Septic acute kidney injury and gut microbiome: Should we change our approach? / Lesión renal aguda secundaria a sepsis y microbioma intestinal: ¿debemos modificar nuestro enfoque?

Incidence of acute kidney injury (AKI) remained relatively stable over the last decade and the adjusted risks for it and mortality are similar across different continents and regions. Also, the mortality of septic-AKI can reach 70% in critically-ill patients. These sole facts can give rise to a question: is there something we do not understand yet? Currently, there are no specific therapies for septic AKI and the treatment aims only to maintain the mean arterial pressure over 65mmHg by ensuring a good fluid resuscitation and by using vasopressors, along with antibiotics. On the other hand, there is an increased concern about the different hemodynamic changes in septic AKI versus other forms and the link between the gut microbiome and the severity of septic AKI. Fortunately, progress has been made in the form of administration of pre- and probiotics, short chain fatty acids (SCFA), especially acetate, and also broad-spectrum antibiotics or selective decontaminants of the digestive tract in a successful attempt to modulate the microbial flora and to decrease both the severity of AKI and mortality. In conclusion, septic-AKI is a severe form of kidney injury, with particular hemodynamic changes and with a strong link between the kidney and the gut microbiome. By modulating the immune response we could not only treat but also prevent severe forms. The most difficult part is to categorize patients and to better understand the key mechanisms of inflammation and cellular adaptation to the injury, as these mechanisms can serve in the future as target therapies.(AU)

La incidencia de la lesión renal aguda (LRA) se ha mantenido relativamente estable a lo largo de la última década, con unos riesgos ajustados de padecer y morir a consecuencia de esta enfermedad similares en los distintos continentes y regiones. La mortalidad asociada a la LRA secundaria a sepsis puede llegar a 70% en los pacientes que se encuentran en estado crítico. Estos hechos, por sí mismos, deben llevarnos a plantearnos la siguiente pregunta: ¿se nos escapa algo que aún no comprendemos? Actualmente no se dispone de terapias específicas para la LRA secundaria a sepsis y el tratamiento se centra únicamente en mantener la presión arterial media por encima de los 65mmHg mediante una rehidratación adecuada, vasopresores y antibióticos. Asimismo, cada vez existe mayor interés por las diferentes alteraciones hemodinámicas que se producen en comparación con otras formas de la enfermedad, así como por la relación existente entre el microbioma intestinal y la gravedad. Afortunadamente, se ha avanzado notablemente en la forma en la que se administran los prebióticos y los probióticos, los ácidos grasos de cadena corta (AGCC), especialmente el acetato, los antibióticos de amplio espectro o los detoxificantes selectivos del tracto digestivo, en un intento exitoso de modular la flora microbiana y disminuir tanto la gravedad de la LRA como su mortalidad. En conclusión, la LRA secundaria a sepsis es una forma grave de lesión renal que provoca unos cambios hemodinámicos específicos y en la que se observa una estrecha relación entre la función renal y el microbioma intestinal. La modulación de la respuesta inmunitaria no solo permitiría tratar esta enfermedad, sino también prevenir las formas graves de la misma. La parte más difícil de este enfoque radica en clasificar correctamente a los pacientes y comprender mejor los mecanismos clave de la inflamación y la adaptación celular a la lesión, ya que estos pueden convertirse en futuras dianas terapéuticas.(AU)

Predictors and Prognostic Impact of Early Acute Kidney Injury in Cardiogenic Shock: Results from a Monocentric, Prospective Registry.

INTRODUCTION: The presence of acute kidney injury (AKI) was shown to increase the risk of mortality following acute myocardial infarction; however, data regarding the prognostic impact of early AKI in patients with concomitant cardiogenic shock (CS) is limited. The study investigates predictors and the prognostic impact of AKI in patients with CS. METHODS: Consecutive patients with CS from 2019 to 2021 were included at one institution. Laboratory values were retrieved from day of disease onset (day 1) and days 2, 3, 4, and 8 thereafter. Predictors for AKI (defined as an increase of plasma creatinine >50% within 48 h referring to pre-admission or baseline creatinine on day 1 and/or the need for continuous veno-venous hemodiafiltration [CVVHDF]) and the prognostic impact of early AKI with regard to 30-day all-cause mortality were assessed. Statistical analyses included t test, Spearman's correlation, C-statistics, Kaplan-Meier, and Cox proportional regression analyses. RESULTS: A total of 219 CS patients were included with an incidence of early CS-related AKI of 52%. With an area under the curve of up to 0.689 (p = 0.001), creatine discriminated 30-day mortality in CS. Increasing lactate levels (OR = 1.194; 95% CI: 1.083-1.316; p = 0.001; per increase of 1 mmol/L) was associated with the occurrence of AKI. The presence of AKI was associated with an increased risk of 30-day all-cause mortality (63% vs. 36%; HR = 2.138; 95% CI: 1.441-3.171; p = 0.001), even after multivariable adjustment (HR = 1.861; 95% CI: 1.207-2.869; p = 0.005). Finally, highest risk of all-cause mortality was observed in patients with AKI requiring CVVHDF (75% vs. 44%; log rank p = 0.001; HR = 2.211; 95% CI: 1.315-3.718; p = 0.003). CONCLUSION: Early AKI affects more than half of patients with CS and is independently associated with 30-day all-cause mortality in CS, with highest risk of death among patients with AKI requiring CVVHDF.

Fluid balance, biomarkers of renal function and mortality in critically ill patients with AKI diagnosed before, or within 24 h of intensive care unit admission: a prospective study.

BACKGROUND: To evaluate fluid balance, biomarkers of renal function and its relation to mortality in patients with acute kidney injury (AKI) diagnosed before, or within 24 h of intensive care unit admission. METHODS: A prospective cohort study considered 773 critically ill patients observed over six years. Pre-intensive care unit-onset AKI was defined as AKI diagnosed before, or within 24 h of intensive care unit admission. Body weight-adjusted fluid balance and fluid balance-adjusted biomarkers of renal function were measured daily for the first three days of intensive care unit admission. Primary outcome was mortality in the intensive care unit. RESULTS: Prevalence of pre-intensive care unit-onset AKI was 55.1%, of which 55.6% of cases were hospital-acquired and 44.4% were community-acquired. Fluid balance was higher in AKI patients than in non-AKI patients (p < 0.001) and had a negative correlation with urine output (p < 0.01). Positive fluid balance and biomarkers of renal function were independently related to mortality. Multivariate analysis identified the following AKI-related variables associated with increased mortality: (1) In AKI patients: type 1 cardiorenal syndrome (OR 2.00), intra-abdominal hypertension (OR 1.71), AKI stage 3 (OR 2.15) and increase in AKI stage (OR 4.99); 2) In patients with community-acquired AKI: type 1 cardiorenal syndrome (OR 5.16), AKI stage 2 (OR 2.72), AKI stage 3 (OR 4.95) and renal replacement therapy (OR 3.05); and 3) In patients with hospital-acquired AKI: intra-abdominal hypertension (OR 2.31) and increase in AKI stage (OR 4.51). CONCLUSIONS: In patients with pre-intensive care unit-onset AKI, positive fluid balance is associated with worse renal outcomes. Positive fluid balance and decline in biomarkers of renal function are related to increased mortality, thus in this subpopulation of critically ill patients, positive fluid balance is not recommended and renal function must be closely monitored.

Mortality and Cumulative Kidney Score are Associated with Transient and Persistent Acute Kidney Injury in Septic Patients: A Retrospective Study Based on MIMIC-IV

Background: Acute kidney injury (AKI) is frequently caused by sepsis. Recently, the Acute Disease Quality Initiative (ADQI) workgroup further classified AKI as transient or persistent. Oliguria and increased serum creatinine represent two different kinds of renal impairment. The aim of the study was to assess mortality and cumulative AKI score associated with transient and persistent AKI in septic patients. Methods: Septic patients were stratified according to the presence and AKI development (considered persistent when remaining >48 h) were included. An adjusted logistic regression model was used to determine hospital mortality. In addition, we calculated an AKI score by combining both Kidney Disease: Improving Global Outcomes (KDIGO) criteria of urine output and creatinine AKI stages. The relationship between the cumulative AKI score and persistent AKI was further examined using the logistic regression model and receiver operating characteristic (ROC) curve analysis. Results: 12928 septic patients were enrolled in the study. AKI occurred in 73.7% of septic patients, in 39.5% was transient and in 60.5% was persistent. Patients with persistent AKI had higher severity scores and more severe renal dysfunction upon admission. Persistent AKI, but not transient AKI, was associated with increased intensive care units (ICUs) and hospital mortality. Then we found that the cumulative AKI score was associated with an increased risk of persistent AKI. This association was consistent across three original KDIGO severity stages and subgroup analyses. Conclusions: It was found that persistent AKI was independently associated with mortality in septic patients. Furthermore, serum creatinine and urine output criteria had cumulative effects on KDIGO AKI staging and provided more information about the relationship between AKI and outcomes (AU)

Association of Preoperative Neutrophil-to-Lymphocyte Ratio with Postoperative Acute Kidney Injury and Mortality Following Major Noncardiac Surgeries.

BACKGROUND: Acute kidney injury (AKI) is a major complication that occurs following an operation. Therefore, there is an increasing need to discover new predictors of AKI. We hypothesized that the preoperative neutrophil-to-lymphocyte ratio (NLR) was associated with postoperative AKI and in-hospital mortality following noncardiac surgery. METHODS: This is a retrospective observational study of patients who underwent noncardiac surgery at Sichuan University West China Hospital from 2018 to 2020. Multivariable logistic regression was performed as the major analytic method. In addition, sensitivity and subgroup analyses were performed to validate the results. RESULTS: A total of 44,065 patients were included in this study. The prevalence of postoperative AKI was 5.62%, and the in-hospital mortality was 1.58%. Multivariable analysis demonstrated that NLR ≥ 5 was independently associated with the development of postoperative AKI (OR 1.42, 1.24-1.73; P < 0.001) and in-hospital mortality (OR 2.03, 1.63-2.52; P < 0.001). Similar results were achieved when propensity-score matching was performed for patients with NLR ≥ 5 and < 5 on the baseline. In stratified analysis, the associations remained persistent in most subgroups. For the sensitivity analysis, we took NLR as a continuous variable and demonstrated the potential linear relationship between NLR and postoperative AKI and mortality. CONCLUSIONS: Our results indicated that preoperative NLR is associated with the prevalence of postoperative AKI and in-hospital mortality that occur after major noncardiac surgery. These findings suggest that NLR has the potential to be a significant correlation biomarker associated with perioperative risk assessment of patients undergoing noncardiac surgeries.

The attributable mortality of sepsis for acute kidney injury: a propensity-matched analysis based on multicenter prospective cohort study.

BACKGROUND: Both sepsis and AKI are diseases of major concern in intensive care unit (ICU). This study aimed to evaluate the excess mortality attributable to sepsis for acute kidney injury (AKI). METHODS: A propensity score-matched analysis on a multicenter prospective cohort study in 18 Chinese ICUs was performed. Propensity score was sequentially conducted to match AKI patients with and without sepsis on day 1, day 2, and day 3-5. The primary outcome was hospital death of AKI patients. RESULTS: A total of 2008 AKI patients (40.9%) were eligible for the study. Of the 1010 AKI patients with sepsis, 619 (61.3%) were matched to 619 AKI patients in whom sepsis did not develop during the screening period of the study. The hospital mortality rate of matched AKI patients with sepsis was 205 of 619 (33.1%) compared with 150 of 619 (24.0%) for their matched AKI controls without sepsis (p = 0.001). The attributable mortality of total sepsis for AKI patients was 9.1% (95% CI: 4.8-13.3%). Of the matched patients with sepsis, 328 (53.0%) diagnosed septic shock. The attributable mortality of septic shock for AKI was 16.2% (95% CI: 11.3-20.8%, p < 0.001). Further, the attributable mortality of sepsis for AKI was 1.4% (95% CI: 4.1-5.9%, p = 0.825). CONCLUSIONS: The attributable hospital mortality of total sepsis for AKI were 9.1%. Septic shock contributes to major excess mortality rate for AKI than sepsis. REGISTRATION FOR THE MULTICENTER PROSPECTIVE COHORT STUDY: registration number ChiCTR-ECH-13003934.

Association between C-reactive protein and all-cause mortality among critically ill patients with acute kidney injury.

AIM: To explore the relationship between C-reactive protein (CRP) and mortality in critically ill patients with acute kidney injury (AKI). MATERIALS AND METHODS: A total of 580 patients diagnosed with AKI within 48 hours of ICU admission between September 2017 and August 2019 were enrolled. Patients were followed for all-cause mortality in-hospital and then up to 2 years after discharge. We performed two multivariate regression analysis to assess the association between CRP and mortality, and conducted stratified analysis to assess whether the effect of the CRP differed across subgroups. RESULTS: According to initial CRP quartiles, patients were divided into 4 groups (quartile 1, CRP ≤ 2.87 mg/L; quartile 2, CRP: 2.87 - 25.95 mg/L; quartile 3, CRP: 25.95 - 111.51 mg/L; quartile 4, CRP > 111.51 mg/L). Patients with high CRP levels have higher APACHE-II score, longer length of stay in the ICU, and higher mortality. In multivariate regression analysis, high CRP was associated with the increased risk of in-hospital mortality after adjusting for age, gender, surgical grade, heart rate, serum potassium, serum chloride, coronary heart disease, and atherosclerotic cerebral infarction (quartile 4 vs. quartile 1, OR: 3.810, 95% CI: 2.081 - 6.973). For 2-year mortality, the increased trend was still significant with the OR (95% CI) of the quartile 4 group of 5.117 (2.678 - 9.780) after adjusting for confounders. Subgroup analyses detected in each group showed that the in-hospital and 2-year risk of mortality increased with higher CRP levels. CONCLUSION: Higher CRP level was associated with the increased risk of mortality in critically ill patients with AKI.

Predictive Values of Procalcitonin and Presepsin for Acute Kidney Injury and 30-Day Hospital Mortality in Patients with COVID-19.

Background and Objectives: Acute kidney injury (AKI) is a common complication in patients with coronavirus disease 2019 (COVID-19). We investigated the values of procalcitonin (PCT) and presepsin (PSS) for predicting AKI and 30-day hospital mortality in patients with COVID-19. Materials and Methods: We retrospectively evaluated 151 patients with COVID-19 who were admitted to the hospital via the emergency department. The diagnosis of AKI was based on the Kidney Disease: Improving Global Outcomes clinical practice guidelines. Results: The median patient age was 77 years, and 86 patients (57%) were male. Fifty-six patients (37.1%) developed AKI, and 19 patients (12.6%) died within 30 days of hospital admission. PCT and PSS levels were significantly higher in patients with AKI and non-survivors. The cutoff values of PCT levels for predicting AKI and mortality were 2.26 ng/mL (sensitivity, 64.3%; specificity, 89.5%) and 2.67 ng/mL (sensitivity, 68.4%; specificity, 77.3%), respectively. The cutoff values of PSS levels for predicting AKI and mortality were 572 pg/mL (sensitivity, 66.0%; specificity, 69.1%) and 865 pg/mL (sensitivity, 84.6%; specificity, 76.0%), respectively. Conclusion: PCT and PSS are valuable biomarkers for predicting AKI and 30-day hospital mortality in patients with COVID-19.

COVID-19 in Kidney Transplant Recipients: A Multicenter Experience from the First Two Waves of Pandemic.

BACKGROUND: Kidney transplant recipients have an increased risk of complications from COVID-19. However, data on the risk of allograft damage or death in kidney transplant recipients recovering from COVID-19 is limited. In addition, the first and second waves of the pandemic occurred at different times all over the world. In Turkey, the Health Minister confirmed the first case in March 2020; after that, the first wave occurred between March and August 2020; afterward, the second wave began in September 2020. This study aims to demonstrate the clinical presentations of kidney transplant recipients in the first two waves of the pandemic in Turkey and explore the impact of COVID-19 on clinical outcomes after the initial episode. METHODS: Patients with COVID-19 from seven centers were included in this retrospective cohort study. Initially, four hundred and eighty-eight kidney transplant recipients diagnosed with COVID-19 between 1 March 2020 to 28 February 2021 were enrolled. The endpoints were the occurrence of all-cause mortality, acute kidney injury, cytokine storm, and acute respiratory distress syndrome. In addition, longer-term outcomes such as mortality, need for dialysis, and allograft function of the surviving patients was analyzed. RESULTS: Four hundred seventy-five patients were followed up for a median of 132 days after COVID-19. Forty-seven patients (9.9%) died after a median length of hospitalization of 15 days. Although the mortality rate (10.1% vs. 9.8%) and intensive care unit admission (14.5% vs. 14.5%) were similar in the first two waves, hospitalization (68.8% vs. 29.7%; p < 0.001), acute kidney injury (44.2% vs. 31.8%; p = 0.009), acute respiratory distress syndrome (18.8% vs. 16%; p = 0.456), and cytokine storm rate (15.9% vs. 10.1%; p = 0.072) were higher in first wave compared to the second wave. These 47 patients died within the first month of COVID-19. Six (1.4%) of the surviving patients lost allografts during treatment. There was no difference in the median serum creatinine clearance of the surviving patients at baseline (52 mL/min [IQR, 47-66]), first- (56 mL/min [IQR, 51-68]), third- (51 mL/min [IQR,48-67]) and sixth-months (52 mL/min [IQR, 48-81]). Development of cytokine storm and posttransplant diabetes mellitus were independent predictors for mortality. CONCLUSIONS: Mortality remains a problem in COVID-19. All the deaths occur in the first month of COVID-19. Also, acute kidney injury is common in hospitalized patients, and some of the patients suffer from graft loss after the initial episode.

In hospital risk factors for acute kidney injury and its burden in patients with Sars-Cov-2 infection: a longitudinal multinational study.

Acute kidney injury (AKI) is associated with increased mortality in most critical settings. However, it is unclear whether its mild form (i.e. AKI stage 1) is associated with increased mortality also in non-critical settings. Here we conducted an international study in patients hospitalized with SARS-CoV-2 infection aiming 1. to estimate the incidence of AKI at each stage and its impact on mortality 2. to identify AKI risk factors at admission (susceptibility) and during hospitalization (exposures) and factors contributing to AKI-associated mortality. We included 939 patients from medical departments in Moscow (Russia) and Padua (Italy). In-hospital AKI onset was identified in 140 (14.9%) patients, mainly with stage 1 (65%). Mortality was remarkably higher in patients with AKI compared to those without AKI (55 [39.3%] vs. 34 [4.3%], respectively). Such association remained significant after adjustment for other clinical conditions at admission (relative risk [RR] 5.6; CI 3.5- 8.8) or restricting to AKI stage 1 (RR 3.2; CI 1.8-5.5) or to subjects with AKI onset preceding deterioration of clinical conditions. After hospital admission, worsening of hypoxic damage, inflammation, hyperglycemia, and coagulopathy were identified as hospital-acquired risk factors predicting AKI onset. Following AKI onset, the AKI-associated worsening of respiratory function was identified as the main contributor to AKI-induced increase in mortality risk. In conclusion, AKI is a common complication of Sars-CoV2 infection in non-intensive care settings where it markedly increases mortality risk also at stage 1. The identification of hospital-acquired risk factors and exposures might help prevention of AKI onset and of its complications.

Acute Kidney Injury in Patients with Liver Cirrhosis: Prevalence, Predictors, and In-Hospital Mortality at a District Hospital in Ghana.

BACKGROUND: Acute kidney injury (AKI) is one of the most severe complications of cirrhosis and portends an ominous prognosis with an estimated mortality of about 50% in a month and 65% within a year. Infection and hypovolemia have been found to be the main precipitating factors of AKI in liver cirrhosis. Early detection and treatment of AKI may improve outcomes. AKI in patients with liver cirrhosis in Ghana and their impact on inpatient mortality are largely unknown. This study was aimed at determining the prevalence, precipitating factors, predictors, and in-hospital mortality of AKI in patients with liver cirrhosis admitted to a district hospital in Ghana. METHODS: Consecutive hospitalized patients with liver cirrhosis from 1 January 2018 to 30 April 2020 were recruited. Patient's demographic data and clinical features were collected using a standardized questionnaire. Biochemical and haematological tests as well as abdominal ultrasound scans were done for all patients. All patients were then followed up until discharge or death. RESULTS: There were 117 (65.4%) males out of the 179 patients with a mean age of 49.94 and 45.84 years for those with and without AKI, respectively. The prevalence of AKI was 27.9% (50/179). Out of 50 participants with AKI, 64.0% (32/50) died, contributing 41.0% of all in-patient mortality amongst participants. There was a significant association between AKI and death (p ≤ 0.001). The major precipitating factors of AKI were infections (60.0%), hypovolemia (20.0%) due to gastrointestinal bleeding and gastroenteritis, and refractory ascites (16.0%). Alkaline phosphatase, INR, model for end-stage liver disease sodium, sodium, and blood urea nitrogen were independent predictors of AKI. CONCLUSION: AKI was common among patients with liver cirrhosis with high in-patient mortality. Identification of these precipitants and independent predictors of AKI may lead to prompt and targeted treatment with reduction in patient mortality.

In-Hospital and 1-Year Mortality Trends in a National Cohort of US Veterans with Acute Kidney Injury.

BACKGROUND AND OBJECTIVES: AKI, a frequent complication among hospitalized patients, confers excess short- and long-term mortality. We sought to determine trends in in-hospital and 1-year mortality associated with AKI as defined by Kidney Disease Improving Global Outcomes consensus criteria. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study used data from the national Veterans Health Administration on all patients hospitalized from October 1, 2008 to September 31, 2017. AKI was defined by Kidney Disease Improving Global Outcomes serum creatinine criteria. In-hospital and 1-year mortality trends were analyzed in patients with and without AKI using Cox regression with year as a continuous variable. RESULTS: We identified 1,688,457 patients and 2,689,093 hospitalizations across the study period. Among patients with AKI, 6% died in hospital, and 28% died within 1 year. In contrast, in-hospital and 1-year mortality rates were 0.8% and 14%, respectively, among non-AKI hospitalizations. During the study period, there was a slight decline in crude in-hospital AKI-associated mortality (hazard ratio, 0.98 per year; 95% confidence interval, 0.98 to 0.99) that was attenuated after accounting for patient demographics, comorbid conditions, and acute hospitalization characteristics (adjusted hazard ratio, 0.99 per year; 95% confidence interval, 0.99 to 1.00). This stable temporal trend in mortality persisted at 1 year (adjusted hazard ratio, 1.00 per year; 95% confidence interval, 0.99 to 1.00). CONCLUSIONS: AKI associated mortality remains high, as greater than one in four patients with AKI died within 1 year of hospitalization. Over the past decade, there seems to have been no significant progress toward improving in-hospital or long-term AKI survivorship.

Effects of dexmedetomidine on surgery for type A acute aortic dissection outcome.

No study has evaluated the effect of dexmedetomidine in patients who received surgery for type A aortic dissection. This is the first study to evaluate the effect of dexmedetomidine in aortic dissection patients. This study was executed using data from the Chang Gung Research Database in Taiwan. The CGRD contains the multi-institutional standardized electronic medical records from seven Chang Gung Memorial hospitals, the largest medical system in Taiwan. We retrospectively evaluate patients who received surgery for acute type A aortic dissection between January 2014 and December 2018. Overall, 511 patients were included, of whom 104 has received dexmedetomidine infusion in the postoperative period. One-to-two propensity score-matching yielded 86 cases in the dexmedetomidine group and 158 cases in the non-dexmedetomidine group. The in-hospital mortality and composite outcome including all-cause mortality, acute kidney injury, delirium, postoperative atrial fibrillation, and respiratory failure, were considered primary outcomes. The in-hospital mortality and composite outcome were similar between groups. The risk of Acute Kidney Injury Network stage 3 acute kidney injury was significantly lower in the dexmedetomidine group than in the non-dexmedetomidine group (8.1% vs 19.0%; OR, 0.38; 95% CI, 0.17-0.86; p = 0.020. The risk of newly-onset dialysis was also significantly lower in the dexmedetomidine group than in the non-dexmedetomidine group (4.7% vs 13.3%; OR, 0.32; 95% CI, 0.11-0.90; p = 0.031). Post-operative dexmedetomidine infusion significantly reduced the rate of severe acute kidney injury and newly-onset dialysis in patients who received surgery for acute type A aortic dissection.

Role of Urinary Kidney Stress Biomarkers for Early Recognition of Subclinical Acute Kidney Injury in Critically Ill COVID-19 Patients.

A high proportion of critically ill patients with COVID-19 develop acute kidney injury (AKI) and die. The early recognition of subclinical AKI could contribute to AKI prevention. Therefore, this study was aimed at exploring the role of the urinary biomarkers NGAL and [TIMP-2] × [IGFBP7] for the early detection of AKI in this population. This prospective, longitudinal cohort study included critically ill COVID-19 patients without AKI at study entry. Urine samples were collected on admission to critical care areas for determination of NGAL and [TIMP-2] × [IGFBP7] concentrations. The demographic information, comorbidities, clinical, and laboratory data were recorded. The study outcomes were the development of AKI and mortality during hospitalization. Of the 51 individuals that were studied, 25 developed AKI during hospitalization (49%). Of those, 12 had persistent AKI (23.5%). The risk factors for AKI were male gender (HR = 7.57, 95% CI: 1.28-44.8; p = 0.026) and [TIMP-2] × [IGFBP7] ≥ 0.2 (ng/mL)2/1000 (HR = 7.23, 95% CI: 0.99-52.4; p = 0.050). Mortality during hospitalization was significantly higher in the group with AKI than in the group without AKI (p = 0.004). Persistent AKI was a risk factor for mortality (HR = 7.42, 95% CI: 1.04-53.04; p = 0.046). AKI was frequent in critically ill COVID-19 patients. The combination of [TIMP-2] × [IGFBP7] together with clinical information, were useful for the identification of subclinical AKI in critically ill COVID-19 patients. The role of additional biomarkers and their possible combinations for detection of AKI in ritically ill COVID-19 patients remains to be explored in large clinical trials.

Kidney Injury in COVID-19: Epidemiology, Molecular Mechanisms and Potential Therapeutic Targets.

As of December 2021, SARS-CoV-2 had caused over 250 million infections and 5 million deaths worldwide. Furthermore, despite the development of highly effective vaccines, novel variants of SARS-CoV-2 continue to sustain the pandemic, and the search for effective therapies for COVID-19 remains as urgent as ever. Though the primary manifestation of COVID-19 is pneumonia, the disease can affect multiple organs, including the kidneys, with acute kidney injury (AKI) being among the most common extrapulmonary manifestations of severe COVID-19. In this article, we start by reflecting on the epidemiology of kidney disease in COVID-19, which overwhelmingly demonstrates that AKI is common in COVID-19 and is strongly associated with poor outcomes. We also present emerging data showing that COVID-19 may result in long-term renal impairment and delve into the ongoing debate about whether AKI in COVID-19 is mediated by direct viral injury. Next, we focus on the molecular pathogenesis of SARS-CoV-2 infection by both reviewing previously published data and presenting some novel data on the mechanisms of cellular viral entry. Finally, we relate these molecular mechanisms to a series of therapies currently under investigation and propose additional novel therapeutic targets for COVID-19.

Albumin levels predict mortality in sepsis patients with acute kidney injury undergoing continuous renal replacement therapy: a secondary analysis based on a retrospective cohort study.

BACKGROUND: Albumin (ALB) levels are negatively associated with mortality in patients with sepsis. However, among sepsis patients with acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT), there has been no similar study on the correlation between ALB levels and mortality alone. This study tested the hypothesis that ALB levels are negatively associated with mortality among such patients. METHODS: We conducted a secondary analysis of 794 septic patients who were diagnosed with AKI and underwent CRRT in South Korea. For the Kaplan-Meier survival analysis, Cox proportional hazards models were used to study the hypotheses, with adjustments for the pertinent covariables. We also explore the possible nonlinear relationship and conducted sensitivity analyses including subgroup analyses and tests for interactions to investigate the association further. Additionally, ALB was used to construct model and we then compared the performance of ALB with that of APACHE II and SOFA in predicting mortality. RESULTS: The ALB level was an independent prognostic factor for death at 28 and 90 days after CRRT initiation (HR = 0.75, 95% CI: 0.62-0.90, P = 0.0024 for death at 28 days and HR = 0.73, 95% CI: 0.63-0.86, P < 0.0001 for death at 90 days). A nonlinear association was not identified between ALB levels and the endpoints. Subgroup analyses and tests for interactions indicated that HCO3 and CRP played an interactive role in the association. ROC analysis indicated ALB, SOFA and APACHE-II were separately inadequate for clinical applications. CONCLUSION: A 1 g/dL increase in ALB levels was independently associated with a 25 and 27% decrease in the risk of death at 28 and 90 days, respectively. However, this conclusion needs to be taken with caution as this study has several limitations.

Utilization of Palliative Care for Patients with COVID-19 and Acute Kidney Injury during a COVID-19 Surge.

BACKGROUND AND OBJECTIVES: AKI is a common complication of coronavirus disease 2019 (COVID-19) and is associated with high mortality. Palliative care, a specialty that supports patients with serious illness, is valuable for these patients but is historically underutilized in AKI. The objectives of this paper are to describe the use of palliative care in patients with AKI and COVID-19 and their subsequent health care utilization. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective analysis of New York University Langone Health electronic health data of COVID-19 hospitalizations between March 2, 2020 and August 25, 2020. Regression models were used to examine characteristics associated with receiving a palliative care consult. RESULTS: Among patients with COVID-19 (n=4276; 40%), those with AKI (n=1310; 31%) were more likely than those without AKI (n=2966; 69%) to receive palliative care (AKI without KRT: adjusted odds ratio, 1.81; 95% confidence interval, 1.40 to 2.33; P<0.001; AKI with KRT: adjusted odds ratio, 2.45; 95% confidence interval, 1.52 to 3.97; P<0.001), even after controlling for markers of critical illness (admission to intensive care units, mechanical ventilation, or modified sequential organ failure assessment score); however, consults came significantly later (10 days from admission versus 5 days; P<0.001). Similarly, 66% of patients initiated on KRT received palliative care versus 37% (P<0.001) of those with AKI not receiving KRT, and timing was also later (12 days from admission versus 9 days; P=0.002). Despite greater use of palliative care, patients with AKI had a significantly longer length of stay, more intensive care unit admissions, and more use of mechanical ventilation. Those with AKI did have a higher frequency of discharges to inpatient hospice (6% versus 3%) and change in code status (34% versus 7%) than those without AKI. CONCLUSIONS: Palliative care was utilized more frequently for patients with AKI and COVID-19 than historically reported in AKI. Despite high mortality, consultation occurred late in the hospital course and was not associated with reduced initiation of life-sustaining interventions. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_02_24_CJN11030821.mp3.