Related Acute Kidney Injury Research Articles

Editor's Choice Articles for July.

Editor's Choice Articles for July.

Efficacy and Safety of Two Comparable Single Low Doses of Rasburicase Followed By Allopurinol in Adult Patients with Acute Leukemia

BACKGROUND: Hyperuricemia is a major cause of tumor lysis syndrome (TLS) related acute kidney injury. Certain hematologic malignancies (acute leukemia, high-grade lymphoma) pose a high-risk for spontaneous and chemotherapy-induced TLS. Allopurinol, a xanthine oxidase inhibitor, can inhibit formation of new uric acid (UA), but it does not eliminate the already formed UA. Alternatively, urate oxidases like rasburicase (ELITEK®, Sanofi Genzyme) can markedly and rapidly decrease UA levels through oxidation of UA to allantoin and hydrogen peroxide. In a phase III trial, rasburicase therapy more rapidly controlled UA than allopurinol in adults with hyperuricemia or at high-risk for TLS. However, rasburicase is expensive, especially when used as per the manufacturer's recommended dosage of 0.2mg/kg/day for up to 5 days. Numerous reports have shown that lower, and even single, doses are effective in lowering UA levels.OBJECTIVES: To determine the efficacy and safety of two single low doses of rasburicase (1.5mg vs. 3mg) in adult patients with acute leukemia and elevated plasma uric acid ≥ 7.5mg/dL.METHODS: Patients ≥ 18 years treated inpatient for acute leukemia with UA ≥ 7.5 mg/dL and at risk for TLS were randomized to one of two treatment arms (ClinicalTrials.gov Identifier: NCT01564277). Patients received either rasburicase 1.5mg (Arm A) or rasburicase 3mg (Arm B) intravenously over 30 minutes on day 1 in an open-label and unblinded fashion. All patients received allopurinol 300mg daily on days 1-6 (dose reduced for reduced calculated creatinine clearance). Plasma samples for UA evaluation were collected at baseline, and at approximately 4, 24, 48, 72, 96, 120, 144 hours after the Day 1 dose of rasburicase. If UA > 7.5 mg/dL at 24 or 48 hours, then additional dose of rasburicase could be administered (1.5mg for Arm A, 3mg for Arm B). Primary endpoint was the response rate of obtaining UA ≤ 7.5mg/dL within 24 hrs of rasburicase treatment. Secondary endpoints included rate of patients that maintained UA ≤ 7.5 mg/dl on days 2-6, rate of patients who required additional rasburicase doses, rate of patients experiencing significant worsening of renal function, as well as safety of low single-dose rasburicase. Patients were followed for adverse events (AE; as defined in CTCAE version 4) for up to 30 days after last dose of rasburicase or resolution of drug-related AE.RESULTS: 24 patients were enrolled on this phase 2 study (12 on each arm; Table 1). 83% of patients in both arms achieved UA response by 24 hours (Table 2). Two pts in Arm A (baseline UA: 14.2 and 17.6 mg/dL) and three pts in Arm B (baseline UA: 15.3, 10.2, 11.9 mg/dL) were given one additional rasburicase dose. Only one pt (from Arm A) had UA > 7.5 mg/dL between days 2-6. None of the patients had doubling of their baseline serum creatinine or required hemodialysis support. Average decrease in UA was lower in Arm A as compared to Arm B (5.5 vs. 6.8 mg/dL). AE data from 21 pts showed that both low doses were overall well tolerated and most toxicities were unrelated to rasburicase. No patient deaths were attributed to rasburicase. An ad-hoc analysis showed significant rasburicase specific cost benefits using either of the low doses as compared to FDA approved dosage and other studied regimens (Table 3).CONCLUSIONS: Single low doses of rasburicase (1.5mg and 3mg) plus allopurinol are well tolerated and appear to be equally efficacious in decreasing UA levels in adult patients with leukemia at high risk for TLS. If baseline UA is elevated (>12 mg/dL), a 3mg or higher dose of rasburicase might be preferable. Preliminary cost analysis profiling favors the use of the low dose rasburicase. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Acute Kidney Injury in Chemotherapy for Children with Pediatric Malignancy

Background: Acute kidney injury (AKI) is one of severe complications during the anti-cancer chemotherapy. The study by Lahoti et al. revealed that 36% of adult patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome developed AKI on chemotherapy, and the 8-weeks mortality rates were about 15% of AKI patients in contrast to 3% of non-AKI patients. Therefore, it is very important to diagnose of AKI early and accurately.Purpose: The purpose of this study is to identify the predictive biomarker of AKI in children with pediatric cancer.Materials and Methods: In the present study, 16 children with cancer were enrolled. To evaluate AKI, we used RIFLE criteria modified by AKI Network group. The severity of AKI based on RIFLE criteria divided into 5 categories (Risk, Injury, Failure, Loss and End-stage). We measured five urinary biomarkers (total protein (TP), albumin (Alb), N-Acetyl-glucosaminidase (NAG), β2-microglobulin (BMG), and liver-type fatty acid-binding protein (L-FABP)) related AKI because these five biomarkers could measure commercially.Results: We obtained the Laboratory data of 16 children received total 58 courses of chemotherapy. In 31 (53.4%) of 58 courses, AKI developed. To reveal a predictive biomarker, we investigated as follows in total 31 times developed AKI; 1) the frequency that each biomarker increased, and 2) the day when each biomarker increased based on the day when AKI developed based on RIFLE criteria. In total, TP, Alb, NAG, BMG, and L-FABP increased 17 (55%), 16 (52%), 18 (58%), 20 (65%), and 24 (77%) in AKI of total 31 times, respectively. Also, the median day when TP, Alb, NAG, BMG, and L-FABP increased was 9.0 (range: 0-29), 8.5 (range: 0-29), 9.5 (range: 0-42), 6.0 (range: 0-35), and 13.0 (range: 0-42) days before the day when AKI developed, respectively. L-FABP was found to be a predictive marker of AKI showing the best area under the ROC curve value (AUC) during chemotherapy (AUC = 0.753, sensitivity = 77.4%, specificity = 63.3%).Conclusion: These results showed that L-FABP is a possible predict biomarker of AKI in chemotherapy for children with pediatric cancer. DisclosuresNo relevant conflicts of interest to declare.

Clinical value of neutrophil/lymphocyte ratio in early prediction of the incidence of organ dysfunction and 28-day mortality in patients with sepsis

To evaluate the clinical value of neutrophil/lymphocyte ratio (NLR) in early prediction of the incidence of sepsis-induced organ dysfunction and 28-day mortality. A retrospective study was conducted in 815 adult patients with sepsis admitted to the department of critical care medicine of the First Affiliated Hospital of China Medical University from January 2017 to December 2019. The clinical data including age, gender and complication were collected, and the peripheral blood routine indexes at 24, 48 and 72 hours after the diagnosis of sepsis were collected, and the NLR was calculated. The primary endpoint of the study was the incidences of sepsis related acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC) and acute liver failure (ALF); the secondary endpoint was the 28-day in-hospital mortality in septic patients with organ dysfunction. Univariate and multivariate Logistic regression were used to analyze the risk factors of organ dysfunction and 28-day mortality in patients with sepsis, the receiver operating characteristic curve (ROC curve) was drawn and the area under the ROC curve (AUC) was calculated to evaluate the predictive value of NLR for organ dysfunction and 28-day mortality in patients with sepsis. A total of 714 patients with sepsis were enrolled for final statistical analysis. There was no significant difference in NLR at 24, 48 and 72 hours in patients with or without organ dysfunction (such as AKI, ARDS, DIC and ALF). Logistic regression analysis showed that there was no significant difference in NLR at 24 hours with 28-day in-hospital mortality [odds ratio (OR) = 1.006, 95% confidence interval (95%CI) was 0.994-1.019, P = 0.323]. However, NLR at 48 hours and 72 hours had a significant difference with 28-day mortality (48 hours: OR = 1.026, 95%CI was 1.013-1.040, P = 0.000; 72 hours: OR = 1.021, 95%CI was 1.005-1.037, P = 0.010), which suggested that NLR at 48 hours and 72 hours after diagnosis were independent risks factor for 28-day mortality in patients with sepsis. ROC curve showed that the AUC of NLR at 48 hours was 0.598, 95%CI was 0.540-0.658, P = 0.02; when the cut-off value was 10.1, the sensitivity and specificity for predicting 28-day mortality was 75.2% and 58.0%, respectively; the AUC of NLR at 72 hours was 0.595, 95%CI was 0.536-0.655, P = 0.03; when the cut-off value was 9.24, the sensitivity and specificity for predicting 28-day mortality was 75.3% and 59.9%, respectively. NLR cannot predict the occurrence of AKI, ARDS, DIC and ALF in sepsis in early stage. NLR has a certain clinical value in predicting 28-day mortality in patients with sepsis, but its predictive efficiency is low.

MO341VALUE OF THE CELL CYCLE ARREST BIOMARKERS IN THE DIAGNOSIS OF PREGNANCY RELATED ACUTE KIDNEY INURY

Abstract Background and Aims Pregnancy related acute kidney injury (PRAKI) is still a common serious problem in developing countries. Insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor metalloproteinases-2 (TIMP-2) can identify critically ill patients at risk for the development of severe AKI. Aims: To identify main causes and timing of PRAKI and to study the G1 cell cycle arrest biomarkers in cases diagnosed with (PRAKI) as a diagnostic tool. Method 80 pregnant women diagnosed with PRAKI were recruited from a single hospital as well as 30 age-matched pregnant women with normal pregnancy participated in this study. A urine specimen was collected from all study participants with established AKI within 24 hours of ICU admission to measure [TIMP-2]*[IGFBP7]. Results The incidence of PRAKI was 1.1%. The most common cause of PRAKI is preeclampsia/eclampsia spectrum (61%). Most of the cases occur in the third trimester (60%) and postpartum period (23%). At a cutoff 0.33 ng/mL, the estimated sensitivity and specificity of urinary [TIMP-2]*[IGFBP7] in predicting PRAKI is 100% (95% CI) with NPV and PPV are 100%. Conclusion Urinary [TIMP-2]*[IGFBP7] serves as a sensitive and specific biomarker in the diagnosis of PRAKI.

MO370PREGNANCY-RELATED ACUTE KIDNEY INJURY IN TUNISIA: A CLINICAL CHALLENGE

Abstract Background and Aims Acute kidney injury (AKI) is a complex disorder that occurs in several clinical settings. During pregnancy, there are additional unique conditions that contribute to AKI. The clinical manifestations of Pregnancy related acute kidney injury(PRAKI) range from a minimal elevation in serum creatinine to severe renal failure requiring renal replacement therapy and may be associated with significant morbidity and mortality in young healthy women. This study aims to describe epidemiologic features, study clinical profile and outcomes of women with PRAKI and identify risk factors related to requiring hemodialysis among patients. Method We performed a retrospective study over a 5-year period (2015–2019) in a Tunisian intensive care unit. All patients presenting PRAKI were included. Results Ninety-six cases of PRAKI were listed. The rate of AKI during pregnancy-related hospitalizations was 16% .the average age was 31 ± 5 years. Most women were from urban areas (62%) but with insufficient prenatal care (57%).Seventy-eight percent underwent cesarean section delivery. PRAKI occurred in the postpartum in 79%of the cases. Oligo-anuria was the most common clinical feature of PRAKI, noted in 82% of our patients. The leading etiological causes were pre eclampsia, eclampsia, postpartum haemorrhage and sepsis respectively, in 49%, 38%, and 24% of the cases. Hemodialysis was required in 23% of cases. In the adjusted regression analysis, factors associated with dialysis were insufficient prenatal care (p=0,010 ; O Ra=24,113), HELLP syndrome (p=0,003 ; ORa=35,129), disseminated intravascular coagulation (p=0,007 ; OR=11,854), average duration of oliguria (p=0,001; ORa=3,025) , Failure stage of RIFLE criteria while admitted (p=0,009; ORa=2,09) and length of ICU stay (p=0,042 ; ORa=1,118). Renal outcome was favorable, with a complete renal function recovery for 72 patients (75%). Only four patients (4%) developed chronic renal failure. Mortality rate was 13%. Conclusion PRAKI is a dreaded complication of pregnancy with high morbidity and mortality. Prevention of PRAKI requires an improvement of the sanitary infrastructures with the implementation of an obligatory prenatal consultation in order to prompt management of the underlying risk factors

Factors associated with acute kidney injury during delivery or the postpartum period: A case control study

IntroductionTo investigate the incidence of risk factors associated with acute kidney injury(AKI) occurring during the intrapartum or the immediate postpartum period. Material and MethodsA retrospective case control study in a tertiary UK hospital of pregnant women identified with AKI in labour or in the postpartum period between July 2019 and June 2020 was carried out. Women identified with pregnancy related AKI (pr-AKI) in labour or postpartum were compared with a matched cohort of women with no evidence of pr-AKI, using multiple regression analysis. ResultsIn 4600 births, 71 women with pr-AKI and 142 control women were identified. The antenatal and intrapartum risk factors strongly associated with pr-AKI were pre-eclampsia, prolonged ruptured membranes, delivery by emergency caesarean section and greater blood loss at delivery (all p < 0.001 in multivariable regression). ConclusionPr-AKI is relatively common, occurring in 1.5 % of our cohort. Women who are overweight, have prolonged rupture of the membranes, an emergency caesarean section and/or a postpartum haemorrhage are at greatest risk. Clinicians should be check renal function before prescribing non-steroidal medication for postpartum pain relief if there are risk factors for AKI.

Alterations in the lipid profile associate with a dysregulated inflammatory, prothrombotic, anti-fibrinolytic state and development of severe acute kidney injury in coronavirus disease 2019 (COVID-19): A study from Cincinnati, USA

Background and aimsReduction of atherogenic lipoproteins is often the ultimate goal of nutritional interventions, however this is complicated given that hypolipidemia is frequently observed in coronavirus disease 2019 (COVID-19) patients. We aimed to explore the association of hypolipidemia with patient outcomes in terms of immunothrombosis and multiorgan injury, focusing on specialized apolipoproteins apo A1 and apo B. MethodsLipid profiles of 50 COVID-19 patients and 30 sick controls presenting to the Emergency Department (ED) were measured in this prospective observational study. The primary outcome was development of severe acute kidney injury (AKI). Need for hospitalization and ICU admission were secondary outcomes. Lipoproteins were analyzed for independent association with serum creatinine (SCr) increase ratio and correlated with a wide panel of biomarkers. ResultsCOVID-19 cohort had significantly lower apo A1 (p = 0.006), and higher apo B/apo A1 ratio (p = 0.041). Patients developing severe AKI had significantly lower LDL-C (p = 0.021). Apo B/apo A1 was associated with 2.25-fold decrease in serum SCr increase ratio, while LDL-C with a 1.5% decrease. Hypolipidemia correlated with low plasminogen, ADAMTS13 activity/VWF:Ag, and high inflammatory biomarkers (CRP, IL-6, IL-8, IL-10), plasminogen activator inhibitor-1 (PAI-1), ED creatinine, and SCr increase ratio. ConclusionAlthough favored in dietetics, findings of a low LDL-C in COVID-19 patients should be alarming in light of our observations. Low apo B/apo A1 ratio and LDL-C are predictive of renal deterioration in COVID-19 patients, and low LDL-C in particular may potentially serve to indicate COVID-19 related AKI driven by disrupted fibrinolysis and a secondary thrombotic microangiopathy-like process.

POS-040 DIAGNOSTIC VALUE OF URINE MICROSCOPY IN PREDICTING OUTCOME OF HOSPITALIZED PATIENTS WITH ACUTE KIDNEY INJURY: A SINGLE-CENTER PROSPECTIVE STUDY

Acute kidney injury (AKI) is common in hospitalized and critically ill patients and has an important modifying effect on mortality, kidney recovery and health resources. Evaluation of the urine sediment is often viewed as a complementary measure for providing additional insight into the diagnosis and severity of AKI; however, it has not formally been integrated in consensus definitions. This is a prospective observational cohort study aimed at identifying the diagnostic value of urine microscopy of in-patients admitted at Perpetual Succour Hospital from May 2016 to May 2017 with AKI, specifically intrinsic and prerenal AKI in relation to predicting outcome such as worsening AKI, need for in-hospital dialysis, or in-hospital death. Eligible patients had clinical data and serum creatinine levels extracted. Urine samples were collected, and each had a dipstick test done. A single investigator did the evaluation of urine sediment. A urine microscopy scoring system was derived based from the number of granular casts, muddy-brown casts and renal tubular epithelial cells. The urine microscopy score was correlated to mortality, worsening or recovery of renal function, and need for renal replacement therapy (RRT). A total of 102 patients were eligible. The average age was 63.47 years old, and majority were males (59.8%). Sepsis was the most common cause of AKI (48%) followed by Cardiorenal Syndrome (20.6%). Most patients were hypertensive and diabetic (33.3%). As for patients’ creatinine results, their average baseline was 1.93 mg/dl with an eGFR of 43.32 ml/min. Creatinine levels during urine microscopy averaged at 4.72 + 2.97, and upon discharge, creatinine levels were 2.39 + 1.93 with corresponding eGFR of 39.94 + 34.75 ml/min. The urine microscopy score did not show a statistically significant association with regards to greater need for dialysis and its discontinuation (p value of 0.131 and 0.500 respectively). However, there is a trend towards an association with the patient’s mortality, though not statistically significant (p value= 0.084). Tests of correlations using Pearsons test showed that the relationship between urine microscopy scoring system and rise in creatinine percentage from baseline (r = 0.075, p = 0.475), as well as between the percent decrease in creatinine (r = 0.105, p = 0.349) were weak and not statistically significant. The presence of hematuria on patient’s outcome showed that the presence of RBC >10/hpf was significantly associated with the need for RRT (p= 0.015) and mortality (p= 0.039). Also, the presence of Renal Tubular Cells was significantly associated with dialysis (p= 0.002), while its absence was associated with no need for RRT (p= 0.002). Most importantly, the absence of Renal Tubular cells was significantly associated with renal recovery (p= 0.047). Moreover, there is a trend towards the association of the presence of Muddy Brown Casts and mortality (p=0.066). The presence of Renal tubular epithelial cells, muddy brown casts and hematuria are associated with mortality and need for RRT. More importantly, there is a trend towards an association of a higher urine microscopy score with mortality. Septic AKI seems to have higher urine microscopy scores; this finding may imply that the urine microscopy scoring system may be most useful in septic AKI in predicting outcome.

POS-185 POINT OF CARE TESTING FOR CAPILLARY CREATININE CONCENTRATION IN PREGNANT WOMEN AT LOW AND HIGH RISK FOR PREGNANCY-RELATED ACUTE KIDNEY INJURY

Pregnancy related acute kidney injury (PR-AKI) is associated with increased morbidity and mortality. Diagnosis remains challenging due to gestational physiological adaptations affecting serum creatinine and a lack of definitions validated perinatally. Point of care testing (PoCT) for creatinine has potential to enhance identification and triaging of women at risk of PR-AKI, and may in turn improve prevention, diagnosis and timely treatment. Before implementing creatinine PoCT within maternity care, accuracy must be established in both low-and high-risk pregnant women. This study aimed to i) perform a validation study of PoCT for capillary creatinine using the StatSensor Xpress Creatinine analyser (Nova Biomedical) across all gestations in low-risk women with normal renal function ii) to develop a model to improve PoCT accuracy in low-risk women and to test the model in a second cohort of women with PR-AKI risk factors. A multi-centre prospective cohort study was undertaken recruiting 138 women low-risk for PR-AKI and 49 women with risk factors for PR-AKI. Serum creatinine and capillary creatinine concentrations were compared in low-risk women to assess device accuracy. Regression analysis was used to develop a model to accurately estimate serum creatinine from PoCT creatinine concentrations and validated on serum creatinine and capillary creatinine from participants with PR-AKI risk factors. Accuracy was low in the low-risk cohort (Figure 1). Results indicated that, on average, the PoCT was significantly higher than the serum creatinine results (mean result 62.3 µmol/L (SD 13.6) vs. 46.2 µmol/L (SD 8.3), p<0.001). However, the accuracy of the device improved following the implementation of an adjustment factor. In women with risk factors for PR-AKI, predicted and true creatinine concentrations did not differ (46.4 µmol/L (SD 4.6) vs. 46.3 µmol/L (SD 8.3), respectively, p=0.86) (Figure 2).View Large Image Figure ViewerDownload Hi-res image Download (PPT) These data suggest that PoCT creatinine may be used to accurately predict serum creatinine concentrations in a pregnant population but requires an adjustment factor. PoCT capillary creatinine has potential to be used in midwifery-led and low-income settings to identify women at risk of PR-AKI, but further work is needed to confirm its role in clinical care.

Valproate attenuates hypertonic glycerol-induced rhabdomyolysis and acute kidney injury

Background and aimThe current study investigated the effects of treatment with 300 mg/kg valproic acid on rhabdomyolysis and acute kidney injury induced by intramuscular injection of hypertonic glycerol in rats. MethodsFour groups of male wistar rats: control and hypertonic glycerol, valproic acid and valproic acid + hypertonic glycerol treated groups were used. Blood urea nitrogen, serum creatinine, creatinine kinase (CK) and CK MB, myoglobin and renal reduced glutathione (GSH) levels were measured. Histopathological examination of the kidneys was carried out to evaluate the degree of renal injury in each group. The expression of interleukin-1 beta “IL-1β” in renal tissue was detected using immunohistochemistry. ResultsHypertonic glycerol administration led to severe renal tubular damage with a significant elevation of blood urea nitrogen, serum creatinine, creatinine kinase, CK MB and myoglobin levels and overexpression of IL-1β compared to control group. Valproic acid administration attenuated both the muscle injury and the acute kidney injury induced by hypertonic glycerol, estimated through a significant reduction of creatinine kinase, myoglobin, and serum creatinine. Valproic acid administration caused a significant increase in GSH in the hypertonic glycerol + valproic acid group compared to the hypertonic glycerol group. A significant decrease in tubular necrosis grade, and expression of IL-1β in hypertonic glycerol + valproic acid group compared to the hypertonic glycerol group was observed. ConclusionThis study demonstrates, for the first time to the best of our knowledge, that valproic acid could ameliorate the rhabdomyolysis and the related acute kidney injury in rats.

The Predictive Values of Respiratory Rate Oxygenation Index and Chest Computed Tomography Severity Score for High-Flow Nasal Oxygen Failure in Critically Ill Patients with Coronavirus Disease-2019.

Background:The prediction of high-flow nasal oxygen (HFNO) failure in patients with coronavirus disease-2019 (COVID-19) having acute respiratory failure (ARF) may prevent delayed intubation and decrease mortality.Aims:To define the related risk factors to HFNO failure and hospital mortality.Study Design:Retrospective cohort study.Methods:To this study, 85 critically ill patients (≥18 years) with COVID-19 related acute kidney injury who were treated with HFNO were enrolled. Treatment success was defined as the de-escalation of the oxygenation support to the conventional oxygen therapies. HFNO therapy failure was determined as the need for invasive mechanical ventilation or death. The patients were divided into HFNO-failure (HFNO-F) and HFNO-success (HFNO-S) groups. Electronic medical records and laboratory data were screened for all patients. Respiratory rate oxygenation (ROX) index on the first hour and chest computed tomography (CT) severity score were calculated. Factors related to HFNO therapy failure and mortality were defined.Results:This study assessed 85 patients (median age 67 years, 69.4% male) who were divided into two groups as HFNO success (n = 33) and HFNO failure (n = 52). The respiratory rate oxygenation (ROX) was measured at 1 hour and the computed tomography (CT) score indicated HFNO failure and intubation, with an area under the receiver operating characteristic of 0.695 for the ROX index and 0.628 for the CT score. A ROX index of <3.81 and a CT score of >15 in the first hour of therapy were the predictors of HFNO failure and intubation. Age, Acute Physiology and Chronic Health Evaluation II score, arterial blood gas findings “(i.e., partial pressure of oxygen [PaO2], PaO2 [fraction of inspired oxygen]/SO2 [oxygen saturation] ratio)”, and D-dimer levels were also associated with HFNO failure; however, based on logistic regression analysis, a calculated ROX on the first hour of therapy of <3.81 (odds ratio [OR] = 4.78, 95% confidence interval [CI] = 1.75–13.02, P = 0.001) and a chest CT score of >15 (OR = 2.83, 95% CI = 1.01–7.88, P = <0.001) were the only independent risk factors. In logistic regression analysis, a ROX calculated on the first hour of therapy of <3.81 (OR = 4.78, [95% CI = 1.75–13.02], P = 0.001) and a chest CT score of >15 (OR 2.83, 95% CI = 1.01–7.88, P = <0.001) were the independent risk factors for the HFNO failure. The intensive care unit and hospital mortality rates were 80.2% and 82.7%, respectively, in the HFNO failure group.Conclusion:The early prediction of HFNO therapy failure is essential considering the high mortality rate in patients with HFNO therapy failure. Using the ROX index and the chest CT severity score combined with the other clinical parameters may reduce mortality. Additionally, multi-centre observational studies are needed to define the predictive value of ROX and chest CT score not only for COVID-19 but also other causes of ARF.

Impact of Acute Kidney Injury in Hospitalizations with Non-Variceal Upper Gastrointestinal Bleeding

Abstract Background: Acute Kidney Injury (AKI) is a commonly occurring comorbidity in hospitalized patients. Our objective was to identify the role of AKI in relation to the morbidity and mortality in Non-Variceal Upper Gastrointestinal Bleeding (NVUGIB) patients. Study: Nationwide Inpatient Sample (NIS) database was used from the year 2000 to 2014 and queried for patients with NVUGIB. Patients were further stratified with and without the presence of concomitant AKI. Weighed multivariate regression analyses were performed to determine the final conclusions of the study. Results: Total of 4,889,410 patients with NVUGIB were identified during the study period. AKI was a comorbid condition in 6.37% of all patients. Incidence of AKI in NVUGIB patients has increased over five-fold over the study period. After adjusting for confounders through multivariate regression model, patients in the AKI group had higher odds of mortality (OR 2.84, p < 0.001). Additionally, patients with AKI were more likely to receive blood transfusion (OR 1.30, p < 0.001), had longer length of stay (+ 1.73 days, p < 0.001), had higher hospital charges (+ $16,221, p < 0.001), and had higher disposition to intermediate care facility (OR 1.84, p < 0.001). Conclusions: Incidence of AKI in hospitalized NVUGIB patients has increased dramatically. Interestingly, AKI is also associated with higher morbidity and mortality in NVUGIB patients. Consequently, AKI should be used as a marker for disease severity in hospitalized NVUGIB patients.

Metabolomic profiling identifies a novel mechanism for heat stroke‑related acute kidney injury.

Heat stroke can induce a systemic inflammatory response, which may lead to multi-organ dysfunction including acute kidney injury (AKI) and electrolyte disturbances. To investigate the pathogenesis of heat stroke (HS)-related AKI, a mouse model of HS was induced by increasing the animal's core temperature to 41°C. Blood samples obtained from the tail vein were used to measure plasma glucose and creatinine levels. Micro-positron emission tomography-computed tomography (micro-PET/CT), H&E staining and transmission electron microscopy were conducted to examine metabolic and morphological changes in the mouse kidneys. Immunohistochemistry (IHC) and western blot analyses were performed to investigate the expression of apoptosis-inducing factor mitochondria-associated 2 (Aifm2), high-mobility group box 1 (HMGB1) and receptor for advanced glycosylation end products (RAGE). Liquid chromatography-mass spectrometry analysis was conducted to find differential metabolites and signaling pathways. The HS mouse model was built successfully, with significantly increased creatinine levels detected in the serum of HS mice compared with controls, whereas micro-PET/CT revealed active metabolism in the whole body of HS mice. H&E and TUNEL staining revealed that the kidneys of HS mice exhibited signs of hemorrhage and apoptosis. IHC and western blotting demonstrated significant upregulation of Aifm2, HMGB1 and RAGE in response to HS. Finally, 136 differential metabolites were screened out, and enrichment of the ‘biosynthesis of unsaturated fatty acids’ pathway was detected. HS-associated AKI is the renal manifestation of systemic inflammatory response syndrome, and may be triggered by the HMGB1/RAGE pathway. Metabolomics indicated increased adrenic acid, docosahexaenoic acid and eicosapentaenoic acid may serve as metabolic biomarkers for AKI in HS. The findings suggested that a correlation between the HMGB1/RAGE pathway and biosynthesis of unsaturated fatty acids may contribute to the progression of HS-related AKI.

PARP inhibitors and the Kidney

Poly (ADP-ribose) polymerases (PARPs) are crucial in repairing DNA after a damaging event. However, several studies indicate that more extensive DNA disruption causes overactivity of PARP and can ultimately lead to cellular necrosis particularly in the setting of ischemia- related or sepsis-related acute kidney injury (AKI). Though the anti-cancer effects of PARP inhibitors (PARPis) are well known, especially in cases of Breast Cancer gene mutations, there exists a potential for the use of these drugs in treating ischemic AKI. Though the beneficial effects of PARPis in attenuating ischemic AKI has been shown in animal models, testing has yet to be done in humans. Studies have also found that PARPis interact with proximal tubular transporter channels and cause a physiologic increase serum creatinine, however the long- term effects on kidney function, proteinuria and hematuria are unclear. The use of PARPis in patients with chronic kidney disease (CKD) and malignancy may result in the amplification of adverse effects such as anemia and thrombocytopenia. Safe dosing of these agents in patients with advanced CKD and end stage kidney disease (ESKD) is yet to be determined as these populations were excluded from clinical trials. This manuscript reviews the current data on the kidney effects of PARPis and opens the door to further research in this arena.

Long-term outcomes following vehicle trauma related acute kidney injury requiring renal replacement therapy: a nationwide population study

Acute kidney injury (AKI) is a frequent complication of traumatic injury; however, long-term outcomes such as mortality and end-stage kidney disease (ESKD) have been rarely reported in this important patient population. We compared the long-term outcome of vehicle-traumatic and non-traumatic AKI requiring renal replacement therapy (AKI-RRT). This nationwide cohort study used data from the Taiwan National Health Insurance Research Database. Vehicle-trauma patients who were suffered from vehicle accidents developing AKI-RRT during hospitalization were identified, and matching non-traumatic AKI-RRT patients were identified between 2000 and 2010. The incidences of ESKD, 30-day, and long-term mortality were evaluated, and clinical and demographic associations with these outcomes were identified using Cox proportional hazards regression models. 546 vehicle-traumatic AKI-RRT patients, median age 47.6 years (interquartile range: 29.0–64.3) and 76.4% male, were identified. Compared to non-traumatic AKI-RRT, vehicle-traumatic AKI-RRT patients had longer length of stay in hospital [median (IQR):15 (5–34) days vs. 6 (3–11) days; p < 0.001). After propensity matching with non-traumatic AKI-RRT cases with similar demographic and clinical characteristics. Vehicle-traumatic AKI-RRT patients had lower rates of long-term mortality (adjusted hazard ratio (HR), 0.473; 95% CI, 0.392–0.571; p < 0.001), but similar rates of ESKD (HR, 1.166; 95% CI, 0.829–1.638; p = 0.377) and short-term risk of death (HR, 1.134; 95% CI, 0.894–1.438; p = 0.301) as non-traumatic AKI-RRT patients. In competing risk models that focused on ESKD, vehicle-traumatic AKI-RRT patients were associated with lower ESKD rates (HR, 0.552; 95% CI, 0.325–0.937; p = 0.028) than non-traumatic AKI-RRT patients. Despite severe injuries, vehicle-traumatic AKI-RRT patients had better long-term survival than non-traumatic AKI-RRT patients, but a similar risk of ESKD. Our results provide a better understanding of long-term outcomes after vehicle-traumatic AKI-RRT.

Abstract 278: A Novel Resuscitative Agent, Centhaquine (Lyfaquin®), has the Potential to Treat Acute Kidney Injury Following Hemorrhagic Shock

Introduction: Centhaquine (CQ) is being developed as a first-in-class resuscitative agent to treat hemorrhagic shock. Its safety, tolerability and efficacy have been demonstrated through pre-clinical studies and phase I, II and III clinical trials (NCT02408731, NCT04056065 and NCT04045327). Shock is often complicated with acute kidney injury (AKI). Hypothesis: CQ will increase renal blood flow (RBF) and attenuate hypoxia related damage after hemorrhagic shock. We investigated whether CQ improves RBF and provides protection after hemorrhagic shock. Methods: Rats were anesthetized, and carotid artery, femoral artery and femoral vein were catheterized. Renal arteries were clamped, hemorrhage was induced and mean arterial pressure (MAP) was maintained between 35-40 mmHg for 30 min. After 20 min of hemorrhage, renal arteries were de-clamped and hemorrhage continued for 10 more min. Resuscitation was performed with either normal saline (NS) or CQ (0.02 mg/kg) infusion for 10 min. MAP, heart rate and RBF were monitored for 120 min after which rats were sacrificed, kidneys were collected and analyzed with western blots and immunofluorescence. Results: Resuscitation with CQ produced a significant improvement in RBF (at 30 min 257.03±21.2 vs 199.81±42.32, p=0.002 sustained till 120 min 211.76±27.47 vs 148.24±42.39, p=0.002 of infusion) compared to NS. A non-significant increase in MAP was observed in CQ compared to NS. Western blots showed significantly higher expression HIF1-A (1.13±0.19 vs 0.86±0.16) and lower expression of early kidney damage marker, NGAL (0.35±0.16 vs 0.82±0.31) in CQ vs NS. Immunofluorescence showed significantly higher expression of HIF1-A and lower expression of Bax in cortex (HIF1-A 11.19±0.31 vs 8.43±0.39, p=0.03689, Bax 18.09±0.47 vs 24.80±2.01, p=0.0010) of CQ than NS and similar change was observed in medulla. Expression of PHD3 and Cytochrome C was higher in the cortex (PHD3 5.38±0.38 vs 4.05±0.12, p=0.0348, Cytochrome C 24.95±0.65 vs 29.24±1.87, p=0.01429) of CQ than NS. HIF1-B expression was similar in CQ and NS groups. Conclusions: CQ (Lyfaquin®) is a frontline resuscitative agent with a potential to treat hemorrhagic shock related AKI by improving kidney blood flow and decreasing hypoxia related tissue damage.

COVID-19 in lung transplant recipients: A multicenter study.

This study describes the clinical presentation, treatment, and outcomes of SARS-CoV-2 infection in lung transplant recipients (LTRs). This is a multicenter, retrospective study of all adult LTRs with confirmed SARS-CoV-2 infection from March 4 until April 28, 2020 in six Spanish reference hospitals for lung transplantation. Clinical and radiological data, treatment characteristics, and outcomes were reviewed. Forty-four cases were identified in that period. The median time from transplantation was 4.2 (interquartile range: 1.11-7.3) years. Chest radiography showed acute parenchymal abnormalities in 32 (73%) cases. Hydroxychloroquine was prescribed in 41 (93%), lopinavir/ritonavir (LPV/r) in 14 (32%), and tocilizumab in 19 (43%) patients. There was a strong interaction between tacrolimus and LPV/r in all cases. Thirty-seven (84%) patients required some degree of respiratory support and/or oxygen therapy, and 13 (30%) were admitted to intermediate or intensive critical care units. Seventeen (39%) patients had died and 20 (45%) had been discharged at the time of the last follow-up. Deceased patients had a worse respiratory status and chest X-ray on admission and presented with higher D-dimer, interleukin-6, and lactate dehydrogenase levels. In this multicenter LTR cohort, SARS-CoV-2 presented with high mortality. Additionally, the severity of disease on presentation predicted subsequent mortality.

A case of acute renal failure requiring emergency hemodialysis due to hypothermia-associated rhabdomyolysis

Hypothermia is described as a decrease in body temperature below 35 °C. Although the body reacts neuroendocrinally, behaviourally, and cardiovascularly against sudden changes in temperature, uncontrolled hypothermia can lead to severe complications such as rhabdomyolysis, acute renal failure, coma, coagulopathy, malignant cardiac arrhythmia, and cardiac collapse. Herein, we aimed to emphasize hypothermia, its serious complications such as rhabdomyolysis and related acute kidney injury in a 60-year-old male patient exposed to environmental cold.

Predictive value of complement and coagulation indicators in sepsis related acute kidney injury

Objective: To explore the predictive value of complement and coagulation indicators in sepsis related acute kidney injury (AKI). Methods: Clinical data of 217 patients with sepsis admitted to the Department of Internal Medicine and Intensive Care Unit of Affiliated Hospital of Jiangnan University from January 2018 to June 2019 were retrospectively analyzed. All patients were divided into sepsis with AKI group and without AKI group. Laboratory indicators of all patients were collected, including complement C3, complement C4, activated partial thrombin time (APTT), prothrombin time (PT), international normalized ratio (INR), D-dimer, procalcitonin(PCT), etc. logistic regression analysis was used to explore the risk factors of sepsis related AKI. Receiver operating characteristic curve (ROC) was used to evaluate the predictive value of independent risk factors. Results: Among 217 patients, 120 patients developed sepsis related AKI and 97 patients didn't. PCT, lactic acid, PT, APTT, INR and D-dimer in AKI patients were significantly higher than those without AKI (P<0.01). Complement C3 and complement C4 were significantly lower in AKI group (P<0.01). Multivariate logistic regression analysis suggested that blood pressure<90/60 mmHg (1 mmHg=0.133 kPa)(OR=3.705, 95%CI 1.536-8.934,P=0.004), increased lactic acid (OR=1.479, 95%CI 1.089-2.008, P=0.012), decreased complement C3 (OR=0.027, 95%CI 0.005-0.152, P<0.001) and prolonged APTT (OR=1.090, 95%CI 1.047-1.137,P<0.001)were independent risk factors predicting AKI. The area under the ROC curve (AUC) of these multivariates were 0.741 (95%CI 0.675-0.807), 0.798 (95%CI 0.732-0.864), 0.712 (95%CI 0.643-0.781) and 0.716 (95%CI 0.648-0.783) respectively. The relevant sensitivity was 57.5%, 80.8%, 87.5%, 59.2%, and the specificity was 90.7%, 75.3%, 51.5%, 77.3%, respectively. The AUC of the combined four indicators was 0.880 (95%CI 0.835-0.926) with the sensitivity 75.0% and the specificity 90.7%. Conclusion: The low level of complement C3 and prolonged APTT predict sepsis related AKI, and the predictive value can be enhanced if hypotension and hyperlactacidemia are added.