AbstractBackgroundAcute Kidney Injury Research Articles

Platelet to lymphocyte ratio: can it be an early economical mortality predictor of AKI patients?

Abstract Background Acute kidney injury (AKI) affects over 13 million individuals annually worldwide, resulting in 1.7 million deaths. The potential long-term progression to chronic kidney disease (CKD) and renal failure, as well as the acute use of health care resources associated with acute kidney injury (AKI), impose enormous costs on society. The platelet-to-lymphocyte ratio (PLR) has emerged as a useful economical marker for detecting changes in platelet and lymphocyte counts owing to acute inflammatory and prothrombotic states. This study aimed to determine the PLR in patients with AKI and evaluate the in-hospital mortality. Results The median PLR was compared between the non-survivor and survivor groups, and it was determined that the non-survivor group had a significantly higher PLR. ( p < 0.001) For further subgroup analysis, the PLR was stratified into three groups: ≤ 100, 101–200, and > 200. Significantly more patients were demised in the PLR group 101–200 than in the PLR group ≤ 100, while all of the patients died in the PLR group greater than 200. The group with a PLR > 200 had a higher SOFA score > 10 (p = 0.006), a lower eGFR (p = 0.001), and higher platelet counts (p = 0.001), higher serum creatinine (p = 0.001), BUN (p < 0.001), and procalcitonin levels (p = 0.007). In multivariate Logistic regression analysis to predict the mortality outcome, PLR (OR 1.051; 95% CI, 1.016–1.087; p = 0.004) was identified as one of the significant indicators predicting AKI mortality. Other statistically significant indicators included SOFA scores (OR 2.789; 95% CI, 1.478–5.260; p = 0.002), procalcitonin levels (OR 0.898; 95% CI, 0.818–0.987; p = 0.025), and duration of hospital stay (OR 0.494; 95% CI, 0.276–0.886; p = 0.017). The ROC curve for the PLR yielded a value of 0.803 [95% CI, 0.720–0.886; p < 0.001] with the optimal cutoff value for the PLR to determine prognosis being 107.905, with a sensitivity of 82.5% and a specificity of 51.2%. Conclusion PLR plays a significant role in the early prediction of prognosis (survival or death) for patients with AKI in ICU on a short-term basis.

B-289 Acute Kidney Injury Urinary Biomarker, Neutrophil Gelatinase-Associated Lipocalin (NGAL) Analytical Performance Evaluation on Roche Cobas c502 Chemistry Platform

Abstract Background Acute kidney injury (AKI) is a sudden and serious kidney damage condition that affects more than 1.2 million people every year. KDIGO guidelines suggest serum creatinine increase as a diagnostic marker for AKI but elevation of serum creatinine levels can take up to seven days. Neutrophil gelatinase-associated lipocalin (NGAL) has been identified as an early tubular injury biomarker for AKI that is detected within three hours of AKI patients’ urine. In this study, we evaluated technical performance of BioPorto NGAL assay on Roche cobas c502 chemistry analyzer. Methods BioPorto’s (Hellerup, Denmark) particle enhanced turbidimetry immunoassay (PETIA) NGAL assay was installed on cobas c502 chemistry analyzer (Roche, Indianapolis, U.S.A) following vendor-specific application parameters with few modifications. Linearity was determined with BioPorto’s linearity material and verified by serial dilutions of a high NGAL patient urine sample. Limit of quantitation was determined in urine samples with values 20, 25 and 35 ng/mL, run in duplicate for 10 days. Precisions were determined by running urine samples containing 100 ng/mL and 400 ng/ml NGAL 20 times for within-run precision and twice a day × 10 days for between-run precision, respectively. To determine the accuracy of the NGAL method on cobas 502, 40 sample results (provided by the vendor) were compared with those measured on Siemens Atellica using BioPorto’s NGAL assay. Reference interval verification was carried out in 40 urine samples collected from healthy adult volunteer-donors. Results The linearity was found to be excellent from 0–3000 ng/mL. Limit of quantification was found at 26 ng/mL. Precision results are in the table below. Method comparison showed a slope of 0.90 and intercept of 32.9. The reference interval was verified to be <50 ng/mL (in accordance with current NGAL reference cut­off for AKI diagnosis). Conclusion Performance of BioPorto’s NGAL PETIA assay was validated in urine on cobas c502 chemistry analyzer.

Acute Kidney Injury in Polytrauma Patients in Intensive Care Unit: A Prospective Observational Study

Abstract Background Acute Kidney Injury (AKI) is a common complication of severe trauma patients and is associated with increased morbidity and mortality. Injury Severity Score (ISS) > 15 represents approximately 10% of all trauma patients in intensive care unit (ICU). The primary outcome of the study was to correlate between the AKI by using RIFLE criteria and the trauma severity by using ISS. While; the secondary outcomes were; identifying the incidence of AKI in polytrauma patients, the length of ICU and hospital stay and 28 days mortality. Methods This is a prospective observational study which was conducted during the period from May 2020 to September 2020. It Included 60 cases of polytrauma patients who have ISS>15, at Ain shams university hospitals, their ages ranged from 18-70 years. All patients’ data were recorded for: Injury Severity Score (ISS). RIFLE criteria. Length of ICU and hospital stay. 28 days mortality. Results There was no correlation between the incidence of AKI and the severity of the trauma by using ISS. Incidence of AKI the percentage was (45 %) among all the studied cases. According to RIFLE criteria, within this population, patients were classified as (21.7%) of the patients in the Risk stage; (18.3%) of the patients in Injury stage, and (5%) of the patients in Failure stage. There was statistically significant difference between AKI and No AKI regarding risk factors, percentages of sepsis, rhabdomyolysis, drugs, abdominal trauma and hypovolemic shock were higher in AKI patients than No AKI patients. There was no statistically significant difference between AKI patients and No AKI patients regarding mechanical ventilation, ICU stay, Hospital stay and 28 d Mortality. Conclusion The incidence of acute kidney injury in polytrauma patients in the intensive care unit was high and the overall mortality of our patients was as high as that reported in other studies. A better comprehension of risk factors associated with trauma-associated AKI is important, such as rhabdomyolysis, sepsis, abdominal trauma (compartment) and hypovolemic shock.

Predictive Value of Doppler Renal Resistive Index for Prediction of Acute Kidney Injury in Septic Patients in Intensive Care Unit

Abstract Background Acute kidney injury (AKI) occurs as a serious complication in septic patients. In its severe form, AKI requires renal replacement therapy, which is applied in 5–13% of intensive care units (ICU) patients. AKI is common in patients confined in ICU and remains to be associated with poor outcomes. According to the current diagnostic criteria, serum creatinine (SCr) and urine volume are used as diagnostic and staging criteria for AKI. Aim of the Work To evaluate predictive value of renal resistive index in detection of acute kidney injury. Measuring flow resistance in the renal circulation, Renal Resistive Index (RRI) could become part of vital organ function assessment using Doppler ultrasound. Patients and Methods This was a prospective descriptive study conducted on 150 ICU patients with sepsis; to evaluate prediction value of renal resistive index in detection of acute kidney injury. Measuring flow resistance in the renal circulation, RRI could become part of vital organ function assessment using Doppler ultrasound. Results We found that; the mean age of all patients was (38.4 ± 13.5) years. Regarding gender of the patients, the majority (62.7%) of patients were males; while (37.3%) were females. Regarding basic clinical data; the average MAP was (57.6 ± 14.8) mmHg, the average APACHE score was (14.6 ± 3.7), and the average SOFA score was (4.2 ± 0.92). Regarding comorbidities; (24.7%) of patients had septic shock, (20%) had DM, (34%) had HTN, and (14.7%) had IHD. Conclusion High RRI on ICU admission was a significant predictor for development of AKI stage 2 ± 3 during the first week. High RRI can be used as an early warning signal RRI, because of its high specificity. A combined score including RRI, APACHE III and fluid balance improved AKI prediction, suggesting that vasoconstriction or poor vascular compliance, severity of disease and positive fluid balance independently contribute to AKI development.

The Use of Nuetrophil Gelatinase Associated Lipocalin (NGAL) as a Novel Marker in Early Diagnosis of Hepato Renal Syndrome in Advanced Cirrhotic Patients

Abstract Background Acute kidney injury (AKI) in cirrhosis, including hepatorenal syndrome (HRS), is a common and serious complication in cirrhotic patients, leading to significant morbidity and mortality. Objective To predict value of serum and urinary NGAL as an early predictor of hepatorenal syndrome in cirrhotic patients. Patients and Methods The study was conducted on 60 participants with cirrhosis child C on Child-Pugh score, each one was investigated for both Urinary and Plasma NGAL level. Randomized controlled clinical trial. This study is a prospective, random, clinical trial conducted at Kafr El Sheikh Liver Institution Results Group I had Urinary NGAL ranged from 12 - 120, with a mean value of 61.45 ± 36.17. While group II A, ranged from 211-493 with a mean value of 379 ± 72.825. And in group II B, ranged from 306- 732 with a mean value of 438.05 ± 111.26. There was statistical difference between studied groups, p value <0.001. It was found that Urinary NGAL not only good predictor for early renal affection, but also it can differentiate between HRS and non HRS AKI due to the marked difference readings of its level in groups with renal impairment. Conclusion Both Plasma and urinary NGAL levels are markedly elevated in renal affection whatever the cause, so they are highly sensitive in detecting early renal impairment. However, the rate of elevation of plasma NGAL is so close in different types of AKI so it’s not advisable to use it alone to diagnose HRS. On the other hand, Urinary NGAL show noticeable differences between degree of elevation with different causes of AKI, so it’s somehow could be a trusted diagnostic tool to diagnose HRS.

Comparison between Levosimendan versus Beta Agonists in Preservation of Renal Function in Cardiac Surgery Patients with Low Cardiac Output Syndrome

Abstract Background Acute kidney injury post cardiac surgery in patients who develop low cardiac output syndrome (LCOS) postoperatively is a serious complication. Many studies have been performed to assess the effect of inotropic agents on cardiac function when administered postoperatively, some studies performed to evaluate the nephroprotective effect of conventional inotropic agents as compared to levosimendan. Objective To evaluate the possible nephroprotective effect of Levosimendan as compared to betaagonists in cardiac surgery patients with LCOS. Patients and Methods It is a randomized prospective comparative study at Ain Shams university hospitals from December 2020 to May 2021. A total of 60 patients who have developed low cardiac output syndrome post cardiac surgery divided into two groups of 30 patients each. Group A received beta-agonists (dobutamine 2 - 20 µ/kg/min or adrenaline 0.01 to 0.5 mcg/kg/minute) and Group B received levosimendan for 24 h at a rate of 0.1 mcg/kg/min to a target dose of 12.5 mg. we assessed the incidence of renal failure in these patients. We assessed the progress of acute kidney injury in patients who developed acute renal impairment at diagnosis of LCOS in both treatment groups. Parameters assessed include hemodynamics and renal function parameters. Results The incidence of acute kidney injury at diagnosis of LCOS postoperative was 30% (n = 9) in each group, 44% of them in the control group (n = 4) developed renal failure at discharge from ICU and none of the study group patients developed renal failure at discharge. At time of discharge from ICU the incidence of renal failure in beta – agonist group was 13.3% while the incidence in the levosimendan group was 0%. Conclusion Levosimendan has a nephroprotective effect that plays a role in preservation of renal functions and decreasing the incidence of kidney failure in patients with LCOS post cardiac surgery as compared to beta – agonists.

Effect of periprocedural furosemide-induced diuresis with matched isotonic intravenous hydration in patients with chronic kidney disease undergoing transcatheter aortic valve implantation.

Acute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI) is a serious complication which is associated with increased mortality. The RenalGuard system was developed to reduce the risk of AKI after contrast media exposition by furosemide-induced diuresis with matched isotonic intravenous hydration. The aim of this study was to examine the effect of the RenalGuard system on the occurrence of AKI after TAVI in patients with chronic kidney disease. The present study is a single-center randomized trial including patients with severe aortic valve stenosis undergoing TAVI. Overall, a total of 100 patients treated by TAVI between January 2017 and August 2018 were randomly assigned to a periprocedural treatment with the RenalGuard system or standard treatment by pre- and postprocedural intravenous hydration. Primary endpoint was the occurrence of AKI after TAVI, and secondary endpoints were assessed according to valve academic research consortium 2 criteria. Overall, the prevalence of AKI was 18.4% (n = 18). The majority of these patients developed mild AKI according to stage 1. Comparing RenalGuard to standard therapy, no significant differences were observed in the occurrence of AKI (RenalGuard: 21.3%; control group: 15.7%; p = 0.651). In addition, there were no differences between the groups with regard to 30-day and 12-month mortality and procedure-associated complication rates. In this randomized trial, we did not detect a reduction in AKI after TAVI by using the RenalGuard system. A substantial number of patients with chronic kidney disease developed AKI after TAVI, whereas the majority presented with mild AKI according to stage 1 (ClinicalTrials.gov number NCT04537325).

Epidemiology and outcomes of post-AKI proteinuria.

Acute kidney injury (AKI) has been associated with increased risks of new-onset and worsening proteinuria. However, epidemiologic data for post-AKI proteinuria was still lacking. This study aimed to determine the incidence, risk factors and clinical correlations of post-AKI proteinuria among hospitalized patients. This study was conducted in a multicenter cohort including patients aged 18-100 years with hospital-acquired AKI (HA-AKI) hospitalized at 19 medical centers throughout China. The primary outcome was the incidence of post-AKI proteinuria. Secondary outcomes included AKI recovery and kidney disease progression. The results of both quantitative and qualitative urinary protein tests were used to define post-AKI proteinuria. Cox proportional hazard model with stepwise regression was used to determine the risk factors for post-AKI proteinuria. Of 6206 HA-AKI patients without proteinuria at baseline, 2102 (33.9%) had new-onset proteinuria, whereas of 5137 HA-AKI with baseline proteinuria, 894 (17.4%) had worsening proteinuria after AKI. Higher AKI stage and preexisting CKD diagnosis were risk factors for new-onset proteinuria and worsening proteinuria, whereas treatment with renin-angiotensin system inhibitors was associated with an 11% lower risk of incident proteinuria. About 60% and 75% of patients with post-AKI new-onset and worsening proteinuria, respectively, recovered within 3 months. Worsening proteinuria was associated with a lower incidence of AKI recovery and a higher risk of kidney disease progression. Post-AKI proteinuria is common and usually transient among hospitalized patients. The risk profiles for new-onset and worsening post-AKI proteinuria differed markedly. Worsening proteinuria after AKI was associated with adverse kidney outcomes, which emphasized the need for close monitoring of proteinuria after AKI.

Evaluating renal microcirculation in patients with acute kidney injury by contrast-enhanced ultrasonography: a protocol for an observational cohort study.

Acute kidney injury (AKI) in critically ill patients has poor renal outcome with high mortality. Changes in intra-renal microcirculation and tissue oxygenation are currently considered essential pathophysiological mechanisms to the development and progression of AKI. This study aims to investigate the characteristics of contrast-enhanced ultrasonography (CEUS) derived parameters in biopsy-proven AKI patients, and examine the predictive value of these markers for renal outcome. This prospective observational study will enroll AKI patients who are diagnosed and staging following KDIGO (Kidney Disease: Improving Global Outcomes) criteria. All patients undergo a kidney biopsy and pathological tubulointerstitial nephropathy is confirmed. The CEUS examination will be performed at 0, 4 and 12weeks after biopsy to monitor renal microcirculation. The percentage decrease of serum creatinine, 4-week and 12-week eGFR (estimated glomerular filtration rate) will also be reviewed as renal prognosis. The relationship of CEUS parameters with clinical and pathological markers will be analyzed. We perform a lassologit procedure to select potential affecting variables, including clinical, laboratory indexes and CEUS markers, to be included in the logistic regression model, and examine their predictive performance to AKI outcomes. If we are able to show that CEUS derived parameters contribute to diagnosis and prognosis of AKI, the quality of life of patients will be improved while healthcare costs will be reduced. This study is retrospectively registered on the Chinese Medical Research Registration information System( https://61.49.19.26/login ) on December 31, 2021: MR-11-22-003,503. This study has been approved by the Ethics and Scientific Research Department of Peking University First Hospital.

The metabolites of de novo NAD+ synthesis are a valuable predictor of acute kidney injury.

Acute kidney injury (AKI) is often iatrogenic and potentially preventable. Reduced renal nicotinamide adenine dinucleotide (NAD+) is reported to increase the susceptibility of AKI. The present study explored the predictive value of urinary de novo NAD+ synthetic metabolites for AKI using two independent cohorts. The expression of de novo NAD+ synthetic enzymes in human kidney was examined by immunohistochemistry and single-cell transcriptomes. Urine samples were collected from two independent cohorts: the methotrexate (MTX) cohort with high-dose MTX treatment for lymphoma (n=189) and the liver transplantation cohort with orthotopic liver transplantation (n=49). Urinary metabolomics study of NAD+ de novo synthesis was performed by liquid chromatography with mass spectrometry, screening for AKI predictive biomarkers. Nephroseq database and immunohistochemistry were used to analyze kidney de novo NAD+ synthetic enzymes expression in AKI-susceptible conditions. Human proximal tubule was the main structure in the kidney that expressed the necessary enzymes for NAD+ de novo synthesis. In the MTX cohort, the urinary quinolinic acid (QA)/3-hydroxyanthranilic acid (3-OH AA) ratio before chemotherapy was significantly lower in those who developed AKI after chemotherapy compared with those who did not. This finding was consistent in the liver transplantation cohort. The area under the receiver-operating characteristic curve (AUC) of urinary QA/3-OH AA for AKI prediction was 0.749 and 0.729 in two cohorts, respectively. 3-Hydroxyanthranilic acid dioxygenase (HAAO), the enzyme catalyzing QA synthesis from 3-OH AA, decreased in AKI-susceptible diabetic kidneys. The human proximal tubules were important source of NAD+ from the de novo pathway. Reduced urinary QA/3-OH AA ratio, which possibly suggested decreased HAAO activity, could be a potential AKI predictive biomarker.

Infectious consequences of the AKI-to-CKD transition.

Acute kidney injury (AKI) is associated with short- and long-term complications but the consequences of the AKI-to-CKD transition are still poorly understood. We aimed to evaluate the association between the AKI-to-CKD transition and the long-term risk of infection. This retrospective study included patients admitted in a tertiary hospital with community-acquired AKI in 2013 and 2014 who had their estimated glomerular filtration rate (eGFR) assessed at 3months (±2weeks) after serum creatinine peaked in the AKI episode. Key exclusion criteria were baseline CKD or confounding factors (active neoplasia, primary immunodeficiency, human immunodeficiency virus, immunosuppressive drugs). The association between the AKI-to-CKD transition (defined as an eGFR <60ml/min/1.73m2 at 3months) and long-term infections (defined using clinical features, blood/urine analysis, cultures and imaging) was assessed during a follow-up of 9months (range 2-56). Among the 1731 patients admitted with AKI, 367 (21%) were included in the present analysis (64% male, 71±15years). Three months after AKI, 159 (43%) developed AKI-to-CKD transition. Baseline and post-AKI eGFR were independent predictors of AKI-to-CKD transition [hazard ratio (HR) 0.97, P=.044 and HR 0.96, P<.001, respectively].During follow-up, 153 (42%) patients developed an infection. Factors associated with infection were older age, cognitive impairment, lower post-AKI eGFR, eGFR loss from baseline to 3months and AKI-to-CKD transition. Adjusted Cox regression showed that baseline eGFR, 3-month eGFR, eGFR loss and AKI-to-CKD transition were independent predictors of the long-term risk of infection. The AKI-to-CKD transition independently predicts the long-term risk of infection following an episode of AKI.

Optimization of antimicrobial dosing in patients with acute kidney injury: a single-centre observational study.

BackgroundAcute kidney injury (AKI) is a potential complication of systemic infection. Optimizing antimicrobial dosing in this dynamic state can be challenging with sub- or supra-therapeutic dosing risking treatment failure or toxicity, respectively. Locally, unadjusted renal dosing for the first 48 h of infection is recommended.ObjectivesTo determine the outcomes associated with this dosing strategy.MethodsA retrospective cohort analysis was undertaken in patients treated for Gram-negative bacteraemia with concurrent non-filtration dependent AKI from a single-centre NHS acute hospital (April 2016–March 2020). Patient demographics, microbiology data, antimicrobial treatment and patient outcome (in-hospital mortality and kidney function) were analysed.ResultsIn total, 647 episodes of Gram-negative bacteraemia (608 patients) were included; 305/608 (50.2%) were male with median age 71 years (range 18–100). AKI was present in 235/647 (36.3%); 78/647 (12.1%) and 45/647 (7.0%) having Kidney Disease Improving Global Outcomes-defined injury (stage 2) or failure (stage 3), respectively. In-hospital 30 day mortality was 25/352 (7.1%), 14/112 (12.5%), 26/123 (21.1%) and 11/60(18.3%) in patients with normal renal function, AKI stage 1, AKI stage ≥2 and established chronic kidney disease, respectively. Recovery of renal function at Day 21 or discharge was present in 105/106 surviving patients presenting with AKI stage ≥2. Time to recovery of AKI was similar in patients receiving full, low or no aminoglycoside (3 versus 4 versus 3 days, P = 0.612) and those receiving full- and low-dose β-lactam (3 versus 5 days, P = 0.077).ConclusionsThere is a high burden of AKI in patients with Gram-negative bacteraemia. Dose adjustments of β-lactams may not be necessary in the first 48 h of infection-induced AKI and single-dose aminoglycosides may be considered for early empirical coverage.

Blackwater fever and acute kidney injury in children hospitalized with an acute febrile illness: pathophysiology and prognostic significance

BackgroundAcute kidney injury (AKI) and blackwater fever (BWF) are related but distinct renal complications of acute febrile illness in East Africa. The pathogenesis and prognostic significance of BWF and AKI are not well understood.MethodsA prospective observational cohort study was conducted to evaluate the association between BWF and AKI in children hospitalized with an acute febrile illness. Secondary objectives were to examine the association of AKI and BWF with (i) host response biomarkers and (ii) mortality. AKI was defined using the Kidney Disease: Improving Global Outcomes criteria and BWF was based on parental report of tea-colored urine. Host markers of immune and endothelial activation were quantified on admission plasma samples. The relationships between BWF and AKI and clinical and biologic factors were evaluated using multivariable regression.ResultsWe evaluated BWF and AKI in 999 children with acute febrile illness (mean age 1.7 years (standard deviation 1.06), 55.7% male). At enrollment, 8.2% of children had a history of BWF, 49.5% had AKI, and 11.1% had severe AKI. A history of BWF was independently associated with 2.18-fold increased odds of AKI (95% CI 1.15 to 4.16). When examining host response, severe AKI was associated with increased immune and endothelial activation (increased CHI3L1, sTNFR1, sTREM-1, IL-8, Angpt-2, sFlt-1) while BWF was predominantly associated with endothelial activation (increased Angpt-2 and sFlt-1, decreased Angpt-1). The presence of severe AKI, not BWF, was associated with increased risk of in-hospital death (RR, 2.17 95% CI 1.01 to 4.64) adjusting for age, sex, and disease severity.ConclusionsBWF is associated with severe AKI in children hospitalized with a severe febrile illness. Increased awareness of AKI in the setting of BWF, and improved access to AKI diagnostics, is needed to reduce disease progression and in-hospital mortality in this high-risk group of children through early implementation of kidney-protective measures.

Machine learning to predict post-operative acute kidney injury stage 3 after heart transplantation

BackgroundAcute kidney injury (AKI) stage 3, one of the most severe complications in patients with heart transplantation (HT), is associated with substantial morbidity and mortality. We aimed to develop a machine learning (ML) model to predict post-transplant AKI stage 3 based on preoperative and perioperative features.MethodsData from 107 consecutive HT recipients in the provincial center between 2018 and 2020 were included for analysis. Logistic regression with L2 regularization was used for the ML model building. The predictive performance of the ML model was assessed using the area under the curve (AUC) in tenfold stratified cross-validation and was compared with that of the Cleveland-clinical model.ResultsPost-transplant AKI occurred in 76 (71.0%) patients including 15 (14.0%) stage 1, 18 (16.8%) stage 2, and 43 (40.2%) stage 3 cases. The top six features selected for the ML model to predicate AKI stage 3 were serum cystatin C, estimated glomerular filtration rate (eGFR), right atrial long-axis dimension, left atrial anteroposterior dimension, serum creatinine (SCr) and FVII. The predictive performance of the ML model (AUC: 0.821; 95% confidence interval [CI]: 0.740–0.901) was significantly higher compared with that of the Cleveland-clinical model (AUC: 0.654; 95% [CI]: 0.545–0.763, p < 0.05).ConclusionsThe ML model, which achieved an effective predictive performance for post-transplant AKI stage 3, may be helpful for timely intervention to improve the patient’s prognosis.

Preoperative NT-proBNP and LVEF for the prediction of acute kidney injury after noncardiac surgery: a single-centre retrospective study

BackgroundAcute kidney injury (AKI) is one of the most common postoperative complications in noncardiac surgical patients, has an important impact on prognosis and is difficult to predict. Whether preoperative N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations and left ventricular ejection fraction (LVEF) levels can predict postoperative AKI in noncardiac surgical patients is unclear.MethodsWe included 3,314 patients who underwent noncardiac surgery and had measurements of preoperative NT-proBNP concentrations and LVEF levels at a tertiary academic hospital in China between 2008 and 2018. Multiple logistic regression analysis was used to construct a postoperative AKI risk prediction model for this cohort. Then, NT-proBNP concentrations and LVEF levels were included in the abovementioned model as independent variables, and the predictive ability of these two models was compared.ResultsPostoperative AKI occurred in 223 (6.72%) patients within 1 week after surgery. Preoperative NT-proBNP concentrations and LVEF levels were independent predictors of AKI after adjustment for clinical variables. The area under the receiver operating characteristic curve (AUROC) of the AKI risk predictive model established with clinical baseline variables was 0.767 (95% CI: 0.732, 0.802). When NT-proBNP concentrations and LVEF levels were added to the base model, the AUROC was 0.811 (95% CI: 0.779, 0.843). The addition of NT-proBNP concentrations and LVEF levels improved reclassification by 22.9% (95% CI 10.5–34.4%) for patients who developed postoperative AKI and by 36.3% (95% CI 29.5–43.9%) for those who did not, resulting in a significant overall improvement in net reclassification (NRI: 0.591, 95% CI 0.437–0.752, P < 0.000). The integral discrimination improvement was 0.100 (95% CI: 0.075, 0.125, P < 0.000).The final postoperative AKI prediction model was constructed, and had a good discriminative ability and fitted to the dataset.ConclusionsPreoperative NT-proBNP concentrations and LVEF levels were independently associated with the risk of AKI after noncardiac surgery, and they could improve the predictive ability of logistic regression models based on conventional clinical risk factors.Trial registrationThe protocol was preregistered in the Chinese Clinical Trial Registry (ChiCTR1900024056).

Podocyte specific deletion of PKM2 ameliorates LPS-induced podocyte injury through beta-catenin

BackgroundAcute kidney injury (AKI) is associated with a severe decline in kidney function caused by abnormalities within the podocytes' glomerular matrix. Recently, AKI has been linked to alterations in glycolysis and the activity of glycolytic enzymes, including pyruvate kinase M2 (PKM2). However, the contribution of this enzyme to AKI remains largely unexplored.MethodsCre-loxP technology was used to examine the effects of PKM2 specific deletion in podocytes on the activation status of key signaling pathways involved in the pathophysiology of AKI by lipopolysaccharides (LPS). In addition, we used lentiviral shRNA to generate murine podocytes deficient in PKM2 and investigated the molecular mechanisms mediating PKM2 actions in vitro.ResultsSpecific PKM2 deletion in podocytes ameliorated LPS-induced protein excretion and alleviated LPS-induced alterations in blood urea nitrogen and serum albumin levels. In addition, PKM2 deletion in podocytes alleviated LPS-induced structural and morphological alterations to the tubules and to the brush borders. At the molecular level, PKM2 deficiency in podocytes suppressed LPS-induced inflammation and apoptosis. In vitro, PKM2 knockdown in murine podocytes diminished LPS-induced apoptosis. These effects were concomitant with a reduction in LPS-induced activation of β-catenin and the loss of Wilms’ Tumor 1 (WT1) and nephrin. Notably, the overexpression of a constitutively active mutant of β-catenin abolished the protective effect of PKM2 knockdown. Conversely, PKM2 knockdown cells reconstituted with the phosphotyrosine binding–deficient PKM2 mutant (K433E) recapitulated the effect of PKM2 depletion on LPS-induced apoptosis, β-catenin activation, and reduction in WT1 expression.ConclusionsTaken together, our data demonstrates that PKM2 plays a key role in podocyte injury and suggests that targetting PKM2 in podocytes could serve as a promising therapeutic strategy for AKI.Trial registrationNot applicable.66jzd3p7x7ZtqB-vdEamwaVideo abstract

Prediction of acute kidney injury risk after cardiac surgery: using a hybrid machine learning algorithm

BackgroundAcute kidney injury (AKI) is a serious complication after cardiac surgery. We derived and internally validated a Machine Learning preoperative model to predict cardiac surgery-associated AKI of any severity and compared its performance with parametric statistical models.MethodsWe conducted a retrospective study of adult patients who underwent major cardiac surgery requiring cardiopulmonary bypass between November 1st, 2009 and March 31st, 2015. AKI was defined according to the KDIGO criteria as stage 1 or greater, within 7 days of surgery. We randomly split the cohort into derivation and validation datasets. We developed three AKI risk models: (1) a hybrid machine learning (ML) algorithm, using Random Forests for variable selection, followed by high performance logistic regression; (2) a traditional logistic regression model and (3) an enhanced logistic regression model with 500 bootstraps, with backward variable selection. For each model, we assigned risk scores to each of the retained covariate and assessed model discrimination (C statistic) and calibration (Hosmer–Lemeshow goodness-of-fit test) in the validation datasets.ResultsOf 6522 included patients, 1760 (27.0%) developed AKI. The best performance was achieved by the hybrid ML algorithm to predict AKI of any severity. The ML and enhanced statistical models remained robust after internal validation (C statistic = 0.75; Hosmer–Lemeshow p = 0.804, and AUC = 0.74, Hosmer–Lemeshow p = 0.347, respectively).ConclusionsWe demonstrated that a hybrid ML model provides higher accuracy without sacrificing parsimony, computational efficiency, or interpretability, when compared with parametric statistical models. This score-based model can easily be used at the bedside to identify high-risk patients who may benefit from intensive perioperative monitoring and personalized management strategies.

Bombesin receptor-activated protein exacerbates cisplatin-induced AKI by regulating the degradation of SIRT2.

Acute kidney injury (AKI) is a public health problem with no specific therapies in the clinic and the underlying pathogenesis of AKI remains obscure. Bombesin receptor-activated protein (BRAP, C6ORF89 protein) was initially discovered as a ligand for a previously orphan G-protein-coupled receptor bombesin-like receptor-3. At present, accepted biological effects of BRAP include cell cycle progression, wound repair and the activation of histone deacetylases. However, its role in kidney disease is unknown. In this study we have investigated the role of BRAP and underlying mechanisms involved in cisplatin (CP)-induced AKI. Here we used Bc004004 (homologous of C6ORF89 in mice) knockout mice and HK2 cells to investigate the effect of BRAP on AKI in vitro and in vivo. We analyzed ChIP-Seq and RNA-Seq data to search for the upstream regulators of BRAP and downstream mediators of BRAP action in AKI. Immunostaining, real-time polymerase chain reaction (PCR), co-immunoprecipitation, a dual-luciferase reporter assay and ChIP-PCR assay were applied to reveal the upstream and downstream regulation mechanism of BRAP during cisplatin-induced AKI. BRAP was downregulated in mice and human kidneys with AKI. Global Bc004004 deletion alleviated tubular cell apoptosis and necroptosis in CP-induced AKI mice, whereas local overexpression of BRAP in kidneys aggravated them. Pan-caspase inhibitor Z-VAD pretreatment attenuated CP-induced blood creatinine increase and kidney injury in wild-type mice but not in BRAP -/- mice. The activation of mixed lineage kinase like-domain was magnified by Z-VAD in CP-treated mice, especially in BRAP -/- mice. The cytoprotective effect of Z-VAD was more substantial than necrostatin-1 (Nec-1, an inhibitor of necroptosis) in CP-treated human kidney proximal tubular epithelial (HK2) cells. Furthermore, Nec-1 pretreatment reduced the CP-induced cell death in BRAP overexpression HK2 cells but did not work in cells with normal BRAP levels. We determined that CP treatment activated the nuclear factor-κB subunit P65 and inhibition of P65 increased the messenger RNA (mRNA) levels of BRAP in HK2 cells. The chromatin immunoprecipitation assay and dual-luciferase reporter gene assay verified P65 binding to the C6ORF89 promoter and reduced its mRNA expression upon CP treatment. Next we found that sirtuin 2 (SIRT2) was downregulated in CP-induced AKI and BRAP levels directly impacted the protein levels of SIRT2. Our findings further confirmed that BRAP regulates the SIRT2 protein levels by affecting SIRT2's interactions with E3 ubiquitin ligase HRD1 and subsequent proteasomal degradation. Our results demonstrated that BRAP played an important role in tubular cell apoptosis and necroptosis during CP-induced AKI. Safe and efficient BRAP inhibitors might be effective therapeutic options for AKI.

Associations between physical activity levels and renal recovery following acute kidney injury stage 3: a feasibility study

BackgroundAcute kidney injury (AKI) can lead to chronic kidney disease, which results in poor long-term outcomes. There is plausibility that increased levels of physical activity may promote renal recovery post-AKI. This study aimed to investigate associations between physical activity levels and renal recovery following stage 3 AKI, and to assess the feasibility of measuring physical activity levels in this population.MethodsForty One hospitalised patients with AKI stage 3 were enrolled. Serum creatinine and estimated glomerular filtration rate (eGFR) were collected at 12 months prior to the development of AKI, during the hospital admission when the episode of AKI stage 3 occurred, and at 1-, 3- and 6-months post discharge. All participants completed the General Practice Activity Questionnaire (GPPAQ) to assess physical activity levels. A pedometer was also worn for 7 days immediately following discharge and at 6-months post discharge to ascertain an average daily step count. Feasibility outcomes including eligibility, recruitment and retention rates, and losses to follow up were also assessed.ResultsThe average (± SD) baseline eGFR and median (IQR) serum creatinine was 71 ± 20 mL/min/1.73m2 and 85 (49) μmol/L respectively. A threefold increase in creatinine occurred during hospitalisation 436 (265) μmol/L. Greatest renal recovery occurred prior to discharge, with recovery continuing for a further three months. Inactive individuals (low GPPAQ scores) had consistently higher serum creatinine values compared to those who were active: 1 months 122 (111) μmol/L vs 70 (0) μmol/L, 6 months 112 (57) μmol/L vs 68 (0) μmol/L. Individuals with higher step counts also displayed better renal recovery 6-months post discharge (r = -0.600, p = 0.208).ConclusionsHigher levels of physical activity are associated with improved renal recovery after 6- months following an episode of stage 3 AKI. A future randomised controlled trial is feasible and would be required to confirm these initial findings.

Prediction of acute kidney injury after cardiac surgery: model development using a Chinese electronic health record dataset

BackgroundAcute kidney injury (AKI) is a major complication following cardiac surgery that substantially increases morbidity and mortality. Current diagnostic guidelines based on elevated serum creatinine and/or the presence of oliguria potentially delay its diagnosis. We presented a series of models for predicting AKI after cardiac surgery based on electronic health record data.MethodsWe enrolled 1457 adult patients who underwent cardiac surgery at Nanjing First Hospital from January 2017 to June 2019. 193 clinical features, including demographic characteristics, comorbidities and hospital evaluation, laboratory test, medication, and surgical information, were available for each patient. The number of important variables was determined using the sliding windows sequential forward feature selection technique (SWSFS). The following model development methods were introduced: extreme gradient boosting (XGBoost), random forest (RF), deep forest (DF), and logistic regression. Model performance was accessed using the area under the receiver operating characteristic curve (AUROC). We additionally applied SHapley Additive exPlanation (SHAP) values to explain the RF model. AKI was defined according to Kidney Disease Improving Global Outcomes guidelines.ResultsIn the discovery set, SWSFS identified 16 important variables. The top 5 variables in the RF importance matrix plot were central venous pressure, intraoperative urine output, hemoglobin, serum potassium, and lactic dehydrogenase. In the validation set, the DF model exhibited the highest AUROC (0.881, 95% confidence interval [CI] 0.831–0.930), followed by RF (0.872, 95% CI 0.820–0.923) and XGBoost (0.857, 95% CI 0.802–0.912). A nomogram model was constructed based on intraoperative longitudinal features, achieving an AUROC of 0.824 (95% CI 0.763–0.885) in the validation set. The SHAP values successfully illustrated the positive or negative contribution of the 16 variables attributed to the output of the RF model and the individual variable’s effect on model prediction.ConclusionsOur study identified 16 important predictors and provided a series of prediction models to enhance risk stratification of AKI after cardiac surgery. These novel predictors might aid in choosing proper preventive and therapeutic strategies in the perioperative management of AKI patients.