Mortality Analysis in Geriatric Patients With Acute Kidney Injury Admitted in the Intensive Care Unit: A Single-Center Cross-Sectional Study.

Introduction Acute kidney injury (AKI) is an abrupt reduction in kidney function that causes nitrogenous waste and other waste products to be retained. Methods This cross-sectional study was conducted from February 2015 to January 2016. The study received approval from the Independent Ethics Committee, which included patients over 60 with AKI. The study duration was 12 consecutive months to ascertain the etiology, severity, and hospital outcomes of AKI. Results The common etiologies of AKI included drug-induced (25%), age-related (21.67%), cardiac (13.33%), respiratory (20%), tropical (15%), and pancreatitis (15%) cases. Another predominant etiology observed was obstructive nephropathy (55%), with the highest (37.5%) mortality rate. The distribution of patients based on KDIGO criteria showed no significant difference in mortality percentages among classes (p=0.177). Conservative management without renal replacement therapy was the most common approach to treat AKI, with a 39% mortality rate. Conclusion Among different causes of AKI in the geriatric age group, drug-induced AKI, and obstructive nephropathy were predominantly associated with hospital mortality.

Fractional excretion of sodium and potassium and urinary strong ion difference in the evaluation of persistent AKI in sepsis.

OBJECTIVE: To evaluate the diagnostic performance of FENa (Fractional excretion of sodium), FEK (fractional excretion of potassium) and uSID (urinary strong ion difference) in predicting pAKI in sepsis and septic shock. DESIGN: Retrospective cohort study. SETTING: Two intensive care units in Argentina. PATIENTS: Adult patients with a confirmed diagnosis of sepsis or septic shock and AKI, and had a urinary biochemistry within 24h of the AKI diagnosis. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: We evaluated the diagnostic accuracy of FENa, FEK and uSID through a ROC (Receiver Operating Characteristic) curve analysis. RESULTS: 80 patients were included. 40 patients presented pAKI. pAKI group had higher APACHE, SOFA score, and mortality rate. In the ROC curve analysis, uSID had no diagnostic utility (AUC=0.52, p=0.69). FENa presented moderate accuracy showing an AUC of 0.71 (95% CI 0.60-0.83; p=0.001), while FEK presented low accuracy with an AUC of 0.69 (95% CI 0.57-0.80; p=0.04). The optimal Youden point for identifying pAKI was at a FENa higher than 0.51 % with a specificity of 72.5% and a sensitivity of 65.0%. In the case of FEK, a value higher than 21.9 % presented the best relation, with a specificity of 67.5% and a sensitivity of 65.0%. CONCLUSIONS: urine biochemistry interpretation in septic patients must be revised. FENa and FEK are related to the severity of AKI and could be helpful complementary tools for diagnosing pAKI.

The use of extracorporeal blood purification therapies and sequential extracorporeal support in patients with septic shock (EROICASS): a study protocol for a national, non-interventional, observational multicenter, prospective study.

BACKGROUND: Septic shock, a critical condition characterized by organ failure, presents a substantial mortality risk in intensive care units (ICUs), with the 28-day mortality rate possibly reaching 40%. Conventional management of septic shock typically involves the administration of antibiotics, supportive care for organ dysfunction, and, if necessary, surgical intervention to address the source of infection. In recent decades, extracorporeal blood purification therapies (EBPT) have emerged as potential interventions aimed at modulating the inflammatory response and restoring homeostasis in patients with sepsis. Likewise, sequential extracorporeal therapy in sepsis (SETS) interventions offer comprehensive organ support in the setting of multiple organ dysfunction syndrome (MODS). The EROICASS study will assess and describe the utilization of EBPT in patients with septic shock. Additionally, we will evaluate the potential association between EBPT treatment utilization and 90-day mortality in septic shock cases in Italy. METHODS: The EROICASS study is a national, non-interventional, multicenter observational prospective cohort study. All consecutive patients with septic shock at participating centers will be prospectively enrolled, with data collection extending from intensive care unit (ICU) admission to hospital discharge. Variables including patient demographics, clinical parameters, EBPT/SETS utilization, and outcomes will be recorded using a web-based data capture system. Statistical analyses will encompass descriptive statistics, hypothesis testing, multivariable regression models, and survival analysis to elucidate the associations between EBPT/SETS utilization and patient outcomes. CONCLUSIONS: The EROICASS study provides valuable insights into the utilization and outcomes of EBPT and SETS in septic shock management. Through analysis of usage patterns and clinical data, this study aims to guide treatment decisions and enhance patient care. The implications of these findings may impact clinical guidelines, potentially improving survival rates and patient outcomes in septic shock cases.

Community-acquired acute kidney injury in India: data from ISN-acute kidney injury registry.

Background: Acute kidney injury (AKI), particularly community-acquired AKI (CA-AKI), is a major health concern globally. The International Society of Nephrology's "0 by 25" initiative to reduce preventable deaths from AKI to zero by 2025 is not achievable in low and middle income countries, such as India, possibly due to a lack of data and measures to tackle this urgent public health issue. In India, CA-AKI predisposes younger patients to hospitalization, morbidity, and mortality. This is the first multicenter, prospective, cohort study investigating CA-AKI and its consequences in India. Methods: This study included data from patients with CA-AKI (>12 years of age) housed in the Indian Society of Nephrology-AKI registry, involving 9 participating tertiary care centers in India, for the period between November 2016 and October 2019. The etiological spectrum and renal and patient outcomes of CA-AKI at the index visit and at 1-month and 3-month follow-ups were analyzed. The impact of socioeconomic status (SES) on outcomes was also analyzed. Findings: Data from 3711 patients (mean [±SD] age 44.7 ± 16.5 years; 66.6% male) were analyzed. The most common comorbidities included hypertension (21.1%) and diabetes (19.1%). AKI occurred in medical, surgical, and obstetrical settings in 86.7%, 7.3%, and 6%, respectively. The most common causes of AKI were associated with sepsis (34.7%) and tropical fever (9.8%). Mortality at the index admission was 10.8%. Complete recovery (CR), partial recovery (PR), and dialysis dependency among survivors at the time of discharge were 22.1%, 57.7%, and 9.4%, respectively. Overall, at 3 months of follow-up, mortality rate, CR, PR, and dialysis dependency rates were 11.4%, 72.2%, 7.2%, and 1%, respectively. Multivariate analysis revealed that age >65 years, alcoholism, anuria, hypotension at presentation, thrombocytopenia, vasopressor use, transaminitis, and low SES were associated with mortality at the index admission. Interpretation: Sepsis and tropical fever were the most common causes of CA-AKI. Presentation of CA-AKI to tertiary care units was associated with high mortality, and a significant number of patients progressed to CKD. Individuals with a low SES had increased risk of mortality and require immediate attention and intervention. Funding: This study was funded by the Indian Society of Nephrology.

Astragaloside â £ negatively regulates Gpr97-TPL2 signaling to protect against hyperhomocysteine-exacerbated sepsis associated acute kidney injury.

BACKGROUND: Hyperhomocysteine (HHcy) plays an important role in promoting inflammation and cell death of tubular epithelial cells. However, the role of HHcy and Astragaloside IV (AS-IV) in sepsis associated acute kidney injury (S-AKI) remain unclear. PURPOSE: A significant aspect of this study aimed to elucidate the effect of AS-Ⅳ treatment on HHcy-exacerbated S-AKI and reveal its potential mechanism. METHODS: Male C57BL/6 J mice fed with specific diet containing 2% methionine were established as in vivo models, and AS-Ⅳ was orally administrated continuously for 3 weeks, and then LPS (10 mg·kg-1 bodyweight) was given by a single intraperitoneal injection. The renal morphological changes were evaluated by HE and PAS staining. RNA-sequencing analysis was applied to select key signaling. The NRK-52E cells exposed to Hcy or combined with LPS were used as in vitro models. The mRNA and protein expression levels of Gpr97-TPL2 signaling were examined by qRT-PCR and western blotting assays. RESULTS: In vivo, HHcy mice developed more severe renal injury and prevalent tubular inflammation after LPS injection. In vitro, the levels of NGAL, Gpr97 and TPL2 were significantly increased in NRK-52E cells induced by Hcy (1.6 mM) or in combination with LPS. Notably, the effects of Hcy on TPL2 signaling was abolished by transfecting TPL2 siRNA or treating TPL2 inhibitor, without alterations in Gpr97. However, the enhancement of Gpr97-TPL2 signaling induced by Hcy was counteracted by Gpr97 siRNA. Subsequently, our findings demonstrated that AS-Ⅳ treatment can improve renal function in HHcy-exacerbated S-AKI mice. Mechanistically, AS-Ⅳ alleviated renal tubular damage characterized by abnormal increases in KIM-1, NGAL, TPL2, Gpr97, Sema3A and TNF-α, and decreases in survivin in vivo and in vitro mainly through suppressing the activation of Gpr97-TPL2 signaling. CONCLUSION: The present study suggested that HHcy-exacerbated S-AKI was mediated mechanically by activation of Gpr97-TPL2 signaling for the first time. Furthermore, our research also illustrated that AS-Ⅳ protected against HHcy-exacerbated S-AKI by attenuating renal tubular epithelial cells damage through negatively regulating Gpr97-TPL2 signaling, proposing a natural product treatment strategy for HHcy-exacerbated S-AKI.

Epidemiology and outcomes of early versus late septic acute kidney injury in critically ill patients: A retrospective cohort study.

BACKGROUND: It was recently proposed to distinguish early from late sepsis-associated acute kidney injury (SA-AKI). We aimed to determine the relative frequency of these entities in critically ill patients and to describe their characteristics and outcomes. METHODS: We included in this retrospective cohort study all adult patients admitted for sepsis in a tertiary ICU between 2010 and 2020. We excluded those on chronic dialysis or without consent. We extracted serum creatinine, hourly urinary output, and clinical and socio-demographic data from medical records until day 7 or ICU discharge. AKI presence and characteristics were assessed daily using KDIGO criteria. We compared patients with early (occurring within 2 days of admission) or late (occurring between day 2 and day 7) SA-AKI. We conducted sensitivity analyses using different definitions for early/late SA-AKI. RESULTS: Among 1835 patients, 1660 (90%) fulfilled SA-AKI criteria. Of those, 1610 (97%) had early SA-AKI, and 50 (3%) had late SA-AKI. Similar proportions were observed when only considering AKI with elevated sCr (71% vs. 3%), severe AKI (67% vs. 6%), or different time windows for early SA-AKI. Compared with early SA-AKI patients, those with late SA-AKI were younger (median age [IQR] 59 [49-70] vs. 69 [58-76] years, p < 0.001), had lower Charlson comorbidity index (3 [1-5] vs. 5 [3-7], p < 0.001) and lower SAPSII scores (41 [34-50] vs. 53 [43-64], p < 0.001). They had similar (24% vs. 26%, p = 0.75) in-hospital mortality. CONCLUSIONS: AKI is almost ubiquitous in septic critically ill patients and present within two days of admission. The timing from ICU admission might not be relevant to distinguish different phenotypes of SA-AKI. ETHICS APPROVAL: Ethics Committee Vaud, Lausanne, Switzerland (n°2017-00008).

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.

Toll-like Receptor 4 in Acute Kidney Injury.

Acute kidney injury (AKI) is a common and devastating pathologic condition, associated with considerable high morbidity and mortality. Although significant breakthroughs have been made in recent years, to this day no effective pharmacological therapies for its treatment exist. AKI is known to be connected with intrarenal and systemic inflammation. The innate immune system plays an important role as the first defense response mechanism to tissue injury. Toll-like receptor 4 (TLR4) is a well-characterized pattern recognition receptor, and increasing evidence has shown that TLR4 mediated inflammatory response, plays a pivotal role in the pathogenesis of acute kidney injury. Pathogen-associated molecular patterns (PAMPS), which are the conserved microbial motifs, are sensed by these receptors. Endogenous molecules generated during tissue injury, and labeled as damage-associated molecular pattern molecules (DAMPs), also activate pattern recognition receptors, thereby offering an understanding of sterile types of inflammation. Excessive, uncontrolled and/or sustained activation of TLR4, may lead to a chronic inflammatory state. In this review we describe the role of TLR4, its endogenous ligands and activation in the inflammatory response to ischemic/reperfusion-induced AKI and sepsis-associated AKI. The potential regeneration signaling patterns of TLR4 in acute kidney injury, are also discussed.

Impact of indirect bilirubin and uric acid on outcomes of sepsis-associated acute kidney injury (sAKI).

BACKGROUND: Acute kidney injury (AKI) is one of the most frequent pathophysiologic disorders encountered in hospitalized patients, with sepsis frequently implicated in pathogenesis. Reactive oxygen species (ROS) seem to have a significant contribution to sepsis-induced AKI. Proposed mechanisms include induction of cell membrane lipid peroxidation, protein denaturing, and direct DNA damage, all of which have deleterious effect. These changes constitute oxidative injury to the kidneys. OBJECTIVE: To evaluate the antioxidant actions of indirect bilirubin and uric acid on outcomes of sepsis-associated AKI. METHODS: Ninety-eight patients admitted to the intensive care unit (ICU), at a large tertiary center, with sepsis and AKI were evaluated for serum levels of uric acid, bilirubin (primarily indirect), and procalcitonin. The primary endpoints studied were the need for hemodialysis and death. RESULTS: Thirty-two (33%) patients developed AKI requiring hemodialysis (HD). These patients had higher SOFA scores (p < 0.001) and lower levels of indirect bilirubin (p < 0.001) compared to those not requiring HD. There was no statistically significant difference in serum uric acid levels. Logistic regression analysis identified creatinine level, total and indirect bilirubin levels, and leukocyte count as significant predictors of patient death. CONCLUSION: Higher leukocyte counts and creatinine levels were independently associated with poor outcomes in ICU patients with sepsis. Additionally, lower indirect bilirubin levels were also noted to be associated with similar outcomes. The latter provides insights into oxidative stress as a major player in the pathogenesis of sepsis-induced AKI, with a potential protective role of indirect bilirubin.

Benefit of Hemoadsorption Therapy in Patients Suffering Sepsis-Associated Acute Kidney Injury: A Case Series.

INTRODUCTION: Sepsis is defined as life-threatening organ dysfunction in result of the host's dysregulated response to infection and septic shock. Sepsis-associated kidney injury is usually defined as concurrent presence of acute kidney injury (AKI) and sepsis without other significant causative factors. METHOD: The current retrospective study was conducted to elucidate beneficial and side effects of CytoSorb®. A total of 17 patients were primarily treated with continuous renal replacement therapy in combination with CytoSorb. The demand for norepinephrine, mean arterial pressure, lactate, and procalcitonin (PCT) levels, as well as ICU length of stay, was measured. RESULT: The blood lactate levels decreased by 32.30% when comparing mean levels before and after treatment. All patients who survived (n = 14) had reduction in vasopressor demand to 68.96% of their initial dose before the start of treatment. Hospital survival was greater in patients who initially had higher vasopressor demand compared to their nonsurviving counterparts, but in whom vasopressor dosages were reduced significantly during their treatments. Mortality as predicted by APACHE II score in the overall patient population was 79.9%, whereas, the observed ICU mortality was 31%. The baseline PCT levels on patients received 1, 2, and 3 CytoSorbs were 27.08 ± 5.81 ng/mL, 13.28 ± 2.62 ng/mL, and 21.03 ± 6.56 ng/mL, respectively. Observed PCT levels at 24 h after the last treatment on patients received 1, 2, and 3 CytoSorb were 31.55 ± 15.70 ng/mL, 5.61 ± 1.77 ng/mL, and 8.11 ± 3.62 ng/mL, respectively. CONCLUSION: In conclusion, it seems that applying the CytoSorb in combination with CRRT in ICU septic patients with AKI, is related to a significant decrease in mortality, if the integrity and continuity of the treatment be kept, as much as possible. This study presented an effectively positive outcome with cytokine adsorber treatment as an adjuvant along with standard treatment in a high-risk mortality case of septic shock with organ failure.

Influence of contrast media on renal function and outcomes in patients with sepsis-associated acute kidney injury: a propensity-matched cohort study.

BACKGROUND: Recent studies have suggested a low potential risk for contrast medium-induced kidney injury in patients with relatively normal renal function. However, whether contrast media cause additional deterioration of renal function in patients with acute kidney injury (AKI), including those with sepsis-associated AKI, remains unclear. This study aimed to evaluate the effect of contrast media on renal function and mortality in patients with sepsis who already had AKI. METHODS: We performed a propensity score-matched historical cohort study in the medico-surgical intensive care unit of Jichi Medical University Hospital. Adult patients who were diagnosed with sepsis and AKI were enrolled. Records from our sepsis database from 2011 to 2017 were examined. Septic patients with AKI who received contrast media within 24 h of admission (C group) were matched 1:1 with septic patients who did not receive contrast media (NC group). The primary outcome was deterioration of kidney function (DRF), which was defined as an elevation of serum creatinine levels (> 0.3 mg/dL or 1.5-fold from baseline) or induction of renal replacement therapy. RESULTS: A total of 339 septic patients with AKI were included. After propensity score adjustment, the DRF rate was similar between the C and NC groups (34.0% versus 35.0%; P = 1.00). The 7-day mortality (3.0% versus 6.0%; P = 0.50), 28-day mortality (9.2% versus 15.0%; P = 0.25), and 90-day mortality (25.8% versus 32.1%; P = 0.45) rates were comparable between the two groups. In propensity-adjusted subsets of a high-risk subset (AKI stages 2 and 3 on admission), the rate of DRF was also similar between the two groups. CONCLUSIONS: A single administration of contrast media was not associated with exacerbation of AKI or increased short/long-term mortality in patients with sepsis.

Recent early clinical drug development for acute kidney injury.

INTRODUCTION: Despite significant need and historical trials, there are no effective drugs in use for the prevention or treatment of acute kidney injury (AKI). There are several promising agents in early clinical development for AKI and two trials have recently been terminated. There are also exciting new findings in pre-clinical AKI research. There is a need to take stock of current progress in the field to guide future drug development for AKI. Areas covered: The main clinical trial registries, PubMed and pharmaceutical company website searches were used to extract the most recent clinical trials for sterile, transplant and sepsis-associated AKI. We summarise the development of the agents recently in clinical trial, update on their trial progress, consider reasons for failed efficacy of two agents, and discuss new paradigms in pre-clinical targets for AKI. Agents covered include- QPI-1002, THR-184, BB-3, heme arginate, human recombinant alkaline phosphatase (recAP), ciclosporin A, AB103, levosimendan, AC607 and ABT-719. Expert opinion: Due to the heterogenous nature of AKI, agents with the widest pleiotropic effects on multiple pathophysiological pathways are likely to be most effective. Linking preclinical models to clinical indication and improving AKI definition and diagnosis are key areas for improvement in future clinical trials.