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Acute kidney injury (AKI) after transcatheter aortic valve replacement (TAVR) portends a poor prognosis. In the TVT registry, AKI after TAVR occurred in 10% of the patients. The etiology of AKI after TAVR is multifactorial but contrast volume remains one of the few modifiable risk factors. As patients referred for TAVR have multiple touch points within a siloed healthcare system, there remains an unmet clinical need of a well-defined clinical pathway to minimize the risk of AKI from the time of referral for TAVR to the completion of the procedure. This white paper aims to provide such a clinical pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

This consensus paper summarizes the expert consensus and recommendations of the working group "Heart and Kidney" of the German Cardiac Society (DGK) and the German Society of Nephrology (DGfN) on contrast medium-induced acute kidney injury. Potentially nephrotoxic contrast agents containing iodine are frequently used in interventional medicine and for computer tomography diagnostics. Acute kidney injury occurs in approximately 8-17% of patients exposed to contrast media. The risk factors and underlying pathophysiology are discussed and recommendations for the prophylaxis and treatment of contrast medium-induced acute nephropathy are presented.

Renal replacement therapy is after mechanical ventilation one of the most important and frequently used organ replacement therapies in daily routine intensive care practice. In contrast to mechanical ventilation, quality standards for renal replacement therapy are less well known and defined. In this position paper of the German Interdisciplinary Association for Intensive Care and Emergency Medicine, we describe quality standards of renal replacement procedures in order to improve therapy of patients with severe acute kidney injury.

Patients with cancer are subjected to several imaging examinations which frequently require the administration of contrast medium (CM). However, it has been estimated that acute kidney injury (AKI) due to the injection of iodinated CM accounts for 11% of all cases of AKI, and it is reported in up to 2% of all CT examinations. Remarkably, the risks of developing AKI are increased in the elderly, in patients with chronic kidney disease or diabetes, and with dehydration or administration of nephrotoxic chemotherapeutics. Given the common occurrence of postcontrast acute kidney injury (PC-AKI) in clinical practice, primary care physicians and all specialists involved in managing patients with cancer should be aware of the strategies to reduce the risk of this event. In 2018, a panel of four experts from the specialties of radiology, oncology and nephrology were speakers at the annual meeting of the Italian Society of Medical Radiology (Società Italiana di Radiologia Medica e Interventistica), with the aim of commenting on existing evidence and providing their experience on the incidence and management of PC-AKI in patients with cancer. The discussion represented the basis for this white paper, which is intended to be a practical guide organised by statements describing methods to reduce renal injury risks related to CM-enhanced CT examinations in patients with cancer., Competing Interests: Competing interests: LG, CPo, LC and AL acted as speakers and/or consultants for GE Healthcare. GE Healthcare supported the meeting, which led to this paper., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Renal perfusion provides the driving pressure for glomerular filtration and delivers the oxygen and nutrients to fuel solute reabsorption. Renal ischaemia is a major mechanism in acute kidney injury and may promote the progression of chronic kidney disease. Thus, quantifying renal tissue perfusion is critically important for both clinicians and physiologists. Current reference techniques for assessing renal tissue perfusion have significant limitations. Arterial spin labelling (ASL) is a magnetic resonance imaging (MRI) technique that uses magnetic labelling of water in arterial blood as an endogenous tracer to generate maps of absolute regional perfusion without requiring exogenous contrast. The technique holds enormous potential for clinical use but remains restricted to research settings. This statement paper from the PARENCHIMA network briefly outlines the ASL technique and reviews renal perfusion data in 53 studies published in English through January 2018. Renal perfusion by ASL has been validated against reference methods and has good reproducibility. Renal perfusion by ASL reduces with age and excretory function. Technical advancements mean that a renal ASL study can acquire a whole kidney perfusion measurement in less than 5-10 min. The short acquisition time permits combination with other MRI techniques that might inform drug mechanisms and renal physiology. The flexibility of renal ASL has yielded several variants of the technique, but there are limited data comparing these approaches. We make recommendations for acquiring and reporting renal ASL data and outline the knowledge gaps that future research should address.

Nephrotoxicity is one of the more common causes of attrition in nonclinical drug development. Like most tissues, the kidney has a limited number of ways of responding to toxicological insults from diverse mechanistic pathways, which can limit the ability to determine mechanisms of renal injury using the assays routinely performed in preclinical toxicologic studies. In situations where the renal injury is unusual in morphology or if a therapeutic margin is low, additional investigative techniques may be needed to identify a potential mechanism of toxicity in order to inform clinical risk assessment or establish human relevance and translatability of the toxicity. While routine microscopic evaluation can suggest a specific pathogenesis, understanding the mechanism of renal injury often requires additional hypothesis-driven investigations and specialized techniques to obtain the data necessary to identify a nephrotoxic mechanism. Nonclinical mechanistic investigations can be resource-intensive and often yield limited new information. Although there are multiple avenues to investigate renal toxicity, no single mechanistic study or prescriptive battery of tests will identify the pathophysiologic basis for every potential mechanism of renal injury. To aid the nonclinical investigator, we outline a tiered approach for prioritizing investigations to provide a rational and linear road map for the exploration of mechanisms of drug-induced kidney injury. [Box: see text].

Introduction: Acute kidney injury is associated with high mortality in the perioperative period of liver transplantation. The aim of this position paper was to provide an up-to-date overview with special emphases on diagnosis, risk factors, and treatment., Evidence Acquisition: The Liver Intensive Care Group of Europe nominated a panel of recognized international experts who reviewed the available literature published from 1990 to January 2016 and produced clinical recommendations. The level of evidence and strength of recommendation were judged according to the Grading of Recommendations Assessment Development and Evaluation system., Evidence Synthesis: Diagnosis of AKI should be based on the KDIGO criteria. The preoperative risk factors are more related to the patient's predisposing factors and post-operative risk factors tend to be difficult to control. Therefore, focusing on intra-operative risk factors it would be important to maintain an adequate hemodynamics and to keep inferior vena cava clamping as short as possible. Biomarkers to identify AKI at an early stage are available; however, there is a lack of robust data that indicates their true beneficial effect. Intraoperative renal replacement therapy may be beneficial in some selective cases whereas its postoperative timing is still under debate., Conclusions: Perioperative liver transplant risk factors for acute kidney injury are difficult to control. Therefore, the focus should be on intra-operative hemodynamics and nephrotoxic drugs avoidance. Prospective randomized trials are needed to show the beneficial effect of early replacement therapy. In this context, the new biomarkers would be helpful in identifying kidney injury earlier.

The use of human albumin is common in hepatology since international scientific societies support its administration to treat or prevent severe complications of cirrhosis, such as the prevention of post-paracentesis circulatory dysfunction after large-volume paracentesis and renal failure induced by spontaneous bacterial peritonitis, and the treatment of hepatorenal syndrome in association with vasoconstrictors. However, these indications are often disregarded, mainly because the high cost of human albumin leads health authorities and hospital administrations to restrict its use. On the other hand, physicians often prescribe human albumin in patients with advanced cirrhosis for indications that are not supported by solid scientific evidence and/or are still under investigation in clinical trials. In order to implement appropriate prescription of human albumin and to avoid its futile use, the Italian Association for the Study of the Liver (AISF) and the Italian Society of Transfusion Medicine and Immunohaematology (SIMTI) nominated a panel of experts, who reviewed the available clinical literature and produced practical clinical recommendations for the use of human albumin in patients with cirrhosis., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Purpose: More than 20 years ago we reported an analysis of a case series of elderly critically ill patients with acute kidney injury (AKI)--then termed acute renal failure. At that time, AKI was regarded as a "simple" complication, but has since undergone a fundamental change and actually has become one of the central syndromes in the critically ill patient., Methods: We have analyzed elderly patients above 65 years of age with an AKI defined as serum creatinine above 3 mg/dl corresponding to modern KDIGO stage 3, most of them requiring renal replacement therapy (RRT). Using an extremely complete data set the diagnosis differentiated the underlying disease entity, the dominant cause of AKI, acute and chronic risk factors (comorbidities). Special aspects such as severity of disease, early AKI at admission versus late AKI, early versus later start of RRT, AKI not treated by RRT in spite of indication for RRT, various measures of short-term and long-term prognosis, renal outcome, patients dying with resolved AKI, and causes of death were evaluated., Results: Crude mortality was 61% which corresponds to modern studies with gross variation among the different subgroups. Age per se was not a determinant of survival either within the group of elderly patients or as compared to younger age groups. Despite an increase in mean age and disease severity during the observation period prognosis improved. A total of 17% of patients developed a chronic kidney disease. Long-term survival as compared to the general population was low., Conclusions: A look back at the last two decades illustrates a remarkable evolution or rather metamorphosis of a syndrome. AKI has evolved as a central syndrome in intensive care patients, a systemic disease process associated with multiple systemic sequels and extra-renal organ injury and exerting a pronounced effect on the course of disease and short- and long-term prognosis not only of the patient but also of the kidney. Moreover, the "non-renal-naïve" elderly patient with multiple comorbidities has become the most frequent ICU patient in industrialized nations.

Despite 21st century definitions, the management of acute kidney injury remains steadfastly rooted in the 20th century with treatment being principally supportive. Protection from potential causative agents is an essential part of management and to that end protection against contrast-induced nephropathy has received yet more attention. When optimization of volume status, haemodynamic parameters, electrolyte and acid-base disturbances have failed we turn to renal replacement therapy. The time 'bought' on renal support gives a period for renal recovery but although renal replacement therapy is widely employed, many management issues remain unanswered, including the timing, duration and the dose of treatment. In contrast to respiratory support for acute lung injury, for example, there is a paucity of large randomized studies addressing these fundamental issues. We describe some recent studies focusing on these issues with the hope that they may lead to better treatment for our patients.

When faced with the management of the patient on intensive care with acute kidney injury, the clinician has various choices to consider. The conventional therapy, where appropriate, is renal replacement therapy. This technique used to be relatively straightforward but now a relative feast of alternatives is available, not least in choice of buffer and anticoagulant. Two recent studies add to the growing body of literature concerning alternative anticoagulant regimes, and one in particular should lead to a change in practice for many of us. We also review some new studies on biomarkers in the diagnosis of acute kidney injury as well as add yet another nail in the coffin for loop diuretics in the therapy of acute kidney injury.

Objective: This longitudinal study evaluated renal function and acute kidney injury (AKI) over time in US agricultural workers., Methods: We followed Florida agricultural workers from January 2020 to August 2022, collecting blood and urine preworkday and postworkday during five visits., Results: Preworkday estimated glomerular filtration rate function in all participants was lower in summers but relatively consistent over time. In participants who worked almost exclusively in fernery operations (piece-rate compensation), we observed a high incidence of postworkday AKI in 2020 (21%) that increased to 43% by the end of the study. In comparison, 11% of nursery workers (hourly compensation) had AKI, and this rate was fairly stable., Conclusion: AKI risk over time differs according to the type of agricultural work. Piece rate workers who are incentivized to forgo rest breaks and hydration to earn higher wages demonstrate steadily increasing rates of AKI., Competing Interests: Chicas, Elon, Xiuhtecutli, Liang, Houser, Mwarumba, Berra, Hertzberg, Sands, and McCauley have no relationships/conditions/circumstances that present potential conflict of interest., (Copyright © 2024 American College of Occupational and Environmental Medicine.)

Purpose: The role of lower hemoglobin A1c (HbA1c) variability in the effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) on acute kidney injury (AKI) remains unclear. We compared AKI risk between SGLT2i and dipeptidyl peptidase 4 inhibitors (DPP4i) initiators. Additionally, we aimed to explore the extent to which SGLT2i's influence on AKI risk is mediated by reducing long-term HbA1c variability., Methods: Using 2018-2022 year data in Yinzhou Regional Health Care Database, we included adult, type 2 diabetes patients who were new users of SGLT2i or DPP4i. The effect of SGLT2i versus DPP4i on AKI, HbA1c variability, and AKI through HbA1c variability was compared using inverse probability of treatment weighted Cox proportional hazards models, median regression models, and causal mediation analysis., Results: With a median follow-up of 1.76 years, 19 717 adults (for SGLT2i, n = 6008; for DPP4i, n = 13 709) with type 2 diabetes were included. The adjusted hazard ratio for SGLT2i versus DPP4i was 0.79 (95% confidence interval [CI] 0.64-0.98) for AKI. The adjusted differences in median HbA1c variability score (HVS) and HbA1c reduction were -16.67% (95% CI: -27.71% to -5.62%) and -1.98% (95% CI: -14.34% to 10.38%), respectively. Furthermore, lower AKI risk associated with SGLT2i was moderately mediated (22.77%) through HVS. The results remained consistent across various subgroups and sensitivity analyses., Conclusions: Compared to DPP4i, lower AKI risk associated with SGLT2i is moderately mediated through HbA1c variability. These findings enhance our understanding of the effect of SGLT2i on AKI and underscore the importance of considering HbA1c variability in diabetes treatment and management., (© 2024 The Author(s). Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Acute kidney injury (AKI) is associated with persistent renal dysfunction, the receipt of dialysis, dialysis dependence, and mortality. Accordingly, the concept of major adverse kidney events (MAKE) has been adopted as an endpoint for assessing the impact of AKI. However, applied criteria or observation periods for operationalizing MAKE appear to vary across studies. To evaluate this heterogeneity for MAKE evaluation, we performed a systematic scoping review of studies that employed MAKE as an AKI endpoint. Four major academic databases were searched, and we identified 122 studies with increasing numbers over time. We found marked heterogeneity in applied criteria and observation periods for MAKE across these studies, with some even lacking a description of criteria. Moreover, 13 different observation periods were employed, with 30 days and 90 days as the most common. Persistent renal dysfunction was evaluated by estimated glomerular filtration rate (34%) or serum creatinine concentration (48%); however, 37 different definitions for this component were employed in terms of parameters, cut-off criteria, and assessment periods. The definition for the dialysis component also showed significant heterogeneity regarding assessment periods and duration of dialysis requirement (chronic vs temporary). Finally, MAKE rates could vary by 7% [interquartile range: 1.7-16.7%] with different observation periods or by 36.4% with different dialysis component definitions. Our findings revealed marked heterogeneity in MAKE definitions, particularly regarding component assessment and observation periods. Dedicated discussion is needed to establish uniform and acceptable standards to operationalize MAKE in terms of selection and applied criteria of components, observation period, and reporting criteria for future trials on AKI and related conditions., (© 2024. The Author(s).)

Background and Aims: Treatment of hepatorenal syndrome-acute kidney injury (HRS-AKI), with terlipressin and albumin, provides survival benefits, but may be associated with cardiopulmonary complications. We analyzed the predictors of terlipressin response and mortality using point-of-care echocardiography (POC-Echo) and cardiac and renal biomarkers., Approach: Between December 2021 and January 2023, patients with HRS-AKI were assessed with POC-Echo and lung ultrasound within 6 hours of admission, at the time of starting terlipressin (48 h), and at 72 hours. Volume expansion was done with 20% albumin, followed by terlipressin infusion. Clinical data, POC-Echo data, and serum biomarkers were prospectively collected. Cirrhotic cardiomyopathy (CCM) was defined per 2020 criteria., Results: One hundred and forty patients were enrolled (84% men, 59% alcohol-associated disease, mean MELD-Na 25±SD 5.6). A median daily dose of infused terlipressin was 4.3 (interquartile range: 3.9-4.6) mg/day; mean duration 6.4 ± SD 1.9 days; the complete response was in 62% and partial response in 11%. Overall mortality was 14% and 16% at 30 and 90 days, respectively. Cutoffs for prediction of terlipressin nonresponse were cardiac variables [ratio of early mitral inflow velocity and mitral annular early diastolic tissue doppler velocity > 12.5 (indicating increased left filling pressures, C-statistic: 0.774), tissue doppler mitral velocity < 7 cm/s (indicating impaired relaxation; C-statistic: 0.791), > 20.5% reduction in cardiac index at 72 hours (C-statistic: 0.885); p < 0.001] and pretreatment biomarkers (CysC > 2.2 mg/l, C-statistic: 0.640 and N-terminal proBNP > 350 pg/mL, C-statistic: 0.655; p <0.050). About 6% of all patients with HRS-AKI and 26% of patients with CCM had pulmonary edema. The presence of CCM (adjusted HR 1.9; CI: 1.8-4.5, p = 0.009) and terlipressin nonresponse (adjusted HR 5.2; CI: 2.2-12.2, p <0.001) were predictors of mortality independent of age, sex, obesity, DM-2, etiology, and baseline creatinine., Conclusions: CCM and reduction in cardiac index, reliably predict terlipressin nonresponse. CCM is independently associated with poor survival in HRS-AKI., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background: Acute kidney injury (AKI) is a severe postoperative complication associated with poor clinical outcomes, including the development of chronic kidney disease (CKD) and death. This study aimed to investigate the incidence and determinants of AKI following elective surgeries for degenerative lumbar spine disease., Methods: All patient data were extracted from the US Nationwide Inpatient Sample database. After surgery, AKI's incidence and risk factors were identified for lumbar degenerative disease. ICD-9 and ICD-10 codes defined lumbar spine degenerative disease, fusion, decompression, and AKI. The study cohort was categorized by type of surgery, that is, decompression alone or spinal fusion. Regression analysis was used to identify associations between AKI and risk factors organized by surgery type., Results: The incidence of AKI after decompression or fusion was 1.1% and 1.8%, respectively. However, the incidence of AKI in the United States is rising. The strongest predictor of AKI was underlying CKD, which was associated with an 9.0- to 12.9-fold more significant risk of AKI than in subjects without comorbid CKD. In this setting, older age, congestive heart failure, anemia, obesity, coagulopathy and hospital-acquired infections were also strong predictors of AKI. In contrast, long-term aspirin/anticoagulant usage was associated with lowered AKI risk., Conclusion: Findings of this study inform risk stratification for AKI and may help to optimize treatment decisions and care planning after elective surgery for lumbar degenerative disease., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Acute kidney injury (AKI) is a frequent complication of acute liver failure (ALF) and it worsens the already worse prognoses of ALF. ALF is an uncommon disease, with varying etiologies and varying definitions in different parts of the world. There is limited literature on the impact of AKI on the outcome of ALF with or without transplantation. The multifaceted etiology of AKI in ALF encompasses factors such as hemodynamic instability, systemic inflammation, sepsis and direct nephrotoxicity. Indications of renal replacement therapy (RRT) for AKI in ALF patients extend beyond the conventional criteria for dialysis and continuous renal replacement therapy (CRRT) may have a role in transplant-free survival or bridge to liver transplantation (LT). LT is a life-saving option for ALF, so despite somewhat lower survival rates of LT in ALF patients with AKI, LT is not usually deferred. In this review, we will discuss the guidelines' recommended definition and classification of AKI in ALF, the impact of AKI in ALF, the pathophysiology of AKI and the role of CRRT and LT in ALF patients with AKI., (© 2024. Indian Society of Gastroenterology.)

The management of patients with complex comorbidity involving several organ systems can use an approach focused on each organ system independently or can use an approach trying to integrate various injuries and dysfunction into a single syndrome. Cardiorenal syndromes can develop with an initial injury to either the heart or kidney and then sequential involvement of the second organ. This can occur acutely or chronically. Cardiorenal syndrome type 3 is defined by acute renal injury with subsequent cardiac injury and/or dysfunction. Studies on these patients must use strict inclusion criteria. Pavan reported information on 100 patients with acute kidney injury in India to determine the frequency of cardiorenal syndrome type 3. He excluded patients with significant prior comorbidity. The most frequent causes of acute kidney injury in these patients were drug toxicity, gastroenteritis with volume contraction, and obstetrical complications. This study included 100 patients with acute kidney injury, and 29 developed cardiorenal syndrome type 3. Important outcomes included frequent mortality and chronic renal failure. Other studies have reported that cardiorenal syndrome type 3 occurs relatively infrequently. The analysis of large data bases has demonstrated that the development of acute kidney injury in hospitalized patients has important consequences, including the development of heart failure and increased mortality, but the complexity of these cohorts makes it difficult to determine the time course for the development of multisystem disorders. The pathogenesis of cardiorenal syndrome type 3 involves mitochondrial dysfunction, immune dysregulation, and ischemia-reperfusion. Cardiac events occur secondary to fluid overload, electrolyte disorders, and uremic toxins. These patients need increased attention during hospitalization and outpatient management in an effort to slow the progression of the primary disorder and treat complications., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Acute kidney injury (AKI) is a frequent complication of critical illness and carries a significant risk of short- and long-term mortality. The prediction of the progression of AKI to long-term injury has been difficult for renal disease treatment. Radiologists are keen for the early detection of transition from AKI to long-term kidney injury, which would help in the preventive measures. The lack of established methods for early detection of long-term kidney injury underscores the pressing needs of advanced imaging technology that reveals microscopic tissue alterations during the progression of AKI. Fueled by recent advances in data acquisition and post-processing methods of magnetic resonance imaging (MRI), multiparametric MRI is showing great potential as a diagnostic tool for many kidney diseases. Multiparametric MRI studies offer a precious opportunity for real-time noninvasive monitoring of pathological development and progression of AKI to long-term injury. It provides insight into renal vasculature and function (arterial spin labeling, intravoxel incoherent motion), tissue oxygenation (blood oxygen level-dependent), tissue injury and fibrosis (diffusion tensor imaging, diffusion kurtosis imaging, T1 and T2 mapping, quantitative susceptibility mapping). The multiparametric MRI approach is highly promising but the longitudinal investigation on the transition of AKI to irreversible long-term impairment is largely ignored. Further optimization and implementation of renal MR methods in clinical practice will enhance our comprehension of not only AKI but chronic kidney diseases. Novel imaging biomarkers for microscopic renal tissue alterations could be discovered and benefit the preventative interventions. This review explores recent MRI applications on acute and long-term kidney injury while addressing lingering challenges, with emphasis on the potential value of the development of multiparametric MRI for renal imaging on clinical systems. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2., (© 2023 International Society for Magnetic Resonance in Medicine.)

Purpose of Review: To discuss how nutritional management could be optimized to promote protective metabolism in sepsis and associated acute kidney injury., Recent Findings: Recent evidence suggests that sepsis is a metabolically distinct critical illness and that certain metabolic alterations, such as activation of fasting metabolism, may be protective in bacterial sepsis. These findings may explain the lack of survival benefit in recent randomized controlled trials of nutrition therapy for critical illness. These trials are limited by cohort heterogeneity, combining both septic and nonseptic critical illness, and the use of inaccurate caloric estimates to determine energy requirements. These energy estimates are also unable to provide information on specific substrate preferences or the capacity for substrate utilization. As a result, high protein feeding beyond the capacity for protein synthesis could cause harm in septic patients. Excess glucose and insulin exposures suppress fatty acid oxidation, ketogenesis and autophagy, of which emerging evidence suggest are protective against sepsis associated organ damage such as acute kidney injury., Summary: Distinguishing pathogenic and protective sepsis-related metabolic changes are critical to enhancing and individualizing nutrition management for critically ill patients., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Use of continuous renal replacement therapy in children receiving anti-infective drugs may lead to inappropriate concentrations with risks related to treatment failure, toxicity and emergence of multidrug-resistant bacteria. We aimed to describe anti-infective prescribing practices in critically ill children undergoing continuous renal replacement therapy., Methods: An online survey to assess continuous renal replacement therapy, anti-infective prescribing and therapeutic drug monitoring practices was sent by e-mail to physicians working in pediatric intensive care units through the French-speaking Group of Pediatric Intensive Care and Emergency medicine (GFRUP)., Results: From April 1st, 2021 to May 1st, 2021, 26/40 pediatric intensive care units participated in the survey, corresponding to a response rate of 65%. Twenty-one were located in France and five abroad. All pediatric intensive care units administered continuous renal replacement therapy, primarily with Prismaflex™ System. Anti-infective prescriptions were adjusted to the presence of continuous renal replacement therapy in 23 (88%) pediatric intensive care units mainly according to molecular weight in 6 (23%), molecule protein binding in 6 (23%) and elimination routes in 15 (58%) including residual diuresis in 9 (35%), to the continuous renal replacement therapy flow in 6 (23%) and to the modality of continuous renal replacement therapy used in 15 (58%), pediatric intensive care units. There was broad variability among pediatric intensive care units and among physicians within the same unit. Barriers to therapeutic drug monitoring were mainly an excessive delay in obtaining results in 11 (42%) and the lack of an on-site laboratory in 8 (31%) pediatric intensive care units., Conclusions: Our survey reported wide variability in anti-infective prescribing practices in children undergoing continuous renal replacement therapy, thus highlighting a gap in knowledge and the need for education and recommendations., (© 2023. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Abstract: Introduction : The optimal target of mean arterial pressure (MAP) during continuous renal replacement therapy (CRRT) is unknown. Method : We retrospectively collected the hourly MAP data in acute kidney injury patients requiring CRRT who admitted to the intensive care unit in the University of Tokyo hospital during 2011-2019. Patients who died within 48 h of CRRT start and whose average value of hourly MAPs during the first 48 h was <65 mm Hg were excluded. When the average value of MAP was ≤75 mm Hg or >75 mm Hg, patients were allocated to the low or high target group. We estimated the effect of MAP on mortality and RRT independence at 90 days, using multivariable the Cox regression model and Fine and Gray model. Result : Of the 275 patients we analyzed, 95 patients were in the low group. There are no differences in sex, baseline kidney function, and disease severity. At 90 days, the low target group had higher mortality with 38 deaths (40.0%) compared with 57 deaths (31.7%) in the high target group ( P < 0.05). The adjusted hazard ratio of the low target group (≤75 mm Hg) for mortality was 1.72 (95% CI, 1.08-2.74). In addition, the low target group had a lower rate of RRT independence, with 60 patients (63.2%) compared with 136 patients (75.6%) in the high target group ( P < 0.05). The multivariable analysis revealed that the adjusted hazard ratio of the low target group for RRT independence was 0.74 (95% CI, 0.54-1.01). Conclusion : This study found the association with low MAP and mortality. The association with low MAP and delayed renal recovery was not revealed., (Copyright © 2023 by the Shock Society.)

Drug-associated kidney injury is related to longer hospitalization and increased risk of chronic kidney disease and mortality. However, there is currently a lack of large population studies on drug-associated kidney injury in children. This study aimed to study perform data mining to generate hypotheses on drugs, which may deserve to be assessed as per their potential risk of increasing kidney injury in children. We extracted and analyzed reports on drugs associated with kidney injury in children in the FDA Adverse Event Reporting System (FAERS). We conducted a disproportionality analysis using proportional reporting ratio (PRR) to evaluate the association between drugs and kidney injury in children. Meanwhile, comparisons were performed with drug labels to identify drugs that, despite not having kidney injury currently mentioned in their labels, may potentially be associated with risks of kidney injury in children. A total of 6347 children had drug-associated kidney injury in the FAERS database. The top five drugs with the highest PRR were gentamicin (PRR = 12.28, N = 157 cases, Chi-Squared = 1602.77), piperacillin-tazobactam (PRR = 9.77, N = 129 cases, Chi-Squared = 1003.24), amlodipine (PRR = 8.98, N = 271 cases, Chi-Squared = 1861.46), vancomycin (PRR = 8.91, N = 295 cases, Chi-Squared = 1998.64), and ceftriaxone (PRR = 8.00, N = 251 cases, Chi-Squared = 1494.02). According to drug labels, 9 drugs (9/30) were classified as potential nephrotoxins., Conclusions: Approximately one-third of drugs associated with kidney injury in children do not list kidney injury as a side effect in their drug labels. Future studies are therefore warranted to evaluate whether these drugs are associated with such a risk., What Is Known: • Nephrotoxic drugs are an increasingly common cause of acute kidney injury in hospitalized children. • Currently, no study has systematically combed drugs associated with kidney injury in children., What Is New: • Approximately a third of drugs showing signals for potential kidney injury in children in data mining do not mention this side effect in their drug labels. • This study provides data on drugs needing further study to determine whether they might increase the risk of kidney injury in children., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Reports of consensus conferences are usually valued less than reports of clinical trials even when rigorous methodology is used. However, limited data are available comparing the impact of these 2 methods of shaping clinical practice. Objective: Compare the publication impact of consensus conferences and clinical trials. Methods: Consensus publications from the Acute Disease Quality Initiative (ADQI) from 2002 through 2017 were identified and classified by subject matter. Randomized trials were identified in the same publication year and subject in journals, starting with the highest impact factor. Both publication types were matched, and total citations were determined for each using Google Scholar. A secondary analysis compared total costs for each publication type. Results and Conclusions: Seventeen ADQI consensus conference reports and 17 randomized trials were identified. ADQI reports received a similar number of citations per paper (median, interquartile range) compared to randomized trials (132, 54–228; vs. 159, 60–340, p = ns). Similarly, 10 (58.8%) ADQI reports and 10 randomized trials were cited >100 times. On average, ADQI reports appeared in journals with lower impact factors compared to clinical trials (5.4 ± 4.6 vs. 25.4 ± 27.1; p < 0.01). The median cost per citation (USD 2017) for ADQI reports was USD 606.01 compared to almost twice this figure, USD 1,182.59, for clinical trials on the same topics (p = 0.09). Despite being published in lower impact factor journals, consensus reports on topics in critical care nephrology, received similar citations to randomized controlled trials published the same year. [ABSTRACT FROM AUTHOR]

Continuous kidney replacement therapy (CKRT) is often utilized to stabilize patients with severe acute kidney injury associated with significant electrolyte abnormalities and/or oliguria and concomitant fluid accumulation. Circuit downtime may reduce daily treatment time and affect delivered doses of CKRT. Studies have found clotting to be the leading cause of downtime and underdosing, which are associated with negative treatment outcomes. The NxStage Cartridge Express with Speedswap (NxStage Medical, Inc.) was designed to minimize downtime by allowing filter priming to occur in parallel with ongoing CKRT and by permitting filter exchanges without the need to replace the entire cartridge. Data from pilot studies suggest that filter exchanges using this system interrupt treatment by an average of 4 minutes per exchange-a considerable reduction from traditional systems that require treatment to be discontinued while the filter is primed, which can take 30 minutes or more. In addition to increasing patient time on therapy, this system has the potential to reduce costs for patients who require a high number of filter changes, and reduce nursing labor and environmental impact (reduced plastic waste). Future studies should confirm whether patients at higher risk of clotted/clogged filters benefit from CKRT with a system designed for rapid filter changes., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASAIO.)

While the administration of intravenous fluids remains an important treatment, the negative consequences of subsequent fluid overload have raised questions about when and how clinicians should pursue avenues of fluid removal. Decisions regarding fluid removal during critical illness are complex even for patients with preserved kidney function. This article seeks to apply general concepts of fluid management to the care of patients who also require KRT. Because optimal fluid management for any specific patient is likely to change over the course of critical illness, conceptual models using phases of care have been developed. In this review, we will examine the implications of one such model on the use of ultrafiltration during KRT for volume removal in distributive shock. This will also provide a useful lens to re-examine published data of KRT during critical illness. We will highlight recent prospective trials of KRT as well as recent retrospective studies examining ultrafiltration rate and mortality, review the results, and discuss applications and shortcomings of these studies. We also emphasize that current data and techniques suggest that optimal guidelines will not consist of recommendations for or against absolute fluid removal rates but will instead require the development of dynamic protocols involving frequent cycles of reassessment and adjustment of net fluid removal goals. If optimal fluid management is dynamic, then frequent assessment of fluid responsiveness, fluid toxicity, and tolerance of fluid removal will be needed. Innovations in our ability to assess these parameters may improve our management of ultrafiltration in the future., (Copyright © 2023 by the American Society of Nephrology.)

Renal impairment can affect the elimination of hepatically metabolized drugs. Bexarotene (BXT) used for cutaneous T-cell lymphoma is highly bound in plasma and metabolized by CYP3A4. The BXT European Medicine Agency and Food and Drug Administration packages recommended the evaluation of renal impairment on BXT metabolism. The plasma protein binding of BXT can be changed in patients with renal dysfunction due to hypoalbuminemia and accumulation of uremic toxins. In vitro, microsomal stability and plasma protein binding studies were pursued. A preclinical pharmacokinetic study was pursued in control, chronic kidney disease (CKD), and acute kidney injury (AKI) rats. A BXT physiologically based pharmacokinetic (PBPK) model that utilized in vitro-in vivo extrapolation of metabolism was established and verified in healthy rats, customized to CKD and AKI rats, and extrapolated to healthy human subjects and those with CKD stages 3, 4, and 5. In vitro studies showed that AKI and CKD significantly increased the BXT fraction unbound in plasma (from 0.011 to 0.018 and 0.022, respectively) and decreased intrinsic clearance (from 4.1 to 2.5, and 2.2 mL/min/g liver, respectively). This could explain the reduced in vivo clearance observed in CKD rats (from 0.4 to 0.28 L/h/kg) and the 1.3-fold increase in BXT exposure. Changes in BXT disposition in AKI rats were not straightforward due to simultaneous changes in BXT distribution. The human PBPK model predicted an increased BXT exposure by 2-fold in CKD patients, suggesting the need for dose reduction and drug monitoring. The reduced BXT metabolism due to renal impairment is especially relevant in cancer patients with CKD., (© 2022 John Wiley & Sons Ltd.)

Acute kidney injury (AKI) is common in critically ill patients, affecting almost one in four critically ill children and one in three neonates. Higher stages of AKI portend worse outcomes. Identifying AKI timely and instituting appropriate measures to prevent and manage severe AKI is important, since it is independently associated with mortality. Methods to predict severe AKI should be applied to all critically ill patients. Assessment of volume status to prevent the development of fluid overload is useful to prevent adverse outcomes. Patients with metabolic or clinical complications of AKI need prompt kidney replacement therapy (KRT). Various modes of KRT are available, and the choice of modality depends most on the technical competence of the center, patient size, and hemodynamic stability. Given the significant risk of chronic kidney disease, patients with AKI require long-term follow-up. It is important to focus on improving awareness about AKI, incorporate AKI prevention as a quality initiative, and improve detection, prevention, and management of AKI with the aim of reducing acute and long-term morbidity and mortality., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Purpose of Review: Acute kidney injury (AKI) is a common complication in critically ill patients. Understanding the pathophysiology of AKI is essential to guide patient management. Imaging techniques that inform the pathogenesis of AKI in critically ill patients are urgently needed, in both research and ultimately clinical settings. Renal contrast-enhanced ultrasonography (CEUS) and multiparametric MRI appear to be the most promising imaging techniques for exploring the pathophysiological mechanisms involved in AKI., Recent Findings: CEUS and MRI can be used to noninvasively and safely evaluate renal macrocirculation and microcirculation and oxygenation in critical ill patients. These techniques show that a decrease in renal blood flow, particularly cortical blood flow, may be observed in septic AKI and may contribute to its development. MRI may be a valuable method to quantify long-term renal damage after AKI that cannot currently be detected using standard clinical approaches., Summary: CEUS and multiparametric renal MRI are promising imaging techniques but more evidence is needed to show how they can first be more widely used in a research setting to test key hypotheses about the pathophysiology and recovery of AKI, and then ultimately be adopted in clinical practice to guide patient management.

Aim: Tissue hypoxia is an early key feature of acute kidney injury. Assessment of renal oxygenation using magnetic resonance imaging (MRI) markers T 2 and T 2 * enables insights into renal pathophysiology. This assessment can be confounded by changes in the blood and tubular volume fractions, occurring upon pathological insults. These changes are mirrored by changes in kidney size (KS). Here, we used dynamic MRI to monitor KS for physiological interpretation of T 2 * and T 2 changes in acute pathophysiological scenarios., Methods: KS was determined from T 2 *, T 2 mapping in rats. Six interventions that acutely alter renal tissue oxygenation were performed directly within the scanner, including interventions that change the blood and/or tubular volume. A biophysical model was used to estimate changes in O 2 saturation of hemoglobin from changes in T 2 * and KS., Results: Upon aortic occlusion KS decreased; this correlated with a decrease in T 2 *, T 2 . Upon renal vein occlusion KS increased; this negatively correlated with a decrease in T 2 *, T 2 . Upon simultaneous occlusion of both vessels KS remained unchanged; there was no correlation with decreased T 2 *, T 2 . Hypoxemia induced mild reductions in KS and T 2 *, T 2 . Administration of an X-ray contrast medium induced sustained KS increase, with an initial increase in T 2 *, T 2 followed by a decrease. Furosemide caused T 2 *, T 2 elevation and a minor increase in KS. Model calculations yielded physiologically plausible calibration ratios for T 2 *., Conclusion: Monitoring KS allows physiological interpretation of acute renal oxygenation changes obtained by T 2 *, T 2 . KS monitoring should accompany MRI-oximetry, for new insights into renal pathophysiology and swift translation into human studies., (© 2022 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)

Competing Interests: Conflicts of Interest: See Disclosures at the end of the article.

Acute kidney injury (AKI) is a serious renal emergency that is often underdiagnosed and associated with high mortality rates. Early diagnosis of AKI is crucial to improve patient prognosis and reduce healthcare costs. In this study, a paper-based colloidal gold multiplex vertical flow assay was developed for rapid detection of three AKI biomarkers, namely, NGAL, CysC, and RBP4, in a single test kit. In this system, specific capture antibodies were pre-immobilized on the sensing membrane at four spatially isolated immunoreactive sites. Gold nanoparticles were conjugated with detection antibodies as the colorimetrical labels. The resultant images could be read out qualitatively by the naked eyes or quantitatively by a smartphone-based readout device. Three AKI biomarkers could be simultaneously detected in 10–15 min. The detection sensitivity and specificity for clinical serum samples collected from 25 patients with AKI and 25 healthy individuals were determined as 92% and 88%. This vertical flow assay platform is easy to use, rapid, and low cost. It is a promising diagnostic tool for multiplex detection of disease biomarkers at point of care. [Display omitted] • A multiplex colorimetric vertical flow assay was developed by using wax-printed sensing membrane. • Three acute kidney injury biomarkers could be simultaneously detected in 10–15 min. • A miniaturized smartphone-based readout device was developed for result imaging. • Clinical samples were tested by this system with a good accuracy. [ABSTRACT FROM AUTHOR]

Since their introduction into clinical practice a decade ago, immune checkpoint inhibitors (ICIs) have had an overwhelming impact on cancer treatment. Use of these agents in oncology continues to grow; however, the increased use of these agents has been associated with a parallel increase in ICI-associated immune-related adverse events, which can affect virtually any organ, including the kidneys. ICI-associated acute kidney injury (ICI-AKI) occurs in 2-5% of patients treated with ICIs. Its occurrence can have important consequences, including the temporary or permanent discontinuation of ICIs or other concomitant anticancer therapies and the need for prolonged treatment with corticosteroids. Various mechanisms have been proposed to underlie the development of ICI-AKI, including loss of tolerance to self-antigens, reactivation of drug-specific effector T cells, and the production of kidney-specific autoantibodies. ICI-AKI most commonly manifests as acute tubulo-interstitial nephritis on kidney biopsy and generally shows a favourable response to early initiation of corticosteroids, with complete or partial remission achieved in most patients. The evaluation of patients with suspected ICI-AKI requires careful diagnostic work-up and kidney biopsy for patients with moderate-to-severe ICI-AKI to ensure accurate diagnosis and inform appropriate treatment., (© 2022. Springer Nature Limited.)