Chronic heart failure (CHF) is the end stage of cardiac disease with a 5-year mortality rate reaching 50%. Simvastatin is an antioxidant with lipid-lowering effects, which is commonly used to treat CHF. Resistance training is a nondrug treatment for CHF and exerts a positive effect on both the myocardial structure and function.  This study is aimed at exploring the effects and outcomes of simvastatin combined with resistance training on the mitochondrial membrane potential (MMP) of peripheral blood lymphocytes and the Janus kinase/signal transducer and activator of the transcription 3 (JAK/STAT3) signaling pathway in patients with CHF. n = 55) and intervention group (IG) (n = 56) using the random number table method. The CNG received simvastatin treatment only, whereas the IG received simvastatin treatment plus resistance training. Treatment efficacy, diastolic interventricular septal thickness (IVST), left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVDD), MMP fluorescence intensity, JAK mRNA and STAT3 mRNA relative expression levels, serum C-reactive protein (CRP), galectin-3, interleukin-6 (IL-6), N-terminal–probrain natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and heart-type fatty acid-binding protein (H-FABP) levels were compared in both groups.  One hundred and eleven patients with CHF were allocated to the control group (CNG) (P < 0.05), whereas LVEF, JAK and STAT3 mRNA relative expression levels, and MMP fluorescence intensity of peripheral blood lymphocytes were higher in the IG than in the CNG (P < 0.05).  After 6 months of treatment, diastolic IVST, LVDD, and serum levels of CRP, galectin-3, IL-6, NT-proBNP, hs-cTnT, and H-FABP decreased in both groups and were lower in the IG than in the CNG ( Simvastatin combined with resistance training improves heart function and reduces myocardial damage as well as the occurrence of adverse cardiac events compared with simvastatin alone. The mechanism may be related to the increase of expression of MMP, JAK, and STAT3, the regulation of MMP and JAK/STAT3 signaling pathways in peripheral lymphocytes, the alleviation of mitochondrial damage, and the inhibition of inflammatory response. Chronic heart failure (CHF) is the end stage of cardiac disease with a 5-year mortality rate reaching 50% . Mitochon = 55) and intervention (n = 56) groups in accordance with the random number table method. This study was approved by the Ethics Committee of Tongji University School of Medicine.A total of 111 patients with CHF treated at our hospital from January 2019 to January 2020 were enrolled. Inclusion criteria were patients who (1) met the diagnostic criteria for CHF in the Chinese Guidelines for the Diagnosis and Treatment of Heart Failure 2018 , (2) expThe patients in both the groups received symptomatic treatment with furosemide diuresis and oxygen inhalation. In addition to these, CNG received 20 mg oral simvastatin daily. IG received simvastatin combined with resistance training, with the simvastatin dose being same as that for CNG. Resistance training comprised an exercise performed with a maximum load, i.e., one repetition maximum. The starting load was 50% of the maximum load and increased to 60% in week 9. The resistance training included calf raises; quadricep, tricep, and bicep stretches; shoulder push-ups; abdominal tucks; latissimus dorsi pulldowns; lower back stretches; and chest thrusts. Training forms included weight training, dumbbells, squat raises, and extension springs. The training was supervised and directed by a professional trainer. In the first 4 weeks, 10 repetitions (reps) were performed. At weeks 5–8, 15 reps were performed. During weeks 9–12, only 10 reps each of triceps femoris and biceps brachii stretches, shoulder push-ups, and chest thrusts were performed, followed by 1 min of rest and then 10 reps again. Both the groups were treated for 6 months.Intervention was considered markedly effective if the NYHA grade improved by more than two grades or returned to normal. Intervention was considered effective if the NYHA grade improved by one grade. Intervention was considered ineffective if the NYHA grade did not improve. The total efficacy was calculated as 100% − ineffective.Interventricular septal thickness (IVST), LVEF, and left ventricular end-diastolic diameter (LVDD) were measured using color Doppler echocardiography before and after treatment.μL of the mitochondrial sample was added and incubated at 37°C for 10 min. The mitochondrial concentration was measured using a luciferase detector with an excitation wavelength of 490 nm and an emission wavelength of 590 nm.Venous blood (2 mL) was collected before and at 1, 3, and 6 months after treatment. The sample was diluted with 2 mL phosphate-buffered saline (PBS) solution, followed by treatment with 2 mL lymphocyte isolate. Then, diluted anticoagulant solution was added to the sample and centrifuged at 2000 rpm for 20 min. Lymphocytes were aspirated into a centrifuge tube with 2–5 mL of Hank's solution and centrifuged at 1500 rpm for 10 min. PBS precooled in an ice bath was added to resuspend the cells, and a small amount was used for cell counting. The remaining cells were centrifuged at 4°C for 5 min, 1–2.5 mL of mitochondrial isolation reagent was added, and the cells were suspended in an ice bath for 10–15 min. The cells were homogenized into 600 g aliquots and centrifuged at 4°C for 10 min. The cells were then centrifuged in a centrifuge tube at 11,000 rpm at 4°C for 10 min, and mitochondria were obtained via precipitation. Using a fluorescent probe kit, 10 μL 5× buffer, 0.5 μL reverse transcriptase, 0.5 μL oligonucleotides, and 0.5 μL random primers. After adding template RNA, RNase-free water was added to the final volume of 10 10 μg. The reaction conditions were as follows: 37°C for 15 min and 85°C for 5 s. GAPDH was used as the internal reference to calculate the optical density (ΔCt) of JAK and STAT3 miRNAs, and their relative expression levels were calculated using the 2 − ΔCt method.Venous blood (2 ml) was drawn and centrifuged at 2000 rpm for 20 min. The serum was decanted and again centrifuged at 2000 rpm for 20 min. The serum was taken and frozen in RNA enzyme tubes. Total RNA was extracted using an miRNA extraction kit and reverse-transcribed to cDNA; glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as an internal reference: gapDH (5′-3′)-TTGTGATGGGTGAACCTTCTGAGTGGCAGTGATG, length: 166 bp; JAK (5′-3′)-CCATTTTCTGCACAAACCCACGCCCACAGACAGC, length: 172 bp; STAT3 (5′-3′)-GTAGTGACGGAGAAGCAGTCACAGACTGGTTGTTCC, length: 181 bp. The polymerase chain reaction system comprised of 2 Venous blood (3 ml) was collected before and after treatment and was centrifuged in a centrifuge with a radius of rotation of 8 cm at 3000 rpm for 10 min. The supernatant was used to detect CRP levels via the immunoturbidimetric method and galectin-3 and IL-6 levels via an enzyme-linked immunosorbent assay.Peripheral venous blood (5 mL) was collected before and after treatment, centrifuged at 3000 rpm for 10 min, and the supernatant decanted. Serum N-terminal–probrain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) levels were detected via chemiluminescent immunoassays, and heart-type fatty acid-binding protein (H-FABP) levels were detected via colloidal gold immunochromatography.A 30 m line was drawn on a flat surface with a mark at every 5 m. The patients were asked to walk 6 m along the line. If symptoms such as fainting, systolic blood pressure > 240 mmHg, diastolic blood pressure > 130 mmHg, blood pressure drop of >20 mmHg, cardiac arrhythmias, and pain appeared, the test was immediately discontinued and the distance was recorded. The test was performed before treatment as well as at 1, 3, and 6 months after treatment.The patients were observed for the occurrence of any adverse cardiac events during treatment. These events included acute myocardial infarction, persistent myocardial ischemia, cardiogenic shock, and coronary revascularization.t-test. Count data were expressed as percentages and numbers and analyzed using χ2 test.The statistical software SPSS19.0 was applied for data analysis. Measurement data were expressed as P > 0.05; No significant intergroup differences were observed in age, NYHA classification, proportions of patients with CHF along with diabetes, patients with CHF along with hyperlipidemia, and patients with primary disease (P < 0.05), indicating that simvastatin combined with resistance training provides better therapeutic effects than simvastatin alone in patients with CHF  (with CHF .P > 0.05). After 6 months of treatment, IVST and LVDD were noticeably lower, whereas LVEF was remarkably higher than those of pretreatment in both groups (P < 0.05). This suggests that simvastatin combined with resistance training significantly improves the cardiac function of patients with CHF . This suggests that simvastatin combined with resistance training increases JAK and STAT3 mRNA relative expression levels in patients with CHF . This suggests that simvastatin combined with resistance training significantly reduces serum CRP, galectin-3, and IL-6 levels in patients with CHF . This finding indicates that simvastatin combined with resistance training significantly reduces serum NT-proBNP, hs-cTnT, and H-FABP levels in patients with CHF  than in the CNG (18.18%) (CHF can lead to alterations in myocardial structure and function, resulting in impaired ventricular function, decreased ventricular ejection capacity, prolonged disease course, and recurrent episodes; it is a leading cause of death in patients with cardiovascular disease , 9. The Simvastatin lowers lipid levels and acts on hibernating cardiomyocytes to reverse hibernation, thereby improving left ventricular ejection capacity. It also reduces inflammatory cell chemotaxis and aggregation as well as inhibits matrix metalloproteinase expression by macrophages; thus, it reduces myocardial damage and protects the myocardium. Moreover, it inhibits free radical production and exerts antioxidant effects. Resistance training is one of the intervention therapies for CHF that can increase diastolic, but not systolic, blood pressure, thereby increasing coronary blood flow and improving cardiac function. Resistance training regulates vasoconstrictor system activation, reduces ventricular remodeling, improves myocardial function, slows the heart rate, reduces myocardial perfusion, increases myocardial blood supply, improves patients' exercise endurance, and plays a positive role in improving the long-term prognosis of patients with CHF . The preMitochondria maintain the normal activity of cardiomyocytes and provide energy for myocardial activity, and mitochondrial injury is involved in CHF development. The specific mechanism remains unclear, but the current research suggests that mitochondrial injury is one of the pathological mechanisms of the occurrence and development of CHF, and there is an obvious correlation between the degree of mitochondrial injury and the grade of cardiac function , 14. TheMultiple inflammatory factors are involved in the pathophysiological process of heart failure, and myocardial injury in heart failure is closely related to inflammation , 22. CRPIn summary, simvastatin combined with resistance training improves the therapeutic effect, improves cardiac function, and reduces myocardial injury as well as adverse cardiac events in patients with CHF. However, this study has some shortcomings, such as a small sample size and a short follow-up period. Therefore, it is necessary to evaluate a larger group of patients to validate the value of simvastatin combined with resistance training in the prognosis of patients with CHF.


For every 1 unit of Na/K ratio increase, blood pressure increased by 0.46/0.24 mmHg. Blood pressure was 2.75/1.27 mmHg higher in quartile 4 than quartile 1 of Na/K. It remains high sodium and low potassium for hypertensive patients in China. Decreased sodium, Na/K ratio and increased potassium may help for blood pressure management.Sodium and potassium intake in hypertensive patients in China is not clear. The authors aimed to investigate the distribution of sodium and potassium intake in hypertensive patients in China, and to analyze the relationship between sodium and potassium intake and blood pressure. The study was performed in 130 hospitals from 23 provinces across China from 2016 to 2019. Finally, 9501 hypertensive patients average aged 54 years were included. 24 h urinary sodium and potassium excretion were measured. Distribution of urinary electrolytes were described according to age, gender and region. The association between urinary electrolytes and blood pressure was analyzed by multivariate linear regression. Hypertensive patients exhibited an average 24 h urinary sodium and potassium excretion of 156.7 ± 81.5 mmol/d and 39.2 ± 20.2 mmol/d , sodium/potassium ratio (median) of 4.14 . Urinary electrolytes were lower in women than men (sodium: 171.1 vs 138.7,  This program aimed to reduce the average salt intake from 10.5 g/d to less than 5 g/d by 2030 in China. To evaluate sodium and potassium intake in hypertensive patients, 24 h urinary electrolytes were measured in patients with essential hypertension in 130 hospitals of 23 provinces in China between October 2016 and October 2019. This study has been approved by the ethics committee of Peking University People's Hospital, and informed consent was obtained (N0.2016PHB074‐01).2.1Hospitals were recruited according to the geographical distribution, namely each province chooses one tertiary hospital (more than 1000 beds and has hypertension ward) as the leading unit, and each tertiary hospital organizes 5–10 subordinate hospitals to participate in the study. Only hospitals that were able to conduct 24 h urinary electrolyte measurements were included. The working team gathered all researchers in each region to introduce the investigation purpose, requirements and implementation plan of the investigation, to conduct training, and to provide SOPs before participants recruitment.2.2Participants were enrolled in the study according to the sequence of hospitalization in a consecutive manner. Patients’ informed consent were obtained before study. Inclusion criteria were as follows: (1) essential hypertensive patients according to 2010The exclusion criteria were as follows. (1) Patients with serious systemic diseases , secondary hypertension, and other conditions that could cause structural changes, remodeling of the heart, and serious complications . (2) Patients with severe liver and kidney disease, infection, tumors, malnutrition, severe cardiorenal insufficiency, cardiocerebral vascular events in the past 6 months , hypertensive urgency, and poorly controlled diabetes (fasting bloodglucose > 11.1 mmol/L). (3) Patients using glucocorticoids. (4) Patients whose urine could not be collected all day or with a 24‐h urine output of < 500 ml or > 5000 ml.2.3We provided 5‐liter urine buckets for each patient. Under a regular diet, 24 h excreted urine was collected, from 7:00 am on the first day and including the urine at 7:00 am on the second day, with the first urine sample discarded Figure . If the 2.42) were recorded for all participants.Demographic variables: age, gender, habits of smoking and drinking, medication, medical history, height (cm), weight (kg), and body mass index (BMI) = weight/height  was used to measure blood pressure according to clinical practice in each centre. Most patients used adult standard cuff (size 12 × 24 cm). If the upper arm circumference was larger than 36 cm, large cuff was used (size 16 × 30 cm) and if the upper arm circumference was smaller than 27 cm, small cuff was used (size 12 × 22 cm). Two blood pressure readings were taken on the right arm at an interval of 1–2 min. The average of the two readings was calculated.2.5Statistical analysis was performed with SAS 9.4 software .2 test where appropriate. The sodium/potassium ratio was reported by median (mmol/d) due to skewed distribution. One‐way analysis of variance was used for comparison between multiple groups and Tukey method was used for post‐hoc pairwise comparison. Study population was categorized as below: (1) by age: < 45, 45–65, ≥65 years old (2) by gender:men and women (3) by geographical distribution of seven regions and their provinces: northwest , northeast , southwest , east , central (Henan and Hunan), south (Guangdong), and north China . To analyze the association between Na/K ratio and blood pressure, multivariate linear regression analysis was conducted, adjusted for age, gender, BMI, and use of hypertensive medication. P < .05 was considered statistically significant.We first compared gender differences for baseline characteristics. Continuous and categorical variables were reported as mean ± SD, median (IQR), and n (%) and tested by t‐test, Mann Whitney U test, and χ33.12. A total of 81% of the participants received antihypertensive medication treatment (N = 6303). The percentage of antihypertensive medication use for ACEI, ARB, β‐blockers, CCB and low dose diuretics (Single‐Pill Combination included) was 10%, 24%, 19%, 64% and 9%, respectively. Urinary sodium was neither associated with antihypertensive medication use (p = .5645) nor diuretic use (p = .7838). The baseline characteristics of the patients are displayed in Table A total of 9501 patients with hypertension from 130 hospitals in 23 provinces were finally included . The mean urinary potassium was 39 ± 20.24 mmol/d . The median sodium/potassium ratio was 4.14. The proportion of patients with low (< 100 mmol/d), medium (100‐200 mmol/d), and high (≥200 mmol/d)3.3The age distribution was as follows: < 45 years old , 45–65 years old , and > 65 years old . Altogether there were 5309 men and 4192 women. The proportion of women was higher in the older age group Figure . The mea3.4The average urinary sodium was 69.8 ± 21.0 mmol/d, 145.7 ± 28.0 mmol/d, and 268.8 ± 58.9 mmol/d in the low, medium, and high sodium groups, respectively. The average urinary potassium was 27.8 ± 13.1 mmol/d, 38.8 ± 17.8 mmol/d, and 49.7 ± 23.7 mmol/d, respectively Figure . High so3.5A total of 130 hospitals in 23 provinces and cities were included in this study, and 24 h urinary sodium value of > 156.8 mmol/d  were in 14 provinces and cities. Salt intake was > 6 g/d in all 23 provinces and cities involved in the study Figure , whereas3.6Univariate analysis showed that urinary sodium excretion had a non‐linear trend with systolic blood pressure Figure  but a li4China is a country with a high incidence of hypertension and cerebral stroke.Our study suggested an excessive sodium but insufficient potassium consumption and a consequent high sodium/potassium intake ratio in Chinese hypertensive patients. The average intake was 9.2 g/d, 2.9 g/d for sodium and potassium, respectively. The median Na‐K ratio was 4.14. The WHO and 2030 China Health Action Plan set the goal to reduce sodium intake to < 5 g/d.Moreover, our study also showed that among hypertensive patients, sodium intake is 17% higher in those younger than 45 years compared with those older than 65 years. Additional analysis showed similar results after BMI was adjusted (data not shown), which suggested that the higher consumption of salt may not simply be due to higher consumption of food but higher sodium content instead. This warranted further attention. With the urbanization of the country, the dietary patterns and habits have undergone significant changes. Most young people do not eat at home; about 60% of them eating out for at least two meals a day . As the salt content of takeaway and fast food cannot be controlled, it is likely that young people eat a diet with higher sodium content. On the contrary, the elderly are more likely to maintain traditional family eating habits. At present, the supply of low‐sodium chloride in the market, the nation's popularization of education regarding salt intake, and controlling the amount of salt used for cooking have begun to show effects. Our results suggest that the salt control strategies introduced within families could spread to every corner of society.According to the regional distribution of salt content in hypertensive patients in China, northwest China had the highest salt content with an increased sodium/potassium ratio, whereas the intake of sodium chloride was the lowest in south China with a urinary sodium/potassium ratio significantly lower than those in other regions. This further demonstrates the special salt diet pattern in China: ‘high in the north, low in the south’. High sodium and low potassium were associated with increased blood pressure. A recent study in a general Chinese population, which used 24 h‐recall as measurement of diet electrolytes, showed similar findings for regional differences between north and south China.The focus of this study: a large‐scale epidemiological survey involving 130 hospitals in 23 provinces of China was conducted to examine the salt intake status of Chinese hypertensive patients. Our study also assessed salt intake levels of hypertensive patients of different ages. All the participating hospitals performed the implementation plan according to the unified SOP. In this study, we used 24 h urinary sodium and potassium excretion as the gold standard for evaluating salt intake.Limitations of this study: In consideration of the financial limitations and maneuverability of the study, most 24 h urine collections were performed only once. And not all of the participants tested for urinary creatinine. The results would be more accurate with multiple urine collections to account for day‐to‐day variation as well as urinary creatinine measurement to adjust for urine sample completion. Besides, information about season and temperature was not collected, which may affect urinary electrolytes excretion and will be considered in following study. In addition, this study did not include certain provinces and cities , which should be further covered in the future.The authors have no conflict of interest to declare.Ningling Sun proposed the concept and design of this paper, participated in the research and provided a large number of research data. Jiguang Wang supervised the conduct of the study and gave timely guidance. Yifang Yuan conducted data analysis and was part of the writing of Methods and Results, Ningling Sun wrote the Introduction, and Discussion and fully discussed the research data with the statisticians. Dr. Sun and Jiguang Wang reviewed and edited the manuscript and contributed to the discussion section. Other coauthors have suggested modifications to the manuscript. All the authors contributed to data collection and discussion of the paper.None.Figure S1. Urine retention time 24 h a day.Click here for additional data file.Figure S2. Distribution of sodium excretionClick here for additional data file.Figure S3. Urinary electrolytes (A), gender (B), and sodium/potassium ratio (C) according to urinary sodium categories.Click here for additional data file.Figure S4. A) The distribution of urinary sodium in 23 provinces and cities. B) The distribution of urinary potassium in 23 provinces and cities. C) Sodium and potassium in seven regions. D) The sodium/potassium ratio according to seven regions.Click here for additional data file.


This cohort study examines the association of fasting blood glucose level with risk of kidney disease progression among patients with diabetes. What is the optimal glycemic target associated with slowing of the progression of diabetic kidney disease?In this cohort study of 183 049 adults with diabetes using antihyperglycemic agents, among individuals with albuminuria, a fasting blood glucose level of 126 mg/dL to less than 160 mg/dL was associated with decreased risk of the composite outcome of serum creatinine doubling, end-stage kidney disease, or death from chronic kidney disease. Among individuals with no albuminuria, a fasting blood glucose level of 100 mg/dL to less than 126 mg/dL was associated with decreased risk of the composite outcome and a level of less than 140 mg/dL was associated with decreased risk of new-onset albuminuria.These findings suggest that the optimal on-treatment glucose level associated with slowing the progression of established diabetic kidney disease is higher than the level associated with preventing the development of diabetic kidney disease. The appropriate target of glycemic control in diabetic kidney disease is unclear.To investigate optimal on-treatment glycemic levels associated with slowing of diabetic kidney disease progression.This retrospective cohort study was conducted using nationwide Korean cohorts from the National Health Information Database from 2005 to 2019. Included individuals were adults with diabetes using antihyperglycemic agents with and without chronic kidney disease (CKD) identified from participants aged 40 to 74 years in a nationwide health screening survey conducted from 2009 to 2010. Data were analyzed from October 2020 through March 2021.On-treatment fasting blood glucose (FBG) level.The primary outcome was a composite of doubling of serum creatinine, end-stage kidney disease, or death from CKD.2  and 51 648 individuals with no CKD . During 9 years of follow-up, the primary outcome occurred among 13 802 individuals with CKD (10.5%) and 1421 individuals with no CKD (2.8%). On-treatment FBG level had a J-shaped hazard ratio (HR) curve for the primary outcome. Among patients with albuminuria, FBG levels of 126 mg/dL to less than 140 mg/dL  and 140 mg/dL to less than 160 mg/dL  were associated with decreased risk and levels of 160 mg/dL to less than 180 mg/dL were associated with increased risk  compared with FBG levels of 110 mg/dL to less than 126 mg/dL. Among patients with decreased eGFR, FBG levels of 80 mg/dL to less than 100 mg/dL  and levels of 160 mg/dL to less than 180 mg/dL  were associated with increased risk of the primary outcome compared with FBG levels of 110 mg/dL to less than 126 mg/dL. Among patients with no CKD, FBG levels of 80 mg/dL to less than 100 mg/dL  and levels of 126 mg/dL to less than 140 mg/dL  were associated with increased risk compared with FBG levels of 110 mg/dL to less than 126 mg/dL. Among patients with no albuminuria at baseline, FBG levels of 140 mg/dL to less than 160 mg/dL  were associated with increased risk of new-onset albuminuria, while levels of 100 mg/dL to less than 110 mg/dL were not associated with increased risk compared with FBG levels of 110 mg/dL to less than 126 mg/dL. For all-cause mortality, while FBG levels of 160 mg/dL to less than 180 mg/dL  were associated with increased risk among patients with albuminuria, FBG levels of 140 mg/dL to less than 160 mg/dL were associated with increased risk among patients with decreased eGFR  and those with no CKD  compared with levels of 110 mg/dL to less than 126 mg/dL.Among 183 049 adults with diabetes using antihyperglycemic agents , there were 131 401 individuals with dipstick albuminuria or an estimated glomerular filtration rate (eGFR) of 15 to 59 mL/min/1.73 mThese findings suggest that intensive vs standard glucose control may not be associated with increased protection for the progression of established diabetic kidney disease and that timely control is important for prevention. However, careful glycemic control would still be associated with improved overall outcomes among patients with CKD, particularly those with no albuminuria. Decreasing blood glucose levels among patients with diabetes is associated with decreased incidence of diabetic kidney disease. However, the appropriate blood glucose target associated with slowed progression of diabetic kidney disease is unknown.The prevalence of end-stage kidney disease (ESKD) is rapidly increasing worldwide,4 However, trials did not find a clear benefit of intensive control for slowing kidney disease progression. In a 2017 Cochrane review,5 intensive control targeting hemoglobin A1c (HbA1c) levels less than 7%  or fasting blood glucose (FBG) level less than 120 mg/dL , intensive vs less stringent control was not associated with significant differences in risk of doubling serum creatinine, ESKD, or mortality, whereas it was associated with decreased risk of incident or increasing albuminuria. In contrast to the review that included trials with a mean of approximately 5 years of follow-up, an extended 22-year follow-up study of the Diabetes Control and Complications Trial for type 1 diabetes found that intensive control vs conventional control was associated with decreased incidence of an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2.6 It is possible that long-term glucose control is associated with slowed kidney disease progression and eventually prevention of progression to ESKD. However, long-term, large-scale studies will be needed to ascertain the kidney benefit of glycemic control, and there is a lack of data on the appropriate treatment target of blood glucose among patients with diabetic kidney disease. To investigate optimal on-treatment glycemic levels associated with slowing the progression of diabetic kidney disease, we estimated risks for doubling serum creatinine, ESKD, and mortality by on-treatment FBG levels and baseline kidney disease status in population-representative groups of patients with diabetes and chronic kidney disease (CKD) in Korea.In randomized controlled trials that compared different glycemic targets among patients with type 2 diabetes, intensive vs standard control consistently decreased the onset and increase of albuminuria.STROBE) reporting guideline for cohort studies.This cohort study’s design was approved by the institutional review board of Kangwon National University Hospital, which waived the need for informed consent because the data used were deidentified prior to analysis. The study followed the reporting requirements of the Strengthening the Reporting of Observational Studies in Epidemiology  at baseline  were identified. From 315 304 patients with CKD and diabetes, 20 238 individuals with missing or outlier data, 50 984 individuals with a history of heart disease or stroke or an eGFR of less than 15 mL/min/1.73 m2, and 17 183 individuals who died or developed cardiovascular diseases, major cancers, or ESKD before baseline were excluded to minimize confounding by prior diseases. Among the remaining 226 899 patients, 131 401 individuals who had initiated glucose-lowering medication before January 1, 2010, and received the medication regularly to December 31, 2010  were included in the final analysis to evaluate long-term outcomes of on-treatment glycemic levels among patients with CKD and diabetes .diabetes .2 or a history of heart disease or stroke, and 7559 individuals who died or developed ESKD, cardiovascular diseases, or major cancers before baseline were excluded. Among the remaining 144 974 patients, 64 861 individuals who had initiated glucose-lowering medication before 2010 and received the medication regularly to the baseline were included in the final analysis.In addition, among 12 107 000 participants in the nationwide health screening survey, 1 210 715 individuals (10.0%) were randomly selected to generate a nationally representative sample. From these selected survey participants, 174 426 individuals who had diabetes at baseline were identified. Among these, 8951 individuals with missing or outlier data, 12 942 individuals with an eGFR of less than 15 mL/min/1.73 m10 on-treatment and untreated FBG records were separated. On-treatment FBG level was considered to be the FBG level for a patient who had received antihyperglycemic agents for 90 or more days in the year of measurement  and irregular when the prescription was for one-half or less of each period.Participants underwent medical health examinations generally at 2-year intervals. During the examination, FBG level was measured from samples collected after an 8-hour to 12-hour fast. Because the risk thresholds of hyperglycemia were different depending on antidiabetic use status,12With baseline data, the variables of age, sex, albuminuria status, time of antidiabetic initiation, antihypertensive and statin use statuses, systolic blood pressure level, body mass index , family history of cardiovascular disease, income, smoking status, physical exercise frequency, drinking amounts, and total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol levels were categorized  were estimated in Cox models with time-varying covariates. The timely mean of on-treatment and untreated FBG levels were entered as time-varying covariates to obtain HRs of on-treatment FBG level adjusting for untreated levels. Yearly updated antidiabetic use status was also entered as a time-varying covariate. The continuous variable of baseline eGFR and the categorized variables of baseline age, sex, albuminuria status, time of antidiabetic initiation, antihypertensive and statin use statuses, systolic blood pressure, BMI, family history of cardiovascular disease, income level, smoking status, exercise frequency, drinking amount, and total, HDL, and LDL cholesterol levels were entered as fixed covariates . Subgroup analyses stratified by albuminuria or eGFR level were performed to evaluate outcome modification associated with CKD. Analyses stratified by albuminuria level were performed among the albuminuria and general populations and those by eGFR levels were performed among the decreased eGFR and general populations to provide population-representative results. Furthermore, analyses were performed after classifying participants into 1 of 4 groups by the presence or absence of albuminuria and decreased eGFR to evaluate independent and additive outcomes associated with albuminuria and decreased eGFR. In addition, to explore the outcomes associated with transient creatinine increase, the analyses for creatinine doubling were performed after excluding participants whose creatinine doubled from baseline but decreased to less than 2-fold at the last measurement. Analyses including baseline FBG level rather than timely means of levels were also performed to compare outcome risks of baseline and time-updated levels. The proportional hazard assumption in Cox models was tested by including time-dependent interaction terms of on-treatment FBG levels and a log function of follow-up time. Statistical analyses were conducted using SAS statistical software version 9.4 (SAS Institute). Data are presented as numbers and percentages, means and SDs, HRs and 95% CIs, or incidence rates and 95% CIs. 2 to less than 60 mL/min/1.73 m2, and 64 861 individuals from the general population , including 131 401 individuals with CKD  and 51 648 individuals without CKD , there were 72 268 individuals with dipstick albuminuria, 74 717 individuals with an eGFR of 15 mL/min/1.73 mpulation . The dispulation .During 9 years of follow-up, the composite outcome of major kidney events was found in 11 120 individuals (15.4%) in the albuminuria population, 8048 individuals (10.8%) in the decreased eGFR population, and 2787 individuals (4.3%) in the general population  and levels more than 180 mg/dL  were associated with increased risk of the primary outcome compared with FBG levels of 110 mg/dL to less than 126 mg/dL. Among patients with no albuminuria, FBG levels of 80 mg/dL to less than 100 mg/dL  and levels of 126 mg/dL to less than 140 mg/dL  were associated with increased risk compared with FBG levels of 110 mg/dL to less than 126 mg/dL  and 1421 individuals with no CKD (2.8%). In subgroup analyses stratified by albuminuria or eGFR level  was associated with decreased risk of ESKD among patients with preserved kidney function. Nonetheless, intensive glucose control did not decrease the risk of creatinine doubling in that trial,14 and its benefit for preventing ESKD was not found in other trials.15 There are few studies, even observational studies, that investigate the association between glycemic control and risk of kidney disease progression. In a cohort study of 23 296 patients with CKD that had nearly 4 years of follow-up, an HbA1c level of less than 9% was associated with increased risk for creatinine doubling and ESKD among patients with an eGFR of 30 mL/min/1.73 m2 to less than 60 mL/min/1.73 m2, while there was a smaller increase in risk among patients with an eGFR of 15 mL/min/1.73 m2 to less than 30 ml/min/1.73 m2.16 By comparison, in our longer-term and larger-scale study, the curve of on-treatment FBG level HRs for creatinine doubling and kidney failure was J shaped, and the FBG level with the nadir risk was higher among patients with albuminuria or a decreased eGFR than among patients without CKD. Furthermore, the FBG level with the lowest HR for progressive kidney dysfunction was substantially higher than that for incident albuminuria. These findings support the theory of a final common pathway to ESKD18 and may provide epidemiologic evidence that the optimal on-treatment glucose level associated with slowing the progression of diabetic kidney disease is higher than the level associated with preventing the development of diabetic kidney disease.In clinical trials,19 intensive vs standard glucose control  was associated with increased risk for mortality among 3636 patients with CKD but not among 6506 patients with no CKD. The intensive control–associated increase in mortality risk among individuals with CKD may be associated with 3160 patients with a urine albumin to creatinine ratio of 30 mg/g or more rather than 821 patients with an eGFR of 45 mL/min/1.73 m2 to less than 60 mL/min/1.73 m2, as suggested by our study’s funding. Thus, apart from blood glucose control, intensive blood pressure lowering and active use of renin-angiotensin system blockers and sodium-glucose cotransporter 2 inhibitors should be considered in treatment of patients with albuminuria.23 However, among patients with diabetes and CKD but no albuminuria, deliberate glycemic control may still be important to decrease overall health risks.In this study, cardiovascular and mortality HRs were lowest at an FBG level of 110 mg/dL to less than 140 mg/dL among most patients, while the FBG level with the nadir HR for all-cause mortality was higher among patients with albuminuria but not among patients with decreased eGFR. In a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes trial,24 whereas on-treatment glucose has J-shaped risk curves.10 The inclusion of untreated blood glucose could be associated with overestimation of the benefits of glycemic control. The separated on-treatment glucose levels may better reflect treatment outcomes than unseparated levels.This study had several strengths. First, long-term outcome risks could be successfully assessed according to narrow-width glycemic levels and baseline kidney disease status in large-scale cohorts. Additionally, the study included albuminuria and decreased eGFR as representative of diabetic kidney disease. Furthermore, a timely mean of FBG levels was used as the exposure variable to assess the outcome associated with glycemic control during the study follow-up. In particular, on-treatment and untreated FBG levels were separately included in the analysis. In general, untreated FBG level shows linear associations with outcome risks,1c, FBG level was used only to assess glycemic status. Although HbA1c is widely used as a target of glycemic control, it cannot reflect glucose variability or extent of hypoglycemia.25 There is a need to consider FBG level in practice, and the information on optimal on-treatment FBG levels may be relevant in treatment of patients with CKD, among whom hypoglycemia is common.27 In addition, the biennial measurement of urine albumin and serum creatinine could potentially lead to errors in time to event analyses. However, in this 9-year follow-up study, the 1 year or 2 years earlier or later detection of albuminuria or creatinine doubling may not considerably influence the results. In addition, this study did not distinguish between type 1 and type 2 diabetes given that there were no available data to distinguish between the 2 conditions, the risk estimates could potentially be influenced by reverse causality or residual confounding, and drug-specific outcomes associated with antidiabetic treatment were not analyzed, given that many hypoglycemic drugs were used for various periods. Additionally, caution is required when applying the findings to other populations given that this study included residents in Korea aged 40 to 74 years who had no known cardiovascular or cancer disease.This study also has several limitations. Given the lack of data on HbAThis study’s findings suggest that timely blood glucose control is important for preventing diabetic kidney disease and that intensive vs standard glycemic control may not be associated with greater protection for the progression of established diabetic kidney disease. An individualized and comprehensive approach is necessary for treating patients with diabetes and CKD. Nonetheless, careful glycemic control may still be associated with decreasing overall health risks among patients with CKD, particularly those with no albuminuria.


Kidney dysfunction may lead to increased mortality and morbidity in patients who undergo living donor liver transplantation (LDLT). We investigated the clinical utility of SstO2 during LDLT for identifying postoperative kidney dysfunction.Somatic tissue oxygen saturation -matched.2 values than those with normal kidney function. Low SstO2 (< 66%) 1 h after graft reperfusion was more highly predictive of early kidney dysfunction than the values measured in other intraoperative phases. A decline in the SstO2 was also related to kidney dysfunction.Patients with early kidney dysfunction had significantly lower intraoperative SstO2 in patients undergoing LDLT. A low SstO2 (< 66%), particularly 1 h after graft reperfusion, was significantly associated with early kidney dysfunction after surgery. SstO2 monitoring may facilitate the identification of early kidney dysfunction and enable early management of patients.Kidney dysfunction after LDLT is associated with patient morbidity and mortality. Our results may assist in the detection of early kidney dysfunction by providing a basis for analyzing SstO Living donor liver transplantation (LDLT) is a critical treatment for patients with end-stage liver disease (ESLD). Kidney dysfunction is one of the most common complications after liver transplantation (LT), affecting short- and/or long-term outcomes. Therefore, it is essential to identify intraoperative risk factors for the development of kidney dysfunction . Many fa2) [cerebral (SctO2) and somatic (SstO2) tissue oxygen saturations] can be determined , or hepatorenal syndrome), and missing laboratory data. Thirty-six patients were excluded based on the exclusion criteria, of which twelve (33.3%) were excluded because of missing data. In total, 268 adults were analyzed, and 200 were matched via 1:1 propensity score (PS) matching (Data from 304 adults (aged > 19 years) undergoing elective LDLT between January 2015 and February 2020 at Seoul St. Mary’s Hospital were retrospectively collected from the electronic medical records system. Exclusion criteria included a preoperative history of kidney dysfunction  < 60 mL/min/1.73 mmatching .All patients were monitored using the INVOS 5100c oximeter  which consists of a light source and detectors. Based on the difference in NIR light absorption between oxygenated and unoxygenated hemoglobin, the oximeter system calculates hemoglobin saturation of the blood, in the brain or other tissues beneath the sensor, using the Beer-Lambert law , 16.2) and cerebral (SctO2) oximetry values were recorded five times after inducing anesthesia .In the present study, a somatic sensor was placed on the forearm on the opposite side of the peripheral venous line . The cer-1.154 × age-0.203 × 1.212 (if black) × 0.742  [2), mild dysfunction (eGFR 89–60 mL/min/1.73 m2), or moderate dysfunction (eGFR 59–30 mL/min/1.73 m2). In our study, early kidney dysfunction was defined as the lowest eGFR < 60 mL/min/1.73 m2 during the first week after surgery.Kidney function was evaluated based on the eGFR, calculated using the Modification of Diet in Renal Disease formula: eGFR = 175 × standardized serum creatinine female) , kidney LT and general anesthesia were performed by expert surgeons and anesthesiologists, respectively. The surgical procedure and anesthetic management were described in detail in our previous study . The surBalanced anesthesia was applied with proper hemodynamic management  under hemodynamic monitoring. According to the transfusion guidelines,  packed rAs calcineurin inhibitor was used as an immunosuppressant after surgery. The trough calcineurin inhibitor level was maintained between 7 and 10ng/mL for the first postopearative month. Other immunosuppressants (mycophenolate mofetil and prednisolone), which were administered according to our hospital’s LDLT protocol, were gradually adjusted and tapered after LDLT , 22.2). Donor findings included age, sex, BMI, graft-recipient weight ratio, total ischemic time, and donor graft fatty change.The preoperative recipient findings included age, sex, BMI, comorbidities (hypertension and DM), ejection fraction, eGFR, MELD score, hepatic decompensation parameters  between the normal and kidney dysfunction groups using analysis of covariance (ANCOVA). Oxygen saturation at each stage was also compared using the Mann-Whitney U test and χ2 or Fisher’s exact test, as appropriate. The predictive accuracy of the models was evaluated based on the AUC. The optimal cut-off of the SstO2 for the prediction of early kidney dysfunction was determined using the AUC. In addition, 1:1 PS matching was used to correct any imbalance in confounders between the low and high SstO2 groups. After matching, we compared perioperative recipient and donor graft factors using the Mann-Whitney U test and χ2 or Fisher’s exact test, as appropriate. The association between low SstO2 1 h after graft reperfusion (< 66%) and postoperative early kidney dysfunction was evaluated by multivariate logistic regression analyses after adjusting for the PS and intraoperative factors, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Continuous data are presented as medians and interquartile range (IQR), and categorical data are presented as frequencies and proportions. A p-value < 0.05 was considered significant in all analyses. Statistical analyses were performed with SPSS for Windows , R software , and MedCalc for Windows .We compared the levels of tissue oxygen saturation .Patients with early kidney dysfunction showed significantly lower intraoperative SstO2 AUC values at different times (2 (< 66%) at T4 was significantly associated with early kidney dysfunction . Regarding the receiver operating characteristics curves of the change in SstO2 compared to saturation at T0, the difference in oxygen saturation between T0 and T1 was significantly associated with early kidney dysfunction  and donor-graft parameters  1 h after graft reperfusion was significantly associated with the development of early kidney dysfunction in PS-matched patients (2 remained an independent predictor of early kidney dysfunction (p = 0.001).A low SstOpatients . After a2 group (< 66%) suffered early kidney dysfunction (eGFR < 60 mL/min/1.73 m2) than in the high SstO2 group (≥ 66%)  during the first week in the low SstO2 group (< 66%) after surgery than in the high SstO2 group (≥ 66%) (Significantly more patients suffered kidney dysfunction (eGFR < 60 mL/min/1.73 m (≥ 66%) .p < 0.001, The somatic tissue oxygen saturation (%) at times T1–T4 was significantly associated with the hourly urine output  1 h after graft reperfusion had higher predictive accuracy for early kidney dysfunction than values measured in other intraoperative phases. The low SstO2 (< 66%) in PS-matched patients, adjusted for PS and intraoperative factors, was approximately four-fold more strongly associated with early postoperative kidney dysfunction. A decline in the SstO2 compared to that measured immediately after inducing anesthesia was also related to kidney dysfunction. Thus, SstO2 itself, and deterioration therein, could also be important for predicting kidney dysfunction.The main finding of this study was that intraoperative SstO2 monitoring has been widely performed in pediatric patients, and is usually measured in the renal, splanchnic, or thoracic beds because of the anatomical features . Pediatric cohort studies suggest that SstO2 is closely associated with systemic oxygenation, transfusion of red blood cells, and circulatory indices. Patients with a lower SstO2 level require more extracorporeal membrane oxygenation, inspired nitrogen, and mechanical ventilation than those with a higher SstO2 level [2 is an emerging and reliable non-invasive tool to identify early loss of kidney function. In cardiac surgery with cardiopulmonary bypass and an oximeter sensor at the level of the kidney (T10–L2) for renal oximetry, infants (aged < 1 year) with prolonged lower renal SstO2 values  during surgery and the first 48 h postoperatively showed more frequent AKI than those with higher values. Additionally, renal SstO2 may be better correlated with AKI compared to conventional laboratory markers  [Intraoperative SstOO2 level , 24–26. pocalin) .2 in the trunk beds of adults, including the renal beds, compared to the pediatric setting. One cardiac study reported that the intraoperative duration of renal SstO2 < 55% was associated with the postoperative occurrence of AKI [2 sensors are typically placed over skeletal muscles  [2 recorded from the thenar muscle of the hand was associated with the development of AKI. In that report, the SstO2 20 min after cardiopulmonary bypass had a cut-off value of ≤ 54.5% and acceptable AUC values of around 70% [Few studies have monitored SstOe of AKI . Howeverlf area) . In a pround 70% . Intraopound 70% .2 is an emerging marker of early postoperative complications in patients undergoing LT; however, SstO2 measurement sites differ among LT studies [et al., the oximetry sensor was placed on the dermatome overlying the liver allograft [2 was significantly associated with the cardiac index, hemoglobin, and APACHE II score. Shiba et al. reported that a reduction in SstO2  was associated with an increased risk of acute graft rejection [et al. reported that full drainage of ascites during LT led to an increased leg SstO2; however, IVC clamping and abdominal hypertension caused a significant reduction in the leg SstO2. Somatic leg desaturation was more strongly associated with postoperative complications than arm and cerebral desaturation [2 was measured at the forearm, which is more easily adjusted than a trunk bed. A lower SstO2 (measured at the forearm 1 h after graft reperfusion) increased the likelihood of early postoperative kidney dysfunction. SstO2 measured at the forearm provides an estimate of hemoglobin oxygen saturation in the mixed arterial, capillary, and venous blood in the tissue bed being probed, and is largely determined by the balance between organ/peripheral tissue oxygen consumption/supply and perfusion [2 measured at the forearm may represent organ/peripheral tissue microcirculation, which is closely related to cardiac and systemic resistive indices [2 level measured at the forearm 1 h after graft reperfusion may be a clinical marker of the lowest level of renal perfusion.SstO studies –11. In allograft . SstO2 wejection . Hu et aerfusion . LT pati indices , 33. Lar indices . Therefo2 has been associated with organ dysfunction in previous studies [2 for other organs, particularly the kidneys. Second, the somatic oximeter sensor was placed on the forearm in this study, and not on the renal parenchymal surface. Therefore, although SstO2 may reflect tissue oxygen perfusion status, it does not directly reflect the renal perfusion or saturation conditions. Therefore, further studies are required to determine the predictive value of SstO2 according to monitoring site. Third, there are important differences between liver transplants from living and deceased donors. In previous studies, LT with grafts from deceased donors were more than twice as strongly associated with postoperative AKI [2 for kidney dysfunction in LT from deceased donors.Some limitations of this study should be discussed. First, because cerebral oximetry was developed for detecting hypoperfusion of the brain, there is no established reference value for detecting hypoperfusion of other organs. Although a low SstO studies , 27, 33,tive AKI . Further2 in patients undergoing LDLT. A low level of SstO2 during LDLT, particularly 1 h after graft reperfusion, was significantly associated with early kidney dysfunction after surgery. When a low SstO2 is detected, meticulous monitoring and efforts to improve the possible causes of compromised tissue perfusion  are likely important. SstO2 monitoring provided additional information that may facilitate early management of LT patients who are vulnerable to kidney dysfunction.Our results should increase the accuracy of detection of early kidney dysfunction by providing a basis for analyzing intraoperative SstOS1 Fig(TIF)Click here for additional data file.S2 Fig(TIF)Click here for additional data file.S1 TableComparison of changes in the (A) somatic tissue and (B) cerebral oxygen saturation levels between patients with and without early kidney dysfunction.(DOC)Click here for additional data file.S2 Table(DOC)Click here for additional data file.S1 Raw data(XLSX)Click here for additional data file.


The impact of sugammadex in patients with end-stage renal disease undergoing kidney transplantation is still far from being defined. The aim of the study is to compare sugammadex to neostigmine for reversal of rocuronium- and cisatracurium-induced neuromuscular block (NMB), respectively, in patients undergoing kidney transplantation.A single-center, 2014-2017 retrospective cohort case-control study was performed. A total of 350 patients undergoing kidney transplantation, equally divided between a sugammadex group (175 patients) and a neostigmine group (175 patients), were considered. Postoperative kidney function, evaluated by monitoring of serum creatinine and urea and estimated glomerular filtration rate (eGFR), was the endpoint. Other endpoints were anesthetic and surgical times, post-anesthesia care unit length of stay, postoperative intensive care unit admission, and recurrent NMB or complications.p = 0.0128) and serum urea  were lower, while eGFR  was higher in the sugammadex group than in the neostigmine group after surgery. The sugammadex group showed significantly lower incidence of postoperative severe hypoxemia , shorter PACU stay , and reduced ICU admissions .No significant differences in patient or, with the exception of drugs involved in NMB management, anesthetic, and surgical characteristics, were observed between the two groups. Serum creatinine (median [interquartile range]: 596.0 [478.0-749.0] vs 639.0 [527.7-870.0] μmol/L, Compared to cisatracurium-neostigmine, the rocuronium-sugammadex strategy for reversal of NMB showed a better recovery profile in patients undergoing kidney transplantation. Kidney transplantation represents the best option to improve survival and quality of life in patients with end-stage renal disease (ESRD) Kellar, .The surgical procedure of kidney transplantation is generally performed under general anesthesia and presents significant challenges for the anesthesiologist , including those undergoing standard forms of dialysis EMA .The safety profile of sugammadex observed in clinical studies involving subjects with severe renal impairment , which waived the requirement to obtain patients’ written informed consent .A total of 350 patients with ESRD undergoing kidney transplantation at our hospital were evaluated. Patients were recruited consecutively until the sample size was achieved.The anesthesia and medical records and the information system’s computer database were used to retrieve data about all patients (age ≥ 18 years) with ESRD who received sugammadex or neostigmine to reverse rocuronium- or cisatracurium-induced NMB, respectively, during inhalational or intravenous anesthesia for kidney transplantation. Each anesthesia and medical record was reviewed for preoperative, intraoperative, and postoperative data up to 5 days after surgery. Patient demographics, comorbidities , perioperative data including kidney function , and postoperative events were considered.Two distinct time periods that define the matched exposure groups were considered: the pre-sugammadex period, 2014-2015 (from which cisatracurium-neostigmine-treated patients were identified), and the sugammadex period, 2016-2017 (from which rocuronium-sugammadex-treated patients were identified). Sugammadex was introduced in Padua University Hospital in January 2013 and was initially restricted to emergency reversal and routine reversal of rocuronium-induced NMB in selected high-risk patients undergoing anesthesia  ≥ 0.90 was adopted as the criterion for tracheal extubation . Level of consciousness, respiratory rate, pulse oximetry, heart rate, and arterial blood pressure were monitored until discharge to the surgical ward. Pain and postoperative nausea and vomiting (PONV) were assessed using a numeric rating scale (NRS) from 0 = no pain or nausea to 10 = worst possible pain or nausea. Patients were also assessed for clinical evidence of residual or recurrent NMB . Patients with a pain NRS score of > 3 in the PACU received rescue analgesics (paracetamol 1 g and tramadol 1 mg/kg intravenously). Patients with a PONV NRS score of > 3 received a rescue dose of droperidol 0.625-1.25 mg intravenously.2] < 90%, critical respiratory event) or cardiovascular event , PONV NRS score of > 3, pain NRS score of > 3, residual or recurrent NMB, and presence of any other postoperative complications within 24 h after surgery that required treatment.Serum creatinine (primary endpoint) and serum urea and eGFR (secondary endpoints) for monitoring kidney function for up to 5 days after surgery represented the main endpoints of the study. Other endpoints were anesthetic and surgical times, length of PACU stay, intensive care unit (ICU) admission, clinical evidence of postoperative respiratory complications  performed 15-20 min after tracheal extubation was considered. For cardiac function, heart rate (HR) and systolic (SBP) and diastolic (DBP) arterial blood pressures evaluated 15-20 min after tracheal extubation were considered.For respiratory function, gas exchange analysis of arterial blood  and compared using a χ2 or Fisher’s exact test. To determine the strength and direction of association between two variables, Bravais-Pearson’s correlation test was used for normally distributed variables, and Spearman’s rank correlation test was used for non-normally distributed variables. Multiple linear regression analysis was used to examine the relationship between one dependent variable and the independent variables. Using the Akaike information criterion, backward and forward stepwise regression was performed to select the best model. Correlation coefficients (CCs), estimate coefficients (ECs), standard errors (SEs), t values, and p values were determined. Statistical significance was set at p values < 0.05. All statistical analyses were performed using R version 3.4.0 (2017-04-21).Descriptive analysis was used to summarize the sample’s characteristics. The normality of the distribution of quantitative characteristics was analyzed using the Shapiro-Wilk test. Continuous normally distributed variables are expressed as mean ± standard deviation (SD). Median and interquartile range (IQR) values are reported for non-normally distributed variables. The two-tailed Student’s t test or two-tailed Mann-Whitney No significant differences in demographic or other patient characteristics were observed between the sugammadex and neostigmine groups Table . With thp = 0.0128) and serum urea  were lower, while eGFR  was higher in the sugammadex group than in the neostigmine group after surgery . However, the need for postoperative dialysis was higher in the neostigmine group than in the sugammadex group .Regarding perioperative kidney function, serum creatinine , height , body mass index (BMI) , preoperative serum creatinine , and neostigmine  were correlated with postoperative serum creatinine  and preoperative serum creatinine  were the only variables associated with a higher level of postoperative serum creatinine, while rocuronium was associated with a lower level of postoperative serum creatinine .During fitted multiple linear regression analysis, body weight  is renally excreted  cells showed that neostigmine administered in vitro at 50, 100, 250, and 500 μg/mL had greater cytotoxic, genotoxic, and apoptotic effects on HEK-293 cells than the equivalent dosages of sugammadex  and a very low dissociation rate, so the complex is tight, and recurrence of NMB is highly unlikely  were not available for a targeted analysis of postoperative renal function.This study has some limitations. First, it is not a randomized controlled study and therefore has the drawbacks of all observational studies. The evidence of non-inferiority may warrant a specific prospective, randomized clinical trial. Second, the temporal factor may be a potential bias, even if the majority of patients were recruited close to the change in strategy for NMB management and no changes in the surgical team or perioperative care were adopted in the study period. Third, we were unable to compare the exact values of TOFR ≥ 0.90 before extubation, which might cause an unmatched level of recovery after reversal of neuromuscular block at the time of extubation between the two study groups. Fourth, more specific markers (e.g., cystatin C, N-acetyl-glucosaminidase, αIn conclusion, sugammadex should be considered for reversal of rocuronium-induced NMB in patients undergoing kidney transplantation.


We aimed to determine the prevalence of the eosinophilic  age was 48.7 (13.2) years. Forty-five (45%) patients had the eosinophilic phenotype, 50 (50%) had atopic phenotype 1, and 25 (25%) had phenotypic overlap (eosinophilic and atopic 1). Forty-one (41%) patients had atopic phenotype 2 and 23 (23%) had phenotypic overlap (eosinophilic and atopic 2). Asthma control and oral corticosteroid use patterns were similar and there were no significant differences in number of asthma exacerbations across phenotypes.In Saudi Arabia, 45% of patients with severe asthma had the eosinophilic phenotype, which is most likely an underestimation as no clinical features of eosinophilia were taken into account in the definition of eosinophilia. Approximately half of them had phenotypic overlap with the atopic phenotype.Trial registration NCT03931954; ClinicalTrials.gov, April 30, 2019.The online version contains supplementary material available at 10.1186/s12890-022-01856-9. It affedmission . Eosinopdmission , 12. Botdmission , 14. Patdmission , 15. Desrognosis . Blood et visits . Studiesreatment –20. Clasreatment ; howeverreatment  and it ireatment . KnowledAccording to the inclusion criteria, individuals were included in the study if they were ≥ 12 years of age at the time of study entry and had a diagnosis of severe asthma for at least one year, which was defined based on the Global Initiative for Asthma (GINA) 2018 guideline-suggested medications as described in Steps 4–5  , i.e., tThe PREPARE study was a multicenter, cross-sectional study that included retrospective data collection to assess the prevalence of eosinophilic and atopic phenotypes among severe asthma patients. Asthma control was also studied. The study was conducted in centers that specialized in the management of severe asthma located in Saudi Arabia. Patients were identified and consecutively invited to participate in the study at their routine clinical appointment. The enrollment period was planned to be approximately 8 months or until the required number of patients had been recruited, whichever occurred first.Early onset asthma was defined as asthma diagnosed at < 12 years of age; late onset asthma was defined as asthma diagnosed at ≥ 12 years of age . Severe Data from patients who provided written informed consent was obtained from medical records and during the study visit. Immediately after providing informed consent, patients were asked to respond to the GINA 2018 assessment of asthma control questionnaire  and to p3, among severe asthma patients. Although there is no clear definition of the eosinophilic asthma phenotype, we considered this to be appropriate as most clinical trials for anti-IL-5 and anti-IL5 receptor biological therapy used a cutoff of ≥ 300 cells/mm3 as a biomarker for severe eosinophilic asthma and an indication of therapy initiation [3 were associated with a significantly increased risk of exacerbation  [The primary objective was to determine the prevalence of the eosinophilic asthma phenotype, defined as a blood eosinophil count ≥ 300 cells/mmitiation –20. Addi04–1.51) . Seconda04–1.51) . Skin te04–1.51) .3) [3) was used in the present study. For a sample size of 100 patients, the expected 95% confidence interval for an observed proportion of 50% was expected to be between 39.8 and 60.2%; therefore, a minimum sample size of 100 patients was considered adequate to provide sufficient precision in the estimation of the primary outcome measure.Sample size was determined as follows. Schleich et al. found that 53% of patients from the Belgian Severe Asthma Registry had elevated blood eosinophil counts (> 220 cells/mm3) . Based op-value ≤ 0.05 was considered statistically significant. All statistical analyses were of an explorative and descriptive nature. No allocations were made for missing values. Data were analyzed using R statistics version 3.6.4.Continuous variables were summarized with descriptive statistics and categorical variables were summarized with frequency counts and percentages. Analysis of variance (ANOVA) was used to analyze the mean differences among more than two groups. All statistical tests were two-sided and a Between May 2019 and December 2019, 101 patients were enrolled in the study from five study sites located throughout Saudi Arabia; all 101 were included in the full analysis set. Patient characteristics (demographic and lifestyle) for the total participants and according to phenotype are described in Table 3) was 45% (n = 45) among patients with severe asthma. The number of patients with blood eosinophil counts of 150–299 or < 150 cells/mm3 was 21% and 35%, respectively. As for the definition of eosinophilic phenotype, a definitive diagnosis requires evidence of eosinophilia in bronchial biopsies or induced sputum, which is challenging in clinical practice [The prevalence of the eosinophilic phenotype  for total serum IgE was 99.5  IU/mL  duration of asthma was 17.6 (12.1) years and 87 (86%) patients had late-onset asthma. The majority of patients (82%) did not have a history of atopy. Prevalence of comorbidities of interest among the 65 patients  with comorbidities was as follows: rhinitis, 65%; nasal polyps, 26%; atopic dermatitis, 3%; sinusitis, 22%; and eczema, 2%. In total, 77% of patients had at least one asthma exacerbation within the previous 12 months, and 32% had ≥ 3 exacerbations in the same time period. Among patients with the eosinophilic phenotype, 29% had ≥ 3 exacerbations in the previous 12 months. Additionally, clinical parameters for the total participants are shown in Table Asthma treatments in the 12 months prior to study enrollment for the total participants are shown in Table At the time of the study visit, 69% (n = 70) of patients had uncontrolled asthma, 22% (n = 22) had partially controlled asthma, and 9% (n = 9) had well-controlled asthma Fig. B. The diP = 0.315; Fig. P = 0.244; Fig. There were no significant differences in the number of severe asthma exacerbations (in the year prior to study enrollment) among patients with only atopic 1, only eosinophilic, or overlap 1 asthma phenotypes . Given that only 18% of patients had positive specific IgE values, which is evidence of sensitization to perennial allergens, the prevalence of the atopic phenotypes 1 and 2 are most likely overestimated. Approximately half of patients with the eosinophilic phenotype had phenotypic overlap with the suggested atopic phenotype; overlap patients accounted for approximately one-quarter of patients overall. Most patients (70%) had uncontrolled asthma and 60% received corticosteroid burst treatment in the past 12 months of which 45% received three or more bursts. The pattern of corticosteroid use and level of asthma control were similar across phenotypes. There were no significant differences in the number of asthma exacerbations in the 12 months prior to the study among phenotypes. It should be noted that the large amount of overlap within the phenotypic groups may have accounted for the observation that characteristics and outcomes were similar among phenotypes.3. This is most likely an underestimation of the real prevalence as clinical features of eosinophilia, like nasal polyps, adult-onset asthma, and chronic OCS use were not taken into account [The prevalence of the eosinophilic asthma phenotype among severe asthma patients reported in the present study is similar to that reported in other geographic regions  –33. In t account .The management of severe asthma is complex and requires a thorough and up to date understanding of the pathophysiologic characteristics of this patient population to facilitate effective therapeutic decision-making. The high incidence of overweight or obese participants observed in the present study warrants a call to action among patients with severe asthma in Saudi Arabia, as an increased BMI is associated with an increased risk of asthma exacerbations , and weiThis study had several limitations. This study utilized consecutive enrollment, which may have resulted in low internal validity and limited generalizability given the non-probabilistic sampling technique. The cross-sectional study design does not allow for the establishment of cause-effect relationships and the partial reliance on retrospectively collected data may have resulted in some incidences of incomplete, poorly recorded, or absent data. The definitions of eosinophilic and atopic phenotypes were only based on blood eosinophil and serum IgE levels, respectively, and did not include any clinical features of eosinophilic asthma nor were data on sensitization of perennial allergens included. Comorbidities of sleep apnea, gastroesophageal reflux, anxiety, and depression, which are relevant for patients with asthma , 42, wer3) among patients with severe asthma in Saudi Arabia, which is most likely an underestimation of the real prevalence. Additionally, 41–50% of patients with severe asthma had the atopic phenotype , which is most likely an overestimation of the real prevalence given the limitations in defining the atopic phenotype. In total, 23–25% of patients had phenotypic overlap between eosinophilic and atopic phenotypes, which accounted for approximately half of the patients with each phenotype. Patient demographic and clinical characteristics were similar across the different phenotypes, as were corticosteroid use patterns, level of asthma control, and incidence of exacerbations. Considering the impact of severe asthma on healthcare systems and the current lack of data around available biomarkers to guide precision therapy, it is important to have prospective local registries to better capture patient data, which may help to guide treatment. The results of the present study serve to inform treating physicians of the importance of phenotyping to select the right biologic treatment.Overall, this study reported a prevalence of 45% for the eosinophilic phenotype (≥ 300 cells/mmAdditional file 1. Statistical Analysis Report.


Objective: This study aimed to examine the relationship between microalbuminuria and long-term life expectancy or limb events in patients with peripheral arterial disease (PAD).Materials and Methods: A prospective cohort study was performed in 714 patients with PAD. The primary outcomes were cardiovascular or cerebrovascular death (CCVD) and all-cause death (AD), and secondary outcomes were major adverse cardiovascular events (MACE) and cardiovascular and/or limb events (CVLE).Results: The 5, 10, and 15 year survival rates were 82.4%, 53.1%, and 33.0%, respectively. The prevalence of patients with increased microalbuminuria was 39.2%. Higher microalbuminuria, age, C-reactive protein (CRP), lower serum albumin, estimated glomerular filtration rate (eGFR), ankle–brachial pressure index (ABI), diabetes, cerebral infarction, and coronary heart disease (CHD) were associated with CCVD; higher microalbuminuria, age, CRP, D-dimer, lower serum albumin, eGFR, and critical limb ischemia were related to AD; higher microalbuminuria, age, CRP, lower serum albumin, ABI, diabetes, and CHD were related to MACE; higher microalbuminuria, age, lower ABI, cerebral infarction, and CHD were related to CVLE in Cox multivariate analyses (p<0.05). Statins reduced CCVD, AD, MACE, and CVLE (p<0.001).Conclusion: Higher microalbuminuria was a significant predictor for CCVD, AD, MACE, and CVLE in PAD patients. PAD is frequently associated with chronic kidney disease (CKD), which is a risk factor for cardiovascular disease and stroke. Moreover, increased urinary level of microalbumin (MA) is related to a higher risk of CHD and cardiovascular morbidity. In patients with established heart failure, reduced estimated glomerular filtration rate (eGFR) and increased urinary MA are independent predictors for heart failure progression and mortality. Hence, CKD is classified on the basis of Cause, eGFR categories, and Albuminuria categories, abbreviated as CGA categories.Peripheral arterial disease (PAD) has been associated with reduced survival because of coronary heart disease (CHD) and cerebral infarction.However, long-term cardiovascular or all-cause mortality and cardiovascular or limb event related to the urinary level of MA have not been examined clearly in PAD patients. In the present study, we analyzed the relationship between microalbuminuria and long-term life expectancy or leg event in patients with PAD.A total of 725 patients with PAD at the Cardiovascular Hospital of Central Japan were recruited from February 1, 2000, and January 31, 2021. Before initiation, the study protocol was approved by the Medical Ethical Committee of our hospital (CCJ-EA-006), and the study was conducted according to the Declaration of Helsinki. The patients received a full explanation of the study and gave written informed consent. The criteria used for PAD included an ankle–brachial pressure index (ABI) of <0.90, clinical symptoms, and iliac or femoropopliteal artery stenosis of ≥70% defined with ultrasound or angiography. Patients with nephrosis syndrome or those on hemodialysis were excluded from this study. All assays were performed at the Health Science Research Institute, Inc. .Baseline clinical characteristics for each patient included age, body mass index (BMI), ABI, smoking history, diabetes mellitus (fasting plasma glucose level of >126 mg/dL at least two measurements or a requirement for antidiabetic therapy), and hypertension . A fasting blood sample was collected to measure serum basic metabolic panels. Moreover, we collected a morning urine sample for urinary albumin and creatinine measures. Urinary albumin concentration was measured via turbidimetric immunological technique . The urine albumin/creatinine ratio was calculated as mg/g of creatinine (Cr). Patients with an albumin level of <30 mg/gCr were defined as having normoalbuminuria (A1), those with an albumin level of 30–300 mg/gCr (A2), and those with an albumin level of >300 mg/gCr (A3), according to CGA categories.An electrocardiogram was recorded for each patient. CHD was determined as a positive sign in stress/rest myocardial perfusion scintigraphy or coronary angiography and a history of this treatment. The eGFR was calculated with the Modification of Diet in Renal Disease equation with Cr level.Each subject was followed up at 1, 2, and 4 months after the procedure and assessed intervals were 4 or 6 months. Medical statuses were evaluated using hospital records and questionnaires for life statuses assessed by the Foot Care Club in our hospital. Cerebral infarction was determined as the presence of a new focal neurological deficit confirmed with computed tomography or magnetic resonance imaging. Restenosis was determined as a decrease in ABI of ≥0.15 and ≥50% stenosis on ultrasonography or angiography, and major amputation was determined as above-the-ankle amputation.The definition of myocardial infarction was described previously.The primary outcomes were cardiovascular or cerebrovascular death (CCVD) and all-cause death (AD), and secondary outcomes were major adverse cardiovascular events  and cardiovascular and/or limb events .All calculations were performed with IBM SPSS Statistics ver. 25.0 . We used a median (interquartile range) to express continuous variables compared via the Wilcoxon test, and a number (%) to express categorical variables compared via chi-square test. In the follow-up term, the Kaplan–Meier estimates were used to define CCVD, AD, MACE, and CVLE and compared using the log-rank test with Bonferroni correction. In Cox univariate analysis, a hazard ratio and 95% confidence interval were calculated for each factor. In this analysis, risk factors with p<0.05 were used to define significant factors related to outcomes in Cox multivariate analysis. In all analyses, p<0.05 was defined as significant.Among 725 subjects, follow-up was available for 714 patients. The median follow-up time was 78  months. The mean age of the 714 patients was 72.4±9.3 years. The patients who died were 328 (45.9%) throughout the follow-up time. The causes of deaths were cardiovascular disease , cerebrovascular disease , malignancy , pneumonia , and other causes . The prevalence of CCVD was 49.4% (n=162). In all patients, the 5, 10, and 15 year freedom from AD rates were 82.4%, 53.1%, and 33.0%, respectively.Before patients were separated into two subgroups, the prevalence of urinary MA level of A1, A2, or A3 was 60.8% (n=434), 28.2% (n=201), or 11.1% (n=79), respectively. The 5, 10, and 15 year rates for freedom from CCVD among A1, A2, or A3 with significant differences (p<0.01) are shown in The 5, 10, and 15 year rates for freedom from AD among A1, A2, and A3 with significant differences (p<0.05) are shown in The 5, 10, and 15 year rates for freedom from MACE are shown in The 5, 10, and 15 year rates for freedom from CVLE are shown in  and cardiovascular death is markedly accelerated in patients on hemodialysis. Moreover, microalbuminuria is independently related to increased cardiovascular risks and morbidity. We have reported that urinary level of MA is related to low-density lipoprotein cholesterol, age, CHD, CLI, and diabetes in patients with PAD. Hence, CKD is classified on the basis of eGFR categories, and urinary levels of MA are added in CGA categories.Our data represented the first clinical evidence for the relationship between microalbuminuria and long-term life expectancy or leg events in PAD patients. In this study, the prevalence of albuminuria categories (A2 or A3) was 39.2%, and the higher level of urinary MA was a predictive factor for CCVD and AD. In this study, CCVD was correlated with the higher urinary level of MA, age, CRP, lower level of serum albumin, eGFR, ABI, diabetes, cerebral infarction, and CHD. And AD was correlated with the higher urinary level of MA, age, CRP, D-dimer, lower level of serum albumin, eGFR, and CLI. Some studies have reported that CKD is a risk factor for CHD, valvular heart disease, and cerebrovascular disease, Cardiovascular and cerebrovascular diseases were major causes of AD. Moreover, malnutrition is a strong risk factor for AD. We have reported that the geriatric nutritional risk index is a meaningful predictor for AD, MACE, and major adverse cardiovascular and limb events in PAD patients. These results suggest that patients with lower serum albumin, lower ABI, or CLI have causes of higher mortality based on systemic severe atherosclerosis.CLI and lower ABI are associated with a higher risk of cardiovascular events because of systemic or severe atherosclerosis. Moreover, reduced eGFR and albuminuria are independent predictors of heart failure progression and mortality in patients with heart failure. We have reported that cerebral infarction, diabetes, and CKD are predictive risk factors for aggravation of stages of PAD. Sensory disturbance, decreased physical faculties, and systemic atherosclerosis may be related to the causes of these outcomes. Urinary MA levels are associated linearly with an increasing likelihood for the presence of PAD, even in the normal range of albuminuria in the Japanese general population. Systemic vascular atherosclerosis reflected by a higher level of urinary MA might be responsible for MACE and CVLE. In this study, a higher level of urinary MA was a significant risk factor associated with CVLE. Hence, higher urinary MA level was related to systemic vascular atherosclerosis including limb vessels in patients with PAD.In this study, higher albuminuria was also an independent predictive factor for MACE and CVLE. Higher level of urinary MA, age, CRP, lower level of serum albumin, ABI, diabetes, and CHD were related to MACE, and higher urinary MA level, age, lower ABI, cerebral infarction, and CHD were related to CVLE. Microalbuminuria has been reported to be independently related to increased cardiovascular risk factors and MACE. Treatments with statins are efficient for improving AD and MACE in PAD patients with or without symptoms detected via the measurements of ABI. However, treatments with statins appear to be less effective in decreasing risks of CHD in patients with CKD and those on hemodialysis treatment. Additionally, statins are recommended for all patients with PAD in recent guidelines. Our findings also suggested that statins improve long-term CCVD and AD and decrease the risks of MACE and CVLE in patients with PAD.Statin therapy has an antiatherogenic effect on CHD and reduces MACE.The present study had some limitations: 1) the number of patients was relatively small; 2) this study was based on the data from a single institution; 3) a single morning urine sample was used to measure albumin and creatinine levels; 4) the prevalence of CLI was low as a result of the inclusion criteria in which patients on hemodialysis were excluded; and 5) the rate of statin therapy was relatively lower than in the recent guidelines, but the rate has risen over time. These limitations need further study with a larger patient cohort with PAD for CCVD, AD, MACE, and CVLE.The urinary level of MA was a significant predictor for CCVD, AD, MACE, and CVLE in patients with PAD.


These factors were also independently correlated with BCL in subgroups, including non-dialysis CKD, hypertensive patients, non-smokers, and male patients. In conclusion, female sex, smoking, and CKD stage 5D were the major risk factors for elevated BCL; additionally, statins were negatively associated with BCL in CKD.Low-level cadmium exposure has adverse effects on chronic kidney disease (CKD); however, the risk factors for elevated blood cadmium levels (BCLs) have not been studied in CKD. We conducted a cross-sectional investigation in 200 CKD patients and stratified them by the tertiles of BCL to compare their demographic, environmental, and biochemical data. The factors associated with BCL were identified, and their effects were examined in subgroups. In the analyses, female sex, smoking, and CKD stage 5D were associated with high BCL, and statin was inversely correlated with BCL (odds ratio , 6.858 [2.381–19.746],  Cadmium, a toxic heavy metal derived from agricultural and industrial sources, has multiple adverse effects on human health, including chronic kidney disease (CKD), bone disease, cardiovascular disease, infertility, and malignancy. With a long half-life of up to 30 years, cadmium accumulates in the kidney, liver, and bone, and the impact on the health could be long-lasting ,2. In adIn this cross-sectional investigation, we assessed the blood cadmium in CKD patients and analyzed the demographic, environmental, lifestyle, and biochemical risk factors of elevated blood cadmium concentrations in the CKD population.The study protocol was approved by the Institutional Review Board and Ethics Committee of Chang Gung Medical Foundation, Taipei, Taiwan (IRB No. 202001027B0) and adhered to the principles of the Declaration of Helsinki and Declaration of Istanbul. All the patients provided informed consent. The patients living in geographically different areas in southern Taiwan were recruited from the CKD health consultation unit and the HD center in Kaohsiung Chang Gung Memorial Hospital between December 2020 and March 2021. The inclusion criteria were as follows: (1) adult patients (≥20-year-old) with CKD stage 3a–5D  and (2) patients receiving follow-up treatment for at least one year in the nephrology outpatient department or HD center of the hospital. Patients with a history of occupational or accidental heavy metal poisoning, liver cirrhosis, malignancy under chemotherapy or radiotherapy, active infectious disease, active alcoholism, PD, or drug abuse were excluded. Pregnant patients and those who were hospitalized within 3 months of enrollment were also excluded.2) = 175 × SCr−1.154 × age−0.203 × 0.742 , was used to retrieve the eGFR , p = 0.023, and 0.212 [0.055–0.822], p = 0.025, respectively). On the other hand, the OR of high BCL associated with female sex increased slightly in non-smokers .In the subgroup analyses , female In our study, female sex, smoking, and late-stage CKD, especially CKD stage 5D, were identified as the independent risk factors for elevated BCL in the CKD population with low-level environmental cadmium exposure. In contrast, statin use was inversely correlated with high BCL in this population. In the subgroup analyses, these factors were still independently correlated with BCL in all the analyzed subgroups, including non-dialysis CKD, hypertensive patients, non-smokers, and men. The associations of BCL with other medical , demographic, environmental, and lifestyle factors in CKD patients were not proven in our study. There have been studies indicating that low-level environmental cadmium exposure has harmful effects on human health and complex interactions with other environmental contaminants; additionally, the blood cadmium elevation also deteriorates the risks and outcomes of CKD ,20,22,27In the general population, occupational exposure, living in industrial region, old age, smoking, dietary preference, female sex, and iron deficiency were identified as the risk factors for cadmium exposure or elevated blood cadmium in the literature ,13,28,29Tobacco smoking is a well known source of chronic toxic metal exposure including cadmium, and the BCL of smokers is 4–5 times higher than that of non-smokers ,39. The In the human body, the kidney is the major organ of accumulation and the main elimination route of cadmium, and previous studies have suggested that BCL is positively associated with renal dysfunction ,43,44. OIn our study, the statin use was inversely correlated with high BCL even after adjusting for other covariates; moreover, the risk of high BCL was about one-third lower in statin users with a 2.07 nmol/L reduction of BCL, which has not been reported before. The association between statin use and BCL was independent of the lipid profile or underlying dyslipidemia. Statins, a group of β-hydroxy-β-methylglutaryl-CoA (HMG-CoA) reductase inhibitors, have pleiotropic roles in human diseases, including lipid-lowering effects, antioxidant properties, and anti-inflammatory activities . Animal The subgroup analyses of our study demonstrates that sex differences with regard to BCL tended to increase in non-smokers; moreover, the influences of smoking, statin, and CKD stage 5D on BCL increased slightly in CKD patients who were men. A previous study also revealed that the differences in BCL between women and men in non-smokers were more prominent than in smokers (3.51 vs. 2.15 nmol/L); the elevation of BCL with smoking was more obvious in men than in women (4.57 vs. 3.22 nmol/L) . Althoug2 were not included in our study, as well as PD patients, and specific research in the populations is crucial in the future. The zinc supplementation, which might be protective for cadmium toxicity [There were limitations to our study. Lifestyle and environmental characteristics, except smoking, were not identified as independent risk factors for high BCL in this CKD study. Diet is the major source of cadmium in low-level environmental exposure settings, and rice has been viewed as the leading source of cadmium burden in Asian populations ,56. In otoxicity , could nIn conclusion, our study indicates that female sex, smoking, and late-stage CKD, especially CKD stage 5D, were the major risk factors for elevated blood cadmium in CKD patients, and statin use was negatively associated with blood cadmium in this population. These factors were also independently correlated with blood cadmium in subgroups, including non-dialysis CKD, hypertensive patients, non-smokers, and male patients. Further studies are required to verify these results.


Acute kidney injury (AKI) is frequently encountered in people with acute decompensated heart failure (ADHF) and is associated with increased morbidity and mortality. Early detection of a urinary biomarker of kidney injury might allow a prompt diagnosis and improve outcomes. Levels of urinary aquaporin 2 (UAQP2), which is also associated with several renal diseases, are increased with ADHF. We aimed to determine whether UAQP2 predicted AKI in patients with ADHF. We conducted a prospective observation study in the coronary care unit (CCU) in a tertiary care university hospital in Taiwan. Individuals with ADHF admitted to the CCU between November 2009 and November 2014 were enrolled, and serum and urinary samples were collected. AKI was diagnosed in 69 (36.5%) of 189 adult patients (mean age: 68 years). Area under the receiver operating characteristic curve (AUROC) of biomarkers was evaluated to evaluate the diagnostic power for AKI. Both brain natriuretic peptide and UAQP2 demonstrated acceptable AUROCs . A combination of the markers had an AUROC of 0.802. UAQP2 is a potential biomarker of AKI in CCU patients with ADHF. Additional research on this novel biomarker is required. Acute kidney injury (AKI) is common in individuals with acute decompensated heart failure (ADHF), and several subtypes of cardiorenal syndrome were proposed in 2008 . More thAquaporin 2 (AQP2) is a water channel present mainly in the principal cells of collecting ducts. It is regulated by arginine vasopressin (AVP) and responsible for regulating urine concentration ,18,19. A2, were receiving kidney replacement therapy, were aged <18 years, or had reported any prior organ transplantation. No enrolled patients had been exposed to vasopressin V2 receptor antagonist such as tolvaptan during admission. The study protocol was approved by the local institutional review board (no. 201401993B0). We prospectively collected the following data: demographic characteristics, routine hemogram and biochemistry test results, and hospital outcomes. Biochemistry and hemogram values were measured by the central laboratory of Chang Gung Memorial Hospital.We conducted a prospective, observational study in the coronary care unit (CCU) of a 3700-bed tertiary care referral center in Taiwan between November 2009 and November 2014. Patients diagnosed as having ADHF were enrolled. We included a total of 189 patients and divided enrollees into AKI and non-AKI groups. We excluded patients who had a baseline estimated glomerular filtration rate (eGFR) of <30 mL/min/1.73 mThe diagnosis of ADHF was based on European Society of Cardiology criteria . All theg for 30 min at 4 °C to remove cells and debris. The clarified supernatants were extracted and then stored at −80 °C until further analysis. UAQP2 was measured using the ELISA Kit for Aquaporin 2 . The test protocol adhered to the manufacturer’s specifications.Urine samples were collected in sterile nonheparinized tubes immediately after admission into the CCU. Collected samples were centrifuged at 5000× t test. The biomarkers of interest  were compared using the Mann–Whitney U test due to a lack of normality. Categorical variables, including outcomes, were compared using Fisher’s exact test. The trends of UAQP2 and serum BNP across AKI stages were assessed using the Jonckheere–Terpstra trend test. The association between the biomarkers of interest and the risk of AKI was investigated through logistic regression analysis. Several well-established risk factors of AKI and HF were adjusted in the multivariable logistic regression model, including age, sex, diabetes, hypertension, mean atrial pressure, left ventricular ejection fraction (LVEF), hemoglobin, and baseline serum creatinine.Continuous variables  of the AKI and non-AKI groups were compared using the independent samples p value of less than 0.05 was considered statistically significant in our study. We used SPSS 25  for data analyses.Area under the receiver operating characteristic curve (AUROC) was used to examine the discrimination abilities of the biomarkers in diagnosing AKI. We further compared the AUROC of BNP alone to that of BNP plus UAQP2 and that of BNP plus UAQP2/UCr. The standard error of the AUROC was calculated using DeLong’s nonparametric method. The composite outcome of AKI stage 3 and in-hospital mortality was also analyzed, in addition to AKI stages 1–3. Last, according to the optimal cutoffs of UAQP2 and UAQP2/UCr determined by the Youden index, we compared the 180-day survival rates of the higher and lower subgroups by using the log-rank test. A two-tailed p < 0.05). Regarding the biomarkers of interest, the median serum BNP levels were 1210 pg/mL and 479 pg/mL, and the median UAQP2 levels were 61.5 ng/mL and 30.9 ng/mL, respectively, in the AKI and non-AKI groups (p < 0.001). To compensate for variation in urine dilution, urine UAQP2 values were adjusted according to UCr. The median UAQP2/Cr levels in the AKI and non-AKI groups were 1.09 fmol/mg and 0.35 fmol/mg, respectively  were investigated. AKI was diagnosed in 69 (36.5%) patients. Compared with patients in the non-AKI group, those in the AKI group had the following characteristics: they were older, were less likely to have LVEF and more likely to have chronic kidney disease (CKD) or hypertension, and had higher baseline serum creatinine, lower hemoglobin, and higher potassium levels  69.0–82.9), 79.5% (95% CI 73.2–85.7), and 76.1% (95% CI 69.1–83.2), respectively, with acceptable performance a. The AUThe optimal cutoffs of UAQP2 and normalized UAQP2 were >35.3 ng/mL and >0.83 fmol/mg, respectively . HoweverTo our knowledge, this is the first study to evaluate UAQP2 levels in AKI among CCU patients with ADHF. Regardless of whether they were normalized by UCr, UAQP2 levels were significantly higher in those with AKI than in those without. In addition, UAQP2 levels increased with AKI stage. Even after age, sex, diabetes mellitus, hypertension, mean arterial pressure, LVEF, and baseline creatinine were adjusted for, the UAQP2 level was associated with the risk of AKI. UAQP2 also demonstrated fair discriminating power for AKI and the composite outcome of stage 3 AKI and in-hospital mortality. Our findings support the diagnostic potential of UAQP2 in AKI for individuals with ADHF.Neurohormonal activation plays a key role in cardiorenal syndrome. As heart failure becomes more severe, blood pressure lowers and renal perfusion worsens, causing baroreceptor and renin–angiotensin–aldosterone system activation, respectively . NeurohoAKI is common in individuals with ADHF, and a traditional diagnosis of AKI through the creatinine method is limited by its 24–72 h delay from onset to elevation . PreviouThe UAQP2 elevation in ADHF-induced AKI may not be universal in all AKI scenarios. Decreases in exosomal UAQP2 levels have been measured in several animal models of AKI, including I/R, lipopolysaccharide (LPS)-induced, cisplatin-induced, and gentamicin-induced kidney injury ,32,39,52Our study has several limitations. First, we measured UAQP2 only once to predict AKI in ADHF patients. Sequential measurement of biomarkers may better reflect kidney injury and improve predictive power. In addition, plasma AVP levels were unavailable in our study. Second, both the roles and the expression of UAQP2 in AKI with ADHF require additional investigation. The mechanism of urinary secretion of AQP2 is still poorly understood. Further animal modeling may help to extrapolate the exact mechanism and applications of UAQP2 in ADHF with AKI. Third, urinary exosomes were not evaluated in our study due to technical limitations. Finally, additional prospective trials are warranted to explore the use of UAQP2 for AKI, given the small sample size and observational design of our study.In summary, UAQP2 demonstrates acceptable discriminative power for early detection of AKI in patients with ADHF, as well as serum BNP. In addition, the combination of the two markers may serve as a novel, noninvasive biomarker to differentiate AKI. The combination had the highest AUROC; thus, it has potential in early identification of AKI. Further study is required to evaluate the relation between UAQP2 levels and tolvaptan responsiveness in AKI for patients with ADHF.