Episode Of Acute Kidney Injury Research Articles

#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.

INCIDENCE AND MORTALITY RISK OF AKD AND AKI IN THE PRIMARY CARE

Objective: Objective: The aim of the present study was to assess the impact of hypertension in the incidence of Acute Kidney Damage and Acute Kidney Injury episodes in the community, defined by changes in serum creatinine and temporal window. Design and method: The study analyzed the EHR of a community of 1,863,731 adult subjects >23 years of age with serum creatinine before, during and after the AKD episode for a variable period of time. eGFR was calculated using the CKD-EPI formula. AKD and AKI were defined according to the harmonized KDIGO criteria (Lameire 2021). The acute event was defined as having occurred when the blood creatinine was at least 150% of the mean of the previous creatinine measurement. AKD is considered to have ended when the creatinine falls to at least the threshold created by the pre-event mean plus half the increment produced during the episode within three months. AKI was defined as a sudden drop in creatinine within seven days. The RIFLE scale was used to classify episodes. HTN was considered when it was recorded in the EHR (CIE9 and 10). Results: During a mean follow-up of 4.8 years, 56,850 episodes of AKD were identified in 47,670 patients. The incidence was 4.49 and 19.0/1000 patients/year in non-CKD and CKD subjects, respectively. Overall, HTN was present in 62.8% of patients, 49,9% among those without CKD before the event and in 92.6% in CKD patients. In patients without CKD, HTN increases the risk of more severe RIFLE class of AKD (Risk 47.4%, Injury 64.1% and Failure 66.0%). The prevalence of HTN in patients with AKI was 76.6% without differences in the RIFLE class (Risk 76.3%, Injury 77.2% and Failure 76.9%). A higher mortality was recorded among the AKI patients. Conclusions: The data from this study reinforce the concept that acute elevations in serum creatinine occurring and managed in the community may pose a health risk and HTN is an important risk factor. Future work should consider how best eAlerts can be utilized, targeted and implemented.

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.

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.

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).

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.

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.

HOSPITAL READMISSION AND MORTALITY RATES IN PATIENTS WITH CONCURRENT DEPRESSION AND INFLAMMATORY BOWEL DISEASE: INSIGHTS FROM THE NATIONAL READMISSIONS DATABASE, 2016–2019

Abstract BACKGROUND Inflammatory Bowel Disease (IBD) is a proinflammatory condition that is known to be associated with depression. Research examining causality suggests that Crohn's disease (CD) or ulcerative colitis (UC) patients are vulnerable to triggering pre-existing mental health conditions and that conversely, a pre-existing disorder such as depression may have an effect on the disease process and course of IBD. There is a paucity of comprehensive studies examining the downstream effects of depression on patients with IBD such as readmission rates and mortality. The complexity of the interaction between depression and IBD remains a fertile ground for further investigations in terms of pathological reciprocity and downstream consequences. METHODS In this retrospective observational study, patients were queried from the National Readmissions Database from 2016 to 2019. ICD-10 codes were used to identify patients with Crohn’s disease, ulcerative colitis, and depression. Primary outcomes were mortality and readmission rates at 30 days and 90 days. Secondary outcomes were index admission mortality, hospital length of stay (LOS), and total hospitalization charges (TOTHC) at 30 and 90 days respectively. The top 10 readmission diagnoses in each subgroup were also identified. RESULTS For patients with CD and depression, the mean age at readmission was 51.6 years with a high readmission and mortality rate at 30 days (readmission rate 5.2%, p&amp;lt;0.01; mortality rate 2.8%, p&amp;lt;0.01) which increased significantly at 90 days (readmission rate 8.4%, p&amp;lt;0.01). Hospital LOS and TOTHC remained relatively the same compared to the index admission for both 30-day and 90-day readmissions (Table 1,2). A similar trend was seen for UC and depression as well: mean age at readmission was 51.4 years with a high readmission rate and mortality at 30 days (readmission rate 5.0%, p&amp;lt;0.01; mortality rate 2.6%, p&amp;lt;0.01) which increased significantly at 90 days (readmission rate 8.4%, p&amp;lt;0.01; mortality rate 2.9%, p&amp;lt;0.01). Sepsis, hypertensive heart disease accompanied by heart failure and/or chronic kidney disease, acute kidney injury, hypoxia, and acute depressive episodes were the top primary associated readmission etiologies at 30 days and 90 days when correlated with a diagnosis of UC or CD. (Table 1, 2). CONCLUSION Our investigation revealed that patients affected by both depression and either UC or Crohn’s disease exhibited elevated readmission rates and a notably amplified mortality risk at 30 days post-readmission, with a more substantial increase observed at the 90-day mark. These findings underscore the significance of healthcare providers routinely screening for depression, addressing the management of mental health, and acknowledging the considerable impact it has on patients with co-occurring chronic diseases like UC or CD as an integral facet of comprehensive care. Table 1 Table 2

Molecular insights into P2X signalling cascades in acute kidney injury.

Acute kidney injury (AKI) is a critical health issuewith high mortality and morbidity rates in hospitalized individuals. The complex pathophysiology and underlying health conditions further complicate AKI management. Growing evidence suggests the pivotal role of ion channels in AKI progression, through promoting tubular cell death and altering immune cell functions. Among these channels, P2X purinergic receptors emerge as key players in AKI pathophysiology. P2X receptors gated by adenosine triphosphate (ATP), exhibit increased extracellular levels of ATP during AKI episodes. More importantly, certain P2X receptor subtypes upon activation exacerbate the situation by promoting the release of extracellular ATP. While therapeutic investigations have primarily focused on P2X4 and P2X7 subtypes in the context of AKI, while understandingabout other subtypes still remains limited. Whilst some P2X antagonists show promising results against different types of kidney diseases, their role in managing AKI remains unexplored. Henceforth, understanding the intricate interplay between P2X receptors and AKI is crucial for developing targeted interventions. This review elucidates the functional alterations of all P2X receptors during normal kidney function and AKI, offering insights into their involvement in AKI. Notably, we have highlighted the current knowledge of P2X receptor antagonists and the possibilities to use them against AKI in the future. Furthermore, the review delves into the pathways influenced by activated P2X receptors during AKI, presenting potential targets for future therapeutic interventions against this critical condition.

Kidney Disease Awareness and Knowledge Among Families and Pediatric Survivors of Severe Acute Kidney In

Background: Acute kidney injury (AKI) is common in pediatric patients and is associated with poor outcomes including increased risk of chronic kidney disease. It is unknown whether pediatric AKI survivors and their families are aware of their AKI diagnosis and understand the associated risks. We are seeking to identify awareness and disease-specific knowledge among pediatric AKI survivors and their families.&#x0D; Objectives: We hypothesize that pediatric AKI survivors and their families have a low awareness of their diagnosis and want more information about kidney health.&#x0D; Design/Methods: We performed a cross-sectional survey of AKI awareness and knowledge in pediatric patients with KDIGO Stage II or III AKI and their families near the time of discharge from Riley Hospital for Children. Families answered questions on AKI diagnosis awareness and AKI knowledge using the Kidney Knowledge Survey (KiKS).&#x0D; Results: Of 16 families included in this analysis, 75% were unaware they had experienced AKI and 94% were unaware they had a ‘problem with their kidneys’. Overall, the median AKI objective knowledge score was 60% (IQR: 31%, 69%). There was no difference in knowledge score between those that recognized their episode of AKI and those that did not. In total, 69% of families correctly defined AKI as when ‘your kidneys suddenly stop working well’. Most families recognized dehydration (56%) and infection (81%) as risk factors for AKI, however fewer recognized other risk factors such as ibuprofen use (31%). Only 38% of families reported that someone had discussed AKI during their admission, and 88% stated they wanted to learn more about AKI.&#x0D; Conclusion: Most families of pediatric survivors of severe AKI were unaware that their child had AKI or problems with their kidneys. Many lacked understanding of AKI risk factors and knowledge of kidney health and desired more information.

Long-Term Mortality and Health-Related Quality of Life After Continuous Versus Intermittent Renal Replacement Therapy in ICU Survivors: A Secondary Analysis of the Quality of Life After ICU Study.

Purpose: We assessed long-term outcomes in intensive care unit (ICU) survivors with acute kidney injury (AKI) submitted to intermittent or continuous renal replacement therapy (RRT) for comparisons between groups. Methods: The multicenter prospective cohort study included 195 adult ICU survivors with an ICU stay >72 h in 10 ICUs that had at least one episode of AKI treated with intermittent RRT (IRRT) or continuous RRT (CRRT) during ICU stay. The main outcomes were mortality and health-related quality of life (HRQoL). Hospital readmissions and physical dependence were also assessed. Results: Regarding RRT, 83 (42.6%) patients received IRRT and 112 (57.4%) received CRRT. Despite the similarity regarding sociodemographic characteristics, pre-ICU state of health and type of admission between groups, the risk of death (23.5% vs 42.7%; P < .001), the prevalence of sepsis (60.7%) and acute respiratory distress syndrome (17%) were higher at ICU admission among CRRT patients. The severity of critical illness was higher among CRRT patients, regarding the need for mechanical ventilation (75.0% vs 50.6%, P = .002) and vasopressors (91.1% vs 63.9%, P < .001). One year after ICU discharge, 67 of 195 ICU survivors died (34.4%) and, after adjustment for confounders, there were no significant differences in mortality when comparing IRRT and CRTT patients (34.9% vs 33.9%; P = .590), on HRQoL in both physical (41.9% vs 42.2%; P = .926) and mental dimensions (57.6% vs 56.6%; P = .340), and on the number of hospital readmissions and physical dependence. Conclusions: Our study suggests that among ICU survivors RRT modality (IRRT vs CRRT) in the ICU does not impact long-term outcomes after ICU discharge.