Non-septic Acute Kidney Injury Research Articles

#1708 Mortality and kidney function recovery in patients with sepsis-associated vs non-septic acute kidney injury treated with CRRT

Abstract Background and Aims It was recently suggested that sepsis-associated acute kidney injury (SA-AKI) is characterized by different pathogenesis and outcomes compared to non-Septic AKI (NS-AKI). However, limited data are available focusing on the clinical outcomes of SA-AKI versus NS-AKI. The aim of this study is to examine risk factors and outcomes of SA-AKI vs NS-AKI among critically ill patients who developed AKI requiring renal replacement therapy (RRT). Methods We performed a single-center retrospective analysis, examining all patients admitted to ICU who developed AKI requiring RRT at Policlinico of Bari, from January 2021 to July 2023. We classified patients in two groups based on the leading cause of AKI: NS-AKI and SA-AKI. We collected clinical and laboratory data, including maximum AKI stage reached during hospitalization, RRT indications, modality and duration. The primary outcome was to assess mortality rate between SA-AKI and NS-AKI groups. The cumulative 28-day survival probability was calculated using the Kaplan–Meier method. The analysis of the risk factors associated with in-hospital mortality was performed using Cox's proportional hazard regression models. Kidney Functional Recovery (KFR) from, RRT discontinuation and length of ICU and hospital stay were also analyzed. Results 320 patients were included in the study; 131 patients developed SA-AKI (40.9%), while the remaining 189 were classified as NS-AKI (59.1%). Median age was 67 years (IQR 57-73) with a predominance of male gender (67.8%), without significant differences between groups. A significant percentage of patients had an history of cardiovascular disease in NS-AKI group compared to SA-AKI group (54.5% vs 29%, p < 0.001). Conversely, the proportion of patients with a history of chronic respiratory disease was significantly higher in the SA-AKI group (23.7% vs 9.5%, p = 0.001). 268 patients (83.8%) developed AKI Stage 3 and 40 patients AKI stage 2 (12.5%) at RRT initiation. All patients were treated with continuous modalities (CRRT). There was no significant difference in CRRT duration between groups (median days 5, IQR 2-12) (Table 1). The timing of CRRT initiation from ICU admission was significant different and we reported a late CRRT initiation in the SA-AKI group (3 vs 1 days, p = 0.002). The median length of ICU stay was 12 days (IQR 4-25) and did not differ between groups. 184 patients (57.5%) died at 28 days, with a higher percentage in the SA-AKI (70.2 vs 48.6%, p < 0.001). Similarly, in-hospital mortality was reported in 221 patients (69%), with impressive percentages in the SA-AKI group (82.45 vs 69.3%, p < 0.001) (Fig. 1). KFR at 28 days from CRRT initiation was significantly higher in the NS-AKI (28.5%) compared to the SA-AKI group (13.7%, p = 0.002). Median time of KFR was similar between groups (p = 0.833). Multivariate Cox Regression analysis showed that only SA-AKI (HR 1.442, 95% CI 1.052-1.978, p = 0.023) was independently associated with increased risk of mortality. Conclusions Sepsis-associated AKI was associated with high mortality rate and lower likelihood of renal recovery compared to non-septic AKI in critically ill patients requiring RRT. These findings emphasize the importance of identifying specific AKI phenotypes characterized by different pathophysiology and clinical outcomes.

Assessment of urine CCL2 as a potential diagnostic biomarker for acute kidney injury and septic acute kidney injury in intensive care unit patients

Acute kidney injury (AKI) is a prevalent and serious condition in the intensive care unit (ICU), associated with significant morbidity and mortality. Septic acute kidney injury (SAKI) contributes substantially to AKI cases in the ICU. However, current diagnostic methods have limitations, necessitating the exploration of novel biomarkers. In this study, we investigated the potential of plasma and urine CCL2 levels as diagnostic markers for AKI and SAKI in 216 ICU patients. Our findings revealed significant differences in plasma (p < 0.01) and urine CCL2 (p < 0.0001) levels between AKI and non-AKI patients in the ICU. Notably, urine CCL2 demonstrated promising predictive value for AKI, exhibiting high specificity and sensitivity (AUC = 0.8976; p < 0.0001). Furthermore, we observed higher urine CCL2 levels in SAKI compared to non-septic AKI (p < 0.001) and urine CCL2 could also differentiate SAKI from non-septic AKI (AUC = 0.7597; p < 0.0001). These results suggest that urine CCL2 levels hold promise as early biomarkers for AKI and SAKI, offering valuable insights for timely intervention and improved management of ICU patients.

CLINICAL UTILITY OF URINE NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN (UNGAL) AS A MARKER IN DISCRIMINATION OF SEPTIC VERSUS NON-SEPTIC ACUTE KIDNEY INJURY

Background &amp; Aim:This study was aimed to determine whether there are unique patterns to urine neutrophil gelatinase-associated lipocalin (uNGAL) in septic compared with non-septic acute kidney injury (AKI)and also to evaluate whether uNGAL could discriminate between septic and non-septic AKI. Materials&amp; Methods:This prospective observational study screened critically ill AKI patientsand evaluated them for presenting complaints, and on evaluation, those who satisfied Systemic inflammatory response syndrome (SIRS) criteria were taken up for study. Those patients with evidence of infection and positive for at least two criteria for SIRS are taken up as cases (n=30) and the rest as controls (n=30). All the patients were serially monitored for urine output, renal parameters, urine NGAL, APACHE II score and SOFA score. Patient urine was collected immediately after admission, followed by 12h, 24 h &amp; 48 h for measuring uNGAL. Results:Mean change in uNGAL(ng/ml) at 12h, 24h and 48h was 12.5±5, 20.5±6.7 and 29.3±10.2 respectively in septic AKI and was 0.9±6.1, 0.9±6.3 and 0.1±6.1 respectively in non-septic AKI. Within the group, the analysis showed statistically high significance (p-value&lt;0.0001) in septic AKI but not in the non-septic AKI group (p-value=0.97). On evaluating between-group analyses, we found a significantly high difference of NGAL in septic AKI at 12h, 24h and 48h compared to non-septic AKI(p-value&lt;0.0001). Conclusions:Septic AKI patients have higher detectable uNGAL than non-septic AKI patients. These differences in uNGAL values in septic AKI may have diagnostic and clinical relevance and pathogenetic implications.

Extracorporeal blood purification therapies for sepsis-associated acute kidney injury in critically ill patients: expert opinion from the SIAARTI-SIN joint commission

Sepsis-Associated Acute Kidney Injury is a life-threatening condition leading to high morbidity and mortality in critically ill patients admitted to the intensive care unit. Over the past decades, several extracorporeal blood purification therapies have been developed for both sepsis and sepsis-associated acute kidney injury management. Despite the widespread use of extracorporeal blood purification therapies in clinical practice, it is still unclear when to start this kind of treatment and how to define its efficacy. Indeed, several questions on sepsis-associated acute kidney injury and extracorporeal blood purification therapy still remain unresolved, including the indications and timing of renal replacement therapy in patients with septic vs. non-septic acute kidney injury, the optimal dialysis dose for renal replacement therapy modalities in sepsis-associated acute kidney injury patients, and the rationale for using extracorporeal blood purification therapies in septic patients without acute kidney injury. Moreover, the development of novel extracorporeal blood purification therapies, including those based on the use of adsorption devices, raised the attention of the scientific community both on the clearance of specific mediators released by microorganisms and by injured cells and potentially involved in the pathogenic mechanisms of organ dysfunction including sepsis-associated acute kidney injury, and on antibiotic removal. Based on these considerations, the joint commission of the Italian Society of Anesthesiology and Critical Care (SIAARTI) and the Italian Society of Nephrology (SIN) herein addressed some of these issues, proposed some recommendations for clinical practice and developed a common framework for future clinical research in this field.Graphical abstract

Clinico-Etiological Spectrum and Outcome in Patients With Septic Acute Kidney Injury and Its Comparison With Non-septic Acute Kidney Injury: A Hospital-Based Prospective Study Conducted in a Tertiary Care Hospital in North India.

Background Acute kidney injury (AKI) is a heterogenous syndrome defined by the impairment of kidney filtration and excretory function over days to weeks, resulting in the retention of nitrogenous and other waste products normally cleared by the kidneys. In addition, AKI is frequently recognized to be associated with sepsis and contributes to an unfavorable outcome in sepsis. This study was undertaken to study and compare the etiology and clinical profile of patients with septic and non-septicAKI and to study and compare the outcome in both groups. Materials and methods This is a prospective, observational, and comparative study with a total sample size of 200 patients selected randomly having sustained an acute kidney injury. Data was collected, recorded, analyzed, and compared for two groups of patients with septic and non-septic AKI. Results A total of 200 cases of AKIwere enrolled, out of which 120 (60%) were due to non-septic etiology and 80 (40%) were of septic etiology. Urosepsis (37.5%) due to various urinary tract infections including pyelonephritis and chest sepsis (18.75%) including community-acquired pneumonia (CAP) and aspiration pneumoniawere the predominant causes of sepsis. AKI secondary to nephrotoxic agents (27.5%) was the commonest cause in the non-septic group, followed by glomerulonephritis (13.3%), vitamin D intoxication-related hypercalcemia (12.5%), acute gastroenteritis (10.8%), etc. Patients of septic AKI had a significantly higher mean of maximum urea and creatinine than their non-septic AKI counterparts. In addition to having an increased duration of hospital stay, mortality was significantly higher in patients with septic AKI (27.5%) than in patients with non-septic AKI (4.1%). However, sepsis had no effect on renal functions, measured by urea and creatinine, at discharge. In patients with AKI, certain factors were found to increase the risk of mortality. These factors include being over 65 years old, needing mechanical ventilation or vasopressors, requiring renal replacement therapy (RRT), and having multiorgan dysfunction syndrome (MODS), septic shock, or acute coronary syndrome (ACS). However, pre-existing conditions such as diabetes, hypertension, malignancy, previous stroke, chronic kidney disease (CKD), and chronic liver disease (CLD) did not affect the overall mortality risk. Conclusion In the septic AKI group, urosepsis was the most frequent etiology of AKI, whilethe most frequent etiology of AKIin the non-septic group was nephrotoxin exposure. Patients with septic AKI had considerably longer hospital stays and greater in-hospital mortality rates than patients with non-septic AKI. The renal functions as determined by urea and creatinine at discharge were unaffected by sepsis. Finally, death was significantly impacted by age of >65 years, the necessity for mechanical ventilation, the use of vasopressors and RRT, and the presence of MODS, septic shock, and ACS.

Clinical use of plasmafiltration coupled with adsorption

Coupled plasma filtration adsorption is an extracorporeal therapy that combines plasma separation and adsorption of inflammatory mediators and toxins, followed by hemofiltration to control volume overload and removal of small and medium-sized water-soluble mediators. Although it is not new, there are still doubts about its clinical role. Evidence indicates that the coupled plasma filtration adsorption is highly efficient in removing inflammatory molecules in sepsis. So far it has not been shown to reduce mortality, but it is possible to achieve a better hemodynamic benefit over convective therapies. On the other hand, the absorptive component makes it possible to purify larger mediators associated with causes of non-septic acute kidney injury, such as myoglobin, toxins associated with liver failure and others, allowing that coupled plasma filtration adsorption indications to be expanded to various clinical settings with a high inflammatory component, particularly when it is required to manage several organ dysfunctions simultaneously.

Incidence, risk factors and clinical outcomes of septic acute renal injury in cancer patients with sepsis admitted to the ICU: A retrospective study.

The purpose of this study was to clarify the incidence, risk factors, and clinical outcomes of septic acute kidney injury (AKI) in cancer patients with sepsis admitted to the intensive care unit (ICU). A total of 356 cancer patients admitted to the ICU due to sepsis from January 2016 to October 2021 were analyzed retrospectively. According to the incidence of septic AKI, all patients were divided into the non-AKI group (n = 279) and the AKI group (n = 77). The clinical data after ICU admission were compared between the above two groups, and the risk factors and the clinical outcomes of septic AKI in the ICU were identified. The incidence of septic AKI in all patients was 21.6% (77/356). LASSO regression and logistic regression all showed that lactate, sequential organ failure assessment (SOFA) score and septic shock were closely related to the occurrence of septic AKI. In terms of clinical outcomes after ICU admission, the rate of mechanical ventilation (MV) and continuous renal replacement therapy (CRRT), MV time, hospitalization time and 28-day mortality in the ICU were significantly higher in the septic AKI group than in the non-septic AKI group. Among the three subgroups of septic AKI (AKI combined with septic shock, septic cardiac dysfunction or acute respiratory failure), the mortality of patients in the subgroup of AKI combined with septic shock was significantly higher than others. CRRT has no significant effect on the short-term outcome of these patients. Lactate level, SOFA score and septic shock were closely related to the occurrence of septic AKI in the ICU. The clinical outcomes within 28 days after ICU admission of cancer patients with septic AKI were worse than those without septic AKI. The short-term outcome was worse in patients with septic AKI complicated with septic shock. CRRT does not have any significant effect on the short-term prognosis of cancer patients with septic AKI in the ICU.

Predictors in-hospital mortality of septic vs non-septic acute kidney injury patients: an observational cohort study

Background: To compare the predictors In-hospital mortality of patients with septic Acute Kidney Injury (S-AKI) and non-septic AKI (NS-AKI). Methods: a cohort study of critically ill patients with AKI admitted to the emergency room at a tertiary hospital from January to June 2019. The primary outcome was hospital mortality. Results: There were 116 patients who met the inclusion criteria. Compared with NS-AKI, patients with S-AKI had significantly lower mean MAP, median eGFR, and urine output. (UO). S-AKI had higher mortality and vasopressor requirements and had a lower renal recovery than NS-AKI (63.2% vs 31.4%, p=0.001; 30.8% vs 13.7%, p=0.031, and 36.9% vs 60.8%, p=0.011, respectively). AKI stage 3 and vasopressor requirements were dependent risk factors for both S-AKI and NS-AKI mortality. Meanwhile, SOFA score &gt; 7 and the need for dialysis are dependent and independent risk factors for mortality in S-AKI. Worsening and/or persistence in UO, serum urea and creatinine levels at 48 h after admission were predictors of mortality in S-AKI and NS-AKI. Improvement in UO in surviving patients was more pronounced in S-AKI than in NS-AKI (50% vs 17.1%, p=0.007). The surviving S-AKI patients had a longer hospital stay than surviving NS-AKI [8 (6-14.5) vs 5 (4 – 8), p=0.004]. S-AKI have higher mortality and vasopressor requirements and have lower renal recovery than NS-AKI. Conclusion: S-AKI have higher mortality and vasopressor requirements and a lower renal recovery than NS-AKI. Independent predictors of mortality in S-AKI were high SOFA scores and the need for dialysis.

Acute Kidney Injury in Severe COVID-19 Has Similarities to Sepsis-Associated Kidney Injury: A Multi-Omics Study

ObjectiveTo compare coronavirus disease 2019 (COVID-19) acute kidney injury (AKI) to sepsis-AKI (S-AKI). The morphology and transcriptomic and proteomic characteristics of autopsy kidneys were analyzed. Patients and MethodsIndividuals 18 years of age and older who died from COVID-19 and had an autopsy performed at Mayo Clinic between April 2020 to October 2020 were included. Morphological evaluation of the kidneys of 17 individuals with COVID-19 was performed. In a subset of seven COVID-19 cases with postmortem interval of less than or equal to 20 hours, ultrastructural and molecular characteristics (targeted transcriptome and proteomics analyses of tubulointerstitium) were evaluated. Molecular characteristics were compared with archived cases of S-AKI and nonsepsis causes of AKI. ResultsThe spectrum of COVID-19 renal pathology included macrophage-dominant microvascular inflammation (glomerulitis and peritubular capillaritis), vascular dysfunction (peritubular capillary congestion and endothelial injury), and tubular injury with ultrastructural evidence of mitochondrial damage. Investigation of the spatial architecture using a novel imaging mass cytometry revealed enrichment of CD3+CD4+ T cells in close proximity to antigen-presenting cells, and macrophage-enriched glomerular and interstitial infiltrates, suggesting an innate and adaptive immune tissue response. Coronavirus disease 2019 AKI and S-AKI, as compared to nonseptic AKI, had an enrichment of transcriptional pathways involved in inflammation (apoptosis, autophagy, major histocompatibility complex class I and II, and type 1 T helper cell differentiation). Proteomic pathway analysis showed that COVID-19 AKI and to a lesser extent S-AKI were enriched in necroptosis and sirtuin-signaling pathways, both involved in regulatory response to inflammation. Upregulation of the ceramide-signaling pathway and downregulation of oxidative phosphorylation in COVID-19 AKI were noted. ConclusionThis data highlights the similarities between S-AKI and COVID-19 AKI and suggests that mitochondrial dysfunction may play a pivotal role in COVID-19 AKI. This data may allow the development of novel diagnostic and therapeutic targets.

Study on Related Factors of Acute Kidney Injury in Patients under Intensive Care

Objectives: To study the related factors of acute kidney injury (AKI) in intensive care unit (ICU) patients. Methods: The clinical data of 879 patients in the intensive care unit were retrospectively analyzed. AKI patients were selected according to the AKI clinical diagnostic criteria, the causal analysis was performed, the indicators of AKI patients were tested, and the urine volume and the time of admission to the ICU were recorded. Finally, logistic regression analysis was used to analyze the risk factors that affect the prognosis. Results: Among the 879 patients in the intensive care unit, 96 patients (10.9%) met the KDIGO-AKI diagnostic criteria, of which 29 (30.31%) died and 49 (51.04%) required renal replacement therapy. As the age and stage of AKI patients increase, the mortality rate also increases. The pathology constituted 46 septic patients (47.92%) and 50 non-septic patients (52.08%). Patients with septic AKI have longer ICU and hospital stay than patients with non-septic AKI (t=2.291, 0.023; t=2.082, 0.041), and the rate of renal replacement therapy is higher(?2=4.091?P=0.042). Logistic regression analysis shows that old age, low urine volume, shock, acidosis, stage 3 of AKI, intake of blood pressure drugs, infections, and the need for renal replacement therapy are relevant factors that affect AKI. Conclusions: In the intensive care unit, the incidence and mortality of AKI are very high; the treatment of AKI is related to many factors; early detection and treatment is very crucial to reduce the mortality of AKI.

Association of Acute Kidney Injury With Subsequent Sepsis in Critically Ill Children.

Acute kidney injury is a major cause of morbidity and mortality in critically ill children. A growing body of evidence has shown that acute kidney injury affects immune function, yet little is known about the association between acute kidney injury and subsequent infection in pediatric patients. Our objective was to examine the association of non-septic acute kidney injury with the development of subsequent sepsis in critically ill children. A single-center retrospective cohort study. The pediatric and cardiac ICUs at a tertiary pediatric care center. All patients 0-18 years old without a history of chronic kidney disease, who did not have sepsis prior to or within the initial 48 hours of ICU admission. None. We analyzed data for 5,538 children (median age, 5.3 yr; 58.2% male), and identified 255 (4.6%) with stage 2 or 3 acute kidney injury. Suspected sepsis occurred in 46 children (18%) with stage 2 or 3 acute kidney injury compared to 286 children (5.4%) with stage 1 or no acute kidney injury. On adjusted analysis, children with stage 2 or 3 acute kidney injury had 2.05 times greater odds of developing sepsis compared to those with stage 1 or no acute kidney injury (95% CI, 1.39-3.03; p < 0.001). Looking at acute kidney injury severity, children with stage 2 and 3 acute kidney injury had a 1.79-fold (95% CI, 1.15-2.79; p = 0.01) and 3.24-fold (95% CI, 1.55-6.80; p = 0.002) increased odds of developing suspected sepsis, respectively. Acute kidney injury is associated with an increased risk for subsequent infection in critically ill children. These results further support the concept of acute kidney injury as a clinically relevant immunocompromised state.

Comparison of Epidemiology and Outcomes of Acute Kidney Injury in Critically Ill Patients with and without Sepsis.

ABSTRACTObjectivesIn critically ill patients, acute kidney injury (AKI) and sepsis often coexist. This confounds the assessment of outcomes of both sepsis and AKI in these patients. Hence, in this study, we compare the outcomes of AKI with sepsis, AKI without sepsis, and sepsis without AKI against a control cohort comprising patients with neither AKI nor sepsis.Materials and methodsProspective observational study conducted in our critical care unit (CCU) between January and July 2009. Data including demographic details, acute physiology and chronic health evaluation (APACHE) III score, presence of AKI, presence of sepsis, intensive care unit (ICU) length of stay (LOS), and outcomes were collected for all patients. Acute Kidney Injury Network (AKIN) criteria were used to define the presence of AKI and American College of Critical Care Medicine 2001 definition was used to define the presence of sepsis.ResultsA total of 250 patients were included in the study and 8 patients were excluded from analysis as they were discharged from hospital against medical advice. The remaining 242 patients (mean age 52.8 ± 17 years; 61.6% male; APACHE III score: 48.2 ± 24.1) were analyzed, and AKI was seen in 111 patients (45.8%). Among the patients with AKI, 55.8% (62/111) had sepsis and 44.2% (49/111) had nonseptic AKI. There was a higher need for renal replacement therapy (RRT) among patients with septic AKI in comparison to those with nonseptic AKI (19.3% vs 6.1%; p = 0.04), but no mortality difference was seen between the two groups (25.8% vs 20.4%, p = 0.5). Patients with sepsis and AKI had a significantly higher mortality (25.8%) compared to the patients with sepsis alone (5.6%; p < 0.01).ConclusionPatients with septic AKI had a higher RRT requirement compared to patients with nonseptic AKI, but no significant differences in mortality were seen between the groups. Occurrence of AKI in septic patients substantially increases their mortality.How to cite this articleNandagopal N, Reddy PK, Ranganathan L, Ramakrishnan N, Annigeri R, Venkataraman R. Comparison of Epidemiology and Outcomes of Acute Kidney Injury in Critically Ill Patients with and without Sepsis. Indian J Crit Care Med 2020;24(4):258–262.

Clinical characteristics and prognosis of acute kidney injury in elderly patients with sepsis

To analyze the incidence of acute kidney injury (AKI) in elderly patients with sepsis, compare the clinical characteristics and prognosis between AKI and non-AKI elderly patients with sepsis, and to investigate the impact of classification of AKI and renal replacement therapy (RRT) on the outcome of elderly patients with sepsis. The clinical data of 490 septic patients over 65 years old, admitted to intensive care unit (ICU) of Tianjin First Center Hospital from April 1st, 2016 to December 31st, 2018 were retrospectively analyzed. The patients were divided into two groups according to those with or without AKI. The clinical characteristics of patients were compared, and subgroup analysis of elderly septic patients with AKI was performed according to Kidney Disease: Improving Global Outcomes (KDIGO) staging criteria and whether RRT was performed, to observe the effects of AKI staging and RRT on the prognosis of elderly septic patients with AKI. Multivariate Cox regression analysis was used to screen the risk factors of death in elderly patients with sepsis associated AKI. (1) A total of 490 septic elderly patients were enrolled, including 249 patients with AKI and 241 patients without AKI, with the AKI incidence of 50.8%. Compared with non-AKI group, the patients in AKI group were older (years old: 72.0±7.2 vs. 68.8±5.1), acute physiology and chronic health evaluation II (APACHE II) score and sequential organ failure assessment (SOFA) score were evidently higher (23.1±6.1 vs. 22.0±3.7, 9.4±3.8 vs. 6.1±3.5); the duration of mechanical ventilation [days: 7.0 (5.0, 10.0) vs. 6.0 (3.0, 9.0)], length of ICU stay [days: 12.0 (7.0, 15.0) vs. 7.0 (4.0, 13.0)] and total length of hospital stay [days: 15.0 (10.0, 21.5) vs. 12.0 (7.0, 15.0)] were longer, and ICU mortality and 28-day mortality were evidently higher [22.9% (57/249) vs. 14.1% (34/241), 36.1% (90/249) vs. 24.5% (59/241), all P < 0.05]. (2) According to KDIGO staging, 93 patients were in stage 1, 70 in stage 2 and 86 in stage 3 of AKI. The rate of RRT was increased with increase in KDIGO staging [14.0% (13/93), 30.0% (21/70), 88.4% (76/86)], the duration without mechanical ventilation within 28 days was shortened [days: 20.0 (0, 23.0), 8.0 (0, 20.5), 8.0 (0, 13.0)], the rate of kidney recovery was decreased [71.0% (66/93), 51.4% (36/70), 37.2% (32/86)], meanwhile, the ICU and 28-day mortality was increased [12.9% (12/93), 38.6% (27/70), 20.9% (18/86), and 26.9% (25/93), 35.7% (25/70), 46.5% (40/86), all P < 0.05]. (3) 110 elderly septic patients with AKI were treated with RRT, and 139 without RRT. Compared with non-RRT group, the ratio of mechanical ventilation in RRT group was lowered [46.4% (51/110) vs. 68.3% (95/139)], the duration without mechanical ventilation within 28 days [days: 18.0 (0, 23.0) vs. 10.0 (0, 13.0)], the length of ICU stay [days: 13.0 (12.0, 17.9) vs. 10.0 (6.0, 14.0)] and the total length of hospital stay [days: 22.5 (15.0, 46.0) vs. 16.0 (12.0, 23.0)] were prolonged, and the 28-day mortality was evidently increased [50.0% (55/110) vs. 25.2% (35/139), all P < 0.01], however, no significant difference in ICU mortality was found [27.3% (30/110) vs. 19.4% (27/139), P > 0.05]. (4) Cox regression analysis showed that SOFA score [relative risk (RR) = 1.214, 95% confidence interval (95%CI) = 1.117-1.319], KDIGO stage (RR = 4.077, 95%CI = 1.850-8.982), vasoactive substance usage (RR = 2.896, 95%CI = 1.502-5.584), and mechanical ventilation (RR = 5.787, 95%CI = 1.512-22.156) were the risk factors of 28-day mortality in elderly septic patients with AKI (all P < 0.05). The incidence of AKI for elderly septic patients with AKI was about 50%, who had a worse prognosis as compared with non-septic AKI patients. The higher the stage of KDIGO, the higher the mortality in elderly septic patients with AKI was. RRT can decrease the rate of mechanical ventilation, whereas, it may not improve the prognosis of elderly septic patients with AKI.

The Effect of Serum Neutrophil Gelatinase-Associated Lipocalin on the Discontinuation of Continuous Renal Replacement Therapy in Critically Ill Patients with Acute Kidney Injury

Background: To determine the optimal time for discontinuing continuous renal replacement therapy (CRRT) by evaluating serum neutrophil gelatinase-associated lipocalin (NGAL) in critically ill patients with acute kidney injury (AKI). Methods: A prospective observational study was conducted from September 2015 to March 2018. AKI patients treated with CRRT for at least 24 h were divided into “success” and “failure” groups according to their RRT requirement within 7 days after the initial discontinuation of CRRT. The prefilter and effluent NGAL concentrations were measured to calculate the sieving coefficient (SC) of NGAL in all included subjects from 0 to 72 h. Results: In total, 110 patients were divided into success (n = 78) and failure groups (n = 32). The mean SC of NGAL during CRRT was less than 0.05. The patients in the failure group were associated with higher mortality compared with patients in the success group (37.5 vs. 12.8%, respectively, p = 0.013). There were significant differences in serum NGAL, creatinine, and urine output at discontinuation. In patients without sepsis (n = 70), serum NGAL and urine output were significant predictors of successful cessation. The area under the receiver operating characteristic to predict the successful discontinuation of CRRT was 0.88 for NGAL and 0.86 for urine output. An NGAL level of 403 ng/mL had the highest sensitivity (81%) and specificity (89%) and a urine output of 695 mL/day had the highest sensitivity (83%) and specificity (88%). However, in septic patients (n = 40), urine output but not serum NGAL (OR 0.999, p = 0.69) was a significant variable (OR 1.002, p = 0.005), with a cutoff of 796 mL/day (sensitivity 83%, specificity 88%). Conclusions: Serum NGAL was a significant factor for predicting successful CRRT discontinuation in nonseptic AKI patients. However, urine output, rather than serum NGAL, was a significant predictor in septic AKI patients.

Septic acute kidney injury (SAKI)

Acute kidney injury (AKI) is a common and potentially fatal complication of sepsis. Septic acute kidney injury (SAKI) remains an important challenge in critical care medicine. SAKI has a complex pathophysiology than previously anticipated. The pathophysiologic mechanisms of sepsis-induced AKI are different from non-septic AKI. Sepsis- induced systemic inflammation triggers protective mechanisms within the nephron, affecting tubular and glomerular functions. A varying degree of kidney impairment can be expected, from a small decrease in GFR to complete shutdown and permanent dysfunction, depending on the severity of the inflammatory response. It is likely that progression of septic AKI can be prevented by avoiding hypotension, fluid overload, and venous congestion. There is no specific therapy for septic AKI at present. Even though novel drugs and blood purification techniques for sepsis-induced AKI are being tested, supportive care to prevent further kidney insults is likely to allow kidney structure and function to more easily recover once the septic state has resolved.

MiR-107 induces TNF-α secretion in endothelial cells causing tubular cell injury in patients with septic acute kidney injury

Activation of endothelial cells plays a key role in septic acute kidney injury (AKI). This study investigated the role of miRNA in endothelial-induced tubular cell injury in sepsis. Circulating endothelial cells (CECs) from septic AKI, non-septic AKI, septic non-AKI patients and healthy volunteers were isolated and cultured, and HK2 cells were exposed to CEC-conditioned medium. CEC-conditioned medium prepared from septic AKI patients led to cell shrinkage, decreased E-cadherin, the release of NAG and cell apoptosis in HK2 cells. TNF-α mediated the tubular cell injury induced by CEC-conditioned medium prepared from septic AKI patients. PCR array analysis detected that miR-107 was significantly increased in the CECs of septic AKI patients. MiR-107 was verified to target the 3′UTR of Dual-specificity phosphatase 7(DUSP7). Transfection of miR-107 ASO recovered the expression of DUSP7, suppressed the phosphorylation of ERK, and decreased the secretion of TNF-α in the CECs of septic AKI patients and in the peritubular endothelial cells of septic AKI mice. The inhibition of miR-107 prevented the decrease of E-cadherin, the release of NAG and cell apoptosis in HK2 cells exposed to CEC-conditioned medium prepared from septic AKI patients, and preserved the normal renal morphology and decreased the serum creatinine level in septic AKI mice. In conclusion, our study suggests that the increased miR-107 induces TNF-α secretion by targeting DUSP7 in endothelial cells, which may directly cause tubular cell injury in septic AKI.

Sepsis may not be a risk factor for mortality in patients with acute kidney injury treated with continuous renal replacement therapy

PurposeWe aimed to study the clinical characteristics, courses, and outcomes of critically ill patients with septic acute kidney injury (AKI) treated with continuous renal replacement therapy (CRRT) in comparison with nonseptic AKI treated with CRRT. MethodsThis is a multicenter retrospective observational study conducted in 14 Japanese intensive care units in 2010. All adult patients with severe AKI treated with CRRT were eligible (n = 343), and information on patient characteristics, variables at CRRT initiation, CRRT settings, and outcomes was collected. Patients were categorized into the septic AKI group and the nonseptic AKI group according to contributing factors to AKI. ResultsApproximately half of study patients (48.7%) had sepsis/septic shock as a contributing factor to AKI, and patients with septic AKI treated with CRRT had more serious clinical conditions than patients with nonseptic AKI. However, no significant difference was observed in intensive care unit mortality (48.5% vs 43.8%; P = .44) and hospital mortality (61.1% vs 56.3%; P = .42) between patients with septic and nonseptic AKIs treated with CRRT. Furthermore, sepsis was associated with lower hospital mortality (odds ratio, 0.378; P = .012) in multivariable regression analysis. ConclusionSepsis may not be a risk factor for mortality in patients with AKI whose condition has become severe enough to require CRRT.

Renal Function Outcome Prognosis in Septic and Non-septic Acute Kidney Injury Patients.

Aim:The objective of this study was to evaluate prognostic impact of clinical factors on outcome of renal function in septic and non-septic acute kidney injury (AKI) patients.Methods:The prospective, observational, clinical study was performed at Nephrology Clinic and Clinic for Infectious Diseases, University Clinical Centre Sarajevo. One hundred patients with diagnosis of AKI were enrolled in the study, and divided into two groups: septic and non-septic AKI patients. Clinical parameters included causes and type of AKI, pre-existing comorbidities and different treatment modalities. Patients were followed up until discharge or death. Renal function outcome was defined by creatinine clearance values at discharge.Results:Septic AKI patients had significantly longer hospital stay (p=0.03), significantly worse renal function outcome (p<0.001), and higher burden of comorbidities (70.6% vs. 60.6%), compared to non-septic patients. Septic AKI patients were almost three times less likely to receive renal replacement therapy (8.8% vs. 24.4%) and they had significant delay in initiation of dialysis (p=0.03). By multivariate analysis, sepsis (95% CI 0.128-0.967, p=0.043) and hypertension (95% CI 0.114-0.788, p=0.015) were independent predictors of adverse renal function outcome in AKI patients. Postrenal type of AKI was independent predictor of renal function recovery in non-septic AKI patients (95% CI 1.174-92.264, p=0.035), while Failure, as third class of AKI, was independent predictor of non-recovered renal function only in septic AKI patients (95% CI 0.026 to 0.868, p=0.034).Conclusion:Septic AKI patients are clinically distinct compared to non-septic AKI patients with different prognostic factors and poorer renal function outcome.

Comparison of characteristics and prognosis between septic and non-septic acute kidney injury in Japanese intensive care units

Comparison of characteristics and prognosis between septic and non-septic acute kidney injury in Japanese intensive care units

Soluble CD25 is increased in patients with sepsis‐induced acute kidney injury

Sepsis has been shown to induce the expansion of CD4+CD25+ regulatory T cells (Tregs), and this paradoxical immune suppression has been suggested to be closely associated with the development of sepsis-induced organ dysfunction. In the present study, we aimed to investigate the possible link between immune suppression and the development of septic acute kidney injury (AKI). We prospectively enrolled patients with a diagnosis of sepsis, with or without AKI and as well as patients with AKI but without sepsis. Serum and urine samples at the time of the diagnosis were collected to measure neutrophil gelatinase-associated lipocalin (NGAL), cytokines, and soluble CD25 (sCD25). Of the 82 patients enrolled, 44, 18, and 20 patients were classified into septic-AKI, sepsis-non AKI and non-septic AKI groups. There were no differences in the baseline characteristics in all three groups and the severity of infection in the two sepsis groups. Serum levels of interleukin (IL)-10 were significantly elevated in patients with septic-AKI compared to the other two groups. Serum and urine NGAL levels and the level of serum sCD25, a marker of regulatory T cells, were significantly elevated in patients with septic AKI group, indicating the potential association of paradoxical immune suppression and the development of septic-AKI. These results suggest that immune suppression in sepsis may be closely linked to the development of AKI and that sCD25 or IL-10 may be useful as novel biomarkers for the development of septic AKI.