AimsAcute Kidney Injury Research Articles

#3971 INJURY INDUCED RENAL FIBROSIS PROMOTES CYSTOGENESIS AND CYST GROWTH IN ADULT MICE WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

Abstract Background and Aims Acute kidney injury (AKI) is not a merely transient event, which can lead to a subsequent progression to chronic kidney disease (CKD). Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent inherited kidney disease caused by mutations in PKD1 or PKD2 gene. Previous studies showed that acute kidney injuries promote cystogenesis in adult mice with ADPKD. Fibrosis is a hallmark of AKI to CKD (AKI-CKD) transition, and positively correlated with renal cyst growth in humans. All these data imply a role of AKI-CKD transition in ADPKD.In this study, we aimed to determine the role of AKI-CKD transition in the ADPKD. Method We established AKI-CKD transition model by toxic or surgical injuries, and Pkd gene inactivation in adult mice was performed in different time point of AKI-CKD transition. The progression of renal fibrosis was shown by Western blotting analysis in toxic or surgical injury induced AKI-CKD transition model. Results We showed that renal injury before or after Pkd gene inactivation can both induce renal cyst formation in adult Pkd1 or Pkd2 mice, and the extent of cyst formation was correlated with the initial fibrosis level of three hits (injury and gene inactivation). Inactivation of Pkd1 gene at fibrosis recovery stage in surgery induced less cyst formation in adult Pkd1 mice. Enhanced renal fibrosis by repeated toxic injuries before gene inactivation accelerated renal cyst growth in Pkd1 mice. We further showed that the speed of cyst growth at the early stage in adult Pkd1 mice was decided by the baseline of renal fibrosis. Finally, we showed that conditional knockout of Ezh2 gene attenuated renal fibrosis and cyst growth in adult Pkd1 mice with established renal fibrosis. Conclusion Fibrotic responses in AKI-CKD transition is a driving force for renal cyst formation and growth in adult kidneys and inhibition of renal fibrosis through targeting EZH2 might be new therapeutic strategy for adult ADPKD.

#2524 RESOLVIN D1 ATTENUATES SEPSIS INDUCED ACUTE KIDNEY INJURY TARGETING MITOCHONDRIA AND NF-κB SIGNALING PATHWAY

Abstract Background and Aims Acute kidney injury is a highly common and multifactorial renal disease resulting in significant morbidity and mortality, especially sepsis-induced acute kidney injury. There is no effective therapy available to treat or prevent sepsis-induced acute kidney injury. One of the specialized pro-resolving mediators, Resolvin D1 exhibits special anti-inflammatory effects in several inflammatory disease models, but there is little evidence about the effect and mechanism of Resolvin D1 in sepsis-induced acute kidney injury. To explore the renal protective role of RvD1 in SI-AKI and to further explore the inherent pathophysiological mechanism, especially the role of mitochondrial function and NF-κB signaling pathway, in vitro and in vivo experiments were conducted. Method We conducted experiments to explore the effect and mechanism of Resolvin D1 in sepsis-induced acute kidney injury. In vitro, human proximal tubular epithelial cells were used to test the apoptosis ratio, cell viability and reactive oxygen species level. In vivo, C57BL/6 mice were injected with lipopolysaccharide to establish a sepsis-induced acute kidney injury model. Renal function and structure, apoptosis ratio of kidney cells, mitochondrial structure and function and related protein and gene levels were assessed. Results In vitro, the resolvin D1-treated group showed higher cell viability and lower reactive oxygen species levels and apoptosis ratios than the LPS group. In vivo, Resolvin D1 can not only improve renal function and mitochondrial function but also reduce the apoptosis ratio, while mediating mitochondrial dynamics and inhibiting NF-κB pathway. Conclusion Resolvin D1 has a good renoprotective effect by maintaining mitochondrial dynamics and inhibiting the NF-κB pathway. This provides an important basis for us to further develop the clinical therapeutic value of RvD1 in acute renal injury in sepsis.

#6306 SUSTAINED LOW-EFFICIENCY DIALYSIS VERSUS CONTINUOUS VENO-VENOUS HEMODIAFILTRATION OUTCOME IN CRITICALLY ILL PATIENTS

Abstract Background and Aims Acute kidney injury due to sepsis is the most common cause of AKI in critical care settings. Different modalities of renal replacement therapies (RRT) have been used to manage this condition including Continuous Renal Replacement Therapy (CRRT) and sustained low efficiency dialysis (SLED). The aim of this work was to compare the outcome of SLED and CRRT in the form of continuous veno-venous hemodiafiltration (CVVDHF) as methods of dialysis in sepsis induced AKI. Method We retrospectively analysed data from 120 patients; 20 patients received CVVHDF to manage AKI in the context of sepsis, 47 patients received SLED to manage AKI in the context of sepsis and the third group included 53 patients who have been treated with SLED to manage AKI not due to sepsis. Age was found to be significantly higher in sepsis induced AKI patients treated with SLED than patients treated with CVVHDF (65±10.1# 59.5±9.3 y, p = 0.03). Sex distribution or incidences of hypertension, diabetes mellitus, malignancy or liver disease were not statistically different between groups. Results Unadjusted 30 day mortality was 44.7% (21pt) in the SLED group Vs 50% (10pt) in the CVVHDF group, p = 0.07. Adjusted mortality was not statically significant between SLED and CVVHDF (OR 0.97, CI = 0.95-1.06). Hypotension occurred more frequently in patients treated with SLED (24 pt = 51.1% #5 pt = 25%, p < 0.001).Clotting occurred more frequently in the CVVHDF group as compared to SLED group (7 pt = 35% Vs 4pt = 8.5% p < 0.001). Conclusion Sustained low efficiency dialysis (SLED) and CVVHDF had comparable 30 day mortality as modalities of RRT in critically ill Patients with sepsis induced AKI. SLED still an attractive alternative to CRRT modalities due to lower cost and lower incidence of complications. Further larger studies are recommended.

#4641 RISK FACTORS FOR RRT RESTART AFTER CESSATION OF CRRT: A MULTICENTER STUDY

Abstract Background and Aims Acute Kidney Injury occurs frequently in patients admitted to the Intensive Care Unit (ICU) and continuous renal replacement therapy (CRRT) is a commonly used treatment modality in these patients. Restart of renal replacement therapy (RRT) after initial discontinuation of CRRT is also frequently needed. The purpose of this study is to identify clinical characteristics and biomarkers influencing the restart of RRT after the cessation of CRRT, and to build a predictive model using these parameters. Method This multicenter retrospective study includes 891 patients who were treated using CRRT from July 2012 to December 2020 in the ICU of 3 academic hospitals. The primary end point observed was the restart of RRT during hospitalization. Baseline characteristics were compared between the no restart and restart RRT groups. Using univariate analysis and logistic regression, a prospective index was developed, and receiver operator characteristic (ROC) curve analysis was performed to confirm the predictivity of the prognostic index. Results Restart of RRT was needed in 632 (71.2%) patients. Compared to patients that did not restarting, patients in the restart RRT group demonstrated higher age, higher BMI, higher baseline serum creatinine (Cr), lower urine output, longer ICU admission, and more comorbid conditions (HTN, DM, HF, ischemic heart disease). In the multivariate analysis, five parameters demonstrated independent influence on restart of RRT: HTN, Cr, ICU admission duration, BMI, and mean blood pressure. The prognostic index, which was calculated from these variables, showed a satisfactory potential to predict the restart of RRT after discontinuation of CRRT. ROC analysis revealed an area under the curve of 0.738 (95% CI, 0.703-0.773, p<0.001). Conclusion We found that 5 of the 40 parameters observed in our study were independent risk factors for the restart of RRT during admission and we successfully developed a prognostic index based on these variables to predict the restart of RRT after discontinuation of CRRT.

Regulation of pericyte metabolic reprogramming restricts the AKI to CKD transition

Background and aimsAcute kidney injury (AKI) is associated with high morbidity and mortality and is recognized as a long-term risk factor for progression to chronic kidney disease (CKD). The AKI to CKD transition is characterized by interstitial fibrosis and the proliferation of collagen-secreting myofibroblasts. Pericytes are the major source of myofibroblasts in kidney fibrosis. However, the underlying mechanism of pericyte-myofibroblast transition (PMT) is still unclear. Here we investigated the role of metabolic reprogramming in PMT. MethodsUnilateral ischemia/reperfusion-induced AKI to CKD mouse model and TGF-β-treated pericyte-like cells were used to detect the levels of fatty acid oxidation (FAO) and glycolysis, and the critical signaling pathways during PMT under the treatment of drugs regulating metabolic reprogramming. ResultsPMT is characterized by a decrease in FAO and an increase in glycolysis. Enhancement of FAO by the peroxisome proliferator-activated receptor gamma coactivator-1α (PGC1α) activator ZLN-005 or suppression of glycolysis by the hexokinase 2 (HK2) inhibitor 2-DG can inhibit PMT, preventing the transition of AKI to CKD. Mechanistically, AMPK modulates various pathways involved in the metabolic switch from glycolysis to FAO. Specifically, the PGC1α-CPT1A pathway activates FAO, while inhibition of the HIF1α-HK2 pathway drives glycolysis inhibition. The modulations of these pathways by AMPK contribute to inhibiting PMT. ConclusionsMetabolic reprogramming controls the fate of pericyte transdifferentiation and targets the abnormal metabolism of pericytes can effectively prevent AKI to CKD transition.

Acute kidney injury: a strong risk factor for hypoglycaemia in hospitalized patients with type 2 diabetes

AimsAcute kidney injury (AKI) is highly prevalent during hospitalization of patients with type 2 diabetes (T2D). We aimed to assess the impact of AKI and its severity and duration on the risk of hypoglycaemia in hospitalized patients with T2D.MethodsRetrospective cohort analysis of patients with T2D, admitted at a University Hospital in 2018–2019. AKI was defined as an increase in serum creatinine by ≥ 0.3 mg/dl (48 h) or ≥ 1.5 times baseline (7 days), and hypoglycaemia as blood glucose concentration < 70 mg/dl. Patients with chronic kidney disease stage ≥ 4 were excluded. We registered 239 hospitalizations with AKI and randomly selected 239 without AKI (control). Multiple logistic regression was used to adjust for confounding factors and ROC curve analysis to determine a cutoff for AKI duration.ResultsThe risk of hypoglycaemia was higher in the AKI group (crude OR 3.6, 95%CI 1.8–9.6), even after adjusting for covariates (OR 4.2, 95%CI 1.8–9.6). Each day of AKI duration was associated with a 14% increase in the risk of hypoglycaemia (95%CI 1.1–1.2), and a cutoff of 5.5 days of AKI duration was obtained for increased risk of hypoglycaemia and mortality. AKI severity was also associated with mortality, but showed no significant association with hypoglycaemia. Patients with hypoglycaemia had 4.4 times greater risk of mortality (95%CI 2.4–8.2).ConclusionsAKI increased the risk of hypoglycaemia during hospitalization of patients with T2D, and its duration was the main risk factor. These results highlight the need for specific protocols to avoid hypoglycaemia and its burden in patients with AKI.

MiR-21-5p in extracellular vesicles obtained from adipose tissue-derived stromal cells facilitates tubular epithelial cell repair in acute kidney injury

Background aimsAcute kidney injury (AKI) is often associated with poor patient outcomes. Extracellular vesicles (EVs) have a marked therapeutic effect on renal recovery. This study sought to explore the functional mechanism of EVs from adipose tissue-derived stromal cells (ADSCs) in tubular epithelial cell (TEC) repair in AKI. MethodsADSCs were cultured and EVs were isolated and identified. In vivo and in vitro AKI models were established using lipopolysaccharide (LPS). ResultsEVs increased human kidney 2 (HK-2) cell viability; decreased terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells and levels of kidney injury molecule 1, cleaved caspase-1, apoptosis-associated speck-like protein containing a CARD, gasdermin D-N, IL-18 and IL-1β; and elevated pro-caspase-1. EVs carried miR-21-5p into LPS-induced HK-2 cells. Silencing miR-21-5p partly eliminated the ability of EVs to suppress HK-2 cell pyroptosis and inflammation. miR-21-5p targeted toll-like receptor 4 (TLR4) and inhibited TEC pyroptosis and inflammation after AKI by inhibiting TLR4. TLR4 overexpression blocked the inhibitory effects of EVs on TEC pyroptosis and inflammation. EVs suppressed the nuclear factor-κB/NOD-like receptor family pyrin domain-containing 3 (NF-κB/NLRP3) pathway via miR-21-5p/TLR4. Finally, AKI mouse models were established and in vivo assays verified that ADSC-EVs reduced TEC pyroptosis and inflammatory response and potentiated cell repair by mediating miR-21-5p in AKI mice. ConclusionsADSC-EVs inhibited inflammation and TEC pyroptosis and promoted TEC repair in AKI by mediating miR-21-5p to target TLR4 and inhibiting the NF-κB/NLRP3 pathway.

Downregulation of nesfatin-1 expression in acute kidney injury in vivo in wistar rats and in vitro in cultured cells

AimsAcute kidney injury (AKI) is a debilitating condition followed by sudden kidney damage or failure within hours or days of its occurrence. AKI is characterized by rapid increase in serum creatinine/BUN and decrease in urine output. Nesfatin-1 is an endogenous peptide reported to possess anorexic, antioxidant and anti-apoptotic properties. Although few clinical studies have shown altered nesfatin-1 levels in hemodialysis patients, however, there are no reports investigating the distribution and expression pattern of nesfatin-1 in AKI. Materials and methodsNesfatin-1 expression was determined in different disease induced models of AKI by immunoblotting, immunofluorescence and RT-PCR. Gene markers of oxidative stress and inflammation were determined by RT-PCR. The expression of different markers of AKI was measured by assay kits and RT-PCR analysis. Key findingsThere was a significant increase in serum levels of creatinine and BUN in AKI rats followed by significant increase in KIM-1 in the kidneys. Significant decrease in nesfatin-1 expression along with increased expression of IL-1β, TNF-α and decreased expression of SOD and catalase was observed in doxorubicin and cisplatin induced AKI rats. However, SOD and catalase expression were upregulated in glycerol induced AKI rats. Moreover, in vitro treatment of renal NRK-52E epithelial cells with nesfatin-1 reversed the changes induced by doxorubicin. SignificanceOur study reports for the first time, nesfatin-1 expression is decreased in kidneys of different models of AKI induced rats as well as cultured NRK-52E renal epithelial cells. Further studies are required to understand the possible molecular mechanism and therapeutic potential of nesfatin-1 in acute kidney injury.

MO1030: Aki Awareness and Survival in Paediatric Patients in a Western Romania Emergency Hospital—a 7 Years Retrospective Cohort Study

Abstract BACKGROUND AND AIMS Acute kidney injury (AKI) is a globally increasing healthcare problem being usually associated with low awareness and high mortality. Several large studies have drawn attention to the increasing cases of AKI in the paediatric population, mostly in the neonatal setting but also in critically ill patients and young adults. It was suggested that increased awareness could lead to early diagnosis and intervention, therefore improved survival. METHOD We performed a retrospective cohort study in ‘Louis Turcanu’ Emergency County Hospital for Children in Timisoara, Romania. Data have been extracted from the hospital electronic database, between 1 January 2014 and 31 December 2020. The cohort included 127 457 patients (aged 1 day–18 years) who had at least two serum creatinine levels determined during the same hospital admission. AKI was defined and staged according to Kidney Disease Improving Global Outcomes (KDIGO) guidelines (and 2021 Consensus conference). AKI awareness was considered the recognition of AKI diagnosis during admission as noted in the medical records according to ICD-10 Clinical Modification codes (N17.0, N17.1, N17.2, N17.8, N19, N99.0 and P96.0). AKI non-awareness was considered in patients presenting AKI criteria without diagnoses recognition in the medical records. We considered baseline serum creatinine the lowest serum creatinine value in 7 days from admission. RESULTS Over the 7-year period, 1867 patients developed AKI out of 127 457 hospital admissions. The overall AKI incidence was 1.46% and the annual incidence increased 3.95-fold during the 7 years (from 0.6% in the first year to 2.37% in the seventh). Staging AKI according to Acute Kidney Injury Network (AKIN), stage 1 was identified by us in 23.2% of the AKI cases, stage 2 in 31.3% and stage 3 in 45.5%. AKI awareness (as defined above) was 27.5% (overall), being significantly increased in premature babies (P &amp;lt; .012), full-term neonates (P &amp;lt; .0001) and toddlers (P &amp;lt; .0001). In AKI stages 1 and 2 the diagnosis of AKI (included in the patient's documents according to ICD 10) was less frequent as compared to stage 3. So, we considered that AKI awareness is significantly lower in early AKI stages (1 and 2) (i.e.16.9 and 19.7% respectively) as compared with late AKI (stage 3) 38.3% (P &amp;lt; .001). Only 19 patients (1.01%) required renal replacement therapy (RRT). During the 7-year period, the all-cause mortality in our cohort was 0.32% (410 patients died) being 0.13% in the no AKI patients and 12.8% in the AKI group (57.89% in patients treated with RRT). Odds ratio (OR) of death in the AKI diagnosed patients (aware and non-aware) was 107.67 versus non-AKI patients (P &amp;lt; .0001). The risk of death in the AKI aware group was 3.3 higher versus AKI non-aware group (P &amp;lt; .001). These not expected, reverse results, are attributable to a very low awareness (as defined by us in Methods) in the early stages of AKI. A higher mortality rate was associated with AKIN stage 3—OR of 1.53 (P &amp;lt; .001). The average length of hospital stay was significantly higher in AKI patients (20.79 days) as compared with the no AKI group (5.74 days). CONCLUSION The awareness of AKI in children remains a problem worldwide with implications on the survival of patients. Being aware of AKI means early identifying the risk of AKI, early diagnosis and early intervention. As it was presented above late diagnosis and awareness are associated with high mortality rate and the need for interventions (RRT) associated with high mortality risk.

FC 127: Acute Kidney Injury and Exposure to Nephrotoxic Drugs in Critically Ill Patients: A Report From the Multicenter Rescue Project in the Netherlands

Abstract BACKGROUND AND AIMS Acute kidney injury (AKI) is a common problem in patients admitted to the intensive care unit (ICU). Nephrotoxic drugs play a causal role in 14–28% of the ICU AKI cases and are one of the few preventable AKI causes. The Dutch multicenter project ‘Towards a leaRning mEdication Safety system in a national network of Intensive Care Units—timely detection of adverse drug Events’ (RESCUE) aims to improve medication safety in ICU patients with respect to drug-induced AKI. This requires knowledge on which drugs may cause AKI and the strength of their effects. Obtaining such knowledge is challenging due to confounding. Especially in the ICU, where patients often have multiple comorbidities, AKI risk factors may also be indications or contraindications for drugs. We aimed to estimate the independent associations between nephrotoxic drug groups and AKI in ICU patients by adjusting for drug group-specific confounders. METHOD We used a detailed electronic health record database of ICU patients admitted to 13 different ICUs between 2010 and 2019 in the Netherlands. The database contains admission characteristics, (chronic) comorbidities, physiology measurements, Acute Physiology and Chronic Health Evaluation IV admission diagnoses and predicted mortality probabilities, serum creatinine (SCr), drug administrations, arterial blood pressure and renal replacement therapy (RRT) treatments. We included admissions with at least two SCr values and excluded admissions with one or more missing AKI risk factor values. Using the Kidney Disease: Improving Global Outcomes Clinical Practice Guideline for Acute Kidney Injury, we diagnosed and staged AKI according to the SCr and RRT criteria. We recorded exposure to eight drug groups widely regarded as acutely nephrotoxic [1] until AKI onset, discharge or death. Multilevel logistic regression models were applied to estimate the independent association between each drug group and AKI. The estimates were adjusted for drug group-specific confounders: we registered which AKI risk factors were indications or contraindications for each drug group. RESULTS We included 98 391 ICU admissions, of which 14 074 (14%) were diagnosed with AKI, ranging between 6 and 21% across the ICUs. Of all admissions with AKI, 8962 (64%), 1283 (9%) and 3829 (27%) developed AKI stage 1, stage 2 or stage 3, respectively (Figure 1). The percentage of admissions exposed to nephrotoxic drug groups was 7% for aminoglycosides, 6% for nonsteroidal anti-inflammatory drugs (NSAIDs), 6% for penicillin combinations, 5% for glycopeptide antibiotics, 2% for sulfonamides, 2% for antivirals for herpes infections, 1% for immunosuppressants and 1% for antimycotic antibiotics. All drug groups were associated with a higher odds of AKI except NSAIDs and penicillin combinations (Table 1). While penicillin combinations were not associated with AKI, NSAIDs were associated with a lower odds of AKI. The drug groups with the highest odds of AKI were immunosuppressants [odds ratio (OR) 2.26, 95% confidence interval (95% CI) 1.97–2.60; P &amp;lt; 0.001), sulfonamides (OR 1.84, 95% CI 1.65–2.04; P &amp;lt; 0.001) and aminoglycosides (OR 1.70, 95% CI 1.59–1.81; P &amp;lt; 0.001). The NSAID group was the only group that showed a higher OR after adjustment. CONCLUSION We estimated the independent associations between nephrotoxic drug groups and AKI by adjusting for drug-group specific confounders. Our results provide new estimates of the strengths of the associations. Surprisingly, NSAIDs were associated with a lower odds of AKI. This association might be biased due to residual confounding by contraindication. Future studies may investigate strategies to avoid drug-induced AKI.

MO328: Acute Renal Failure in COVID-19: Aetiology and Renal Evolution. AKI-COVID Registry of the Spanish Society of Nephrology

BACKGROUND AND AIMSAcute kidney injury (AKI) has been described as a frequent complication in patients with COVID-19. The incidence of AKI is estimated to be around 5%–80% depending on the series; however, data characterizing the type of AKI and the evolution of renal function parameters in the medium-long term are still limited.METHODBased on the initial AKI-COVID Registry, we developed an extended registry where we registered retrospectively new variables that included clinical and demographic characteristics, infection severity parameters and data related to AKI (ethology, KDIGO classification, need of renal replacement therapy, analytic values: baseline creatinine, maximum creatinine during admission, creatinine at discharge or death, creatinine at 1 month after hospitalization and urinary parameters). Recovery of kidney function was defined as difference in at discharge or posthospitalization creatinine < 0.3 mg/dL with respect basal creatinine.RESULTSOur analysis included 196 patients: 74% male, mean age 66 + 13 years; 65% hypertensive, 33% diabetic and 22% chronic kidney disease. According to the KDIGO classification: 66% AKI KDIGO3, 17% KDIGO2 and 15% KDIGO1. Creatinine values ​​are summarized in Table 1. We found significant differences in the baseline/high creatinine differential; these differences were lost after hospitalization.Table 1.Analytical evolution of the patients included in the study. ANOVA test for independent samples The main types of AKI were prerenal (35%) and acute tubular necrosis secondary to sepsis (ATN) (53%). 89% of patients with ATN presented AKI KDIGO 3, compared with 57% in the prerenal group (P < .001). Patients with prerenal AKI had greater comorbidity. On the other hand, patients with ATN AKI developed more serious COVID-19 infection: higher percentage of severe pneumonia, admission to the intensive care unit and need for orotracheal intubation. The analytical parameters were more extreme in patients with ATN AKI, except for creatinine and urea upon admission, which were higher in the prerenal AKI group.A total of 89 patients died during the study; 65% of ATN AKI patients versus 31% of prerenal-AKI patients (P < .001). The ATN was a mortality risk factor, whit a hazard ratio 2.74 [95% confidence interval (95% CI )1.29–5.7] (P = .008) compared with the prerenal AKI.CONCLUSIONAKI in hospitalized patients with COVID19 presented with two different clinical patterns. Prerenal AKI more frequently affected older, more comorbid patients, and with a mild COVID19 infection. The NTA AKI affected younger patients, with criteria of severity of infection and multiplying mortality almost three times. In analytical control 1-month post-hospitalization, most of the patients recovered their kidney function. Although the implications of AKI associated with COVID-19 in the development of chronic kidney disease are still unclear, our data suggest that most patients will recover kidney function in a medium term.

MO289: IL33 Exerts Toxicity in the Heart as Secreted by Renal Inflammation

Abstract BACKGROUND AND AIMS Acute kidney injury (AKI) is a major cardiovascular risk factor, regardless of the severity or the origin of the AKI. Among this risk, AKI imparts an array of signals and long-term physiologic alterations that can precipitate heart insufficiency and hypertrophy. However, few direct molecular mechanisms have been identified that show how AKI leads to cardiac disease and maladaptation. The aims of this project are to assess the role of IL33 in remote cardiac damage after AKI. METHOD AKI was induced in mice by ischemia–reperfusion injury of both right and left kidneys by 30min of reversible artery occlusion. To examine the role of renal inflammation more specifically, we used the unilateral ureteral obstruction (UUO) model, which does not cause acute injury. For UUO, an incision was made in the lower left quadrant of the abdomen and the left ureter was isolated and ligated permanently. Mice were treated to manipulate select signaling pathways with either Adenovirus-associated virus 9 (AAV9) or recombinant proteins. We generated AAV9 carrying the IL33 gene or an empty vector (EV) under a CMV promoter and injected 1012 viral particles intrathoracically in 6 to 9 days old pups. Recombinant IL33 (rIL33) or vehicle were injected intraperitoneally in IL33 KO adult mice after AKI (at D0, D1 and D2). Echocardiography was performed either at baseline or after 28 days of surgery. Hearts were fixed in 4% paraformaldehyde overnight and paraffin-embedded for fibrosis (picrosirius staining) and cardiomyocyte area measurement (WGA staining and ImageJ software). IL33 citrine reporter mice (IL33cit) in the heterozygous state were used to show IL33 expression. RESULTS Our data showed that UUO and AKI were strong inducers of cardiac dysfunction after 28 days in adult mice, measured with echocardiography (mean ejectional fraction (EF): 58, 46, 47% in Sham, AKI and UUO group respectively, P &amp;lt; .05). Cardiac pathology was also present such as increased fibrosis in hearts from WT mice after AKI compared with Sham (2.3%, 4.5%, 8.3% of fibrosis area in Sham, AKI and UUO respectively, P &amp;lt; 0.05) and an increased mean cardiomyocyte area indicative of hypertrophy (333, 597, 1246 µm2 in Sham, AKI and UUO respectively, P &amp;lt; .05). However, cardiac function and architecture were preserved either after 28 days of AKI or UUO in IL33 KO mice. In parallel, WT mice injected with AAV9-CMV-IL33 showed impaired cardiac function compared with mice injected with a control AAV9-empty vector after 8 weeks (EF 58% versus 42% in AAV-EV and AAV-IL33 respectively, P &amp;lt; .05). After AKI, AAV9-IL33 mice had even more impaired cardiac function compared to AAV-empty control mice (EF 42% versus 35% in AAV-EV and AAV-IL33 respectively). In IL33 KO mice, the injection of 1 µg of rIL33 in the early days of AKI restored cardiac dysfunction and fibrosis after 28 days of AKI (EF 59 versus 43% in Sham and AKI respectively, P &amp;lt; .05), yet vehicle injected mice were still protected. IL33 expression viewed with the Citrine reporter mice showed that it was locally downregulated in the heart after AKI, which was strictly localized in pericytes in the heart (PDGFRß+ cells). ELISA for protein levels of IL33 confirmed the reduction of this cytokine in hearts from WT AKI and UUO mice after 28 days compared with Sham (29.6, 4.2 and 2.7 fg of IL33/µg of protein in Sham, AKI and UUO hearts respectively, P &amp;lt; .05). CONCLUSION IL33 seems to exert toxicity in the heart as secreted by renal inflammation, which is against some previous reports in the literature where it was suggested to be a protective factor to the heart (whether released from the kidney or from within the heart).

MO357: Nephrology Consultation to Improve Acute Kidney Injury Outcome on General Wards

Abstract BACKGROUND AND AIMS Acute kidney injury (AKI) affects up to one in five hospitalized patients and is independently associated with high morbidity and mortality. Additionally, patients have an increased risk for developing chronic kidney disease (CKD) after AKI. The combined impact of short- and long-term consequences and the high incidence of AKI results in a significant financial burden. Adequate intervention and follow-up might reduce the clinical impact of AKI, however the evidence for this remains inconclusive. The aim of this prospective cohort study was to evaluate whether nephrology consultation had an impact on patient follow-up and clinical outcome after AKI. METHOD All patients, admitted to VU medical centre in Amsterdam between October 2018 and April 2019, were screened for AKI by an automatic warning system integrated into the hospital's electronic patient record. This warning system sent a signal if serum creatinine would rise &amp;gt;27 µmol/L in 48 h or increased by a factor of at least 1.5 within 7 days (KDIGO criteria for AKI). The nephrology or internal medicine resident would then assess eligibility. Exclusion criteria were: a rise in serum creatinine that did not represent an actual AKI, admittance to the intensive care unit at the time of the signal, admission for kidney transplantation and patients that died before consultation was possible. After identification, nephrology consultation was provided. For the least severe AKI cases (KDIGO stage 1), this was done by telephone after review of the patient record, and for severe AKI cases (KDIGO stage 2 and 3) by full clinical review. Patients were grouped according to adherence (consult or no consult) to this protocol. Adequate follow-up was defined as a specific post-AKI referral to a nephrologist or general practitioner after hospital discharge. Recovery of serum creatinine and 6-month mortality were used as primary measures of clinical outcome. RESULTS A total of 371 cases of possible AKI were identified by the warning system. Of those case, 218 cases were eligible for inclusion. In 160 cases, nephrology consultation was performed (consult group). In 58 cases, there was no consult (no-consult group). The average age was 67.4 years. The consult and no-consult groups were similar at baseline (mean age, male/female, incidence of hypertension and diabetes), besides a higher incidence of CKD in the consult group (79% versus 64%; P = 0.034). The consult group had a significantly larger percentage of severe AKI cases (stage 2 or 3 in 29.4% of cases versus 12.1%; P = 0.021). Treatment was initiated in 93.1% of consult cases and in 70.6% of no-consult cases (P &amp;lt; 0.001) and there was a more profound decrease in the serum creatinine level from peak till 6 months (–33.7% versus –19.4%; P = 0.033)). All-cause mortality (34.1% versus 27.6%; P = 0.510), post-AKI follow-up (83% versus 73.2%; P = 0.116) and median serum creatinine value at six months (119 µmol/L versus 100 µmol/L; P = 0.334) did not differ between the consult and no-consult group. A 6-month serum creatinine was only available for 50% of cases in both groups. CONCLUSION When compared with cases of generally less severe AKI in which nephrology consultation was not performed, cases with nephrology consultation were associated with higher rates of treatment of AKI, faster recovery of kidney function and similar mortality. The data are in line with earlier non-randomized research which concluded that nephrology consultation can be linked to improved outcome in AKI. Before any definitive conclusions can be drawn, these associations should be found replicable in a randomized multi-centre setting and cost-effectiveness and feasibility should be analysed.

MO295: Acute Kidney Injury in COVID-19 Patients: Medium-Term Evolution of Renal Function

BACKGROUND AND AIMSAcute kidney injury (AKI) is a common complication among patients hospitalized with COVID-19. The incidence of AKI is estimated to be around 5%–80%, according to the series, but data on renal function evolution is limited. Our main objective was to describe the incidence of AKI in patients with SARS-CoV-2 infection; secondarily, we analysed the severity of AKI and medium-term renal function evolution in these patients.METHODA retrospective observational study that included patients hospitalized a single hospital, diagnosed with SARS-CoV-2 infection, who developed AKI (March-May 2020). We register clinical and demographic characteristics, creatinine upon admission and prior to discharge, as well as creatinine and CKD-EPI glomerular filtration rate (eGFR) after at least 3 months after discharge. CKD was defined according to KDIGO stages based on the eGFR (G3-G5). The KDIGO classification was used to define and classify AKI. Recovery of kidney function was defined as difference in at discharge or post-hospitalization creatinine < 0.3 mg/dL with respect basal creatinine. The clinical follow-up ranged from admission to death or end of study.RESULTSOf 258 patients hospitalized with SARS-CoV-2 infection, AKI occurred in 73 (28.3%). 63% (n = 46) were men; the mean of age was 69 years (57–76). DRA severity: 35 (48%) KDIGO-1, 15 (21%) KDIGO-2 and 23 (31%) KDIGO-3. The mean stay was associated with the severity of AKI: 7 days (3–11) for KDIGO-1, 11 days for KDIGO-2 (5–22) and 12 days (8–35) for KDIGO-3 (P = .02).The stage of CKD established differences in the severity of AKI: 66.6% (n = 6) of the patients with CKD G4–G5 presented AKI-KDIGO 3 versus only 25.0% (n = 4) in the CKD-G3 patients (P = .02). Admission to the ICU was more frequent in KDIGO 2–3 versus KDIGO-1 [39% (n = 15) versus 9% (n = 3); P < .01]. Of the 48 patients discharged, 30 (62.5%) had recovered their baseline renal function upon discharge. Only 2 are still on RRT after 8 months (2.7% of all patients). Of the 25 patients died (34% of patients with AKI) with a median time of 3 days from DRA diagnosis (1–8).Renal function of 35 patients was monitored, which correspond to 19 (54%) KDIGO-1, 8 (23%) KDIGO-2, 8 (23%) KDIGO-3 stages. In these patients, analytical control starting 3 months after hospitalization revealed FG 66 (SD 30; 56–76) mL/min/1.73 m2. We have not found differences in renal function between pre- and post-hospitalization in related test. A total of 77% (n = 37) of discharged patients recovered their baseline renal function in the post-hospitalization control.CONCLUSIONThe incidence of AKI in the context of COVID-19 in our series was 28.3%, with an associated mortality of 34.2%. Most of the patients presented with AKI KDIGO 1 (47.9%). The severity of AKI is associated with a longer hospital stay, admission to the ICU and the requirement for RRT. The advanced stages of CKD pre-admission showed more severity of AKI. The maintenance in TRS in our series has been 2.7%. Patients who were discharged for recovery/improvement of COVID-19 had normalized kidney function during subsequent follow-up, regardless of the severity of the AKI developed on admission for COVID-19.

MO613: Acute Kidney Injury and Hypoglycaemia Risk in Hospitalized Diabetic Patients

Abstract BACKGROUND AND AIMS Acute kidney injury (AKI) remains one of the most common complications in hospitalized diabetic patients. The relationship between chronic kidney disease (CKD) and hypoglycaemia is well established: both renal neoglucogenesis and insulin clearance are diminished in this population, increasing the risk for hypoglycaemic episodes. A correlation between AKI and hypoglycaemia remains to be proven. A recent study stated that AKI increases hypoglycaemia risk in critically ill patients; other showed higher risk for hypoglycaemic episodes after hospital discharge. We focused on a correlation between AKI and hypoglycaemia risk in hospitalized diabetic patients. METHOD We performed an observational retrospective analysis of all hospitalized diabetic patients in Internal Medicine's ward between 2018 and 2019. Our sample was divided according to the presence/absence of AKI during hospitalization. We considered AKI as a rise of serum creatinine (SCr) &amp;gt;0.3 mg/dL in 48 h or &amp;gt;50% in a week. Baseline kidney function was calculated using CKD-EPI equation, according to the mean ambulatory SCr from the previous 6 months. All patients with CKD stage ≥4 were excluded. We collected 240 diabetic patients with AKI and, to obtain similar sample sizes, aleatory selected 240 diabetic patients without AKI. Hypoglycaemia was defined as peripheral blood sugar levels &amp;lt;70 mg/dL and stratified according to American Diabetes Association classification. IBM SPSS 23.0 was used to perform all statistical analysis. RESULTS We selected 480 diabetic patients with an average age of 81.2 ± 9.2 years; most were women (59.8%) and 36.0% were treated with insulin. Across both populations, hypoglycaemic episodes were more prevalent in insulin-treated patients, with lower baseline glomerular filtration rates (GFR) and higher age and were associated with longer hospitalizations (16.6 ± 12.4 days) and higher 30-day mortality rate {OR 3.7 [confidence interval (CI) 95% 1.6–8.7], P &amp;lt; 0.001}. Diabetic patients with AKI were older (82.7 versus 80.1 years, P = .001), had lower baseline GFR (59.1 versus 70 mL/min/1.73 m2 P &amp;lt; 0.001), longer hospital stays (13.8 ± 11.3 days, P = 0.007) and higher mortality rate (14.0% versus 7.3%, P = 0.05). Hypoglycaemic episodes were more prevalent in diabetic patients with AKI (40.8% versus 15.8%, P &amp;lt; 0.001); the occurrence of AKI during hospitalization increased hypoglycaemia risk by 4.2 times [OR 4.21 (CI 2.56–6.97), P &amp;lt; 0.001]. This relationship maintained after multivariate analysis, which accounted the differences between both groups. The first hypoglycaemic event occurred, on average, 6.7 ± 6.1 days after AKI; a longer time in AKI, irrespective of the severity, associated with higher hypoglycaemia risk and 30-day mortality rate, with a cut-off of 5.5 days resulting in higher frequency of this adverse event. CONCLUSION We found that AKI constitutes an important risk factor for hypoglycaemic episodes in hospitalized diabetic patients, mainly in elderly patients and those with lower baseline GFR. AKI's duration, irrespective of the severity, was the main contributor to higher hypoglycaemia risk. Our data support the need for individualized risk stratification for hypoglycaemic events—we should adapt our clinical practice to prevent or mitigate the impact of these adverse events during hospitalization and after discharge.

MO342: Impact of COVID-19 Pandemic on In-Hospital Acute Kidney Injury Epidemiology and Outcomes: A Retrospective Cohort Study

BACKGROUND AND AIMSAcute kidney injury (AKI) is a common complication in patients affected by coronavirus disease-19 (COVID-19) and its development is associated with high mortality [1]. However, it is also clear that the COVID-19 pandemic has effects on the management of diseases not directly related to COVID-19 [2]. In this study, we investigated the impact of the COVID-19 pandemic on general intrahospital AKI incidence and outcomes.METHODWe performed a retrospective cohort study comparing data on AKI epidemiology and outcomes of patients hospitalized from January 2016 to December 2019 (pre-COVID-19 period) and from January to December 2020 (COVID-19 period, including both SARS-CoV-2 negative and positive patients). AKI was defined and classified by evaluating the kinetics of intra-hospital creatinine (comparing the peak to the minimum serum creatinine level, considered as the basal value) [3]. The prevalence of chronic kidney disease (CKD) (i.e. eGFR < 60 mL/min) was calculated in patients with previous creatinine values available. Patients with CKD stage 4–5 (i.e. eGFR < 30 mL/min/1.73 m2) and with a length of hospital stay > 30 days were excluded.RESULTSA total of 51 681 patients during the pre-COVID-19 period and 10 ,062 during the COVID-19 period (9026 SARS-CoV-2 negative and 1036 SARS-CoV-2 positive patients) were analysed. Patients admitted in the COVID-19 period were significantly older, with a higher prevalence of males and a reduced prevalence of chronic conditions. In-hospital AKI incidence was 31.7% during the COVID-19 period (30.5% in SARS-CoV-2 negative patients and 42.2% in SARS-CoV-2 positive ones) as compared with 25.9% during the pre-COVID-19 period (P < .0001) (Fig. 1). Similarly, the COVID-19 period showed an increase in AKI stage 2–3 incidence both for AKI on CKD and for ‘de novo AKI’. In multivariate analysis, demographic characteristics, length of hospital stay, ICU admission, main comorbidities, basal sCr, admission period (pre-COVID-19 or COVID-19) and SARS-CoV-2 infection were significantly associated with the risk of AKI. In particular, the admission in the COVID-19 period increased the risk of AKI [OR 1.18, 95% confidence interval (95% CI) 1.12–2.25] regardless of SARS-CoV-2 infection. Moreover, we found that in the COVID-19 period, there was an increased number of patients admitted to ICU, accompanied by a significant increase in the length of hospital stay and intrahospital mortality. In the multivariate analysis, development of AKI, admission in the COVID-19 period and active SARS-CoV-2 infection remained significantly and independently associated with mortality risk (Fig. 2).Figure 1:Incidence and staging of in-hospital AKI. Comparison of AKI incidence and stages between patients hospitalized in the pre-COVID-19 period (2016–2019) versus COVID-19 period (2020). *P < 0.0001 versus pre-COVID-19; § P < .0001 versus pre-COVID-19 and SARS-CoV-2 negative.Figure 2:Cox regression analyses for intra-hospital mortality in hospitalized patients between 2016 and 2020.CONCLUSIONOverall, we found that AKI was more common and severe in the COVID-19 period, regardless of SARS-CoV-2 infection, when compared with patients admitted to the same hospital during the four years before the pandemic. So, we provide evidence that the COVID-19 pandemic has changed general in-hospital AKI epidemiology. These findings call attention to the need to adapt the resources dedicated to the prevention and management of the intra-hospital AKI in response to health emergencies.

MO288: Kidney Tubule Polyploidization Preserves Residual Kidney Function and Assures Survival During Acute Kidney Injury

Abstract BACKGROUND AND AIMS Acute Kidney Injury (AKI) is characterized by a rapid deterioration of kidney function. Recently, we showed that tubular epithelial cells (TC) respond to AKI by triggering polyploidy, a condition in which a normally diploid cell acquires additional sets of chromosomes. Polyploidy offers several advantages, but in the kidney the biological significance of polyploidization remains unclear. In this study we hypothesized that polyploidy (i) is the predominant cellular response early during AKI and (ii) that is an adaptive stress response required to maintain a residual kidney function assuring survival. METHOD To address these hypotheses, we employed in vivo transgenic models based on the Fluorescence Ubiquitin Cell Cycle Indicator (FUCCI) technology in combination with YAP1 downregulation. In these models, mice were subjected to unilateral ischemia reperfusion injury (IRI) or glycerol-induced rhabdomyolysis to induce AKI. Polyploid cells have been then characterized by single cell-RNA sequencing analysis, cell sorting, FACS analysis, super-resolution and transmission electron microscopy. RESULTS After AKI, YAP1 is activated triggering TC polyploidization. Polyploid TC increase in parallel to massive cell death triggered by AKI suggesting that polyploidization could be a means to escape cell death. Indeed, we found that polyploid TC tends to accumulate genome instability and survive, while diploid TC do not. Of note, virtually all dying cells were cycling cells based on the Fucci2aR reporter suggesting that TC death occurred during the S or G2/M phase. As polyploid TC increase immediately following AKI, they may be required to survive injury and damage by sustaining renal function. In order to evaluate the functional role of polyploid cells during AKI, we generated mice where YAP1 is knocked-out specifically in TC (YAP1ko mice). Indeed, after AKI, YAP1ko mice showed a reduced number of polyploid cells, worsened kidney function and a dramatic reduction of mouse survival, proving that polyploidization is required to survive AKI. CONCLUSION We demonstrated that (i) after AKI TC accumulate genome instability and die or become polyploidy; (ii) TC polyploidy is essential to preserve residual kidney function immediately after AKI.

MO365: Single-Cell Profiling Analysis Reveals the Transcriptomic Landscape Of Kidneys in Patients With Acute Kidney Injury

Abstract BACKGROUND AND AIMS Acute kidney injury (AKI) is a common clinical syndrome associated with considerable mortality and healthcare costs. Up to now, the underlying pathological mechanisms of AKI are still unclear, and specific strategies for early diagnosis and treatment of AKI are lacking. In this research, single-cell RNA sequencing (scRNA-seq) was applied to kidney biopsies of patients with AKI to elucidate novel molecular mechanisms and intercellular communications. METHOD The transcriptomes of human kidney specimens obtained from subjects with AKI and renal transplant healthy living donors were defined by scRNA-seq technology. Differentially expressed genes (DEGs) and cell clusters of the kidney were determined. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed, and cell–cell crosstalk communication analysis among distince cell subtypes were conducted. RESULTS A total of 16 distinct cell clusters were determined in kidney from subjects of AKI and control. Proximal tubule cells of AKI had up-regulation of novel pro-apoptotic genes including USP47, RASSF4, EBAG9, IER3 and NUB1, which have not been reported previously. Further, proximal tubule cells highly expressed endoplasmic reticulum stress related genes (PDIA6, ATF6, HSPA5 and DNAJC3), autophagy related genes (S100A11, CLDN1, TMBIM6, RB1CC1 and VMP1) and genes enriched in RIG-1 signaling. PALM3 was overexpressed in proximal tubule cells of AKI at both mRNA and protein levels, which is involved in cell adhesion, TLR4 signaling and infammation response. DEGs overexpressed in other tubular cells were primarily enriched in NOD-like receptor signaling, estrogen signaling, interleukin-12-mediated signaling and IL-17 signaling. Glomerular cells such as EC upregulated DEGs participating in cell adhesion, apoptosis and chemotaxis. Overexpressed genes in kidney-resident immune cells including macrophages, NK-T cells, monocytes and dendritic cells suggested abnormal regulation related with leukocyte activation, chemotaxis, cell adhesion and complement activation. In addition, the ligand-receptor interactions analysis revealed cell–cell communication contributing to adhesion, recruitment and infiltration of inflammatory cells into the kidneys, and cytokine production in the process of AKI. CONCLUSION Together, this study reveals distinct cell-specific transcriptional landscapes of kidney in AKI patients, also altered signaling pathways and potential cell-cell crosstalk in development of AKI. These data may provide new insights into the pathogenesis and potential therapeutic strategies of AKI.

MO275: A Biomarker of Acute Kidney Injury from Proven Renal Origin

Abstract BACKGROUND AND AIMS Acute kidney injury (AKI) is a threatening, multi-aetiological syndrome encompassing a variety of forms and damage patterns. AKI lacks sufficiently specific diagnostic tools to evaluate the distinct combination of pathophysiological events underlying each case, which limits personalized and optimized handling. Therefore, a pathophysiological diagnosis based on new urinary biomarkers is sought for practical (readiness and non-invasiveness) and conceptual reasons, as the urine is a direct product of the kidneys. However, biomarkers found in the urine may also have extra-renal origin, thus conveying pathophysiological information from other organs or tissues. In fact, very few biomarkers of AKI have been proven to have a renal origin. Urinary plasminogen activator inhibitor 1 (PAI-1) has been associated to AKI in experimental models, although its origin and traffic to the urine are not known. The aim of this study was to investigate whether the urinary PAI-1 found in the urine following AKI is shed directly by renal structures or has a blood-borne origin. A further objective was to study whether urinary PAI-1 also associates to human AKI. METHOD AKI was induced in male Wistar rats by a single dose of cisplatin or by ischemia-reperfusion to study the blood or renal origin of urinary PAI-1. Blood and urine samples were collected on day 0 (basal) and on the day of maximal damage. The kidneys were collected at sacrifice (i.e. the day of maximal damage). The origin of urinary PAI-1 was studied with the in situ renal perfusion method. At maximal damage time, the right kidney was ligated, and the left kidney was perfused with Krebs-dextran solution. Urine was collected during perfusion. If PAI-1 was secreted by tubule cells directly to the urine, it should be detected in the urine during perfusion. If PAI-1 had a blood borne origin, PAI-1 should disappear from the urine during perfusion. The level of PAI-1 was also analyzed in the urine of AKI patients. RESULTS Our results show that urinary PAI-1 levels increase after AKI and correlate with an increased expression in kidney tissue. During in situ renal perfusion with Krebs–dextran solution, PAI-1 remained in the urine of AKI rats, suggesting that renal cells shed this protein directly to the urine. PAI-1 is also significantly increased in the urine of AKI patients. Its low correlation with other urinary markers such as neutrophil gelatinase-associated lipocalin or NAG suggests that PAI-1 provides complementary and distinct pathophysiological information. CONCLUSION Urinary PAI-1 is produced by the kidneys after AKI and secreted directly to the urine providing specific pathological information, which needs to be explored further. Urinary PAI-1 is one of the few biomarkers of AKI with proven renal origin and therefore a potentially valuable tool for a prospective pathophysiological diagnostic panel.

MO1024: Exposures and Susceptibilities in Paediatric Acute Kidney Injury—Impact on Awareness and Survival

Abstract BACKGROUND AND AIMS Acute kidney injury (AKI) is a growing global healthcare problem in the adult and paediatric population. In comparison with the adult population where the coexisting chronic conditions (e.g. diabetes, hypertension) increase the mortality risk during AKI, in children without chronic conditions one can assess the direct impact of AKI on mortality. Current paediatric studies state the need for increased awareness of AKI, for identifying susceptibilities and for the need to correct modifiable exposures in order to improve outcomes. METHOD We conducted a retrospective observational study in the ‘Louis Turcanu’ Emergency County Hospital for Children in Timisoara, Romania. Data were extracted from the hospital electronic database, between 1 January 2014 and 31 December 2020. The study cohort included 127 457 patients (aged 1 day–18 years) who had at least two serum creatinine levels determined during the same hospital admission. AKI was defined and staged according to Kidney Disease Improving Global Outcome (KDIGO) guidelines (and 2021 Consensus Conference) using Acute Kidney Injury Network (AKIN) criteria. Baseline serum creatinine was considered the nadir serum creatinine in 7 days from admission. AKI awareness in different medical clinics was considered the recognition of AKI diagnosis during admission as noted in the medical records according to ICD-10 Clinical Modification codes (N17.0, N17.1, N17.2, N17.8, N19, N99.0 and P96.0). AKI non-awareness was considered in patients presenting AKI according to AKIN without diagnoses recognition in the medical reports. RESULTS Over the 7-year study, 1867 patients developed AKI (out of 127 457 hospital admissions). The overall AKI incidence was 1.46%. The diagnosis of AKI was lacking (non-awareness) in 72.5% of AKI cases. We evaluated the exposures and susceptibilities of AKI patients and their impact on awareness and mortality. Taking into account the fact that the study addressed paediatric patients, exposures and susceptibilities have been changed accordingly. The considered exposures were: sepsis, critical illness, circulatory shock, burns, trauma, major non-cardiac surgery, nephrotoxic drugs, contact with poisonous plants and mechanical ventilation. Our regression equation proved to be a good fit for the model, explaining only 3.8% of AKI awareness (R2 = 0.038) and 22.9% of death events (R2 = 0.229). AKI awareness increases with the presence of dehydration (by 2.29-fold, P &amp;lt; .05) and heart failure (by 2.54-fold, P &amp;lt; .001). The risk of death increases with the presence of prematurity (by 2.33-fold, P &amp;lt; .0001), cancer (by 2.45-fold, P &amp;lt; .0001), anaemia (by 4.06-fold, P &amp;lt; .0001) and chronic illness (by 2.65-fold, P &amp;lt; .0001). The susceptibilities were: female gender, chronic kidney disease, chronic diseases (heart, lung, liver), diabetes mellitus, cancer, anaemia, very low birth weight, heart failure, arterial hypertension and stem cell transplant. Our regression equation proved to be a good fit for the model, explaining only 9.4% of AKI awareness (R2 = 0.094) and 43.6% of deaths (R2 = 0.436). The awareness increases with the presence of sepsis (by 1.73-fold, P &amp;lt; .0001), of critical illness (by 2.41-fold, P &amp;lt; .0001) and mechanical ventilation (by 1.54-fold, P &amp;lt; .0001). The risk of death increases in the presence of sepsis (by 3.26-fold, P &amp;lt; .0001), of critical illness (by 7.42-fold, P &amp;lt; .0001), of mechanical ventilation (by 10.58-fold, P &amp;lt; .0001) and hypovolemic shock (by 10.58-fold, P &amp;lt; .0001). CONCLUSION The presence of more severe exposures and susceptibilities increased the awareness of AKI but also increased the risk of death. The diagnosis of AKI in our medical records is late, therefore late diagnosis has no benefits concerning the evolution and mortality of paediatric patients with AKI.