of BP control in hypertensive patients during follow-up. In particular, the aim of this study was to elucidate whether LVH is associated with BP control achievement rates in a Chinese population using a large community-based sample of treated hypertensive patients. We first evaluated whether the LVH-systolic BP (SBP) control relationship could be affected by types of antihypertensive drugs or other variables, including gender, age, body mass index (BMI), and baseline SBP. We further explored other factors that influence SBP and diastolic BP (DBP) control.22.1 Eligible participants included hypertensive men and women who were 45 to 75 years of age. The major exclusion criteria included a history of stroke, myocardial infarction, heart failure, coronary revascularization, and/or congenital heart disease. Individuals with missing electrocardiogram measurements, indecipherable electrocardiogram results, and/or electrocardiogram abnormalities with inconsistent changes  at baseline .2.2 Standard 12-lead electrocardiography was routinely performed at baseline and again after 5 years. Electrocardiography was conducted with the patient in a supine position at rest, using electrocardiogram devices routinely used by the institutes. Electrocardiograms were recorded with a calibration mark of 10 mm/mV (or 5 mm/mV) and a paper speed of 25 mm/s, marked on each trace, against which standardized measurements could be made. All electrocardiogram results were read by 2 trained medical practitioners unaware of the participants’ clinical outcome group, and discrepancies were resolved by a third senior medical practitioner.The China Stroke Primary Prevention Trial was a multicommunity, randomized, double-blind clinical trial conducted between May 19, 2008, and August 24, 2013, in 32 communities in the Jiangsu and Anhui provinces of China. The trial consisted of 3 stages: a screening and recruitment period, a 3-week run-in treatment period, and a 5-year randomized treatment period. The 17,312 eligible participants with baseline electrocardiogram measures were stratified according to the presence and/or absence of LVH (the LVH group and the non-LVH group) using the Sokolow–Lyon criteria.2.3The Sokolow–Lyon criteria for LVH were used, and the criteria were defined as follows: SV1 + RV5/6 > 3.8 mV.2.4Participants were placed in a sitting position with their right arm supported at the level of the heart. Trained volunteers who had been recruited from local medical colleges obtained participant BP measurements using automatic digital sphygmomanometers . The participants were given 3 minutes of rest between each of 3 successive BP readings. The average of the 3 readings was used as the baseline BP value. Hypertension was defined as a SBP of 140 mm Hg or a DBP of 90 mm Hg or higher.2.5BP was measured every 3 months during follow-up from 2008 to 2013. The average of 20 measurements at 20 different visits was used as the final BP value. The overall goal of BP control was defined as a SBP of 140 mm Hg and a DBP of 90 mm Hg.2.62 and/or proteinuria at baseline were classified as having chronic kidney disease. BMI was calculated as weight in kilograms divided by height in meters squared (m2). Serum folate and vitamin B12 levels at both the baseline and the exit visits were measured by a commercial laboratory kit using a chemiluminescent immunoassay . Serum homocysteine, fasting lipids, and glucose levels at the baseline and the exit visit were measured using automatic clinical analyzers (Beckman Coulter) at the core laboratory of the National Clinical Research Center for Kidney Disease in Nanfang Hospital, Guangzhou, China.Diabetes mellitus was defined as self-reported clinically diagnosed diabetes, use of hypoglycemic agents, or a fasting blood glucose concentration greater than or equal to 7.0 mmol/L (≥7.0 mmol/L). Participants with an eGFR less than 60 mL/min/1.73 m2.7http://www.empowerstats.com) and the statistical package R. Data are presented as the mean ± standard deviation or proportions. Comparisons between groups were performed using Chi-squared tests for categorical variables and 2-sample t tests for continuous variables. Multiple linear and logistic regression analyses were used to assess the associations between baseline ECG LVH and BP control. Values for BP decline after treatment (ΔBP = baseline BP − BP after treatment), relative percentage SBP decline (ΔBP/baseline BP), and unsatisfactory BP control (SBP ≥140 mm Hg or DBP ≥90 mm Hg after treatment) were calculated as indicators of BP control. A 2-tailed P value below .05 was considered statistically significant (P < .05).All analyses were performed using EmpowerStats . In addition, these patients exhibited lower values for the relative percentage decrease in SBP and DBP  and a trend toward lower values for the relative percentage decrease in DBP . There was significant failure to achieve BP treatment goals in patients with ECG-LVH . After a further adjustment for baseline SBP and DBP, sex, age, pulse, self-reported arrhythmia, antihypertensive drugs use, β-blocker use, smoking, alcohol consumption, glucose, homocysteine, folate, vitamin B12, total cholesterol, triglycerides, high-density lipoprotein cholesterol, estimated glomerular filtration rate, incidence of failure to achieve BP treatment goals, and changes in SBP and DBP were significantly higher in patients with ECG-LVH, whereas values for the relative percentage decrease in SBP and DBP were significantly lower in patients with ECG-LVH.The relationship between baseline ECG LVH and failure to achieve BP treatment goals is presented in Table 3.3P < .001) with LVH exhibited higher failure rates for achieving BP goals than male subjects with LVH . In addition, females with baseline LVH exhibited significantly smaller changes in SBP and DBP . Males with baseline LVH exhibited significantly smaller changes in SBP ; importantly, differences in DBP decreases were not noted in male subjects . Similarly, female patients exhibited lower values for the relative percentage decrease in SBP and DBP. Differences in DBP decreases were not noted in male subjects.As summarized in Table 3.4P = .004). No significant differences were found in patients with baseline eGFR levels lower than 60 mL/min/1.732 m2, but the BP control rate was significantly lower in patients with normal BMI  than in overweight patients .As clinical diversity was observed in the study, we used subgroup analysis to further examine the results. Figure 4 Given the well-characterized population, the standardized assessment of electrocardiograms using the Sokolow–Lyon criteria, and the 4.5-year longitudinal follow-up period, this study presented a unique opportunity to assess the prevalence of ECG LVH, identify differences between men and women, and explore whether baseline ECG LVH is associated with an increased risk of unsatisfactory BP control in a Chinese hypertensive population. Furthermore, the study provided insight regarding the potential predictive value of unsatisfactory BP control.A major advantage of the present study is the large sample size derived from the China Stroke Primary Prevention Trial. The China Stroke Primary Prevention Trial was a large randomized trial conducted in adult subjects with hypertension in China without a history of stroke or myocardial infarction. The results of the trial demonstrated that enalapril-folic acid therapy significantly reduced the relative risk of an initial stroke incident  .,11 Furthermore, untreated hypertension patients with target organ damage were less likely to receive sufficient antihypertensive treatment. However, the current study demonstrated that ECG LVH in hypertensive patients can be used to identify those at a greater risk of unsatisfactory BP control, notably female patients and patients with comorbid diabetes. However, little is known about the prevalence of ECG LVH in the Asian hypertension population. Our study was the first to report that the prevalence of ECG LVH is 8.1%, and the prevalence is greater in men (12.8%) in a Chinese hypertension population. A nationwide epidemiological survey in Finland determined that the morbidity of ECG LVH was 12.6% in a hypertensive population according to the Sokolow–Lyon voltage criteria, which is higher than the result of our study. Therefore, our study, which is a large randomized multicommunity trial, may better reflect the prevalence of ECG LVH after taking into account differences in lifestyle habits and genetics, and it has been demonstrated from previous studies that ECG has a relatively lower sensitivity than echocardiography in determining LVH. Compared with Caucasians, black individuals have greater precordial QRS voltages. Therefore, many of the LVH criteria have higher sensitivity and lower specificity in detecting LVH in blacks.,16 Moreover, geographical differences exist between Asian and European populations. In our study, the prevalence was greater in men (12.8%) than in women. This finding is consistent with those of previous studies.–19The previous study demonstrated that BP, short-term BP variability, and OSA are independently associated with increased left ventricular mass. Therefore, ECG LVH could be considered an early indicator of poor BP management. After adjusting for multiplicity, the current study indicated that hypertensive patients with baseline ECG LVH exhibited a higher rate of unsatisfactory BP control  was not significant. Several studies have shown that LVH is common in patients with end-stage renal disease, which is an independent predictor of cardiovascular disease and mortality.–35 In several studies, LVH was also an independent predictor of cardiovascular disease mortality and heart failure in patients with ≥stage 3 chronic kidney disease.–38 In these patients, chronic kidney disease was a greater risk factor for poor BP control than ECG LVH. We could not address the relationship between ECG LVH and BP control in chronic kidney disease patients due to the small sample size. In addition, the risk of unsatisfactory BP control was significantly higher in normal-weight than in overweight patients. Several studies have reported that LVH confers an increased risk of cardiovascular events in overweight patients.,40 Even in genetic heart disease, such as hypertrophic cardiomyopathy, obesity is independently associated with increased left ventricular mass and may dictate the progression of heart failure symptoms. In these patients, obesity was a greater risk factor for poor BP control than ECG LVH. This result is different from those obtained in the present study; we could not address the relationship between ECG LVH and BP control in overweight patients due to the small sample size.In subgroup analyses, the findings of a higher unsatisfactory BP control rate among females or hypertensive patients with diabetes with baseline ECG LVH were compared with those of patients without ECG LVH after adjustment for confounders. The mechanism responsible for the higher risk of unsatisfactory BP control in females with LVH remains uncertain. However, hypertensive females may be more prone to developing higher relative cardiac wall thickness than men.Some study limitations should also be taken into consideration. One of the limitations encountered was the single measurement of cardiac activity by electrocardiogram during the baseline physical examination, preventing the exclusion of subsequent abnormalities during the follow-up period. Second, Sokolow–Lyon may be less sensitive in women, and the results may vary with Cornell Voltage criterion. However, we utilized optimal control methods for the LVH criteria. Third, BP measurements were not performed at trough for patients who received antihypertensive drugs, and consequently, the assessment of BP control may have been influenced to a certain extent. In the future, ambulatory BP monitoring may be a favorable method for BP management and evaluation.We conclude that ECG LVH appears to be an independent predictive risk factor for poor BP control, which suggests that hypertensive patients with LVH have more difficulty achieving target BP and maintaining clinical follow-up, especially female patients and patients with comorbid diabetes.The authors appreciate the participants who volunteered to participate in the study and the data collection staff of the CSPPT team.Conceptualization: Xiao Huang.Data curation: Fangfang Fan.Formal analysis: Yan Zhao, Juxiang Li.Funding acquisition: Jing Chen.Investigation: Kui Hong.Methodology: Ping Li.Project administration: Yanqing Wu.Resources: Qinghua Wu.Software: Binyan Wang.Supervision: Xiping Xu.Validation: Yigang Li.Visualization: Xiaoshu Cheng.Writing – original draft: Zhen Wang, Chunyan Zhang.Writing – review & editing: Huihui Bao, Yong Huo, Xiaoshu Cheng.


Monoclonal antibodies (mAbs) approved for use as add-on therapy in patients with severe asthma target the underlying pathogenesis of asthma.Omalizumab binds immunoglobulin E (IgE), thereby inhibiting its interaction with the high-affinity IgE receptor and reducing the quantity of free IgE available to trigger the allergic cascade. Anti-interleukin (IL)-5 mAbs mepolizumab, benralizumab and reslizumab block the interaction between IL-5 and its receptor on eosinophils, thus targeting the eosinophilic pathway in asthma. Most mAbs are available as intravenous (IV) or subcutaneous (SC) formulations, as their high molecular weight and gastric degradation preclude oral administration. This review compares the pharmacology, efficacy, immunogenicity, injection- and infusion-related adverse drug reactions of subcutaneously administered omalizumab and mepolizumab with the intravenously administered reslizumab. In terms of pharmacokinetics, IV route of administration appears to be superior to the SC route due to quicker absorption, greater bioavailability, shorter time to maximum serum concentration and similar elimination half-life. Route of administration does not appear to translate into striking differences in efficacy and safety of mAbs used for the treatment of severe asthma, as all are generally considered to be effective and well tolerated. Hypersensitivity and administration-related reactions have been described with both IV and SC mAbs.mABs are effective and have low immunogenicity due to their nature as humanised antibodies. Evidence on the use of mAbs in indications other than severe asthma suggest that both the SC and the IV routes of administrations have their respective advantages and disadvantages; but their full utility remains to be elucidated. In poduction , which aoduction , 26, 30.The therapeutic effect of mepolizumab, benralizumab and reslizumab is related to their capacity to bind with high affinity to IL-5  and thus to block the interaction between IL-5 and its receptor on the surface of eosinophils , 7.Mepolizumab is an IgG1 kappa mAb. In patients with asthma and blood eosinophil counts > 300 cells/μL, dose- and time-dependent decreases in blood eosinophil counts were observed with IV mepolizumab 75 mg and SC mepolizumab 125 or 250 mg administration . HoweverThe biological effects of SC mepolizumab have translated into clinical therapeutic efficacy. SC mepolizumab was associated with a significant corticosteroid-sparing effect in patients with severe eosinophilic asthma who required daily oral corticosteroids for asthma control in the SIRIUS study . The MEN1), were observed. At the end of treatment, benralizumab patients had a 24% improvement from mean baseline in FEV1 of 1.66 L. In addition, studies also showed greater improvements in FEV1 in patients with higher baseline blood eosinophil counts and more frequent prior exacerbation history [Benralizumab is a humanised, afucosylated, monoclonal antibody  that directly binds to the alpha subunit of the human interleukin-5 receptor (IL-5Rα). The IL-5 receptor is expressed on the surface of eosinophils and basophils. In an in vitro setting, the absence of fucose in the Fc domain of benralizumab facilitates binding to FC gamma R (FcɣRIII) receptors on immune effectors cells, such as natural killer (NK) cells, leading to apoptosis of eosinophils and basophils through antibody-dependent cell-mediated cytotoxicity (ADCC). Benralizumab is indicated as an add-on maintenance treatment in adult patients with severe eosinophilic asthma inadequately controlled despite high-dose ICS plus LABA. Benralizumab is administered at the dose of 30 mg by SC injection given every 4 weeks for the first 3 doses, then every 8 weeks. In patients with an eosinophil count of ≥300 cells/μL, significant improvements in lung function, as defined by forced expiratory volume over 1 s (FEV history . Interes history .p = 0.05 vs placebo) [Reslizumab is an IgG4 kappa mAb. The biological activity of reslizumab has been described in patients with severe persistent asthma treated with high-dose ICS or oral corticosteroids, in which a single dose of IV reslizumab 0.3 or 1 mg/kg reduced peripheral eosinophil counts from baseline in a dose-dependent manner after 48 h . Compareplacebo) .1, asthma quality of life (AQLQ) and ACQ-7 scores, in two identically designed phase III studies [1 and ACQ scores, as well as reductions short acting β-agonist use [These biological effects correspond with clinical results for asthma control with IV reslizumab. In patients with inadequately controlled asthma and elevated blood eosinophil levels (≥400 cells/μL), IV reslizumab 3.0 mg/kg every 4 weeks was associated with a significant reduction in the frequency of asthma exacerbations, as well as significant improvements in FEV studies . In anotnist use . Reslizunist use , 38.1 response (≥100 ml) and/or ACQ response within the first 16 weeks have greater improvements in the clinical asthma exacerbation rate that those who do not [1, ACQ, asthma quality of life and clinical asthma exacerbation rate at baseline and at week 16 has been developed to predict early response to reslizumab and help guide treatment decisions [Several post hoc analyses have been conducted to identify the subgroups of traditionally difficult-to-treat patients who may respond to reslizumab treatment. These groups include patients with chronic sinusitis and nasal polyps, asthma severity corresponding to step 4 and 5 of the GINA classification, oral corticosteroid-dependent patients and those aged ≥65 years , 39, 40.o do not . Furtherecisions .1, ACQ-7 and Asthma Symptom Utility Index (ASUI) at first assessment, which occurred 4 weeks after treatment initiation [Overall, the main clinical outcomes from the key clinical studies of omalizumab, mepolizumab and reslizumab are summarised in Table itiation . On the Biological agents have the potential to induce an immune response leading to the production of specific anti-drug antibodies (ADAs). ADAs are particularly relevant when they neutralise the drug , 44, becIn comparison with the immunogenicity of the mAbs for rheumatoid arthritis adalimumab and infliximab (mentioned earlier), mAbs used for severe asthma appear to present less of a problem. Humanised mAbs such as omalizumab, mepolizumab and reslizumab, are mostly derived from human Ig sequences, with only the complementarity-determining regions being of murine Ig origin . There wIn an analysis of pooled data from all four phase III placebo-controlled reslizumab studies in patients with asthma, 5% 53/938) of reslizumab 3 mg/kg recipients had anti-reslizumab antibodies, but readings were of low titre and frequently transient [38 of resWhile data suggest the possibility of an immunogenic response to anti-IL-5 mAbs, the potential clinical implications in patients with asthma are not yet firmly established.Many factors influence the development of immunogenicity: drug dose, administration route, but also concomitant medications, underlying disease and the drug structure . ImmunogIn fact, immunogenicity appears to be associated not only with route of administration, but also with drug dose  and duraStudies in mice have indicated that the strength of an immune response towards the biological agent may be dependent on the route of administration , 52. GenCompared with IV administration, SC injection of large molecules such as mAbs is thought to increase the risk of immunogenicity via DC processing . DCs areThe adverse effects characteristic of mAbs relate to the body’s immune response to the drug. This response may range from being a minor, transient, subclinical reaction to a serious, potentially fatal, reaction when the immune system overreacts (hypersensitivity) . Infusion = 274) than with placebo (n = 272) in one study (11.8% vs 7.7%); omalizumab was more frequently associated with redness, warmth and itching symptoms [Adverse reactions highlighted in the prescribing information for the anti-IL5 mAbs mepolizumab and reslizumab and the anti-IgE mAb omalizumab include such hypersensitivity reactions and administration-related reactions , 10, altsymptoms . Most ofsymptoms . Severe symptoms . In a thsymptoms . It seemSC mepolizumab appears to be similarly well tolerated. In the SIRIUS study in 135 patients with severe eosinophilic asthma, local injection-site reactions occurred in only four patients (6%) on SC mepolizumab 100 mg and two (3%) on placebo . Four meThe greater frequency of injection-site reactions with the SC route versus the IV route was confirmed in the only head-to-head comparison to date of IV versus SC administration of monoclonal antibodies in patients with severe asthma  . In thisAlthough serious infusion reactions are a rare event for biological agents used in asthma, in three studies of patients with inadequately controlled asthma and elevated eosinophil levels, IV reslizumab was associated with anaphylactic reactions in three ADA-negative patients, who responded to standard treatment and were withdrawn from the studies , 63.Treatment with biological agents, specifically mAbs, is associated with the formation of circulating immunocomplexes, leading to the activation of the complement system. Activation of C1 fraction occurs at significant levels only when it binds to the CH2 domains of IgG molecules. Furthermore, only certain subclasses of IgG are effective complement activators and exert this activity in human IgG1, but not IgG4. Regarding mAbs used in asthmatic patients, it is important to underline that reslizumab is an IgG4 and that it does not activate the complement system.Besides drug efficacy and tolerability, the rational choice of mAb and route of administration is also influenced by patient preference, pharmacoeconomic considerations and other factors, as discussed below.In general, selecting the appropriate route of administration should be driven by efficacy and safety, as well as cost effectiveness and patient preference, as this will ensure optimal treatment adherence .As discussed previously, mAbs are often administered by the IV route, which provides maximum bioavailability with minimal risk of immunogenicity. In addition, IV administration is suitable for medications that are administered in large volumes and those that may cause irritation . The draSC administration is less invasive than IV administration, it may be performed by the patient and therefore, is associated with shorter clinic visits and more optimised use of healthcare resources , 65. On As highlighted in a recent systematic review (encompassing any drug class and indication), there are limited data on these various factors influencing choice of injection route . Thus, dIn an observational study of 201 patients with rheumatoid arthritis who were receiving treatment with IV infusions when asked if they would switch to SC administration, patients (54.2%) who chose to switch from IV to SC administration found SC injections more convenient than continuing IV therapy .Studies examining patient preference and/or adherence to IV or SC formulations of mAbs for severe asthma are required to further aid clinicians in determining the optimal drug and route of administration for their patients.Of the three mAbs that are available as add-on therapy in patients with severe asthma, IV and SC routes of administration may be utilised: reslizumab for the former and mepolizumab, benralizumab and omalizumab for the latter. Route of administration influences their pharmacology, but this does not appear to translate into striking differences in efficacy and safety, with all three drugs considered efficacious and generally well tolerated.max of IV reslizumab is much shorter than SC mepolizumab, benralizumab and omalizumab. Generally, mAbs have low Vd and t1/2 because of their large molecular size and hydrophilic nature [1/2 with IV versus SC administration of mepolizumab [max and similar t1/2.One of the main effects of route of administration on drug PK profile is on absorption, which is slower after SC dosing compared with IV dosing . Higher c nature , with soolizumab . TherefoIn clinical studies, reslizumab, benralizumab, mepolizumab and omalizumab have been consistently found effective in the treatment of patients with severe allergic asthma, reducing the number of clinical exacerbations experienced by patients in a year. Of the different drugs, mepolizumab has been studied for both IV and SC administration. The results of the MENSA clinical trial indicate that the SC mepolizumab may have superior efficacy over the IV formulation with regard to reducing the rate of serious asthma exacerbations . On the Immunogenicity is an important component of the pharmacology of mAbs. In this respect, the IV route of administration is likely to be superior, as it is associated with lower immunogenicity, as well as fewer local hypersensitivity reactions . HoweverCurrently available mAbs for the treatment of severe asthma include omalizumab, mepolizumab and reslizumab. These drugs are effective and have low immunogenicity due to their nature as humanised antibodies. Data collected on mAbs used in indications other than severe asthma suggest that both the SC and the IV routes of administrations have their respective advantages and disadvantages. Further research into this area is necessary.


The thrombolysis in myocardial infarction risk index (TRI) was developed to estimate prognosis at the initial contact of the healthcare provider in coronary artery disease patients without laboratory parameters. In this study, we aimed to investigate the relationship of the baseline TRI and contrast-induced nephropathy (CIN) in patients with ST-elevation myocardial infarction (STEMI).  A total of 963 consecutive STEMI diagnosed patients who underwent primary percutaneous intervention were included in the study. TRI was calculated using the formula “heart rate × (age/10) 2/SBP” on admission. CIN was defined as an increase in serum creatinine concentration ≥25%, 48 hours later over the baseline. n=128). TRI was significantly higher in the CIN (+) group compared with the CIN (−) group . There was a stronger correlation between CIN and age, diastolic blood pressure, heart rate, Killip class, left ventricular ejection fraction, amount of contrast media, and diabetes mellitus. The amount of contrast media  and TRI  were independent predictors of CIN. The best threshold TRI for predicting CIN was ≥25.8, with a 67.1% sensitivity and 80.4% specificity (area under the curve (AUC): 0.740, 95% CI: 0.711–0.768, P < 0.001).  Of the total of 963 patients, CIN was observed in 13% ( TRI is an independent predictor of CIN, and it may be used as a simple and reliable risk assessment of CIN in STEMI patients without the need for laboratory parameters. Contrast nephropathy (CIN) is characterized by an acute disruption in renal functions following exposure to contrast agents, and different studies have reported its incidence as 5–25% , 2. ManyThe thrombolysis in myocardial infarction risk index (TRI) is a simple risk score designed for using at initial presentation to predict mortality in STEMI patients; it does not include any laboratory variables. The TRI is derived from three readily available clinical variables and is calculated using the equation (heart rate × (age/10) 2/systolic blood pressure) , 8. TRI Various laboratory parameters and scoring systems have shown to be successful at predicting the development of CIN . In thisA total of 963 patients who presented with the diagnosis of STEMI between September 2015 and January 2018 and underwent primary PCI (p-PCI) were retrospectively included. Patients with known allergy against contrast agents, those presented with cardiogenic shock, patients using oral anticoagulants, those with hematologic disease, chronic inflammatory or autoimmune disease, patients with a creatinine clearance < 60 mL/min, and patients with chronic renal failure who required dialysis were excluded from the study. Age, systolic blood pressure (SBP), and heart rate (HR) were obtained at the time of admission in all patients. For each patient, TRI score was calculated before PCI, and the relationship between TRI and the development of CIN was investigated. Patients' TRI was calculated using the formula “heart rate × (age/10) 2/SBP” . Blood sSTEMI was defined as the presence of ST elevation at least 1 mm in two or more continuous leads (2 mm for V1–V3) or new-onset left bundle branch block. All patients underwent p-PCI within the first 12 hours after the onset of the chest pain. Before PCI, all patients were given acetylsalicylic acid (ASA) (300 mg) and clopidogrel (600 mg) as well as unfractioned heparin (70 IU/kg IV). After the intervention, all patients were given 1 mg/kg of subcutaneous enoxaparin twice daily, 100 mg/day of ASA, and 75 mg/day of clopidogrel. Patients who were using antihypertensive agents or those have a systolic blood pressure, which was measured at rest with five minutes intervals in different time periods higher than 140 mmHg or a diastolic blood pressure higher than 90 mmHg, were considered hypertensive .Patients who were using antidiabetics or having a postprandial blood glucose level higher than 200 mg/dL or fasting plasma glucose of at least two times above 126 mg/dL were considered diabetic [2.Hyperlipidemia (HL) was defined as a total cholesterol higher than 200 mg/dL, triglycerides level higher than 160 mg/dL, and low-density lipoprotein level higher than 130 mg/dL . PreexisP < 0.05 were included in the multiple logistic analysis. Receiver operating characteristic (ROC) curves were used to predict the future incidence of CIN.The data analysis was conducted using SPSS  and MedCalc statistical software . Continuous variables are expressed as the mean ± standard deviation. Categorical variables were compared using Chi-square or Fisher's exact tests and summarized as percentages. The Kolmogorov–Smirnov test was used to evaluate the distribution of the continuous variables. To predict CIN, age, gender, DM, HT, HL, systolic and diastolic blood pressure, heart rate, history of prior myocardial infarction (MI), Killip ≥3, pre-MI medication, syntax score, TIMI flow, GFR, creatinine, contrast amount, and TRI were included in the univariate analysis. The parameters with In this study, a total of 963 patients were included . A total of 128 (13.3%) patients developed CIN. Among these, 7.6% had grade 1 CIN and 5.7% had grade 2 CIN. The clinical characteristics as well as the angiographic and PCI features of the findings are listed in Tables 1Age, gender, DM, HT, SBP, diastolic blood pressure (DBP), heart rate, Killip >2, EF, basal creatinine, basal GFR, amount contrast agent, syntax score, TIMI flow, and TRI were statistically different in the CIN-positive group compared with the CIN-negative group.P < 0.001) and TRI ((OR) = 1.047, (CI): 1.020–1.075, P < 0.001) , those that were also found to be significant in the multiple regression analysis included contrast amount (odds ratio (OR) = 1.010, 95% confidence interval (CI): 1.007–1.012, < 0.001) .P < 0.001). TRI ≥ 25.8 predicted CIN development with 67.1% sensitivity and 80.4% specificity (The best TRI for CIN prediction was found to be 25.8 in the ROC curve analysis (AUC: 0.740, 95% CI: 0.711–0.768, cificity .In our study, TRI was found to predict the development of contrast-induced nephropathy in STEMI patients who underwent PCI. It was found to be an independent predictor of CIN without the need for laboratory parameters.CIN is a condition characterized by acute disruption in renal functions after exposure to contrast agents . MedullaPrevious studies have shown the association between the development of CIN and hospitalization duration, morbidity, and mortality . TherefoTIMI risk index is a score obtained by the formulation of age, systolic blood pressure, and heart rate, with a proven correlation with mortality and other outcome points in STEMI . In a stThe incidence of CIN has been reported to be higher compared with exposure to other elective contrast agents, because of the hemodynamic instability in primary percutaneous coronary intervention, the procedure itself, and the inability to take precautionary measure , 5. ConsThis is an observational, single-institution study, which had a relatively small sample size and was thus subject to various unaccounted confounders inherent in such an analysis. Our findings should be confirmed and the application of the risk score validated in a large multicenter trial. Our patient group included only STEMI patients, and other patients with acute coronary syndrome or stable angina were not included.In this study, we showed that increased TRI is an easily applicable simple and useful score without laboratory parameters. TRI is an independent early predictor of CIN in STEMI patients who are undergoing coronary intervention. Early prediction may provide time to prevent the progression of CIN and improve its negative impacts on outcome.