A service evaluation of measuring fluid responsiveness in acutely unwell hypotensive patients outside of critical care.

INTRODUCTION: Early recognition and prompt, appropriate management may reduce mortality in patients with sepsis. The Surviving Sepsis Campaign's guidelines suggest the use of dynamic measurements to guide fluid resuscitation in sepsis; although these methods are rarely employed to monitor cardiac output in response to fluid administration outside intensive care units. This service evaluation investigated the introduction of a nurse led protocolised goal-directed fluid management using a non-invasive cardiac output monitor to the standard assessment of hypotensive ward patients. METHODS: We introduced the use of a goal-directed fluid management protocol into our critical care outreach teams' standard clinical assessment. Forty-nine sequential patients before and thirty-nine after its introduction were included in the assessment. RESULTS: Patients in the post-intervention cohort received less fluid in the 6 h following outreach assessment (750mls vs 1200mls). There were no differences in clinical background or rates of renal replacement therapy, but rates of invasive and non-invasive ventilation were reduced (0% vs 31%). Although the groups were similar, the post-intervention patients had lower recorded blood pressures. CONCLUSION: IV fluid therapy in the patient with hypotension complicating sepsis can be challenging. Excessive IV fluid administration is commonplace and associated with harm, and the use of advanced non-invasive haemodynamic monitoring by trained nurses can provide objective evaluation of individualised response to treatment. Avoiding excessive IV fluid and earlier institution of appropriate vasopressor therapy may improve patient outcomes. IMPLICATIONS FOR CLINICAL PRACTICE: Adoption of dynamic measures of cardiac output outside of critical care by trained critical care nurses is feasible and may translate into improved patient outcomes. In hospitals with a nurse-led critical care outreach service, consideration should be given to such an approach.

Hemoadsorption: Consensus report of the 30th Acute Disease Quality Initiative workgroup.

Adsorption-based extracorporeal therapies have been subject to technical developments and clinical application for close to five decades. More recently, new technological developments in membrane and sorbent manipulation have made it possible to deliver more biocompatible extracorporeal adsorption therapies to patients with a variety of conditions. There are several key rationales based on physicochemical principles and clinical considerations that justify the application and investigation of such therapies as evidenced by multiple ex-vivo, experimental, and clinical observations. Accordingly, unspecific adsorptive extracorporeal therapies have now been applied to the treatment of a wide array of conditions from poisoning to drug overdoses, to inflammatory states and sepsis, and acute or chronic liver and kidney failure. In response to the rapidly expanding knowledge base and increased clinical evidence, we convened an Acute Disease Quality Initiative (ADQI) consensus conference dedicated to such treatment. The data show that hemoadsorption has clinically acceptable short-term biocompatibility and safety, technical feasibility, and experimental demonstration of specified target molecule removal. Pilot studies demonstrate potentially beneficial effects on physiology and larger studies of endotoxin-based hemoadsorption have identified possible target phenotypes for larger randomized controlled trials (RCTs). Moreover, in a variety of endogenous and exogenous intoxications, removal of target molecules has been confirmed in vivo. However, some studies have raised concerns about harm or failed to deliver benefits. Thus, despite many achievements, modern hemoadsorption remains a novel and experimental intervention with limited data, and a large research agenda.

Biomarkers of acute kidney injury: From discovery to the future of clinical practice.

Purpose of this review Acute kidney injury (AKI) is a complex syndrome whose development is associated with an increased morbidity and mortality. Recent studies show that this syndrome is a common complication in critically ill and surgical patients the trajectory of which may differ. As AKI can be induced by different triggers, it is complex and therefore challenging to manage patients with AKI. This review strives to provide a brief historical perspective on AKI, elucidate recent developments in diagnosing and managing AKI, and show the current usage of novel biomarkers in both clinical routine and research. In addition, we provide a perspective on potential future developments and their impact of AKI understanding and management. Recent findings/developments Recent studies show the merits of stress and damage biomarkers, highlighting limitations of the current KDIGO definition that only uses the functional biomarkers serum creatinine and urine output. The use of novel biomarkers led to the introduction of the concept of "subclinical AKI". This new classification may allow a more distinct management of affected or at risk patients. Ongoing studies, such as BigpAK-2 and PrevProgAKI, investigate the implementation of biomarker-guided interventions in clinical practice and may demonstrate an improvement in patients' outcome. Summary The ongoing scientific efforts surrounding AKI have deepened our understanding of the syndrome prompting an expansion of existing concepts. A future integration of stress and damage biomarkers in AKI management, may lead to an individualized therapy in this area.

"Renal": the first forbidden word in the medical lexicon.

In October 2023 a letter appeared in The Lancet summarizing the view, of more than 200 physicians from 25 countries, that attempts to censor physician communication by forbidding the word Renal are both misguided and harmful [1]. Since letters are necessarily constrained by length, we now present a more comprehensive report on this issue.

Assessing the role of Chemokine (C-C motif) ligand 14 in AKI: a European consensus meeting.

BACKGROUND: Urinary Chemokine (C-C motif) ligand 14 (CCL14) is a biomarker associated with persistent severe acute kidney injury (AKI). There is limited data to support the implementation of this AKI biomarker to guide therapeutic actions. METHODS: Sixteen AKI experts with clinical CCL14 experience participated in a Delphi-based method to reach consensus on when and how to potentially use CCL14. Consensus was defined as ≥ 80% agreement (participants answered with 'Yes', or three to four points on a five-point Likert Scale). RESULTS: Key consensus areas for CCL14 test implementation were: identifying challenges and mitigations, developing a comprehensive protocol and pairing it with a treatment plan, and defining the target population. The majority agreed that CCL14 results can help to prioritize AKI management decisions. CCL14 levels above the high cutoff (> 13 ng/mL) significantly changed the level of concern for modifying the AKI treatment plan (p < 0.001). The highest level of concern to modify the treatment plan was for discussions on renal replacement therapy (RRT) initiation for CCL14 levels > 13 ng/mL. The level of concern for discussion on RRT initiation between High and Low, and between Medium and Low CCL14 levels, showed significant differences. CONCLUSION: Real world urinary CCL14 use appears to provide improved care options to patients at risk for persistent severe AKI. Experts believe there is a role for CCL14 in AKI management and it may potentially reduce AKI-disease burden. There is, however, an urgent need for evidence on treatment decisions and adjustments based on CCL14 results.

CCL14 Predicts Oliguria and Dialysis Requirement in Patients with Moderate to Severe Acute Kidney Injury.

INTRODUCTION: AKI is a frequent complication of critical illness and portends poor outcome. CCL14 is a validated predictor of persistent severe AKI in critically ill patients. We examined the association of CCL14 with urine output within 48 h. METHODS: In pooled data from 2 studies of critically ill patients with KDIGO stage 2-3 AKI, CCL14 was measured by NEPHROCLEAR™ CCL14 Test on the Astute 140® Meter (low, intermediate, and high categories [1.3 and 13 ng/mL]). Average hourly urine output over 48 h, stage 3 AKI per urine output criterion on day 2, and composite of dialysis or death within 7 days were examined using multivariable mixed and logistic regression models. RESULTS: Of the 497 subjects with median age of 65 (56-74) years, 49% (242/497) were on diuretics. CCL14 concentration was low in 219 (44%), intermediate in 217 (44%), and high in 61 (12%) patients. In mixed regression analysis, hourly urine output over time was different within each CCL14 risk category based on diuretic use due to significant three-way interaction (p < 0.001). In logistic regression analysis, CCL14 risk category was independently associated with low urine output on day 2 per KDIGO stage 3 (adjusted for diuretic use and baseline clinical variables), and composite of dialysis or death within 7 days (adjusted for urine output within 48 h of CCL14 measurement). CONCLUSIONS: CCL14 measured in patients with moderate to severe AKI is associated with urine output trajectory within 48 h, oliguria on day 2, and dialysis within 7 days.

Vitamin D metabolism in critically ill patients with acute kidney injury: a prospective observational study.

BACKGROUND: Vitamin D deficiency in critically ill patients is associated with poor outcomes, and vitamin D supplementation is recommended for patients with chronic kidney disease. Whether acute kidney injury (AKI) is associated with altered Vitamin D metabolism is unknown. We aimed to compare the longitudinal profiles of serum 25(OH)D and 1,25(OH)2D concentrations in critically ill patients with and without moderate to severe AKI and explore the impact of renal recovery and parathyroid hormone (PTH). METHODS: In this prospective, observational study in two centres in the UK, critically ill patients with and without AKI underwent serial measurement of serum 25(OH)D and 1,25(OH)2D and plasma PTH concentrations for 5 days. Linear mixed model analysis and sensitivity analyses were performed. RESULTS: Serial data of 137 patients were analysed. Seventy-one patients had AKI stage II/III of whom 23 recovered kidney function during the 5-day study period; 66 patients did not have AKI at enrolment of whom 14 developed new AKI. On day of enrolment, patients' serum 25(OH)D concentrations were low (median 18 nmol/L) but there was no significant difference between patients with and without AKI. Median serum 1,25(OH)2D levels were significantly lower in patients with AKI II/III (41 pmol/L [IQR 26, 58]) compared to similarly unwell patients without AKI (54 pmol/L [IQR 33, 69]) during the 5-day period. Recovery of kidney function in patients with AKI was associated with a rise in 1,25(OH)2D concentrations. Plasma PTH results were impacted by serum calcium and magnesium levels but not associated with 1,25(OH)2D levels. CONCLUSIONS: Critically ill patients with moderate-to-severe AKI have significantly lower serum 1,25(OH)2D concentrations than similarly sick patients without AKI but there was no difference in serum 25(OH)D concentrations. Recovery of AKI was associated with a rise in serum 1,25(OH)2D concentrations. More research is needed to investigate the health benefits and safety of supplementation with active vitamin D in critically ill patients with moderate-to-severe AKI. Trial registration Clinicaltrials.gov (NCT02869919), registered on 16 May 2016.

CCL14 testing to guide clinical practice in patients with AKI: Results from an international expert panel.

PURPOSE: Urinary C-C motif chemokine ligand 14 (CCL14) is a strong predictor of persistent stage 3 acute kidney injury (AKI). Multiple clinical actions are recommended for AKI but how these are applied in individual patients and how the CCL14 test results may impact their application is unknown. METHODS: We assembled an international panel of 12 experts and conducted a modified Delphi process to evaluate patients at risk for persistent stage 3 AKI (lasting 72 hours or longer). Using a Likert scale, we rated 11 clinical actions based on international guidelines applied to each case before and after CCL14 testing and analyzed the association between the strength and direction of recommendations and CCL14 results. RESULTS: The strength and direction of clinical recommendations were strongly influenced by CCL14 results (P < 0.001 for the interaction). Nine (82%) recommendations for clinical actions were significantly impacted by CCL14 results (P < 0.001 comparing low to highest CCL14 risk category). CONCLUSIONS: Most recommendations for care of patients with stage 2-3 by an international panel of experts were strongly modified by CCL14 test results. This work should set the stage for clinical practice protocols and studies to determine the effects of recommended actions informed by CCL14.

Acute kidney injury in patients with cirrhosis: Acute Disease Quality Initiative (ADQI) and International Club of Ascites (ICA) joint multidisciplinary consensus meeting.

Patients with cirrhosis are prone to developing acute kidney injury (AKI), a complication associated with a markedly increased in-hospital morbidity and mortality, along with a risk of progression to chronic kidney disease. Whereas patients with cirrhosis are at increased risk of developing any phenotype of AKI, hepatorenal syndrome (HRS), a specific form of AKI (HRS-AKI) in patients with advanced cirrhosis and ascites, carries an especially high mortality risk. Early recognition of HRS-AKI is crucial since administration of splanchnic vasoconstrictors may reverse the AKI and serve as a bridge to liver transplantation, the only curative option. In 2023, a joint meeting of the International Club of Ascites (ICA) and the Acute Disease Quality Initiative (ADQI) was convened to develop new diagnostic criteria for HRS-AKI, to provide graded recommendations for the work-up, management and post-discharge follow-up of patients with cirrhosis and AKI, and to highlight priorities for further research.

Prognostic Biomarkers and AKI: Potential to Enhance the Identification of Post-Operative Patients at Risk of Loss of Renal Function.

Acute kidney injury (AKI) is a common complication after surgery and the more complex the surgery, the greater the risk. During surgery, patients are exposed to a combination of factors all of which are associated with the development of AKI. These include hypotension and hypovolaemia, sepsis, systemic inflammation, the use of nephrotoxic agents, tissue injury, the infusion of blood or blood products, ischaemia, oxidative stress and reperfusion injury. Given the risks of AKI, it would seem logical to conclude that early identification of patients at risk of AKI would translate into benefit. The conventional markers of AKI, namely serum creatinine and urine output are the mainstay of defining chronic kidney disease but are less suited to the acute phase. Such concerns are compounded in surgical patients given they often have significantly reduced mobility, suboptimal levels of nutrition and reduced muscle bulk. Many patients may also have misleadingly low serum creatinine and high urine output due to aggressive fluid resuscitation, particularly in intensive care units. Over the last two decades, considerable information has accrued with regard to the performance of what was termed "novel" biomarkers of AKI, and here, we discuss the most examined molecules and performance in surgical settings. We also discuss the application of biomarkers to guide patients' postoperative care.

Kidney damage is common after major surgery with a recent study showing almost 1 in 5 patients suffer kidney damage. The usual tests for measuring kidney function are excellent in the outpatient but not so good in acute scenario's. Therefore, there has been a lot of interest in new markers of kidney damage (so-called novel biomarkers) which perform well acutely and allow earlier detection of damage allowing treatment to be started earlier. This article summarises the currently available biomarkers for use post-operatively and points out the different information that can be achieved by using them routinely.

Acute kidney disease beyond day 7 after major surgery: a secondary analysis of the EPIS-AKI trial.

PURPOSE: Acute kidney disease (AKD) is a significant health care burden worldwide. However, little is known about this complication after major surgery. METHODS: We conducted an international prospective, observational, multi-center study among patients undergoing major surgery. The primary study endpoint was the incidence of AKD (defined as new onset of estimated glomerular filtration rate (eCFR) < 60 ml/min/1.73 m2 present on day 7 or later) among survivors. Secondary endpoints included the relationship between early postoperative acute kidney injury (AKI) (within 72 h after major surgery) and subsequent AKD, the identification of risk factors for AKD, and the rate of chronic kidney disease (CKD) progression in patients with pre-existing CKD. RESULTS: We studied 9510 patients without pre-existing CKD. Of these, 940 (9.9%) developed AKD after 7 days of whom 34.1% experiencing an episode of early postoperative-AKI. Rates of AKD after 7 days significantly increased with the severity (19.1% Kidney Disease Improving Global Outcomes [KDIGO] 1, 24.5% KDIGO2, 34.3% KDIGO3; P < 0.001) and duration (15.5% transient vs 38.3% persistent AKI; P < 0.001) of early postoperative-AKI. Independent risk factors for AKD included early postoperative-AKI, exposure to perioperative nephrotoxic agents, and postoperative pneumonia. Early postoperative-AKI carried an independent odds ratio for AKD of 2.64 (95% confidence interval [CI] 2.21-3.15). Of 663 patients with pre-existing CKD, 42 (6.3%) had worsening CKD at day 90. In patients with CKD and an episode of early AKI, CKD progression occurred in 11.6%. CONCLUSION: One in ten major surgery patients developed AKD beyond 7 days after surgery, in most cases without an episode of early postoperative-AKI. However, early postoperative-AKI severity and duration were associated with an increased rate of AKD and early postoperative-AKI was strongly associated with AKD independent of all other potential risk factors.

Designing acute kidney injury clinical trials.

Acute kidney injury (AKI) is a common clinical condition with various causes and is associated with increased mortality. Despite advances in supportive care, AKI increases not only the risk of premature death compared with the general population but also the risk of developing chronic kidney disease and progressing towards kidney failure. Currently, no specific therapy exists for preventing or treating AKI other than mitigating further injury and supportive care. To address this unmet need, novel therapeutic interventions targeting the underlying pathophysiology must be developed. New and well-designed clinical trials with appropriate end points must be subsequently designed and implemented to test the efficacy of such new interventions. Herein, we discuss predictive and prognostic enrichment strategies for patient selection, as well as primary and secondary end points that can be used in different clinical trial designs (specifically, prevention and treatment trials) to evaluate novel interventions and improve the outcomes of patients at a high risk of AKI or with established AKI.

New biomarkers in acute kidney injury.

Acute kidney injury (AKI) is a commonly encountered clinical syndrome. Although it often complicates community acquired illness, it is more common in hospitalized patients, particularly those who are critically ill or who have undergone major surgery. Approximately 20% of hospitalized adult patients develop an AKI during their hospital care, and this rises to nearly 60% in the critically ill, depending on the population being considered. In general, AKI is more common in older adults, in those with preexisting chronic kidney disease and in those with known risk factors for AKI (including diabetes and hypertension). The development of AKI is associated with an increase in both mortality and morbidity, including the development of post-AKI chronic kidney disease. Currently, AKI is defined by a rise in serum creatinine from either a known or derived baseline value and/or oliguria or anuria. However, clinicians may fail to recognize the initial development of AKI because of a delay in the rise of serum creatinine or because of inaccurate urine output monitoring. This, in turn, delays any putative measures to treat AKI or to limit its degree. Consequently, efforts have focused on new biomarkers associated with AKI that may allow early recognition of this syndrome with the intent that this will translate into improved patient outcomes. Here we outline current biomarkers associated with AKI and explore their potential in aiding diagnosis, understanding the pathophysiology and directing therapy.

Proenkephalin as a biomarker correlates with acute kidney injury: a systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Proenkephalin A 119-159 (PENK) is freely filtered in the glomerulus with plasma levels correlating with glomerular filtration rate. Therefore, PENK has been proposed as an early indicator of acute kidney injury (AKI) although its performance is dependent on the clinical setting. This meta-analysis aimed to investigate the correlation between PENK levels and the development of AKI. METHODS: We conducted a comprehensive search on the PubMed, Embase, Cochrane databases, the website ClinicalTrials.gov and Cnki.net until June 26, 2023. Summary receiver operating characteristic (SROC) curves were used to amalgamate the overall test performance. Diagnostic odds ratio (DOR) was employed to compare the diagnostic accuracy of PENK with other biomarkers. Quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria. RESULTS: We incorporated 11 observational studies with 3969 patients with an incidence of AKI of 23.4% (929 out of 3969 patients) with the best optimal cutoff value of PENK for early detection of AKI being 57.3 pmol/L. The overall sensitivity and specificity of PENK in identifying AKI were 0.69 (95% CI 0.62-0.75) and 0.76 (95% CI 0.68-0.82), respectively. The combined positive likelihood ratio (LR) stood at 2.83 (95% CI 2.06-3.88), and the negative LR was 0.41 (95% CI 0.33-0.52). The SROC curve showcased pooled diagnostic accuracy of 0.77 (95% CI 0.73-0.81). Interestingly, patients with a history of hypertension or heart failure demonstrated a lower specificity of PENK in correlating the development of AKI. CONCLUSION: Our results indicate that PENK possesses significant potential as a biomarker for the early detection of the development of AKI, using a cutoff point of 57.3 pmol/L for PENK.

When to discontinue renal replacement therapy. what do we know?

PURPOSE OF REVIEW: Acute kidney injury is common in intensive care patients. Supportive care involves the use of renal replacement therapies as organ support. Initiation of renal replacement therapy has been the subject of much interest over the last few years with several randomised controlled studies examining the optimal time to commence treatment. In contrast to this, little evidence has been generated regarding cessation of therapy. Given that this treatment is complex, not without risk and expensive it seems timely that efforts should be expended at examining this vexing issue. RECENT FINDINGS: Although several studies have been reported examining the successful discontinuation of renal replacement therapies all studies reported to-date are observational in nature. Conventional biochemical criteria have been used as well as physiological parameters including urine output. More recently, more novel biomarkers of renal function have been studied. Although to-date no optimal variable nor threshold for discontinuation can be established. SUMMARY: Several variables have been described which may have a role in determining which patients may be successfully weaned from renal replacement therapy. However, few have been exposed to vigorous examination and evidence is sparse in support of any potential approach although urine output currently is the most often described. More recently novel biomarkers have also been examined but again are limited by study design and heterogeneity. Further research is clearly needed focussing on proposed variables preferably in multivariate models to improve predictive ability and successful cessation of therapy.

Feasibility of an electronic fluid balance chart to detect and understand the significance of oliguric acute kidney injury in a general ward setting: a prospective observational cohort study.

Background: Outside critical care environments, few studies have assessed the significance of oliguric acute kidney injury (AKI). This study investigated the feasibility of an electronic fluid balance chart to diagnose oliguric AKI. Data were used to determine if oliguric AKI was met earlier than creatinine AKI and to establish outcomes of those who developed AKI. Methods: A single-centre prospective cohort study investigated Kidney Disease Improving Global Outcomes oliguric and creatinine AKI criteria on general surgical wards. Results: 2,149 cases were included in the analysis. Incidence of oliguric AKI was significantly higher than creatinine criteria (73 versus 10.1%) and detection occurred earlier (2.1 versus 6.1 days, p<0.05). In cases with oliguric AKI, 8.1% also developed AKI by creatinine criteria. In cases not meeting oliguric AKI criteria, fewer cases developed creatinine AKI, as compared to those meeting oliguric AKI criteria (7.9% versus 11%, p=0.043). There was a high incidence of missing data. Conclusions: Oliguric AKI was met in a high proportion of cases and occurred earlier than by changes in creatinine. Barriers to consistency of recording must be addressed before oliguric criteria could be implemented in clinical practice.