Persistent Kidney Injury Research Articles

PASS: A scoring system to evaluate persistent kidney injury in critically ill ICU adult patients

Background We evaluated if the course of recovery from sepsis-induced acute kidney injury (AKI) can be predicted using variables collected at admission. Methods A total of 63 patients admitted for sepsis-induced AKI in our Mangalore ICU were evaluated and baseline demographic and clinical/laboratory parameters, including serum creatinine (SCr), base excess (BE), Plethysmographic Variability Index (PVI), Caval Index, R wave variability index (RVI), mean arterial pressure (MAP) and renal resistivity index (RI) using renal doppler and need for inotropes were assessed on admission. Patients were managed as per standard protocol. After six hours of fluid resuscitation, patients were classified as volume responders or non-responders. Re-assessment was done at 24 hours and 72 hours after admission. Primary outcome was persistent AKI after 72 hours. Secondary outcome was initiation of dialysis or death within 15 days of admission. Results A total of 34 subjects recovered from AKI, of whom 32 patients were volume responders and 31 were non-responders. Response to fluid, MAP at admission and six hours, BE at admission, inotrope requirement, and PVI at admission did not correlate with recovery. Multiple logistic regression showed that SCr < 2.36 mg%, RVI > 14.45 and RI < 0.8 on admission correlated with recovery and they were evaluated further to model AKI recovery and develop PASS. PASS score = (SCr points × 5.4) + (RVI points × 4.0) + (RI points × 6.2). One point each was allotted if SCr was < 2.36, RVI was > 14.45 and RI was <0.8, and 0 otherwise. A score > 7.8 predicted recovery with a sensitivity of 79.4%, specificity of 72.4%, PPV 81.8%, NPV 76.7% and AuROC of 0.85. Conclusions The PASS score can be used to identify salvageable cases of sepsis-AKI, guiding fluid resuscitation and aiding early referral from rural to tertiary care centers for better management.

Cognitive Impairment in Liver Tranplant Recipients: A Cross-Sectional Study.

The proportion of older transplant recipients has increased. Cognitive impairment is not rare after kidney transplant, but data on this issue in liver transplant recipients are scarse. In this cross-sectional study, we evaluated all liver transplant recipients from a single center in Brazil from July 2018 to June 2020 in terms of cognitive performance to determine the prevalence of neurocognitive disorder. We compared liver transplant recipients with neurocognitive disorder with liver transplant recipients without neurocognitive disorder. We also compared those with an alcoholic cause of liver transplant with other patients. The presence of depressive symptoms was assessed. We performed correlations of clinical data with cognitive scores. In a sample of 100 recipients with median age of 62 years (interquartile range, 56.2-69 y), neurocognitive disorder was present in 21% of the group. Patients with cognitive impairment were older (68 y [61-72] vs 61 y [52-68]; P = .019) and had a trend to higher proportion of persistent kidney injury (33.3% vs 13.9%; P = .055) versus patients without cognitive impairment. Recipients with alcoholic cause of liver transplant exhibited worse cognitive performance in the Mini-Mental State Examination (score of 26 [23.7-28.2] vs 28 [26-29]; P = .024) and the Alzheimer Disease Assessment Scale-cognitive (score of 10.4 [8.6-14.2] vs 8 [6.3-10]; P = .008) than other patients. Weak negative correlations were shown in cognitive performance scores versus recipient age (Semantic Verbal Fluency test, r = -0.334 [P = .001]; Clock Drawing test, r = -0.209 [P = .037]; Alzheimer Disease Assessment Scale-cognitive, r = -0.323 [P = .001]). Neurocognitive disorder was common in liver transplant recipients, in part due to increased age. This study also suggested a role for alcoholic cause of liver transplant and persistent kidney injury in the development of cognitive impairment.

Unusual course of glyphosate-induced acute kidney injury: a case report of tubulointerstitial nephritis treated with steroids.

Glyphosate is a widely used herbicide that is generally considered safe; however, acute kidney injury (AKI) caused by glyphosate ingestion can be severe and require hemodialysis. We present a unique case of a 68-year-old Japanese man who developed AKI after accidental ingestion of glyphosate and required hemodialysis. Based on the clinical presentation and findings, the patient was diagnosed with renal AKI with severe tubulointerstitial damage. However, the precise pathogenesis of the tubulointerstitial damage remained unclear. An elevated beta-2 microglobulin level discovered by the urinalysis during admission raised the suspicion of tubulointerstitial nephritis caused by glyphosate. Gallium scintigraphy revealed accumulation in both kidneys. A renal biopsy revealed acute tubulointerstitial nephritis rather than acute tubular necrosis, which is commonly observed with glyphosate-induced renal injury. After initiating steroid therapy, his kidney function gradually improved and he was weaned from hemodialysis. This report is the first to describe glyphosate-induced acute tubulointerstitial nephritis that was successfully treated with immunosuppressive therapy. Furthermore, this report highlights the importance of steroid therapy for cases of persistent kidney injury after the discontinuation of agents associated with acute tubulointerstitial nephritis.

PASS: A scoring system to evaluate persistent kidney injury in critically ill ICU adult patients

Background We evaluated if the course of recovery from sepsis-induced acute kidney injury (AKI) can be predicted using variables collected at admission. Methods A total of 63 patients admitted for sepsis-induced AKI in our Mangalore ICU were evaluated and baseline demographic and clinical/laboratory parameters, including serum creatinine (SCr), base excess (BE), Plethysmographic Variability Index (PVI), Caval Index, R wave variability index (RVI), mean arterial pressure (MAP) and renal resistivity index (RI) using renal doppler and need for inotropes were assessed on admission. Patients were managed as per standard protocol. After six hours of fluid resuscitation, patients were classified as volume responders or non-responders. Re-assessment was done at 24 hours and 72 hours after admission. Primary outcome was persistent AKI after 72 hours. Secondary outcome was initiation of dialysis or death within 15 days of admission. Results A total of 34 subjects recovered from AKI, of whom 32 patients were volume responders and 31 were non-responders. Response to fluid, MAP at admission and six hours, BE at admission, inotrope requirement, and PVI at admission did not correlate with recovery. Multiple logistic regression showed that SCr < 2.36 mg%, RVI > 14.45 and RI < 0.8 on admission correlated with recovery and they were evaluated further to model AKI recovery and develop PASS. PASS score = (SCr points × 5.4) + (RVI points × 4.0) + (RI points × 6.2). One point each was allotted if SCr was < 2.36, RVI was > 14.45 and RI was <0.8, and 0 otherwise. A score > 7.8 predicted recovery with a sensitivity of 79.4%, specificity of 72.4%, PPV 81.8%, NPV 76.7% and AuROC of 0.85. Conclusions The PASS score can be used to identify salvageable cases of sepsis-AKI, guiding fluid resuscitation and aiding early referral from rural to tertiary care centers for better management.

Low HDL-C can be a biomarker to predict persistent severe AKI in septic patients? A retrospective cohort study

PurposesLow HDL-C is associated with an increased risk of sepsis-associated AKI and subsequent decline in eGFR. HDL-C possesses anti-inflammatory, antioxidant, and endothelial repair-promoting properties. The use of Apo A-I mimetic peptides, which are the main structural components of HDL-C, has been shown to improve renal function in animal models of sepsis. However, the diagnostic value of low HDL-C in persistent sepsis-associated AKI remains unclear.MethodsThis is a retrospective cohort study based on MIMIC IV (V 2.2). The study population consisted of all adult septic patients admitted to the Beth Israel Deaconess Medical Center Intensive Care Unit from 2008 to 2019, with plasma HDL-C measured within 24 h of ICU admission. The primary endpoint was persistent severe sepsis-associated acute kidney injury (SA-AKI) and the secondary endpoint is kidney replacement therapy (KRT). Logistic regression was used to assess the correlation between HDL-C and persistent severe SA-AKI and KRT, and receiver operating characteristic (ROC) curve analysis was performed to evaluate predictive ability.ResultsA total of 604 cases of SA-AKI patients were included in the analysis, among which 88 cases (14.5%) experienced persistent severe SA-AKI. The median (IQR) HDL-C level in the group with persistent severe SA-AKI was lower (33.0 [24.0–45.5]) compared to the non-persistent severe SA-AKI group (42.0 [31.0–53.0]). However, HDL-C showed poor discriminatory ability with an AUROC [95%CI] of 0.62 [0.56–0.69]. Clinical prediction models based on serum creatinine concentration, 24-h creatinine change, APSIIIscore, lactate levels, APTT, and heart rate performed well in predicting persistent severe SA-AKI with an AUROC [95%CI] of 0.876 [0.84–0.91]. However, adding HDL-C to this model did not improve predictive performance.ConclusionsThe plasma HDL-C measured within 24 h after admission to the ICU does not provide a good prediction for persistent severe SA-AKI, and it does not improve the clinical predictive ability compared to conventional variables.

Acute Kidney Injury-Induced Circulating TNFR1/2 Elevations Correlate with Persistent Kidney Injury and Progression to Fibrosis.

Elevated levels of circulating tumor necrosis factor receptors 1 and 2 (cTNFR1/2) predict chronic kidney disease (CKD) progression; however, the mechanisms of their release remain unknown. Whether acute kidney injury (AKI) drives cTNFR1/2 elevations and whether they predict disease outcomes after AKI remain unknown. In this study, we used AKI patient serum and urine samples, mouse models of kidney injury (ischemic, obstructive, and toxic), and progression to fibrosis, nephrectomy, and related single-cell RNA-sequencing datasets to experimentally test the role of kidney injury on cTNFR1/2 levels. We show that TNFR1/2 serum and urine levels are highly elevated in all of the mouse models of kidney injury tested, beginning within one hour post injury, and correlate with its severity. Consistent with this, serum and urine TNFR1/2 levels are increased in AKI patients and correlate with the severity of kidney failure. Kidney tissue expression of TNFR1/2 after AKI is only slightly increased and bilateral nephrectomies lead to strong cTNFR1/2 elevations, suggesting the release of these receptors by extrarenal sources. The injection of the uremic toxin indoxyl sulfate in healthy mice induces moderate cTNFR1/2 elevations. Moreover, TNF neutralization does not affect early cTNFR1/2 elevations after AKI. These data suggest that cTNFR1/2 levels in AKI do not reflect injury-induced TNF activity, but rather a rapid response to loss of kidney function and uremia. In contrast to traditional disease biomarkers, such as serum creatinine or BUN, cTNFR1/2 levels remain elevated for weeks after severe kidney injury. At these later timepoints, cTNFR1/2 levels positively correlate with remaining kidney injury. During the AKI-to-CKD transition, elevations of TNFR1/2 kidney expression and of cTNFR2 levels correlate with kidney fibrosis levels. In conclusion, our data demonstrate that kidney injury drives acute increases in cTNFR1/2 serum levels, which negatively correlate with kidney function. Sustained TNFR1/2 elevations after kidney injury during AKI-to-CKD transition reflect persistent tissue injury and progression to kidney fibrosis.

PASS: A scoring system to evaluate persistent kidney injury in critically ill ICU adult patients

Background: We evaluated if the course of recovery from sepsis-induced acute kidney injury (AKI) can be predicted using variables collected at admission. Methods: A total of 63 patients admitted for sepsis-induced AKI in our Mangalore ICU were evaluated and baseline demographic and clinical/laboratory parameters, including serum creatinine (SCr), base excess (BE), Plethysmographic Variability Index (PVI), Caval Index, R wave variability index (RVI), mean arterial pressure (MAP) and renal resistivity index (RI) using renal doppler and need for inotropes were assessed on admission. Patients were managed as per standard protocol. After six hours of fluid resuscitation, patients were classified as volume responders or non-responders. Re-assessment was done at 24 hours and 72 hours after admission. Primary outcome was persistent AKI after 72 hours. Secondary outcome was initiation of dialysis or death within 15 days of admission. Results: A total of 34 subjects recovered from AKI, of whom 32 patients were volume responders and 31 were non-responders. Response to fluid, MAP at admission and six hours, BE at admission, inotrope requirement, and PVI at admission did not correlate with recovery. Multiple logistic regression showed that SCr < 2.36 mg%, RVI > 14.45 and RI < 0.8 on admission correlated with recovery and they were evaluated further to model AKI recovery and develop PASS. PASS score = (SCr points × 5.4) + (RVI points × 4.0) + (RI points × 6.2). One point each was allotted if SCr was < 2.36, RVI was > 14.45 and RI was <0.8, and 0 otherwise. A score > 7.8 predicted recovery with a sensitivity of 79.4%, specificity of 72.4%, PPV 81.8%, NPV 76.7% and AuROC of 0.85. Conclusions: The PASS score can be used to identify salvageable cases of sepsis-AKI, guiding fluid resuscitation and aiding early referral from rural to tertiary care centers for better management.

Cyclopeptide mushroom poisoning: A retrospective series of 204 patients.

Cyclopeptide mushroom poisoning is responsible for 90%-95% of deaths from macrofungi ingestion. The main objectives of this study are to describe cases of cyclopeptide mushroom poisoning and to determine risk factors that may influence the severity/mortality of poisoned patients. We included all cases of amatoxin toxicity reported to two French Poison Centers from 2013 through 2019. We compared the severity with the Poison Severity Score (PSS) and the outcomes of patients using simple logistic regression and multinomial logistic regression. We included 204 cases of amatoxin toxicity. More than three-quarters developed an increase in AST and/or ALT (78.1%), and over half developed a decrease in prothrombin ratio (<70%: 53%) and/or Factor V (<70%: 54%). One-third developed an acute renal injury (AKI). Twelve patients (5.9%) developed post-poisoning sequelae (persistent kidney injury more than 1 month after ingestion and liver transplant). Five patients (2.5%) received a liver transplant, and nine died (4.4%). The mean time to onset of digestive disorders was shorter in PSS2 and PSS3-4 patients (10.9 ± 3.9/11.3 ± 6.3h) than in PSS1 patients (14 ± 6.5h; p < 0.05). Patients who died or developed post-poisoning sequelae had more frequent cardiovascular comorbidities compared with recovered patients (60.0% versus 29.5%; p < 0.01).

Neutrophil gelatinase-associated lipocalin monitoring reveals persistent subclinical kidney injury following intraarterial administration of iodinated contrast agents

Clinically overt contrast-induced nephropathy (CIN) is one of the most feared complications in patients exposed to iodinated contrast media and has been extensively studied over the years. Meanwhile, the incidence and evolution of subclinical contrast-induced kidney injury remain elusive. With the continuous increase in the number of patients that are repeatedly exposed to contrast media, elucidating these issues is of critical importance. Accordingly, we aimed to evaluate the incidence and the evolution of clinical and subclinical kidney injury in patients exposed to contrast media. A total of 178 patients who underwent elective percutaneous angioplasty procedures were evaluated prospectively. Serum creatinine and neutrophil gelatinase-associated lipocalin (NGAL) levels were evaluated pre-procedurally, 48 h and 1 month after administration of contrast media. The evolution of creatinine and NGAL levels was analyzed at the three time points, and the potential predictors of contrast-induced clinical and subclinical renal injury were evaluated. Clinically overt CIN occurred in 10 (5.6%) patients. Baseline serum creatinine and the volume of contrast media were the only independent predictors of CIN and in all 10 patients creatinine levels returned to baseline by 1 month (p = 0.32). Subclinical contrast-induced kidney injury was much more common, affecting 32 (17.9%) patients, was only predicted by the baseline serum creatinine, and persisted in 53.1% of patients after 1 month. This study showed that whereas clinically overt CIN is rather rare and regressive, subclinical contrast-induced kidney injury is considerably more frequent, affecting almost 18% of patients that receive intraarterial contrast media. More importantly, subclinical kidney injury persisted after 1 month in more than 50% of the initially affected patients, who may thus be at increased risk for further renal impairment, particularly if exposed to nephrotoxic agents or repeated administration of contrast media.

Evaluation of mortality of COVID-19 patients with acute kidney injury (AKI) in comparison to the non-AKI patients

Introduction: Acute kidney injury (AKI) is prevalent in the coronavirus disease-2019 (COVID-19). There are little data on the relationship between renal dysfunction and COVID-19 prognosis. Objectives: The aim of this research was to investigate the effects of AKI in COVID-19 patients hospitalized to the Golestan and Razi hospitals in Ahvaz, Iran. Patients and Methods: In this retrospective cohort study, a total of 194 COVID-19 patients were included, consisting of 79 patients with AKI and 115 patients without AKI. Primary and secondary outcomes were compared between the two groups. Results: According to the findings, mortality was significantly different between the two groups, and mortality was higher in the AKI group (P&lt; 0.001). The mean length of hospital stay was statistically significantly higher in the AKI group (P=0.024). Moreover, there was a significant correlation between intensive care unit (ICU) admission and the study group (P&lt;0.001). Staging of AKI group were seen as; stage I (49.37%), stage II (36.71%), and stage III (13.92%). No significant correlation was observed between outcome and the stages of AKI (P=0.496). Furthermore, 14 patients (17.72%) needed renal replacement therapy (RRT) in the AKI group. Conclusion: Although AKI is a common finding in COVID-19 patients, most patients were in stage I disease, which returned to normal after COVID-19 treatment. According to our research, COVID-19 rarely leads to serious and persistent kidney injury. However, the risk of death is increased in COVID-19 patients with AKI. Therefore, it is necessary to evaluate the renal function tests during the course of disease.

The incidence and outcome of AKI in patients with sepsis in the emergency department applying different definitions of AKI and sepsis

BackgroundSepsis is often accompanied with acute kidney injury (AKI). The incidence of AKI in patients visiting the emergency department (ED) with sepsis according to the new SOFA criteria is not exactly known, because the definition of sepsis has changed and many definitions of AKI exist. Given the important consequences of early recognition of AKI in sepsis, our aim was to assess the epidemiology of sepsis-associated AKI using different AKI definitions (RIFLE, AKIN, AKIB, delta check, and KDIGO) for the different sepsis classifications (SIRS, qSOFA, and SOFA).MethodsWe retrospectively enrolled patients with sepsis in the ED in three hospitals and applied different AKI definitions to determine the incidence of sepsis-associated AKI. In addition, the association between the different AKI definitions and persistent kidney injury, hospital length of stay, and 30-day mortality were evaluated.ResultsIn total, 2065 patients were included. The incidence of AKI was 17.7–51.1%, depending on sepsis and AKI definition. The highest incidence of AKI was found in qSOFA patients when the AKIN and KDIGO definitions were applied (51.1%). Applying the AKIN and KDIGO definitions in patients with sepsis according to the SOFA criteria, AKI was present in 37.3% of patients, and using the SIRS criteria, AKI was present in 25.4% of patients. Crude 30-day mortality, prolonged length of stay, and persistent kidney injury were comparable for patients diagnosed with AKI, regardless of the definition used.ConclusionThe incidence of AKI in patients with sepsis is highly dependent on how patients with sepsis are categorised and how AKI is defined. When AKI (any definition) was already present at the ED, 30-day mortality was high (22.2%). The diagnosis of AKI in sepsis can be considered as a sign of severe disease and helps to identify patients at high risk of adverse outcome at an early stage.

PSIII-10 Heat Stress Causes Persistent Multisystemic Dysfunction

Abstract Heat stress (HS) causes multisystemic dysfunction and negatively impacts animal production. That the deleterious effects on production persist after HS abates raises the possibility of continuing injury and pathology that is not remediated by reestablishing euthermia. We hypothesized that a single bout of HS would cause immediate and persistent heart, liver, and kidney injury. To test this hypothesis, we collected blood from 3 month-old crossbred pigs (n = 12; 8 barrows, 4 gilts) under thermoneutral (TN; Pre) conditions (20.6 ± 0.2 ºC), following a 24 h HS (37.4 ± 0.2 ºC, 24hP), and 3 mo following HS (3mP). Skeletal muscle and cardiac muscle injury were apparent as creatine kinase (P &amp;lt; 0.05), myoglobin (P &amp;lt; 0.05), cardiac troponin I (cTnI; P &amp;lt; 0.05) and NT-proBNP (P &amp;lt; 0.05) were increased in 24hP compared with Pre, and elevations in NT-proBNP in 3mP raise the possibility of lasting cardiac injury. Additionally, cTnI and NT-proBNP were greater in gilts than barrows as a main effect of sex (P &amp;lt; 0.05). Increased creatinine, Mg, and blood urea nitrogen (BUN) in 24hP, and chronic elevations in creatinine, Cl, Mg, Na, Ca, bicarbonate, and BUN and reduced phosphorus and K (P &amp;lt; 0.05 &amp;lt; 0.1) in 3mP, indicate a single HS causes rapid and lasting impairments in renal function. Heat stress also increased aspartate aminotransferase (AST; P &amp;lt; 0.05) 24hP but decreased alkaline phosphatase (P &amp;lt; 0.05) and total bilirubin in 24hP (P &amp;lt; 0.1) and AST (P &amp;lt; 0.05) and total bilirubin in 3mP (P &amp;lt; 0.05). In total, these data suggest that HS causes both immediate and long-term cardiac, liver, and renal dysfunction and this appears to be influenced, at least in part, by biological sex.

Transient and persistent acute kidney injury phenotypes following the Norwood operation: a retrospective study.

Acute kidney injury is a common complication following the Norwood operation. Most neonatal studies report acute kidney injury peaking within the first 48 hours after cardiac surgery. The aim of this study was to evaluate if persistent acute kidney injury (>48 postoperative hours) after the Norwood operation was associated with clinically relevant outcomes. Two-centre retrospective study among neonates undergoing the Norwood operation. Acute kidney injury was initially identified as developing within the first 48 hours after cardiac surgery and stratified into transient (≤48 hours) and persistent (>48 hours) using the neonatal modification of the Kidney Disease: Improving Global Outcomes serum creatinine criteria. Severe was defined as stage ≥2. Primary and secondary outcomes were mortality and duration of ventilation and hospital length of stay. One hundred sixty-eight patients were included. Transient and persistent acute kidney injuries occurred in 24 and 17%, respectively. Cardiopulmonary bypass and aortic cross clamp duration, and incidence of cardiac arrest were greater among those with persistent kidney injury. Mortality was four times higher (41 versus 12%, p < 0.001) and mechanical ventilation duration 50 hours longer in persistent acute kidney injury patients (158 versus 107 hours; p < 0.001). In multivariable analysis, persistent acute kidney injury was not associated with mortality, duration of ventilation or length of stay. Severe persistent acute kidney injury was associated with a 59% increase in expected ventilation duration (aIRR:1.59, 95% CI:1.16, 2.18; p = 0.004). Future large studies are needed to determine if risk factors and outcomes change by delineating acute kidney injury into discrete timing phenotypes.

Renal microsporidiosis due to Encephalitozoon cuniculi in an HIV/AIDS patient with persistent fever and kidney injury

A 44-year-old Filipino man recently diagnosed with HIV infection presented to our clinic complaining of fever and asthenia for a few days. Virological and immunological parameters displayed a severe immunodepression (CD4+ T lymphocytes: 2/μL, 0%) with an HIV viraemia of 80 141 copies/mL.

MO363CHECKPOINT-INHIBITOR-ASSOCIATED ACUTE KIDNEY INJURY AND MORTALITY: AN OBSERVATIONAL STUDY

Abstract Background and Aims Immune checkpoint inhibitors, approved for the treatment of various types of cancer, are known to cause a unique spectrum of autoimmune-related side effects, including acute kidney injury (AKI). The aim of this study was to describe the incidence, risk factors, renal outcomes, and mortality of AKI in patients receiving checkpoint inhibitors. Method Patients receiving checkpoint inhibitors between January 2013 and May 2020 were identified using the Utrecht Patient Oriented Database. AKI was defined as an increase in creatinine of ≥1.5 times the baseline value. Cox proportional hazard regression analysis was used to assess risk factors for AKI and to evaluate the relationship between AKI and mortality. Persistent kidney injury was diagnosed in AKI patients with a final creatinine measurement of &amp;gt;1.3 times the baseline value. Results Out of 676 patients receiving checkpoint inhibitors, AKI occurred in 96 (14.2%) patients. Chart review showed that AKI was checkpoint inhibitor-associated in 32 (4.7%) patients. Baseline variables associated with AKI were a primary gynecological malignancy (HR 3.91, 95% CI 1.55 to 9.85), treatment with checkpoint inhibitor ipilimumab (HR 2.31, 95% CI 1.03 to 5.20), and pre-existent use of a diuretic (HR 2.61, 95% CI 1.21 to 5.60), an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker (HR 2.49, 95% CI 1.10 to 5.60), and a proton pump inhibitor (HR 1.69, 95% CI 1.04 to 2.75). In 35.4% of the patients who had developed AKI, persistent kidney dysfunction was observed at the end of follow-up. Patients who developed AKI had a 2.13-fold (95% CI 1.58 to 2.87) increased mortality risk compared to patients who did not develop AKI. Mortality risk was not increased by checkpoint inhibitor-associated AKI (HR 1.11, 95% CI 0.64 to 1.92), but only by AKI related to other causes (HR 2.87, 95% CI 2.04 to 4.04). Conclusion Patients receiving checkpoint inhibitors frequently develop AKI, however, checkpoint inhibitor-associated AKI does not seem to increase mortality.

Mortality and serum hepcidin are associated with persistent and transient acute kidney injury in septic patients.

Acute kidney injury (AKI) is a common complication of sepsis and has high mortality. The 2017 Acute Disease Quality Initiative (AQDI) workgroup proposed new definitions for AKI - transient AKI and persistent AKI; however, very little is known about the effect of transient and persistent septic AKI on short-term mortality among critically ill patients with sepsis. The purpose of this study was to assess the impact of persistent AKI on mortality and to evaluate whether serum hepcidin can predict the occurrence of persistent AKI in critically ill patients with sepsis. This prospective observational study was performed in a general hospital mixed surgical-medical ICU in Pudong, China. Consecutive adults with sepsis admitted to the ICU with absence of chronic kidney disease, renal transplant, and AKI were included. AKI was defined according to the KDIGO criteria and classified as transient (&lt; 48-hour duration) or persistent (48-hour duration). Blood samples were obtained within 6 hours from when AKI was diagnosed. A total of 90 patients with sepsis or septic shock were included in the analysis. 44 (48.89%) patients developed AKI during ICU stay: 20 (45.45%) had transient and 24 (54.55%) had persistent AKI. Persistent AKI has a higher mortality than transient AKI (66.7 vs. 30.0%, p = 0.002). Persistent AKI and sequential organ failure assessment (SOFA) scores were an independent predictor of 60-day mortality. Patients with persistent AKI had higher concentrations of serum creatinine (SCr) and hepcidin than transient AKI patients when AKI was diagnosed. Logistic regression indicated that serum hepcidin was an independent predictor of persistent AKI in septic patients, with a fairly predictive value (AUC 0.71, 95% CI: 0.47 - 0.87; p = 0.02). Persistent AKI was associated with increased 60-day mortality compared with transient AKI in septic patients. The serum hepcidin levels measured when AKI was diagnosed have a fair predictive value to predict the occurrence of persistent AKI in septic patients.

Association Between Acute Kidney Injury Duration and Outcomes in Critically Ill Children.

Acute kidney injury occurs frequently in children during critical illness and is associated with increased morbidity, mortality, and health resource utilization. We aimed to examine the association between acute kidney injury duration and these outcomes. Retrospective cohort study. PICUs in Alberta, Canada. All children admitted to PICUs in Alberta, Canada between January 1, 2015, and December 31, 2015. None. In total, 1,017 children were included, and 308 (30.3%) developed acute kidney injury during PICU stay. Acute kidney injury was categorized based on duration to transient (48 hr or less) or persistent (more than 48 hr). Transient acute kidney injury occurred in 240 children (77.9%), whereas 68 children (22.1%) had persistent acute kidney injury. Persistent acute kidney injury had a higher proportion of stage 2 and stage 3 acute kidney injury compared with transient acute kidney injury and was more likely to start within 24 hours from PICU admission. Persistent acute kidney injury occurred more frequently in those with higher illness severity and in those admitted with shock, sepsis, or with a history of transplant. Mortality varied significantly according to acute kidney injury status: 1.8% of children with no acute kidney injury, 5.4% with transient acute kidney injury, and 17.6% with persistent acute kidney injury died during hospital stay (p < 0.001). On multivariable analysis adjusting for illness and acute kidney injury severity, transient and persistent acute kidney injury were both associated with fewer ventilation-free days at 28 days (-1.28 d; 95% CI, -2.29 to -0.26 and -4.85 d; 95% CI, -6.82 to -2.88), vasoactive support-free days (-1.07 d; 95% CI, -2.00 to -0.15 and -4.24 d; 95% CI, -6.03 to -2.45), and hospital-free days (-1.93 d; 95% CI, -3.36 to -0.49 and -5.25 d; 95% CI, -8.03 to -2.47), respectively. In critically ill children, persistent and transient acute kidney injury have different clinical characteristics and association with outcomes. Acute kidney injury, even when its duration is short, carries significant association with worse outcomes. This risk increases further if acute kidney injury persists longer independent of the degree of its severity.

Cardiac Manifestations of Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 Infection

Context: Multisystem inflammatory syndrome in children (MIS-C) is an emerging condition after the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, termed COVID-19. This study aimed to describe the cardiac manifestations of children diagnosed with MIS-C. Evidence Acquisition: This narrative review was conducted by searching the PubMed, Scopus, and Google Scholar databases to review MIS-C cardiac manifestations up to September 30, 2020. The demographic features, past medical history, clinical signs and symptoms, cardiac involvement, and the type of COVID-19 diagnosis confirmation were extracted. Results: In many children, MIS-C seems to be a post-infectious complication of the COVID-19 infection. This syndrome affects multiple organs and has various clinical manifestations mimicking Kawasaki disease. Patients frequently present with persistent fever, kidney injury, gastrointestinal (GI) problems, neurologic symptoms, mucosal changes, conjunctivitis, and cardiac involvement. Children with MIS are more likely to present with hypotension, shock, and cardiac dysfunction, rather than coronary artery abnormalities and arrhythmia. Children with MIS need close observation; some need to be hospitalized, and a few may need a Pediatric Intensive Care Unit (PICU) admission. Treatment currently includes anticoagulants, IV immunoglobulin, and anti-inflammatory drugs. Conclusions: As a novel syndrome associated with SARS-CoV-2 infection, MIS-C is potentially lethal. Cardiac manifestations, including coronary and myocardial involvement, are common and should be carefully identified. With prompt diagnosis and proper treatment, most children will survive, but the outcomes of the disease are unknown, so long-term follow-ups are required.

Clinical Trajectories of Acute Kidney Injury in Surgical Sepsis: A Prospective Observational Study.

To characterize endothelial function, inflammation, and immunosuppression in surgical patients with distinct clinical trajectories of AKI and to determine the impact of persistent kidney injury and renal non-recovery on clinical outcomes, resource utilization, and long-term disability and survival. AKI is associated with increased healthcare costs and mortality. Trajectories that account for duration and recovery of AKI have not been described for sepsis patients, who are uniquely vulnerable to renal dysfunction. This prospective observational study included 239 sepsis patients admitted and enrolled between January 2015 and July 2017. Kidney Disease: Improving Global Outcomes (KDIGO) and Acute Disease Quality Initiative (ADQI) criteria were used to classify subjects as having no AKI, rapidly reversed AKI, persistent AKI with renal recovery, or persistent AKI without renal recovery. Serial biomarker profiles, clinical outcomes, resource utilization, and long-term physical performance status and survival were compared among AKI trajectories. Sixty-two percent of the study population developed AKI. Only one-third of AKI episodes rapidly reversed within 48 hours; the remaining had persistent AKI, among which 57% did not have renal recovery by discharge. One-year survival and proportion of subjects fully active 1 year after sepsis was lowest among patients with persistent AKI compared with other groups. Long-term mortality hazard rates were 5-fold higher for persistent AKI without renal recovery compared with no AKI. Among critically ill surgical sepsis patients, persistent AKI and the absence of renal recovery are associated with distinct early and sustained immunologic and endothelial biomarker signatures and decreased long-term physical function and survival.

P0513NECROINFLAMMATION VERSUS CRYSTAL CLOTS AS THERAPEUTIC TARGET IN CHOLESTEROL CRYSTAL EMBOLISM-RELATED KIDNEY INFARCT

Abstract Background and Aims Cholesterol crystal embolism (CCE) is usually a consequence of the rupture of atheromatous plaques in patients with advanced atherosclerosis. We hypothesized that necroinflammation contributes to CCE-related kidney injury/disease (AKI/AKD). Method Injection of cholesterol crystal (CC) into C56BL/6 WT mice kidney via the left kidney artery induced vascular obstruction, kidney infarction, and GFR loss (measured by transcutaneous monitoring of sinistrin clearance in awake and unrestricted mice). GFR recovered to baseline at 2 weeks despite persistent kidney injury and scarring, probably because the non-injected right kidney developed compensatory hypertrophy. To study the role of necroinflammation in this process, we injected CC to either Mlkl-/- mice or WT mice pre-treated with PBS, the necroptosis inhibitor Nec-1s or the NLRP3 inhibitor MCC950 30 min before CC injection. Results At 24h, Nec-1s, MCC950 treatment had significantly reduced infarct size, kidney injury, neutrophil infiltration, and vascular injury compared to PBS control group. Reduced infarct size, e.g. with Nec-1s persistented until day 14. CC injection into Mlkl-/- mice gave the same results. However, none of these interventions had an effect on GFR loss, i.e. AKI because they did not affect crystal clot formation in the arteria afferent to glomerular perfusion. In contrast, anticoagulant treatment prevented infarcts and GFR loss. Conclusion In this new model of unilateral CCE-induced AKI/AKD global kidney function recovers within 14 d, presumably due to adaptive responses in the contralateral kidney as the post-infarct tissue injury persists and leads to kidney atrophy. As both the NLRP3 inflammasome as well as necroptosis are involved in kidney infarct formation, we conclude on necroinflammation as the central mechanism of CCE-induced AKI/AKD. However, what defines AKI is renal function. We found that crystal clot formation is upstream of kidney infarction but independent of necroinflammation. We conclude, despite necroinflammation is central in kidney infarct formation, crystal clots are the better therapeutic target to prevent CCE-related AKI.