Episode Of Acute Kidney Injury Research Articles

Galectin-8 counteracts folic acid-induced acute kidney injury and prevents its transition to fibrosis

Acute kidney injury (AKI), characterized by a sudden decline in kidney function involving tubular damage and epithelial cell death, can lead to progressive tissue fibrosis and chronic kidney disease due to interstitial fibroblast activation and tissue repair failures that lack direct treatments. After an AKI episode, surviving renal tubular cells undergo cycles of dedifferentiation, proliferation and redifferentiation while fibroblast activity increases and then declines to avoid an exaggerated extracellular matrix deposition. Appropriate tissue recovery versus pathogenic fibrotic progression depends on fine-tuning all these processes. Identifying endogenous factors able to affect any of them may offer new therapeutic opportunities to improve AKI outcomes. Galectin-8 (Gal-8) is an endogenous carbohydrate-binding protein that is secreted through an unconventional mechanism, binds to glycosylated proteins at the cell surface and modifies various cellular activities, including cell proliferation and survival against stress conditions. Here, using a mouse model of AKI induced by folic acid, we show that pre-treatment with Gal-8 protects against cell death, promotes epithelial cell redifferentiation and improves renal function. In addition, Gal-8 decreases fibroblast activation, resulting in less expression of fibrotic genes. Gal-8 added after AKI induction is also effective in maintaining renal function against damage, improving epithelial cell survival. The ability to protect kidneys from injury during both pre- and post-treatments, coupled with its anti-fibrotic effect, highlights Gal-8 as an endogenous factor to be considered in therapeutic strategies aimed at improving renal function and mitigating chronic pathogenic progression.

Development and external validation of a machine learning model for the prediction of persistent acute kidney injury stage 3 in multi-centric, multi-national intensive care cohorts

BackgroundThe aim of this retrospective cohort study was to develop and validate on multiple international datasets a real-time machine learning model able to accurately predict persistent acute kidney injury (AKI) in the intensive care unit (ICU).MethodsWe selected adult patients admitted to ICU classified as AKI stage 2 or 3 as defined by the “Kidney Disease: Improving Global Outcomes” criteria. The primary endpoint was the ability to predict AKI stage 3 lasting for at least 72 h while in the ICU. An explainable tree regressor was trained and calibrated on two tertiary, urban, academic, single-center databases and externally validated on two multi-centers databases.ResultsA total of 7759 ICU patients were enrolled for analysis. The incidence of persistent stage 3 AKI varied from 11 to 6% in the development and internal validation cohorts, respectively and 19% in external validation cohorts. The model achieved area under the receiver operating characteristic curve of 0.94 (95% CI 0.92–0.95) in the US external validation cohort and 0.85 (95% CI 0.83–0.88) in the Italian external validation cohort.ConclusionsA machine learning approach fed with the proper data pipeline can accurately predict onset of Persistent AKI Stage 3 during ICU patient stay in retrospective, multi-centric and international datasets. This model has the potential to improve management of AKI episodes in ICU if implemented in clinical practice.

#2379 Acute kidney injury as a key predictor of major adverse cardiovascular events in chronic kidney disease patients

Abstract Background and Aims Chronic kidney disease (CKD) significantly raises cardiovascular event risks. The influence of acute-on-chronic kidney incidents is less understood. This study examines the link between acute kidney injury (AKI) episodes and subsequent Major Adverse Cardiovascular Events (MACE) in CKD patients. Method From 2013 to 2016, the CKD-REIN cohort enrolled 3033 adults with CKD stages 3-5 (average age 67; 66% male; mean eGFR 33 mL/min/1.73m²) from 40 French outpatient nephrology clinics, reflecting national geographic and legal diversity. During a 5-year follow-up, all AKI episodes, whether inpatient or outpatient, were identified, confirmed, and categorized per KDIGO-AKI standards by an expert panel. Cardiovascular events were evaluated using clinical trial Cardiovascular and Stroke Endpoint Definitions. MACE cumulative incidences (myocardial infarction, stroke, heart failure hospitalization, cardiovascular death) post-AKI were calculated using Aalen-Johansen methods, accounting for kidney failure and death risks. The impact of the first AKI episode on MACE risk was analyzed using a multivariable Cox model, treating AKI as a time-variable and stratifying by characteristics (in/outpatient status, AKI stage, pre-renal causes, renal recovery at discharge). Factors like demographics, cardiovascular risks, CKD severity, and treatments were considered. Interaction and sensitivity analyses were performed, excluding those with prior AKI or cardiovascular disease. Results During a median follow-up of 5.2 years, 530 patients experienced an incident AKI episode. The cumulative incidence of MACE at 1 year following this initial episode of AKI was 8.1% [95% confidence interval, 6.1; 10.8], with a median time to occurrence of 6.7 months after AKI. After adjustment for multiple confounders, we observed a substantial increased hazard of MACE associated with a first episode of AKI (HR = 5.99 [4.63; 7.76], p < 0.001), and this association remained significant for each MACE component (Fig. 1A). A dose-response relationship was observed, with higher risks in more severe AKI cases (KDIGO grades 2-3) and among hospitalized versus non-hospitalized patients (Fig. 1B). This association was also observed across all subgroups, without any interaction with age, sex, nor major comorbidities (diabetes, history of AKI, or cardiovascular events), as well as in various sensitivity analyses. Overall, we estimated an attributable risk fraction of 18.1% [13.6; 22.4] for MACE associated with AKI episodes within this population. Conclusion Our study highlights a strong dose-response relationship between incident AKI events and the risk of subsequent major cardiovascular events in CKD patients. These findings suggest that AKI may not only be a marker of increased cardiovascular risk but also a potential mediator of this risk. From a clinical perspective, these results underscore the importance of close monitoring and management of AKI in CKD patients to reduce the risk of MACE. This study improves our understanding of the interplay between renal and cardiovascular health, emphasizing the need for integrated care approaches in this high-risk population.

#2705 Hypertension as a risk factor for mortality and the development of chronic kidney disease after an episode of acute kidney injury in the elderly

Abstract Background and Aims Acute kidney injury (AKI) is a real public health problem due to its severity and its consequences in the short, medium and long term. Hypertension is a very common disease in our country. The association between hypertension and acute and chronic renal failure is not well studied in our country, and given the lack of data, we proposed to carry out this study and even more so the elderly, who are fragile subjects with multiple illnesses. Method We undergone a retrospective study which was carried out in the nephrology department of Fattouma Bourguiba hospital in Monastir. We included patients aged > 65 years, who had an AKI with full recovery who had been hospitalized between January 2002 and December 2015. Our study aimed to assess the impact of hypertension on mortality and the development of chronic kidney disease (CKD) after an episode of AKI. Results Our population was made up of 67 men and 60 women, 30.1% had multiple comorbidities. Pre renal Aki represented the predominant mechanism of AKI which was retained in our study with a rate of 40% and dehydration as the main aetiology in 70 patients. In the short term, 15 patients had progressed to CKD. The mean overall survival in our study was 159 months with a high risk of mortality in elderly (patients aged >65 years), who had multiple comorbidities, hypertensive, diabetics, with vascular disease, Charlson Comorbidity index >5, who presented with hyperkalaemia >5.5 and pre renal mechanism of the AKI episode. In the medium term and the long term, 4 and 2 patients developed CKD respectively. Hypertension was a factor in poor prognosis and mortality in elderly subjects after an episode of acute kidney injury (p=0.005). Conclusion Hypertension is a real public health problem impacting the short, medium and long term prognosis of patients who have had an episode of AKI with full recovery.

#785 The novel fibrosis biomarker LG1M is prognostic for long-term readmission after AKI

Abstract Background and Aims People who survive Acute Kidney Injury (AKI) experience increased risk of long-term adverse outcomes, including a significantly elevated rate of readmission to hospital. This may be related to the pathophysiological consequences of AKI, including extracellular matrix (ECM) remodeling in the kidneys and other organs. Tools to monitor the long-term health risk of patients after AKI are needed to improve patient outcome. Here, we investigated the potential of the novel ECM remodeling biomarker LG1M, reflecting laminin degradation mediated by MMP-9, as a prognostic marker for readmission after AKI. Method We measured LG1M in plasma samples collected 1 year after the episode of AKI using the nordicLG1MTM ELISA assay in plasma samples from 791 patients from the AKI Risk in Derby (ARID) study, who were then followed prospectively until year 3. 390 of the patients had been hospitalized for an episode of AKI and 401 patients who did not sustain AKI were included as controls (non-AKI). Correlation of LG1M levels with age, serum creatinine, eGFR, PCR, ACR, and CRP was tested with Spearman rank correlation (all variables measured at year 1). Uni- and multivariate Cox regression analysis was used to analyze the association of LG1M with the risk of readmission. Results LG1M levels were significantly higher in the AKI group (median [IQR] = 31.9 [25.7-42.8] ng/mL) compared to the control group (median [IQR] = 30.3 [24.9-37.2] ng/mL, P < 0.01). In the AKI group, LG1M correlated with age (r = 0.16, P < 0.01), serum creatinine (r = 0.33, P < 0.0001), eGFR (r = −0.35, P < 0.0001), and ACR (r = 0.23, P < 0.0001). In the control group, LG1M only correlated with serum creatinine (r = 0.22, P < 0.0001) and eGFR (r = −0.22, P < 0.0001). By year 3, 265 out of 390 patients in the AKI group and 258 out of 401 patients in the control group were readmitted (Chi-squared test, P = 0.28). In a univariate Cox model with readmission as outcome, LG1M was significant associated with readmission in the AKI group (HR [95% CI] = 1.007 [1.001-1.013], P < 0.05) but not in the control group (HR [95% CI] = 1.005 [0.997-1.013], P = 0.23). When adjusting for age, sex, ACR, and eGFR measured at year 1 as well as baseline CKD and diabetes status, LG1M lost it significance in the AKI group (HR [95% CI] = 1.004 [0.998-1.011], P = 0.22) and was still non-significant in the control group (HR [95% CI] = 1.002 [0.994-1.011], P = 0.57). Conclusion In this study, we showed that the novel biomarker LG1M is prognostic for readmission in patients after AKI. Our findings may indicate that this biomarker, reflecting laminin degradation, can be used as a novel post-AKI biomarker that can help assess patients’ long-term health risks.

#594 Long-term risk of incident/progressive chronic kidney disease, or end-stage kidney disease post-acute kidney injury: systematic review, meta-analysis

Abstract Background and Aims Little is known about which patients to follow-up after an episode of acute kidney injury (AKI) for future risks. The aim of this review is to assess the association between AKI and the incidence or progression of chronic kidney disease (CKD) or end-stage kidney disease (ESKD), stratified by subcategories of AKI-stages, -durations, and clinical settings. Method A systematic search of the literature in PubMed and Embase was performed by two reviewers to identify studies that examined CKD incidence (development of CKD stage ≥3), CKD progression (worsening of kidney function in patients with CKD stage ≥3), or ESKD, in patients with AKI versus patients without AKI. The risk of bias was assessed using the Newcastle-Ottawa Scale. Relative effect estimates (odds and hazard ratios) were pooled using a random effects model. Results In total, 48 retrospective and 13 prospective studies, encompassing 140.985 patients with AKI, were included in this review. All the studies were of moderate or high quality. The pooled effect ratio was 3.36 (95% confidence interval (CI) 2.68-4.03) for CKD incidence (n = 31 studies). This remained 3.40 (95% CI 1.79-5.00) in a sub analysis including patients with a recovered kidney function post-AKI, and 1.49 (95% CI 1.44-1.55) in a sub analysis including patients with an AKI lasting less than 3 days (Fig. 1). Overall, the effect ratio for CKD progression (n = 11 studies) was 1.70 (95% CI 1.38-2.01) and 3.81 (95% CI 2.58-5.04) for ESKD (n = 24 studies). The increased risk of these two outcomes were not seen in the sub analyses only including patients with AKI lasting less than 3 days. Overall, there is an observable higher risk for CKD incidence, CKD progression, and ESKD with increased AKI staging, although not always statistically significant. Minimal variations were observed across clinical settings. Conclusion In our review, including over 60 studies, we found that AKI was associated with an increased risk of CKD incidence, CKD progression, and ESKD. Patients with higher AKI-stages had even larger risks. Notably, even brief episodes of AKI (lasting less than 3 days) were associated with a higher risk of CKD incidence compared to patients without AKI. In contrary, the risk for ESKD is not enlarged in a sub analysis including patients with recovered kidney function compared to patients without AKI. These result warrant close monitoring of the kidney function post-AKI, specifically in patients with AKI lasting 3 days or longer. Future research should focus more on the risk of CKD progression in order to tailor follow-up care in these more vulnerable patients.

#2974 Serial multiparametric magnetic resonance imaging in a prospective cohort of patients with acute kidney injury

Abstract Background and Aims Recovery from acute kidney injury (AKI) is traditionally measured using serum creatinine but this can often over-estimate the degree of renal recovery. It is known, however, that failure of recovery of serum creatinine 90 days after AKI strongly associates with subsequent long-term reductions in renal function making it an important clinical timepoint. Magnetic resonance imaging (MRI) is an imaging modality with promise to improve the understanding and characterisation of renal pathophysiology. In a single multiparametric MRI (mpMRI) scan, multiple measures can assess renal morphology, tissue microstructure (T1 relaxation time and diffusion-weighted-imaging (DWI)), oxygenation, perfusion and blood flow. We previously published the first study of renal mpMRI at the time of AKI and during follow up, this showed increased total kidney volume (TKV) and T1 as a measure of inflammation/fibrosis at the time of AKI which remained elevated in some participants at 3 and 12 months despite normalisation of serum creatinine. This study aimed to assess the degree of change between 30 and 90 days post AKI, as the first 90 days after AKI appear to be the important in terms of outcomes. Method Prospective observational study of 10 participants with AKI of all stages recruited at the time of AKI and followed up with monthly bloods and urine. MRI scans were collected on a Philips Ingenia 3T at day 30-60 and day 90. The 1-hour protocol included: T2-weighted scans for automated segmentation to compute total kidney volume (TKV), as well as T1 & T2 mapping, DWI, ASL and phase contrast MRI for kidney perfusion and blood flow, and TRUST-MRI and BOLD R2* for kidney oxygenation, and MRE for stiffness. Results 10 participants were scanned at 2 timepoints, (mean day 45 for 1st scan, 95 for 2nd scan). Baseline characteristics are summarised in Table 1 along with key clinical measures in Table 2. 2 participants had CKD at baseline. Despite a range of peak creatinine values and AKI stages the majority of participants serum creatinine normalised to within 20% of baseline by 30 days (v3) (Fig. 1). Fig. 2 shows the TKV for AKI patients across the 2 visits as compared with healthy values. Despite normalisation of biochemistry, 5 participants had enlarged TKV. The predominant AKI aetiology for these patients was sepsis. Across all participants there is little dynamic change between visits. The participant with the small TKV across both visits had pre-existing CKD, as well as the highest peak creatine. The participant did not recover renal function by day 90 (Figs 1(j) and 2). Conclusion Despite recovery of biochemistry, at least half of this AKI cohort had abnormal MR measures at that persisted through one and three months after the AKI episode. There is a trend towards larger TKV in patients with AKI due to sepsis, which needs to be explored in a larger cohort. Analysis of more parameters as well as the addition of liquid biomarkers will enrich these preliminary findings.

#462 Initiation of SGLT2i vs GLP1-RA and incidence of AKI in persons with type 2 diabetes mellitus

Abstract Background and Aims Adverse kidney outcomes, including acute kidney injury (AKI), are frequent complications in people with diabetes mellitus type 2. In large placebo-controlled randomized trials, both sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) have shown efficacy in reducing the risk of kidney outcomes; however, no trial has compared the kidney protective effects of these drug classes head-to-head. We therefore conducted an emulated target trial to compare the effect of SGLT2i to that of GLP1-RA on the incidence of AKI. Method Using routinely collected data from nationwide Danish population-based registries, we included all adults with diabetes mellitus type 2 initiating SGLT2i or GLP1-RA in 2015-2020. Patients with prevalent kidney failure (defined as eGFR < 15 mL/min/1.73m2, dialysis, or kidney transplant), and patients initiating GLP1-RA marketed specifically for treatment of obesity were excluded. We assessed demographic and diabetes-related baseline characteristics along with comorbidities and comedication. We used propensity scores, estimated by logistic regression, to compute stabilized inverse probability of treatment weights, which were applied in all analyses to reduce confounding. Using an intention to treat approach, we followed patients from treatment initiation until the first of death, emigration, or end of follow-up (31 December 2021). Using creatinine measurements from in- and outpatient settings, we applied the KDIGO definition of AKI to record each episode of AKI during follow-up. We estimated the risk of a first AKI episode over time using the Aalen-Johansen estimator. Furthermore, to estimate the mean number of AKIs over time, i.e., including recurrent AKIs, we used the mean cumulative count estimator. Both estimators account for the competing risk of death. Comparing SGLT2i to GLP1-RA, we reported differences in risks and counts at 1, 3 and 5 years of follow-up. Finally, we estimated all-cause mortality using the Kaplan-Meier estimator. We used bootstrapping to obtain 95% confidence intervals (95% CI). Results We included 68 010 individuals, of which 44 034 (65%) initiated SGLT2i, and 23 976 (35%) initiated GLP1-RA. Initiators of SGLT2i were slightly older (median age 63 vs 62 years) and more often male (63% vs 56%) than initiators of GLP1-RA, but with similar diabetes duration (7 vs 7 years). The annual number of initiators of each drug in Denmark increased over the study period. Compared to GLP1-RA, initiators of SGLT2i generally had better estimated glomerular filtration rate (eGFR) at baseline (9% vs 18% had eGFR < 60 mL/min/1.73m2), more frequently used metformin (91% vs 84%), but less frequently insulin (11% vs 28%). Initiators of SGLT2i had a lower prevalence of hospital-diagnosed retinopathy (7% vs 9%), neuropathy (5% vs 6%), and obesity (13% vs 23%) than initiators of GLP1-RA. After inverse probability of treatment weighting, each variable was well balanced with absolute standardized mean differences below 0.02. During a median follow-up of 2.8 years, the weighted absolute risks of first time AKI at 1, 3, and 5 years were 4.8%, 11.2%, and 17.0% for initiators of SGLT2i, and 5.4%, 12.3%, and 19.1% for initiators of GLP1-RA, resulting in AKI risk differences of −0.6% (95% CI: −1.0% to −0.3%), −1.0% (95% CI: −1.7% to −0.5%), and −2.0% (95% CI: −3.0% to −1.1%). The mean cumulative counts showed a similar pattern, with SGLT2i initiators experiencing slightly fewer AKI episodes than GLP1-RA initiators on average (Fig. 1). After 5 years, an estimated 10.3% of SGLT2i initiators and 9.6% of GLP1-RA initiators had died, resulting in a risk difference of 0.7% (95% CI: -0.1% to 1.5%). Conclusion People with diabetes mellitus type 2 who initiated SGLT2i had slightly lower weighted incidence of AKI over 5 years than those initiating GLP1-RA.

Seeing and Sensing the Hepatorenal Syndrome (HRS): The Growing Role of Ultrasound-Based Techniques as Non-Invasive Tools for the Diagnosis of HRS.

More than half of patients hospitalized with liver cirrhosis are dealing with an episode of acute kidney injury; the most severe pattern is hepatorenal syndrome due to its negative prognosis. The main physiopathology mechanisms involve renal vasoconstriction and systemic inflammation. During the last decade, the definition of hepatorenal syndrome changed, but the validated criteria of diagnosis are still based on the serum creatinine level, which is a biomarker with multiple limitations. This is the reason why novel serum and urinary biomarkers have been intensively studied in recent years. Meanwhile, the imaging studies that use shear wave elastography are using renal stiffness as a surrogate for an early diagnosis. In this article, we focus on the physiopathology definition and highlight the novel tools used in the diagnosis of hepatorenal syndrome.

The association between mean arterial pressure and acute kidney injury reversal among patients with decompensated cirrhosis.

This study informs how mean arterial pressure (MAP) impacts acute kidney injury (AKI) recovery among all patients hospitalized with cirrhosis, regardless of etiology. We identified incident AKI episodes among subjects in our cohort of patients with decompensated cirrhosis. AKI was defined as a ≥50% increase in creatinine from an outpatient baseline (≥7 days prior) that required hospitalization. Linear mixed effects models were completed to determine the impact between AKI recovery, MAP, and time. To determine the impact of MAP on AKI reversal, we completed time-dependent Cox regression models with time beginning at the time of peak creatinine and ending at death, discharge, or AKI reversal, among those hospitalized with AKI and those with persistent AKI (≥48h) We identified 702 hospitalized patients with cirrhosis with AKI. We found those with AKI reversal had, on average, higher MAP (2.1mmHg, p <0.05) and a greater increase in MAP over time (0.1mmHg per hour, p <0.001). Among all 702 hospitalized patients with AKI and adjusted for confounders, each 5mmHg increase in MAP was associated with 1.07× the hazard of AKI reversal ( p <0.01). Similarly, among those with persistent AKI after adjusting for confounders, each 5mmHg increase in MAP was associated with a 1.19× greater likelihood of AKI reversal ( p <0.001). Our data demonstrate that MAP significantly increases the likelihood of AKI recovery regardless of severity or injury or AKI phenotype. We believe these data highlight the importance of MAP as a clinical tool to promote kidney function recovery among patients with cirrhosis hospitalized with AKI.

Acute kidney injury following treatment with CD19-specific CAR T-cell therapy in children, adolescent, and young adult patients with B-cell acute lymphoblastic leukemia.

CD19-specific chimeric antigen receptor (CAR) T-cell therapy has shown promising disease responses in patients with high-risk B-cell malignancies. However, its use may be related to complications such as immune-mediated complications, infections, and end-organ dysfunction. The incidence of post-CAR T-cell therapy acute kidney injury (AKI) in the children, adolescent, and young adult (CAYA) patient population is largely unreported. The objectives of this study were to determine the incidence of AKI in CAYA patients with high-risk B-cell malignancies treated with CD19-CAR T-cell therapy, evaluate potential risk factors for developing AKI, and determine patterns of kidney function recovery. We conducted a retrospective analysis of 34 CAYA patients treated with CD19-CAR T-cell at a single institution. There was a cumulative incidence of any grade AKI by day 30 post-infusion of 20% (n = 7), with four cases being severe AKI (stages 2-3) and one patient requiring kidney replacement therapy. All episodes of AKI developed within the first 14days after receiving CAR T-cell therapy and 50% of patients with AKI recovered kidney function to baseline within 30days post-infusion. No evaluated pre-treatment risk factors were associated with the development of subsequent AKI; there was an association between AKI and cytokine release syndrome and neurotoxicity. We conclude that the risk of developing AKI following CD19-CAR T-cell therapy is highest early post-infusion, with most cases of AKI being severe. Frequent monitoring to facilitate early recognition and subsequent management of kidney complications after CD19-CAR T-cell therapy may reduce the severity of AKI in the CAYA patient population.

Interpretable machine learning-based individual analysis of acute kidney injury in immune checkpoint inhibitor therapy.

Acute kidney injury (AKI) is a critical complication of immune checkpoint inhibitor therapy. Since the etiology of AKI in patients undergoing cancer therapy varies, clarifying underlying causes in individual cases is critical for optimal cancer treatment. Although it is essential to individually analyze immune checkpoint inhibitor-treated patients for underlying pathologies for each AKI episode, these analyses have not been realized. Herein, we aimed to individually clarify the underlying causes of AKI in immune checkpoint inhibitor-treated patients using a new clustering approach with Shapley Additive exPlanations (SHAP). We developed a gradient-boosting decision tree-based machine learning model continuously predicting AKI within 7 days, using the medical records of 616 immune checkpoint inhibitor-treated patients. The temporal changes in individual predictive reasoning in AKI prediction models represented the key features contributing to each AKI prediction and clustered AKI patients based on the features with high predictive contribution quantified in time series by SHAP. We searched for common clinical backgrounds of AKI patients in each cluster, compared with annotation by three nephrologists. One hundred and twelve patients (18.2%) had at least one AKI episode. They were clustered per the key feature, and their SHAP value patterns, and the nephrologists assessed the clusters' clinical relevance. Receiver operating characteristic analysis revealed that the area under the curve was 0.880. Patients with AKI were categorized into four clusters with significant prognostic differences (p = 0.010). The leading causes of AKI for each cluster, such as hypovolemia, drug-related, and cancer cachexia, were all clinically interpretable, which conventional approaches cannot obtain. Our results suggest that the clustering method of individual predictive reasoning in machine learning models can be applied to infer clinically critical factors for developing each episode of AKI among patients with multiple AKI risk factors, such as immune checkpoint inhibitor-treated patients.

Effect of Renin-Angiotensin System Blockers in Acute Myocardial Infarction Patients with Acute Kidney Injury

Introduction: Renin-angiotensin system blockers (RASBs) are known to improve mortality after acute myocardial infarction (AMI). However, there remain uncertainties regarding treatment with RASBs after AMI in patients with renal dysfunction and especially in the setting of acute kidney injury (AKI). Methods: Patients from a multicenter AMI registry undergoing percutaneous coronary intervention in Korea were stratified and analyzed according to the presence of AKI, defined as an increase in serum creatinine levels of ≥0.3 mg/dL or ≥50% increase from baseline during admission, and RASB prescription at discharge. The primary outcome of interest was 5-year all-cause mortality. Results: In total 9,629 patients were selected for initial analysis, of which 2,405 had an episode of AKI. After adjustment using multivariable Cox regression, treatment with RASBs at discharge was associated with decreased all-cause mortality in the entire cohort (hazard ratio [HR] 0.849, confidence interval [CI] 0.753–0.956), but not for the patients with AKI (HR 0.988, CI 0.808–1.208). In subgroup analysis, RASBs reduced all-cause mortality in patients with stage I AKI (HR 0.760, CI 0.584–0.989) but not for stage II and III AKI (HR 1.200, CI 0.899–1.601, interaction p value 0.002). Similar heterogeneities between RASB use and AKI severity were also observed for other clinical outcomes of interest. Conclusion: Treatment with RASBs in patients with AMI and concomitant AKI is associated with favorable outcomes in non-severe AKI, but not in severe AKI. Further studies to confirm these results and to develop strategies to minimize the occurrence of adverse effects arising from RASB treatment are needed.

Two acute kidney injury episodes after ICI therapy: a case report.

A 74-year-old Japanese male with lung squamous cell carcinoma received his first dose of immune checkpoint inhibitors (ICIs): ipilimumab and nivolumab. He developed acute kidney injury (AKI) and was admitted to our department. We diagnosed kidney immune-related adverse effects (irAE), and a kidney biopsy revealed acute tubulointerstitial nephritis. We started oral prednisolone (PSL) and his AKI immediately improved. The patient maintained stable findings after PSL was tapered off. However, seven months after the ICI administration, he developed rapid progressive glomerular nephritis and was admitted to our department again. The second kidney biopsy showed findings consistent with anti-glomerular basement membrane glomerulonephritis. Although the patient was treated with pulse methylprednisolone followed by oral PSL and plasma exchange, he became dependent on maintenance hemodialysis. To our knowledge, no case report has described two different types of biopsy-proven nephritis. In cases of suspected relapsing kidney irAEs, both a relapse of previous nephritis and the development of another type of nephritis should be considered.

Intervention treatment reducing cellular senescence inhibits tubulointerstitial fibrosis in diabetic mice following acute kidney injury.

Senescence of kidney tubules leads to tubulointerstitial fibrosis (TIF). Proximal tubular epithelial cells undergo stress-induced senescence during diabetes and episodes of acute kidney injury (AKI), and combining these injuries promotes the progression of diabetic kidney disease (DKD). Since TIF is crucial to progression of DKD, we examined the therapeutic potential of targeting senescence with a senolytic drug (HSP90 inhibitor) and/or a senostatic drug (ASK1 inhibitor) in a model of TIF in which AKI is superimposed on diabetes. After 8 weeks of streptozotocin-induced diabetes, mice underwent bilateral clamping of renal pedicles to induce mild AKI, followed by 28 days of reperfusion. Groups of mice (n=10-12) received either vehicle, HSP90 inhibitor (alvespimycin), ASK1 inhibitor (GS-444217), or both treatments. Vehicle-treated mice displayed tubular injury at day 3 and extensive tubular cell senescence at day 10, which remained unresolved at day 28. Markers of senescence (Cdkn1a and Cdkn2a), inflammation (Cd68, Tnf, and Ccl2), and TIF (Col1a1, Col4a3, α-Sma/Acta2, and Tgfb1) were elevated at day 28, coinciding with renal function impairment. Treatment with alvespimycin alone reduced kidney senescence and levels of Col1a1, Acta2, Tgfb1, and Cd68; however, further treatment with GS-444217 also reduced Col4a3, Tnf, Ccl2, and renal function impairment. Senolytic therapy can inhibit TIF during DKD, but its effectiveness can be improved by follow-up treatment with a senostatic inhibitor, which has important implications for treating progressive DKD.

Ambient heat and acute kidney injury: case-crossover analysis of 1 354 675 automated e-alert episodes linked to high-resolution climate data

As global temperatures continue to rise, the effects of ambient heat on acute kidney injury (AKI) are of growing concern. We used a novel nationwide electronic alert (e-alert) system to detect increases in AKI risk associated with high temperatures. We used a case-crossover design to link 1 354 675 AKI episodes occurring in England between April and September in years 2017-2021 to daily maximum temperature data at postcode sector level. AKI episode data were obtained from the UK Renal Registry. There were no further inclusion or exclusion criteria. Conditional logistic regression employing distributed lag non-linear models was used to assess odds of AKI episode on case days compared with day-of-week matched control days. Effects during heatwaves were also assessed using heat-episode analysis. There were strongly increased odds of AKI episode associated with high temperatures, with odds ratio (OR) 1·623 (95% CI 1·319-1·997) on a day of temperature 32°C compared with one of 17°C, the effects being strongest on a lag of 1 day. There was an OR of 1·020 (1·019-1·020) per 1°C increase in temperature above 17°C. The odds of a heat-related AKI episode were similar between AKI stages 1 and 2, but considerably lower for stage 3 events. A 7-day heatwave in July 2021 was associated with a 28·6% increase in AKI counts (95% CI 26·5-30·7). Heat-related AKI is a growing public health challenge. As even small changes in renal function can affect patient outcomes, susceptible individuals should be advised to take preventive measures whenever hot weather is forecast. Use of an e-alert system allows effects in milder cases that do not require secondary care to also be detected. National Institute for Health and Care Research (NIHR).

Nephrologist follow-up care for the acute kidney injury-chronic kidney disease continuum and clinical outcomes: A systematic review and meta-analysis.

Acute kidney injury (AKI) to chronic kidney disease (CKD) continuum will increase patients' risk of mortality and long-term dialysis. The aim of the present meta-analysis is to explore the effectiveness of nephrologist care and focus on the follow-up in patients with AKI. A systematic search of studies on nephrologist care for the AKI to CKD continuum has been conducted from PubMed and other different databases. Briefly, the primary outcome is the odds ratio of mortality as well as the secondary outcome is de novo renal replacement therapy. This research includes one randomized controlled trial (RCT) and four cohort studies comprised of 15 541 participants in total. The quantitative analysis displays a lower mortality rate with nephrologist care versus non-nephrologist care in patients' discharge after a hospitalization complicated by AKI (odds ratio: 0.768; 95% CI, 0.616-0.956). By means of Trial Sequential Analysis (TSA), we conclude that nephrologist care after an AKI episode declines 30% relative risks of all-cause mortality. Nephrologist care for AKI patients after a hospitalization significantly has reduced mortality compared to those followed up by non-nephrologists. There is a trend toward a potentially superior survival rate with nephrologist care has been going well in the recent years.

Prospective validation of the EASL management algorithm for acute kidney injury in cirrhosis

The management of acute kidney injury (AKI) in cirrhosis is challenging. The EASL guidelines proposed an algorithm for the management of AKI, but this has never been validated. We aimed to prospectively evaluate this algorithm in clinical practice. We performed a prospective cohort study in consecutive hospitalized patients with cirrhosis and AKI. The EASL management algorithm includes identification/treatment of precipitating factors, 2-day albumin infusion in patients with AKI ≥stage 1B, and treatment with terlipressin in patients with hepatorenal syndrome (HRS-AKI). The primary outcome was treatment response, which included both full and partial response. Secondary outcomes were survival and adverse events associated with terlipressin therapy. A total of 202 AKI episodes in 139 patients were included. Overall treatment response was 80%, while renal replacement therapy was required in only 8%. Response to albumin infusion was achieved in one-third of episodes. Of patients not responding to albumin, most (74%) did not meet the diagnostic criteria of HRS-AKI, with acute tubular necrosis (ATN) being the most common phenotype. The response rate in patients not meeting the criteria for HRS-AKI was 70%. Only 30 patients met the diagnostic criteria for HRS-AKI, and their response rate to terlipressin was 61%. Median time from AKI diagnosis to terlipressin initiation was only 2.5 days. While uNGAL (urinary neutrophil gelatinase-associated lipocalin) could differentiate ATN from other phenotypes (AUROC 0.78), it did not predict response to therapy in HRS-AKI. Ninety-day transplant-free survival was negatively associated with MELD-Na, ATN and HRS-AKI as well as uNGAL. Three patients treated with terlipressin developed pulmonary edema. The application of the EASL AKI algorithm is associated with very good response rates and does not significantly delay initiation of terlipressin therapy. The occurrence of acute kidney injury (AKI) in patients with cirrhosis is associated with poor short-term mortality. Improving its rapid identification and prompt management was the focus of the recently proposed EASL AKI algorithm. This is the first prospective study demonstrating that high AKI response rates are achieved with the use of this algorithm, which includes identification of AKI, treatment of precipitating factors, a 2-day albumin challenge in patients with AKI ≥1B, and supportive therapy in patients with persistent AKI not meeting HRS-AKI criteria or terlipressin with albumin in those with HRS-AKI. These findings support the use of this algorithm in clinical practice.

Strategies to mitigate acute kidney injury risk during physical work in hot environments.

Prolonged physical work in the heat can reduce renal function and increase the risk of acute kidney injury (AKI). This is concerning given that the latest climate change projections forecast a rise in global temperature as well as the frequency, intensity, and duration of heatwaves. This means that outdoor and indoor workers in the agriculture or construction industries will be exposed to higher heat stress in the years ahead. Several studies indicate a higher incidence of chronic kidney disease from nontraditional origins (CKDnt) in individuals exposed to high temperatures, intense physical work, and/or recurrent dehydration. It has been proposed that prolonged physical work in the heat accompanied by dehydration results in recurrent episodes of AKI that ultimately lead to permanent kidney damage and the development of CKDnt. Thus, there is a need to identify and test strategies that can alleviate AKI risk during physical work in the heat. The purpose of this review is to present strategies that might prevent and mitigate the risk of AKI induced by physical work in the heat.

Acute kidney disease beyond day 7 after major surgery: a secondary analysis of the EPIS-AKI trial

PurposeAcute kidney disease (AKD) is a significant health care burden worldwide. However, little is known about this complication after major surgery.MethodsWe conducted an international prospective, observational, multi-center study among patients undergoing major surgery. The primary study endpoint was the incidence of AKD (defined as new onset of estimated glomerular filtration rate (eCFR) < 60 ml/min/1.73 m2 present on day 7 or later) among survivors. Secondary endpoints included the relationship between early postoperative acute kidney injury (AKI) (within 72 h after major surgery) and subsequent AKD, the identification of risk factors for AKD, and the rate of chronic kidney disease (CKD) progression in patients with pre-existing CKD.ResultsWe studied 9510 patients without pre-existing CKD. Of these, 940 (9.9%) developed AKD after 7 days of whom 34.1% experiencing an episode of early postoperative-AKI. Rates of AKD after 7 days significantly increased with the severity (19.1% Kidney Disease Improving Global Outcomes [KDIGO] 1, 24.5% KDIGO2, 34.3% KDIGO3; P < 0.001) and duration (15.5% transient vs 38.3% persistent AKI; P < 0.001) of early postoperative-AKI. Independent risk factors for AKD included early postoperative-AKI, exposure to perioperative nephrotoxic agents, and postoperative pneumonia. Early postoperative-AKI carried an independent odds ratio for AKD of 2.64 (95% confidence interval [CI] 2.21–3.15). Of 663 patients with pre-existing CKD, 42 (6.3%) had worsening CKD at day 90. In patients with CKD and an episode of early AKI, CKD progression occurred in 11.6%.ConclusionOne in ten major surgery patients developed AKD beyond 7 days after surgery, in most cases without an episode of early postoperative-AKI. However, early postoperative-AKI severity and duration were associated with an increased rate of AKD and early postoperative-AKI was strongly associated with AKD independent of all other potential risk factors.