Acute kidney injury (AKI) in kidney transplant recipients (KTRs) is a common, yet poorly investigated, complication of urinary tract infections (UTI) and urosepsis. A retrospective comparative analysis was performed, recruiting 101 KTRs with urosepsis, 100 KTRs with UTI, and 100 KTRs without history of UTI or sepsis. The incidences of AKI in the urosepsis and UTI groups were 75.2% and 41%, respectively. The urosepsis group has also presented with a significantly higher prevalence of AKI stage 2 and 3 than the UTI group. The rates of recovery from AKI stages 1, 2 and 3, were 75,6%, 55% and 26.1%, respectively. Factors independently associated with renal recovery from AKI were: AKI severity grade (AKI stage 2 with OR = 0.25 and AKI stage 3 with OR = 0.1), transfusion of red blood cells (RBC) (OR = 0.22), and the use of steroid bolus in the acute phase of treatment (OR = 4). The septic status (urosepsis vs UTI) did not influence the rates of renal recovery from AKI after adjustment for the remaining variables. The dominant cause of RBC transfusions in the whole population was upper GI-bleeding. In multivariable analyses, the occurrence of AKI was also independently associated with a greater decline of eGFR at 1-year post-discharge and with a greater risk of graft loss. In KTRs with both urosepsis and UTI, the occurrence of AKI portends poor transplantation outcomes. The local transfusion policy, modulation of immunosuppression and stress ulcer prophylaxis (which is not routinely administered in KTRs) in the acute setting may be modifiable factors that significantly impact long-term transplantation outcomes. The occurrence of AKI is significantly associated with in-hospital mortality, especially in ICUs, but also with a decline of long-term renal function in both native and transplanted kidneys6. The most common cause of AKI in kidney transplant recipients (KTRs) is urinary sepsis (US) followed by other urinary tract infections (UTI)4. For this study, the term: “UTI-related acute kidney injury” (UTI-AKI) has been coined. The urinary tract remains the most common infection site in this patient group, presumably due to the anatomic characteristics of transplanted kidneys9. These characteristic features include a short ureter, lacking gravity barrier for urinary reflux, and insufficient anti-reflux properties of vesicourethral anastomosis. As the post-transplantation occurrence of UTI is a known factor that impairs renal function, no studies have analyzed the prevalence of AKI in KTRs with UTI or urosepsis as well as their parallel impact on the allograft function14. Due to the paucity of clinical papers available at this point (data search performed in May 2021), the real renal burden of septic- and UTI-related AKI in KTRs is unknown. Except for anatomic characteristics of kidney allograft in KTRs, there are plenty of other specific factors contributing to the development of UTI and AKI. These include residual foreign bodies in the urinary tract such as ureteric stents or Foley catheter, urinary obstruction , malnutrition, urolithiasis, low urine output and many others16. Additionally, in KTRs the continuous immunosuppressant treatment also impairs the immune response to any ongoing inflammatory processes in the urinary tract, at the cost of optimal kidney allograft function. As infections remain the most frequent cause of death in KTRs, the intensity of immunosuppression must be always balanced with infection risk, for which statistical models have already been developed17. This study aimed to elucidate the incidence and identify the modifiable risk factors of UTI-related AKI in KTRs, with a focus on the impact of implemented treatment on long-term transplantation outcomes.Acute kidney injury (AKI) is a frequent complication of infections in the general inpatient population, with prevalence ranging up to 50% of cases in Intensive Care Units (ICUs), depending on the profile of the departmentThe study was designed as a retrospective observational study. The study group comprised of 301 KTRs including 101 KTRs hospitalized for urinary sepsis, 100 KTRs hospitalized for UTI, and 100 healthy KTRs serving as a control group. The follow-up time was set for 12 months, including 4 routine visits to the outpatient clinic. The permission for the use of retrospective data was obtained from appropriate authorities.The study aimed to recruit all primary cases of urosepsis and about 100 KTR with non-septic UTI and 100 KTRs without history of prior UTI or US. For this purpose, hospital records for the years 2014 to 2019 were screened for cases of urinary sepsis in KTRs (using appropriate ICD-10 coding) identifying 148 potential cases. From this group, 101 cases were included in the urosepsis group, using the following inclusion and exclusion criteria:Symptomatic and laboratory-confirmed UTIDocumented increase of SOFA —score of 2 points or moreInclusion criteria:Allograft dysfunction caused by an acute disease other than UTI  at the time of presentationOccurrence of another episode of urosepsis within 2 years before the presentation (to exclude the impact of another urosepsis on transplantation outcomes)A diagnosis of any disease with a life expectancy lower than 2 yearsExclusion criteria:18 and The Third International Consensus Definitions for Sepsis and Septic Shock19. The second group named the UTI group, comprised of 100 random KTRs hospitalized for non-septic UTI within the same timespan. The patients were selected randomly out of 576 KTRs hospitalized for UTI, using MS Excel coomands (“RAND” and “INDEX” functions). The third group which consisted of 100 healthy KTRs (with no history of UTI or sepsis) who attended a routine visit in March 2015, were used as a control group (CG). The selection process of patients to all 3 study groups is presented on the flowchart in Fig. The inclusion criteria were based on the European Association of Urology guidelines on Urinary Tract Infections20. A one-year follow-up was applied to all the study subjects using the records from the local outpatient transplantation unit. During the follow-up period, the incidence of graft loss and acute rejection, as well as allograft function after 1, 3, 6 and 12 months were recorded. Recovery from AKI was defined as a difference between creatinine levels at 1-month post-discharge and at baseline equal to or less than 0.3 mg/dL. Graft loss was defined as the return to chronic dialysis at any time of the follow-up period. Additionally, kidney function at 3 and 12-months before inclusion to the study was registered. eGFR values were calculated using the MDRD-4 formula. Baseline kidney graft function was defined as either last known eGFR measurement or a mean from two last eGFR values.The clinical data regarding hospitalization was collected. The incidence of AKI was assessed using the KDIGO 2012 criteria22. The CKD-EPI has been shown to be the most accurate formula in general CKD population, however in KTRs it is the MDRD-4 that shows the lowest bias in comparison to a reference method23. In addition, the CKD-EPI formula seems to overestimate real eGFR values especially in patients with eGFR above 23.There are several formulas destined for calculation of estimated effective Glomerular Filtration Rate (eGFR). The most popular ones are MDRD-4 and CKD-EPI, which rely on patients age, sex, ethnicity and serum creatinine concentration. Other formulas utilising patients weight or serum concentrations of other biomarkers as cystatine C have not been widely accepted as golden standard, despite being significantly more precise than the ones based on creatinine levels. Our choice of MDRD-4 over CKD-EPI formula for estimation of eGFR in this study has been motivated by previous literature search. Both formulas have been validated in the populations of KTRsWe have performed a Bland-Altman analysis comparing eGFR values estimated by MDRD-4 and CKD-EPI equations. The eGFR calculated by both formulas have shown a wide range of agreement ranging from 0 up to 60–Binominal and discrete data were presented as total counts and percentages. The differences between these variables were tested using the Fisher exact test and Chi-square test. The study used the Shapiro-Wilk test for continuous variables to assess the assumption of normality and presented the results as either mean standard deviation (SD) or median and interquartile range (IQR), as appropriate. The significance of differences between the two groups was tested using the independent Student’s t-test for normally distributed variables and the Mann–Whitney U-test for skewed variables. For multiple comparisons, univariable ANOVA and Kruskal-Wallis ANOVA were implemented. For comparison of dependent variables, a dependent t-test and Wilcoxon test were used as appropriate. The risk factors of AKI were identified using a multivariable logistic regression model. To identify variables associated with outcomes, a multivariable linear regression, logistic regression and Cox hazards regression models were implemented. Some models were manually adjusted for variables which would not normally be included in the model . The occurrence of events in time was presented using Kaplan Meier survival curves and differences between them were tested using the log-rank test. A two-tailed p-value of The study was approved by the local ethics committee of Wroclaw Medical University , and the need for obtaining informed consent has been waived due to the retrospective character of the study. The study was performed in compliance with the Declaration of Helsinki.Consent for retrospective use and publication of clinical data was obtained from the local data administrator .The manuscript complies with the STROBE checklist for reporting of observational studies. Filled checklist was attached to the manuscript.18. The in-hospital mortality was observed only in the urosepsis group and reached 8%. All-cause mortality at 1 year post-discharge in all 3 groups equaled 1%. The 1-year death-censored graft loss (DCGL) was significantly higher in the urosepsis group as compared to both UTI and control group . After 1 year of follow-up, the urosepsis group also exhibited the lowest eGFR, followed by the UTI group, and the highest eGFR was observed in the control group , acute rejection and recurrence of UTI, are presented in Figs. 25. It is however a significant source of complications, as it may lead to allograft injury and its sequelae. To our best knowledge, this is one of the very few studies which analyze risk factors for the development of UTI-AKI in KTRs and its impact on long-term transplantation outcomes. It also adresses the impact of implemented treatment strategies, including the changes of immunosuppressive regimen in the acute phase of illness. The development of UTI-AKI was observed in 75% and 41% of patients in the urosepsis and UTI groups in our study, respectively. The distribution of each severity grade of AKI was different as well across these two groups, with a preponderance of AKI stages 2 and 3 in the urosepsis group. Multivariable analyses have shown that the occurrence of UTI-AKI was independently associated with both increased rates of graft loss at 1 year and a decline of eGFR at 1 year, independently of urinary tract infection occurrence. In patients with UTI who did not develop AKI, the recorded graft loss rates equaled the values registered in the general KTR population (of about 3–5% yearly)26. Therefore it may be possible that AKI, but not UTI alone, directly promotes renal graft failure and loss. According to the authors’ knowledge, reports on these two events studied alongside each other have not been published. It is also noteworthy that in the presented study, only AKI stages 2 and 3, but not AKI stage 1 (irrespectively of sepsis development) contributed to the impairment of allograft function, which remains in agreement with the observed high probability of renal function recovery in KTRs with AKI stage 1. Additionally, the recovery rates from AKI stages 2 and 3 were significantly lower than from AKI stage 1. Therefore, a hypothesis is proposed that AKI stage 1 related to UTI or urinary sepsis shows somehow benign character and may not influence the long-term outcome after infection, although such impact might have been revealed in an analysis of a larger patient cohort.Sepsis, including urosepsis, in transplant recipients seems to be associated with lower mortality than in the non-transplant population4. Therefore, other alternative causes of AKI must always be sought proactively, as is is not uncommon for the AKI etiology to be multifactorial. Additional AKI causes in KTRs include: other severe infections , intravascular volume depletion, viral infections (CMV and BKV), immune-mediated injury, calcineurin inhibitor toxicity (CNI), recurrence of primary kidney disease (FSGS and HUS), drug-induced microangiopathy, use of contrast media and other nephrotoxic drugs, graft vessel thrombosis, ureteral stenosis and surgical complications30. Furthermore, there is also a wide selection of risk factors portending occurrence of AKI in this patient group, which in turn include: suboptimal graft function, the need for mechanical ventilation, vasopressor use, the time of dialysis before transplantation, a history of delayed graft function and proteinuria31.In our study, except for the development of AKI, three other independent predictors of DCGL have been identified: FSGS as primary kidney disease, the need for PRBC transfusion, and the reduction of immunosuppression in the acute phase of illness to standalone steroid therapy. The exposure to transfusion of red blood cells was also a negative predictor of renal recovery after UTI-AKI. Except for the recurrence of FSGS, these factors have not yet been described as potentially modifiable risk factors of kidney graft loss in the infection setting. According to the scarce literature, urinary sepsis and urinary tract infections contribute to 35% of AKI cases in KTRsBased upon the findings of this study and the performed literature review, several suggestions regarding the optimal management of acute UTI and urosepsis in KTRs outcomes are put forward. Each of these suggestions is discussed in the following sections and summarized  in a form of care bundle presented on Fig. 32. Furthermore, the association between transfusions of blood products and impaired renal recovery as well as graft loss has also been clearly documented by the present authors. This observation confirms previous findings described in two recent studies, where peri-transplant PRBC transfusion was also associated with increased graft loss after 1 year34. Therefore, a restrictive transfusion policy in these cases may potentially improve recovery post-AKI by preventing alloimmunization and autoimmune response against kidney allograft which may occur after transfusion of blood products35. Furthermore, in the setting of septic shock, a liberal transfusion trigger does not seem to offer any advantages over a restrictive strategy, both in terms of 90-day survival and the rate of ischemic events37.First, as in 95% of the cases, the transfusion of PRBC concentrate was dictated by upper- or lower gastrointestinal bleeding with subsequent anemia, the authors of this study highlight the need for effective stress ulcer prevention in KTRs hospitalized with severe infections and sepsis. Despite concerns being constantly raised about the safety of early and extended stress ulcer prophylaxis (both with PPI and H2-blockers), we have failed to identify any study, where any damage resulting from such interventions has been shown39. Moreover, the use of additional steroids in KTRs may prevent the development and potentially treat the early stages of beginning acute graft rejection, minimizing immune-mediated injury to the kidney graft40. The standard dosing administered in our center was methylprednisolone every 12 h, dosed 20–40 mg daily until the improvement of clinical state was noted .Secondly, the authors strongly advocate for the use of a stress dose of corticosteroids in KTRs admitted acutely to the hospital due to UTI or urosepsis . In this study, the use of intravenous steroid boluses in the acute phase of illness was associated with increased odds of renal recovery after UTI-AKI, independeetly from stage of AKI. The rationale for such a strategy includes the fact that the stress dose of steroids in an acute infective or septic setting, may help optimize peripheral perfusion and prevent hypovolemia related to adrenal insufficiency in steroid-exposed patients, thus potentially preventing the development or aggravation of AKI41. On the contrary, many trials and observational studies have shown a clear association between the reduction of immunosuppression (both drug discontinuation and dose reduction) in the non-infective setting and increased incidence of acute rejections42. This observation remains in agreement with both the presented study and the study by Yahav et al. who have observed a trend towards increased graft loss rates in KTRs with acute infection in whom immunosuppression was discontinued (however they do not state the extent of drug discontinuation)39. As the study presented in this paper probably underestimates the frequency of AGR occurrence, no association between the reduction of immunosuppression and AGR has been observed . Several studies have already shown that acute graft rejection may have an asymptomatic-subacute course and may remain undiagnosed in KTRs until symptomatic graft failure is developed43. Therefore, based upon the observations of this study and available literature, the routine reduction of immunosuppression to sole steroid regimen in the acute phase of infection is not recommended as it may portend detrimental transplant outcomes.Thirdly, the reduction of immunosuppression in the acute phase of UTI and urosepsis to isolated steroid therapy seems to be associated with more frequent graft loss at 1 year. So far, the scientific literature does not support the hypothesis that any reduction of immunosuppression in KTRs with acute infection does enhance patients’ recovery. The authors of this study have identified no clinical trials addressing this topic and one propensity-matched retrospective study by Yahav et al., in which no clinical benefit, such as reduction of mortality, readmission rates, or enhanced recovery, has been observed2. There is also increasing evidence that a positive fluid balance in the course of sepsis, AKI and other acute diseases is a strong and independent predictor of poor clinical outcomes47. Kidney transplant recipients are in turn particularly susceptible to excessive fluid accumulation due to a decreased filtration reserve, frequent UOO, and cardiovascular disease . Furthermore, the evidence documenting damage inflicted by volume-underdosing is scarce, except the setting of major elective abdominal surgery, where restrictive fluid strategy is associated with increased incidence of AKI48. In a recently published single-center randomized controlled trial by Permpikul et al., the authors have randomized 310 adult patients with sepsis and hypotension in the emergency department to either standard fluid resuscitation versus standard fluid regimen and low dose norepinephrine infusion49. In the norepinephrine group, the shock control rate at 6 h was significantly higher than in the control group, but also the incidence of new-onset arrhythmia and cardiogenic pulmonary edema was significantly lower . It is, therefore, possible that early low-dose norepinephrine administration in septic-hypotensive patients may allow to reduce the number of complications related to fluid overload  and achieve quicker shock control—by keeping the administered fluid volume intravassaly. This in turn may prevent the development of septic hypovolemia and provide better perfusion of the renal allograft (which lacks autonomic innervation and autoregulation mechanisms)—thus preventing the development of progression of UTI-AKI.Fourthly, about 20% of KTRs with urinary sepsis after initial fluid resuscitation in our study, have presented with clinical signs of pulmonary and peripheral congestion on admission to the Transplantation Unit. Meanwhile, the rates of lacking shock control and vasopressor requirement after fluid resuscitation were very low as compared to types of sepsis other than urosepsis (where the frequency of these complications reaches 30–50%)50. Studies show that even 75% of cases of urinary sepsis in the general population are induced by urine outflow obstruction, which might as well be the case in KTRs51. According to previous studies, the early recognition and relief of urine obstruction may allow for reduction of AKI-related burden and even prevent the development of urosepsis and uroseptic shock52. The relief of UOO in case of urinary sepsis should thus be treated as “source control” which, alongside fluid resuscitation and administration of antimicrobials, remain the cornerstone of successful sepsis treatment54. Therefore it is strongly recommended that early ultrasonographic screening for urine outflow obstruction be conducted in every KTR admitted to the hospital for any UTI or acute infection.In secondary analyses, several risk factors associated with the development of UTI-AKI have also been identified. These included: admission for urinary sepsis, hypoalbuminemia, suboptimal allograft function, and urine outflow obstruction (UOO) which are well-known and documented factors that increase the odds of developing acute kidney injury56. Therefore, in KTRs with significant urine output and significant albuminuria, the supplementation of albumin may frequently be ineffective in terms of normalizing albuminemia and for that reason should not be routinely implemented. However, such an intervention should be considered in KTRs with sepsis and lacking shock-control as an adjunct for fluid resuscitation as stated in SSC 2016 Guidelines59. This allows hypothesizing that the relationship between hypoalbuminemia and late allograft loss is partially due to preexisting glomerulopathy but also secondary to increased incidence of AKI or altered pharmacokinetics of immunosuppressive drugs60.Lastly, a potentially modifiable risk factor for AKI is hypoalbuminemia. Both pre- and post-transplant hypoalbuminemia remain an independent factor portending allograft loss as well. However, the substitution of albumins in kidney transplant recipients (irrespectively of whether considered in acute or non-acute setting) remains controversial. Studies show that hypoalbuminemia in KTRs is developed almost exclusively due to renal protein loss which occurs due to primary glomerular kidney pathology (predominantly FSGS and membranous nephropathy) or due to sirolimus treatment61. Furthermore, the results presented on Fig. It is acknowledged that there are several limitations to this study. First of all, a non-random selection bias can not be excluded due to the retrospective-observational character of the study. Second, the relatively small sample size might have caused underpowering and underestimations of the impact of some variables on transplantation outcomes. What is more, eGFR values used for patient follow-up and diagnosis of AKI were based on serum creatinine measurements, which is an imperfect and labile marker of kidney filtration function. Although newer and more accurate markers as cystatine C or IGFBP-7 are known, their use remains limited only to clinical trailsSupplementary Information.


The Chinese Government initiated the Donation after Citizens' Death policy in 2010. To now, it has been a major source of organs for transplant. Since it is still a young policy, corresponding clinical evidence is still urgently needed for its improvement. Compared to kidneys donated by SCD (standard criteria donor), increasing the use of ECD (expanded criteria donor) derived kidneys is a way to expand the donor pool but is also a result of the aging demography of China. This study is based on the data of kidney transplantation in our center with the Donation after Citizens' Death policy, aiming to provide a reference for the clinical use of ECD kidneys.A retrospective study enrolled 415 kidney transplants derived from 211 donors performed between October 2011 and October 2019. A total of 311 (74.9%) organs were donated from 159 (75.4%) SCDs, and the remaining 104 (25.1%) were from 52 (24.6%) ECDs. The log-rank test was used to compare the difference in survival and postoperative complications. The Chi-square test was used to compare the occurrence of postoperative complications and postoperative renal function. The Cox regression analysis was used for risk factor screening.P = 0.013), while their recipients had comparable (P = 0.16) survival. Moreover, it also was an independent risk factor for graft loss . There were significantly more AR occurrences in the ECD group compared with SCD group , but no significant difference was found in infection  and DGF  between them. Similarly, fewer recipients in the ECD group were free from AR within 1 year after transplantation (P = 0.040), with no statistical difference in all-cause infection prevalence in 1 year (P = 0.168). The eGFR in the ECD group was significantly worse than that in the SCD group at 3 months, 6 months, 1 year, 3 years, and the highest value posttransplant , but no difference at 5 years posttransplant. Besides, results showed cardiac arrest , HLA mismatch , and AR occurrence  were demonstrated to be independent risk factors for graft loss.Analysis showed that grafts from ECD were poorer in survival (The ECD-derived kidney was worse than the SCD-derived kidney in terms of graft survival and AR occurrence, and trend to an inferior renal function postoperative. However, the recipient survival, DGF occurrence, and all-cause infection occurrence were similar. Even though kidney transplantation is the best treatment for end-stage renal disease, the severe shortage of transplantable organs remains an unavoidable topic , 2. WithThe Chinese Government initiated the Donation after Citizens' Death policy in 2010, which was then promoted nationwide after a 3-year pilot implementation period . To now,This study is based on the data of kidney transplantation in our center with the Donation after Citizens' Death policy to compare the long-term outcomes of ECD and SCD organs in multi-aspects, aiming to provide a reference for the clinical use of ECD kidneys.This retrospective study enrolled 415 kidney transplants from 211 donors based on the Donation after Citizens’ Death conducted between October 2011 and October 2019. The ECD meets that the donor is older than 60 years old, or between 50 and 59 years old, and meets at least two of the following criteria: 1. Final serum creatinine > 1.5 mg/dL132 μmol/L), 2. Cerebrovascular accident as the cause of death, 3. History of hypertension [2 μmol/L,All patients awaiting kidney transplants with end-stage renal disease were registered in the China Organ Transplant Response System (COTRS). Patients with contraindications for kidney transplantation  were excluded. The CORTS algorithm was rigorously adhered to. Higher panel-reactive antibody (PRA) levels led to a lower priority for transplant, and we avoided transplantation in patients with PRA > 30%. To lower the rate of rejection following transplantation, prophylactic therapies  were administered to enrolled patients with high immunogenicity (peak PRA > 50%).The donor family members  consented to organ donation after death and signed the appropriate informed consent paperwork voluntarily. Donors who did not meet the usage criteria based on a needle biopsy performed prior to transplantation were ruled out .Data were collected from the electronic medical record system and the registry system of the organ donation database of our center, which were analyzed anonymously. Following surgery, recipients were intensively monitored during the hospitalization and then followed up by the out-patient clinic at regular intervals after discharge. Table Before kidney transplantation, three pairs of the six human leukocyte antigens (HLA) –A, -B, and –DR were tested. Crossmatch testing for complement-dependent cytotoxicity (CDC) was negative in all recipients. PRA of recipients was routinely tested before transplantation by an enzyme-linked immunosorbent assay (ELISA) including PRA –I and PRA-II. We defined peak PRA < 10% as negative.Induction therapy mainly consisted of anti-interleukin-2 receptor monoclonal antibody  or anti-thymocyte globulin . Patients without the HLA antibodies received basiliximab, which was administered in two 20 mg doses by bolus intravenous injection. The first bolus was given within the 2 h before revascularization of the graft and the second one is on day 4 post-transplant. Patients with HLA antibodies were given single bolus ATG induction therapy at a dose of 50-75 mg. ATG was regular intravenous infusion within 6 h before graft’s revascularization and maintain 25 mg daily until 3 days post-transplant. Before starting induction therapy, 40 mg of methylprednisolone was injected intravenously to prevent the side effects of ATG and basiliximab.Standard immunosuppressive triple therapy consists of tacrolimus (FK-506) or ciclosporin A (CsA), mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), and prednisone. MMF (1 to 2 g/day) or MPS (0.72 to 1.44 g/day) was administered immediately following the transplant. The dosage was adjusted based on the blood routine examination of patients and tapered over time. The administration of CsA (6 ~ 8 mg/kg/day) or FK-506 (0.1 ~ 0.15 mg/kg/day) was initiated from day 1 of post-transplant, and the doses were adjusted according to the trough levels of the drugs.0), and for CsA, serum was collected at C0 and 2 h following medication (C2).The serum concentrations of FK-506 and CsA were routinely monitored following kidney transplantation. For FK-506, serum was obtained half an hour prior to administration  or MPS (0.72 to 1.44 g/day) also continued to be used for maintenance immunosuppressive therapy and individually modified according to the patient’s conditions. Oral prednisone was subsequently prescribed at a daily dose of 20 mg. Then the daily dose was tapered to 10 mg in 6 months.The target levels were timely varying at 1 month, 1 to 3 months, 4 to 12 months, and > 1 year following transplantation. The CDelayed graft function (DGF) is used to describe the status of transplanted kidneys that fail to function immediately after transplantation and is a significant complication of kidney transplantation. In this study, DGF was defined as the need for dialysis during the first week after transplantation .Acute rejection (AR) was suggested clinically by an unexplained rise in serum creatinine concentration of > 0.3 mg/dL or a 25% increase from baseline . The diaWarm ischemia time (WIT) was defined as the time interval between the withdrawal of life support to cold perfusion.The all-cause infections in 1-year post-transplant were also analyzed, including surgical site infection, and pulmonary, and urinary tract infections.The estimated glomerular filtration rate (eGFR) was calculated by using the CKD-EPI eGFR equation based on gender, age, and serum creatine (Scr) .P values < 0.05 were regarded as statistically significant.Results were expressed as percentages for categorical variables and numerical values for continuous variables, respectively. The baseline features of the SCD and ECD groups were compared using the Chi-square test, Mann–Whitney U test, and Student’s t-test as appropriate. The Kaplan–Meier method and Log-rank test were used to compare the graft/recipient survival, occurrence of AR and all-cause infection between the two groups and generated the survival curve. The log-rank test was used to analyze statistical differences between curves. Differences in the incidence of DGF between the two groups were determined by using the Chi-square test. Comparisons of eGFR were using the Mann–Whitney U test. Cox univariate/multivariate regression analysis was utilized to determine risk factors and the hazard ratio for graft failure. Every test was two-tailed. p < 0.001). No other significant difference was observed for other characteristics between the two groups.In this retrospective study, we included and analyzed 211 donors and their corresponding 415 donated kidneys, of which 7 kidneys were discarded because the needle biopsy results did not meet the criteria for use. The kidney utilization rate is 98.3%. A total of 311 (74.9%) organs were donated from 159 (75.4%) SCDs, and the remaining 104 (25.1%) were from 52 (24.6%) ECDs. The median follow-up period of this study was 1069 (range from 147 to 3074) days. The comparisons of baseline characteristics between the ECD group and the SCD group are shown in detail in Table P = 0.001 in the first year, P = 0.011 in the second year, and P = 0.007 in the third year), and this disparity continued throughout our follow-up period , while except for the first year, their recipients had comparable long-term survival  cases of early graft loss (loss within 90 days after transplantation). Among all cases of graft failure, the most common causes were rejection , infection , and graft hemorrhage . The 1-, 3-, 5-years of graft survival rates in the ECD group were 86.3%, 84.7%, and 78.0%, while those in the SCD group were 95.1%, 93.5%, and 91.0%. The 1-, 3-, and 5-years recipient survival rates were consistently at 95.0% in the ECD group, while in the SCD group, the recipient survival rates were 98.7%, 97.4%, and 97.4%, respectively. According to the log-rank test, kidneys from ECD had poorer survival in the early period after transplantation (P = 0.004). Nevertheless, no significant difference was found in infection  and DGF  between ECD group and SCD group.The occurrence of complications post-transplant, including AR, all-cause infection, and DGF, has shown in Table P = 0.040), while no statistical difference was found in all-cause infection prevalence (P = 0.168).Since AR and infection may occur several times, and the incidence is higher within 1 year after transplantation, we analyzed their incidence that did not occur within 1 year by the Kaplan–Meier method and Log-rank test Figs.  and 4. SP < 0.001 at 3 months, 6 months, and 1 year, P = 0.002 at 3 years), while eGFR tended to be similar at 5 years (P = 0.502). In addition, the highest eGFR in the SCD group was better than that in the ECD group (P < 0.001).As a main post-transplant efficacy parameter, eGFR was calculated with the CKD-EPI equation and compared by groups Table . We founP = 0.041), which is the focus of this study, cardiac arrest , HLA mismatch , AR occurrence , and prolonged dialysis duration were also statistically significant , donors' terminal Scr, recipients' age, recipients' BMI, recipient history of diabetes, graft volume, HBV infection, and cold ischemia time (CIT) were not prognostic factors for the graft loss Table . MultivaDue to the severe imbalance between the supply and demand of transplantable kidneys, some patients remain on dialysis and experience long waits on the waitlist. In 2020, only about a quarter of waitlisted patients received a deceased donated kidney transplant within 5 years . While tP = 0.013; Multivariate cox regression, P = 0.044, HR = 2.27). However, the results of this study were slightly higher than those of similar studies in terms of patient and graft survival. This may be because our center is cautious in the selection of donated kidneys, and the age of both donors and recipients  is slightly lower than that of them, leading to a better prognosis. In addition, in the results of this study, the eGFR of ECD-derived kidney recipients was significantly worse than that of SCD-derived kidney recipients at 3 months, 6 months, 1 year, 3 years, and the highest value posttransplant. That has a similar result to the cohort from Nagaraja et al. [This study presented the results of 415 kidney transplants at our center since the implementation of the Donation after Citizens' Death policy. Its primary outcomes were satisfying and comparable to established international practices . This sta et al. . The staThe results of postoperative complications in this study showed that ECD-derived kidney recipients were more frequent to develop AR after surgery, while there was no difference in DGF and all-cause infection. Similar results can be observed in other clinical practices , 17. TheThe value of ECD-derived kidney clinical use is still controversial . A studyThis study also showed that the occurrence of AR, more mismatches HLA loci, and uncontrolled cardiac arrest, prolonged dialysis duration as predictors of graft loss. Among them, AR occurrence and more HLA mismatch may cause immunogenic injury, uncontrolled cardiac arrest leads to longer ischemia time and ischemia–reperfusion injury, the adverse effects of the prolonged period of dialysis on kidney graft survival have been demonstrated in clinical studies , 23. TheThere were still several limitations to our study. Some factors have been confirmed to be independent risk factors for kidney allograft loss ,The ECD-derived kidney was worse than the SCD-derived kidney in terms of graft survival and AR occurrence, and trend to an inferior renal function postoperative. However, the recipient survival, DGF occurrence, and all-cause infection occurrence were similar. The findings of this study provide evidence for the clinical use of ECD-derived kidneys and improve organ procurement policy in China.


Chronic kidney disease (CKD) has been a global public health problem and a major source of suffering and poor quality of life for those afflicted. Using data from the global burden of disease (GBD) study 2019, we estimated the magnitude of the burden of CKD as well as the underlying causes of CKD in the Zambian population.The data used for this study were extracted from the GBD 2019 study. The GBD 2019 provides estimates of several metrics of disease burden including the commonly used disability-adjusted life year (DALYs) for over 369 diseases and injuries, and 87 risk factors and combinations of these in 204 countries and territories from 1990 to 2019. We estimated the burden of CKD as the number and rates  of DALYs, disaggregated by year, sex, and age group. We examined the underlying causes of CKD by estimating the population attributable fraction as the percentage contributions of risk factors to CKD DALY.The number of DALYs for CKD was estimated as 76.03 million (95% UI: 61.01 to 93.36) in 2019 compared to 39.42 million (95% UI: 33.09 to 45.90) in 1990, representing 93% increase whereas the DALYs rate per 100,000 population was estimated as 416.89 (95% UI: 334.53 to 511.93) in 2019 compared to 496.38 (95% UI: 416.55 to 577.87) in 1990, representing 16% reduction. CKD due to hypertension accounted for 18.7% of CKD DALYs and CKD due to diabetes (types 1 and 2) accounted for 22.7%, while CKD from glomerulonephritis accounted for the most DALYs at 33%. The age group most impacted from CKD were adolescents and young adults.The burden of CKD remains high in the Zambian population with diabetes, high blood pressure, and glomerulonephritis as important causes. The results highlight the need to develop a comprehensive action plan to prevent and treat kidney disease. Increasing the awareness of CKD among the public as well as adaptation of guidelines for treating patients with end stage kidney disease are important considerations. Chronic kidney disease (CKD), a condition in which the kidneys are damaged and cannot filter blood as well as they should , has beeCKD is a major source of suffering and poor quality of life. They are associated with multiple adverse outcomes, including increased risk of death, progression to end-stage kidney disease (ESKD) , and increased risk of other co-morbid diseases like hypertension and cardiovascular diseases. In a prospective cohort study of people with CKD stage 3, Shardlow and colleagues  found thUsing data from the global burden of disease (GBD) study 2019, we aimed to estimate the magnitude of the burden of CKD as well as the average annual rate of change in the burden of CKD between 1990 and 2019 in Zambia. We also examined the underlying causes of CKD in the Zambian population. The results of this study can help stakeholders develop a comprehensive action plan to prevent and treat kidney disease. Though these results are specific to Zambia, their reach is important for the entire SSA sub-continent given the paucity of CKD data, particularly among children.The disability-adjusted life year (DALY) is the primary metric used to assess the global burden of disease . One DALh occurs . It is aWhere The YLDs for a particular cause in a particular time period can be estimated as the number of incident cases in that period multiplied by the average duration of the disease and a weight factor that reflects the severity of the disease on a scale from 0  to 1 (dead) . It measwhere ferences .The data used for this study were extracted from the GBD study 2019 , 10–12. 2 [Compared with earlier GBD studies –17, the 2 .We estimated the burden of CKD as the number and rates  of DALYs, disaggregated by year, sex, and age group. To examine the change in DALYs between 1990 and 2019, we calculated the arithmetic difference in DALYs between 2019 and 1990 expressed as a percent of 1990 DALYs. For each estimated rate and number of DALYs, we reported 95% uncertainty interval (UI), which was calculated by taking 1000 draws from the posterior distribution of each quantity and using the 25th and 975th ordered draw of the uncertainty distribution [We used linear regression model with robust standard error to estimate the average annual rate of change in the burden of CKD since 1990. We examined the underlying causes of CKD by estimating the population attributable fraction as the percentage contributions of risk factors to CKD DALY. All analyses were performed using Stata 17 MP8 .The number of DALYs for CKD was estimated as 76.03 million (95% UI: 61.01 to 93.36) in 2019 compared to 39.42 million (95% UI: 33.09 to 45.90) in 1990, representing 93% increase whereas the DALYs rate per 100,000 population was estimated as 416.89 (95% UI: 334.53 to 511.93) in 2019 compared to 496.38 (95% UI: 416.55 to 577.87) in 1990, representing 16% reduction. : 416.55 to 577.87) in 1990 to 520.11 per 100,000 population (95%UI: 433.68 to 606.40) in 1996 and decreases thereafter to 416.88 per 100,000 population (95%UI: 334.53 to 511.92) in 2019  CKD DALYs in 2019, about 14.25 million (95% UI: 10.70 to 18.74) were due to hypertension, 25.07 million ((95% UI: 19.01 to 32.84) due to glomerulonephritis, 5.79 million (95% UI: 3.67 to 8.46) due to diabetes mellitus type 1, 11.50 million (95% UI: 8.29 to 15.50) due to diabetes mellitus type 2, and 19.40 million ((95% UI: 14.78 to 24.61) due to other and unspecified causes. These suggest that CKD due to diabetes (types 1 and 2) accounted for 22.7% of CKD DALY while CKD due to hypertension accounted for 18.7% of CKD DALYs in 2019. The CKD due to glomerulonephritis accounted for 33.0% of CKD DALYs, the largest contribution in terms of absolute number of DALYs of any cause in 2019. In 2019, CKD due to glomerulonephritis impact adolescent (15–19 years) and young adults (20–24 years) whereas CKD due to hypertension impact adults 60 years and above . The International Society of Nephrology 2019 report estimates that less than 10% of the Zambian population with ESKD has access to life-sustaining therapy with dialysis . Only a Most concerning is the disparities seen in our analyses in number of DALYs for CKD by age group, with the highest burden occurring among adolescents aged 15–19 years. This is reflected as well at the young age of dialysis patients in Zambia; 66% of the Zambian dialysis population is < 50 years  –25. One Our results may under-estimate the true burden of CKD in Zambia as the GBD is reliant on published cohort, clinical trials, and model estimates. A cross-sectional survey of adults in the Kabwe District showed that up to 30% had abnormal creatinine values, suggesting undiagnosed CKD . Among tIn Zambia, hypertension and diabetes are important causes of chronic kidney disease with an estimated 18.7% of CKD DALYs due to hypertension while 22.7% of CKD DALYs were due to diabetes. Estimates suggest hypertension and its subsequent end organ damage  may impact up to 1 in 5 people worldwide but low- middle-income countries (LMICs) face the heaviest burden –34. For Prevalent hypertension in Zambia is 100 times the rate of cancer, 5 timesGiven the high burden of DALYs attributable to CKD in adolescents and young adults, it is imperative to address the largest contributor to CKD is glomerulonephritis, contributing to 33% of all CKD DALYs. There is limited data on glomerulonephritis in Africa; the few reports out there suggest quite poor outcomes. A systematic review  revealed 5-year survival from lupus nephritis ranged from 54 to 94% with worse outcomes in sub-Saharan Africa . There iIf diagnosed early and treated effectively, glomerulonephritis can be managed yet access to expedient biopsy results and induction therapies are imperative. However, Zambia’s public sector has limited access to these resources. Currently kidney biopsies in both public and private sectors are processed and analyzed in India and South Africa, taking 10–14 days to get results, limiting the effectiveness of early therapies. Standard corticosteroids are typically available but steroid-sparing agents such as mycophenolate mofetil, cyclophosphamide, or rituximab are limited in their availability. Plasmapheresis is only available in two public hospitals in capital city of Lusaka.The limitations of GBD have been discussed elsewhere , 50. We The burden of CKD remains high in the Zambian population with diabetes, high blood pressure, and glomerulonephritis as important causes. Particularly important is the impact of CKD and its sequalae on the young Zambian working force. The results highlight the need to develop a comprehensive action plan to prevent and treat kidney disease, including public awareness of CKD, educational programmes for health-care personnel, early treatment of potential causes of CKD, and improved access to diagnostic and therapeutic tools that are available elsewhere. The high burden of CKD among Zambians with limited adaptation of existing international guidelines for ease of screening, prevention and treatment necessitates improved government, private, and non-profit support for kidney disease in Zambia.


Renal artery stenosis (RAS) is associated with an increased risk of renal function deterioration (RFD). Our previous study showed that renal cortical blood perfusion assessed by contrast-enhanced ultrasound (CEUS) was an important related factor for RFD in RAS patients. Based on several conventional related factors confirmed by previous studies, we aimed to establish and verify a CEUS+ scoring system to evaluate the risk of RFD at 1 year of follow-up in RAS patients.This study was a single-center retrospective study. A total of 497 elderly RAS patients (247 in the training group and 250 in the verification group) admitted to the Beijing Hospital from January 2016 to December 2019 were included. The baseline characteristics of the patients on admission  and renal function [glomerular filtration rate (GFR)] at 1-year of follow-up were collected. We used the univariate and multivariate logistic regressions to establish a CEUS+ scoring system model, the receiver operating characteristic (ROC) curve and area under the curve (AUC) to evaluate prediction accuracy, and the decision curve analysis and nomogram to evaluate the clinical application value of CEUS+ scoring system model.p > 0.05). Multivariate logistic regression analysis results showed that age [Odds ratio (OR) = 1.937, 95% confidence interval (CI): 1.104–3.397), diabetes , blood pressure , RAS , and area under ascending curve (AUCi)  were related factors for the renal function deterioration after 1 year of follow-up . The AUC of the ROC curve of the CEUS+ scoring system model of the training group was 0.801, and the Youden index was 0.725 ; the AUC of the ROC curve of the validation group was 0.853, Youden index was 0.718 . There was no significant difference in ROC curves between the two groups . In addition, the calibration charts of the training and verification groups showed that the calibration curve of the CEUS+ scoring system was close to the standard curve .Among the 497 patients enrolled, 266 (53.5%) were men, with an average age of (51.7 ± 19.3) years. The baseline clinical-radiomic data of the training group and the verification group were similar (all The CEUS+ scoring system model is helpful in predicting the risk of worsening renal function in elderly RAS patients. Renal artery stenosis (RAS) mainly refers to the narrowing of the main artery or branch of the renal artery, which leads to renal ischemia, and the activity of the renin-angiotensin system is significantly increased, resulting in hypertension and renal dysfunction , 2. WhenPrevious studies have mostly investigated the prognosis of RAS patients in terms of clinical characteristics. Several studies have confirmed that age, diabetes, and severe hypertension were conventional factors for RFD in RAS patients . In addiThis was a single-center retrospective study. A total of 497 elderly RAS patients admitted to the Beijing Hospital from January 2016 to December 2019 were included. Among the 497 patients, 266 (53.5%) were men with an average age of (51.7 ± 19.3) years. Patients were assigned to the training group (247 cases) and the verification group (250 cases) in a 1:1 ratio.Inclusion criteria: (1) clinically diagnosed RAS patients , CT angiography (CTA), or CEUS; the lumen diameter is reduced by 30% to 99%) ; (2) ageExclusion criteria: (1) primary hypertension; (2) combined with severe cardiopulmonary dysfunction; (3) hypersensitivity to the contrast agent sulfur hexafluoride; (4) no stenosis of the renal artery (decrease in lumen diameter < 30%) or renal artery occlusion (100% reduction in lumen diameter); (5) ultrasound and other imaging images were not clear; (6) with advanced tumors; (7) pregnant women; (8) did not cooperate to treatment; (9) refused to sign informed consent. This study has been registered in the China Clinical Trial Registration Center (ChiCTR1800016252), meets medical ethics requirements, and has been reviewed and approved by the ethics committee of our hospital (2018BJYYEC-043-02).Patients’ baseline characteristics, such as demographic data, clinical data, and biochemical examinations, as well as imaging data  and follow-up data  were recorded.Contrast-enhanced ultrasound examination was performed on all patients with a Samsung ultrasound system to evaluate renal cortical blood flow perfusion. The starting imaging conditions were as follows: mechanical index 0.12, image depth 15 cm, and gain 30 dB. The patient was injected twice with the contrast agent on each side of the kidney, and the main renal artery (dose 1.0 ml/kidney) and renal cortical perfusion (dose 1.2 ml/kidney) were observed. First, the patient was made to lie on the side, and the long-axis section of the kidney was fixed so that it was perpendicular to the direction of the sound beam. The contrast mode was opened. The contrast agent was then injected through the cubital vein, and the renal cortex contrast agent perfusion storage image was dynamically observed for 3 min. Renal cortex blood perfusion parameters were analyzed, including area under ascending curve (AUCi), area under the descending curve (AUCo), peak intensity (PI), time to peak intensity (TTP), and mean transit time (MTT)  of the kidney, with Symbia E-type SPECT or Symbia T16-type SPECT/CT  under a low-energy high-resolution collimator. Images were collected by GATES method, and the radioactivity counts of the full and empty needles were measured at 30 cm before the probe, before and after injection for 6 s. The patient was placed in a supine position, and the probe field included both kidneys. After injection of 99mTc-DTPA (Atom High-Tech Co. Ltd.), 1.85 Bq × 108 Bq, through the cubital vein, the computer dynamic collection was started immediately. The operation process was divided into two groups and images acquisition matrix was 64 × 64. In the first group of blood perfusion phase: 2 s/frame, 30 frames were collected. In the second group of intake and excretion phase: 60 s/frame, 20 frames were collected, for a total of 20 min. Using region of interest (ROI) technology, the images were processed to draw the blood flow perfusion, uptake, and excretion curves of the bilateral kidneys. The GATES method was used to determine the total GFR and sub-renal GFR (ml/min).Deterioration of renal function refers to the estimated GFR (eGFR), which is reduced by ≥ 30% after treatment compared with before treatment, and lasts for at least 60 days, while the deterioration of renal function caused by other reasons is excluded , 5.t-test or continuous correction t-test. Count data was expressed as percentage composition ratio, and comparison of rate between the groups was by χ2 test.Stata 16.0 statistical software was used, and normal distribution measurement data was expressed by mean ± standard deviation. Comparison between the groups was performed by independent sample p < 0.05 was considered statistically significant.Univariate and multivariate logistic regressions were used to evaluate the related factors for renal function deterioration and to establish the CEUS+ scoring system model. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to evaluate the prediction accuracy. The decision curve analysis and nomogram were used to evaluate the CEUS+ scoring system model. Clinical application value of p > 0.05)  .p < 0.05).Univariate logistic regression analysis showed that age, diabetes, systolic blood pressure, diastolic blood pressure, blood creatinine, GFR, AUCi, AUCo, PI, and MTT were risk factors for function deterioration  , diabetes , blood pressure , RAS , and AUCi  were related factors for the renal function deterioration after 1 year of follow-up  .According to the results of multivariate logistic regression analysis, a prognostic prediction model, i.e., a nomogram of the CEUS+ scoring system, was drawn, and its C-Index was 0.733 (95% CI: 0.653–0.822) . We usedD = 1.338, p = 0.325).The AUC of the ROC curve of the CEUS+ scoring system model of the training group was 0.801, and the Youden index was 0.725  . The AUCp = 0.701, p = 0.823, both p > 0.10)  .This study established and validated a CEUS+ scoring system for predicting the risk of RFD in RAS patients who were followed for 1 year. The model consists of clinical risk factors  and CEUS imaging features (AUCi). The visualization of the model was achieved through the application of nomograms, and the clinical application value of the CEUS+ scoring system model was confirmed through verification. Therefore, the CEUS+ scoring system can help predict the short-term risk of RFD, thereby helping to stratify patients .Various clinical risk factors can affect the prognosis of RAS patients. A number of previous studies have confirmed that advanced age, diabetes, and severe hypertension were important factors for prognosis in RAS patients, but the degree of RAS was not a related factor , 15. SimRenal cortical blood perfusion was an important imaging index that affected the prognosis of RAS patients. Feng Qichen et al.  found thAt present, although many studies have found that age, diabetes, and blood pressure are risk factors affecting the prognosis of elderly RAS patients –17, no pThis study has some limitations, which are listed below. (1) This study was a single-center study, and more centers were needed to verify the versatility of this study. (2) We changed the continuous variables to categorical variables, which may affect the accuracy of the model. (3) We used the cortical blood perfusion parameters assessed on admission, not the changes of cortical blood perfusion before and after treatment, which may affect the predictive accuracy of the model. (4) We used the logistic regression analyses method. However, logistic regression analyses had multicollinearity problem and the occurrence of renal function deterioration depended on the follow-up duration. LASSO regression and Cox regression methods could reduce these risk. (5) The follow-up time of this study was short, and the risk of RFD was used as the primary outcome indicator. Adopting the hard index of adverse cardiovascular and renal events will also reduce the clinical value of this model. Therefore, we need to further optimize the prediction model in subsequent research to improve the accuracy of prediction –26.In summary, clinical-imaging features such as age, diabetes, blood pressure, RAS, and AUCi were risk factors for RFD at 1 year of follow-up. The CEUS+ scoring system established on this basis can accurately predict the prognosis, and thus can be used to stratify patients and guide treatment. Therefore, the CEUS+ scoring system has high clinical application value, but more studies are needed to confirm it.The raw data supporting the conclusions of this article will be made available from the corresponding author by request.The studies involving human participants were reviewed and approved by the Beijing Hospital. The patients/participants provided their written informed consent to participate in this study.YaL: data collection and analyses. JR: study supervision. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The aim of this study was to explore whether or to what extent metabolic syndrome (METs) and its components were associated with hypoxemia in acute type A aortic dissection (ATAAD) patients after surgery.This study involved 271 inpatients who underwent surgery. Demographic and clinical data were collected. Subgroup analysis, mixed model regression analysis, and receiver operating characteristic (ROC) curve analysis were performed, and a scoring system was evaluated.The 271 inpatients were assigned to the hypoxemia group (n = 48) or no hypoxemia group (n = 223) regardless of METs status. Compared to the no hypoxemia group, the hypoxemia group had a higher incidence of METs. Hypoxemia was present in 0%, 3.7%, 19.8%, 51.5%, 90.0% and 100% in the groups of individuals who met the diagnostic criteria of MetS 0, 1, 2, 3, 4 and 5 times, respectively. In the multivariable logistic regression analysis, BMI quartile was still a risk factor for hypoxemia after adjustment for other risk factors. After adjustment for potential confounding factors, METs was an independent risk factor for hypoxemia in several models. After assigning a score for each METs component present, the AUCs were 0.852 (95% CI 0.789–0.914) in all patients, 0.728 (95% CI 0.573–0.882) in patients with METs and 0.744 (95% CI 0.636–0.853) in patients without METs according to receiver operating characteristic analysis.METs, especially body mass index, confers a greater risk of hypoxemia in ATAAD after surgery. Despiteortality –6. In adortality . In geneortality , 11 3049ortality . In valvortality . However2/FiO2 ≤ 300 mmHg for the first 2 days after the operation were included in the hypoxemia group. Patients with PaO2/FiO2 greater than 300 mmHg formed the no hypoxemia group. The study was approved by the Institutional Review Board of the First Hospital of Hebei Medical University. All subjects provided written informed consent. The detailed recruitment process is shown in Fig. This is an observational and retrospective study. A total of 271 consecutive ATAAD patients who received treatment in the Department of General Surgery at the First Hospital of Hebei Medical University were enrolled in this study from January 2015 to January 2021. The inclusion criteria were as follows: (1) diagnosed with ATAAD confirmed by CT angiography of the aorta and (2) underwent surgical treatment. The major exclusion criteria included the following: (1) patients with respiratory system diseases; (2) patients who did not undergo surgery; and (3) patients who suffered from any perioperative complications. According to arterial blood gas analysis, patients with PaO2, high-density lipoprotein (HDL) < 50 mg/dL among women and < 40 mg/dL among men, fasting plasma triglycerides (TG) ≥ 150 mg/dL, systolic blood pressure (SBP) ≥ 130 mmHg, diastolic blood pressure (DBP) ≥ 85 mmHg, fasting plasma glucose (FPG) ≥ 100 mg/dL or previously diagnosed type 2 diabetes mellitus (T2DM).According to the criteria of the American National Cholesterol Education Program , MetS waData regarding sex, age, body mass index (BMI), blood pressure, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), ventricular ejection fraction (LVEF), history of hypertension (HT), type 2 diabetes mellitus (T2DM), coronary artery disease (CAD) and thoracic surgery were collected. Preoperative laboratory tests were performed within 24 h before surgery, including tests for fasting blood glucose (FBG), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), white blood cells (WBCs), platelets (PLTs), creatinine (Cr), uric acid (UA), troponin I, and red blood cells (RBCs). Surgery variables included length of surgery, cardiopulmonary bypass time, cross-clamp time, circulatory arrest, minimum temperature, ICU stay time, hospital stay time, PaO2/FiO2 and mechanical ventilation time.p value < 0.05 was considered statistically significant.Statistical computations were performed using SPSS v24.0 . Continuous variables are reported as the mean ± standard deviation for normally distributed data or as the median and quartiles  for nonnormally distributed data. Discrete variables are expressed as frequencies and percentages and were compared using the chi-square test. Multivariable logistic regression analyses were performed to detect the relationship between hypoxemia and METs. In the multivariate analysis, odds ratios (ORs) and 95% confidence intervals (CIs) for hypoxemia were calculated using a logistic regression model after adjusting for potential confounding variables. To verify the robustness of our results, subgroup analyses were performed to explore the association between the number of MetS components and hypoxemia. These predictors of metabolic syndrome components were assigned points based on their regression coefficient, and a scoring system was produced. Receiver operating characteristic (ROC) curves were constructed, and the areas under the curves (AUCs) were calculated to assess the discriminatory power of the scoring system for MetS. A two-sided p > 0.05). Compared to the control group, the hypoxemia group had significantly greater BMI, SBP, TG and WBC values and a longer length of surgery, ICU stay time, hospital stay time and mechanical ventilation time, and the differences were statistically significant . Similarly, there were statistically significant differences in the incidence of HT, T2DM, metabolic syndrome and smoking .Table p < 0.05, Table p < 0.001). The MetS components BMI, HT, T2DM, SBP, and TG increased with increasing numbers of traits. For comparisons among groups, the greatest difference was in BMI. , 136 (50.2%), 81 (29.9%), 33 (12.2%), 10 (3.7%) and 1 (0.3%) individuals in the respective groups. Hypoxemia was present in 0%, 3.7%, 19.8%, 51.5%, 90.0% and 100% of the six groups, with significant differences among groups (p < 0.001), HDL  and SBP  remained independent factors of hypoxemia. People with T2DM had a significantly increased risk of hypoxemia compared with those with no T2DM in all groups . Compared with the first BMI quartile, the second, third and fourth BMI quartiles had ORs of incident hypoxemia of 6.124 (95% CI 1.056–35.493), 6.269 (95% CI 1.142–34.409), and 33.918 (95% CI 6.084–189.102), respectively, after adjusting for potential risk factors .Table Based on the regression coefficient, a point was assigned to each METs component. Elevated BMI was given 2 points, elevated BP was given 2 points, elevated FBG was given 1 point, reduced HDL was given 1 point, and elevated TG was given 1 point Table . ROC curIn this study, we demonstrated that METs components could significantly predict the incidence of hypoxemia in ATAAD patients according to multivariable and subgroup analyses. After adjusting for confounding factors, METs was also an independent risk factor for hypoxemia. Among METs components, BMI was the strongest predictor of hypoxemia, and the scoring system showed good predictive power.As a result of high blood pressure, the aortic intima tears and progressive separation of the aortic wall layers results in the formation of a false lumen; this involves the ascending aorta and is classified as ATAAD . With thMETs comprises five components, BMI, blood pressure, fasting plasma glucose, high-density lipoprotein and triglycerides, which are often ignored in clinic practice . It alsovs. 1.4%, P = 0.05) [Several studies have found that BMI is an independent risk factor for hypoxemia , 6. Abun = 0.05) . There i = 0.05) . When th = 0.05) . Lipids, = 0.05) . Triglyc = 0.05) . In our To date, several METs diagnostic criteria, including the National Cholesterol Education Program (NCEP), International Diabetes Federation (IDF), and American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) criteria, have been proposed. Considering cardiovascular disease, the NCEP METs definition may be more suitable in the Chinese population. Compared to the AHA/NHLBI and IDF criteria, the NCEP criteria better detect the prevalence of cardiovascular disease (OR: 1.40) . TherefoOur study has some limitations. First, this was an observational study with a single center and a small number of enrolled patients, which may have introduced selection bias. In future, enlarging the sample size and randomized controlled trials need to be performed to confirm our results. Second, the underlying mechanistic link between MetS and hypoxemia is not clear, and unidentified risk factors may affect the incidence of hypoxemia. Animal model studies and prospective clinical observations will perform to explore deeper relationship. Furthermore, we focus on the the occurrence of hypoxemia after surgery and explore the prognosis value of METs. In this study, we not explore if interventions can reduce morbidity and mortality after hypoxemia. In further,Long-term follow up is necessary and find the influences of different treatments on the outcome.For ATAAD patients, the occurrence of hypoxemia after surgery seems tightly linked to METs, especially BMI. After adjusting for potential risk factors and establishing a scoring system, METs was an independent risk factor for hypoxemia. Our research indicates that hypoxemia may be a multifactorial process and that endocrine disorders that activate systemic inflammation may play an important role in ATAAD patients after surgery.


P = .001). Microbially mediated β-glucuronidase activity may be a critical determinant in the amount of mycophenolate entering the systemic circulation and an important factor to consider for precision dosing of MMF.The intestinal microbiota produces β-glucuronidase that plays an essential role in the metabolism of the immunosuppressant mycophenolate mofetil (MMF). This drug is commonly used in organ and hematopoietic cell transplantation (HCT), with variations in dosing across transplant types. We hypothesized that β-glucuronidase activity differs between transplant types, which may account for differences in dosing requirements. We evaluated fecal β-glucuronidase activity in patients receiving MMF post-allogeneic HCT and post-kidney transplant. Kidney transplant patients had significantly greater β-glucuronidase activity (8.48 ± 6.21 nmol/hr/g) than HCT patients (3.50 ± 3.29 nmol/hr/g;  The active form of MMF, mycophenolic acid (MPA), inhibits the proliferation of T and B lymphocytes thereby reducing the risk of graft-versus-host disease (GVHD), improves stem cell engraftment after HCT, and reduces the risk of allograft rejection after kidney transplant.9 Blood MPA concentrations are influenced by enterohepatic recycling (EHR) of MPA due to the de-glucuronidation of MPA glucuronide  by microbial β-glucuronidase post-biliary excretion.10 We recently showed that therapeutic concentrations of MPA in the blood of HCT patients were associated with the microbiome composition measured in their fecal samples, although the mechanism for this finding remains unknown.4 We observed that individuals with therapeutic MPA concentrations were more likely to have β-glucuronidase-producing bacteria in their stool and significantly greater EHR and reformation of MPA.The intestinal microbiota is associated with human health and performs many functions for the body including protective, metabolic, and structural functions.11 and 5–10% of kidney transplant recipients with have an acute rejection event leading to a higher risk of kidney graft loss.12 Variability in MPA plasma concentrations among patients affects the potential for adverse clinical outcomes. Lower concentrations increase the risk of GVHD and rejection, while higher concentrations are associated with toxicity.14 There is a well-known difference in the doses of MMF needed to achieve therapeutic concentrations in HCT and kidney transplant recipients. Lower MPA exposure is observed in HCT recipients compared to kidney transplant recipients receiving a similar MMF dose.15–17 Reasons for this difference are not understood but may be due to lower β-glucuronidase activity in the stool of HCT recipients, resulting in lower enterohepatic recirculation and reformation of MPA, lower MPA exposure in the blood, and the need for higher MMF doses. Understanding microbially mediated processes that affect MPA exposure is required to inform precision MMF dosing and for other drugs that undergo β-glucuronidase-mediated enterohepatic recirculation (e.g. irinotecan).18Despite the importance of MMF in facilitating donor engraftment and preventing GVHD, 50% of patients suffer from GVHD and associated non-relapse mortality,P = .001; 19–21 and dosing of the IS drug tacrolimus (TAC) in kidney transplant recipients.22 In addition, greater abundances of the genera Blautia and Enterococcus, and decreasing abundances of clostridia have been associated with a lower incidence of GVHD-related mortality in HCT patients.19–21 In kidney transplant patients, Lee, et al.22 hypothesized that the abundance of Faecalibacterium prausnitzii was associated with a healthy and diverse colon and found a positive correlation between TAC dosage and F. prausnitzii. This hypothesis was tested in vitro by Guo, et al.23 with results suggesting involvement of F. prausnitzii in metabolism of TAC. Taken together, these results suggest that improved understanding of the role of the microbiota in biotransformation and transporting IS drugs will be critical to inform precision therapy to maximize efficacy.We compared β-glucuronidase activity from stool samples of patients receiving MMF and tacrolimus post-HCT or kidney transplant. We hypothesized that, based on observed differences in therapeutic dosing regimens between transplantation types, β-glucuronidase activity would differ between transplant types. We observed that fecal β-glucuronidase activity was over two-fold lower in HCT patients (3.50 ± 3.29 nmol/h/g) than in kidney transplant patients .25 Similarly, an earlier study of children with inflammatory bowel disease (IBD), compared to healthy controls, found that while there was a non-significant difference in fecal β-glucuronidase activity between groups, the activity from children with IBD  was less than half that of controls . In a study of kidney transplantation patients who received MMF, no differences in fecal β-glucuronidase activity were observed among patients who had diarrhea vs. those who did not .26 A significantly greater percentage of diarrheal patients with high β-glucuronidase activity (91%) had a prolonged course (≥7 days) of diarrhea, while only 40% of low β-glucuronidase-activity patients had a prolonged course.27 In a murine study, exposure to MMF resulted in an altered microbial community composition with increased β-glucuronidase activity that was ablated when vancomycin was given.28 Results of these studies highlight the role of microbial β-glucuronidase in MMF-related toxicity and adverse side effects.There have been few studies that have similarly assessed fecal β-glucuronidase activity in human studies, and results are difficult to compare due to the various methodologies reported.30 There are also several important drug interactions with MPA. The combination of TAC with MPA results in higher MPA plasma concentrations and all of our patients received TAC. Antibiotics such as norfloxacin and metronidazole, ciprofloxacin, amoxicillin-clavulanic acid result in significantly lower MPA concentrations.31–33 These interactions have been hypothesized to be due to antimicrobial-related alterations in gut microbiota that change enterohepatic recirculation and reabsorption of MPA. HCT patients receive chemotherapy and more anti-infective agents than kidney transplant recipients in the early post-transplant period. Our observation that β-glucuronidase activity is significantly lower in HCT recipients is highly consistent with the consequences of high antibacterial drug pressure and elimination of β-glucuronidase producing bacteria.Several factors have been associated with variability in MPA concentrations including kidney function, albumin, weight, diabetes and time post-transplant, although they have not been consistently observed in all studies.4 The HCT study protocol was IRB approved (Study#00005621) and all patients provided written, informed consent. All HCT participants received prophylactic MMF (Cellcept or generic) and TAC (Prograf or generic) at time of stool collection on day +7. Mycophenolate mofetil was administered 1 g every 8 h intravenously (IV) over 2 h, every 8 hours beginning on day +5. Tacrolimus (0.03 mg/kg/day) was administered IV beginning at post-transplant day 5 to promote stem cell engraftment and to prevent GVHD. In our kidney transplant study, patients were enrolled in the Microbiome and Immunosuppression (MISSION) study (NCT04953715). This study was IRB approved (Study#00032309) and patients provided written, informed consent. Twenty-two adult patients (≥18 years) were studied and the stool collected a median of 69 days of receiving a living or deceased donor kidney transplant. Patients were receiving MMF (Cellcept or generic) 500 mg/g twice a day and TAC (Prograf or generic) orally as maintenance IS.In our HCT population, 20 adult (18–75 years) participants undergoing allogeneic transplant for hematologic malignancies were enrolled and are described in our previous study.g for 5 min at 4°C. The supernatant volume was adjusted to 90 µl with BGA before adding 10 µl of proprietary substrate (provided with the ab234625 kit). All reactions were performed in Microfluor™ 96-well black plates with flat bottoms (Thermo Fisher Scientific). Fluorescence measurement (Ex/Em = 330/450 nm) was done on a Biotek ELISA reader  immediately after adding substrate for 0–60 mins at 37°C. A background (no substrate) control, positive control and standard  dilutions were also included while performing the assay. Enzyme activity was expressed as nmol 4-MU hr−1 gm−1 sample. Differences in β-glucuronidase activity were evaluated using the non-parametric Kruskal Wallis test. Statistical analyses were performed using XLSTAT software version 2020.3.1  at α = 0.05.Stool samples were collected in single-use specimen collector pans and transferred to 30 mL polystyrene tubes for storage. Single samples were collected from each patient. Samples were refrigerated immediately and transferred to the lab frozen (−20°C) and stored at −80°C prior to assay. Samples from patients in both the HCT and kidney-transplantation studies were treated identically for lab analysis. β-glucuronidase activity was measured in stool samples using a fluorometric assay kit  according to the manufacturer’s instructions. Briefly, 100 µl of β-glucuronidase assay buffer (BGA) was added to a 10 mg (wet weight) stool sample. The sample was homogenized at room temperature for 10 min using an ultrasonic bath . The lysates were then centrifuged at 10,000 ×


N = 85, passed both criteria for the standard. Mean (SD) differences in paired SBP and DBP determinations between the test device and reference were 0.5 (7.7) and 2.5 (6.8) mm Hg. The BP5450, N = 86, passed both criteria. Mean (SD) differences in paired SBP and DBP determinations were 1.9 (7.0) and 3.6 (6.4) mm Hg. The UA-8000WM, N = 85, did not meet the first criterion for the standard. Mean (SD) differences in paired SBP and DBP determinations were 2.5 (8.0) and 5.1 (6.4) mm Hg. The WGNBPA-240BT, N = 85, did not meet the first criterion for the standard. Mean (SD) differences in paired SBP and DBP determinations were 7.9 (8.5) and 5.5 (6.7) mm Hg. The BP3MW1-4YCVS, N = 85, did not meet the first criterion for the standard. Mean (SD) differences in paired SBP and DBP determinations were 5.8 (8.7) and 3.1 (5.6) mm Hg. These findings emphasize the importance of verifying the validation status of home blood pressure monitors before use by consumers.The accuracy of Omron 10 Series BP7450 (HEM-7342T-Z), Omron Platinum BP5450 (HEM-7343T-Z), Walmart Equate Premium 8000 Series UA-8000WM, Walgreens Premium 15+ WGNBPA-960BT, and CVS Series 800 BP3MW1-4YCVS were assessed in an adult general population compared to a mercury sphygmomanometer standard according to the ISO 81060-2:2018/AMD 1:2020 validation procedure. Omron selected the monitors and included three non-Omron monitors because they were from large retail vendors in the United States and these monitors did not have accessible results from validation testing. The BP7450,  Out-of-office blood pressure measurement is widely recommended due to its ability to provide more accurate measurements to guide diagnosis and treatment compared to infrequent office BP measurements. Multiple guidelines recommend out-of-office blood pressure measurement for hypertension diagnosis and management –4. AccurRetailers provide blood pressure monitors for home use without access to published results of validation testing. The aim of this study was to determine the accuracy of five digital blood pressure monitors intended for home use that are widely available through major retailers in the US. Omron 10 Series BP7450 , Omron Platinum BP5450 , Walmart Equate Premium 8000 Series UA-8000WM , Walgreens Premium 15+ WGNBPA-960BT , and CVS Series 800 BP3MW1-4YCVS  in a general adult population using the validation requirements of the American National Standards Institute/Association for the Advancement of Medical Instrumentation/International Organization for Standardization (ISO 81060-2:2018/AMD 1:2020) standard . With the addition of the next eligible subject, the distribution requirements were still met and the second criterion was also met. For the BP5450 (N = 86) the small cuff was tested in 14 subjects, mean SBP difference (SD) −1.5 (4.3), mean DBP difference (SD) −0.2 (5.1). The large cuff was tested in 72, mean SBP difference (SD) 2.5 (6.2), mean DBP difference (SD) 4.30 (5.8). Participant characteristics of the cohorts for all 5 devices are presented in Table The number of participants screened, number ineligible, the number removed by blinded backwards removal and the number included in the analytic cohorts are detailed in Table e 3.67 5.3]. With The comparison of the test devices BP measurements and the reference measurements are provided in Table Bland–Altman scatter plots of the differences between the device under test and observer measurements for SBP and DBP against their average value and scatterplots of test-reference BP differences by subject’s arm circumference are shown in Figs. We tested five automated blood pressure monitors intended for home use using the ISO 81060-2:2018/AMD 1:2020 standard. Two devices (BP5450 and BP7450) fulfilled this standard for a general adult population, although for BP5450 the standard deviation of the subject-level diastolic blood pressure difference was borderline. UA-8000WM, WGNBPA-240BT and BP3MW1-4YCVS did not meet this validation standard in our test. Using the ANSI/AAMI/ISO 81060-2:2018 + A1:2020 protocol as a guide, we removed measurements with discrepant observer readings based on our interpretation of the technical document and the recommendations we received from an expert consultant who trained the study team.These findings suggest that the accuracy of automated home blood pressure monitors available in the U.S. market that have not been validated cannot be assumed and underscores the importance of verifying the validation status of at-home blood pressure monitors prior to use for diagnosis or clinical monitoring. Prior observers have noted that many BP monitors available for home use have not been validated , 11, andSince monitors that have been validated for accuracy are recommended for BP measurement, it is important that consumers and patients are advised to check whether a blood pressure monitor has been validated for accuracy . FortunaStrengths of this study include the testing of multiple commercial home BP monitors under similar rigorous conditions and achieving the required distribution of subjects by arm size, blood pressure and sex. Limitations are that the study population was limited to a general adult population, and the generalizability of these findings to other populations  is unknown. Additionally, while we followed the recommendations for which data points to include or exclude from an expert consultant who trained the study team, we removed and repeated reference measurements with discrepant observer readings but did not remove and repeat the preceding test device measurement when the repeated reference measurement met the criteria for observer agreement. While we believe that this choice is consistent with the ISO 81060-2:2018 + A1:2020 protocol , we acknThe importance of out-of-office BP is increasingly recognized for hypertension diagnosis and management.Many devices marketed for home use do not have published validation information available testing them using an international standard.BP5450 and BP7450 are accurate enough for home use in a general adult population.UA-8000WM, WGNBPA-240BT and BP3MW1-4YCVS did not meet the applied ISO standard for home use.Supplement Table 1


The physiological effects of prone ventilation in ARDS patients have been discussed for a long time but have not been fully elucidated. Electrical impedance tomography (EIT) has emerged as a tool for bedside monitoring of pulmonary ventilation and perfusion, allowing the opportunity to obtain data. This study aimed to investigate the effect of prone positioning (PP) on ventilation–perfusion matching by contrast-enhanced EIT in patients with ARDS.Monocenter prospective physiologic study.University medical ICU.Ten mechanically ventilated ARDS patients who underwent PP.We performed EIT evaluation at the initiation of PP, 3 h after PP initiation and the end of PP during the first PP session.2/FiO2 by PP, which was attributed mainly to reduced shunt in the lung.The regional distribution of ventilation and perfusion was analyzed based on EIT images and compared to the clinical variables regarding respiratory and hemodynamic status. Prolonged prone ventilation improved oxygenation in the ARDS patients. Based on EIT measurements, the distribution of ventilation was homogenized and dorsal lung ventilation was significantly improved by PP administration, while the effect of PP on lung perfusion was relatively mild, with increased dorsal lung perfusion observed. The ventilation–perfusion matched region was found to increase and correlate with the increased PaOProlonged prone ventilation increased dorsal ventilation and perfusion, which resulted in improved ventilation–perfusion matching and oxygenation.Trial registration: ClinicalTrials.gov, NCT04725227. Registered on 25 January 2021.The online version contains supplementary material available at 10.1186/s13054-022-04021-0. Prone positioning (PP) has been used for a long time in ARDS patients who received mechanical ventilation for oxygenation improvement and lung protection purposes , 2 and hThe emergence of electrical impedance tomography (EIT) has been promising in removing the bottleneck. As a radiation-free and noninvasive technique, EIT, which images regional impedance distribution in a cross-sectional area of the body, provides real-time visualization of lung ventilation at the bedside . In addiIn this study, we aimed to evaluate the impact of PP on ventilation and pulmonary perfusion in patients with moderate-to-severe ARDS using contrast-enhanced EIT, trying to unveil the underlying physiological alterations beyond the improved oxygenation to some extent.2/FiO2 < 150 mmHg with positive end-expiratory pressure (PEEP) ≥ 5 cmH2O, and FiO2 ≥ 0.6 according to the Berlin definition [This prospective study was conducted in the intensive care unit (ICU) of Zhongshan Hospital, Fudan University, and was approved by the Institutional Ethics Committee of the hospital (NO.B2019-230R). All patients were recruited upon obtaining written informed consent. The inclusion criteria included moderate-to-severe ARDS patient (defined as PaOfinition ) who und2/FiO2) ratio. Before PP upon clinical decision-making, patients were initially transported to the CT scan facility in the supine position.The following information on the baseline characteristics of the patients was collected at enrollment: sex, height, body mass index (BMI), acute physiology and chronic health evaluation II (APACHE II) score at ICU admission, etiology of ARDS, and the arterial partial oxygen pressure to fractional concentration of inspired oxygen (PaO0), 3 h after PP initiation (T1), and at the end of PP (T2) within the first PP session. Arterial blood gas (ABG) analysis results, end-tidal expiratory carbon dioxide pressure, ventilator parameters, and hemodynamic parameters, including heart rate (HR), central venous pressure (CVP), and mean arterial pressure (MAP), were also recorded at T0, T1, and T2. Patients were deeply sedated, paralyzed, and mechanically ventilated in synchronized intermittent mandatory ventilation (SIMV) mode. Ventilator settings were standardized for all patients during all study measures as follows: tidal volume (Vt) 6–8 mL/kg of predicted body weight, respiratory rate to maintain pH between 7.35 and 7.45, and PEEP based on EIT[EIT assessment was administered in the supine position  = the relative pixel-level ventilation / the relative pixel-level detected lung size .The percentage of ventilated pixels in the respective region   = Tidal image region-global × the ventral/ dorsal fraction of ventilation distributionThe Global Inhomogeneity (GI) index The EIT belt containing 16 electrodes was placed around the chest wall at the fourth or fifth intercostal space and connected to the EIT monitor . Technical details of EIT have been previously described . The EITRegarding relative pixel-level perfusion, after preprocessing, the steepest  slope of the temporal EIT signal deflection during saline bolus injection in each pixel was normalized to the overall detected signal, yielding the relative pixel perfusion. Pixels were classified as nonperfused if pixel perfusion was ≤ 10% of the highest pixel-level value measured in that patient.Blood flow region-global (%) = the relative pixel-level perfusion / the relative pixel-level detected lung size.The percentage of perfusion in each region   = Blood flow region-global (%) × the ventral/ dorsal fraction of perfusion distribution.The GI index .EIT perfusion maps , the Greenhouse–Geisser method was used for correction. Correlation between continuous variables was assessed by the Pearson regression coefficient. All statistical tests were two-tailed, and p < 0.05 was considered statistically significant.The sample size was similar to previous physiologic studies , 22. Sta2. The average APACHE II score at ICU admission was 14 ± 9. Three patients (30%) had moderate ARDS, and 7 patients (70%) had severe ARDS. All patients underwent continuous PP with an average duration of 15.45 ± 2.5 h. More detailed clinical characteristics of the study population are presented in Additional file A total of 10 ARDS patients who underwent mechanical ventilation in the ICU of Zhongshan Hospital, Fudan University, from February 2021 to July 2021 were enrolled  and PaO2/FiO2  of the patients significantly increased. No significant difference was identified in minute ventilation (MV) (p = 0.536), PaCO2 (p = 0.257), end-tidal expired carbon dioxide pressure (ETCO2) (p = 0.348) or dead space percentage estimated by ABG (Dead space-ABG) (p = 0.740) among the 3 time points.Clinical parameters regarding respiratory and hemodynamic status at Tp < 0.05), indicating the improvement in hemodynamic stability in the patients  and increases of systolic blood pressure (SBP), MAP and CVP were observed but with no significant difference reached. However, the dose of norepinephrine significantly decreased after the initiation of PP (p < 0.0005). The increments took place mainly in the dorsal region , while no significant decrease in the ventral region was observed    and negative correlation with the level of shunt estimated by EIT , while there was no significant correlation with Dead Space-EIT %. Moreover, in our study, most of the patients’ lungs had good recruitability by from CT scan after three PP sessions  Fig. A. Intrigion Fig. C  The increased ventilation was distributed mainly to the dorsal region, while ventral ventilation was hardly changed, suggesting that the aeration increment in dorsal lung regions was not offset by the loss of aeration in ventral regions. Changes in ventilation were observed early in the prone position. (2) The redistribution effect of PP on lung perfusion was relatively mild compared to ventilation, with the dorsal lung perfusion increased and the trend of ventral perfusion decreased, while global perfusion remained constant. Changes in blood flow were observed during prolonged prone positions. (3) The ventilation–perfusion matched region was increased and correlated with the increased PaOIn classic ARDS, with the lung less compliant with the four- to fivefold increase in its mass, the superimposed pressure increases the pleural pressure gradient substantially with consequent severe compression atelectasis in gravitationally dependent lung regions and regional overdistension in the nondependent lung , 24. TheThe human lung, as with other mammalian lungs, is structurally optimized to function in the prone posture, in terms of both gross lung shape and vascular architecture. Theoretically, the gravitational distribution of pulmonary blood flow is only minimally altered by pronation , 30, whi2/FiO2, which was in accordance with previous studies [p) group, and four patients to the extrapulmonary cause (ARDSexp). In terms of the trend of change, the effect of prone position was more pronounced early in the ARDSp group compared to the ARDS exp group  distribution. B. Representative image of the perfusion (red-color map) distribution. C. Representative map obtained by integrating ventilation and perfusion maps: The gray area indicates matched units which are both ventilated and perfused, while red area indicated only perfused units and blue area only ventilated units. D. Representative map with the percentage of ventilation (blue numbers) and perfusion (red numbers) distribution in the four horizontal regions of interest (ROIs). This choice allowed us to obtain more superimposable regions of interest. Figure S2. The change in norepinephrine dose during the prone position for each patient. Figure S3.A. The change in Matched Region (%) during the prone position for each patient. B. The change in Shunt-EIT (%) during the prone position for each patient. C. The change in Dead Space (%) during the prone position for each patient. Figure S4. Representative chest CT images obtained before prone position and after three prone position sessions. Figure S5. Evolution of tidal image region (%), blood flow region (%) at T0, T1, and T2 in the ARDSp and ARDSexp groups. Six patients could be categorized to the pulmonary cause (ARDSp) group, and four patients to the extrapulmonary cause (ARDSexp). In terms of the trend of change, the effect of prone position was more pronounced early in the ARDSp group compared to the ARDSexp group. However, prolonged prone ventilation finally both increases dorsal ventilation and perfusion in the lung in two groups, which results in improved ventilation–perfusion matching.