Risk of graft loss was not associated with CP status. In conclusion, an advanced CP was independently associated with increased risk of DWFG, but not all-cause or cardiovascular mortality after renal transplantation.Chronic periodontitis (CP) is associated with cardiovascular disease and mortality in different populations. The aim of this study was to examine an association of CP with hard endpoints in patients after kidney transplantation during a 15-year follow-up period. Study group consist of 117 patients  divided into two subgroups: those with initially advanced CP (CPITN 3–4) and those with no or moderate CP (CPITN 0–2). All cardiovascular events, graft losses, and re-transplantations were recorded. All deaths were noted and verified, including those occurred after the return to dialysis therapy, the causes of death were identified. Cox regression with Firth’s penalized maximum likelihood models were used for data analysis. During the observation period, 49 deaths occurred. Advanced CP ( Chronic periodontitis (CP) is an inflammatory disease of the oral cavity caused by the accumulation of bacterial plaque on the tooth surface. It manifests itself as pain, bleeding, and weakening of tooth-supporting structures with the eventual loosening and loss of teeth. CP causes local dental problems but also has systemic consequences . Among oPatients suffering from CKD have significantly higher cardiovascular and all-cause mortality as compared to general population. It is also known that cardiovascular complications are the main cause of death in this population . On the In kidney transplant recipients, some inflammatory markers were shown to be associated with death with a functioning graft ,9. Also,Originally, we investigated 199 unselected kidney transplant recipients, who were at least 12 months after kidney transplantation and still attended our out-patient clinic during the study enrollment period (2002–2003). At the start, any potential sources of infection were carefully screened through physical examination, blood tests, as well as radiologic and ultrasound imaging . After tIn all study subjects, a dental examination was performed by one experienced dentist and the periodontal status according to the Community Periodontal Index of Treatment Needs (CPITN)  was asseBefore transplantation, all patients were routinely screened and must have been dentally treated, if appropriate, according to the transplant center requirements. However, no detailed data are available concerning their dental status prior to kidney transplantation. After the transplant, no regular screening was provided, and each patient attended the dentist (or not) individually. Until the time of the study, no patient was treated due to periodontal disease.In the present follow-up study, in order to assess the long-term influence of initial CP status on the clinical outcomes of both patients and kidney grafts, we collected information concerning the major study endpoints, effective on 31 October 2019. All patient deaths were noted and verified using the National Death Registry. Notably, we also recorded all deaths which occurred with a functioning graft and during the dialysis treatment. Furthermore, based on the original medical records, we clarified the particular cause of death, including cardiovascular or cerebrovascular episodes, infectious complications, malignancy, and accidental death. Additionally, we recorded all cardiovascular complications and procedures, including stent placement or coronary aortic bypass grafting (CABG), myocardial infarction, stroke , based on the claims issued to the national health care cost payer.Information about return to dialysis therapy and re-transplantations were also collected. After the loss of adequate kidney graft function, the general policy was to maintain the graft with diuresis, ceasing the calcineurin inhibitors and antimetabolite drug, and maintaining prednisone at a dose of 5–7.5 mg/day. The subsequent graftectomy was performed, if there were medical indications, i.e., clinical signs of rejection, recurrent urinary infections, or the clinical reason to stop steroids .In patients with a functioning graft, we noted the current serum creatinine concentration and the presence of proteinuria.https://cran.r-project.org/web/packages/coxphf/coxphf.pdf). Values are presented as means and 95% confidence intervals or frequencies. Variables with skewed distribution were presented as medians and Q25–Q75 values. The initial comparison of two groups based on the baseline CP status was performed using the Student’s t-test or χ2 test  or Mann–Whitney U test . The univariate analyses were performed using linear logistic regression.The statistical analysis was performed using the Statistica 13.3 for Windows software package , MedCalc v19.2.1  and R software with the ‘coxphf’ package  and 63 (53.8%) lost their kidney graft and returned to hemodialysis therapy. The causes of graft loss are given in After 15 years of follow-up, in 37 patients with still functioning kidney graft, median serum creatinine concentration was 1.5  mg/dL. In a whole study cohort, including patients who have been re-transplanted, the current median serum creatinine concentration was 1.4 (1.1–2.0) mg/dL and only 3 patients had daily proteinuria ≥1.0 g.n = 62). The initial and follow-up CPITN values are shown in During a follow-up period, roughly 7 years after the initial examination, the CP status was re-evaluated in all patients with functioning graft  1.04  1.01–1.07; p < 0.05), IMT ; p < 0.05) and graft loss ; p < 0.05) were independently associated with increased risk of overall death ; p = 0.065).The Cox regression with Firth’s penalized maximum likelihood analysis revealed that age ; p < 0.05), male sex ; p < 0.05), and CPITN ; p < 0.05) were independently associated with increased of DWFG ; p = 0.07).We also investigated the effect of CP status on the death with functioning graft, which was observed in 17 patients (14.5%). The Cox regression with Firth’s penalized maximum likelihood analysis revealed that age (χ of DWFG . The simn = 20) was calculated. The Cox regression with Firth’s penalized maximum likelihood analysis revealed that only MACE ; p < 0.001) was independently associated with increased risk of CVD death, whereas the effect of age did not reach statistical significance ; p = 0.05)  .2 = 8.3; HR 1.05 (1.01–1.08); p < 0.01) and HLA class I mismatch ; p < 0.05) were independently associated with increased risk of MACE during the follow-up period ; p = 0.053) and CPITN status ; p = 0.11) with MACE occurrence did not reach statistical significance. During the 15-year follow-up period, 60 MACE episodes occurred in 36 patients (30.8%), including fatal complications. Overall, there were 16 strokes, 12 myocardial infarctions, 4 CABG procedures, and 28 single or multiple stent placements. In 19 patients (53%), the first MACE episode was diagnosed with a functioning graft, whereas in 17 patients (47%)—during the dialysis therapy after the kidney graft loss. Out of all MACE episodes, 50% occurred in patients with a functioning graft, and 50% during dialysis therapy. The Cox regression with Firth’s penalized maximum likelihood analysis revealed that age ; p < 0.001), HLA class II mismatch ; p < 0.05) and smoking ; p < 0.01), but not CPITN status (The Cox regression with Firth’s penalized maximum likelihood analysis revealed that serum creatinine concentration at the time of entering the study (χN status  were indIn the present study, we re-evaluated the effect of advanced CP on the 15-year kidney graft and recipient survival in our previously analyzed cohort of kidney transplant patients. After such a long-term follow-up period, we did not find significant influence of the initial periodontal status on all-cause and CVD mortality or kidney graft survival. However, worse periodontal status was independently associated with increased risk of death with a functioning graft. As expected, age and male sex were found to be important confounding factors in the latter analysis.To our best knowledge, aside from the present study, there is only one study to date which analyzed the relationship between a cross-sectionally assessed oral health and patient and graft survival in the setting of kidney transplantation. Boratyńska et al. reported a numerically higher rate of kidney graft loss and patient mortality in a 10-year follow-up in transplant recipients with gingival overgrowth . HoweverIn contrast to our recent findings, in the previous analysis of the same cohort, advanced CP was associated with increased risk of death in a 5-year follow-up period . Such a The independent influence of periodontal disease on all-cause and cardiovascular mortality ,15 as weIn contrast, the current literature concerning this topic in CKD patients presents contradictory results. Many reports, including a large, NHANES III cohort-based studies, confirmed the association between periodontal disease and all-cause ,24,25,26As CP was previously shown to accelerate the progression of CKD ,33 and iThe main limitation of this study is the low number of participants. As CP status might be considered as relatively low-potent risk factor of cardiovascular complications and mortality, only a larger multicenter study can definitely confirm its independent influence on the analyzed outcome measures. Another limitation is insufficient longitudinal data concerning the periodontal status and treatment, which hence cannot be adequately analyzed. Besides, many limitations are associated with CPITN itself as a screening method because it gives only a rough estimate of the periodontal treatment needs and does not measure important signs of periodontal disease . NeverthIn conclusion, in our long-term observation we did not find any evidence that advanced chronic periodontitis independently influenced the risk of all-cause and cardiovascular mortality in patients after renal transplantation. However, CP status was associated with the risk of death with functioning graft in our cohort. An interventional prospective study should be carried out as to whether a routine oral examination and appropriate dental treatment may have a role in risk reduction and should be advised as a standard element of long-term care in kidney graft recipients.


This study aimed to investigate the association of acute kidney injury (AKI) with change in estimated glomerular filtration rate (eGFR) in children with advanced chronic kidney disease (CKD).Single centre, retrospective longitudinal study including all prevalent children aged 1–18 years with nondialysis CKD stages 3–5. Variables associated with CKD were analysed for their potential effect on annualised eGFR change (ΔGFR/year) following multiple regression analysis. Composite end-point including 25% reduction in eGFR or progression to kidney replacement therapy was evaluated.2 with 79 (68%) boys and 82 (71%) with congenital abnormalities of kidneys and urinary tract (CAKUT). Thirty-nine (33.6%) had at least one episode of AKI. Mean ΔGFR/year for all patients was − 1.08 ± 5.64 ml/min/1.73 m2 but reduced significantly from 2.03 ± 5.82 to − 3.99 ± 5.78 ml/min/1.73 m2 from youngest to oldest age tertiles (P < 0.001). There was a significant difference in primary kidney disease (PKD)  but no difference in AKI incidence  between age tertiles. Multiple regression analysis identified age  and AKI  as independent predictors of ΔGFR/year. 48.7% versus 22.1% with and without AKI reached composite end-point (P = 0.01).Of 147 children, 116 had at least 1-year follow-up in a dedicated CKD clinic with mean age 7.3 ± 4.9 years with 91 (78.4%) and 77 (66.4%) with 2- and 3-year follow-up respectively. Mean eGFR at baseline was 29.8 ± 11.9 ml/min/1.73 mWe report AKI in established CKD as a predictor of accelerated kidney disease progression and highlight this as an additional modifiable risk factor to reduce progression of kidney dysfunction.Graphical abstractThe online version of this article (10.1007/s00467-020-04777-z) contains supplementary material, which is available to authorized users. There has been extensive interest in understanding and controlling modifiable risk factors for kidney disease progression in chronic kidney disease (CKD) in both adults and children. Mortality in children with kidney failure with replacement therapy is up to 30 times higher than the general population, making our understanding and management of pre-dialysis CKD crucial to achieving improved outcomes . HyperteThere remains a paucity of data evaluating the effects of acute kidney injury (AKI) in children with CKD, and its possible role in accelerating kidney disease progression. This is despite an increasing understanding that AKI and CKD are not distinct clinical entities but closely interconnected . One canOur objective in this study was to evaluate the impact of AKI on disease progression in children with non-dialysis stages 3–5 of CKD.We report a single-centre retrospective longitudinal observational study, including all children aged 1 year to 18 years, over a 3-year period of follow-up (April 2016 to March 2019) who were receiving care in a dedicated children’s CKD clinic. The CKD clinic at the Evelina London Children’s Hospital, London, has a team of three paediatric nephrologists , a CKD senior nurse specialist (PR), and a paediatric renal dietician (TJ), with additional input as required from the wider nephro-urology department.2 at baseline, and (iii) minimum of 3 creatinine measurements per year were available; all performed as part of routine clinical care. Patients were excluded from the study if (i) CKD was being managed on a conservative care pathway or (ii) follow-up in the dedicated CKD clinic was for < 1 year.Patients were included if all of the following criteria were met: (i) under the care of the specialist CKD clinic for a minimum of 1 year, (ii) eGFR < 60 ml/min/1.73 m2 was calculated using the modified Schwartz formula with our previously described correction factor [z-score was calculated using data from the fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents [All included patients routinely attended the specialist CKD clinic at a minimum frequency of 4 months. Pre-defined clinical and laboratory parameters were collated from the electronic hospital records for each patient at annual intervals over a recent 3-year period. For all patients we aimed to collect data including (i) haemoglobin, serum creatinine, albumin, urea, corrected calcium, phosphate, intact parathyroid hormone (PTH), and urine protein creatinine ratio (uPCR) on a random urine specimen. The estimated glomerular filtration rate (eGFR) in ml/min/1.73 mn factor –13, and n factor . (ii) Allescents . Data re2 was omitted from our criteria to avoid bias in our population with already very low GFR. Additionally, we also classified as AKI if there was a rise in serum creatinine of > 20% from baseline, as we considered this a clinically significant increase in this low GFR population. Episodes of AKI were identified from health records and were analysed for change in serum creatinine level in each patient when compared with previous measurements.The incidence, cause, severity, and outcome of AKI were recorded from the electronic health record. To differentiate AKI from rapid disease progression, an increase in creatinine level was required to show reversibility. Reversal to baseline was defined as a return of creatinine value to within < 10% of previous baseline serum creatinine measurement. An episode of AKI was defined as per KDIGO criteria . A creatThe following outcome measures were evaluated: (i) the annualised change in eGFR (ΔGFR/year), calculated by dividing the overall change in eGFR from baseline to last follow-up by the number of years observed during the study period, and (ii) the composite end-point including 25% reduction in eGFR from baseline or progression to kidney replacement therapy. Annual GFR values were distinct from change in creatinine (and GFR) at the time of any AKI episodes as they did not show evidence of reversal towards a previous baseline and were taken whilst patients were clinically well.z-score. Goodness of fit was expressed as the adjusted r2, and multicollinearity was evaluated using the variance inflation factor.Subject characteristics are summarised as means ± standard deviation (SD) or median and interquartile range (IQR) as appropriate. We divided our population in to three equally distributed age tertiles for comparison of disease progression between different developmental stages. Multiple regression analysis was used to examine the association of potential independent predictors with ΔGFR/year. Variables were considered if clinically relevant or known to be associated with disease progression. The final regression model included age, sex, ethnicity, primary kidney disease (PKD) as CAKUT/glomerular/other, stage of CKD at baseline, AKI episode (yes/no), angiotensin converting enzyme (ACE) inhibitor use, and systolic blood pressure 2/> 30 ml/min/1.73 m2), RAAS inhibition (Yes/No), BP category , and age. The level of statistical significance selected was P < 0.05 throughout. Statistical analyses were performed using IBM SPSS statistics version 24.The proportion of subjects to reach composite end-point was analysed using Kaplan–Meier survival analysis with log-rank test to examine the differences in the rates of end points between those with AKI and those without AKI. Cox proportional-hazard analysis was performed to assess the impact of other potential variables on reaching composite end-point. Variables included in the Cox proportional-hazard model were AKI occurrence (Yes/No), sex, ethnicity (white/other), PKD (CAKUT/other), low baseline GFR  17 who had less than one year follow-up, and (iv) two with insufficient creatinine measurements performed. Characteristics of included versus excluded patients are displayed in Table 2 and/or follow-up of less than 12 months.A total of 147 patients with stages 3–5 of CKD attended the dedicated specialist CKD clinic over the 3-year study period, 116 (79%) of whom were included in this study. Follow-up was available for 116 (100%), 91 (78.4%), and 77 (66.4%) patients at 1, 2, and 3 years. We excluded 31 (21.1%) patients from analysis, including (i) six who were managed on a conservative care pathway, (ii) six with an eGFR > 60 ml/min/1.73m2, of whom 79 (68.1%) were boys and 82 (70.6%) had CAKUT. Fifty-five (47.4%), 48 (41.4%), and 13 (11.2%) patients had stages 3, 4, and 5 of CKD. Mean ± SD systolic and diastolic BP z-score was − 0.44 ± 1.43 and − 0.41 ± 1.60 respectively. A total of 33 (28.4%) patients had random uPCR measurements with a median (IQR) level of 96  mg/mmol.Of the 116 included patients, mean ± SD age at baseline was 7.3 ± 4.9 years and mean ± SD eGFR was 29.8 ± 11.9 ml/min/1.73 m2. Children with CAKUT had a mean ± SD ΔGFR/year of − 0.22 ± 4.35 ml/min/1.73 m2 (95% CI − 1.18 to 0.74), whereas those with other causes of PKD had a faster decline of − 3.17 ± 7.62 ml/min/1.73 m2 (95% CI − 5.83 to − 0.51), P = 0.04. A total of 40/116 patients (34.5%) showed improvement in eGFR at last follow-up when compared with baseline, and the median (IQR) age of this group was 6.5 years . Fifty-five (47.4%) patients had random uPCR measurements with a median (IQR) level of 100  mg/mmol. Mean ± SD systolic and diastolic BP z-score was 0.17 ± 1.25 and 0.27 ± 1.15 respectively. Thirty-three (28.4%) were on RAAS inhibitor therapy in combination with other antihypertensive medication, and 20 (17.2%) were on RAAS inhibitor therapy alone. Ten (18%) patients with stage 3 CKD, 7 (21%) patients with stage 4 CKD, and 3 (10%) patients with stage 5 CKD continued on RAAS inhibition at last follow-up.At last follow-up, mean ± SD age was 9.7 ± 4.9 years and mean ± SD eGFR was 28.1 ± 14.3 ml/min/1.73 m2, − 1.21 ± 3.39 ml/min/1.73 m2, and − 3.99 ± 5.78 ml/min/1.73 m2 respectively (P < 0.001). There was significant difference in PKD by age tertiles with 76%, 77%, and 59% patients with CAKUT in tertiles 1, 2, and 3 respectively (P = 0.048) and significant difference in baseline systolic BP z-scores by age tertiles with z-scores of 0.48 ± 1.43, − 0.39 ± 0.88, and − 0.92 ± 1.76 in tertiles 1, 2, and 3 respectively (P = 0.02). There were no significant differences between tertiles for sex, ethnicity, height z-score, episodes of AKI, ACE inhibitor use, haemoglobin, albumin, intact PTH, or vitamin D concentrations  patients. During the observation period, 26 (22.4%) patients had a single AKI episode, 9 (7.8%) patients had 2 discrete episodes, and 4 (3.4%) patients had 3 discrete episodes. All episodes showed reversal of creatinine levels towards baseline. Exactly 47 out of 56 (84%) episodes of AKI showed reversal of creatinine levels back to within 10% of baseline value. Causes of AKI included urinary tract infections (26.8%); dehydration associated with vomiting, diarrhoea, and upper respiratory tract infections (26.8%); elective surgery (14.3%); obstructive uropathy not related to infection (5.4%); kidney toxicity secondary to medication (1.8%); and reversible primary disease decompensation or unidentified cause (19.6%). Of the 56 episodes of AKI, 29 (51.8%), 5 (8.9%), and 16 (28.6%) were stages 1, 2, and 3 of AKI, and 6 (10.7%) had an AKI episode which did not meet AKIN criteria that was > 20% but < 50% rise of creatinine from baseline.2 (95% CI − 0.92 to 1.02) compared with − 3.32 ± 7.22 ml/min/1.73 m2 (95% CI − 5.66 to − 0.98) in the group with AKI (P = 0.01)  and − 4.69 ± 8.45 ml/min/1.73m2 (95% CI − 9.19 to − 0.19) respectively. When comparing the mean ∆GFRs/year in those with no AKI, stage 1 of AKI, and stage 2 or 3 of AKI, severity was associated with a significantly higher rate of decline (P = 0.004). In those with multiple episodes of AKI, there was no significant difference in ∆GFR/year when compared with those with a single episode of AKI (P = 0.11). There was no significant difference found in sex, ethnicity, age group, PKD, ethnicity, baseline CKD stage, level of BP, ACE inhibitor use, or evaluated laboratory indices between the two groups  and presence of AKI  were independent predictors of ΔGFR/year   Table .Table 4MP = 0.01 log-rank test) . Other variables associated with an increased risk of reaching the composite end-point included low baseline GFR  and older age .During the observation period, 19 of 39 patients (48.7%) versus 17 of 77 patients (22.1%) with and without AKI reached composite end-point , tubulointerstitial fibrosis , and inflammation  . In paedThere are important limitations relating to the retrospective nature of this study, including the following: (i) There were limited numbers of patients with glomerular disease. Patients with glomerular disease have a more rapid progression of kidney disease compared with patients with CAKUT. Some patients with rapid disease progression may not have achieved the 1-year follow-up in the chronic kidney disease clinic required for inclusion. Additionally, AKI may be more relevant to patients at earlier stages of CKD as their potential to recover kidney function following AKI may be blunted due to ongoing glomerular inflammation at later stages. This is an important subgroup of patients to investigate, and more work is needed to prospectively examine this cohort. Notably, the aetiology of CKD did not associate with rate of eGFR decline in our study, but this may have been due to the small numbers of glomerular disease patients included. (ii) Whilst most episodes of AKI were captured on the electronic patient record, some will have been missed from patients not seeking medical attention for mild AKI, or presenting to other hospitals for acute management. We believe very few of these episodes would not have been reported as it is our standard practice to update our hospital records regarding admissions to other hospitals, and the clinical management is usually discussed by telephone and guided by our team. We accept though that there may have been variation to this practice resulting in an under-estimation of AKI in this population. (iii) The retrospective nature of our study means that unfortunately we cannot be certain that all episodes of UTI/diarrhoea and vomiting were uniformly recorded. Hence, such clinical episodes which did not result in AKI were not analysed due to incomplete recording of this data outside of our organisation. We recognise that knowledge of these episodes may inform development of a more pro-active management plan including fluid management and stopping ACE inhibitors that might mitigate risks of AKI-induced GFR decline. This should be the focus of further prospective work. (iv) Tanner staging of puberty was not routinely performed in our study cohort and when performed not formally documented. We accept that faster decline in GFR in the oldest patients may be additionally related to pubertal development. (v) We chose the composite endpoint of 25% reduction in GFR or commencement of kidney replacement therapy similar to the ESCAPE trial, but accept that this may not always be clinically meaningful, especially in those with better GFR. Evaluation of single or a panel of biomarkers may be a useful adjunct to evaluate relevant outcomes following AKI in this population. (vi) Lastly, the follow-up period of 3 years limits extrapolation to much longer-term outcomes, especially in the youngest age group.In conclusion, the most significant finding of this study is that AKI in patients with CKD is significantly associated with an increase in the rate of kidney disease progression. Drug-induced kidney toxicity as a cause of AKI is less prevalent in this population. In addition to strict blood pressure control and minimisation of proteinuria, strategies to prevent AKI in this vulnerable population are vital to preserve longer-term kidney function. Further prospective studies are needed in this important area to build upon these findings.ESM 1(PPTX 121 kb)


Large observational studies showed a U-shaped association of clinic blood pressure (BP) with mortality among patients undergoing peritoneal dialysis (PD). Whether ambulatory BP provides a more direct risk signal in this population remains unknown. In a prospective cohort of 108 PD patients, standardized clinic BP was recorded at baseline with the validated device HEM-705  and 24-h ambulatory BP monitoring was performed using the Mobil-O-Graph monitor . Over a median follow-up of 16 months (interquartile range: 19 months), 47.2% of the overall population reached the composite outcome of non-fatal myocardial infarction, non-fatal stroke, or all-cause death. In Cox-regression analysis, systolic but not diastolic BP was prognostically informative. Compared with the reference quartile 1 of 24-h systolic BP (SBP), the multivariate-adjusted hazard ratio for the composite outcome was 1.098 : 0.434–2.777) in quartile 2, 1.004 (95% CI: 0.382–2.235) in quartile 3 and 2.449 (95% CI: 1.156–5.190) in quartile 4. In contrast, no such association was observed between increasing quartiles of clinic SBP and composite outcome. The present study shows that among PD patients, increasing ambulatory SBP is independently associated with higher risk of adverse cardiovascular events and mortality, providing superior prognostic information than standardized clinic SBP. Hypertension is an established cardiovascular risk factor both in the general population and in patients with chronic kidney disease not yet on dialysis . Unlike The reverse epidemiology of hypertension among patients on dialysis requires a closer examination. Prior studies revealed that confounding factors with an opposing effect on BP, such as underlying congestive heart failure (CHF), inflammation, or the level of illness, magnify the inverse relation of BP with mortality, limiting the ability of hypertension to predict risk . Other sBased on the above observations, we hypothesized that among patients on PD, ambulatory BP provides a more precise reflection of the patient’s actual BP load over the entire 24-h period and may therefore be of greater prognostic significance than clinic BP. Accordingly, the aim of this study was to explore for first time the association of BP with the risk of future cardiovascular events and all-cause mortality using standardized clinic BP recordings and the reference-standard method of ambulatory BP monitoring (ABPM) as risk predictors in a prospective cohort of 108 prevalent PD patients.2; (v) arteriovenous fistula in both arms that was formerly used as vascular access for hemodialysis; (vi) patients who had a change either in the PD regimen or in the prescribed antihypertensive medications within 2 weeks before enrolment were also excluded from the study.The cross-sectional data on part of this cohort have previously been reported elsewhere . Adult EThe protocol procedures of our study were accordant with the Declaration of Helsinki and its latest Amendments and all patients gave written informed consent before enrolment. The protocol of our study received approval by the ethics committee of School of Medicine, Aristotle University of Thessaloniki .Clinic BP was recorded at baseline visit by nurses trained in this technique under standardized conditions with the validated self-inflating oscillometric device HEM-705 CP  . In detaAfter the completion of baseline assessment at clinic, all patients underwent ABPM with the oscillometric Mobil-O-Graph device . A brachial cuff of appropriate size was fitted to the non-dominant arm and ABPM was performed for 24 h. The BP-detection unit of this device was validated according to the criteria of ESH/ESC and British Society of Hypertension ,14. CompThe primary outcome of our study was prespecified as the composite of time to first occurrence of non-fatal MI, non-fatal stroke, or death from any cause. Patients were prospectively followed up from the day that they successfully completed the baseline evaluations through 28 February 2021. Patients were censored on the date that they received their last PD treatment, if they received a kidney transplant or when they were switched to hemodialysis. The adjudication of deaths and non-mortal cardiovascular events was performed by an independent member of the investigator team (V.V.) after review of medical records that were provided by the 3 participating PD centers.p < 0.05.Continuous variables are presented as mean ± standard deviation (mean ± SD) or median (range), according to the normality of the distribution of each variable assessed using the Kolmogorov–Smirnov test. Categorical data are expressed as absolute frequencies and percentages. The study population was divided into quartiles according to the level of clinic and 24-h ambulatory systolic BP (SBP). Differences in baseline characteristics among quartiles were evaluated using one-way analysis of variance (ANOVA) for continuous variables or with the chi-squared (χ2) test for categorical variables, respectively. Kaplan–Meier curves were created, and the log-rank test was applied to explore the equality in the risk of the primary composite outcome between quartiles of clinic and 24-h ambulatory SBP. Cox proportional hazards regression analysis was applied to explore the prognostic association of baseline BP with the prespecified composite outcome of non-fatal MI, non-fatal stroke, or all-cause death. The analysis was initially performed using unadjusted models. Subsequently, we generated multivariate models that provided adjustment for the following variables: age, sex, time on PD, mode of PD (continuous ambulatory vs. automated), diabetic status, history of pre-existing cardiovascular disease , BP medication use (yes vs. no), the presence of substantial residual diuresis (yes vs. no), hemoglobin, and serum albumin levels at baseline. To calculate the adjusted hazard ratios (HRs), continuous variables  were centered at their group means. All analyses were performed with the Statistical Package for Social Sciences version 23.0 . The probability values reported are 2-sited and considered to be statistically significant at As shown in p < 0.001).The baseline demographic and clinical characteristics of study participants are shown in p < 0.001). p = 0.001) as well as between quartiles of 24-h ambulatory SBP and composite outcome   . However< 0.001) .Large observational studies using conventional clinic BP recordings as risk predictors showed a “reverse epidemiology” of hypertension among patients undergoing long-term PD ,3,7,17. These observations are in line with the results of 2 separate cohort studies showing that the timing or the technique of BP measurement inserts variation in the prognostic association of BP with mortality in the ESRD population ,10. In tThe diverse prognostic association of clinic versus ambulatory SBP that was evident in the present study could be theoretically attributed to the greater number of BP recordings that the technique of ABPM provides. However, we believe that this potential explanation is an oversimplification of the overall value of ABPM in the assessment of hypertension. This issue was illustrated in a prior observational study showing that among hemodialysis patients, interdialytic ambulatory SBP retained its strong prognostic association with all-cause mortality, even when a small subset of randomly selected ambulatory BP measurements was averaged and used as risk predictors . TherefoThe superior predictive value of ambulatory over clinic BP may be explained by the fact that ABPM provides a more precise reflection of the patient’s actual BP burden over the entire 24-h period ,16,20. EStrength of our study is the careful assessment of BP at baseline with the use of standardized clinical BP recordings and the reference-standard method of ABPM. However, the present work has also some limitations that need to be acknowledged. First, the observational design of this study precludes the opportunity to derive direct cause-and-effect associations between BP and risk of future cardiovascular events and all-cause death. However, this limitation is commonly shared across all prior observational studies that attempted to explore the prognostic significance of BP in patients on dialysis. Second, patients with infectious/bleeding complications shortly before study enrolment or those with a recent hospitalization due to acute coronary syndrome or acute stroke were excluded from our analysis. Therefore, larger studies also including patients with more severe underlying illness are warranted to confirm whether our observations are applicable to the whole spectrum of the PD population. Third, even though the survival analysis was adjusted for several established risk factors, we acknowledge that the possibility of residual confounding is still not fully eliminated. Finally, since the assessment of clinic and ambulatory BP was performed only in a single occasion at baseline, our analysis could not provide time-varying risk-associations between BP and clinical outcomes.In conclusion, the present study shows that among patients on long-term PD, increasing ambulatory SBP was associated with increased risk of adverse cardiovascular events and all-cause death independently from several established risk factors. In contrast, the HR for the composite outcome was not significantly higher in the highest quartile of clinic SBP as compared with the reference quartile 1, suggesting that increasing clinic SBP could not provide a direct risk signal. Future studies are warranted to fully elucidate whether the adequate assessment of hypertension with the use of ABPM can improve cardiovascular risk stratification in the PD population.


Despite effective treatments, blood pressure (BP) control remains suboptimal.The SIMPLIFY study aimed at identifying key factors related to therapeutic inertia in Belgium and Luxembourg, and evaluating how uncontrolled treated hypertension is managed in primary care.In a 2017 cross-sectional survey, 245 general practitioners (GP) collected routine clinical data from 1,852 consecutive uncontrolled (Office SBP/DBP ≥ 140/90 mmHg) hypertensive adult patients taking at least one antihypertensive drug.Patients were 64 years old on average, 48% were women, 61% had dyslipidemia, 33% had diabetes mellitus and 22% had established cardiovascular disease. Half of the patients had 2 or more comorbidities. Patients had been treated for hypertension for an average period of 8 years, 40% of patients were in hypertensive stages 2–3, 44% were treated with monotherapy only, 28% with free combinations and 28% with at least one single pill combination (SPC). Therapeutic adherence was rated as ‘good’ in 62% of patients. AHT treatment was modified in 84% of patients.In the group of patients with stage 2–3 hypertension, treatment remained unchanged in 5%. In the group of patients with stage 1 hypertension, treatment remained unchanged in 23% of patients. Patients treated for longer than 10 years were less likely to undergo treatment change (81%) compared to patients treated for less than 10 years (87%). Patients with 1 or 2 comorbidities were more likely to have their treatment modified (87%) compared to those with no comorbidities (61%) and those with ≥ 3 comorbidities (79%). If treatment was modified, a SPC was introduced in 90% of cases; 91% in stage 1–2 hypertension and 84% in stage 3 hypertension. SPCs were less frequently initiated in patients without comorbidities. Main reasons for the GPs to switch from a free association towards SPC were ‘better BP control’ (55%), ‘better therapeutic compliance’ (53%) and ‘simplicity for the patient’ (50%).The SIMPLIFY study confirms therapeutic inertia in hypertension management. After an average of 8 years hypertension treatment, almost 1 in 2 uncontrolled treated patients are on monotherapy. The key inertia drivers seem to be age, mild grade hypertension, isolated systolic hypertension, longer duration of antihypertensive treatment and better therapeutic adherence. When treatment is updated by the GP, the currently preferred strategy is switching towards SPC based therapy to improve BP control, and enhance therapeutic compliance by simplifying treatment for the patient.pharma.be visa number: VI 17/01/20/01ISRCTN16199080.ISRCTN registered study:  Arterial hypertension is an important cause of death worldwide and one of the principal manageable risk factors for cardiovascular diseases . DespiteOn top of non-pharmacological measures to prevent and to treat arterial hypertension, the 2018 guidelines of the European Society of Hypertension and the European Society of Cardiology (ESC/ESH)  shifted Physician-related factors such as therapeutic inertia, that is, failure of modifying treatment regimens when abnormal clinical parameters are recorded, represent an important factor contributing to poor blood pressure control. Previous studies have shown that therapeutic inertia is largely the result of an overestimation of the blood pressure control by treating physicians. In uncontrolled hypertensive patients receiving at least 2 antihypertensive molecules, one out of 3 patients is not evaluated as having uncontrolled hypertension .Studies on blood pressure control rates in Belgian hypertensive populations show control rates of 22% to 45% –12. In BThe observational cross-sectional SIMPLIFY survey used existing patient data recently registered in the patients’ medical record as part of routine clinical practice. Patients included in the study population were intended to be a representative sample of the Belgian and Luxembourgian adult uncontrolled on-treatment hypertensive population  in primary practice. Patients with secondary hypertension were excluded from the study.Over a period of 5 months, from June till November 2017, 270 GPs were recruited nationwide, with a well-balanced geographical distribution. In order to control for selection bias, the investigators were asked to collect the study data of the last 15 consecutive hypertensive patients seen in their clinical practice and corresponding to the inclusion criteria, so as to obtain a cross-sectional snapshot of the current situation in the study population, without information on prior and future management of these patients. At the time of consultation with the GP the patient provided oral informed consent to the GP to have data from their medical records used in research.st line management of hypertension in Belgium and Luxembourg.For each patient included in the study, a case report form (CRF) was provided to the GP in order to collect the following information from the patient medical record: age, gender, anthropometrics, presence of relevant comorbidities, office blood pressures as measured in routine clinical practice, antihypertensive drug use , duration of antihypertensive treatment (years), other drugs relevant to the study, total number of drugs per day. These data were collected without formal definitions of the co-existing comorbidities, BP measurement or adherence status in order to truly reflect real current practice in 1During the consultation the therapeutic decision to modify treatment, whereby modification could be any possible change to the existing treatment was noted, as well as which anti-hypertensive drugs were prescribed after the index consultation , other drugs, total number of drugs per day)and the motivation for the GP to do so .Besides these parameters the treating physician was also asked to report the estimated therapeutic adherence to the existing antihypertensive treatment. The treating physician was asked to give an estimate of the patient’s therapeutic adherence by choosing between “good, moderate, not adherent” during the index consultation.Participating general practitioners were asked to measure blood pressure in the framework of this survey, hence representing real life data on BP measurements and interpretation in primary care. Hypertension was defined as a SBP of at least 140 mmHg and/or a DBP of at least 90 mmHg. Grade I hypertension was defined as having a SBP between 140–159 mmHg and/or a DBP between 90–99 mmHg, grade II hypertension was defined as having a SBP between 160–179 mmHg and/or a DBP between 100–109 mmHg, and grade III hypertension was defined as having a SBP of at least 180 mmHg and/or a DBP of at least 110 mmHg. Isolated systolic hypertension (ISHT) was defined as a SBP of at least 140 mmHg and a DBP of less than 90 mmHg, whereas isolated diastolic hypertension (IDHT) was defined as a SBP of less than 140 mmHg and a DBP of at least 90 mmHg. Therapeutic inertia was defined as no change in the antihypertensive treatment or management by the consulting physician despite an SBP and/or DBP ≥140 mmHg and/or ≥90 mmHg respectively during the index consultation.The antihypertensive molecules used were subdivided in the following major classes: beta-blockers (BB), calcium channel blockers (CCB), ACE inhibitors (ACE-I-), angiotensin II receptor antagonists (ARB), thiazide-type diuretics, thiazide-like diuretics and “other diuretics”.All study data collected were transferred by a clinical research associate into an electronic database. In order to ensure the quality of the data entry, a double-check was performed in a random sample of 5% of the entered records.Patients’ demographics, risk factor profiles and use of medication were described according to means, standard deviations and proportions.The study was conducted according to the quality standards for non-interventional studies outlined in the prevailing Code of Deontology of the Belgian pharmaceutical industry association (pharma.be).Overall, 245 GPs , participated and collected the study data. The GPs enrolled a total of 1852 patients on active antihypertensive treatment with uncontrolled blood pressure (SBP/DBP ≥ 140/90 mmHg).2, with 70% of the patients being overweight and 26% being obese. Mean (SD) systolic blood pressure was 153.0 (±12.4) mmHg, and diastolic blood pressure was 88.5 (±9.4) mmHg. 40% of the patients were classified as having grade II (33%) or III (7%) hypertension. Prevalence of ISH was 41% whereas IDHT was observed in only 3% of the patients. The remaining 56% had both systolic and diastolic BP uncontrolled. The mean (SD) antihypertensive treatment duration before the index consultation was 8.4 (±6.3) years and treatment adherence was rated by the GP as “good” in only 62% of the patients. Almost all patients (96.6%) had at least one comorbidity, and up to 16% of the patients had a burden of at least 3 comorbidities. The most prevalent comorbidities were dyslipidaemia (61%) and diabetes (33%). In 22% of the patients a prior cardiovascular event had occurred.The patient characteristics are shown in Beta-blockers and ACEI were used in 52% and 48% of the patients, followed by CCB in 31%, ARB in 15% and thiazide diuretics in 14%. Monotherapy was used in 44%, free drug combinations in 28% and “SPC only”  and SPC plus  in respectively 16% and 12% . Beta-blAntihypertensive treatment was not modified in 16% of the uncontrolled on-treatment hypertensive patients. This therapeutic inertia seems associated with older age (66.1 vs 63.8 years old), a longer history of prior antihypertensive treatment (10.1 vs 8.1 years of antihypertensive treatment), and a higher rate of good therapeutic adherence (77% vs 59%) . FurtherIn the uncontrolled on-treatment patients whose treatment was modified, the preferred type of treatment in order to improve BP control was in all cases (i.e. regardless of the previous treatment type) the use of SPCs, with 86%, 72%, 83% and 59% switching from monotherapy, free combination, SPC only, or SPC plus respectively towards SPC only. The 83% from SPC only towards SPC only represents a switch in dosage or in classes comprising the SPC.The preferred classes of antihypertensive drugs to improve BP control were ACEIs, and BBs and to a lesser extent calcium channel blockers, as shown in In 84% of the uncontrolled hypertensive patients antihypertensive treatment was modified. The main reasons for general practitioners to modify the treatment of uncontrolled on-treatment hypertensive patients were multiple, but were mainly better BP control (67%), followed by improved therapeutic adherence (31%) and simpler use for the patient (27%) .In this cross-sectional survey in a high-risk population of 1852 uncontrolled treated hypertensive patients with a long treatment duration (8.4 years) it was observed that in 16% of the cases treatment was left unchanged, indicating a sub-optimal management of these high-risk patients. This proportion of observed therapeutic inertia is likely to be biased and is likely to be an underestimation of the true situation in clinical practice given the acknowledgment of study protocol and object are likely to subconsciously change the clinical decision of the participated GPs on whether the drug prescription should be modified.There was a preferred use of beta-blockers (52%) and ACEIs (48%) followed by CCBs (31%). The relatively large use of beta-blockers is in line with the overall high risk profile of our patients with substantial comorbidity burden. Antihypertensive treatments were given as monotherapy in almost half of all patients, followed by free combinations in one third and SPC only or SPC plus in almost another third of patients. In 84% of the patients in whom treatment was modified, beta-blockers and ACEIs were still the preferred classes, with a preferential switch to mainly SPC type treatments. The switch towards a situation with SPC treatments in 90% of the patients may be an overestimation of the true situation in clinical practice. The acknowledgment of study protocol and object are likely to subconsciously change the clinical decision of the participated GPs on whether SPCs should be prescribed.Uncontrolled blood pressure, excluding true resistant hypertension, is an issue of the patient, physician and the community.As emphasized in the ESH/ESC 2018 hypertension guidelines, low adherence to treatment is a major cause of poor BP control and should hence be monitored.Thirty-eight percent of the patients in our study were judged by the GP to have insufficient treatment adherence.Besides patient non-adherence, longstanding therapeutic inertia by the physician is one of the key contributors to insufficient blood pressure control. Reasons for this therapeutic inertia are multiple. In our study, therapeutic inertia seemed associated with age, hypertension stage, isolated systolic hypertension, longer treatment duration and better therapeutic adherence.Therapeutic inertia, defined as failure of healthcare providers to initiate or intensify therapy when indicated , might bTherapeutic inertia is a major cause of not reaching target blood pressure in regular clinical practice. Investigator inertia has even been observed in clinical study settings. Kjeldsen et al analysed the LIFE and ASCOT data to find out why SBP levelled off after 6 months of blinded treatment with many patients with SBP > 140 mmHg remaining at their initial dose and not being uptitrated. Their conclusion was that there was no other reason than investigator inertia for the levelling off of the BP [In our study, the fact that many patients remained on monotherapy, despite their BP being above target, points towards therapeutic inertia. The underlying causes of this therapeutic inertia are unclear. While it was actively asked why the GP did modify the treatment, it was not actively asked why the GP did not modify the treatment, which is certainly a complex entity. However, we could identify factors associated with therapeutic inertia: older age, grade 1 hypertension, isolated systolic hypertension, longer treatment duration and better therapeutic adherence.Gil-Guillén et al, quantified diagnostic and therapeutic inertia in hypertension and identified patient-associated variables in a cross-sectional, multicentre study in 35000 people in 428 health centres and primary care centres, and found that diagnostic inertia and therapeutic inertia were present in respectively 32.5% and 37% of the cases . FactorsThe “Objetivo Kontrol” study  analysedTo address inertia, adequate interventions are needed. Kjeldsen and the VALUE investigators  launchedIn our study, the GPs who modified the treatment, which consisted mainly of a switch towards single-pill combination, indicated better BP control, better therapeutic adherence and a simpler treatment regimen as the main drivers to intensify therapy. In the ACHIEVE study, a cross-sectional observational survey in primary care in Belgium and Luxembourg, Leeman et al. evaluated the actual blood pressure control rate and its estimation by general practitioners, the use of single-pill or free combinations, and the attitude towards single-pill combinations in primary care . In patiIn addition, combinations of therapies can reduce side effects, for example by adding a thiazide-type diuretic to a calcium-antagonist, the symptoms of peripheral edemas can be reduced .Finally, treatment simplification could improve adherence and could represent a tool to decrease therapeutic inertia in order to improve blood pressure control rate, which has been shown to lead to reduced morbidity and mortality .st line management of hypertension in Belgium and Luxembourg. The study is a pure cross-sectional design study, so no predictions or causal relationships can be made. The strengths of the study might be the simplicity of the study protocol (which might be seen as a weakness at the same time). Although there might be some selection bias, the study reflects well the common current management of hypertension in GP practices.This study has several limitations. Physicians participated to the study on a voluntary basis, which may reflect a particular interest in the management of high blood pressure, and therefore maybe not fully representative for the overall GP population. Also the patients may not fully reflect the overall general population of hypertensive patients in Belgium and Luxembourg. The data were collected without formal definitions of the co-existing comorbidities, BP measurement or adherence status-which were left to the GPs judgement- in order to truly reflect current practice in 1The SIMPLIFY study confirms the existing therapeutic inertia in treatment of arterial hypertension in routine clinical practice conditions in Belgium and in Luxembourg. After an average of 8 years hypertension treatment, almost 1 in 2 uncontrolled treated patients are still on monotherapy. The key inertia drivers seem to be age, mild grade hypertension, isolated systolic hypertension, longer duration of antihypertensive treatment and better therapeutic adherence. When treatment is updated by the GP, the currently preferred strategy is switching towards SPC-based therapy to improve BP control, and enhance therapeutic adherence by simplifying treatment for the patient.S1 Checklist(PDF)Click here for additional data file.S1 File(DOC)Click here for additional data file.S2 File(DOC)Click here for additional data file.S3 File(PPTX)Click here for additional data file.S4 File(DOC)Click here for additional data file.S5 File(DOC)Click here for additional data file.S6 File(DOC)Click here for additional data file.


Results: There were pre vs. post0h changes in all serum biomarkers . The change in these biomarkers correlated with an increase in mechanical load indicators . A total of 40% and 23.4% of participants presented proteinuria and hematuria, respectively. Pain and perceived exertion increased significantly due to effort made during the endurance trail running . Conclusions: Endurance trail running may lead to an increase in blood and urine indicators of transitional AKI. The difference in blood and urine markers was significantly related to the mechanical load during running, suggesting potential kidney overload and cumulative mechanical load.Background: This study aimed to globally assess heat strain, dehydration, and mechanical load as acute kidney injury (AKI) indicators in amateur endurance trail athletes during a 35.3 km run. Methods: Thirty amateur experienced trail runners completed an endurance trail run . The following assessments were performed at four measurement time points (pre-, during, immediately post [-post There are activities of increasing popularity in endurance sports, such as running, cycling, triathlon, and open water swimming. This widespread endurance sports practice responds to the economic prosperity of some populations, relatively inexpensive travel cost, and the relatively affordable and user-friendly required equipment for its practice . EnduranMuscle damage is a common consequence of trail running . Still, There are several methods to quantify renal function. It is commonly assessed by chemical waste molecules generated from muscle metabolism. During exercise, due to muscle damage, the protein-waste products released to the bloodstream could overload the kidney. Among these biochemical markers of kidney damage are serum creatine kinase (sCK), serum creatinine (sCr), serum blood ureic nitrogen (sBUN), serum albumin (ALB), and recently through Cystatin-C (Cyst-C) ,12. OtheAKI is understood as a multi etiology condition. There are three factors proposed as enhancers of AKI development in sports: high mechanical load, heat strain, and dehydration ,16. ReceAKI has been studied in populations with the abovementioned conditions, such as athletes, agricultural workers, firefighters, and builders ,20. AlthThe prevalence and severity of AKI episodes among endurance athletes have been debated without reaching a consensus. Some authors point out that AKI should be considered a health problem or issue , and othThirty male amateur trail runners took part in this study . Participants were selected from different trail running clubs. Participants were required to be >18 years old, experienced (5.69 ± 2.77 years), trained (9.02 ± 3.57 h/week), and heat acclimatized  endurance runners. Participants reported no neuromuscular or metabolic disturbance or injury at least six months before the study.The experimental protocol was approved by the Institutional Review Board of the National University of Costa Rica (Reg. Code UNA-CECUNA-2019-P005) and the University of Extremadura (Reg. Code 139/2020). All the participants were informed of the details of the experiment procedures, the associated risks and discomforts, and their benefits and rights. Each subject gave written informed consent, according to the criteria of the Declaration of Helsinki, regarding biomedical research involving human subjects .0h, and -post24h)  . All parad libitum as typical in trail running races. Perceived pain and exertion data was collected ~10 min before, after, and during the run. Mechanical load variables were monitored all over the trail run using wearable devices.As shown in in-situ from the antecubital vein using a 5 mL blood collection sterile tube  that contained spray-coated silica particles activator and gel polymer to facilitate serum separation during centrifugation . Centrifugation was performed using a tube centrifuge .For serum test analysis, blood was extracted TM, California, USA) until serum samples were frozen at −20 °C (~5 h after blood extraction). Samples analyses and processing were performed 24 h after data collection in an isolated and temperature-controlled laboratory using an automatic biochemical analyzer  by photometry method. All procedures were executed under relevant protocols for the handling and disposal of biological materials, according to the manufacturer’s instructions for the equipment and reagents used.Blood samples were stored on ice in a special cooler , CrClearance (mL/min) and sBUN/sCr ratio. CrClearance was predicted from sCr using the Cockcroft and Gault [The variables analyzed were serum creatinine , creatine kinase , ureic nitrogen , and albumin . The following variables were also estimated: eGFR , previously used in distance running settings [TM, Misco, OH, USA). USG results were classified following the hydration status ranges: well-hydrated <1.01, minimal dehydration 1.01–1.02, significant dehydration 1.02–1.03, and severe dehydration >1.03 [Urine samples were collected in-situ in a 30 mL polypropylene sterile urine container  and analyzed with highly sensitive and accurate dipsticks for urine screening   to assess hematocrit (Htc). The capillary micro-hematocrit tubes were centrifuged , and hematocrit values were evaluated using a special reader .Participant’s body mass (kg) was assessed semi-nude (underwear only) immediately pre and post-event using a digital balance  in an isolated tent. Percentage body weight change was categorized as follow: well-hydrated +1% to −1%, minimal dehydration −1% to −3%, significant dehydration −3% to −5% and serious dehydration >5% . Liquid TM 36, 3MTM, Saint Paul, MN, USA) every 15 min. Equipment was calibrated and mounted in a stable tripod at the start and finish of the event.During the whole event, variations of the WetBulb-Globe Temperature (WBGT) were registered with a heat stress monitor  attached to different anatomical spots . IMUs were mounted using special spandex dark suit to avoid non-desired movement or shaking during running, as reported in previous studies [Mechanical load variables were assessed using six inertial measurement units  per body segment. Player Load is defined as the vector sum of accelerometer data points in the three axes of movement [g-forces) where 1 g = 9.81 m/s [The analyzed variables were selected considering similar studies investigating mechanical load and AKI in endurance events . The extmovement , represe9.81 m/s ,29.Perceived pain and rate of perceived exertion (RPE) were measured using a 0 to 10 point visual analog scale of pain (VAS-PAIN); cero is understood as no pain, and ten is an extreme pain . This vat-test analysis. The magnitude of the differences (effect size) was qualitatively interpreted using partial omega squared (p²ω) as follows: >0.01 small; >0.06 moderate and >0.14 large and using Cohen d (d) as follows: <0.2 trivial; 0.2–0.49 small; 0.5–0.79 moderate and >0.8 large [Description of variables was reported using mean, standard deviation, and lower and upper limits. The normality of the data was confirmed using the Shapiro–Wilk test. Differences between variables were explored using one-way analysis of variance ; the exploration of the measurement timepoint differences was made using Bonferroni Post Hoch when required. Hematocrit and body weight data were explored using paired .8 large  when corMcNemar non-parametric test was used to explore the possible change in proportion for the paired data of urinalysis. In those observed cases, the intersection frequency value was <5, and the binomial test was performed. The data of pH, glucosuria, proteinuria, hematuria, and USG were paired by measurement timepoints using a 2 × 2 contingency table. A Pearson Correlation matrix was performed and graphed to explore the correlation between serum markers’ change percentage (Δ%) and mechanical load variables.p < 0.05. Data analysis was performed using the Statistical Package for the Social Sciences .Alpha was prior set as 0h and pre and post24h measurement time points, the levels of sCr, sCK, sBUN, sALB, USol, and sBUN/sCr ratio significantly increased (p < 0.01). Moreover, a significant decrease in CrClearance, eGFR, and BW was presented after the trail run (p < 0.01). Some variables, such as sALB, sCK, sCr, eGFR, USG, USol, CrClearance, and sBUN/sCr ratio also recovered the baseline values as evidence in post24h assessment , sBUN , sALB , sCK , CrClearance , and eGFR .0h). The baseline levels were recovered after 24 h in 40.0% of these cases. Hematuria cases increased by 23.4% (pre vs. post0h) and then decreased by 20.0% (post0h vs. post24h). Finally, cases of pH ≤ 5 decrease by 20.0% (pre vs. post24h)  see .p < 0.01) gradually between pre, 1st, and 2nd lap. Lumbar pain increased during the race, but no difference was found between the 1st and 2nd lap , PL VLleft  and PL T2–T4 . Besides, the Δ% of sBUN correlated with PL MPleft  and PL VLleft . Finally, the Δ% of sALB correlated with PL MPleft , PL VLleft , PL L1–L3  and PL T2–T4  (see The percentage of change (Δ%) of sCK correlated significantly with PL MP.04) see .0h assessments in all serum biomarkers  was found, and its percentage of change correlated with mechanical load indicators (Player Load as accelerometry-based load index). A total of 40.0% and 23.4% of cases presented concomitant proteinuria and hematuria, respectively, due to the trail running. Pain and perceived exertion changed significantly after running. Considering selected reference criteria, there was an incidence of 63.0% (19/30) out of range cases in sCr, 40.0% (12/30) in sBUN, 13.0% (4/30) in sALB, 90.0% in CrClearance (27/30), and 30.0% (10/30) in sGFR after endurance running. These out-of-range cases in the AKI biomarker indicators returned to baseline after 24 h, suggesting transitional AKI. The outcomes of this study should be analyzed based on two considerations, mean change between timepoint measures and increase or decrease in cases out of range based on clinical and technical criteria. The isolated analysis of statistical differences could lead to misunderstanding the results and the effect of endurance trail running on AKI.The purpose of this study was to globally assess heat strain, dehydration, and mechanical load variables as AKI indicators in amateur endurance trail athletes during a 35.3 km run. A significant change between pre vs. postF = 5.4–34.5, p < 0.01), previous evidence has suggested an increase in biomarkers related to AKI after endurance running events [As found in this study  between mechanical load indicators  registered in different body segments and some AKI biomarkers (sBUN and sALB) [Clearance, eGFR, hematuria, and proteinuria; similar changes to those found in this study [The physical effort and biomechanical characteristics of trail running could explain the relation found (nd sALB) . Indeed,nd sALB) ,36,37, ais study ,19. In tis study ,38. Runnis study ,38.1-L3). It has been found that, due to higher intensity and higher external load presented in shorter and faster endurance events, runners usually have a more significant impact on kidney health than more extended events [The data presented in this study reinforces the hypothesis of potential cumulative kidney mechanical trauma ,39, by pd events ,9,11,37.Clearance, and sBUN/sCr ratio, with values over the upper reference limits supports this finding [Additionally, based on selected AKI diagnosis criteria, the change in sCr may suggest a risk of AKI after running endurance trail running, but with a return to baseline values after 24 h, as evidenced in previous studies ,37. The  finding ,40. More finding ,24. Endu finding ,37.ad libitum food availability and fluid intake during the race. However, although dehydration could typically contribute to AKI, it seems to have a mild impact, as previously reported [In addition to the mechanical load, it has been reported that heat strain and dehydration during these kinds of events can boost the prevalence of AKI in endurance running as it has been reported in other populations ,19,41, dreported .p < 0.01) in perceived pain and effort values during the race can be a complementary analysis to the biochemical, mechanical, and thermal load assessments to monitor endurance athletes throughout an event to prevent the appearance of AKI. Lumbar pain and its relationship with AKI biomarkers should be explored in future studies.Anecdotally, the change  correlated significantly with the percentage of change (Pre vs. Post0h), sCK, sBUN, and sALB; this was evidence for mechanical muscle damage and strengthened the hypothesis of kidney trauma due to cumulative low to moderate contusions during running [Endurance running could lead to some temporal dysfunctions, such as AKI. These complications were reflected by the increase of some serum changes as sCr, sCK, sBUN, sALB, eGFR, Cr running .Considering endurance trail running could increase some blood and urine samples related to transitory AKI, some factors such as dehydration, heat strain, and mechanical load should be monitored during training and competition to prevent potential future damage.Managing fluid intake and restoring electrolytes before, during, and after endurance events may reduce the number or lessen the severity of AKI cases. Avoiding repeated endurance events without the required rest and recovery between exhaustive efforts could be protective against AKI.Although there is insufficient evidence to relate AKI events with chronic kidney diseases, medical staff and trainers may monitor renal health of long-distance runners frequently to detect any change in renal function that could affect runners’ health.


Patients with gout frequently have low urinary pH, which is associated with the nephrolithiasis. However, the specific distribution of urinary pH and potential relationship of acidic urine pH to broader manifestations of kidney disease in gout are still poorly understood.A 2016–2020 population-based cross-sectional study was conducted among 3565 gout patients in the dedicated gout clinic of the Affiliated Hospital of Qingdao University to investigate the association between low urinary pH and kidney disease. We studied patients that we defined to have “primary gout”, based on the absence of > stage 2 CKD. All subjects underwent 14 days of medication washout and 3-day standardized metabolic diet. We obtained general medical information, blood and urine biochemistries, and renal ultrasound examination on the day of the visit. The primary readouts were urine pH, eGFR, nephrolithiasis, renal cysts, microhematuria, and proteinuria. Patients were assigned into 5 subgroups , aligning with the clinical significance of urine pH.Overall, the median urine pH and eGFR of all patients was 5.63 (IQR 5.37~6.09), and 98.32 (IQR 86.03~110.6), with acidic urine in 46.5% of patients. The prevalence of nephrolithiasis, microhematuria, and proteinuria were 16.9%, 49.5%, and 6.9%, respectively. By univariate analysis, eGFR was significantly associated with age, sex, duration of gout, tophus, body mass index, systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, serum utare, hypertension, diabetes, and urine pH. On multivariable analysis, eGFR was associated with age, sex, diastolic blood pressure, serum uric acid, hypertension, diabetes, and urine pH. Acidic urine pH, especially urine pH < 5.0, was significantly associated with the prevalence of kidney disease, including > stage 1 CKD, nephrolithiasis, kidney cyst, and microhematuria. Patients with 6.2 ≤ urine pH ≤ 6.9 and SU ≤ 480 μmol/L had the highest eGFR with the lowest prevalence of nephrolithiasis, microhematuria, and proteinuria.Approximately half of gout subjects had acidic urine pH. Urine pH < 5.0 was associated with significantly increased nephrolithiasis, renal cyst, microhematuria, and proteinuria. The results support prospective clinical investigation of urinary alkalinization in selected gout patients with acidic urine pH.The online version contains supplementary material available at 10.1186/s13075-022-02725-w. Gout is a highly prevalent disorder  that is Urine pH normally is slightly acidic (averaging ~6.0), and acidic urine has been defined as pH below 5.5 . Acidic n = 3015), (ii) severe gout with inability or secondary gout (n = 3040), and (iii) unable to tolerate 14 days washout of medications (n = 1589). Those excluded because of contraindication to 14 days of medication washout included subjects with diabetes, hypertension, and > stage 2 CKD. We also excluded those who underwent gout flares frequently during washout (n = 56) were not able to follow the fixed metabolic diet (n = 84), withdrew consent (n = 217), had a nonstandard 14-day medication washout (n = 76), had incomplete urinary test data (n = 71), or were missing urine pH values (n = 44). Ultimately, 3565 primary gout patients were included. Patients were assigned into 5 subgroups , aligning with the clinical significance of urine pH. 6.2 ≤ pH ≤ 6.9 as the treatment target of urine alkalization [We conducted a population-based cross-sectional study of patients in the dedicated gout clinic of the Affiliated Hospital of Qingdao University during 2016–2020. The study was conducted according to the principles from the Declaration of Helsinki and was approved by the Ethics Committee of the Affiliated Hospital of Qingdao University. All patients who were involved in this study provided written informed consent. We enrolled 11,757 patients who met the 2015 ACR/European League Against Rheumatism (EULAR) classification criteria for gout . Subjectlization , with urlization .Patients enrolled were required to conduct a 24-h urine collection after a 2-week washout. During the 2-week washout period, all enrolled patients were required to stop taking all drugs for 2 weeks after clinicians assessed that they tolerated medicine withdrawal. Patients were required to maintain a fixed metabolic diet during the last 3 days of the washout period. The diet included most sugars, starches, and fats. Protein is mainly provided by defatted or low-fat milk, eggs, and cereals. Protein and lipid intakes were 50~70 g/day and <50 g/day, respectively. The purine intake was less than 200 mg/day. The recommended fluid intake is more than 2000 mL/day. Total daily calorie intake and calorie allocation per meal were calculated based on height, weight, and work intensity of subjects , and alcohol history . Blood pressure were measured using an Omron electronic sphygmomanometer . Serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), serum fasting blood glucose (FBG), serum triglyceride (TG), serum cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), serum urate (SU), serum creatinine (sCr), 24-h urine volume (recorded by patients), 24-h urine uric acid (uUA), and urine creatinine (uCr) were measured using an automatic biochemical analyzer . Proteinuria was measured using a urine automatic analyzer , proteinuria positive referred to the concentration exceeds 0.15 g/day. Microhematuria was define as >3 red blood cells per high-power field on microscopic evaluation of a single, properly collected urine specimen . Urine pA renal tract ultrasound examination using a standard imaging protocol was done on the day of the visit. The Philips IU22 color ultrasound instrument with a L12-5 broadband probe was used. The size, surface smoothness, parenchyma  echoes of both kidneys, and separate dilatation of both renal sinuses were observed in a single blind examination conducted by a senior ultrasound diagnostic physician. Renal cysts were defined as round anechoic areas with thin and smooth cyst walls and enhanced posterior echogenicity. Renal stones showed enhanced echogenicity. The presence of stone-free, single, or multiple kidney stones were detected by ultrasonography. Multiple kidney stones are defined as more than one stones in the kidney .2) and eGFR were calculated by CKD-EPI creatinine equation. GFR = 144 × (Scr/0.7)-0.329 × (0.993)Age, for female’s Scr < 62 μmol/L; GFR = 144 × (Scr/0.7)-1.209 × (0.993)Age, for female’s Scr > 62 μmol/L; GFR = 141 × (Scr/0.9)-0.411 × (0.993)Age, for male’s Scr < 80 μmol/L; and GFR = 141 × (Scr/0.9)-1.209 × (0.993)Age, for male’s Scr > 80 μmol/ L[2)) [/day/1.73m2 [Body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared. Kidney function measured by estimated glomerular filtration rate ) . The undy/1.73m2 .Data were presented as mean  for continuous variables if normally distributed and median  if not normally distributed. For categorical variables, data were shown as number . For the comparison of general data of patients with different urine pH, ANOVA and chi-squared tests were used for continuous and categorical variables and the Kruskal-Wallis test was used for variables with a skewed distribution. Comparison of proportion in patients with different urine pH values, chi-squared tests were used. The chi-square test of 2×2 used for pairwise comparison between groups and significance was corrected by Bonferroni.P < 0.20 on univariate linear regression analyses were included in multiple linear regression analysis. Both Beta and 95% CI were estimated.Univariate linear regression analyses were conducted to evaluate the respective relation between patients’ characteristics and eGFR. Multiple linear regression analysis was performed by using eGFR as a dependent variable to evaluate the role of the parameters in eGFR. All variables with P < 0.05 was considered statistically significant.To compare the prevalence of kidney disease outcomes of different urine pH metrics, multivariable logistic regression models were constructed. Model 1 represented unadjusted odd ratios (ORs). Model 2 included demographic characteristics, such as age, sex, duration of gout, presence of tophus, and SU. In model 3, further covariates were added to model 2, including history of hypertension and diabetes. eGFR was divided into Yes or No according to whether it was > stage 1 CKD. Furthermore, we examined the effect modification for kidney disease outcomes in prespecified subgroups by SU . Significant differences were found in sex, age, BMI, gout disease duration, smoking history, alcohol history, history of nephrolithiasis, systolic blood pressure (SBP), ALT, AST, TG, TC, sCr, BUN, SU, uCr, uUA, UUE, and FEUA among the groups , sex , DBP , SU , hypertension , and urine pH  , 30.4% (5.0 < urine pH ≤ 5.5), 29.7% (5.5 < urine pH < 6.2), 14.5% (6.2 ≤ urine pH ≤ 6.9), and 9.4% (urine pH > 6.9) , a 1.5-fold higher risk of nephrolithiasis , a 1.6-fold higher risk of kidney cyst , and 1.7-fold higher risk of microhematuria  (Table P = 0.003) and 1.8-fold higher risk of microhematuria    for incident > stage 1 CKD (Table P<0.001). Nevertheless, in the subgroup with SU > 480 μmol/L, participants with 5.0 < urine pH≤ 5.5 had no higher risk of > stage 1 CKD than those with 6.2 ≤ pH ≤ 6.9 (P = 0.773).We examined the effect modification by SU. The significant association of urine pH subgroups with the prevalence of kidney disease outcomes, including nephrolithiasis, microhematuria, and proteinuria was consistent across subgroup by SU. However, there was a significant interaction between SU and urine pH  without increasing urine pH will ultimately not be as successful as alkalinization . Our datLimitations of this study included that the cross-sectional, non-interventional research design, which was undertaken for hypothesis-testing and to provide a potential foundation for interventional trial urine alkalinization in gout. We excluded patients who did not meet the criteria for inclusion in this study, leaving it to be seen whether the results would apply to other geographic regions, ethnicities, or environments. Our work analyzed the prevalence of nephrolithiasis, but did not assess composition of renal calculi. We did not study a control group of asymptomatic hyperuricemia or focus separately on those with frequently gout-associated comorbidities, such as hypertension, obesity, metabolic syndrome, and type 2 diabetes. Only selected blood and urine indicators were analyzed in the current study, whereas serum and urine bicarbonate and urine ammonia may have been informative. Additionally, urine crystals and markers of renal tubular injury were not measured in this study.In conclusion, the acidic urine pH of ~50% Chinese gout patients or above-average urine pH (pH > 6.9) were associated with increased prevalence of proteinuria, microhematuria, renal cyst, and nephrolithiasis. Urate-lowering treatment to target SU is a lifelong strategy for gout patients . HoweverAdditional file 1:Supplementary Table 1. The metabolic diet. Supplementary Figure 1. Distribution, kidney function and prevalence of kidney disease outcomes in patients with different urine pH values. (A) the distribution; (B) eGFR; (C) kidney stone; (D) solitary kidney stone; (E) multiple kidney stones; (F) kidney cyst; (G) urine protein; (H) hematuria. Chi-squared tests were used for categorical variables. The chi-square test of 2*2 used for pairwise comparison between groups and significance was corrected by Bonferroni. P < 0.005 was considered statistically significant. *P.


To determine the diagnostic accuracy of pulmonary artery to aorta ratio in screening for pulmonary hypertension in advanced chronic obstructive pulmonary disease (COPD) patients.A prospective, diagnostic study was conducted in University Hospital Center Zagreb between January 2015 and March 2018. The study enrolled 100 patients who consecutively underwent chest computed tomography (CT), echocardiographic exam, and right heart catheterization. Two independent observers measured pulmonary artery and ascending aorta diameters. The correlation between the ratio and mean pulmonary artery pressure, measured invasively, was assessed. Patients with echocardiographic signs of moderate systolic or diastolic left ventricular dysfunction were excluded (n = 44).P < 0.001). Median pulmonary artery/aorta (PA/A) ratios for patients with and without pulmonary hypertension were 1.05 and 0.81, respectively (P < 0.001). PA/A ratio above 0.95 was an independent predictor of pulmonary hypertension with a specificity of 100% and a sensitivity of 74.51% .Sixty-six patients (55.5% men), with a median age of 61, were identified. Median forced expiratory volume during the first second (FEV1) was 34 ± 12, FEV1/forced vital capacity <0.70. Patients with and without pulmonary hypertension had pulmonary artery diameter of 36 ± 7 mm and 27 ± 4.6 mm, respectively (PA/A ratio as measured on chest CT images can be used as a screening tool instead of echocardiography. In patients suffering from late-stage chronic obstructive pulmonary disease (COPD), pulmonary vasculature disease is a predictor of COPD progression and exacerbation. The association may be explained by the resultant pulmonary arterial hypertension -3. As puPulmonary hypertension remains a diagnostic challenge due to its non-specific symptoms: malaise, dyspnea on exertion, and fatigue, along with many other pulmonary disease presentations. Pulmonary hypertension is ultimately treated by surgery: single lung transplant, bilateral lung transplant, or heart and lung transplant . HoweverCurrently, right heart catheterization (RHC) is the gold standard in pulmonary hypertension verification ,10, but A non-invasive, widely available method of measurement of the right heart and pulmonary artery pressures is echocardiography; it is validated and well-established in clinical practice for pulmonary hypertension detection. However, in COPD patients it is often burdened with inadequate acoustic windows due to hyperinflation .Late-stage COPD patients require routine follow-up computed tomography (CT) scanning. CT enables pulmonary artery (PA) and aorta (A) diameter measurement and PA/A ratio determination on a single scan. Hence, in these patients the PA/A ratio could be used as a valuable diagnostic tool for pulmonary hypertension assessment, obviating the need for RHC. On the other hand, patients with a high PA/A score could benefit from a timely referral for invasive diagnostic assessment. Recent studies suggested that PA/A ratio could be a relevant marker of PH in COPD patients ,12,13. HThis prospective, diagnostic study enrolled all patients diagnosed with COPD in the group C or D according to the GOLD standards. All patients were evaluated for lung transplantation from January 2015 to March 2018 in the University Hospital Center Zagreb. The patients' data obtained by clinical assessment, RHC, echocardiography (ECHO), and CT were collected within a six-month period. The inclusion criteria included stable disease with no patient in acute exacerbation during CT, ECHO examination, or RHC. We excluded the patients with another pulmonary pathology , those with systolic dysfunction of the left ventricle, those with greater than mild diastolic dysfunction or any valvular pathology, and non-compliant patients.One hundred patients with verified end-stage COPD based on spirometry findings were consecutively enrolled . We presDemographic and clinical variables obtained were sex, age, body mass index (BMI), and smoking habits. Functional status was derived from the BODE index including 6-minute walking test (6-MWT). All patients completed the COPD Assessment Test (CAT) questionnaire and modified Medical Research Council (mMRC) dyspnea scale.Spirometry revealed information regarding forced expiratory volume in the first second of exhalation (FEV1); predicted values of FEV1, predicted values of total lung capacity, and functional vital capacity (FVC). A patient with COPD was defined as one with post-bronchodilator spirometry FEV1/FVC ratio of less than 70%.ECHO examination included the assessment of the systolic and diastolic left ventricular function. Pulmonary hypertension values were obtained by calculating the maximum velocity of the jet of tricuspid insufficiency using the Bernoulli equation and adding the presumed pressure in the right atrium (regarding flow in the inferior vena cava).RHC was carried out by three different specialists, and the data collected were mean mPAP, systolic arterial pressure, and diastolic pulmonary arterial pressure, cardiac output, cardiac index, and pulmonary capillary wedge pressure. Pulmonary hypertension was defined as mPAP≥25 mm Hg.1 = 0.874, K2 = 0.836, respectively). The patients with abnormal pulmonary CT findings were excluded from the study .Pulmonary CT angiography was performed using a 40-detector row CT scanner  with breath-hold technique. CT scans were analyzed by two radiology specialists blinded to patients’ clinical history. The measurements were performed at the level of the bifurcation of the main PA, and the aorta diameter was measured at the same slice . Both raP values lower than 0.05 were considered statistically significant. Data were analyzed with MedCalc Statistical Software, version 18.2.1 .Demographic and clinical characteristics were summarized as medians and 25th and 75th percentile for continuous variables and as the number and percentage for categorical variables. The Shapiro-Wilk test was used to test the normality of distribution. The Fischer exact and Fischer-Freeman-Halton exact tests were used to assess the differences in categorical variables. The Mann-Whitney U test was implemented to analyze the difference between PA and aorta dimensions in patients with and without pulmonary hypertension. Changes in the specificity and sensitivity of PA/A ratio for the detection of pulmonary hypertension were analyzed by receiver operating characteristic (ROC) curve. Youden index was used to determine the cut/off value of PA/A ratio with the best specificity/sensitivity relationship for pulmonary hypertension prediction. The baseline clinical characteristics are shown in Median (standard deviation [SD]) FEV1% was 32.5 (20.4-50) in the control group and 33.7 (22.2–46.0) in the pulmonary hypertension group, with no significant difference between the groups. The median mPAP in the control group was 23 (21.7–24) mmHg and that in the pulmonary hypertension group was 40.5 (34.0-47.75) mmHg.Our study group consisted of 52 patients (78.8%) with pulmonary hypertension; 23 were women (44.2%). The PH group and controls did not significantly differ in age, sex, BMI, FEV1, and FEV1/FVC.P = 0.052). The groups did not differ in the CAT questionnaire results. Patients with pulmonary hypertension had a significantly higher BODE index  than controls: 6.0 (4.3-7.0) vs 5.5 (2.0-6.3) (P = 0.006).Six-minute walking test result was lower in the pulmonary hypertension group, but the difference did not reach significance (P < 0.001) and a significantly higher median PA/A ratio   .P < 0.001), and accuracy of 82.97% (95% CI 71.71-91.10). The odds ratio for having PA/A ratio above 0.95 in late-stage COPD patients was 42.25 .ROC analysis showed an excellent area under the curve when PA/A ratio was explored as a diagnostic tool for the presence of pulmonary hypertension . The higP = 0.006). In the control group, the correlation coefficient was not significant . The difference between the two correlation coefficients was significant , confirming the importance of the PA/A ratio as a marker of pulmonary hypertension. The difference in correlation coefficients of PA/A ratio and mPAP was assessed by z-statistics . Additionally, due to the small number of published studies on this subject there is no reference standard for PA/A ratio. The advantages of the study include no risk of bias due to flow and timing, and no inter-rater bias.To summarize, according to our data, the PA/A ratio ≥0.95 as measured by CT could be a highly accurate tool to predict the presence of pulmonary hypertension in end-stage COPD patients. The odds ratio, due to small sample size, had a huge 95% confidence interval. Stage C and D COPD patients who had a PA/A ratio ≥0.95 had a 42 times greater probability of having pulmonary hypertension in comparison with patients with PA/A ratio <0.95, or at least a 5 times greater risk, if we take the lower value of 95% confidence interval. However, the presence of pulmonary hypertension cannot be excluded in patients with PA/A<0.95. Meta-analyses including more data are necessary to confirm the reliability and accuracy of PA/A ratio as a measure of the pulmonary hypertension risk in stage C and D COPD patients. Therefore, invasive RHC measurement remains the most important and unavoidable method for detecting pulmonary hypertension.


Emergency physicians frequently encounter critically ill patients in circulatory shock requiring definitive airway procedures. Performing rapid sequence intubation in these patients without blood pressure correction has lethal complications. Questioning the efficacy and fearing side effects of push-dose pressors (PDP) has created an obstacle for their use in the emergency department (ED) setting. In this case series we describe the efficacy and side effects of PDP use during peri-intubation hypotension in the ED.We included 11 patients receiving PDPs in this case series. The mean increase in systolic blood pressure was 41.3%, in diastolic blood pressure 44.3%, and in mean arterial pressure 35.1%. No adverse events were documented in this case series.The use of push-dose pressors during peri-intubation hypotension may potentially improve hemodynamic status when used carefully in the ED. P = 0.01).6Rapid sequence intubation (RSI) is the cornerstone of emergency airway management. Nonetheless, if not executed carefully the complications can be deadly.The emergency department (ED) environment poses unique challenges in ensuring seamless and safe administration; treatment of unfamiliar patients, crowding, reliance on verbal orders, dispensing and administering medications without verification by a pharmacist, and understaffing.The use of PDP during peri-intubation hypotension was part of a quality improvement program within the ED. We implemented a RSI bundle; this included instructions for PDP mixing . These iPush-dose pressors are prepared (following mixing instructions) and administered via large bore (14–18 gauge) peripheral intravenous (IV) access over one minute by the primary nurse. Vital signs were documented in the note at five minutes before and after the procedure. Adverse effects including extravasation and dysrhythmias were monitored for 30 minutes of PDP administration; standard procedure for nursing staff is to monitor for these adverse effects and document in the electronic health record if they do occur. Study investigators raised awareness of the new RSI bundle and PDP mixing instructions via departmental educational activities, bedside clinical demonstration, didactic lectures, and procedure note review. The bundle was approved by the department’s chair and clinical practice committee.We included patients undergoing the following: 1) RSI in the ED; or 2) receiving PDPs for a systolic blood pressure less than or equal to 100 mm Hg and/or diastolic blood pressure less than or equal to 60 mm Hg. During the one-year study period (January 2019–January 2020), a total of 86 patients underwent RSI by emergency physicians. Of those, only 11 patients received PDP for hypotension . What do we already know about this clinical entity?Push-dose pressor (PDP) is common practice for rapid hemodynamic correction in the operating room. However, there is scant research examining the use of PDP in the emergency department.What makes this presentation of disease reportable?Understanding the effects of PDPs duringperi-intubation hypotension will aid emergency physicians in clinical practice.What is the major learning point?Consider careful use of PDP for peri-intubation hypotension in the ED.How might this improve emergency medicine practice?Rapid correction of hemodynamic parameters prior to rapid sequence intubation, is crucial to lower deadly complications such as peri-intubation cardiac arrest.We assessed the efficacy based on pre- and post-PDP vital signs in 11 patients . The oveIt is standard procedure to document any side effects from medication administration given intravenously. This is especially true for high-risk medications such as peripheral vasopressors. No events of extravasation or local tissue injury were documented in patients receiving PDP via peripheral IV route. Additionally, no documented cardiac dysrhythmias were found.Significant data exist on the utilization and benefit of phenylephrine for hypotension induced by spinal anesthesia and neurologic emergencies.13First, this is a small sample size without comparison and therefore results are not generalizable. Second, the most commonly used PDP was epinephrine in 10 patients, while phenylephrine was only used in 1 patient. Third, this case series lacks data on patients requiring continuous vasopressor infusion after PDP. Fourth, dysrhythmias and extravasation was only monitored for 30-minutes post administration. While these PDPs are short-acting it is unclear if side effects may develop after the 3-minute time point.Based on this small case series we conclude that the use of push-dose pressors causes a significant increase in systolic, diastolic, and mean arterial blood pressure (defined as >20% change). Therefore, if implemented with strict monitoring guidelines and appropriate education, we do not anticipate significant adverse events.