Diabetes mellitus and hypertension are two conditions that can coexist in obese individuals. Roux-en-Y gastric bypass (RYGB) surgery, are used to control obesity. Complications such as steatorrhea, hyperoxaluria, and decreased bone mineral density, may occur after RYGB.A 58-year-old woman referred to the emergency department complaining of pain on the right side of her lower abdomen. Her past medical history was RYGB surgery, COVID-19 with 40% pulmonary involvement, and Chronic Kidney Disease (CKD). Rapid progressive glomerulonephritis (RPGN) was predicted based on extensive laboratory test results. A kidney biopsy demonstrated oxalate nephropathy. Along with the findings from the kidney biopsy, acute tubulointerstitial nephritis with tubular injury secondary oxalosis was diagnosed.RYGB surgery and chronic kidney disease, can increase the risk of secondary oxalosis. Recent studies introduce enteric hyperoxaluria as an important marker for diagnosing end-stage kidney disease. Renal biopsy is often prescribed for absolute recognition of oxalosis. On the other hand, our patient has a recent history of COVID-19 infection. The use of anti-Covid-19 drugs in patients with renal insufficiency should be considered with caution.It is important to monitor kidney function following RYGB surgery, particularly in patients with underlying diseases such as diabetes or hypertension. •Diabetes mellitus and hypertension are two conditions that can coexist in obese individuals.•Roux-en-Y gastric bypass (gastric bypass), are used to control obesity.•Gastric bypass surgery and chronic kidney disease both increase the risk of secondary oxalosis. On the other hand, obesity independent of diabetes or hypertension can cause increase glomerular filtration and glomerular capillary pressure related to early stages of chronic kidney disease .Different strategies, including bariatric surgery, sleeve gastrectomy, and Roux-en-Y gastric bypass (gastric bypass), are used to control obesity. Roux-en-Y gastric bypass (RYGB) surgery leads to long-term weight loss and reduced incidence and remission of diabetes and hypertension. However, this process is associated with various metabolic and mineral disorders . It was Third, decreased oxalate excretion in Chronic Kidney Disease (CKD). CKD gradually impairs kidney function over months to years. Diabetes mellitus (DM) and high blood pressure are important risk factors for CKD .It was reported that, in 1–3.5 years of follow-up after RYGB, the incidence of hyperoxaluria was 42–67% . Second The fourth reason is a deficiency of a specific vitamin, such as thiamine (B1) or pyridoxine (B6). A recent study demonstrated that vitamin B6 deficiency significantly enhances the activities of hepatic glycolate oxidase and glycolate dehydrogenase, whereas vitamin B1 deficiency only amplifies the activity of the glycolate oxidase enzyme. Consequently, thiamine and pyridoxine deficiencies stimulate oxalate formation .This case report discussed acute kidney injury caused by secondary oxalosis following Roux-en-Y Gastric Bypass Surgery in conjunction with Chronic Kidney Disease (CKD).22.1This study was conducted according to the Declaration of Helsinki principles, as well as CARE guidelines and methodology . A 58-ye2. Her Medications included pregabalin 50mg/hs, lamotrigine 50mg/hs haloperidol 0.5mg/hss, quetiapine 25mg/1/2hs, levothyroxine 0.1mg/d, duloxetine10mg/d, amlodipine5mg/d, atorvastatin 20/d, vitamin B1 300mg/d, and detemir insulin 20 IU/d. Additionally, she received a remdesivir for less than ten days during the COVID-19 infection.Seven months ago, her CKD was diagnosed at stage 3 with a serum creatinine level of 2mg/dl and an estimated glomerular filtration rate (GFR) of 33mL/min/1.73 mInitial laboratory data are summarized in 2.2A biopsy of the kidney was performed. The microscopic examination revealed glomerular enlargement with mild mesangial expansion and hypercellularity in both arterioles without the formation of nodules or hyalinosis, consistent with diabetic nephropathy. Observation by light microscopy showed interstitial infiltration of lymphocytes with tubulitis that revealed interstitial nephritis and. numerous calcium oxalate crystals accumulated within tubules, resulting in tubular injury.Immunofluorescence microscopy was used to stain frozen sections containing two glomeruli with IgG, IgA, IgM, C1q, C4, C3, Fibrinogen, and polyvalent antisera that demonstrated negative immune reaction.2.3Specialists predicted rapid progressive glomerulonephritis (RPGN) based on significant laboratory test results , Table 22.4During the hospitalization period, emergency hemodialysis was performed, and the patient was treated with methylprednisolone 500mg (only the first three days) and then exchanged to prednisolone 75mg/d. Additionally, potassium citrate (UROCITRA ®) 10mEq/BD, sevelamer (Renagel ®) 800mg TDS, hydrochlorothiazide 50mg/BD, vitamin B6 10mg/BD, and hydration were prescribed following an emergency report of biopsy results. After the fourth day of hospitalization, serum creatinine and serum urea nitrogen levels decreased to 5.6mg/dL and 116mg/dL, respectively , and kid3We reported the patient with AKI on CKD and hyperoxaluria. In addition to CKD, her past medical history, included diabetes mellitus, gastric bypass surgery, COVID-19, hypertension, and hypothyroidism. Roux-en-Y gastric bypass surgery and possibility of inflammation can injure the gastrointestinal tract and cause oxalate nephropathy. Both passive diffusion and active transport can perform oxalate absorption. Oxalate crystals can cause tubular damage, interstitial fibrosis and progression of kidney disease.Fatty acids and bile salts stimulate passively oxalate fluxes .Since weight loss following bariatric surgery can affect both creatinine generation and serum creatinine levels, it has been demonstrated that bariatric surgery can cause CKD. Because serum creatinine is dependent on muscle mass in the body, it is not a sensitive indicator. Following RYGB, muscle mass decreased in order to facilitate weight loss. Recognize the extent of renal damage and renal clearance is critical ,19,20.Hypocalcemia, Hyperparathyroidism, and Hyperphosphatemia were observed in the patient. Calcium is typically bound to oxalate in the intestine, but following bypass surgery, calcium binds to fatty acids and a decrease in free intestinal calcium results in an increase in unbound and free oxalates. After absorption in the large bowel, oxalate is transferred to the kidney and dissolves in the kidney tissue. A low-oxalate diet and sufficient calcium can control secondary oxalosis because calcium acts as an oxalate chelator .Forward to the study results, serum C3 and urinary C3 measurement can be an accurate marker for glomerulonephritis because it is indicative of C3 deposition in glomerular capillary walls. Urinary C3 excretion indicated the importance of adequate countermeasures for disease control. Both low serum C3 levels and elevated urinary C3 levels may be sensitive indicators of glomerular disease and nephrotic syndrome .Recent studies introduce enteric hyperoxaluria as an important marker for diagnosing end-stage kidney disease. Renal biopsy is often prescribed for absolute recognition of oxalosis. Specific transporters have an important role in oxalate absorption or secretion, and these factors require further studies ,25.Approximately seven months before the study, the patient used remdesivir for a brief time for COVID-19 treatment. Remdesivir may cause a few complications in the kidneys and liver during medical treatment for COVID-19 infection. Remdesivir is counter-indicated in patients with liver disease and dialysis patients or those with transient AKI. Therefore, in these patients, prescribing remdesivir requires adequate caution .4This report presented an acute kidney injury caused by secondary oxalosis following gastric bypass surgery in conjunction with chronic kidney disease. Oxalosis and mild mesangial expansion were diagnosed via kidney biopsies. This recognition is critical for specialists and surgeons to keep in mind how critical it is to monitor kidney function following gastric bypass surgery, particularly in patients with underlying diseases such as diabetes or hypertension, or in patients treated with remdesivir (which excretes approximately 18%t of its dose in the urine) during COVID-19 infection.The study was approved by our local ethics committee.This research received no funding.Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request..F.GH involved in interpretation and collecting of data, and editing the manuscript. JB, ZA and S.K involved in writing, editing and preparing the final version of manuscript. All authors reviewed the paper and approved the final version of the manuscript1.Name of the registry:2.Unique Identifying number or registration ID:3.Hyperlink to your specific registration (must be publicly accessible and will be checked):The data are available with the correspondence author and can be achieved on request.Dr, Farhad Gholami.Not commissioned, externally peer-reviewed.The authors confirm that this article content has no conflict of interest.


The KDIGO risk classification is useful to screen for the presence of HF in T2DM patients. Therefore, we believe that it is necessary to carry out a systematic screening for HF in the high- and very high-risk KDIGO categories.The objectives of this study were to determine the main characteristics associated with the presence of heart failure (HF) in patients with type 2 diabetes (T2DM), and specifically to assess the association of the risk classification proposed by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines with HF. The DIABET-IC study is a multicentre, observational, prospective and analytical study in T2DM patients recruited in Spanish hospitals. This work, which features a cross-sectional design, has been conducted with the data obtained at the inclusion visit. The main dependent variable analysed was the presence of HF. The predictive variables evaluated were the demography, clinic, laboratory testing (including natriuretic peptides) and echocardiography. Patients were classified according to the number of vascular territories with atherosclerotic involvement and the KDIGO risk category. Multivariate logistic regression models were performed to determine the risk posed by the various baseline variables to present HF at the time of study inclusion. The study included 1517 patients from 58 hospitals, with a mean age of 67.3 (standard deviation (SD): 10) years, out of which 33% were women. The mean DM duration was 14 (SD: 11) years. The prevalence of HF was 37%. In a multivariate analysis, the independent predictors of HF were increased age (odds ratio (OR) per 1 year = 1.02;  It is widely known that patients with diabetes have an increased risk of cardiovascular disease (CVD) . The prePathophysiologically, the increased risk of HF in T2DM patients can be attributed to the presence of ischemic heart disease , high blood pressure and the presence of a specific diabetic cardiomyopathy . InsulinThe development of diabetic chronic kidney disease (CKD) is an additional factor that increases the likelihood of HF, mainly because it facilitates the development of atherosclerotic lesions, fibrosis, left ventricular hypertrophy and valvular calcifications . The 201Treatment with SGLT2 inhibitors has been associated with reduced risk of HF. Currently, all guidelines recommend the use of SGLT2 inhibitors in the presence of HF, especially with reduced ejection fraction ,10. SincRecent international guidelines acknowledge the relevance of HF in DM patients and recommend atrial fibrillation screening . HoweverOur hypothesis was that the probability of a T2DM patient having HF could be predicted from the existence or absence of easily identifiable clinical risk conditions. After natriuretic peptide-based screening, the performance of specific tests (echocardiogram) could confirm the diagnosis and lead to an appropriate treatment.Our objective, based on the baseline data from the DIABET-IC study , was to determine the main characteristics associated with the risk of presenting HF, with a special focus on evaluating the usefulness of the risk classification proposed by the KDIGO guidelines.The DIABET-IC study is a multicentre, observational, prospective and analytical study conducted in Spanish hospitals promoted by the Spanish Society of Diabetes (SED) and the Spanish Society of Cardiology (SEC). It has an observational, pragmatic design, with a follow-up of patients under conditions of routine clinical practice. After the initial visit, the planned follow-up was 3 years. The study was conducted in accordance with the Declaration of Helsinki, and it was approved by the Ethics Committee of Toledo Hospital Complex on 28 March 2018 (project identification code 243). All patients signed an informed consent to participate.This work, with a cross-sectional design, has been conducted with the data obtained from patients in the inclusion visit between 2018 and 2019.The inclusion criteria were patients aged 18 years or older, with type 2 diabetes diagnosed at least 1 year before the study start according to the Criteria of the American Diabetes Association (ADA) in force at that time . PatientThe subjects were to be seen in external endocrinology and/or cardiology consultation rooms. Each participating centre could include a maximum of 40 patients (20 from endocrinology and 20 from cardiology units). Recruitment was consecutive to avoid selection bias.The expected sample size was 2400 patients distributed in 60 centres. This sample size, with a confidence level of 95%, would allow the estimation of the incidence of HF for 3 years with an absolute accuracy of 0.6%. However, due to recruitment problems, the desired number of patients was not reached.The main dependent variable analysed was the presence of HF at the inclusion visit. The definition of HF was collected in the guidelines of the European Society of Cardiology (ESC)  in 2016.Demographic data , lifestyle  and concomitant pathologies: coronary artery disease (CAD), defined as a history of acute myocardial infarction, revascularization or coronary stenosis > 50%; cerebrovascular disease (CD), defined as a history of stroke or carotid stenosis > 50%; peripheral artery disease (PAD), defined as lower limb artery disease; atherosclerotic cardiovascular disease (ACVD), defined as CAD and/or CD and/or PAD, with classification of the number of affected territories into 3 categories ; chronic obstructive pulmonary disease (COPD); obstructive sleep apnoea syndrome (OSA); high blood pressure (HBP), defined as blood pressure > 140/90 mmHg or taking hypotensive drugs; atrial fibrillation (AF); fatty liver disease (FLD); and finally the Charlson score.2 and/or urinary albumin excretion rate (UAER) ≥ 30 mg/g.Data related to T2DM: disease duration; result of the ocular fundus examination, classifying the findings as normal, simple retinopathy or proliferative retinopathy; presence of neuropathy by clinical diagnosis; presence of nephropathy, defined as glomerular filtration rate (GFR) < 60 mL/min/1.73 m2; measurement of systolic and diastolic blood pressure, with the patient seated, after at least 5 min of rest, and with a cuff appropriate to the circumference of the arm.Physical examination: weight and height measurements in light clothing and without footwear, with estimation of body mass index (BMI) in the form of weight (Kg)/height (m)Fasting blood sample collection to measure: glycaemia (mg/dL); HbA1c (%); lipid profile , with non-HDL cholesterol (NHDLC) calculation  expressed in mg/dL; creatinine (mg/dL), with determination of GFR using the CKD-EPI formula; UAER in a morning urine sample, expressed in mg/g of creatinine; haemoglobin (g/dL); natriuretic peptides (BNP or NT-proBNP) expressed in pg/mL. Measurements were made in each participating hospital following routine procedures.Electrocardiogram, with rhythm assessment.Echocardiogram, with measurement of left ventricular ejection fraction (LVEF). The procedure was conducted in each of the participating centres, and patients were classified in 3 categories: preserved (≥50%), intermediate (40–49%) and reduced (<40%), with subsequent recoding into 2 categories: preserved (≥40%) or reduced (<40%).2) and UAER (expressed in mg/g of creatinine) in 4 risk categories, following the indications of the KDIGO guideline [Patients were also classified based on their GFR (expressed in mL/min/1.73 muideline :Low risk: GFR ≥ 60 and UAER < 30.Moderate risk: GFR ≥ 60 and UAER 30–300 or GFR 45–59 and UAER < 30.High risk: GFR ≥ 60 and UAER > 300 or GFR 45-59 and UAER 30–300 or GFR 30–44 and UAER < 30.Very high risk: GFR 45–59 and UAER > 300 or GFR 30–44 and UAER ≥ 30 or GFR < 30.The quantitative variables were described with their mean and standard deviation (SD) or as median with interquartile range. Qualitative variables were expressed as frequency distribution in %.2 test.A comparison of quantitative variables was made with the student’s t test on independent samples or ANOVA, or with non-parametric tests if the assumptions of normality were violated. The comparison of qualitative variables was done with Xp < 0.05) or on their clinical meaning. Highly correlated variables were not included simultaneously.Logistic regression models were performed to determine the risk conferred by the different variables to show HF at the time of study inclusion, calculating the odds ratio (OR) with its 95% confidence interval (CI). Univariate and multivariate analyses were performed. The criteria for the inclusion of the variables in the models were based on their significance in the univariate analysis , NHDLC, BMI, OSA, FLD, T2DM duration, presence of retinopathy, HbA1c, haemoglobin, KDIGO risk classification, , AF, CAD, CD and PAD . The values of natriuretic peptide tests were not included because they were involved in the diagnostic process. Finally, a sequential exclusion procedure was performed to obtain the independent risk factors of presenting HF.In a sensitivity analysis, we included in the multivariate models a variable named “origin of the patients.”p < 0.05 were considered significant.Associations with a A total of 1517 patients from 58 Spanish hospitals were included, with a mean age of 67.3 (SD 10) years, of which 33% were women. The mean T2DM duration was 14 (SD 11) years, with 42.6% of patients receiving insulin treatment. The proportion of patients with chronic complications was: 12.5% retinopathy (7.6% simple and 4.9% proliferative), 30.3% nephropathy, 5.6% neuropathy and 49% ACVD (38.2% with an affected territory and 10.8% with more than one affected territory). Regarding the KDIGO risk categories, 56.3% of the patients were low risk, 23.3% moderate, 12% high and 8.4% very high.The proportion of patients with protective cardiovascular treatments was high: 40.5% on SGLT2 inhibitors, 16.5% on GLP1 receptor agonists, 68.6% on ACEI or ARB, 58.5% on beta-blockers, 21.2% on mineralocorticoid receptor antagonists, 11% on sacubitril-valsartan, 84% on statins, 0.9% on PCSK9 inhibitors, 52.7% on antiplatelet agents and 25.7% on oral anticoagulants.Valid data were obtained for the HF classification in 1497 patients. The prevalence of HF was 37% . The prevalence of HF increased statistically significantly in patients with OSA, in patients with AF, in the presence of ACVD  and in the successive risk categories according to the KDIGO classification . The prep < 0.001). The distribution of patients with EF < 40% and ≥40% was different between both units: 25.1% and 26.5%, respectively, in cardiology vs 2.9% and 13.1%, respectively, in endocrinology (p < 0.001). There was also a higher proportion of patients with ACVD  in the cardiology sample.As expected, the prevalence of HF was higher in patients coming from the cardiology units than in those coming from the endocrinology units , decreased systolic blood pressure  and haemoglobin , the presence of OSA , KDIGO risk classification  and the presence of ACVD . Conversely, the presence of FLD was a protective factor in the limit of statistical significance . The statistical significance of FLD was lost after adjusting for origin of the patients .In the multivariate analyses, the independent predictors of the presence of HF  were incIn our work, conducted in a patient sample with T2DM coming from outpatient cardiology and endocrinology units, with a prevalence of HF of 37%, we found that the main clinical conditions independently associated with the presence of HF were age, the presence of OSA, atherosclerotic CVD and renal involvement.The prevalence of HF has increased in recent years, justified by the aging of the population and better survival after diagnosis . T2DM anSimilarly, in a meta-analysis of cardiovascular safety trials in patients with T2DM, the prevalence of HF has been detected to be between 9% and 28%, although without systematic performance of natriuretic peptide tests or echocardiogram . The preOn the other hand, the number of comorbidities associated with the presence of HF has been described as high , rangingPatients with OSA are characterized by higher blood pressure, insulin resistance and activity of the sympathetic nervous system, which favours the appearance of arrhythmias and HF . In addiPAD is the manifestation of ACVD most strongly associated with DM, and its presence may increase the risk of major cardiovascular events (MACE) even more than CAD  itself. The last aspect, and probably the most important, was that we found a great impact of the KDIGO risk classification (high- and very high-risk levels) on the prevalence of HF. This finding is biologically plausible , and hasIt was surprising to find a lower prevalence of FLD in patients with HF, since the association between hepatic fibrosis and diastolic dysfunction has been described . HoweverAs the strengths of our work, we highlight the recruitment of a large sample of T2DM patients, the systematic performance of natriuretic peptide tests and echocardiograms to accurately diagnose the prevalence of HF, and the collection of multiple demographics, clinical and analytical variables to evaluate factors associated with the presence of HF. As for the weaknesses, it should be noted that the origin of the patients implies a selection bias, that the desired sample size was not reached due to recruitment problems, that the cross-sectional design did not allow the establishment of the causal effect of the associations found and that the multicentre design did not allow the standardization of biochemical and echocardiographic measurements. In fact, the associations of FLD and lower blood pressures with HF may be related to which clinic the diabetes patients came from and not potential etiologic associations.In conclusion, we found that the KDIGO risk classification (high- and very high-risk categories), the presence of OSA and the existence of ACVD  are useful to predict the presence of HF in T2DM patients. Therefore, we consider it necessary to perform a systematic screening of HF in T2DM patients who meet these criteria to administer the appropriate treatment and improve the prognosis.


The effects of pharmacological blood pressure lowering at normal or high-normal blood pressure ranges in people with or without pre-existing cardiovascular disease remains uncertain. We analysed individual participant data from randomised trials to investigate the effects of blood pressure lowering treatment on the risk of major cardiovascular events by baseline levels of systolic blood pressure.We did a meta-analysis of individual participant-level data from 48 randomised trials of pharmacological blood pressure lowering medications versus placebo or other classes of blood pressure-lowering medications, or between more versus less intensive treatment regimens, which had at least 1000 persons-years of follow-up in each group. Trials exclusively done with participants with heart failure or short-term interventions in participants with acute myocardial infarction or other acute settings were excluded. Data from 51 studies published between 1972 and 2013 were obtained by the Blood Pressure Lowering Treatment Trialists' Collaboration . We pooled the data to investigate the stratified effects of blood pressure-lowering treatment in participants with and without prevalent cardiovascular disease , overall and across seven systolic blood pressure categories (ranging from <120 to ≥170 mm Hg). The primary outcome was a major cardiovascular event , analysed as per intention to treat.Data for 344 716 participants from 48 randomised clinical trials were available for this analysis. Pre-randomisation mean systolic/diastolic blood pressures were 146/84 mm Hg in participants with previous cardiovascular disease (n=157 728) and 157/89 mm Hg in participants without previous cardiovascular disease (n=186 988). There was substantial spread in participants' blood pressure at baseline, with 31 239 (19·8%) of participants with previous cardiovascular disease and 14 928 (8·0%) of individuals without previous cardiovascular disease having a systolic blood pressure of less than 130 mm Hg. The relative effects of blood pressure-lowering treatment were proportional to the intensity of systolic blood pressure reduction. After a median 4·15 years' follow-up (Q1–Q3 2·97–4·96), 42 324 participants (12·3%) had at least one major cardiovascular event. In participants without previous cardiovascular disease at baseline, the incidence rate for developing a major cardiovascular event per 1000 person-years was 31·9 (95% CI 31·3–32·5) in the comparator group and 25·9 (25·4–26·4) in the intervention group. In participants with previous cardiovascular disease at baseline, the corresponding rates were 39·7 (95% CI 39·0–40·5) and 36·0 (95% CI 35·3–36·7), in the comparator and intervention groups, respectively. Hazard ratios (HR) associated with a reduction of systolic blood pressure by 5 mm Hg for a major cardiovascular event were 0·91, 95% CI 0·89–0·94 for partipants without previous cardiovascular disease and 0·89, 0·86–0·92, for those with previous cardiovascular disease. In stratified analyses, there was no reliable evidence of heterogeneity of treatment effects on major cardiovascular events by baseline cardiovascular disease status or systolic blood pressure categories.In this large-scale analysis of randomised trials, a 5 mm Hg reduction of systolic blood pressure reduced the risk of major cardiovascular events by about 10%, irrespective of previous diagnoses of cardiovascular disease, and even at normal or high–normal blood pressure values. These findings suggest that a fixed degree of pharmacological blood pressure lowering is similarly effective for primary and secondary prevention of major cardiovascular disease, even at blood pressure levels currently not considered for treatment. Physicians communicating the indication for blood pressure lowering treatment to their patients should emphasise its importance on reducing cardiovascular risk rather than focusing on blood pressure reduction itself.British Heart Foundation, UK National Institute for Health Research, and Oxford Martin School. Evidence before this studyClinicalTrials.gov for randomised controlled trials investigating blood pressure-lowering drug treatment, covering the period between Jan 1, 1966, and Sept 1, 2019, with no language restrictions. We searched MEDLINE using and expanding on the MeSH terms for “hypertension”, “blood pressure”, and “antihypertensive agents” including possible variations of the terms and relevant antihypertensive drug classes. We identified several individual trials and tabular meta-analyses with conflicting or little information on the effect of blood pressure-lowering treatment stratified by baseline blood pressure and previous cardiovascular disease status. In particular, information relating to heterogeneous treatment effects at normal or high-normal blood pressure categories was scant.We searched PubMed, MEDLINE, the Cochrane central register of controlled trials, and Added value of this studyIn this collaborative project, we gathered individual participant-level data (IPD) from eligible large-scale trials of blood pressure-lowering treatment. With access to IPD from about 350 000 patients randomly assigned to treatment in 48 trials, this analysis is the largest and most detailed investigation of the stratified effects of pharmacological blood pressure-lowering. Participants were first divided into two groups: those with a previous diagnosis of cardiovascular disease and those without. Each group was then divided further into seven subgroups based on systolic blood pressure at study entry . Over an average 4 years of follow-up, a 5 mm Hg reduction in systolic blood pressure lowered the relative risk of major cardiovascular events by 10%. The risks for stroke, heart failure, ischaemic heart disease, and death from cardiovascular disease were reduced by 13%, 13%, 8%, and 5%, respectively. Relative risk reductions were proportional to the intensity of blood pressure-lowering. Neither the presence of cardiovascular disease or the level of blood pressure at study entry modified the effect of treatment.Implications of all the available evidenceThis study calls for a change in clinical practice that predominantly confines antihypertensive treatment to people with higher than average blood pressure values. On the basis of this study, the decision to prescribe blood pressure medication should not be based simply on a previous diagnosis of cardiovascular disease or an individual's current blood pressure. Rather, blood pressure medication should be viewed as an effective tool for preventing cardiovascular disease when an individual's cardiovascular risk is elevated. Recommendations that specify a minimum blood pressure threshold for initiation or intensification of treatment, or a floor level for blood pressure reduction are not substantiated by this study.Randomised trials of treatments to lower blood pressure have established that pharmacological reduction of blood pressure is an effective strategy to reduce the risk of cardiovascular events in a range of at-risk populations.Evidence for blood pressure-lowering treatment interactions with previous cardiovascular disease and baseline blood pressure values from tabular meta-analyses of randomised trials has been conflicting. A large-scale tabular meta-analysisBPLTTC; a group of the principal investigators of major randomised trials of pharmacological blood pressure-lowering treatment) provides the largest collection of individual participant-level information on blood pressure-lowering trials currently available.The current cycle of the Blood Pressure Lowering Treatment Trialists' Collaboration , and has currently access to IPD from 51 randomised trials.For this study, we included BPLTTC trials that had collected and shared information about (1) baseline blood pressure measurements, (2) primary and secondary outcomes, with the timing of events, and (3) the presence or absence of previous cardiovascular disease at baseline. Cardiovascular disease status at baseline was defined as any reports of stroke, myocardial infarction, or ischaemic heart disease before randomisation. Participants with a known diagnosis of heart failure at baseline were excluded in our analysis from trials that had included such participants, consistent with our overall protocol of excluding trials exclusively done with participants with heart failure.The primary outcome was a major cardiovascular event, defined as a composite of fatal or non-fatal stroke, fatal or non-fatal myocardial infarction or ischaemic heart disease, or heart failure causing death or requiring admission to hospital. The secondary outcomes were all-cause death, death due to cardiovascular disease, and each component of the primary outcome (as defined previously). Individual trials were categorised into two groups of intervention and comparator. For placebo-controlled trials, the placebo group was considered as the comparator and the active drug group as the intervention. For trials with two or more active groups, including trials comparing different drug classes, the group in which the blood pressure reduction was greater was considered as the intervention and the other treatment group(s) as the comparator. Trials that compared more intense versus less intense treatment were classified as the intervention and comparator groups, respectively. Detailed information about the comparison groups, trial design, participant characteristics, and level of blood pressure reduction for each trial have been reported previously.vs comparator). Data for each individual participant of each trial were harmonised before statistical analysis and merged into a single dataset to facilitate a one-stage IPD meta-analysis. We used stratified Cox proportional hazard models, with fixed treatment effects, and participants as the unit of analysis.We analysed the data as per intention to treat on the basis of the groups to which each participant had initially been assigned , 42 324 participants (12·3%) had at least one major cardiovascular event, including 13 772 participants (4·0%) with stroke, 19 452 (5·6%) with ischaemic heart disease and 7833 (2·4%) with heart failure. Of the 28 895 participants (8·4%) who died, 10 935 (3·4%) were due to cardiovascular disease. Among participants without previous cardiovascular disease at baseline, the incidence rate for developing a major cardiovascular events per 1000 person-years was 31·9 (95% CI 31·3–32·5) in the comparator group and 25·9 (25·4–26·4) in the intervention group. In participants with previous cardiovascular disease at baseline, the corresponding rates were 39·7 (95% CI 39·0–40·5) in the comparator group and 36·0 (35·3–36·7) in the intervention group, respectively . The HRsMeta-regression analyses showed the HRs for major cardiovascular events to be proportional to the magnitude of the systolic blood pressure reduction achieved at the level of a trial . Overallinteraction >0·28). Additionally, in no subgroup was the HR above 1·0, and there was no pattern of diminishing proportional effects in subgroups with lower (or higher) baseline blood pressure.When we repeated the analyses stratified by baseline cardiovascular disease status and blood pressure categories unstandardised for blood pressure reduction, the findings were broadly similar to the overall analysis . There wIn this largest source of randomised evidence of blood pressure-lowering effects on cardiovascular disease and death, we found the proportional effects of blood pressure-lowering on cardiovascular outcomes to be similar in people with or without previous cardiovascular disease and across categories of baseline systolic blood pressure down to less than 120 mm Hg. On average, a 5 mm Hg reduction of systolic blood pressure reduced the risk of a major cardiovascular event by about 10%; the corresponding proportional risk reductions for stroke, heart failure, ischaemic heart disease, and cardiovascular death were 13%, 13%, 8%, and 5%, respectively.Landmark epidemiological studies have provided compelling evidence for a log-linear relationship between blood pressure and risk of cardiovascular disease across the full physiological blood pressure range, with no threshold below which associations were shown to differ materially.25Our study fills the aforementioned gaps in evidence and provides compelling evidence from randomised trials for the beneficial effects of blood pressure-lowering treatment across the spectrum of systolic blood pressure in people with or without a known diagnosis of cardiovascular disease. Our findings do not substantiate concerns about a J-shaped association between blood pressure and cardiovascular outcomes in observational studies, and dismiss the suggestions that blood pressure-lowering treatment is only effective when blood pressure is above a certain threshold.These findings have important implications for clinical practice. Currently, the approach to prescribing antihypertensives depends on an individual's previous history of cardiovascular disease and blood pressure value. Although guidelines vary on the degree of their emphasis on these two risk factors, they invariably modify recommendations based on them. For instance, New Zealand has largely abandoned the approach of treating hypertension and recommends screening adults for overall cardiovascular risk as the first stage towards clinical decision making.Our study calls for a revision of these guidelines. The finding that a fixed and modest degree of blood pressure reduction is expected to lead to similar relative reductions in risk of cardiovascular events, regardless of current blood pressure or presence of ischaemic heart disease and stroke, calls for consideration of blood pressure-lowering treatment for any individual who has a sufficiently high absolute risk of cardiovascular disease. By considering antihypertensives as a tool for reducing cardiovascular risk, rather than simply reducing blood pressure, clinicians are no longer required to make decisions according to an arbitrary and confusing classification of hypertension. The need for and the burden of exact measurement of blood pressure is also reduced. This will not only simplify decision-making, management, and communication of treatment strategies with participants but, as shown in previous modelling studies, will also lead to more efficient care compared with alternative strategies that rely more heavily on absolute blood pressure values.27However, the fact that stratified effects were similar among the phenotypes investigated does not necessarily mean that it is worthwhile treating every patient, or that there is no particular subgroup for whom proportional risk reductions will be greater or smaller. Even in the absence of heterogeneous treatment effects by baseline blood pressure and cardiovascular disease status, clinical decisions for treating raised blood pressure will require consideration of factors such as an individual's overall risk of future cardiovascular events, potential risk of adverse effects, the cost of treatment, and patient preferences.Our results also do not mean that it is appropriate to simply aim for blood pressure reduction to a common threshold for all individuals. Determining the optimal magnitude of blood pressure reduction ideally requires a comparison of varying intensities of blood pressure reduction at differing baseline blood pressure. The design of our study is unable to directly address this question. Rather, we showed that the same fixed level of blood pressure reduction is expected to lead to similar levels of relative risk reduction across a wide range of baseline levels of blood pressure regardless of cardiovascular disease status. In our pre-specified analysis, we report effects for a 5 mm Hg systolic blood pressure reduction. However, as our meta-regression analysis shows, greater relative risk reductions are expected with larger blood pressure reductions, as is the case with multiple blood pressure lowering drugs. Thus, the feasibility of modest systolic blood pressure reductions of about 15 mm Hg across all blood pressure strata, as shown in another BPLTTC study,A key strength of our study is that, with access to the largest IPD resource from randomised trials to date, we were able to stratify the participants simultaneously by baseline cardiovascular disease status and systolic blood pressure, with still several thousand participants included in the lower blood pressure strata. For instance, in those with and without previous cardiovascular disease, 11 839 and 4794, respectively had a baseline systolic blood pressure value of less than 120 mm Hg. Overall, 42 324 had a major cardiovascular event during follow-up, among whom 5720 had a pre-randomisation systolic blood pressure less than 130 mm Hg. This total number of events is about 36% larger than a previous landmark tabular meta-analysis27This study had also some limitations. We stratified analyses based on two variables, which is often insufficient for identifying distinct groups of individuals.This study provides evidence against the widely held view that an individual's blood pressure or previous diagnosis of cardiovascular disease per se are key factors for selecting or deselecting participants for blood pressure-lowering treatment. These findings call for revision of clinical guideline recommendations globally and suggest that antihypertensive medications are better viewed as treatment options for prevention of cardiovascular disease regardless of an individual's blood pressure level and their previous history of cardiovascular disease. For people at risk of cardiovascular disease, pharmacological blood pressure-lowering treatment should become a cornerstone of risk prevention irrespective of cardiovascular disease status or blood pressure.kazem.rahimi@wrh.ox.ac.ukCorrespondence to: Prof Kazem Rahimi, Deep Medicine, Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford OX1 2BQ, UK The governance of the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) has been reported previously.British Medical Journal Heart and Public Library of Science Medicine. JC reports grants from the National Health and Medical Research Council of Australia. EC, ZB, RR, KKT, CJP, A-CP-G, and BRD declare no competing interests.MW reports personal fees from Amgen, Kyowa Kirin, and Freeline. MN and DC report grants from the British Heart Foundation (BHF). KR reports grants from BHF, the UK Research and Innovation Global Challenges Research Fund, Oxford Martin School , and National Institute for Health Research Oxford Biomedical Research Centre (University of Oxford); and personal fees from


Chronic kidney disease (CKD) is a progressive and irreversible loss of kidney function. After stage 3, there will be increased risks of hypertension, heart failure, bone disease, anemia, gastrointestinal symptoms, and progression to end-stage kidney failure without proper intervention and treatment. Compound α-ketoacid tablets (KA) administration plays an important role in clinical CKD adjunctive therapy for patients with restricted protein intake. Bailing Capsule (BC), a commonly used Chinese patent medicine for renal diseases, could regulate human immune function, repair renal tubular epithelial cells, prevent renal tubular atrophy, and reduce kidney damage to improve renal function. In this study, we try to conduct a double-blinded, randomized, controlled trial to observe the efficacy and safety of BC combined with KA in treating patients with stage 3 CKD.This is a double-blinded, randomized, controlled trial. Patients will be randomly divided into treatment group (BC and KT) and control group (BC-simulation and KT) in a 1:1 ratio according to random number table. The treatment course will be 8 weeks, and the changes of subjective symptoms, patient global assessment (PGA) scale, serum creatinine, cystatin C, and estimated glomerular filtration rate, all related adverse events, vital sign measurements, and physical examinations will be recorded. SPSS 21.0 will be used for data analysis.The results will show whether BC combined with KA could alleviate the symptoms of fatigue, anorexia, halitosis, nausea, itching, and edema, improve kidney function in patients with CKD at stage 3.OSF Registration number: DOI 10.17605/OSF.IO/24AJ7. After stage 3, the above symptoms become more obvious, with increased risks of hypertension, heart failure, bone disease, anemia, gastrointestinal symptoms, and a progress to end-stage kidney failure without proper intervention and treatment.,6Chronic kidney disease (CKD) is a progressive and irreversible loss of kidney function, with an increased prevalence in recent years.,8 With appropriate proportioned essential amino acids, KA could promptly meet the needs of human synthesis to improve the protein metabolism disorder. In addition, KA could reduce insulin resistance and increase esterase activity, thereby improving patients’ glucose and lipid metabolism.At present, the main principles for CKD are treating original diseases, low-protein diet, essential amino acids intake, and management of complications. Although it could slow down the damage to kidney function, long-term low-protein diet can aggravate malnutrition in patients. Compound α-ketoacid tablets (KA) administration plays an important role in clinical CKD adjunctive therapy for patients with restricted protein intake.,10 It is composed of Cordyceps mycelium, which is rich in a variety of trace elements, amino acids, adenosine, and cordycepin to improve blood circulation, inhibit neurotransmitter release and regulate adenylate cyclase activity. Studies have shown that BC could regulate human immune function,–13 repair renal tubular epithelial cells, prevent renal tubular atrophy, and reduce kidney damage to improve renal function.,15 Our group tried to use the combination of BC and KA to treat CKD patients, and we preliminarily found the therapy could improve the symptoms of fatigue and dizziness to improve the quality of life. However, there are few highquality studies to observe the efficacy of BCs and α-ketoacid tablets in the treatment of stage 3 CKD. In this study, we try to conduct a double-blinded, randomized controlled trial to observe the efficacy and safety of BC combined with KA in treating patients with stage 3 CKD.In China, Bailing Capsule (BC) is a commonly used Chinese patent medicine for renal diseases.22.1From June 1st, 2021 to May 31st, 2022, the double-blinded, randomized controlled trial with a registration number of DOI 10.17605/OSF.IO/24AJ7 will be conducted in the First Hospital of Hebei Medical University. The trial has been approved by the Health Research Ethics Board in the hospital. The procedure will be in accordance with the Declaration of Helsinki. The study design is shown is Figure 2.2CKD patients referring to the First Hospital of Hebei Medical University will be assessed for screening. Before randomization, a written informed consent will be signed for all the patients or or authorized persons, and they are free to discontinue the trial at any time.The inclusion criteria are as follows:1.aged 18 to 80 years’ old;2.2<estimated glomerular filtration rate<59 mL/min/1.73 m2);CKD in stage 3  >10% and hypertension (systolic blood presuure ≥170 mmHg or diastolic blood pressure ≥100 mmHg);4.complicated with hepatic impairment, infection, or malignant tumor;5.women in pregnant or lactating.2.3Patients will be randomly divided into treatment group (BC and KT) and control group (BC-simulation and KT) in a 1:1 ratio according to random number table. The physician, patients, assessors, and analysts will all be blinded to the allocation. The BC-simulation is presented in the same package, appearance, and taste with BC to maintain blinding.2.4The same initial treatment will be applied to patients in both groups with medicines to protect the kidney, reducing blood pressure, regulating lipid. Patients will also be educated to take high-quality low-protein diet and regular exercise and rest.In the treatment group, patients will take 2 g BCs  3 times daily and 2.52 g Compound α-ketoacid tablets  3 times daily simultaneously for 8 weeks.In the control group, patients will take 2 g BC-simulations  3 times daily and 2.52 g Compound α-ketoacid tablets  3 times daily simultaneously for 8 weeks.2.5The primary outcomes are the changes of subjective symptoms of fatigue, anorexia, halitosis, nausea, itching, and edema evaluated at week 0, week 4, and week 8. The corresponding score will be 2, 4, and 6, respectively, according to the degree of mild, moderate, and severe. The secondary outcomes are patient global assessment scale, serum creatinine, cystatin C, and estimated glomerular filtration rate at week 0 and 8. The patients will be followed for another 4 weeks after the treatment. The incidence and types of related adverse events, vital sign measurements, and physical examinations will also be recorded.2.6In our preliminary study, the change of subjective symptoms in the treatment group was 7.21 ± 4.36 and 4.35 ± 3.15 in the control group. Taking α as 0.05, β as 0.2 with a 2-sided test, and considering a dropout of 20%, 72 patients will be needed totally.2.7t test, or nonparametric test will be applied for the changes between the 2 groups. Repeated measurement analysis of variance or generalized linear model will be applied for repeated measurement data. P < .05 will be considered statistically significant.SPSS 21.0  will be used for data analysis. The measurement data will be expressed as mean ± standard deviation. Considering the normality and homogeneity, 3CKD refers to chronic injury caused by various primary or secondary renal diseases, and it is characterized by insidious and slow progression. In the early stages, there are generally no symptoms or the symptoms vary with different primary diseases. Without proper intervention, it will eventually develop into uremia with the progression and the deterioration of renal function to threaten patients’ life. Therefore, it is important to effectively slow down or even halt the progression of CKD in the early stage. Also, it has been reported that BCs could effectively improve the kidney function in patients with nephrotic syndrome and type 2 diabetic nephropathy.,15 Although the combination of BC and KA against CKD was rarely reported in high-quality designed trials. In this study, we try to conduct a double-blinded, randomized, controlled trial to observe whether BC combined with KA could alleviate the symptoms of fatigue, anorexia, halitosis, nausea, itching, and edema, improve kidney function in patients with stage 3 CKD. However, there are several limitations in the study. First, it is a single-centered study. Second, the study period may not be long enough to explore whether the combined treatment could delay the CKD progression.Compound KA administration could function in renoprotective effect as adjunctive therapy for CKD.Data collection: Xiuhong Hu and Jing Wang.Data curation: Xiuhong Hu, Jing Wang.Funding acquisition: Hongrui Cui.Funding support: Hongrui Cui.Investigation: Suhua Ji and Yuhong Li.Resources: Suhua Ji and Baozhen Xu.Software operating: Jing Wang and Hongjuan Yang.Software: Jing Wang, Hongjuan Yang.Supervision: Yuhong Li and Baozhen Xu.Writing – original draft: Xiuhong Hu and Jing Wang and Hongjuan Yang.Writing – review & editing: Xiuhong Hu and Hongrui Cui.


Iron overload is inevitably related to chronic kidney disease (CKD) treatment. Haemochromatosis leads to multiorgan damage and is associated with increased mortality. Primary haemochromatosis is the most common autosomal recessive disease in white populations. In most cases, the classic form of hereditary haemochromatosis is caused by mutations, mainly C282Y and H63D, in the haemochromatosis gene (HFE). Secondary haemochromatosis can be triggered by iron administration and blood transfusions. Haemochromatosis is rarely reported in kidney transplant recipients. Atypical factors may evoke haemochromatosis in patients without HFE mutations or other standard risk factors.In the current study, we present a patient who started to have haemochromatosis symptoms after kidney transplantation. A 37-year-old man after kidney transplantation from a deceased donor was admitted to the hospital due to high serum ferritin levels and impaired graft function. The patient’s past medical history included arterial hypertension, embolization of both renal arteries and necrosis of the left femoral head. Glomerulonephritis was suspected as a cause of CKD; however, severe kidney failure was diagnosed, kidney biopsy was not performed, and the patient started intermittent haemodialysis. While on dialysis to treat anaemia, the patient had received erythropoietin and iron intravenously, and the maximal serum ferritin level was 2115 ng/ml. After kidney transplantation, ferritin levels started to increase rapidly, with a maximum level of 9468 ng/ml one and a half years after surgery. His genetic study showed HFE C282Y heterozygosity. Symptoms of haemochromatosis, such as skin hyperpigmentation, elevated activity of aminotransferases, impaired glucose tolerance and heart failure, were observed. Therapeutic phlebotomy was started, and 36 procedures were performed. After treatment, graft function significantly improved, most haemochromatosis symptoms resolved, and the serum ferritin level significantly decreased.Haemochromatosis can occur in heterozygotic HFE patients after kidney transplantation. Iron administration, infections, type of immunosuppression and liver dysfunction should be considered potential triggers of haemochromatosis in this group of patients. Haemochromatosis is an iron storage disorder leading to multiple organ damage and premature death . Heavy iEnterococcus faecalis were diagnosed and treated appropriately. Eighteen months after kidney transplantation, the haemochromatosis suspicion was raised, since the ferritin concentration rose to 9468 ng/ml and signs of liver damage were observed. The activity level of alanine aminotransferase was 50–134 U/l , aspartate aminotransferase was 40–59 U/l , gamma-glutamyl transferase was 384 U/l , alkaline phosphatase was 134 U/l (limit 129 U/l) and amylase was 85 U/l (limit 53 U/l). Infection markers (including CMV DNA) and cancer markers were negative. Gastroscopy and colonoscopy did not reveal any pathology. The haptoglobin concentration was within the normal range, excluding intravascular haemolysis. Wilson’s disease was ruled out after ceruloplasmin level analysis. The patient reported poor exercise tolerance, darkening of the skin was observed on physical examination, and impaired glucose tolerance was diagnosed. Computed tomography of the abdomen revealed liver steatosis  and Epstein-Barr virus infection were negative. During 33 months of dialysis, the patient received 8200 mg of iron intravenously (from 200 mg to 500 mg per month) and two blood units for the treatment of secondary anaemia. His TS and ferritin level varied, with maximal values reported shortly before kidney transplantation of 44% and 2115 ng/ml, respectively (Fig. Iron overload is an important problem in kidney transplant recipients. Supplementation with iron secondary to erythropoiesis-stimulating agent administration in patients with CKD or on haemodialysis may have serious clinical implications. According to Lorenz et al., high serum ferritin levels and TS were observed in 9.4% of patients after kidney transplantation . AdditioPhlebotomy is the method of choice in the treatment of haemochromatosis. Other therapies, namely, erythrocytapheresis and iron binders such as desferroxamine mesylate or deferasirox, are considered alternative treatments . In patiA limitation of our study is that only HFE mutations were analysed, since testing of other genes was not available in our laboratory. However, because non-HFE mutations occur in different age groups, they were not taken under consideration for our patient.Our study presents the case of a post-kidney transplantation patient in whom haemochromatosis symptoms became clinically apparent after kidney transplantation. Repeated phlebotomies significantly improved the haemochromatosis course and prevented disease complications. Since reports about haemochromatosis in kidney transplant recipients are rare and their results remain inconclusive, more information is needed about haemochromatosis pathogenesis in this group of patients. Special care is necessary for CKD and kidney transplant patients to prevent iron overload and its consequences.


Endovascular thrombectomy (EVT) has changed the landscape of acute stroke therapy and has become the standard of care for selected patients presenting with anterior circulation large-vessel occlusion (LVO) stroke. Despite successful reperfusion, many patients with LVO stroke do not regain functional independence. Particularly, patients presenting with extremes of blood pressure (BP) or hemodynamic variability are found to have a worse clinical recovery, suggesting blood pressure optimization as a potential neuroprotective strategy. Current guidelines acknowledge the lack of randomized trials to evaluate the optimal hemodynamic management during the immediate post-stroke period. Following reperfusion, lower blood pressure targets may be warranted to prevent reperfusion injury and promote penumbral recovery, but adequate BP targets adjusted to individual patient factors such as degree of reperfusion, infarct size, and overall hemodynamic status remain undefined. This narrative review outlines the physiological mechanisms of BP control after EVT and summarizes key observational studies and clinical trials evaluating post-EVT BP targets. It also discusses novel treatment strategies and areas of future research that could aid in the determination of the optimal post-EVT blood pressure. Large vessel occlusions (LVO) account for approximately one third of ischemic strokes but contribute to more than half of all stroke-related mortality and severe disability –3. Over This narrative review aims to describe the physiological mechanisms of how BP influences outcome after EVT, provide an overview of observational studies, and discuss completed and ongoing clinical trials of BP management after EVT. We will also discuss recent advances in personalized blood pressure management approaches and suggest potential areas of future research.CBF = ABP/CVR  depends on the pressure gradient between the cerebral arteries and veins. The cerebral arterial pressure is equivalent to the systemic arterial blood pressure (ABP), while the cerebral venous pressure is equivalent to the intracranial pressure (ICP) , 10. Cer ABP/CVR , 13.Following vessel occlusion, there is a reduction in CBF to the dependent vascular territory. Below a critical threshold of ~10 ml/100 g brain tissue/min, disruption of ion homeostasis and membrane depolarization lead to a loss of neuronal electrical activity , 15. UnlIschemia-induced vasoparalysis in the penumbra leads to loss of intrinsic autoregulatory function , 20. TheTargeted BP therapies aim to maintain BP below or above a fixed threshold. However, BP is one of the most dynamic physiologic variables with significant changes during the early phase after LVO stroke. Sustained increases in BP variability (BPV) may reflect alterations in the mechanisms responsible for cardiovascular homeostasis and represent a potentially modifiable contributor to end-organ damage and poor neurological recovery after LVO stroke –30. AlthCurrent guidelines by the American Heart Association released in 2019 recommend maintaining a BP goal of ≤ 180/105 for the first 24 h after mechanical thrombectomy . These gSeveral studies have suggested that the optimal BP target may depend on the degree of recanalization , 39, 40.Whether the association between lower post-EVT BP and better functional outcome in patients with successful recanalization is causal or just a reflection of other stroke-related factors, such as better collaterals, remains unclear. However, physiological consideration and the results mentioned above have led many stroke centers to adopt a tiered approach to BP management after thrombectomy stratified by reperfusion status. An online survey regarding BP management post EVT performed across StrokeNet sites in the United States found that most institutions (39%) used a target SBP of 120–139 mmHg on recanalized patients and permissive hypertension on non-recanalized patients . HoweverSeveral observational studies have investigated the effect of differing BP treatment protocols after thrombectomy on radiographic and clinical outcomes. Goyal et al. separated patients into three groups based on post-EVT achieved SBPs of <140, <160, and <180 mmHg. Actual BP targets varied and depended on the treating physician's preference and the patient's clinical status. The investigators found that achieving an SBP goal of <160 mmHg during the first 24 h post-EVT was associated with lower odds of mortality than permissive hypertension . This stBesides BP targets, BPV has emerged as an important aspect of post-EVT hemodynamic management. Studies found that BPV is elevated in patients with larger strokes and associated with higher rates of death and disability in stroke patients that did not undergo EVT , 45. Furpost-hoc analysis of the BEST study, patients were stratified by recanalization status , and high BPV was associated with poor outcomes for patients with TICI 3 exclusively  was a prospective, randomized, multicenter, controlled, open-label trial aimed to evaluate if BP control with a goal of 100–129 mmHg could reduce the incidence of sICH and improve functional outcomes compared to a goal of 130–185 mmHg in successfully recanalized post-EVT patients . A totalSeveral ongoing prospective randomized control trials are further evaluating the impact of BP after successful EVT. The Blood pressure After Endovascular Stroke Therapy  is a phase 2 clinical trial that randomly assigns patients with TICI 2b-3 to BP targets of ≤140, ≤160, and ≤180 mmHg. These BPs will be maintained for 24-h post-EVT, and the outcomes measures will be final infarct volume at 36-h and 3-month mRS. The Outcome in patients Treated with Intraarterial Thrombectomy- Optimal Blood Pressure Control  is a clinical trial evaluating the impact of SBP targets <140 vs. <180 mmHg on 36-h sICH, 90-day mRS, and mortality on patients with successful reperfusion after EVT. Similarly, the Second Enhanced Control of Hypertension and Thrombectomy Stroke Study  trial will assign patients to an SBP target of <120 vs. 140–180 mmHg during the first 72 h after EVT to evaluate the effect on 90-day mRS. Finally, the Invasive Control of Blood Pressure in Acute Ischemic Stroke After Endovascular Therapy on Clinical Outcomes  trial will compare SBP targets of <140 and <120 mmHg on 90-day sICH and mRS. All ongoing clinical trials will evaluate patients with successful EVT with TICI 2b-3, which is achieved in over 80% of patients with modern EVT techniques. The results of these trials will provide much-needed high-quality evidence and inform blood pressure management after thrombectomy. A summary of completed and ongoing prospective studies can be found in Despite the consistent findings of better outcomes with lower post-thrombectomy BP, reducing BP to the same fixed target may be an oversimplification of the complex physiology. The neutral results of the BP TARGET trial suggest that stratification by reperfusion status may be inadequate for the heterogenous EVT patient population. A one-size-fits-all approach does not account for individual patient factors such a collateral status, infarct size, or history of hypertension. For example, a patient with chronic hypertension may have a rightward shifted autoregulatory curve , and aggBesides maintaining BP below a fixed, predetermined value, there is a strong rationale for a more personalized BP management. We recently compared fixed vs. personalized autoregulation-oriented BP thresholds after EVT . Near-inAnother easily implementable and generalizable approach to personalized BP management is currently being tested in the Effect of Individualized vs. Standard Blood Pressure Management during Mechanical Thrombectomy for Anterior Ischemic Stroke Trial . The study will compare maintaining the BP within 10% of the first MAP measured in the angiography suite vs. a fixed blood pressure goal of 140–180 mmHg. Selecting BP targets based on an individual patients' baseline BP could represent a valid method to incorporate patient-specific factors without the need for advanced monitoring. A similar approach could potentially also be implemented in the post-EVT setting.post-hoc analyses of these trials will be necessary to assess if stroke or patient characteristics have any effect on outcome.Management of hemodynamics in the post-EVT patient is complex and requires careful BP control to ensure adequate CBF to supply the ischemic penumbra while avoiding reperfusion injury. Several clinical trials are underway to evaluate different fixed BP thresholds after EVT with successful recanalization. These studies will provide insight and guidance on the optimal post-EVT BP target. Still, future Patients with high SBP trajectories during the first 24 h after mechanical thrombectomy are at increased risk of an unfavorable outcome. Future research should focus on the early identification of patients with high-risk trajectories that are most likely to benefit from intense post-EVT BP management. Autoregulation-guided blood pressure management may present an elegant alternative over the classical approach of maintaining blood pressure below a fixed, predetermined value. Clinical trials are needed to test autoregulation-based treatment strategies, including tailored pharmacologic blood pressure augmentation and lowering therapies based on patients' real-time autoregulatory status. Parallel lines of inquiry have begun in Europe targeting autoregulation in traumatic brain injury, further suggesting that this approach is timely and feasible in a multicenter clinical trial.Other approaches to post-EVT BP management include the reduction of potentially harmful BP fluctuations. There is ample evidence showing that higher BPV is associated with worse functional outcomes and increased ICH risk. Although it is unclear if this is causative or an epiphenomenon related to the stroke itself, studies aiming to decrease BPV should be pursued , 51, 53.Cerebral perfusion optimization in the immediate post-EVT period is a research priority in acute stroke. Current research is focused on elucidating the best hemodynamic biomarker for defining and monitoring the ideal BP target after stroke. Results from ongoing and future clinical trials will be critical to reduce reperfusion injury and maximize neurological recovery for all stroke patients undergoing endovascular therapy.NP conceived the review. TP drafted the manuscript. SO-G, AH, and NP made critical revisions to the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Diabetic kidney disease (DKD) is the most frequent cause of kidney failure (KF). There are large variations in the incidence rates of kidney replacement therapy (KRT). Late referral to nephrology services has been associated with an increased risk of adverse outcomes. In many countries, when patients reach severely reduced glomerular filtration rate (GFR), they are managed by multidisciplinary teams led by nephrologists. In these clinics, efforts will continue to halt chronic kidney disease (CKD) progression and to prevent cardiovascular mortality and morbidity. In patients with diabetes and severely reduced GFR and KF, treating hyperglycemia is a challenge, since some drugs are contraindicated and most of them require dose adjustments. Even more, a decision-making process will help in deciding whether the patient would prefer comprehensive conservative care or KRT. On many occasions, this decision will be conditioned by diabetes mellitus itself. Effective education should cover the necessary information for the patient and family to answer these questions: 1. Should I go for KRT or not? 2. If the answer is KRT, dialysis and/or transplantation? 3. Dialysis at home or in center? 4. If dialysis at home, peritoneal dialysis or home hemodialysis? 5. If transplantation is desired, discuss the options of whether the donation would be from a living or deceased donor. This review addresses the determinant factors with an impact on DKD, aiming to shed light on the specific needs that arise in the management and recommendations on how to achieve a comprehensive approach to the diabetic patient with chronic kidney disease. Kidney replacement therapy (KRT) may consist of either the realization of a renal transplant or the initiation of dialysis therapy.Patients with DKD have an eight-fold increased risk of cardiovascular and all-cause mortality compared to those without DM and CKD ,3,4. FurFor the evaluation of those patients who are candidates to receive a renal transplant, there are guidelines to guide the decision making process regarding the convenience of transplantation and the appropriate time to perform it . On the Based on the above, it is important to educate the healthcare community about the benefits of a referral protocol for patients with progressive kidney function decline, since late referral to nephrology services has been associated with an increased risk of adverse outcomes . For insIn this review we will address the factors that influence CKD in the patient with DM, including those that predict the occurrence of cardiovascular events and progression to kidney failure in DKD. The aim is to shed light on the specific needs that arise in the management of DKD and recommendations on how to achieve a comprehensive approach, either conservatively or through KRT. For this, the role of the nursing team as well as the collaboration between nephrologists, endocrinologists, vascular surgeons, general surgeons, interventional radiologists, nutritionists, psychologists and physical exercise specialists, among others, will be of great importance.2 per year) in DM than in healthy individuals, particularly in patients with a long duration of diabetes (more than 10 years), severely increased albuminuria, or low baseline eGFR [2 ≤ annual decline < 0 mL/min/1.73 m2) and 15% of them presented severe decline  [Due to its complex pathogenesis, DKD presents a wide clinical variability. The incidence rate of KF in type 2 DM (T2DM) is 0.29% at 10 years and 0.74% at 20 years from the diagnosis of diabetes . Howeverine eGFR . Still, 1.73 m2) .2 independently of albuminuria [Unfortunately, the traditionally employed clinical biomarkers, although very useful in the diagnosis and long-term follow-up of the disease, are usually not sensitive enough to detect early kidney injury. To illustrate, the absence of albuminuria does not exclude the presence of diabetic kidney injury or subclinical renal damage . On the uminuria . Moreoveuminuria .Numerous risk factors  have beeAs mentioned above, one of the most determinant factors in CKD progression is the time course of diabetes. Cumulative risk of KFRT was 0.29% at 10 years and 0.74% at 20 years from diagnosis of T2DM .The risk of developing DKD has a polygenetic component ,21,22. D2, the shortening of erythrocyte life biases the measurement of low HbA1c, especially in patients receiving erythropoietin-stimulating agents.Hyperglycemia is an important risk factor for the progression of albuminuria in diabetic subjects; however, its influence is more modest in the progression to kidney failure than the effect exerted by hypertension, hypercholesterolemia and genetic factors . Among p2), regardless of the presence or absence of diabetes, when comparing dapaglifozin with placebo (hazard ratio (HR), 0.61; 95% confidence interval (CI), 0.51 to 0.72; p < 0.001). Dapagliflozin has proven to be effective as a cardiovascular and renal protective treatment, showing a significant decrease in mortality, in the incidence of KFRT and in suffering a decline of at least 50% in the estimated GFR . Previously, the CREDENCE study [p < 0.001) at a median follow-up of 2.62 years. These findings show that SGLT2 inhibitors can be an effective therapy option for renal and cardiovascular protection in patients with type 2 diabetes with chronic kidney disease. Additionally, a subgroup analysis of the CREDENCE trial [2 , whose effects were maintained in those subjects with an eGFR < 30 mL/min/1.73 m2 . There was also no difference in the rate of kidney-related adverse events or AKI, associated with canagliflozin, between participants with eGFR < 30 and ≥30 mL/min/1.73 m2. The results support the use and continuation of SGLT2 inhibitors until initiation of dialysis or kidney transplantation (KT).The goals and treatments for the management of diabetes in CKD are described in the new KDIGO guidelines . CardiovCE study  analyzedCE trial  showed t2 [2, either in combination with metformin or when metformin cannot be used [2; however, in accordance with the approach followed in the CREDENCE trial [2, the SGLT2 inhibitor can be continued until initiation of kidney replacement therapy. Furthermore, when diabetic patients with CKD require additional treatment for glycemic control, or cannot use metformin and/or SGLT2 inhibitors, the KDIGO guidelines recommend glucagon-like peptide-1 receptor agonists (GLP-1 RA) as the preferred option, due to the cardiovascular and renal benefit they have proven in the recent trials [2 [2 are DPP-4 inhibitors, insulin, and thiazolidinediones [In summary, for adequate glycemic control in the diabetic patient with CKD, it is important to take into account the need for lifestyle therapy through physical exercise, nutritional intervention and weight loss. The KDIGO guidelines recommend as first-line antihyperglycemic therapy the use of metformin, as long as the GFR ≥ 30 mL/min/1.73 m2 . Metform2 ,37,38. I be used . Differe be used ,39,40,41CE trial , in thost trials ,44,45,46t trials , ADA [48rials [2 . Optionsnediones . It is i2; G2: GFR 60-89 mL/min per 1.73 m2, G3a: GFR 45–59 mL/min per 1.73 m2; G3b: GFR 30–44 mL/min per 1.73 m2; G4: GFR 15–29 mL/min per 1.73 m2; G5: GFR <15 mL/min per 1.73 m2 or treated by dialysis. (1) A. S. Levey et al., “Nomenclature for kidney function and disease: executive summary and glossary from a Kidney Disease: Improving Global Outcomes (KDIGO) consensus conference,” Journal of Nephrology, vol. 33, no. 4. pp. 639–648, 2020. (2) I. H. de Boer et al., “Executive summary of the 2020 KDIGO Diabetes Management in CKD Guideline: evidence-based advances in monitoring and treatment,” Kidney Int., vol. 98, no. 4, pp. 839–848, Octorber 2020.First-line antiglycemic medications (green) are metformin and SGLT2 inhibitor. As second-line therapy (purple) it is recommended to prioritize GLP-1 AR over other antiglycemic medications due to its cardiovascular and renal benefits. Other drugs that can be used are iDPP4, insulin, thiazolidinedione, sulfonylureas and alpha-glucosidase inhibitor. In patients with KF, iDPP4, insulin and thiazolidinedione are more suitable options. CKD, Chronic kidney disease; GFR, Glomerular filtration rate; SGLT2, Sodium-glucose cotransporter-2; GLP-1 RA, Glucagon-like peptide-1 receptor agonists; DPP-4, Dipeptidyl peptidase-4; KF, Kidney failure; KRT, Kidney replacement therapy; G1: GFR ≥90 mL/min per 1.73 mMany authors recommend a blood pressure (BP) target of 140/90 mmHg for patients with DM, regardless of CKD . In pati2, the European guidelines advise starting treatment with ACEi if there is a cardiac indication, but also advise to stop it if there are side effects. If renal function progresses to an eGFR < 15 mL/min/1.73 m2, due to the risk of a cardiovascular event or the initiation of dialysis, it is advisable to evaluate its interruption in an attempt to delay the start of dialysis [Finally, and in reference to the RAAS axis blockade, in patients with an eGFR < 30 mL/min/1.73 mp = 0.034), as well as a decreased in kidney events  in patients with GFR 25–75 mL/min/1.73 m2 [Another drug of interest is finerenone . In the FIDELIO-DKD study, it shows a decrease in the incidence of cardiovascular events  found that the association of statin plus ezetimibe significantly reduced major atherosclerotic events. The relative effect was similar when diabetes was present (23% of 9438 patients had diabetes). This study did not detect any effect of lipid-lowering therapy on the frequency of doubling of baseline serum creatinine concentration or progression to KFRT [People with diabetes and severely reduced GFR typically have significant hypertriglyceridemia, high LDL and low HDL cholesterol levels . These a to KFRT . The rol to KFRT . No effe to KFRT .Long-term high protein intake accelerates structural and functional injury in models of DKD, whereas low protein provides kidney protection . NeverthAdequate salt intake has been associated with reduced BP and improved control of albuminuria. In fact, sodium intake is the single most important factor in CKD progression and the control of hypertension. Dietary sodium is known to significantly modulate the nephroprotective response to RAAS blockade, while a persistent proteinuria is found in those subjects with high dietary sodium intake . The inc2, 95% CI, 24.42 to 22.14), along with a reduced risk of progression to KF .A recent meta-analysis including 14 trials and 1394 participants  found thEfforts to prevent and treat DKD progression factors with the available measures have not reduced the morbidity and mortality of these patients to the desired level.2. Typically, in these situations the histological injury is at the vascular and interstitial compartments rather than in the glomerular area. This presentation does not seem to depend on glycemic control and is associated with higher CV risk [Different epidemiological studies have revealed the heterogenicity of DKD features within different rates of CKD progression. Between 19% and 31% of patients may have a non-linear GFR decline . In addi CV risk .The use of predictive models of KF such as the kidney failure risk equation (KFRE), or those associated with the histological classification of diabetic nephropathy score (D-Score) can be useful. However, in DKD these tools present a lower predictive value than in the general cohort of CKD (c-statistic: 0.80 (0.74–0.86)) .In the prediction of CV events, screening for coronary disease in asymptomatic patients is not indicated. Nonetheless, the indication for coronary arteriography should not be restricted, when necessary, despite the risk of kidney injury exacerbation. A carotid and/or femoral ultrasound should be considered to assess the presence of atheromatous disease in patients without cardiovascular disease, as it predicts CV events ,68,69.The prediction of CV events and CKD progression can be interfered with by different factors. The incorporation of new drugs to CKD G4, which go beyond glycemic control, with a double objective (cardio and nephro-protection), opens up hope for the future of patients with DKD, in whom the risk of suffering from any of the two events is very high.The transition from CKD G4 to KF (G5) represents a vulnerable period for the patient with elevated risk of adverse events and multiple physiologic and psychosocial changes. It is also a period in which nephrologists must make decisions together with the patient and family members . In patiPatient education and involvement make this transition easier. A meta-analysis found that self-management support interventions may improve self-management activities . These iEffective education should cover the necessary information for the patient and family members to answer the following questions : 1. ShouWhen kidney function is failing, discussion of the different KRT modalities and selection of a specific therapy should be started promptly . There iIf there are no contraindications for KRT (patient candidacy or eligibility profile), it is not clear in subjects with diabetes whether the KRT modality  or peritoneal dialysis (PD)) selected as first-choice has a major impact on outcomes, metabolic profile, diabetes complications and technique survival of the KRT. Therefore, the patient’s preference in selecting KRT should be the driving force for kidney replacement modality. Obviously, patients should be provided with unbiased information . EducatiPhysicians have the responsibility for initiating and guiding through the advance care planning process. Information needs to be personalized, integrating how their medical and interventions would affect their life and relationships most .Kidney transplantation (KT) is the treatment of choice for the diabetic patient with KFRT, as it increases quality of life and prolongs long-term patient survival . In spit2 [2. Living donor KT has the added advantage of the reduced waiting time, thus increasing the possibilities to avoid dialysis initiation [The timing for KT is a relevant aspect to consider. Many studies demonstrate that transplantation in the predialysis phase (preemptive transplantation) is associated with an increased patient survival, both in diabetic and non-diabetic patients ,84,85,86itiation .Combined kidney-pancreas transplantation in patients with T1DM and KF brings an additional benefit associated with the normalization of glucose metabolism, the slowing down of progression of organ damage induced by diabetes , as well as a significant improvement in quality of life .Patients with diabetes have an increased surgical risk related to the severity of CV disease. As a consequence, they have a reduced survival rate compared with patients without diabetes ,91. ThisIn 2001, the NKF-KDOQI guidelines published their recommendations, indications and contraindications of peritoneal dialysis (PD)   . An obseThe associated multi-comorbidity that affects diabetic and non-diabetic patients alike may be present from the beginning of treatment, and the numerous barriers that may arise over time  must be There are no specific contraindications for performing HD in patients with DKD. However, patients with diabetes may present important complications to be taken into account. These complications are related to atherosclerosis and cardiomyopathy, which cause most morbidity and mortality, as well as problems with the vascular access . The excIn 1972, Chavanian wrote: “…there is little prospect of improving the quality of life for patients with diabetic nephropathy and renal failure, and survival is likely to be short. Dialysis for such patients may be considered as a palliative measure with little prospect of long-term survival” . Since tThere is a series of specific problems in patients with diabetes, such as intradialytic hypotension , anemia,In patients with diabetes on hemodialysis, blood glucose levels are associated not only with factors related to KF but also with HD. In patients on HD, predialysis glucose levels are used instead of fasting glucose. Glycosylated hemoglobin (HbA1c) values tend to be lower in HD patients, indicating a glycemic control apparently better than what they actually have ,124. TheSince a considerable number of hemodialysis patients are diabetic and elderly, the vascular access issue is one of the major challenges for nephrologists and vascular surgeons. Both the creation and proper development of the vascular access are crucial for adequate dialysis treatment, while ensuring adequate longevity of use, sufficient blood flow to achieve the necessary dialysis dose, and a minimal complication rate . Howevern = 166) did atherosclerosis pose a significant obstacle to AVF creation, despite requiring additional procedures. Regarding the site of AVF creation, the authors agree that the preferred site is the wrist region; however, in patients with diabetes, due to atherosclerotic changes, the elbow area is frequently used.A study by Gołębiowski et al.  analyzedAnother important study  analyzinAs a recommendation, it is important to bear in mind that a detailed and systematic preoperative study helps in the choice of the anatomical area to be preferred for the first AVF, since adequate maturation of the AVF requires a healthy vascular tree, free of calcifications. If the arteries are calcified, the elbow should be the first choice for AVF creation, as calcification at this level is less pronounced than in the wrist arteries. However, these present an increased risk of steal syndrome, as involvement of arteries distal to the elbow results in increased peripheral resistance, diverting most of the flow into the fistula, leading to hand ischemia . JenningThe EUDIAL group  reminds The increased incidence and prevalence of patients with diabetes and CKD G5 who require dialysis is a challenge to optimizing accessibility to the current available kidney replacement therapy (KRT).Home HD offers the possibility of increasing the frequency, duration of the session, tolerance, and efficacy of substitution treatment since it directly affects not only a series of very prevalent factors in patients with advanced and elderly DKD, such as BP control, ventricular hypertrophy, anemia, mineral metabolism, peripheral vascular disease, autonomic dysfunction, hemodynamic instability and nutrition but also their quality of life, with a favorable impact on survival ,139,140.International  clinicalIn patients with diabetes and CKD G5 on home HD, due to its comorbidities, special attention is required to its stability during medical follow-up. Also, is important to avoid major clinical or hemodynamic incidences during HD sessions, to have an adequate vascular access and commitment to self-care, as well as socio-family support that, on occasions, includes a caregiver committed to performing the Home HD and/or assisting it .For patients with DKD, the absolute and relative contraindications for performing home HD  are the Whilst KRT offers better results, it is our obligation to offer patients with DKD the option of home HD in the informed decision-making process. We must offer them the best adequate dialysis possible, individualized and respecting their autonomy wherever their preferences are located and their lifestyle at the center of choice.For people with diabetes, KF is a potentially devastating condition, markedly increasing cardiovascular risk and potentially leading to premature death . PatientComprehensive conservative kidney care is understood as a holistic patient-centered care that not only includes interventions to delay CKD progression and minimize complications but also provides detailed communication, shared decision-making, advance care planning, and psychological and family support; however, it does not include dialysis . Older pKnowledge of the main etiologies of CKD and the metabolic alterations and associated symptoms is an important element in providing patients with good palliative care. It should be noted that excessive decreases in blood pressure and glucose levels may be linked with severe complications in CKD G5. Approaches to managing diabetes vary. Individuals previously on insulin therapy are often required to decrease dosages, since insulin is metabolized in the renal tubular cells and has its half-life prolonged in CKD G5 . A recenIn the absence of robust evidence in favor of comprehensive conservative care in patients with diabetes, nephrologists may consider this option in older patients or in those who have higher levels of comorbidity and poorer functional status, independent of the age.When patients with DKD progress to severely reduced GFR (CKD G4), they are in a vulnerable situation in which it will be necessary to continue efforts to delay the progression to KF (CKD G5), while controlling CV risk factors and/or vascular complications associated with diabetes. It should also be borne in mind that in the situation of advanced kidney injury, less scientific evidence is available and the use of certain pharmacological tools is restricted. At the same time, it is important to recall that when the progression of kidney disease cannot be delayed, other possibilities to improve the patient’s quality of life, such as dialysis, renal transplantation or conservative management, should be explored. Therefore, a shared decision-making process between health care agents, patients and family members should be initiated at this point. In this process, the clinical circumstances and preferences of the patient should be taken into account. In certain cases, it should be considered whether comprehensive conservative care is appropriate. For all this, it is essential to have an adequate multidisciplinary team and sufficient time to devote to the patient and his or her family.


Introduction2) monitoring without special equipment  for predicting AKI after elective cardiovascular surgery requiring cardiopulmonary bypass (CPB).Novel biomarkers of acute kidney injury (AKI) are being developed and commercialized. However, none are universally available. The aim of this preliminary prospective observational study was to explore the effectiveness of intermittent urine oxygen tension  for predicting the onset of AKI was calculated. The odds ratio (OR) and 95% confidence interval (CI) of each time point were calculated using logistic regression analysis or exact logistic regression method. P < 0.05 was considered significant.Fifty patients who underwent elective cardiovascular surgery requiring CPB were enrolled in the study with written informed consent. Urine samples were intermittently collected from a urethral catheter at four points: T1, immediately after induction of general anesthesia in the operating room; T2, immediately after intensive care unit (ICU) admission; T3, six hours after ICU admission; and T4, 12 hours after ICU admission. PuOResults2 for predicting onset of AKI at the four time points were T1, PuO2 ≥ 132.4 mmHg ; T2, PuO2 ≥ 153.3 mmHg ; T3, PuO2 ≥ 130.1 mmHg ; T4, PuO2 ≥ 88.6 mmHg .Twelve patients were diagnosed with AKI (24% morbidity). The cut-off values of PuOConclusion2 values at six and 12 hours after ICU admission may be predictors of AKI, although the AUCs to predict AKI were low (0.68 and 0.64). AKI prediction by PuO2 was not possible immediately after induction of general anesthesia  and immediately after ICU admission (AUC was very low). Further studies are required to confirm the validity of intermittent PuO2 monitoring.Intermittent PuO Perioperative organ injury is a leading contributing factor to morbidity and mortality in surgical patients . Among s2) of the bladder was highly correlated with oxygen tension of the renal medulla in animal studies  [Patients scheduled for elective cardiac surgery requiring CPB at a university hospital between January 2018 and December 2019 were enrolled in the study. Patients meeting any of the following criteria were excluded: estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 mfemale)] . PatientDue to the exploratory nature of the study and the difficulty of establishing a sample size using statistical methodology, the target number of patients was tentatively set at 50. As a result, the study period was two years.Anesthesia and perfusionTM Sensor, Edwards Lifesciences, Irvine, CA) was inserted into the radial artery, and a central venous catheter  was inserted in the internal jugular vein. The arterial pressure, cardiac index (APCI), stroke volume variation (SVV), central venous pressure (CVP), and central venous oxygen saturation (ScvO2) were monitored as hemodynamic parameters. Red blood cell transfusions were performed with a target Hb >8.0 g/dL.Anesthesia was induced with intravenous administration of midazolam (0.02-0.1 mg/kg), fentanyl (1-2 μg/kg), and rocuronium (0.6-1 mg/kg), and maintained with sevoflurane (0-2%), propofol (1-6 mg/kg/h), remifentanil (0.02-0.2 μg/kg/min), fentanyl and rocuronium. An invasive arterial pressure line , a roller pump , and a hard-shell membrane oxygenator , and was primed with a mixed solution . Non-pulsatile pump flow of 2.2-2.6 L/min/m2, hematocrit of >23%, and venous oxygen saturation of >70% were maintained as target. Body temperature was maintained between 28 and 32℃ (25℃ in circulatory arrest) using a standard heater-cooler system . Cardiac arrest was induced and maintained by intermittent anterograde or retrograde cardioplegia with mixed infusion solution  and patient blood at a ratio of 4:1. After weaning from CPB and removal of the cannula, heparin was reversed with protamine. In addition to patient characteristics  and clinical signs , rotational thromboelastometry  was used to evaluate the need for fresh frozen plasma and platelet transfusions, and the amount of protamine.CPB was established by cannulation of the ascending aorta and of the superior and inferior vena cava. Heparin was administered to achieve an activated clotting time above 480 s. The CPB circuit included an arterial line filter  was inserted. The catheter was connected to a system of standard urine collection. Urine samples were anaerobically collected from a urine sampling port using a 1-ml syringe with a needle. PuO2 was measured with a blood gas analyzer  at the following four points: T1, immediately after induction of general anesthesia in the operating room; T2, immediately after intensive care unit (ICU) admission; T3, six hours after ICU admission; T4, 12 hours after ICU admission. In the present ICU, approximately 80% of the patients who were potentially eligible for the study left the ICU within 12 hours after admission, and PuO2 measurement could not be continued in the general ward because blood gas analysis could not be performed immediately after urine collection. We did not measure the data after 12 hours of ICU admission because the number of patients who could be measured was too small to allow comparison.After induction of general anesthesia, a urinary catheter with a temperature sensor (SafeedDefinition of AKISerum creatinine (sCr) was measured preoperatively, at admission to the ICU, and six and 12 hours after admission to the ICU. Thereafter, sCr was measured every 12 hours until peak out and every 24 hours after peak out for seven days after surgery. The baseline for sCr was defined as the last value before surgery. Urine output continued to be measured by storing urine for seven days after ICU discharge and removal of the urethral catheter. AKI was defined by KDIGO criteria: increase in sCr by ≥0.3 mg/dL within 48 hours; or increase in sCr to ≥1.5 times baseline within seven days after surgery; or urine output <0.5 ml/kg/h for six hours .Outcomes, confounders and bias2) and urine output were considered as potential factors affecting PuO2 . The PaO2 of a small amount of bovine blood mixed with a saline solution equilibrated under air has been reported to be 165.8 ± 1.2 mmHg [In animal studies, the baseline for PuO-50 mmHg -20, but -50 mmHg , 65.5 ± -50 mmHg , and 50 -50 mmHg . Inserti1.2 mmHg .2 is not constant unless the urine volume is >6 ml/min [2 values may be higher due to greater exposure of urine to air and the bladder wall. Ngo et al. have suggested that the confounding factors for PuO2 are high systemic PaO2 and low urine volume [PuO6 ml/min . In prev6 ml/min  and 4-6 6 ml/min . In conte volume .TM  that calculates the risk of renal injury using the product of urinary TIMP-2 and IGFBP-7 was authorized by the Food and Drug Administration in 2014 and achieved high sensitivity while maintaining acceptable specificity [2 measurement can predict postoperative AKI at intraoperative time points according to the severity and duration of the PuO2 decrease [2 measurement cannot measure the duration of PuO2 decrease, and thus is considered inferior to the diagnostic capability of continuous PuO2. However, it is possible to capture the severity of PuO2 decrease by increasing the number of measurement points, especially during CPB, and this can be done worldwide using blood gas analyzers.Numerous clinical trials have examined the sensitivity and specificity of novel acute kidney biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL) , kidney decrease . Intermi2. Furthermore, it is most important to collect urine during CPB because PuO2 is the lowest, as reported by Zhu et al. [2 values, the number of cases required exceeded the number of patients enrolled (n = 50). Therefore, the cut-off for PuO2 at each time point might not be accurately assessed. Third, although chronic kidney disease was one of the risk factors of postoperative AKI [2 measurements cannot be made in anuric patients). However, forced diuresis may lead to progression of renal damage [2). Fourth, the validity of measurements on the urine samples is not certain because a blood gas analyzer for whole blood measurement was used, although this should be an acceptable method.There are several limitations in the study, in part because it is a small preliminary observational study. First, no special equipment was used, and exposure to large amounts of air at the urine collection site leads to a high PuOu et al. . Althougu et al.  and suggtive AKI , maintail damage . Therefo2 in predicting AKI and indicates that PuO2 ≥130.1 mmHg  at six hours after ICU admission and PuO2 ≥ 88.6 mmHg  at 12 hours after ICU admission may be a predictor of AKI. However, the AUCs are low and still insufficient to predict AKI. In order to improve the accuracy of predicting AKI, it is necessary to develop a urine collection method that allows anaerobic urine collection at any time point and to increase the timing of urine collection especially during CPB.This preliminary study examined the cutoff value of PuO