The risk of developing a persistent reduction in renal function after postoperative acute kidney injury (pAKI) is not well established. The goal of this investigation was to evaluate whether patients who develop pAKI have a greater decline in long-term renal function than patients who do not.

In this multicentre retrospective propensity-matched study, anaesthesia data warehouses at three tertiary care hospitals were queried. Adult patients undergoing surgery with available preoperative and postoperative creatinine results and without baseline haemodialysis requirements were included. Patients were stratified by occurrence of pAKI as defined by the Acute Kidney Injury Network classification. The primary outcome was a decline in follow-up glomerular filtration rate (GFR) of 40% relative to baseline, based on follow-up outpatient visits from 0 to 36 months after hospital discharge. A propensity score-matched sample was used in Kaplan-Meier analysis and a piecewise Cox model to compare the time to reach a 40% decline in GFR for patients with and without pAKI.

In 95 213 patients, the rate of pAKI ranged from 9.9% to 13.7%. In the piecewise Cox model, pAKI was associated with a significantly increased hazard of a 40% decline in GFR. The common-effect hazard ratio was 13.35 (95% confidence interval [CI] 10.79-16.51, P<0.001) for 0-6 months, 7.07 (5.52-9.05, P<0.001) for 6-12 months, 6.02 (4.69-7.74, P<0.001) for 12-24 months, and 4.32 (2.65-7.05, P<0.001) for 24-36 months.

pAKI is associated with a significantly increased hazard of a 40% decline in GFR up to 36 months after surgery across three institutions.

Acute kidney injury (AKI) affects a significant percentage of the pediatric population. Currently, the diagnosis of AKI in children still uses traditional laboratory methods (ex. creatinine or urea serum concentration and measurement of urine output). It has significant limitations. Early stages of AKI in children may be almost asymptomatic. In-depth assessment with the pRIFLE scale is helpful, but requires bladder catheterization and precise monitoring of hourly diuresis, as well as multiple blood draws to determine changes in creatinine concentration and estimate glomerular filtration rate (eGFR). The diagnostic methods lack a marker that would the early and potentially reversible phase of kidney damage. This paper reviews recent data on selected AKI markers in children, including their diagnostic and prognostic potential.

Acute kidney injury (AKI) is common in hospitalized adults and a risk factor for chronic kidney disease and mortality. The effect of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) post-AKI on mortality and long-term kidney function remains unclear.

Propensity-weighted retrospective observational cohort study.

A total of 3,289 patients with AKI admitted to a tertiary care hospital from November 2015-October 2016, with follow-up until September 2020.

ACEi/ARB use within 180 days post-AKI.

All-cause mortality, and major adverse kidney events (MAKE) as defined by composite of renal replacement therapy post-AKI, sustained estimated glomerular filtration rate (eGFR) decline >30% from baseline, or eGFR ≤15 mL/min/1.73 m2.

We generated propensity weights for ACEi/ARB use post-AKI, using age, sex, comorbid conditions, prior medication, intensive care unit admission, severe sepsis, and index AKI Kidney Disease: Improving Global Outcomes severity. Cox proportional hazard models were used to test associations of post-AKI ACEi/ARB with mortality, MAKE, and joint models for eGFR slopes.

A total of 2,309 (70.2%) participants died or experienced MAKE by end of follow-up. 161 (4.9%) and 406 (12.3%) patients initiated or resumed prior ACEi/ARB use within 180 days post-AKI, respectively. Although the overall cohort had no significant mortality association with post-AKI ACEi/ARB use, a significant association with lower mortality was observed in patients with KDIGO 3 AKI (HR, 0.40; 95% CI, 0.21-0.75; P interaction = 0.003). However, post-AKI ACEi/ARB use was associated with increased MAKE in patients without cardiovascular indications for ACEi/ARB use (HR, 1.52; 95% CI, 1.17-1.98; P interaction = 0.03). Although post-AKI use of ACEi/ARB was associated with acute eGFR decline (initial eGFR change -2.3 mL/min/1.73 m2/year; 95% CI, -3.1 to -1.5; P < 0.001), no association with longer-term eGFR decline was observed.

Retrospective observational study on heterogeneous AKI cohort without data on ACEi/ARB cumulative exposure.

Early ACEi/ARB post-AKI was not associated with better long-term survival or kidney function but was associated with lower mortality in patients with KDIGO 3 AKI.

Although various factors contribute to the transition from acute kidney injury (AKI) to chronic kidney disease (CKD), no clinically effective pharmacological treatment has been established. We investigated whether chymase inhibition is effective in preventing renal fibrosis, a key process in the transition from AKI to CKD. Male BALB/c mice were subjected to unilateral ischemia-reperfusion (I/R) injury, and TY-51469, a chymase-specific inhibitor, was administered intraperitoneally at a dose of 10 mg/kg/day for 6 weeks. The 45 min ischemic period followed by 6 weeks of reperfusion resulted in severe renal atrophy. Renal fibrosis was particularly pronounced in the transition region between the cortex and medulla in placebo-treated mice. The expression of mouse mast cell protease 4 (MMCP-4, a mouse chymase) mRNA, the number of chymase-positive mast cells, and fibrosis-related factors, such as transforming growth factor (TGF)-β1 and collagen I, were all significantly increased in I/R-injured kidneys. However, treatment with TY-51469 significantly suppressed fibrosis formation, along with the inhibition of renal chymase and TGF-β1 expression. These findings suggest that chymase inhibition may be a potential therapeutic strategy for preventing the transition from AKI to CKD by reducing fibrosis.

This study explored the relationship between acute kidney injury (AKI) and chronic kidney disease (CKD), focusing on autophagy-related genes and their immune infiltration during the transition from AKI to CKD. We performed weighted correlation network analysis (WGCNA) using two microarray datasets (GSE139061 and GSE66494) in the GEO database and identified autophagy signatures by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and GSEA enrichment analysis. Machine learning algorithms such as LASSO, random forest, and XGBoost were used to construct the diagnostic model, and the diagnostic performance of GSE30718 (AKI) and GSE37171 (CKD) was used as validation cohorts to evaluate its diagnostic performance. The study identified 14 autophagy candidate genes, among which ATP6V1C1 and COPA were identified as key biomarkers that were able to effectively distinguish between AKI and CKD. Immune cell infiltration and GSEA analysis revealed immune dysregulation in AKI, and these genes were associated with inflammation and immune pathways. Single-cell analysis showed that ATP6V1C1 and COPA were specifically expressed in AKI and CKD, which may be related to renal fibrosis. In addition, drug prediction and molecular docking analysis proposed SZ(+)-(S)-202-791 and PDE4 inhibitor 16 as potential therapeutic agents. In summary, this study provides new insights into the relationship between AKI and CKD and lays a foundation for the development of new treatment strategies.

Introduction: Chronic kidney disease (CKD) is characterized by a decline in renal function, increased mortality, and significant impairments in the immune system and function of immune cells. These alterations are often derived by uremic toxins, which, in turn, modify the immune system's response to infections. Our research investigates the progression of Porphyromonas gingivalis (P. gingivalis) infection during CKD and its subsequent impact on kidney failure. Methods: We utilized two infectious models, a chamber model representing short-term local inflammation and alveolar bone loss that mimic chronic infection of periodontium, both in conjunction with a CKD model. Additionally, our in vitro studies employed primary macrophages, osteoclasts, and lymphocytes to characterize the immune responses to P. gingivalis and pathogen-associated molecular patterns (PAMPs) in the presence of uremic toxins. Results and Conclusion: Our findings demonstrate that uremic toxins, such as indoxyl sulfate (IS), alter responses of macrophages and lymphocytes to P. gingivalis. In vivo, CKD significantly enhanced P. gingivalis survival and infection-induced alveolar bone loss. The increased distribution of pathogen within peripheral tissues was associated with altered inflammatory responses, indicating that CKD promotes infection. Moreover, P. gingivalis-infected mice exhibited a marked increase in renal inflammation, suggesting that the relationship between uremia and infection is bidirectional, with infection exacerbating kidney dysfunction. Furthermore, we observed that infected CKD mice exhibit decreased serum immunoglobulin G (IgG) levels compared to infected mice without CKD, implying that uremia is associated with immune dysfunction characterized by immunodepression and impaired B lymphocyte function.

In previously published work, we elucidated the role of cutaneous arsenical exposure in promoting acute kidney injury (AKI) in adult healthy mice. Here, we determine whether preexisting chronic kidney disease (CKD) increases the severity of AKI. Following exposure to aristolochic acid (AA) (a nephrotoxic phytochemical in humans), mice manifested classical markers of CKD, including robust interstitial fibrosis and loss in kidney function. Skin challenge with phenylarsine oxide (PAO), a surrogate for warfare arsenicals, led to significantly worse kidney injury, as evidenced by tubulointerstitial fibrosis, glomerulosclerosis, a persistent loss of estimated glomerular filtration rate, and mortality in AA-induced CKD mice compared with mice without CKD. These PAO-challenged CKD mice exhibited enhanced production of serum/urine neutrophil gelatinase-associated lipocalin and a significant rise in serum creatinine along with histological markers of kidney injury, including brush border loss, tubular atrophy, cast formation, glomerular injury, and interstitial inflammatory cell infiltration. Serum cytokines IL-4, IL-6, IFN-γ, IL-12p70, TNF-α, and IL-18 significantly elevated in CKD mice following PAO exposure when compared with animals exposed to PAO alone. Furthermore, we found increased TUNEL-positive tubular cells in the kidneys of CKD mice following PAO exposure, suggesting enhanced PAO-mediated cell death in CKD mice. Mechanistically, we determined that DNA damage-regulated p53 signaling was a major mediator of cellular responses to PAO in CKD mice. In summary, our data demonstrate that CKD significantly increased the severity of AKI following exposure to arsenicals and suggest that human populations with preexisting CKD could be highly susceptible to arsenical-mediated kidney injury and associated morbidity and mortality.NEW & NOTEWORTHY Preexisting chronic kidney disease (CKD) predisposes experimental animals to augmented morbidity and mortality following cutaneous vesicant exposure. The mechanism underlying increased susceptibility to renal injury and associated morbidity involves the DNA damage-regulated p53 signaling pathway.

The incidence of acute kidney injury (AKI) is increasing, and with it, the population of individuals requiring post-AKI care. Postdischarge follow-up for AKI survivors is recommended within 90 days of an AKI episode to promote kidney recovery and potentially prevent progression of kidney disease. However, timely postdischarge care is often lacking or fragmented and poses a missed opportunity to prevent long-term complications of this condition. Suggested elements of follow-up care begin with a scheduled appointment with a physician and involve a bundled approach to care with health care providers' communicating across sites, remote patient monitoring devices, review of medications, education, access, kidney care evaluation, and interdisciplinary collaboration to achieve these patient care goals. This article provides an overview of guidance documents for post-AKI care and the roles of the nurse and pharmacist as part of an interdisciplinary team in postdischarge care after a patient incurs an episode of AKI.

Acute kidney injury (AKI) is associated with a significant burden of mortality worldwide. Each episode of AKI increases the long-term risk of death, especially if there is no recovery or insufficient renal recovery (i.e. restoration of kidney function). This narrative review summarizes relevant studies on the definition and prediction of renal recovery. The following databases were searched for references: PubMed, Web of Science, Cochrane Library, Scopus. The period lasted from 1990 until 2024. The currently available criteria for renal recovery have been identified and discussed. Regarding restoration of kidney function prediction, seven studies on alternative or novel biomarkers have been reviewed. In the context of kidney replacement therapy and renal recovery, findings from four large, prospective randomized studies have been summarized. A standardized definition of renal recovery is presently not available. Specific biomarkers allow for an estimation of the likelihood of renal recovery under certain conditions. According to current knowledge, no dialysis method has been definitively shown to be advantageous for the recovery process.

The global incidence of acute kidney injury (AKI) is increasing. AKI is associated with both short- and long-term risks, including increased risk of chronic kidney disease and kidney failure, cardiovascular events, and all-cause death. This review summarizes existing posthospitalization AKI care guidelines, interprets the current state of evidence for AKI survivor care models including nephrology-specific and multidisciplinary team interventions, and details the health policy landscape for AKI survivors receiving outpatient dialysis in the United States. The main finding of this review is that evidence supporting specific posthospitalization AKI care interventions is very limited, resulting in imprecise consensus-based practice recommendations by national and international kidney societies for AKI survivors. The main implication of this work is to highlight the urgent need for additional research evaluating the efficacy of different care models among AKI survivors at high risk of maintenance dialysis, progression of kidney disease, rehospitalization, and death to devise value-based care models and clinical interventions that improve patient outcomes.

Acute kidney injury (AKI) is a critical clinical syndrome associated with both innate and adaptive immune responses and thus increases mortality. Nevertheless, specific therapeutics for AKI are scarce so far. Recent studies have revealed that knockout of STING alleviate AKI, suggesting that STING could be an attractive target for AKI therapy. SN-011, a promising STING inhibitor, has not been reported in studies of its anti-AKI activity. In this study, we sought to examine the effects of SN-011 on AKI and explore its underlying mechanism. Our findings indicate that SN-011 could modulate the NF-κB and MAPK pathways, suppress the expression of inflammatory factors, and decrease ROS release in the cisplatin-induced cell model. In addition, SN-011 blocked the nuclear translocation of NF-κB p65, further mitigating the inflammatory response. In vivo, SN-011 enhanced survival rates and alleviated renal dysfunction. According to gene set enrichment analysis of sequencing data from mouse kidneys, we further confirm that SN-011 modulates the NF-κB and MAPK pathways. Our study suggests that SN-011 could be an attractive anti-inflammatory agent for further anti-AKI research.

Acute kidney injury (AKI) is a syndrome with high mortality and morbidity in part due to delayed recognition based on changes in creatinine. A marker for AKI based on a single measurement is needed and therefore the performance of a single measurement of plasma neutrophil gelatinase-associated lipocalin (pNGAL) to predict AKI in patients admitted to the emergency department was tested.

Samples from the Triage study which included 6005 consecutive adult patients admitted to the emergency department were tested for pNGAL. The optimal cutoff for pNGAL was determined by the AUC and compared to AKI based on creatinine using different estimations of the premorbid kidney function.

In 4833 patients, two or more plasma creatinine (pCr) measurements were available allowing the detection of AKI. The highest prevalence of AKI (10%) was found when defining AKI as an increase in pCr ≥26.5 μmol/L from the prior year's mean pCr. At these conditions the AUC for pNGAL to predict AKI was 85% giving an optimal cutoff of 142.5 ng/mL with a negative predictive value of 0.96, a positive predictive value of 0.35, a specificity of 0.87 and a sensitivity of 0.70.

The study illustrates that the value of a single measurement of pNGAL is primarily in excluding AKI whereas it`s poorer in predicting the presence of AKI. When diagnosing AKI with pCr the optimal baseline pCr level is the mean of available pCr (mb-pCr) measurements from up to a year prior to the current event.

Although contrast-induced (CI) acute kidney injury (AKI) is a common complication in high-risk individuals requiring evaluation with contrast-enhanced angiography, the possible predictors of CI-AKI in patients with obesity are not fully understood. The aim of this study was to elucidate plausible factors associated with the irreversibility of CI-AKI in individuals with obesity undergoing contrast-enhanced computed tomography coronary angiography.

A total of 96 adult patients with obesity and the KDIGO criteria of CI-AKI (increase of serum levels of creatinine ≥ 25% or ≥ 500 µmol/L at 48 h after procedure) were retrospectively screened from the cohort of 1833 patients who underwent iodine contrast medium (ICM)-enhanced computed tomography coronary angiography, and were included in the study. The patients were divided into two cohorts: 96 adult patients with obesity and recovery of CI-AKI in 7 days after initiating of the event, and 57 individuals with irreversibility of CI-AKI. Serum concentrations of conventional biochemistry and urine biomarkers [i.e., hemoglobin, creatinine, high-sensitivity C-reactive protein, urinary albumin/creatinine ratio (UACR)] as well as natriuretic peptide, adropin, apelin, irisin, tumor necrosis factor-alpha (TNF-alpha), were determined at baseline. The levels of creatinine were measured at baseline, at the event, and in 7 days after the event.

We identified 12 variables, which were associated with irreversibility of CI-AKI: age > 75 years [odds ratio (OR) = 1.22. P = 0.001], male gender (OR = 1.03, P = 0.042), stable coronary artery disease (OR = 1.06, P = 0.048), chronic kidney disease (CKD) 1-3 grade (OR = 1.60, P = 0.001), heart failure with preserved ejection fraction (HFpEF) (OR = 1.07, P = 0.046), baseline estimated GFR < 80 mL/min/1.73 m2 (OR = 1.10, P = 0.040), UACR > 17.5 mg/g Cr (OR = 1.05, P = 0.048), TNF-alpha > 3.11 pg/mL (OR = 1.12, P = 0.001), and adropin < 2.43 ng/mL (OR = 1.18, P = 0.001). After adjustment for CKD and UACR > 17.5 mg/g Cr, only HFpEF (OR = 1.06, P = 0.042) and adropin < 2.43 ng/mL (OR = 1.11, P = 0.001) remained independent predictors of CI-AKI irreversibility. Yet, adropin < 2.43 ng/mL at baseline exerted sufficiently better predictive ability than both HFpEF and preexisting CKD 1-3 grade.

In a multivariate prediction model adjusted for CKD and urinary albumin/creatinine ratio > 17.5 mg/g Cr, low levels of adropin (< 2.43 ng/mL) in individuals with non-morbid obesity together with the presence of HFpEF were independent predictors of CI-AKI irreversibility after ICM-enhanced computed tomography coronary angiography.

Among critically ill patients, acute kidney injury (AKI) has a high incidence and leads to poor prognosis. As AKI is often only detected well after onset, early risk stratification is crucial. This study aimed to develop and internally validate the first clinical prediction model for different stages of AKI in critically ill adults.

We utilized data from the Simple Intensive Care Studies II (SICS-II), a prospective cohort study at the University Medical Center Groningen, the Netherlands. The prognostic outcome was the highest KDIGO-based stage of AKI within the first 7 days of ICU stay. Candidate predictors included fifty-nine readily available variables in critical care. Least absolute shrinkage and selection operator and proportional odds logistic regression were used for variable selection and model estimation, respectively. Receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis were applied to evaluate model performance and clinical usefulness.

Of the SICS-II cohort, 976 patients were eligible for our analyses (median [interquartile range] age 64 [52-72] years, 38% female). Within 7 days after ICU admission, 29%, 23%, and 14% of patients progressed to their highest severity of AKI at stages 1, 2, and 3, respectively. We derived a 15-variable model for predicting this maximum ordinal outcome with an area under the ROC curve of 0.76 (95% CI, 0.74-0.78) in bootstrap validation. The model showed good calibration and improved net benefit in decision curve analysis over a range of clinically plausible thresholds.

Using readily available predictors in the ICU setting, we could develop a prediction model for different stages of AKI with good performance and promising clinical usefulness. Our findings serve as an initial step towards applying a valid and timely prediction model for AKI severity, possibly helping to limit morbidity and improve patient outcomes.

Community-acquired acute kidney injury (CA-acute kidney injury) is under-recognized in the outpatient setting and is associated with adverse outcomes.

We analyzed the incidence of CA-acute kidney injury in an academic primary care practice and community health center and assessed recognition and follow-up as determined by repeat creatinine measurement (closed-loop). We reviewed 93,259 specimens for 36,593 unique patients from January 1, 2018, through December 31, 2021.

There were 220 unique patients with CA-acute kidney injury, defined as a > 75% increase in creatinine from baseline (incidence: 150/100,000; 0.15% per year). One hundred thirty seven patients (62.3%) had repeat serum creatinine performed within 30 days. Chart reviews of the 83 (37.72%) patients with open loops found there was no follow-up creatinine ordered in 69/83 (83.1%) patients. Mean baseline creatinine was higher and estimated glomerular filtration rate (eGFR) was lower in the closed-loop group (0.92 ± 0.4 mg/dL; 84.45 ± 27.49 mL/min) vs the open-loop group (0.63 ± 0.34 mg/dL; 105.19 ± 26.67 mL/min) (P < .0001). Preexisting chronic kidney disease was more prevalent in closed-loop patients (35/137; 25.6%) compared with those with open loops (3/83; 3.6%). Patients with baseline chronic kidney disease were more likely to have closed loops. Progression to new chronic kidney disease was common among CA-acute kidney injury patients, occurring in 25% of open-loop and 24.1% of closed-loop patients. New baseline eGFR was lower in all groups.

Clinicians frequently overlooked a clinically significant change in eGFR, especially when the baseline creatinine and incident creatinine levels were in the "normal" range.

Acute kidney injury (AKI) is a common and life-threatening condition associated with cell death, where ferroptosis plays a critical role. Chemerin, primarily produced in white adipose tissue, has multiple biological functions in renal pathophysiology. However, to date, whether and how chemerin regulates the progression of AKI remain unclear. Here, we found that chemerin expression was reduced in both AKI model mice and cells. Similarly, serum chemerin levels were also decreased in AKI patients. The administration of recombinant chemerin improves renal function in ischemia-reperfusion (I/R) model mice. Chemerin significantly attenuates ferroptosis in kidneys. In TCMK-1 cells, chemerin knockdown further aggravates ferroptosis. Mechanistically, chemerin activates AMP-activated protein kinase (AMPK), which induces the phosphorylation of nuclear factor erythroid 2-related factor 2 (NRF2) in renal tubular cells. Subsequently, NRF2 translocates into the nucleus, where it stimulates the expression of cystine/glutamate antiporter solute carrier (SLC7A11). As a result, cystine uptake and glutathione (GSH) biosynthesis in renal tubular cells were increased, which confers cells with higher capacity against ferroptosis. Overall, our findings indicate that chemerin plays a protective role in AKI by repressing ferroptosis in renal tubular cells, which is likely due to the activation in the AMPK/NRF2/SLC7A11 axis.

Outcomes among acute kidney injury (AKI) patients are poor in United Kingdom (UK) hospitals, and electronic alerts and care bundles may improve them. We implemented such a system at West Suffolk Hospital (WSH) called the 'AKI order set'. We aimed to assess its impact on all-cause mortality, length of stay (LOS) and renal function among AKI patients, and its utilization.

Retrospective, single-center cohort study of patients ≥ 18 years old with AKI at WSH, a 430-bed general hospital serving a rural UK population of approximately 280,000. 7243 unique AKI events representing 5728 patients with full data were identified automatically from our electronic health record (EHR) between 02 September 2018 and 1 July 2021 (median age 78 years, 51% male). All-cause mortality, LOS and improvement in AKI stage, demographic and comorbidity data, medications and AKI order set use were automatically collected from the EHR.

The AKI order set was used in 9.8% of AKI events and was associated with 28% lower odds of all-cause mortality (multivariable odds ratio [OR] 0.72, 95% confidence interval [CI] 0.57-0.91). Median LOS was longer when the AKI order set was utilized than when not (11.8 versus 8.8 days, p < .001), but was independently associated with improvement in the AKI stage (28.9% versus 8.7%, p < .001; univariable OR 4.25, 95% CI 3.53-5.10, multivariable OR 4.27, 95% CI 3.54-5.14).

AKI order set use led to improvements in all-cause mortality and renal function, but longer LOS, among AKI patients at WSH.

Cardiovascular diseases are a leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). Acute kidney injury (AKI) has been increasingly recognized as a potential exacerbating factor for cardiovascular events in these patients. The CKD-REIN study aims to explore the relationship between AKI and the risk of major adverse cardiovascular events (MACE) in a cohort of CKD patients. We hypothesize that AKI is a significant and independent predictor of MACE in patients with CKD, and that the severity of AKI correlates with the risk of subsequent cardiovascular events.

This prospective cohort study included 3033 adult CKD patients from 40 outpatient nephrology clinics in France. Patients were followed for a median of 5.2 years. AKI episodes were identified and staged based on the KDIGO-AKI criteria. Cardiovascular events, including myocardial infarction, stroke, heart failure hospitalization, and cardiovascular death, were systematically recorded. The association between AKI and MACE was analyzed using a multivariable Cox model, adjusting for confounders such as demographic characteristics, medical history, and baseline kidney function.

During the follow-up, 530 patients experienced at least one episode of AKI. The cumulative incidence of MACE at 1 year post-AKI was 8.1%. Patients with AKI had a significantly increased risk of MACE, with an adjusted hazard ratio (HR) of 5.78 (P < .001). The risk was consistent across different MACE components and was independent of age, sex, CKD stage, or comorbidities. The risk of MACE was higher for more severe AKI stages and for AKI events requiring hospitalization or associated with incomplete renal recovery.

The findings of this study confirm that AKI is a significant independent predictor of MACE in CKD patients, demonstrating a strong severity-response relationship. These results underscore the importance of vigilant cardiovascular monitoring and preventive strategies in CKD patients following AKI episodes. Understanding the mechanisms linking AKI to cardiovascular outcomes is crucial for developing targeted interventions to mitigate these risks.

Patients with diabetes are susceptible to acute kidney injury (AKI) as compared to counterparts without diabetes. However, data on the long-term clinical outcome of AKI specifically in people with diabetes are still scarce. We sought to study risk factors for and adverse cardio-renal outcomes of AKI in multi-ethnic Southeast Asian people with type 2 diabetes. 1684 participants with type 2 diabetes from a regional hospital were followed an average of 4.2 (SD 2.0) years. Risks for end stage kidney disease (ESKD), major adverse cardiovascular events (MACE) and all-cause death after AKI were assessed by survival analyses. 219 participants experienced at least one AKI episode. Age, cardiovascular disease history, minor ethnicity, diuretics usage, HbA1c, baseline eGFR and albuminuria independently predicted risk for AKI with good discrimination. Compared to those without AKI, participants with any AKI episode had a significantly high risk for ESKD, MACE and all-cause death after adjustment for multiple risk factors including baseline eGFR and albuminuria. Even AKI defined by a mild serum creatinine elevation (0.3 mg/dL) was independently associated with a significantly high risk for premature death. Therefore, individuals with diabetes and any episode of AKI deserve intensive surveillance for cardio-renal dysfunction.

Mitophagy significantly influences renal ischemia/reperfusion (I/R) injury and recovery. NLRX1 is recognized for its regulatory role in governing mitochondrial damage, autophagy, and the expression of pro-inflammatory factors. Despite the acknowledged involvement of NLRX1 in these crucial cellular processes, its specific function in renal I/R injury remains unclear. We detected the expression of NLRX1, the cGAS-STING pathway, and autophagy-related proteins using Western Blot analysis. RT-qPCR was utilized to measure the expression of NLRX1 mRNA and cytokines, and changes in mitochondrial DNA (mtDNA) within the cytoplasm. Immunofluorescence was applied to observe alterations in DNA distribution within the cytoplasm. The EtBr drug, which depletes mtDNA, and the Mdivi-1 mitophagy inhibitor, were used to verify the promotion of mitophagy by NLRX1. The results demonstrated that NLRX1 was downregulated after hypoxic/reoxygenation (H/R) injury, and there was an increase in cytoplasmic DNA. NLRX1 overexpression not only reduced IL-1β and IL-6 levels, but also decreased mtDNA in the cytoplasm. Additionally, NLRX1 further increases mitochondrial LC3 lipidation after H/R injury, and this effect is inhibited by Mdivi-1 drugs. The activation of the cGAS-STING pathway after H/R injury is inhibited by EtBr drugs and NLRX1. Co-immunoprecipitation results showed that NLRX1 could bind to STING. Moreover, inhibiting STING reversed NLRX1-induced mitochondrial LC3 lipidation. Our study reveals that NLRX1 can bind to STING to promote mitophagy and inhibits inflammation caused by mtDNA/cGAS/STING signaling.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are increasingly recognized as interconnected conditions with overlapping pathophysiological mechanisms. This review examines the transition from AKI to CKD, focusing on the molecular mechanisms, animal models, and biomarkers essential for understanding and managing this progression. AKI often progresses to CKD due to maladaptive repair processes, persistent inflammation, and fibrosis, with both conditions sharing common pathways involving cell death, inflammation, and extracellular matrix (ECM) deposition. Current animal models, including ischemia-reperfusion injury (IRI) and nephrotoxic damage, help elucidate these mechanisms but have limitations in replicating the complexity of human disease. Emerging biomarkers such as kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and soluble tumor necrosis factor receptors (TNFRs) show promise in early detection and monitoring of disease progression. This review highlights the need for improved animal models and biomarker validation to better mimic human disease and enhance clinical translation. Advancing our understanding of the AKI-to-CKD transition through targeted therapies and refined research approaches holds the potential to significantly improve patient outcomes.

Cardiopulmonary bypass (CPB) is a common procedure in cardiac surgery. CPB is a high-risk factor for acute kidney injury (AKI), and diabetes is also such a factor. Diabetes can lead to copper overload. It is currently unclear whether AKI after CPB in diabetic patients is related to copper overload.

To explore whether the occurrence of CPB-AKI in diabetic patients is associated with cuproptosis.

Blood and urine were collected from clinical diabetic and non-diabetic patients before and after CPB. Levels of copper ion, lactate, glucose, heat shock protein-70 (HSP-70), and dihydrolipoamide dehydrogenase (DLAT) were determined. A diabetic rat model was established and CPB was performed. The rats were assessed for the development of CPB-AKI, and for the association of AKI with cuproptosis by detecting copper levels, iron-sulfur cluster proteins and observation of mitochondrial structure by electron microscopy.

CPB resulted in elevations of copper, lactate, HSP-70 and DLAT in blood and urine in both diabetic and non-diabetic patients. CPB was associated with pathologic and mitochondrial damage in the kidneys of diabetic rats. Cuproptosis-related proteins also appeared to be significantly reduced.

CPB-AKI is associated with cuproptosis. Diabetes mellitus is an important factor aggravating CPB-AKI and cuproptosis.

To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund antimicrobials based on an evaluation of their value as opposed to the volumes used. The aim of this project was to evaluate the population-level health benefit of ceftazidime-avibactam in the NHS in England, for the treatment of severe aerobic Gram-negative bacterial infections when used within its licensed indications. The results were used to inform National Institute for Health and Care Excellence guidance in support of commercial discussions regarding contract value between the manufacturer and NHS England.

The health benefit of ceftazidime-avibactam was first derived for a series of high-value clinical scenarios. These represented uses that were expected to have a significant impact on patients' mortality risks and health-related quality of life. Patient-level costs and health-related quality of life of ceftazidime-avibactam under various usage scenarios compared with alternative management strategies in the high-value clinical scenarios were quantified using decision modelling. Results were reported as incremental net health effects expressed in quality-adjusted life-years, which were scaled to 20-year population in quality-adjusted life-years using infection number forecasts based on data from Public Health England. The outcomes estimated for the high-value clinical scenarios were extrapolated to other expected uses for ceftazidime-avibactam.

The clinical effectiveness of ceftazidime-avibactam relative to its comparators was estimated by synthesising evidence on susceptibility of the pathogens of interest to the antimicrobials in a network meta-analysis. In the base case, ceftazidime-avibactam was associated with a statistically significantly higher susceptibility relative to colistin (odds ratio 7.24, 95% credible interval 2.58 to 20.94). The remainder of the treatments were associated with lower susceptibility than colistin (odds ratio < 1). The results were sensitive to the definition of resistance and the studies included in the analysis. In the base case, patient-level benefit of ceftazidime-avibactam was between 0.08 and 0.16 quality-adjusted life-years, depending on the site of infection and the usage scenario. There was a high degree of uncertainty surrounding the benefits of ceftazidime-avibactam across all subgroups, and the results were sensitive to assumptions in the meta-analysis used to estimate susceptibility. There was substantial uncertainty in the number of infections that are suitable for treatment with ceftazidime-avibactam, so population-level results are presented for a range of scenarios for the current infection numbers, the expected increases in infections over time, and rates of emergence of resistance. The population-level benefit varied substantially across the scenarios, from 531 to 2342 quality-adjusted life-years over 20 years.

This work has provided quantitative estimates of the value of ceftazidime-avibactam within its areas of expected usage within the NHS.

Given existing evidence, the estimates of the value of ceftazidime-avibactam are highly uncertain.

Future evaluations of antimicrobials would benefit from improvements to NHS data linkages, research to support appropriate synthesis of susceptibility studies, and application of routine data and decision modelling to assess enablement value.

No registration of this study was undertaken.

This award was funded by the National Institute for Health and Care Research (NIHR) Policy Research Programme (NIHR award ref: NIHR135592), conducted through the Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions, PR-PRU-1217-20401, and is published in full in Health Technology Assessment; Vol. 28, No. 73. See the NIHR Funding and Awards website for further award information.

Acute kidney injury (AKI) is associated with adverse outcomes, including death and dialysis. The goal of this study was to identify prognostic biomarkers of AKI that could be used across multiple phenotypes of AKI and across different species.

Liquid chromatography/tandem mass spectrometry analysis of urine samples from three species (human, rat, and mouse) and four etiologies of AKI identified five potential biomarkers, of which two were validated, complement C3 and vitamin D-binding protein, in a cohort of 157 patients that developed AKI following cardiothoracic surgery. We studied the relationship between the biomarker's concentration in the urine and the development of a composite primary endpoint (stage 3 AKI within 10 days or death within 30 days).

Of the 153 patients who developed AKI following cardiovascular surgery, 17 met the combined primary outcome. The median concentration of urine complement C3 adjusted to urine creatinine had the best predictive value and was significantly higher in the primary outcome group than in the controls. Similarly, the median concentration of vitamin D-binding protein was higher in the primary outcome group.

The studies provide proof in principle that cross-species discovery analyses could be a valuable tool for identifying novel prognostic biomarkers in AKI. Urine complement C3 and vitamin D-binding protein could be promising early predictors of adverse outcomes in patients who develop AKI after cardiac surgery.

Acute kidney injury (AKI) is a severe complication of coronavirus disease 2019 (COVID-19) and is associated with a higher risk of mortality. Understanding the risk factors contributing to COVID-19-related AKI and mortality before vaccination is important for the initiation of preventative measures and early treatment strategies.

This study included patients aged ≥18 years diagnosed with COVID-19 through polymerase chain reaction from May 2020 to July 2021, admitted in three local hospitals in Taiwan, with an extended follow-up until June 30, 2022. A median follow-up period of 250 days was used to assess AKI development and mortality. AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. Multivarible Cox regression analysis of AKI and mortality-related risk factors were performed.

Of the 720 hospitalized patients with COVID-19, 90 (22%) developed AKI. Moreover, 80%, 10.1%, and 8.9% of the patients had stage 1, 2, and 3 AKI, respectively. Patients with stage 1 to 3 AKI had significantly lower survival rates than those without AKI ( p = 0.001). The mean duration of post-admission AKI occurrence was 9.50 ± 11.32 days. Older age, hypoalbuminemia, and higher D-dimer and ferritin levels were associated with COVID-19 mortality. In COVID-19 AKI, in addition to older age and high D-dimer and ferritin levels, chronic kidney disease emerged as an independent risk factor.

COVID-19-related AKI develops early, exhibits a temporal association with respiratory failure, and is linked to an unfavorable prognosis. The mortality rate increased according to the AKI stage ( p = 0.001). Age, albumin, D-dimer, and ferritin levels, and the underlying chronic kidney disease status upon admission are crucial factors for predicting AKI development, which increases the mortality risk. Monitoring the renal function not only within 10 days of COVID-19 onset, but also within 1 month after the disease onset.

It remains unclear whether the incidence of post-operative acute kidney injury (PO-AKI) has been reduced despite the recent emphasis on its early recognition and prevention in clinical practice. We aimed to investigate the trend in the incidence of PO-AKI and to identify the associated factors affecting its changes.

We gathered clinical data from patients who underwent non-cardiac major surgeries at three referral hospitals from 2005 to 2020. PO-AKI was defined as KDIGO AKI criteria within 7 days after surgery. Severe PO-AKI (S-PO-AKI) was defined as stage 2 or 3 AKI. The temporal change of PO-AKI was evaluated by joinpoint regression analysis and multivariable logistic regression based on a 3-year interval.

Among 138 235 patients, 8156 (5.9%) PO-AKI and 1127 (0.8%) S-PO-AKI occurred, respectively. The patients enrolled in recent years were older and more were women. They had more comorbidities and a higher PO-AKI risk compared with those included in past years. As time passed, the PO-AKI incidence decreased from 8.6% in 2005-07 to 5.1% in 2017-20, whereas S-PO-AKI incidence did not change (0.8% to 0.9%). In joinpoint analysis, PO-AKI incidence tended to decrease with annual percentage change (APC) of -4.2% per year [95% confidence interval (CI) -5.5% to -2.8%, P-value <.001), although S-PO-AKI did not (APC 0.9%, 95% CI -1.1 to 2.9%, P-value = .347). Similarly, the overall PO-AKI incidence decreased but S-PO-AKI did not, even after adjusting covariables.

The incidence of PO-AKI has decreased recently despite the increase in known risk factors; however, the incidence of S-PO-AKI has not decreased in recent years.

ClinicalTrials.gov Identifier: NCT05986474. Name of registry: Development of Synthetic Medical Data Generation Technology to Predict Postoperative Complications. URL: https://classic.clinicaltrials.gov/ct2/show/NCT05986474. Date of registration: 14 August 2023. Date of enrollment of the first participant to the trial: 27 September 2022, retrospectively registered.

Acute tubular injury (ATI) is a common diagnosis on renal biopsy. There are no accepted parameters to assess the severity of injury or predict recovery. An objective histologic grading system would be of immense value in clinical practice. The macrophage response to injury involves the MI phenotype which is proinflammatory and M2 which is prorepair. The study of these macrophages could aid in studying the severity and the recovery.

A total of 58 native kidney biopsies with features of ATI and a minimum follow-up of 12 weeks were graded into mild, moderate and severe, using scores for simplification, sloughing, and mitosis. These scores and the density of macrophages stained with CD68, CD163, and HLA-DR were correlated with serum creatinine at presentation and with recovery. The effect of chronicity index as measured by glomerulosclerosis, tubular atrophy, and interstitial fibrosis and of co-morbidities of age, hypertension, and diabetes on the recovery pattern was also studied.

All three histologic scores and the grades of ATI showed positive correlation with the serum creatinine level. The densities of CD 68 + and CD163 + macrophages also showed a significant correlation with serum creatinine level. However, none of these these histological features nor the macrophage densities predicted clinical recovery. Age >60 years, hypertension, diabetes, and chronicity score on biopsy were indicators of partial and delayed recovery.

The histopathological semiquantitative scoring system can be used routinely to grade ATI. However none of the studied parameters predicted recovery.

Examining regional variation in acute kidney injury (AKI) and associated outcomes may reveal inequalities and possibilities for optimization of the quality of care. Using the Danish medical databases, we examined regional variation in the incidence, follow-up and prognosis of AKI in Denmark.

Patients with one or more AKI episodes in 2017 were identified using population-based creatinine measurements covering all Danish residents. Crude and sex-and-age-standardized incidence rates of AKI were estimated using census statistics for each municipality. Adjusted hazard ratios (aHR) of chronic kidney disease (CKD), all-cause death, biochemical follow-up and outpatient contact with a nephrology department after AKI were estimated across geographical regions and categories of municipalities, accounting for differences in demographics, comorbidities, medication use, lifestyle and social factors, and baseline kidney function.

We identified 63 382 AKI episodes in 58 356 adults in 2017. The regional standardized AKI incidence rates ranged from 12.9 to 14.9 per 1000 person-years. Compared with the Capital Region of Denmark, the aHRs across regions ranged from 1.04 to 1.25 for CKD, from 0.97 to 1.04 for all-cause death, from 1.09 to 1.15 for biochemical follow-up and from 1.08 to 1.49 for outpatient contact with a nephrology department after AKI. Similar variations were found across municipality categories.

Within the uniform Danish healthcare system, we found modest regional variation in AKI incidence. The mortality after AKI was similar; however, CKD, biochemical follow-up and nephrology follow-up after AKI varied across regions and municipality categories.

The risk of developing a persistent reduction in renal function after postoperative acute kidney injury (pAKI) is not well-established.

Perform a multi-center retrospective propensity matched study evaluating whether patients that develop pAKI have a greater decline in long-term renal function than patients that did not develop postoperative AKI.

Multi-center retrospective propensity matched study.

Anesthesia data warehouses at three tertiary care hospitals were queried.

Adult patients undergoing surgery with available preoperative and postoperative creatinine results and without baseline hemodialysis requirements.

The primary outcome was a decline in follow-up glomerular filtration rate (GFR) of 40% relative to baseline, based on follow-up outpatient visits from 0-36 months after hospital discharge. A propensity score matched sample was used in Kaplan-Meier analysis and in a piecewise Cox model to compare time to first 40% decline in GFR for patients with and without pAKI.

A total of 95,208 patients were included. The rate of pAKI ranged from 9.9% to 13.7%. In the piecewise Cox model, pAKI significantly increased the hazard of a 40% decline in GFR. The common effect hazard ratio was 13.35 (95% CI: 10.79 to 16.51, p<0.001) for 0-6 months, 7.07 (5.52 to 9.05, p<0.001) for 6-12 months, 6.02 (4.69 to 7.74, p<0.001) for 12-24 months, and 4.32 (2.65 to 7.05, p<0.001) for 24-36 months.

Retrospective; Patients undergoing ambulatory surgery without postoperative lab tests drawn before discharge were not captured; certain variables like postoperative urine output were not reliably available.

Postoperative AKI significantly increases the risk of a 40% decline in GFR up to 36 months after the index surgery across three institutions.

Sepsis-induced acute kidney injury (S-AKI) is the most common type of acute kidney injury (AKI), accompanied by elevated morbidity and mortality rates. This study investigated the mechanism by which lipid droplets (LDs) degraded via autophagy (lipophagy)required for RAB7 regulated ferroptosis in the pathogenesis of S-AKI. Here, we constructed the S-AKI model in vitro and in vivo to elucidate the potential relationship of lipophagy and ferroptosis, and we first confirmed that the activation of lipophagy promoted renal tubular epithelial cell ferroptosis and renal damage in S-AKI. The results showed that lipopolysaccharide (LPS) induced a marked increase in lipid peroxidation and ferroptosis, which were rescued by ferrstain-1 (Fer-1), an inhibitor of ferroptosis. In addition, LPS induced the remarkable activation of RAB7-mediated lipophagy. Importantly, silencing RAB7 alleviated LPS-induced lipid peroxidation and ferroptosis. Thus, the present study demonstrated the potential significant role of ferroptosis and lipophagy in sepsis-induced AKI, and contributed to better understanding of the pathogenesis and treatment targets of AKI.

To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund antimicrobials based on an evaluation of their value as opposed to the volumes used. The aim of this project was to evaluate the population-level health benefit of cefiderocol in the NHS in England, for the treatment of severe aerobic Gram-negative bacterial infections when used within its licensed indications. The results were used to inform the National Institute for Health and Care Excellence guidance in support of commercial discussions regarding contract value between the manufacturer and NHS England.

The health benefit of cefiderocol was first derived for a series of high-value clinical scenarios. These represented uses that were expected to have a significant impact on patients' mortality risks and health-related quality of life. The clinical effectiveness of cefiderocol relative to its comparators was estimated by synthesising evidence on susceptibility of the pathogens of interest to the antimicrobials in a network meta-analysis. Patient-level costs and health outcomes of cefiderocol under various usage scenarios compared with alternative management strategies were quantified using decision modelling. Results were reported as incremental net health effects expressed in quality-adjusted life-years, which were scaled to 20-year population values using infection number forecasts based on data from Public Health England. The outcomes estimated for the high-value clinical scenarios were extrapolated to other expected uses for cefiderocol.

Among Enterobacterales isolates with the metallo-beta-lactamase resistance mechanism, the base-case network meta-analysis found that cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.32, 95% credible intervals 0.04 to 2.47), but the result was not statistically significant. The other treatments were also associated with lower susceptibility than colistin, but the results were not statistically significant. In the metallo-beta-lactamase Pseudomonas aeruginosa base-case network meta-analysis, cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.44, 95% credible intervals 0.03 to 3.94), but the result was not statistically significant. The other treatments were associated with no susceptibility. In the base case, patient-level benefit of cefiderocol was between 0.02 and 0.15 quality-adjusted life-years, depending on the site of infection, the pathogen and the usage scenario. There was a high degree of uncertainty surrounding the benefits of cefiderocol across all subgroups. There was substantial uncertainty in the number of infections that are suitable for treatment with cefiderocol, so population-level results are presented for a range of scenarios for the current infection numbers, the expected increases in infections over time and rates of emergence of resistance. The population-level benefits varied substantially across the base-case scenarios, from 896 to 3559 quality-adjusted life-years over 20 years.

This work has provided quantitative estimates of the value of cefiderocol within its areas of expected usage within the NHS.

Given existing evidence, the estimates of the value of cefiderocol are highly uncertain.

Future evaluations of antimicrobials would benefit from improvements to NHS data linkages; research to support appropriate synthesis of susceptibility studies; and application of routine data and decision modelling to assess enablement value.

No registration of this study was undertaken.

This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment Policy Research Programme (NIHR award ref: NIHR135591), conducted through the Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions, PR-PRU-1217-20401, and is published in full in Health Technology Assessment; Vol. 28, No. 28. See the NIHR Funding and Awards website for further award information.

Our goal was to create a simple risk-prediction model for renal function decline after cardiac surgery to help focus renal follow-up efforts on patients most likely to benefit.

This single-center retrospective cohort study enrolled 24 904 patients who underwent cardiac surgery from 2012 to 2019 at Fuwai Hospital, Beijing, China. An estimated glomerular filtration rate (eGFR) reduction of ≥30% 3 months after surgery was considered evidence of renal function decline. Relative to patients with eGFR 60 to 89 mL/min per 1.73 m2 (4.5% [531/11733]), those with eGFR ≥90 mL/min per 1.73 m2 (10.9% [1200/11042]) had a higher risk of renal function decline, whereas those with eGFR ≤59 mL/min per 1.73 m2 (5.8% [124/2129]) did not. Each eGFR stratum had a different strongest contributor to renal function decline: increased baseline eGFR levels for patients with eGFR ≥90 mL/min per 1.73 m2, transfusion of any blood type for patients with eGFR 60 to 89 mL/min per 1.73 m2, and no recovery of renal function at discharge for patients with eGFR ≤59 mL/min per 1.73 m2. Different nomograms were established for the different eGFR strata, which yielded a corrected C-index value of 0.752 for eGFR ≥90 mL/min per 1.73 m2, 0.725 for eGFR 60-89 mL/min per 1.73 m2 and 0.791 for eGFR ≤59 mL/min per 1.73 m2.

Predictors of renal function decline over the follow-up showed marked differences across the eGFR strata. The nomograms incorporated a small number of variables that are readily available in the routine cardiac surgical setting and can be used to predict renal function decline in patients stratified by baseline eGFR.

Contrast-induced acute kidney injury (CI-AKI) has become the third leading cause of hospital-acquired AKI, which seriously threatens the health of patients. To date, the precise pathogenesis of CI-AKI has remained not clear and may be related to the direct cytotoxicity, hypoxia and ischemia of medulla, and oxidative stress caused by iodine contrast medium, which have diverse physicochemical properties, including cytotoxicity, permeability and viscosity. The latest research shows that microRNAs (miRNAs) are also involved in apoptosis, pyroptosis, and autophagy which caused by iodine contrast medium (ICM), which may be implicated in the pathogenesis of CI-AKI. Unfortunately, effective therapy of CI-AKI is very limited at present. Therefore, effective prevention of CI-AKI is of great significance, and several preventive options, including hydration, antagonistic vasoconstriction, and antioxidant drugs, have been developed. Here, we review current knowledge about the features of iodine contrast medium, the definition, pathogenesis, molecular mechanism, risk factors, prevention and treatment of CI-AKI.

The incidence of acute kidney injury (AKI) is identified more frequently in noncritical compared with intensive care settings. The prognosis of malnourished AKI patients is far worse than those with normal nutritional status. However, a method for estimating the optimal amount of energy required to guide nutritional support among noncritically ill AKI patients is yet to be determined.

We evaluated the performance of weight-based formulas (20-30 kcal/kg/day) with the reference values of energy expenditure (EE) measured by indirect calorimetry (IC) among noncritically ill AKI patients during hospitalization. The statistics for assessing agreement, including total deviation index and accuracy within 10% represent the percentage of estimations falling within the IC value range of ±10%, were tested. Parameters for predicting the EE equation were also developed using a regression analysis model.

A total of 40 noncritically ill AKI patients were recruited. The mean age of participants was 62.5 ± 16.5 years with 50% being male. The average IC-derived EE was 1,124.6 ± 278.9 kcal/day with respiratory quotients 0.8-1.3, indicating good validity of the IC test. Receiving dialysis, protein catabolic rate, and age was not significantly associated with measured EE. Nearly all weight-based formulas overestimated measured EE. The magnitude of total deviation index values was broad with the proportion of patients achieving an accuracy of 10% being as low as 20%. The proposed equation to predict EE derived from this study was EE (kcal/day) = 618.27 + (8.98 x weight in kg) + 137.0 if diabetes - 199.7 if female (r2 = 0.68, P < .001). In the validation study with an independent group of noncritically ill AKI patients, predicted EE using the newly derived equation was also significantly correlated with measured EE by IC (r = 0.69, P = .004).

Estimation of EE by weight-based formulas usually overestimated measured EE among noncritically ill AKI patients. In the absence of IC, the proposed predictive equation, specifically for noncritically ill AKI patients might be useful, in addition to weight-based formulas, for guiding caloric dosing in clinical practice.

Acute kidney injury (AKI) is associated with adverse long-term outcomes, but many studies are retrospective, focused on specific patient groups or lack adequate comparators. The ARID (AKI Risk in Derby) Study was a five-year prospective parallel-group cohort study to examine this. Hospitalized cohorts with and without exposure to AKI were matched 1:1 for age, baseline kidney function, and diabetes. Estimated glomerular filtration rate (eGFR) and the urinary albumin:creatinine ratio (uACR) were measured at three-months, one-, three- and five-years. Outcomes included kidney disease progression, heart failure episodes and mortality. In 866 matched individuals, kidney disease progression at five years was found to be significantly increased in 30% of the exposed group versus 7% of those non-exposed (adjusted odds ratio 2.49 [95% confidence interval 1.43 to 4.36]). In the AKI group, this was largely characterized by incomplete recovery of kidney function by three months. Further episodes of AKI during follow-up were significantly more common in the exposed group (odds ratio 2.71 [1.94 to 3.77]) and had an additive effect on risk of kidney disease progression. Mortality and heart failure episodes were more frequent in the exposed group, but the association with AKI was no longer significant when models were adjusted for three-month eGFR and uACR. In a general hospitalized population, kidney disease progression after five years was common and strongly associated with AKI. Thus, the time course of changes and the attenuation of associations with adverse outcomes after adjustment for three-month eGFR and uACR suggest non-recovery of kidney function is an important assessment in post-AKI care and a potential future target for intervention. STUDY REGISTRATION: ISRCTN25405995.