Longitudinal investigations of murine acute kidney injury (AKI) suggest that injury and inflammation may persist long after the initial insult. However, the evolution of these processes and their prognostic values are unknown in patients with AKI.In a prospective cohort of 656 participants hospitalized with AKI, we measured 7 urine and 2 plasma biomarkers of kidney injury, inflammation, and tubular health at multiple time points from the diagnosis to 12 months after AKI. We used linear mixed-effect models to estimate biomarker changes over time, and we used Cox proportional hazard regressions to determine their associations with a composite outcome of chronic kidney disease (CKD) incidence and progression. We compared the gene expression kinetics of biomarkers in murine models of repair and atrophy after ischemic reperfusion injury (IRI).After 4.3 years, 106 and 52 participants developed incident CKD and CKD progression, respectively. Each SD increase in the change of urine KIM-1, MCP-1, and plasma TNFR1 from baseline to 12 months was associated with 2- to 3-fold increased risk for CKD, while the increase in urine uromodulin was associated with 40% reduced risk for CKD. The trajectories of these biological processes were associated with progression to kidney atrophy in mice after IRI.Sustained tissue injury and inflammation, and slower restoration of tubular health, are associated with higher risk of kidney disease progression. Further investigation into these ongoing biological processes may help researchers understand and prevent the AKI-to-CKD transition.NIH and NIDDK .  Acute kidney injury (AKI) represents a sudden decline in kidney function and is typically caused by ischemic, toxic, or inflammatory injury to the renal tubules . AKI comEmerging evidence from longitudinal studies of mouse models of AKI suggest that the tissue recovery course of AKI may last beyond 4–6 weeks after initial injury, especially in cases of severe injury –11. In m2 (49.4–85.2 mL/min/1.73 m2), and 259 (39.5%) participants had baseline CKD prior to hospitalization. After 4.3 years (median) of follow-up from hospitalization, 158 (24.1%) participants developed a composite CKD outcome of incident CKD and CKD progression, including 106 of 397 (26.7%) participants with incident CKD and 52 of 259 (20.1%) participants with progression of preexisting CKD.Among 769 participants with AKI enrolled in the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) study, we excluded 45 participants who developed incident CKD or progression of preexisting CKD prior to their 12 months of study visits because they already developed the outcome before the start of the observation. We also excluded 57 participants who did not develop the CKD outcome but died before their 12-month study visits, because the study outcome could no longer be observed in these participants. Among the remaining 667 participants, 656 participants had blood and urine sample collected during hospitalization , had at least 1 blood and urine sample collected at their 3- and 12-month visits, and were included in the study . The medhttps://doi.org/10.1172/jci.insight.167731DS1).We used linear mixed effect models to estimate the longitudinal changes  in biomarkers of kidney injury , inflammation , and tubular health (urine uromodulin [UMOD]) from the hospitalization time point and over the first year of follow-up. We found that, while most biomarkers decreased over time on average (median), there was a large variability among patients, as represented by the wide ranges (IQR) of biomarker slopes . CompareWe subsequently determined whether the longitudinal changes in biomarkers of kidney injury, inflammation, and tubular health after AKI diagnosis were associated with kidney disease progression after AKI. For participants with similar biomarker levels during hospitalization, each SD increase in the biomarker slopes of kidney injury and inflammation was associated with higher risk of developing the CKD outcome, while each SD increase in the biomarker slope of tubular health  was associated with lower risk of the CKD outcome . The assBecause the associations between biomarker slopes and CKD in participants with resolving injury  and participants with worsening injury  may be qualitatively different, we explored the nonlinear relationships using restrictive cubic splines of the biomarker slopes with the CKD outcome. We observed steadily increasing risks of CKD as biomarker slopes increase for most biomarkers . CompareAlthough the mixed effect models account for the absence of sample collection at 3 months and 12 months after hospitalization, they assume the changes of biomarkers after AKI are linear from hospitalization with AKI to 12 months after hospitalization. Therefore, we conducted a sensitivity analysis by modeling biomarker slopes from hospitalization to 3 months, and from 3 months to 12 months after hospitalization as 2 exposures, in participants who had urine and blood samples collected at all 3 time points. Among the 656 AKI participants, 581 and 541 had urine and blood samples collected, respectively, at all 3 time points. The increase in the slopes of injury and inflammation biomarkers, and the decrease in the slope of tubular health biomarker at both time intervals, were independently associated with higher risks of the composite CKD outcome, and the associations were stronger for biomarker slopes in the first 3 months after AKI .Havcr1 (gene encoding KIM-1) and Lcn2 (gene encoding NGAL), as well as inflammation marker Ccl2 (gene encoding MCP-1) and Tnfrsf1a (gene encoding TNFR1), at 7–14 days after IRI , and there was a lower proportion of thick ascending limb cells expressing tubular health marker Umod in the atrophy model at these time points. These differences in gene expression suggest that sustained expression of injury-associated tubular cell genes and the coincident inflammatory cell activation associate with kidney atrophy during AKI-to-CKD transition.We qualitatively compared the gene expression of these biomarkers using single-cell RNA-Seq (scRNA-Seq) of 95,343 kidney cells at multiple time points in mouse models of IRI followed by kidney atrophy versus kidney repair  14, 15), 1514, 1fter IRI . SimilarHavcr1 expression 1 day after IRI, the decrease was significantly slower for the atrophy model. In the repair model, we observed a steady decrease in Lcn2 expression after day 1. In the atrophy model, however, Lcn2 expression was persistently high in the first 14 days after IRI. In addition, we observed no recovery of the tubular health marker (Umod) in the atrophy model after day 7, consistent with failure to resolve tubular injury in this model. Both atrophy and repair models displayed kidney inflammation — i.e., Il18, Tnfrsf1a, Tnfrsf1b (gene encoding TNFR2), and Ccl2 — in the first 14 days after IRI. However, the peak expression of these inflammation markers was significantly greater in the atrophy model, with inflammation persisting through day 90 in these atrophied kidneys, whereas the repair model exhibited progressive resolution in the inflammatory process.To further explore the associations between gene expression trajectories and fibrosis after IRI, we determined the gene expression kinetics of these markers at the whole kidney mRNA level and compared their longitudinal changes in the atrophy and repair models . For bioIn this study, we measured a panel of noninvasive biomarkers reflecting kidney injury, inflammation, and tubular health at multiple time points in hospitalized patients with AKI. We found that patients with biomarker evidence of sustained injury and inflammation, and slower restoration of tubular health, were at higher risk of developing incident CKD and experiencing progression of preexisting CKD. To gain mechanistic insights into these associations, we performed transcriptomic comparison of 2 mouse models of IRI followed by either repair or atrophy. We found that sustained injury and inflammation, and slower restoration of tubular health, were associated with maladaptive repair of the renal tubule and with subsequent kidney fibrosis and atrophy in mouse models , 15.The repair process in the injured renal tubule starts soon after the initial insult in murine models of AKI. Most injured tubular cells are able to undergo redifferentiation and proliferation and return to the healthy state by 7–10 days . HoweverCcl2, Il18, Tnfrsf1a, Tnfrsf1b, and Chi3l1) even through 90 days after initial IRI. The persistent inflammation is accompanied by slower recovery of tubular health, as reflected by Umod expression, and slower resolution of the injury marker Havcr1. The persistently high expression of injury marker Lcn2 in the early course (days 1–14) after IRI in the atrophy model is likely due to the accumulation of Lcn2-expressing neutrophils. These results harmonize well with our observation in the hospitalized patients. While mild injury to the kidney is associated with rapid adaptive repair and minimal progression to maladaptation, severe injury may lead to progressive accumulation of maladaptive tubular cells, particularly in the proximal tubule, and made lead to the accumulation of immune cells that persistently express these injury and inflammation markers. Our results from the mouse models of kidney atrophy and repair after IRI demonstrate that this maladaptive response may persist through 90 days after IRI, suggesting the need for further mechanistic investigation beyond the 7–14 day time point after AKI for therapeutic development to prevent long-term AKI-to-CKD transition.To gain mechanistic insights into the association between the longitudinal changes in kidney injury and inflammation with AKI-to-CKD transition, we performed transcriptomic analyses using mouse models of atrophy and repair after IRI, as previously reported , 20, 21.Consistent with the findings in our mouse models, participants with biomarker evidence of worsening kidney injury and inflammation in the first 12 months after AKI exhibited a higher risk of CKD than their peers with resolving injury and inflammation. This association is particularly strong in the first 3 months after hospitalization with AKI. The worsening intrinsic kidney injury may be underappreciated due to its lack of correlation with changes in serum creatinine concentration. Clinicians often determine AKI recovery based on the downtrend of serum creatinine concentration after its peak. However, in mice after IRI, serum creatinine and blood urea nitrogen concentrations typically start to decrease after the first 1–2 days, while intrinsic injury and inflammation continues to worsen over 2 weeks . In humaThe lack of recognition of worsening intrinsic injury by traditional measures (serum creatinine) may result in suboptimal patient care that contributes to long-term kidney function decline in the outpatient setting and, eventually, the development of CKD . For insIn this study, we measured noninvasive biomarkers of kidney injury, inflammation, and tubular health at multiple time points after hospitalization in a large prospective cohort of patients with AKI. We used linear mixed effect models to account for the absence of sample collection during follow-up and conducted extensive subgroup and sensitivity analyses to ensure the validity of our findings, including the exclusion of recurrent AKI as an important confounder. The findings from preclinical AKI models and the prospective cohort of patients with AKI have several clinical implications. Longitudinal monitoring of kidney injury and inflammation may differentiate phenotypes of AKI  and provide prognostic value regarding complications of AKI beyond clinical parameters. Future studies could determine the optimal combination of biomarkers that could provide the best predictive performance of future CKD events for clinical implementation. Changes in serum creatinine concentration do not correlate well with the histological and transcriptional changes at the renal tubule level . Our resWe recognize several limitations worth considering. Our study did not account for different etiologies of AKI to determine whether there are distinctive disease categories, such as acute interstitial nephritis, sepsis-associated AKI, and toxic tubular injury from medications, that contribute to higher risk of worsening tubular injury or inflammation. Since study participants did not undergo kidney biopsy for tissue interrogation, we could not determine whether participants with worsening injury have any histological features suggestive of maladaptation. This may be addressed by large scale tissue interrogation studies of hospitalized patients with AKI, such as the Kidney Precision Medicine Project . We onlyIn conclusion, longitudinally monitoring biomarkers of kidney injury, inflammation, and tubular health may help characterize phenotypes of AKI. Worsening of intrinsic kidney injury and inflammation over the course of 12 months after AKI is associated with high risks of kidney disease progression.The ASSESS-AKI study is a prospective cohort study composed of 1,538 hospitalized adults with and without AKI (1:1 matched) enrolled between December 2009 and February 2015 from 4 North American clinical centers involving various hospital settings  31)..31).Details of study design have been previously described in detail , 32. BriIn this study, we limited the analysis to participants with AKI at the initial hospitalization. As we aimed to determine the association between biomarker changes from AKI diagnosis to 12 months after discharge with kidney disease progression, the time origin of our primary survival analysis was set at 12 months after discharge, when the last exposures (biomarkers) were measured. Therefore, we excluded participants who developed incident CKD or CKD progression because they already developed the outcome prior to time origin (left censoring). We also excluded participants who did not develop the study outcome but died before their 12- month visits. We also excluded participants with missing sample collection at hospitalization and participants with missing sample collection at both 3- and 12-month visits.g at room temperature, aliquoted, frozen, and stored at –70°C until measurement . These biomarkers included biomarkers of kidney injury , inflammation , and tubular health (urine UMOD). Samples were collected within 48–96 hours of diagnosis of AKI during hospitalization and were collected in the morning of follow-up 3- and 12-month visits. After collection, samples were placed on ice if they were not processed within 30 minutes. Samples could be processed up to 6 hours after collection, were spun for 10 minutes at 1,000surement . Assays surement .2 among participants without preexisting CKD . In participants with preexisting CKD, we defined CKD progression as ≥ 50% reduction in eGFR compared with baseline, an eGFR < 15 mL/min/1.73 m2, or receiving kidney replacement therapy or kidney transplant. We calculated eGFR using the Chronic Kidney Disease Epidemiology Collaboration 2012 equation (The study composite outcome was incident CKD or CKD progression . We defiequation .n = 10 mice/time point). Baseline control mice were sacrificed and denoted as day 0 for the injury (n = 10 mice).We compared 2 mouse models of IRI (repair and atrophy) that we previously reported, and we examined the gene expression kinetics of 8 biomarkers whose longitudinal slopes were associated with AKI-to-CKD transition , 15. Alln = 2 per time point for each model). The library generation, data preprocessing, and analysis were described in detail in a recent study (The scRNA-Seq data library was generated from mice kidneys from the repair model and the atrophy model on days 0 (control), 7, 14, and 30 (nt study . The genHprt). Primers used include previously published primers for Havcr1, Ccl2, Chi3l1, Umod, and Hprt  and reverse transcribed using the iScript cDNA Synthesis Kit (Bio-Rad). Gene expression analysis was determined by quantitative PCR (qPCR) using an iCycler iQ (Bio-Rad) and normalized to hypoxanthine-guanine phosphoribosyltransferase  of biomarkers of kidney injury, inflammation, and tubular health from hospitalization to 12 months after discharge. Since each participant had 2–3 biomarker measurements, we constructed linear mixed-effect models with the change of log2 biomarker at visits 3 months and 12 months after hospitalization as the dependent variable, and time in months as the independent variable, using maximum likelihood estimation of the random slopes. In these models, the biomarker slopes represented monthly biomarker changes from hospitalization to 12 months after discharge on the log2 scale. We converted the biomarker slopes to monthly percentage change for the interpretation and characterization of their distributions.For analyses in ASSESS-AKI participants, we converted biomarkers to their log2 scale) by their SD so the associations with the composite CKD outcome were comparable across biomarkers  from hospitalization to 3 months after discharge and from 3 months to 12 months after discharge as 2 independent variables in the final adjusted Cox model. For all survival analyses, proportional hazard assumptions were examined by ensuring no correlation between the Schoenfeld residual and time. We considered P < 0.05 as statistically significant and performed all analyses using R 4.1.3.We evaluated nonlinear relationship between biomarker slopes with the CKD outcome using restricted cubic splines with 3 knots  of biomarker slopes in the final adjusted Cox model. We visualized the distribution of hazards ratios by comparing the risk of CKD in participants with different biomarker slopes against participants with the mean biomarker slopes. We conducted a sensitivity analysis by modeling the rates of biomarker change . The study was approved by IRBs in the participating sites. Written informed consent was obtained from participants. All animal protocols were approved by the Yale University Animal Care and Use Committee (IACUC protocol no. 10538).Conceptualization was contributed by YW, LX, LGC, and CRP. Methodology was contributed by YW, LX, HTP, LGC, and CRP. Investigation was contributed by YW, LX, IM, HTP, LGC, and CRP. Funding acquisition was contributed by CRP. Supervision was contributed by DGM, SGC, CYH, ASG, KDL, EDS, TAI, VMC, JSK, PLK, JH, LGC, and CRP. Writing of the original draft was contributed by YW, LX, LGC, and CRP. Review and editing of the manuscript were contributed by YW, LX, HTP, DGM, SGC, CYH, ASG, KDL, EDS, TAI, VMC, JSK, PLK, JH, LGC, and CRP. Members from the ASSESS-AKI consortium contributed to cohort design and study participant enrollment.


What is already known on this subject? Acute kidney injury (AKI) occurred in 12.8% of patients undergoing surgery and is linked to a 22.2% increase in mortality. Chronic kidney disease (CKD) is a well-known risk for death and cardiovascular events. Effects of AKI and CKD on patients undergoing coronary angiography (CAG) remain incompletely defined.What do the results of this study add? This study shows that kidney disease is present in up to one-third of patients undergoing CAG and is associated with a substantially increased mortality. AKI and CKD are independent predicators for mortality in patients undergoing CAG.What are the implications of these findings for clinical practice and/or further research? These findings highlight the importance of perioperative management of kidney function, especially in patients with CKD.Acute kidney injury (AKI) occurred in 12.8% of patients undergoing surgery and is associated with increased mortality. Chronic kidney disease (CKD) is a well-known risk for death and cardiovascular disease (CVD). Effects of AKI and CKD on patients undergoing coronary angiography (CAG) remain incompletely defined. The aim of our study was to investigate the relationship between acute and CKD and mortality in patients undergoing CAG. The cohort study included 49,194 patients in the multicenter cohort from January 2007 to December 2018. Cox regression analyses and Fine-Gray proportional subdistribution risk regression analysis are used to examine the association between kidney disease and all-cause and cardiovascular mortality. In the present study, 13,989 (28.4%) patients had kidney disease. During follow-up, 6144 patients died, of which 4508 (73.4%) were due to CVD. AKI without CKD , CKD without AKI , AKI with CKD , and end-stage kidney disease  were significantly associated with all-cause mortality. Adjusted HR (95% CIs) for cardiovascular mortality was significantly elevated among patients with AKI without CKD (1.78 [1.54–2.06]), CKD without AKI (2.28 [2.09–2.49]), AKI with CKD (3.99 [3.47–4.59]), and ESKD (6.46 [4.93–8.46]). In conclusion, this study shows that acute or CKD is present in up to one-third of patients undergoing CAG and is associated with a substantially increased mortality. These findings highlight the importance of perioperative management of kidney function, especially in patients with CKD. Chronic kidney disease (CKD) has a high prevalence worldwide, which often leads to poor clinical outcomes and a severe health economic burden . The 202Due to a high burden of CVD, patients with CKD often receive coronary angiography (CAG). Acute kidney injury (AKI) is a common complication after CAG and interventional procedures, with an estimated incidence of up to 12% . It is aBased on the relationship of the aforementioned kidney disease with CVD, revascularization and poor prognosis, AKI and CKD were proven to be risk factors for long-term death , but fewSupplementary Figure S1). Clinical data of the study patients were obtained from the CIN-II database, mainly including demographic characteristics, medical history, test reports on admission and discharge with medication. Survival information was obtained by cause-specific surveillance data at the regional Center for Disease Control and prevention and public security system, which was completed September 2021 to assess survival through 1 September 2021. The Ethics Committee of the Guangdong Provincial People’s Hospital approved the study ). It was conducted in accordance with the principles of the Declaration of Helsinki.We identified cohort from January 2007 to December 2018 among all patients from five tertiary hospital undergoing CAG, and getting admitted subsequently for hospitalization, which from Cardiorenal Improvement II (CIN-II) study . Baseline data were ascertained at the time of admission. AKI was defined during post procedure during the hospital stay. Post discharge, for outcome ascertainment, we used other records for all-cause and cardiovascular mortality. A total of 55,310 patients older than 18 years who underwent CAG, had diagnostic information of AKI and CKD and assessable information of the severity of kidney disease, such as serum creatinine and estimated glomerular filtration rate (eGFR), were initially evaluated. Of these participants, 6116 were excluded because of absent information related to follow-up, being on temporary kidney replacement therapy, or with outliers of eGFR. Thus, 49,194 patients were enrolled in the present study (2), CKD stage 3 (eGFR 30–60 mL/min/1.73 m2), CKD stage 4 (eGFR 15–30 mL/min/1.73 m2), and CKD stage 5 (eGFR <15 mL/min/1.73 m2) [All-cause and cardiovascular mortality since the date of CAG were our study outcomes. Cardiovascular mortality was defined as death associated with rheumatic heart disease, hypertension (HT) and its complications, ischemic heart disease, heart failure, inflammatory heart disease, etc. , diagnosed by the International Statistical Classification of Diseases, Tenth Revision, with any other cause of death treated as a competing risk. Preoperative eGFR and/or prior diagnosis of CKD was used to define CKD. CKD was classified according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines: CKD stage 1 or 2 (eGFR 60–90 mL/min/1.73 m1.73 m2) ,9. AKI wThe study population was divided into five groups: no known kidney disease, AKI without CKD, CKD without AKI, AKI with CKD, and end-stage kidney disease (ESKD). We reported descriptive statistics by means (SD), median (interquartile range (IQR)), or number and percentage when appropriate. We used one-way analysis of variance (ANOVA) to analyze differences between different groups. Categorical variables were compared by Pearson’s Chi-squared test.p Values for trend (p trend) were calculated by treating categorical exposure variables as ordinal. We also performed subgroup analyses to investigate whether the risk may be modified by age (≥65 versus <65 years of age), sex, acute myocardial infarction (AMI), and diabetes mellitus (DM). To test whether the pattern of association varies across stratifications, we estimated multiplicative interactions by including the product term (exposure × stratification variable) in the models. All analyses were first unadjusted (model 1), then adjusted for age and sex (model 2), and finally for insurance type, co-morbidity, and contrast media volume (CMV)) (model 3). To assess the robustness of the analytical results under available data only (no imputation), analyses were repeated on all outcomes using multiple regression imputation for the variables included in the regression model correction.To evaluate the association between kidney diseases and all-cause mortality, we used Kaplan–Meier’s estimates to calculate cumulative survival probabilities for all-cause mortality and univariate and multivariate Cox regression analyses, with adjusted hazard ratio (HR) with 95% confidence interval (CI). Characteristic variables with significant baseline differences or clinical significance were used as candidate predictors in the multivariate Cox regression model. In addition, we used the Fine-Gray proportional subdistribution hazards regression analysis to model cardiovascular mortality while treating any other cause of death as a competing risk. First, we analyzed the relationship between the incidence of different kidney diseases during hospitalization and all-cause and cardiovascular mortality. The population-attributable risk percentage (PAR%) related to different kidney diseases was estimated using standard methods . Second,p value <.05 indicated significance for all analyses.All data analyses were performed using R software . A two-sided We analyzed 49,194 patients who underwent CAG between January 2007 and December 2018  females), and 13,989 (28.4%) of them had kidney disease. At the time of hospitalization, 235 patients (0.5%) had ESKD and 10,884 patients (22.1%) had CKD. Among the 10,884 patients with CKD, 1419 (13.0%) subsequently developed AKI. After undergoing CAG, 4289 patients (8.7%) developed AKI, of which 2870 (66.9%) had no potential of CKD. Patients with any form of kidney disease were more likely to have co-morbid congestive heart failure (CHF), stroke. Patients with ESKD and CKD are more likely to be older, more likely to have co-morbid HT, DM. Baseline characteristics stratified by the occurrence of kidney disease are presented in After a median follow-up of 5.04 years, patients with any form of acute or CKD had significantly higher long-term mortality than patients without kidney disease . For allp< .001).The Kaplan–Meier survival analysis curves for assessing the incidence of all-cause and cardiovascular mortality between groups based on different kidney diseases are shown in p< .001), CKD without AKI , AKI with CKD , and ESKD  were significantly associated with long-term all-cause mortality. In the multivariable competing risk model, occurrence of different kidney diseases was likewise independently associated with cardiovascular mortality: AKI without CKD , CKD without AKI , AKI with CKD , and ESKD . The multivariate Cox proportional risk model and multivariable competing risk model were adjusted for confusion factors .p trend <.001). Among patients with CKD, the adjusted HR (95% CI) for all-cause mortality was 1.50 (1.26–1.78), 2.15 (1.99–2.33), 3.66 (3.21–4.17), and 5.98 (4.66–7.69) for patients with CKD stage 1 or 2, CKD stage 3, CKD stage 4, and CKD stage 5, respectively (p trend <.001). Similarly, compared with patients with no known kidney disease, adjusted HR (95% CI) for cardiovascular mortality was significantly increased in patients with AKI stage 1 , AKI stage 2 , AKI stage 3  and CKD stage 1 or 2 , CKD stage 3 , CKD stage 4 , and CKD stage 5 . Additionally, the risk for death tended to increase with growing severity stages of kidney disease .Compared with patients with no known kidney disease, risks for all-cause and cardiovascular mortality were proportional to the severity of the kidney disease. Among patients who developed AKI, adjusted HR (95% CI) for all-cause mortality was significantly increased in patients with stage 1 , stage 2 , and stage 3  kidney injury . In addition, CVD is the top cause of death in hemodialysis patients with CKD. The mortality rate from CVD is estimated to be twice as high in patients with stage 3 CKD and three times higher in patients with stage 4 CKD than in healthy subjects . It is cAKI is commonly presented after CAG, and patients with combined kidney disease are more likely to have a higher risk of AKI, significantly increased long-term prognosis and mortality. A recent study reported a strong association between AKI and subsequent cardiovascular events, with an 86% increased risk of cardiovascular-specific death . AnotherIn our study, we found that post-contrast patients have high cardiovascular mortality associated with AKI and CKD. This finding has important implications for the preoperative and perioperative management of patients undergoing contrast and percutaneous coronary intervention (PCI). This is similar to the findings of Huber et al. who found that patients after vascular or cardiothoracic surgery had CKD-AKI associated cardiovascular-specific deaths . The maiTherefore, efforts must first focus on AKI prevention during contrast procedures, mitigating further injury when AKI has already occurred, and promoting kidney recovery in patients with established AKI. In addition, we should focus on patients with CKD combined with AKI. The indications to perform contrast procedures in people with CKD and prone to AKI should be fully evaluated and a feasible plan should be established, such as Goal-Directed Intraoperative Management . AlthougWe acknowledge that the present study has limitations. First, it is common to all retrospective studies that bias in the results, but our study has attempted to increase the internal validity of the competing risks model through the use of multivariate adjustment and the assessment of model discrimination on validation data sets. Second, our study only focused on the south China, but it was conducted in five tertiary hospitals, representing the entire Chinese sample to some extent. The third point is that we did not examine the GFR directly but estimated it from the serum creatinine. However, it was estimated by the MDRD formula and has been widely used and accepted in previous studies.This large multi-center study shows that up to one third of patients undergoing CAG have combined acute and CKD and is associated with a substantially increased mortality. The more serious the kidney disease is, the higher the all-cause and cardiovascular mortality is. This demonstrates the importance of enhanced risk assessment for kidney injury, surveillance of kidney function in the perioperative period and early intervention, especially in patients with CKD.Click here for additional data file.


Background: The goal of chest compressions during neonatal resuscitation is to increase cerebral and coronary blood flow leading to the return of spontaneous circulation (ROSC). During chest compressions, bilateral femoral occlusion may increase afterload and promote carotid and coronary flow, an effect similar to epinephrine. Our objectives were to determine the impact of bilateral femoral occlusion during chest compressions on the incidence and timing of ROSC and hemodynamics. Methodology: In this randomized study, 19 term fetal lambs in cardiac arrest were resuscitated based on the Neonatal Resuscitation Program guidelines and randomized into two groups: femoral occlusion or controls. Bilateral femoral arteries were occluded by applying pressure using two fingers during chest compressions. Results: Seventy percent (7/10) of the lambs in the femoral occlusion group achieved ROSC in 5 ± 2 min and three lambs (30%) did not receive epinephrine. ROSC was achieved in 44% (4/9) of the controls in 13 ± 6 min and all lambs received epinephrine. The femoral occlusion group had higher diastolic blood pressures, carotid and coronary blood flow. Conclusion: Femoral occlusion resulted in faster and higher incidence of ROSC, most likely due to attaining increased diastolic pressures, coronary and carotid flow. This is a low-tech intervention that can be easily adapted in resource limited settings, with the potential to improve survival and neurodevelopmental outcomes. Newborns who fail to respond to effective ventilation and chest compressions have a low survival rate, with a high incidence of neurodevelopmental disability among survivors ,2. In thIn the past, adult cardiopulmonary resuscitation (CPR) guidelines have recommended elevation of the lower extremities as it may promote venous return, cardiac preload, stroke volume, and augment artificial circulation ,6. It alHemodynamic effects similar to elevation of the lower extremities can be achieved through bilateral femoral occlusion in a neonate . This maneuver can potentially increase the afterload to promote carotid and coronary flow, resulting in higher incidence and quicker ROSC. Additionally, it may act as a rapid intravenous volume expander by shifting blood from the lower extremities towards the intra-thoracic compartment (increasing the preload). Thus, the restricted cardiac output that is generated through CPR can be preferentially directed to the brain and the heart, resulting in higher incidence and quicker ROSC. This hemodynamic effect may be similar to that achieved through the administration of epinephrine and/or increasing the volume through the umbilical vein in the delivery room . A majorThe Institutional Animal Care and Use Committee at the State University of New York at Buffalo approved this study.All procedures were consistent with the ARRIVE guidelines  and were2) were continuously monitored. A midline abdominal incision was made and the fetus within the uterus was partially exteriorized. The lamb was intubated with a 3.5–4.5 mm cuffed ETT and instrumented as previously described [Pregnant sheep (139–141 days gestation) were obtained from May Family Enterprises . The ewes were sedated with intravenous diazepam (0.25–1.5 mg/kg) and ketamine (4 mg/kg) and anesthetized with 2–3% isoflurane. They were placed in a supine position and mechanically ventilated with 21% oxygen. Pulse oximetry and end-tidal carbon dioxide  were placed on the left carotid artery (2 mm), left pulmonary artery (4 mm), and left circumflex coronary artery (2 mm). The umbilical cord was cut, and an 18 g catheter was placed into the umbilical vein, 2–3 cm below the skin, for the administration of epinephrine. A 20 g catheter was placed into the umbilical artery for invasive blood pressure recording. A three-lead electrocardiogram was obtained  and used Acknowledge Software Version 5.0 to record tracings from leads I, II, and III, the invasive pressure, and the rate of blood flow. Cardiac arrest secondary to asphyxia was defined by cessation of the carotid blood flow, arterial blood pressure, and auscultation confirming asystole.2, at a rate of 40 breaths/min and initial pressures of 35/5 cm H2O. The peak inflation pressure (PIP) was adjusted to obtain an adequate chest rise. After ventilation for 30 s, chest compressions were initiated.The lambs were randomized into the femoral occlusion and control group using sealed opaque envelopes. Twins were individually randomized. Due to the nature of the intervention, blinding was not possible. To decrease the chance of ROSC with PPV alone, resuscitation was started after five minutes of cardiac arrest with a T-piece resuscitator, using 21% OIn the study group, the bilateral femoral arteries were continuously occluded using the resuscitator’s thumbs and hip flexion until the ROSC or 20 min had passed, whichever was earlier. The same resuscitator occluded the femoral arteries for all the experiments in this lamb model. The lamb was placed in the supine position and pressure was applied in the crease where the hind limbs join the anterior abdomen, midway between the pubic bone and the anterior superior iliac spine .2 was increased to 100% as per the current American Heart Association (AHA) and Neonatal Resuscitation Program (NRP) recommendations [Upon the initiation of chest compressions, inspired Ondations ,15. If tndations .We defined the ROSC as a sustained heart rate > 100/min, with a systolic blood pressure > 30 mmHg. Resuscitation was stopped at 20 min if there was no ROSC, as per the current AHA and NRP recommendations ,16. ROSC2 was adjusted by 5–10% every 30 s to maintain pre-ductal saturations between 85–95%. A tidal volume of 8 mL/kg was targeted by adjusting the PIP. The hemodynamic parameters were continuously recorded until approximately 2 h after birth. The lambs were then euthanized with 100 mg/kg of pentobarbital sodium .The lambs were placed on mechanical ventilation after achieving the ROSC. The FIOThe plasma epinephrine levels were drawn from the jugular vein at the baseline, every 2 min during resuscitation, and after the ROSC. The levels were analyzed using commercially available ELISA kits . The reduced glutathione (GSH) to oxidized glutathione (GSSG) ratio in the plasma, as a marker of oxidative stress and reperfusion injury, was measured after derivatization with N-ethylmaleimide ,18.Sample size estimation: Based on preliminary data, we needed nine lambs in each group to detect a difference of 180 s in the time to ROSC with femoral occlusion (standard deviation: 60 s), with a power of 80% and a type 1 probability of 0.05.p < 0.05.The statistics were evaluated using StatView 4.0 software. Continuous variables were analyzed using a two-way repeated measures ANOVA between the groups, and with Fisher’s post hoc test within the groups. The results are expressed as the mean and standard deviation. The chi-square test or Fisher’s exact test were used to evaluate the categorical variables when appropriate. Statistical significance was defined as In this prospective, randomized study, 19 term fetal lambs were asphyxiated by umbilical cord occlusion, resulting in severe asphyxia leading to cardiac arrest. Ten lambs were randomized to the femoral occlusion group and nine lambs to the control group.2, and lactate, prior to the start of the experimental protocol. The time to asystole was similar in both of the groups.The baseline characteristics of all the lambs are shown in p = 0.37 using Fisher’s exact test). The average time to achieve ROSC was faster in the femoral occlusion group (5 ± 2 min), as compared to the controls .With femoral occlusion, seven out of ten lambs (70%) achieved ROSC, while four out of nine control lambs achieved ROSC (44%) (2-sided p = 0.034).In the femoral occlusion group, three out of ten lambs achieved ROSC without requiring epinephrine, while all the lambs in the control group required epinephrine. The average number of epinephrine doses needed in the femoral occlusion group was 1.9 ± 1.8 and 3.4 ± 1.1 in the controls (p = 0.02) (p = 0.0003).Blood Pressure: The systolic blood pressure was similar in the femoral occlusion (27.4 ± 1.5 mm Hg) and the control groups (23.5 ± 1 mm Hg) A. Howeve = 0.02) B. The mep = 0.001).Carotid Artery Blood Flow A: Duringp = 0.01) prior to the administration of epinephrine.Coronary Artery Blood Flow B: Femorap = 0.061). Flow across the ductus arteriosus was also similar between the two groups, 82 ± 8.5 mL/kg/min in the femoral occlusion group and 74 ± 3.4 mL/kg/min in the controls (p = 0.12).Pulmonary Artery Blood Flow C: No difIn lambs that achieved ROSC, the femoral pulses were normal and there was no evidence of ischemia in the hind legs in all the lambs.p = 0.04) (Epinephrine Levels : The pla = 0.04) A. Upon a = 0.04) B.p < 0.0001). In the lambs that achieved ROSC, the average oxygen requirement from ROSC to the end of the experiment at 2 h in the femoral occlusion group was much lower (35 ± 25%) than the controls  (p = 0.067 (Oxygen Exposure and Oxidative Stress : The dur 0.0001) A. The ba = 0.067 B.This is the first study evaluating the effect of femoral occlusion in neonatal cardiopulmonary resuscitation. In our study, bilateral femoral occlusion during chest compressions resulted in faster time to the ROSC. We observed higher diastolic pressure and increased carotid and coronary blood flow with femoral occlusion . The goaThe blood flow and coronary perfusion during cardiac arrest are dependent on the quality and continuity of chest compressions . The optResuscitative endovascular balloon occlusion of the aorta has been proposed as a novel approach to managing non-traumatic cardiac arrest in adults . In a swWe also wanted to see the effect of femoral occlusion on epinephrine levels. We anticipated that a reduced volume of distribution (Vd) due to femoral occlusion would result in a higher epinephrine concentration just prior to ROSC. In addition, we speculate that adrenals, being an essential organ, receive increased blood flow with femoral occlusion during chest compressions. This may also result in an inherent epinephrine surge. As expected, the epinephrine levels right before ROSC were higher in femoral occlusion.Reduced glutathione (GSH) is considered to be one of the most important scavengers of reactive oxygen species (ROS), and its ratio with oxidized glutathione (GSSG) in the plasma may be used as a marker of oxidative stress and reperfusion injury . FemoralAHA and NRP recommend the initiation of chest compressions if the neonate’s heart rate remains below 60 bpm after at least 30 s of effective PPV . DespiteIncreasing the coronary perfusion pressure is a critical step in achieving ROSC and there are a number of strategies to increase diastolic pressure or cardiac output during chest compressions in neonatal resuscitation, but not all of them have been studied in humans. Increasing the diastolic pressure during chest compressions is most effectively achieved through umbilical venous (or intraosseous) epinephrine followed by a flush ,28,29 F. SustainSpecies difference was a limitation to our study, but the decision to use fetal lambs is based on their size in relation to the human neonate, and the comparable pulmonary physiology. Due to the technique involved, the resuscitators were not blinded and this might have introduced bias. We speculate that given the thin hind legs in fetal lambs, a human neonate may be a better model to evaluate lower limb flexion over the abdomen.The major advantages of the femoral occlusion technique are that it can be performed quickly, is low tech, and can be used in a low-resource setting.This is the first study evaluating the effect of femoral occlusion in a transitional model of cardiac arrest due to severe asphyxia. Femoral occlusion is a simple maneuver that can be easily adapted during CPR in resource-poor settings. We speculate the increase in diastolic pressure during femoral occlusion increases the coronary perfusion resulting in a faster ROSC. The results from this study are likely to trigger clinical trials that could change the neonatal resuscitation guidelines and significantly impact survival and neurodevelopmental outcomes for approximately 2400 neonates in the US and over 75,000 births worldwide that require extensive resuscitation in the delivery room ,38.


Catheter tip distance > 5 to ≤ 8 cm  and > 8 cm  compared to ≤ 3 cm from HVO were independent predictors of not achieving optimal FHVP. Baseline HVPG ≥ 16 mmHg was strongly associated with deaths due to cirrhosis and liver transplantation for end-stage liver disease compared to HVPG < 16 mmHg when FHVP was optimal (p < 0.001) but not when it was suboptimal (p = 0.359). Our study showed that FHVP is spuriously elevated when measured at > 5 cm from HVO, resulting in inaccurately low HVPG.Hepatic venous pressure gradient (HVPG) is an accurate measure of portal hypertension in cirrhosis. However, the effect of catheter tip distance from hepatic vein ostium (HVO) on HVPG is unknown. We performed a retrospective study on 228 patients with 307 HVPGs in our institution. The objectives of this study were to assess the effect of catheter position on the validity of HVPG and its prognostication in cirrhosis. In this study, free hepatic vein pressure (FHVP) was considered optimal when difference between FHVP and inferior vena cava pressure was ≤ 2 mmHg. HVPG progressively decreased ( Although wedged hepatic venous pressure (WHVP) was described as early as 1951 by Taylor and Myers2, much of the early research on portal hypertension (PH) relied on the more invasive direct measurement of portal vein pressure4. It was subsequently shown that that WHVP was highly correlated with the direct portal vein pressure in cirrhosis of varying aetiologies7, obviating the need for puncture of portal vein for assessment of portal hypertension. In 1979, Groszmann et al.8 introduced the use of balloon catheter to achieve wedged position in the hepatic vein (HV) instead of a straight catheter, allowing for repeated measurement of WHVP and free hepatic vein pressure (FHVP) without the need for multiple catheter manipulations.“Anything worth doing should be done right”. Groszmann and Wongcharatrawee11. Central to the calculation of HVPG is the accurate measurement of free hepatic vein pressure (FHVP) as a surrogate of systemic pressure. The technique of FHVP measurement remains inconsistent, where some have advocated for the catheter to be placed strictly 2–3 cm from hepatic vein ostium (HVO)10 while others measured FHVP at either 2–4 or 4–5 cm from HVO13. It was also suggested that the difference between FHVP and inferior vena cava pressure at the level of hepatic vein (IVCP), or FHVP-IVCP > 2 mmHg, may be clue that FHVP measurements had been too distal1 but there is no data supporting this recommendation.Despite the extensive body of literature supporting the role of HVPG in clinical management, its use remains largely restricted to centres of academic excellence. Despite this, several groups have continued to refine the techniques of HVPG to improve its value as a prognostic toolTherefore, the aims of this study were to evaluate (1) the effect of HVPG measurements at various distance from HVO and (2) the relationship of catheter position on FHVP-IVCP and its impact on the accuracy of HVPG in clinical correlation and prognostication in cirrhosis.14, this study did not require ethics board approval and informed patient consent as it was a retrospective review of service provision. Access to individual patient electronic medical records was approved (Ref: MR1811-21/R) in accordance with our institutional policy for governance of data use by the Office of Data and Digital Governance, SingHealth. This involves review and endorsement by the departmental head, institutional data protection officer and chief executive officer.We conducted a clinical audit in 2021 to evaluate the quality of HVPGs performed at Singapore General Hospital, a tertiary hospital with a liver transplant programme. In keeping with national guidelines on quality assurance and/or service improvement studies by the Ministry of Health Singapore15 but the diagnosis of nonalcoholic steatohepatitis (NASH) cirrhosis was based on the consensus recommendations by the multi-stakeholder Liver Forum for definite (n = 20) and probable (n = 59) NASH16. Briefly, definite NASH required histological confirmation of steatohepatitis while probable NASH was diagnosed in the presence of steatosis without steatohepatitis on histology or steatosis on imaging plus at least two cardiometabolic risk factors and in the absence of competing aetiology. Patients were then assessed for unequivocal signs of clinically significant portal hypertension (CSPH) within three months of each HVPG: gastroesophageal varices, ascites, hepatic hydrothorax and/or abdominal portosystemic collaterals. Exclusion criteria were non-cirrhotic portal hypertension (n = 61), acute liver failure or acute-on-chronic liver failure (n = 2), absence of portal hypertension  (n = 11), HVPGs with technical errors (n = 24) and patients with missing data (n = 13)  performed between 1 January 2009 and 31 December 2019 were assessed for eligibility. Cirrhosis was diagnosed by histology, or combination of clinical, biochemical, ultrasonographic and/or endoscopic findings. The underlying causes of cirrhosis were identified by clinical history, serology and/or histology17. No patient in this study received deep sedation or general anaesthesia during HVPG. Once either the right or middle hepatic vein was cannulated with a 4F Multipurpose A catheter , a 5.5F balloon-tipped catheter  was exchanged and triplicate pressures were recorded with a digital pressure transducer  in the same position. Wedged hepatic vein pressure (WHVP) was obtained when the balloon was fully inflated  which has multiple built-in electronic tools, including for the measurement of length. Catheter tip distance from HVO was measuredThe first part of the study was a technical audit of HVPG procedural quality in our institution Fig. . The aimThe second part of the study was a clinical audit to evaluate the impact of FHVP-IVCP on clinical correlation and prognostic value of HVPG Fig. . In pati18, or ascites/hepatic hydrothorax19 < 10 mmHg in patients with gastric, low risk oesophageal varices 20 < 10 mmHg in patients without gastroesophageal varices, ascites or hepatic hydrothorax but with abdominal portosystemic collaterals seen on any abdominal scans22 < 12 mmHg in patients with non-bleeding, high risk oesophageal varices 23 < 12 mmHg in patients with history of oesophageal variceal bleed within the past three monthsThe baseline HVPG for each patient was compared to the minimum expected HVPG for CSPH. HVPG lower than expected for their respective sign(s) of CSPH were deemed clinically incongruent HVPG (ciHVPG):24 was assessed. Deaths were due to cirrhosis if they were directly related to complications of cirrhosis, within six weeks of variceal bleed or following acute-on-chronic liver failure25. Patients lost to follow-up were censored at last known date alive while those still on follow up were censored on 31 December 2021. Non-cirrhosis-related deaths and liver transplantation for hepatocellular carcinoma only without clinical decompensation were competing risk events.Finally, the association of HVPG ≥ 16 mmHg to the composite endpoints of cirrhosis-related death and liver transplantation for end-stage liver disease (ESLD)2 or Fisher’s exact test. The intra-class correlation coefficient (ICC) was calculated to determine the degree of rater agreement in the measurement of catheter tip distance from HVO. The Jonckheeree-Terpstra test for trend was performed to compare pressure measurements in ordered groups of increasing catheter tip distance from HVO during HVPG measurement. Post-hoc pairwise comparisons of HVPG measurements with Bonferroni correction were also assessed.Continuous variables were expressed as median and interquartile range (IQR) while categorical variables were expressed as numbers and their percentages in parentheses. Continuous variables were compared by means of the Mann–Whitney U test, while categorical variables by either the Pearson’s χp < 0.100 on univariate analysis were selected for inclusion into multivariable analysis. Competing risk Gray’s test was applied to compare cumulative incidence of the composite endpoints of patients with HVPG ≥ 16mHg and < 16 mmHg at baseline. Statistical analysis was performed with SPSS v26.0  and EZR v1.55, a graphical user interface for R software v4.1.2 (https://www.r-project.org)26 where a two-sided p < 0.050 was statistically significant.A multivariable binary logistic regression was conducted to assess independent predictors of optimal FHVP and ciHVPG. All variables with Three-hundred thirty-nine patients underwent 444 HVPGs during the 10-year period. After excluding 111 patients, 228 patients with 307 HVPGs were included in this study , p < 0.001], respectively.Of the 307 HVPGs, FHVP was optimal in 190 (61.9%) and suboptimal in the remaining 117 (38.1%). The catheter tip distance from HVO was 4.9  cm during pressure measurements, where 165 HVPG measurements (53.7%) were obtained at ≤ 5 cm from HVO Table . The intp = 0.343)   with increasing catheter tip distance from HVO    and between > 5 to ≤ 8 and > 8 cm from HVO (p = 1.000) while all other between-group comparisons were significantly different , p = 0.002] from HVO were independent predictors of not achieving optimal FHVP, when compared to ≤ 3 cm from HVO.Table p = 0.399). However, the median (IQR) HVPG for procedures with suboptimal FHVP was significantly lower than HVPGs with optimal FHVP .After excluding 14 patients, the baseline HVPGs of the remaining 214 patients were audited for clinical correlation and prognostication  (Table p = 0.430). Multivariable analysis showed that suboptimal FHVP was the only independent predictor of ciHVPG    months, 67 patients died due to cirrhosis and six patients underwent liver transplantation for ESLD  having signs of CSPH in this smaller cohort, a quarter of patients with suboptimal FHVP had ciHVPG compared to 1 in 10 of patients with optimal FHVP. On multivariable analysis suboptimal FHVP was the only independent factor associated with ciHVPG. Interestingly, we also found that male gender had a higher odds of ciHVPG although the p value was just outside the pre-defined threshold for statistical significance. We believe that this was likely a type I error, as to the best of our knowledge, gender is not known to have any meaningful effect on pressure measurements during HVPG.We further analysed the impact of FHVP-IVCP on the clinical correlation of HVPG to the signs of CSPH and prognostication of survival in a smaller cohort of patients. After excluding patients on NSBB and occlusive portal vein thrombosis, the baseline HVPG of patients where the pressure measurements had suboptimal FHVP was significantly lower compared to those with optimal FHVP. The difference in HVPG between the groups was likely a reflection of the differences in catheter position during pressure measurement as there was no difference in the baseline demographics, complications of liver disease and markers of disease severity  into the lower risk group (HVPG < 16 mmHg) led to the cumulative incidence of the composite endpoints in both groups to converge, resulting in loss of statistically significant difference between HVPG ≥ 16 mmHg and < 16 mmHg, diminishing its prognostic value.In terms of prognostication, HVPG ≥ 16 mmHg was strongly associated with the composite endpoints of cirrhosis-related death and liver transplantation for ESLD only when FHVP was optimal but not when it was suboptimal. In keeping with the findings from other studies32, as we do not routinely perform transient elastography33 or liver biopsy34 in patients already diagnosed with cirrhosis based on clinical, biochemical, sonographic and/or endoscopic findings. Secondly, it is now well described that about 10% of patients with cirrhosis due to NASH can develop signs of portal hypertension or decompensation at HVPG < 10–12 mmHg36. In our study, the prevalence of ciHVPG was numerically higher in patients with NASH compared to non-NASH but the difference was not statistically significant. When NASH as a variable was forced into the multivariable logistic regression model, it also did not emerge as an independent predictor of ciHVPG. This difference between our study and the others may be due to the much smaller number of patients with NASH cirrhosis in our study (n = 79) compared to the studies by Sanyal et al.35 (n = 258) and Bassegoda et al.36 (n = 548). Primary biliary cholangitis (PBC) is another well-described chronic liver disease with a prominent pre-sinusoidal component of portal hypertension and HVPG may also underestimate the actual portal pressure gradient37. We were unable to verify this in our study as the number of patients with PBC was very small (n = 10). Finally, in a study from India, 10.3% of patients with decompensated cirrhosis predominantly due to alcohol use had HVPG < 10 mmHg38. This finding concurs with ours and suggests that approximately 1 in every 10 patients with cirrhosis, not necessarily due to NASH, and presenting with either definite signs of CSPH or clinical decompensation, may have HVPG lower than the traditionally accepted threshold23. This finding is novel, but needs to be validated in larger studies from other centres.In our study, almost 10% of patients with accurate HVPG, in the group of patients with optimal FHVP, had ciHVPG. It may be possible that some of these patients had porto-sinusoidal vascular disease, a condition with lower HVPG but often misdiagnosed as cirrhosis11. This was not assessed in our retrospective study as such repeat pressure measurements in the same patient is not routinely performed in clinical practice. Moreover, the results of our study may need to be interpreted with some caution, as the routine use of 5.5 F catheters in our practice likely allowed measurement of FHVP more distally in the hepatic veins with less relative obstruction or wedging of the veins11 compared to larger 7-8F catheters commonly used in others centres13. Finally, pressure measurement tracings are not permanently recorded in our centre and therefore, were not available for review in this study. As such, we were not able to verify the accuracy of the pressure measurements, especially for WHVP, which requires interpretation of pressure tracings after an adequate period of stabilisation. This may further introduce uncertainties into the findings and conclusions of our study.We would like to acknowledge the limitations of this study. Our study was a single centre series hampered by retrospective analysis. Furthermore, there is no standard method of measuring catheter tip distance from HVO during HVPG, either intra-procedurally or during review of fluoroscopy images, although rater agreement was good to excellent in our study. However, this method of measuring catheter tip distance from HVO relies on static images captured during fluoroscopic projections during HVPG which may not be reflective of the actual procedures in real-time, including the process of WHVP and FHVP measurements. Furthermore, the quality of the images was not standardised, and this may also limit the accuracy of the measured distance. Secondly, our study would not account for the pressure changes due to individual patient variation in the caliber and shape of the hepatic veins as this would require haemodynamic assessments, including FHVP, to be repeated in the same vein of the same patient at different distance from HVOHVPG likely decreases when measured at progressively farther distance from HVO due to its effect on increasing FHVP. HVPGs measured within 5 cm from HVO may be more likely to comply with the quality criterion of FHVP-IVCP ≤ 2 mmHg but pressure measurements beyond this threshold may correlate more poorly with signs of CSPH and lose its prognostic value in cirrhosis. However, due to the limitations of our study, these findings need to be verified in larger prospective studies.Supplementary Table S1.


The objective of this study was to identify risk factors associated with lack of tracheal sealing by an endotracheal cuff inflated to > 30 cmH2O in patients undergoing mechanical ventilation.The cuff pressures > 30 cmHThis prospective cross-sectional study was conducted from 2019 to 2020 in the cardiothoracic intensive care unit and respiratory medical care unit of a Hospital in Nantong, China. Patients aged >16 years undergoing cardiothoracic surgery with mechanical ventilation using endotracheal intubation were included. Patient characteristics and ventilator parameters were analyzed. Cuff pressure was maintained with the minimum leak technique (MLT) and measured with a cuff pressure gauge. Cuff pressure was measured for 30 seconds when ventilation was accompanied by no leak, simultaneously detected by the ventilator or auscultation with a stethoscope.2O. Multivariable analysis showed that cuff manufacturer (Guangzhou Weili) and nasal endotracheal intubation significantly increased the risk of an unsealed trachea. Peak inspiratory pressure, cuff diameter and male sex had a strong inverse association with an unsealed trachea.Of 352 patients undergoing mechanical ventilation, 51 patients (14.5%) had a cuff pressure of >30 cmH2O is adequate for most patients, but lack of a tracheal seal still occurs in a small number of people. An unsealed trachea is most likely because cuff and tracheal diameters do not match.These findings suggest that an endotracheal cuff pressure of 20 to 30 cmHClinical Trial Registration:http://www.chictr.org.cn/index.aspx Unique identifier: ChiCTR-COC-15006459. However, in clinical practice cuff pressures > 30 cmH2OEvidence-based guidelines recommend that cuff pressure is maintained between 20 and 30cm H2O; however, it is unclear why this may not achieve proper sealing between the trachea and the cuff wall in all patients. If cuff pressure is managed in strict accordance with guideline recommendations, leakage around the cuff may impede ventilation and lead to ventilator-associated pneumonia. The objective of this study was to identify risk factors associated with lack of tracheal sealing by a cuff inflated to > 30 cmH2O in patients undergoing mechanical ventilation. In this cross-sectional study, we collected data concerning current clinical practice at an institutional level rather than personal views or opinions. Findings will ensure safe cuff pressures are used in patients undergoing mechanical ventilation.This variability is reflected in a large number of studies, and there is no consensus on optimal cuff pressure targets.http://www.chictr.org.cn/index.aspx.This single-center, prospective cohort study was performed in the cardiothoracic intensive care unit and respiratory medical care unit of a hospital in Nantong, China between June 2019 and October 2020. This study was approved by the Medicine Human Studies of Nantong University affiliated hospital (2015--108) on May 21, 2015. The study was registered with the Chinese Clinical Trial Registry (ChiCTR-COC-15006459) on 29 May 2015, Age ≥16 years;Willingly provided informed consent;Had current anthropometric data. Patients with unstable vital signs or massive pleural effusion were excluded.The following factors were examined to determine their influence on the ability of an endotracheal cuff to maintain a seal within an airway: cuff diameter, duration of time required for endotracheal intubation, timing of intubation, duration of sedation, number of times the patient was repositioned, number of times suctioning was performed,19AVEA ventilator systems  were used in this study. The mode of mechanical ventilation was determined by the physician. Other equipment included reinforced endotracheal tubes , ordinary endotracheal tubes , tracheotomy cannula , cuff pressure gauges , stethoscopes , and retractable tubes with a 1.5-m suction loop .2) were obtained from the hospital information system. Ventilator parameters were set by physicians according to the patients’ weight and clinical characteristics. Mechanical ventilation was initiated in patients with stable vital signs who required assisted spontaneous breathing after two hours in the supine position. Sedatives were administered to patients with strong spontaneous respiratory effort. The method of endotracheal intubation , cuff diameter and cuff manufacturer were recorded. Tidal volume (VT), peak inspiratory pressure (PIP) and respiratory rate (RR) were derived from the ventilator.Patients were evaluated by a nurse from the ICU who informed them orally about the purpose and risks of this study. Written, informed consent was obtained from all patients or their legal representatives. Patient age (years), sex, height (m), weight (kg), and body mass index  or >30 cmH2O .Cuff pressure management was performed by one of four nurses with at least five years of work experience in the ICU. Each nurse used the same brand of cuff pressure gauge . Cuff pressure was maintained with the minimum leak technique (MLT).2O (TLA30). Odds ratios (ORs) and corresponding 95% confidence intervals (CI) were calculated after adjusting for the effects of potential confounding variables.Statistical analyses were conducted using SPSS version 20  and Prism 8 . Data for patients with no cuff pressure values were excluded from the analysis. Descriptive statistics were used to compare patient baseline characteristics and outcomes. Univariate chi-square tests and t tests were used to compare categorical variables and continuous variables, respectively. P < 0.05 was deemed significant. Multivariate logistic regression analysis was used to evaluate the impact of the variables identified as primary risk factors for tracheal leakage at a cuff pressure > 30 cmH2. Most patients underwent oral endotracheal intubation (92.3%), nasal endotracheal intubation was performed in 4.6% of patients, and tracheotomy was performed in 3.1% of patients. Among the ventilator parameters, mean VT was 577.4 ± 95.21 mL and mean RR was 13.61 ± 2.76 breaths/min (2O (48 men and three women), which occurred at an incidence of 14.5% (95% CI: 10.8–18.2%)  .The cuff diameter of the endotracheal tube manufactured by Jiangxi Galanz Medical Equipment Co., Ltd was significantly larger than the cuff diameter of the endotracheal tube manufactured by Guangzhou Weili Medical Equipment Co. Ltd or the tracheotomy cannula manufactured by Guangzhou Weili Medical Equipment .Unadjusted and adjusted binary logistic regression analyses identified several independent risk factors for TLA30 during mechanical ventilation, including male sex, cuff diameter, and PIP  and III.2O during surgery and mechanical ventilation.2O is not ideal for every patient. The optimal cuff pressure should ensure adequate ventilation while concurrently avoiding tissue ischemia, ulceration, and necrosis of the tracheal wall and air leak.Evidence-based guidelines recommend that endotracheal cuff pressure is maintained between 20 and 30 cmHOur analyses showed that male sex was associated with a >10-times higher risk of TLA30 than female sex . The findings are consistent with previous reports. In an observational cross-sectional study in a tertiary metropolitan intensive care unit that assessed the relationship between the MLT and cuff manometry, univariate analysis showed female patients required lower volumes in their cuffs and had smaller endotracheal tubes than males.222O, if cuff and tracheal diameters match (L1 = L2), the pressure within the cuff will equal the pressure of the cuff on the tracheal mucosa (P1 = P2); however, if cuff and tracheal diameters do not match (L1 < L2) the cuff may exert pressure > 30 cmH2O (P1 > P2)  .7,241 < L2 and P1 > P2).Available intubation techniques include oral endotracheal intubation, nasotracheal intubation, and tracheostomy. Findings from the present study suggest that cuff diameter for a given model of endotracheal tube varies across manufacturers. In clinical practice when the patient’s nasal cavity is small, the anesthesiologist may select a small endotracheal tube for nasotracheal intubation. There is the probability that the cuff size may be smaller than the patient’s airway diameter. Consequently, patients with transnasal tracheal intubation may require a higher cuff pressure to seal the trachea. In clinical practice, medical staff are unaware of the factors that influence TLA30. In this case, cuff and tracheal diameters may not match .2O is adequate for most patients but may result in insufficient sealing of the trachea in a small number of patients. There is a need for comprehensive criteria on which to base target cuff pressure. These should include patient anthropometric and clinical data and specifications on the design and size of the endotracheal tube.The present study indicates that an endotracheal cuff pressure of 20 to 30 cmHHLW: Wrote the manuscript, collected data, primary research/study designer.HYS: Collected data, Analyzed data, primary research.JHS: Offered guidance on study design and manuscript.WQS: Analyzed data, Primary research/study designer, Accountable for the accuracy and integrity of the work.


Hypertension is an important risk factor for atherosclerotic cerebral small vessel disease (CSVD). Higher blood pressure is associated with a higher CSVD burden and the presence of relevant magnetic resonance imaging (MRI) markers. However, the effect of blood pressure level on CSVD burden and imaging markers including white matter hyperintensity (WHM), lacune, enlarged perivascular spaces (EPVS), and cerebral microbleed (CMB) remains unknown. The purpose of this study was to investigate the correlation between blood pressure level and CSVD burden at different time periods throughout the day.In total, 144 in-patients with CSVD  were enrolled and underwent brain MRI, and 24-h ambulatory blood pressure was assessed. Patients were categorized into five groups according to their MRI-evaluated total CSVD burden scores (0–4). Spearman's correlation analysis was performed to examine the correlation between blood pressure levels at different time periods and the total CSVD score or the markers of periventricular WMH, deep WMH, lacune, EPVS, and CMB.P = 0.018), daytime (P = 0.018), and nighttime (P = 0.035). Spearman's correlation analysis demonstrated that the SBP of 24 h, daytime, nighttime, and morning and the diastolic blood pressure (DBP) of 24 h and morning positively and significantly correlated with the total CSVD score (P < 0.05). A logistic regression analysis indicated that both morning SBP and DBP were independent risk factors for total CSVD burden . Spearman's correlation analysis indicated a significant positive correlation between morning SBP and higher deep WMH Fazekas score , EPVS grade in the basal ganglia , and the presence of lacune  and CMB . Morning DBP only correlated positively with the presence of CMB .Of the 144 patients, 83.3% (120/144) harbored one or more CSVD markers of interest. The systolic blood pressure (SBP) of 24-h, daytime, nighttime, and morning differed significantly among the five groups. The SBP levels increased significantly with the total CSVD scores during 24 h (Higher SBP signficantly correlated with total CSVD burden in patients with atherosclerotic CSVD. Early morning blood pressure level is an important indicator to reflect the severity of CSVD patients. Cerebral small vessel disease (CSVD) is a group of clinical, imaging, and pathological syndromes caused by structural remodeling of small cerebral arteries and their distal branches, micro-arteries, capillaries, micro-venules, and small veins , frequenThe 24-h ambulatory blood pressure monitoring (ABPM) provides information on a patient's blood pressure levels not only throughout the day but also at different times of the day, including daytime (6:00–22:00), nighttime (22:00–6:00), and early morning. Previous studies have confirmed that 24-h ABPM is more capable of predicting hypertension-related cardiovascular risks than casual clinical blood pressure measurements , 10. EarThere have been many studies on the effect of 24 h, daytime, and nighttime blood pressure levels on CSVD. However, there are few studies on the correlation between EMBP and CSVD. This study aimed to investigate the effect of blood pressure levels on the total burden of CSVD patients at different time periods throughout the day, especially in the early morning.This hospital-based retrospective study involves data from the Department of Neurology, PLA General Hospital, Beijing, China, from 1 May 2021 to 1 September 2022. Patients hospitalized with CSVD  aged betClinical information such as age, sex, body mass index (BMI), history of hypertension, diabetes mellitus, cigarette use, alcohol consumption, hypercholesterolemia, and previous stroke were recorded. Laboratory tests including total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and homocysteine were recorded. All admitted patients underwent 24-h ABPM using an automated ambulatory blood pressure recorder  within 7 days of admission. The recorder was set to record blood pressure every 30 min in the daytime (6:00–22:00) and every 1 h in the nighttime (22:00-next 6:00). The mean systolic blood pressure (SBP) and the mean diastolic blood pressure (DBP) during daytime, nighttime, and 24 h were collected. As each patient woke up at different times, the EMBP results were obtained using the average of blood pressure readings taken between 6:00 and 10:00. If the measurement frequency was below 70%, with less than one measurement per hour during the day and less than six measurements in total at night, a 24-h ABPM recording was considered invalid.Brain MRI scan was performed for the patients within 7 days of admission on one 3.0T MR scanner . The sequences of MRI included T1-weighted, T2-weighted, T2 fluid attenuated inversion recovery (FLAIR), diffusion-weighted imaging (DWI), and susceptibility weighted imaging (SWI). According to the presence of the following four MRI markers of CSVD including lacune, white matter hyperintensity (WMH), microbleed, and enlarged perivascular spaces (EPVS) in the basal ganglia, the total burden score was assessed using the method reported previously . Two radP < 0.05. Data of continuous variables were presented as mean ± SD if normally distributed and median  otherwise. For continuous variables with a normal distribution, ANOVA was used for comparison between groups, while Kruskal-Wallis test was used if the distribution is not normal. Categorical variables were presented as n (%), and the χ2 test was used for determining the difference between groups. Spearman's correlation analysis was performed to examine the correlation of 24 h, daytime, nighttime, and EMBP with the total CSVD score, WHM, lacune, EPVS, and CMB. A multivariate ordered logistic regression analysis was performed to explore whether the EMBP level was an independent risk factor for the burden of CSVD, adjusted for the classical vascular risk factors such as sex, age, diabetes, smoking, and hyperlipidemia.All the analyses were performed using SPSS 23.0 , and the difference was considered statistically significant if the A total of 208 individuals were initially included, of whom 12 were excluded due to inability to complete MRI, 30 were excluded for severe past or acute ischemic or hemorrhagic stroke, and 22 were excluded for invalid ABPM data. Therefore, 144 patients in the Department of Neurology, PLA General Hospital, from 1 May 2021 to 1 September 2022, were included in the subsequent analysis . Of all Age and history of hypertension differed significantly among the five groups . The group with a higher total CSVD burden had a higher mean age and higher prevalence of hypertension. Sex, diabetes, hyperlipidemia, cigarette use, and alcohol consumption did not differ significantly among different groups. No significant difference was observed in the level of BMI, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein cholesterol, and homocysteine .P = 0.015; OR = 1.19, 95% CI: 1.06–1.33, P = 0.005)  . The rel= 0.005) . The regr = 0.292, P < 0.001)  .In this study, we used ABPM to obtain information on blood pressure levels since previous studies have found 24-h ABPM to be more effective than casual blood pressure levels in predicting vascular risk –17. In oThere were no significant differences of the traditional cerebrovascular risk factors –30, inclIn our study, we also found that the EMBP levels were significantly associated with the CSVD burden, and patients with a higher CSVD burden also had higher EMBP levels. Spearman's correlation analysis showed that both morning systolic and diastolic blood pressure levels were significantly and positively associated with CSVD burden. In addition, there was a significant correlation between EMBP levels and four imaging markers, namely, deep WMH Fazekas score, lacune, EPVS grade, and CMB. Among the MRI markers of CSVD, the detection of periventricular and deep WMH and EVPV were correlated only with SBP, while CMB and lacunes were associated both with SBP and with DBP. One possible explanation is that higher SBP leads to endothelial dysfunction, which in turn results in blood–brain barrier disruption and white matter lesions . ImagingP = 0.049, P = 0.002) (P < 0.001) (P = 0.45) , independent of whether the patient is receiving antihypertensive therapy –36. Shep= 0.002) . A study = 0.45) . Our stuThere will be at least two possible explanations for the identified positive correlation between EMBP and CVSD burden. First, although the pathophysiological mechanisms of EMBP elevation are not fully understood, the mechanism of over-activation of the sympathetic nervous system is well accepted . IncreasThis study not only showed that EMBP was significantly and positively associated with CSVD MRI burden but also demonstrated that its elevation was associated with CSVD severity and the presence of multiple CSVD MRI markers. Thus, EMBP was introduced as an independent risk factor for increased CSVD severity. While focusing on blood pressure levels in CSVD patients, an EMBP level may become an important and nonnegligible indicator for blood pressure management in CSVD patients.There are several limitations to be addressed. First, some factors can also affect EMBP levels such as length and quality of sleep. Sudden environmental changes may affect the length and quality of sleep of hospitalized patients and influence the blood pressure levels detected by ABPM. It is possible that ABPM in hospitalized patients may not fully reflect the subject's blood pressure levels in daily life, leading to biased results. Second, atrophy was considered one of the CSVD markers, but there was no widely accepted method and cuto? to assess it up to now. Therefore, we did not include brain atrophy as a marker in our assessment of patients' imaging. Third, given that our study was performed in a single center, the causal-e?ect relationship between the baseline BP levels and the total CSVD burden and its progression in later years could not be obtained and require further explorations in multi-center prospective and randomized clinical trials. Fourth, the types and quantities of antihypertensive medication taken by the participants were not analyzed in this study, and antihypertensive medication might have influenced the results of this study. Finally, 3.0 T high-resolution MRI was employed in the present study, while 1.5T brain MR scans were used by Staals et al. (Higher SBP significantly correlated with total CSVD burden in patients with atherosclerotic CSVD. EMBP elevation was associated with multiple CSVD MRI markers and increased CSVD MRI burden scores. This study helps to elucidate the effect of EMBP levels on CSVD, yet the patients were not followed up to further validate the findings. Future prospective cohort studies may be needed to focus on the effects of EMBP modulation on CSVD burden.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by The Sixth Medical Center of PLA General Hospital Drug Clinical Trial Ethics Committee. The patients/participants provided their written informed consent to participate in this study.HQ had full access to all data in the study and is responsible for the integrity of the data and the accuracy of the data analysis. HY, XF, and XS contributed to the design of the study and statistical analysis. HY, XS, and LLia contributed to the drafting of the manuscript. DH, YZ, and LLiu contributed to the acquisition of the data. HY, XF, LLia, XS, DH, YZ, LLiu, and HQ contributed to the revision of the manuscript for important intellectual content. All authors were involved in the interpretation of the study results and approval of the final version of the manuscript.


Furthermore, patients with CIAKI had significantly higher CRP (p < 0.001) and SUA (p < 0.006). Conclusions: We showed a significant difference in RRI, IMT, SUA and CRP values between the population developing CIAKI and patients without CIAKI. This data appears relevant considering that RRI and IMT are low-cost, non-invasive and easily reproducible markers of endothelial dysfunction and atherosclerosis.Introduction: Contrast-induced acute kidney injury (CIAKI) is one of the main causes of acute renal failure in hospitalized patients, following the administration of iodinated contrast medium used for CT scans and angiographic procedures. CIAKI determines a high cardiovascular risk and appears to be one of the most feared complications of coronary angiography, causing a notable worsening of the prognosis with high morbidity and mortality. Aim: To evaluate a possible association between the renal resistive index (RRI) and the development of CIAKI, as well as an association with the main subclinical markers of atherosclerosis and the main cardiovascular risk factors. Materials and Methods: We enrolled 101 patients with an indication for coronary angiography. Patients underwent an assessment of renal function , inflammation (C reactive protein (CRP), serum calcium and phosphorus, intact parathormone (iPTH), 25-hydroxyvitaminD (25-OH-VitD), serum uric acid (SUA), total cholesterol, serum triglycerides, serum glucose and insulin). All patients also carried out an evaluation of RRI, intima-media thickness (IMT), interventricular septum (IVS) and the ankle-brachial index (ABI). Results: 101 patients , with a mean age of 73.0 ± 15.0 years, were enrolled for the study; 35 are affected by type 2 diabetes mellitus. A total of 19 cases of CIAKI were reported (19%), while among diabetic patients we reported an incidence of 23% (8 patients). In our study, patients with CIAKI had significantly higher RRI ( The definition of contrast-induced acute kidney injury (CIAKI) is an absolute ≥0.5 mg/dl) or relative increase ≥25%) in serum creatinine after 48–72 h from exposure to an iodinate contrast agent . The inc5% in ser mg/dl orGenerally, CIAKI results in mild and transient acute kidney injury (AKI), with some patients requiring dialysis, which increases the mortality rate ,8. The mIn the renal parenchyma, iodinated contrast medium seems to determine transient vasoconstriction of the afferent, efferent and vasa arterioles recta; the hypoxic status could result in tubular damage . AnotherThe aim of the study was to evaluate the association between RRI and the onset of CIAKI. We also evaluated subclinical markers of atherosclerosis , the ankle-brachial index (ABI)), the main cardiovascular risk factors such as C reactive protein (CRP), mineral metabolism , 25-hydroxyvitaminD (25-OH-VitD)) and metabolic indexes (serum uric acid (SUA), total cholesterol, serum triglycerides, serum glucose and insulin) as possible predictive factors of CIAKI.The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board Sapienza University of Rome, Italy .The study conforms to the principles outlined in the Declaration of Helsinki and we obtained written informed consent. We performed a longitudinal, observational study on 101 hospitalized patients at the University Hospital “Policlinico Umberto I” of Rome . We enrolled consecutive patients of both sexes, aged ≥ 18 years, with an estimated glomerular filtration rate (eGFR) between 45 mL/min and 90 mL/min (CKD-EPI) admitted in the Cardiology Dept., Angiology Dept. and Intensive Care Unit candidate to coronary angiography. For CIAKI prevention, according to protocol, saline solution (500 mL) was administered to all patients before the procedure. Metformin was discontinued 48 h before the exam; angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB) and diuretics were discontinued 24 h before the exam. We excluded patients with ongoing sepsis, current infections, hemodynamic instability, hepatorenal syndrome, stenosis and/or hemodynamic obstruction of the renal artery or who refused to consent. Before the angiographic procedure, some clinical and laboratory evaluations were performed.In all patients, creatinine levels were evaluated (mg/dL) the day before (T0), and 48 and 72 h after administration of the contrast media. An increase of ≥0.5 mg/dl or ≥25% was considered diagnostic for CIAKI. Other laboratory tests at T0 were: fasting plasma glucose (mg/dl), serum insulin (µU/mL), serum nitrogen (mg/dl), SUA (mg/dl), serum calcium (mg/dl), serum phosphorus (mg/dl), serum sodium (mEq/L), serum potassium (mEq/L), hemoglobin (g/dl), total serum cholesterol (mg/dl), triglycerides (mg/dl), high-density lipoprotein (HDL) (mg/dl), low-density lipoprotein (LDL) (mg/dl) and CRP (mg/dl). 25-OH-VitD (ng/mL) was assessed using radioimmunoassay and iPTH (pg/mL) using III generation assay. The eGFR was calculated with the abbreviated chronic kidney disease epidemiology formula (CKD-EPI), as defined by Levey et al. . ArteriaClinic blood pressure (BP) measurements were performed three times after 10 min of rest in a seated position using a standard automated sphygmomanometer and cuffs adapted to the arm’s circumference, as per 2017 Cardiology/American Heart Association (ACC/AHA) Hypertension Guidelines. Hypertension was defined by an average systolic BP (SBP) ≥ 130 mmHg or diastolic BP (DBP) ≥ 80 mmHg, on repeated measurements. We considered for statistical analysis the BP values detected before the procedure .Carotid artery imaging was performed before the procedure by a single investigator with a high-resolution B-mode ultrasound machine Toshiba Aplio xV  equipped with a 5- to 12-MHz linear transducer with a 0.01 mm resolution, following a standardized vascular protocol. IMT was sampled in three sites on both right and left sides: internal carotid artery (ICA), carotid bulb and common carotid artery (CCA). Images were captured in end-diastole triggered by electrocardiographic recording. The mean value was calculated and considered normal between 0.55 and 0.9 mm .Participants were studied with the high-resolution B-mode ultrasound machine Toshiba Aplio xV  equipped with a 3–3.5 MHz convex transducer. RRI mean values were assessed with three different measurements in the renal superior pole, interpolar regional and inferior pole on interlobular and interlobar or arcuate arteries in both kidneys. We used an anterior and oblique approach to detect the renal arteries and intra-parenchymal vessels. Three to five reproducible and consecutive waveforms with similar aspects from each kidney were obtained ,17. We dAll patients underwent echocardiographic examination to assess the morphology and performance of the heart. We used a Philips model iE33 xMATRIX equipped with the S5-1 transducer. We evaluated the IVS thickness as well as the posterior wall thickness at end-diastole  and the end-diastolic left ventricular (LV) dimension in M-mode and in parasternal long axis . The following parameters were assessed: LV mass index and the relative wall thickness, the presence of concentric or eccentric hypertrophy and the presence of diastolic dysfunction. In addition, we evaluated the end-systolic and diastolic volume , using Simpson’s biplane method to estimate the ejection fraction  .t-test. Differences between categorical variables were evaluated by the chi-square or Fisher’s exact test. Stepwise logistic regression analysis was used to evaluate the association between a dependent dichotomic variable (CIAKI yes or no) and continuous independent variables  or categorical independent variables (gender). Results were expressed as odds ratio (OR) and 95% confidence interval (95% CI). A p-value < 0.05 was considered significant.Statistical analysis was performed using SPSS 26 software . The Shapiro–Wilk test was used to evaluate the normal distribution of data. Continuous variables were expressed as mean ± standard deviation (SD). Categorical variables were expressed as absolute frequency and percentage. Differences between groups were evaluated by Student’s or Mann–Whitney’s A total of 101 consecutive patients , with a mean age of 73.0 ± 15.0 years, were enrolled on the study. The mean eGFR at baseline was 69.50 (±22.62) and 35 patients (34.6%) were affected by diabetes mellitus. Patients had a mean RRI of 0.68 (±0.05), mean ABI of 1.06 (±0.11) and mean IVS of 11.71 mm (±1.83). p = 0.345).In p < 0.001), IMT (p < 0.001), CRP (p < 0.001) and SUA (p < 0.006). We did not find any significant differences in ABI (p = 0.150), IVS (p = 0.257), total cholesterol (p = 0.158), serum glucose and insulin .The group CIAKI+ had significantly higher RRI (As at the univariate analysis there was not any independent risk factor for the onset of CIAKI, we did not perform multivariate analysis .In our study, the incidence of CIAKI was 19%, which is in accordance with the literature ,6. CIAKIWe conducted an observational study in a small cohort of patients. Considering the relevant impact of CIAKI on hospitalization length, morbidity and mortality, it is necessary to set larger and multicentric studies.Our study showed higher RRI, IMT, CRP and uric acid in CIAKI+ compared to CIAKI- patients.Additional studies are necessary to confirm these results in larger series of patients.