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Acute kidney injury (AKI) is a frequent and serious complication in patients with cancer, associated not only with increased morbidity and mortality, but also with the interruption or modification of anticancer therapy. In critically ill patients with cancer, AKI arises from a complex interplay of cancer-related, treatment-related, and patient-related factors, with many patients requiring renal replacement therapy (RRT) and admission to the intensive care unit (ICU). This narrative review summarizes the etiology of AKI in patients with cancer and discusses the role of extracorporeal organ support (ECOS) therapies, with particular emphasis on continuous renal replacement therapy (CRRT). Understanding the underlying etiology of AKI in this patient population is essential for guiding treatment decisions, particularly when therapeutic plasma exchange, hemadsorption, or other extracorporeal modalities are considered which may directly target the pathophysiology driving organ dysfunction. Although observational data suggest that ECOS use may improve both short- and long-term outcomes, robust evidence demonstrating consistent benefit remains lacking. Furthermore, limited pharmacokinetic data for anticancer drugs in patients undergoing dialysis or RRT creates significant uncertainty regarding optimal dosing strategies. By providing a structured overview of extracorporeal organ support strategies in cancer-associated AKI, this review aims to support multidisciplinary decision-making and facilitate more individualized critical care for this high-risk population.

The sub-field of onco-nephrology has rapidly grown with the proliferation of highly effective cancer therapies and the remarkable improvement in patient survival. Conventional cytotoxic chemotherapy is a backbone of cancer therapy, often employed alone or with targeted agents and immunotherapies. However, beneficial anti-cancer effects are often complicated by nephrotoxicity, which includes acute and chronic kidney injury. While numerous conventional cytotoxic chemotherapy drugs are nephrotoxic, some of the most common offenders that clinicians encounter are cisplatin, ifosfamide, methotrexate, pemetrexed, gemcitabine, melphalan, and mitomycin C. They will be the focus of this review. This ADQI Consensus Conference Workgroup covered cytotoxic chemotherapy nephrotoxicity and reviewed several aspects of their adverse renal complications. Included are 1) epidemiology of each agent’s nephrotoxicity, 2) mechanisms of nephrotoxicity, 3) predisposing risk factors, 4) clinical manifestations of nephrotoxicity, 5) prevention and management of kidney injury, and 6) research agenda addressing knowledge gaps for the noted nephrotoxic cytotoxic chemotherapy.

This study aimed to compare a high (HBF) and low (LBF) bicarbonate (HCO ) replacement fluid over 96 h after continuous veno-venous hemofiltration (CVVH) initiation using regional citrate anticoagulation to determine which fluid achieved better acid-base balance. In this prospective, randomized, controlled, open-label, cross-over, single-center trial, patients were randomized to initially receive either LBF (22 mmol/l HCO ) or HBF (30 mmol/l HCO ) for 48 h (first phase), followed by changing to the other fluid for a further 48 h (second phase). Intracorporeal pH and HCO changes were analyzed by calculating the rates of levels outside the standard values (excursion rates). Generalized estimating equations were performed to estimate the odds ratios for at least one pH/HCO excursion. Time to normalization within the first phase for pH and HCO was assessed using Kaplan-Meier curves and log-rank tests. A total of 88 patients were included. The rates for at least one pH and HCO excursion were higher in patients treated with HBF compared to LBF (pH: first phase 52% vs. 41%; second phase 48% vs. 34%; HCO : first phase 68% vs. 43%; second phase 73% vs. 43%). Adjusted odds ratios were 1.78 (95% CI 1.12-2.82; p = 0.015) for pH and 3.60 (95% CI 2.16-5.99; p 

Acute kidney injury (AKI) is common in critically ill patients and associated with a high risk of mortality, chronic kidney disease (CKD) and cardiovascular morbidity. The risks are higher in patients with incomplete or no renal recovery. The purpose of this review is to summarize the current understanding of the mechanisms of renal recovery, list some key risk factors for nonrecovery and highlight knowledge gaps. Narrative review of key data in the literature. Recovery from AKI is an active process. When damage to the kidney is mild, full regeneration is possible; with extensive damage, fibrosis sets in. Current strategies to achieve renal recovery focus on identification of the mechanism of injury and minimizing further insults. Nephrotoxic exposures and various forms of dialytrauma impair recovery. The likelihood that repair will be maladaptive increases with age and extent/duration of injury. Return of glomerular filtration rate to pre-injury levels does not exclude nephron loss and development of CKD. Post-discharge follow-up of AKI survivors is important, but there are ongoing uncertainties and clinical practice is variable. Research is ongoing to determine the role of pharmacological interventions. The prognosis of AKI is critically tied to renal recovery, and there is great urgency to identify effective therapies.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection and where underlying circulatory, cellular, and metabolic abnormalities contribute to a greater risk of mortality than that posed by sepsis alone this may be considered septic shock where circulatory support is needed in the face of a raised lactate level. The main pillars of therapy remain source control and appropriate timely antibiotics, resuscitation where needed and adequate source control. However in the setting of organ failure further support may be needed. Here we discuss the potential benefits from removal of pathogens using available extracorporeal techniques. Although randomised controlled trials supporting such an approach are remin elusive this is due to change in the next few years with current studies being performed.Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection and where underlying circulatory, cellular, and metabolic abnormalities contribute to a greater risk of mortality than that posed by sepsis alone this may be considered septic shock where circulatory support is needed in the face of a raised lactate level. The main pillars of therapy remain source control and appropriate timely antibiotics, resuscitation where needed and adequate source control. However in the setting of organ failure further support may be needed. Here we discuss the potential benefits from removal of pathogens using available extracorporeal techniques. Although randomised controlled trials supporting such an approach are remin elusive this is due to change in the next few years with current studies being performed.

Ninety percent of all cancer deaths are due to metastatic disease. The majority of patients with metastatic disease are treated with systemic agents and/or radiotherapy, which can provide substantial benefit for many patients, prolong survival and improve symptoms. Patients with metastatic cancer are at risk for drug-related toxicity or disease-related complications leading to development of organ failure such as: rhabdomyolysis-associated AKI, liver failure and multi-organ failure often precipitated by endotoxinemia and sepsis. In cases of systemic hyperinflammatory response, mediated by cytokines, to specific treatment with CAR-T cell therapy or in sepsis with or without development of AKI we do not have an effective and specific target molecule oriented therapy. The predicted survival for cancer patients who develop secondary bacterial infection is decreased and it is only treated by the excessive use of antibiotics with the increased antibiotic resistance. Over the past few decades, numerous experimental and clinical studies have investigated the efficacy of extracorporeal blood purification technologies in the treatment of specific indications like in sepsis and septic shock. Thus far, these therapies have failed to demonstrate an improvement in survival when evaluated in randomized trials. In this review article, our goal is to show the possibility of using different hemoadsorbers in specific indications in patients with cancer-related complications, their reported effectiveness in certain indications listed in the text, and the possibility of applying it in cancer patients not only as a last-stand therapy but as well as preventing development of specific organ or multi-organ failure.Ninety percent of all cancer deaths are due to metastatic disease. The majority of patients with metastatic disease are treated with systemic agents and/or radiotherapy, which can provide substantial benefit for many patients, prolong survival and improve symptoms. Patients with metastatic cancer are at risk for drug-related toxicity or disease-related complications leading to development of organ failure such as: rhabdomyolysis-associated AKI, liver failure and multi-organ failure often precipitated by endotoxinemia and sepsis. In cases of systemic hyperinflammatory response, mediated by cytokines, to specific treatment with CAR-T cell therapy or in sepsis with or without development of AKI we do not have an effective and specific target molecule oriented therapy. The predicted survival for cancer patients who develop secondary bacterial infection is decreased and it is only treated by the excessive use of antibiotics with the increased antibiotic resistance. Over the past few decades, numerous experimental and clinical studies have investigated the efficacy of extracorporeal blood purification technologies in the treatment of specific indications like in sepsis and septic shock. Thus far, these therapies have failed to demonstrate an improvement in survival when evaluated in randomized trials. In this review article, our goal is to show the possibility of using different hemoadsorbers in specific indications in patients with cancer-related complications, their reported effectiveness in certain indications listed in the text, and the possibility of applying it in cancer patients not only as a last-stand therapy but as well as preventing development of specific organ or multi-organ failure.

Hypotension is a common cause of acute kidney injury (AKI), with strong associations between the duration and magnitude of hypotension seen across a range of situations including major surgery. However, it is less clear whether targeting higher intraoperative MAP results in lower rates of AKI. In a prespecified analysis of the Perioperative Ischemic Evaluation-3 (POISE-3) randomized controlled trial, this question is addressed for noncardiac major surgery. Despite an increase in cessation of antihypertensive medications and higher intraoperative mean arterial blood pressure in the intervention arm, no differences were seen in the rates of postoperative AKI. This commentary discusses the strengths and weaknesses of the trial, as well as providing some interpretation of results and their relevance to clinical practice.

Introduction. Novel urinary biomarkers, including Tissue Inhibitor Metallo-protease-2 and Insulin-like Growth Factor Binding Protein 7 ([TIMP-2]*[IGFBP7]), have been developed to identify patients at risk for acute kidney injury (AKI). We investigated the "real world" clinical utility of [TIMP-2]*[IGFBP7] in preventing AKI.Methods. We performed a prospective single-center quality improvement study of intensive care unit (ICU) patients at risk for severe (KDIGO stage 2 or 3) AKI. In the prospective cohort, ICU providers were allowed to order [TIMP-2]*[IGFBP7] for patients at their discretion, then offered AKI practice recommendations based on the result. Outcomes were compared to a historical cohort in which biomarker values were not reported to clinical teams.Results. There was no difference in 7-day progression to severe AKI between the prospective (n=116) and historical cohorts (n=63) when [TIMP-2]*[IGFBP7] & GE;0.3 (24(28%) vs 8(21%), p=0.38) despite more stage 1 AKI at time of biomarker measurement in the prospective cohort (58(67%) vs 9(23%), p

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. Several factors complicate the identification of effective interventions that can improve the outcomes of patients with acute kidney injury (AKI). Here, the authors discuss key design considerations for clinical trials in hospitalized patients with AKI, including the selection of adequate patient cohorts and study end points. Acute kidney injury (AKI) is a very heterogeneous syndrome; therefore, enrichment strategies are required to reduce heterogeneity within the study patient cohort and to reduce sample size. Several factors, including risk scores, biomarkers and clinical features, can be used for prognostic and predictive enrichment.Careful selection of end points is crucial for any trial. Different end points are required for phase II and phase III trials, and for prevention, attenuation and treatment trials.The occurrence of AKI is a key end point in prevention or attenuation trials and is mainly assessed based on current AKI definitions (based on serum creatinine and urine output) but biomarkers can be used as surrogate end points in phase II trials.Major adverse kidney events cannot be used in prevention trials, but different components in this composite end point should always be reported when used in treatment trials.The trajectory of AKI is an important outcome in intervention trials, because clinical measures or drugs might influence the course of AKI and subsequently influence the mortality rate.

Acute kidney injury (AKI), which is a common complication of acute illnesses, affects the health of individuals in community, acute care and post-acute care settings. Although the recognition, prevention and management of AKI has advanced over the past decades, its incidence and related morbidity, mortality and health care burden remain overwhelming. The rapid growth of digital technologies has provided a new platform to improve patient care, and reports show demonstrable benefits in care processes and, in some instances, in patient outcomes. However, despite great progress, the potential benefits of using digital technology to manage AKI has not yet been fully explored or implemented in clinical practice. Digital health studies in AKI have shown variable evidence of benefits, and the digital divide means that access to digital technologies is not equitable. Upstream research and development costs, limited stakeholder participation and acceptance, and poor scalability of digital health solutions have hindered their widespread implementation and use. Here, we provide recommendations from the Acute Disease Quality Initiative consensus meeting, which involved experts in adult and paediatric nephrology, critical care, pharmacy and data science, at which the use of digital health for risk prediction, prevention, identification and management of AKI and its consequences was discussed.

Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research.

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.

Postoperative AKI is a common complication of major surgery and is associated with significant morbidity and mortality. The Kidney Disease Improving Global Outcomes AKI definition allows consensus classification and identification of postoperative AKI through changes in serum creatinine and/or urine output. However, such conventional diagnostic criteria may be inaccurate in the postoperative period, suggesting a potential to refine diagnosis by application of novel diagnostic biomarkers. Risk factors for the development of postoperative AKI can be thought of in terms of preoperative, intraoperative, and postoperative factors and, as such, represent areas that may be targeted perioperatively to minimize the risk of AKI. The treatment of postoperative AKI remains predominantly supportive, although application of management bundles may translate into improved outcomes.

Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the prevention and management of COVID-19 AKI. The emergence of regional 'surges' in COVID-19 cases can limit hospital resources, including dialysis availability and supplies; thus, careful daily assessment of available resources is needed. In this Consensus Statement, the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI based on current literature. We also make recommendations for areas of future research, which are aimed at improving understanding of the underlying processes and improving outcomes for patients with COVID-19 AKI.

Although respiratory failure and hypoxaemia are the main manifestations of COVID-19, kidney involvement is also common. Available evidence supports a number of potential pathophysiological pathways through which acute kidney injury (AKI) can develop in the context of SARS-CoV-2 infection. Histopathological findings have highlighted both similarities and differences between AKI in patients with COVID-19 and in those with AKI in non-COVID-related sepsis. Acute tubular injury is common, although it is often mild, despite markedly reduced kidney function. Systemic haemodynamic instability very likely contributes to tubular injury. Despite descriptions of COVID-19 as a cytokine storm syndrome, levels of circulating cytokines are often lower in patients with COVID-19 than in patients with acute respiratory distress syndrome with causes other than COVID-19. Tissue inflammation and local immune cell infiltration have been repeatedly observed and might have a critical role in kidney injury, as might endothelial injury and microvascular thrombi. Findings of high viral load in patients who have died with AKI suggest a contribution of viral invasion in the kidneys, although the issue of renal tropism remains controversial. An impaired type I interferon response has also been reported in patients with severe COVID-19. In light of these observations, the potential pathophysiological mechanisms of COVID-19-associated AKI may provide insights into therapeutic strategies.

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) D concentrations in critically ill patients with and without moderate to severe AKI and explore the impact of renal recovery and parathyroid hormone (PTH). 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) D and plasma PTH concentrations for 5 days. Linear mixed model analysis and sensitivity analyses were performed. 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) D 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) D concentrations. Plasma PTH results were impacted by serum calcium and magnesium levels but not associated with 1,25(OH) D levels. Critically ill patients with moderate-to-severe AKI have significantly lower serum 1,25(OH) D 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) D 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.

Background A previous National Institute for Health and Care Research study [Harrison DA, Ferrando-Vivas P, Shahin J, Rowan KM. Ensuring comparisons of health-care providers are fair: development and validation of risk prediction models for critically ill patients. Health Serv Deliv Res 2015; 3 (41)] identified the need for more research to understand risk factors and consequences of critical care and subsequent outcomes. Objectives First, to improve risk models for adult general critical care by developing models for mortality at fixed time points and time-to-event outcomes, end-stage renal disease, type 2 diabetes, health-care utilisation and costs. Second, to improve risk models for cardiothoracic critical care by enhancing risk factor data and developing models for longer-term mortality. Third, to improve risk models for in-hospital cardiac arrest by enhancing risk factor data and developing models for longer-term mortality and critical care utilisation. Design Risk modelling study linking existing data. Setting NHS adult critical care units and acute hospitals in England. Participants Patients admitted to an adult critical care unit or experiencing an in-hospital cardiac arrest. Interventions None. Main outcome measures Mortality at hospital discharge, 30 days, 90 days and 1 year following critical care unit admission; mortality at 1 year following discharge from acute hospital; new diagnosis of end-stage renal disease or type 2 diabetes; hospital resource use and costs; return of spontaneous circulation sustained for > 20 minutes; survival to hospital discharge and 1 year; and length of stay in critical care following in-hospital cardiac arrest. Data sources Case Mix Programme, National Cardiac Arrest Audit, UK Renal Registry, National Diabetes Audit, National Adult Cardiac Surgery Audit, Hospital Episode Statistics and Office for National Statistics. Results Data were linked for 965,576 critical care admissions between 1 April 2009 and 31 March 2016, and 83,939 in-hospital cardiac arrests between 1 April 2011 and 31 March 2016. For admissions to adult critical care units, models for 30-day mortality had similar predictors and performance to those for hospital mortality and did not reduce heterogeneity. Models for longer-term outcomes reflected increasing importance of chronic over acute predictors. New models for end-stage renal disease and diabetes will allow benchmarking of critical care units against these important outcomes and identification of patients requiring enhanced follow-up. The strongest predictors of health-care costs were prior hospitalisation, prior dependency and chronic conditions. Adding pre- and intra-operative risk factors to models for cardiothoracic critical care gave little improvement in performance. Adding comorbidities to models for in-hospital cardiac arrest provided modest improvements but were of greater importance for longer-term outcomes. Limitations Delays in obtaining linked data resulted in the data used being 5 years old at the point of publication: models will already require recalibration. Conclusions Data linkage provided enhancements to the risk models underpinning national clinical audits in the form of additional predictors and novel outcomes measures. The new models developed in this report may assist in providing objective estimates of potential outcomes to patients and their families. Future work (1) Develop and test care pathways for recovery following critical illness targeted at those with the greatest need; (2) explore other relevant data sources for longer-term outcomes; (3) widen data linkage for resource use and costs to primary care, outpatient and emergency department data. Study registration This study is registered as NCT02454257. Funding details This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research ; Vol. 10, No. 39. See the NIHR Journals Library website for further project information.