Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up

Immune-related adverse events (irAEs) are a range of complications associated with the use of immune-checkpoint inhibitors (ICIs). Two major classes of ICIs widely used are Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed Cell death-1 (PD-1)/Programmed death-ligand 1 (PD-L1) inhibitors. High-grade irAEs are life-threatening and often cause a severe decline in performance status in such that patients do not qualify for any further anticancer treatments. It is difficult to generalize the evidence in the current literature on risk factors or biomarkers for the entire class of ICIs as the studies so far are either disease-specific (e.g., lung cancer or melanoma) or ICI agent-specific (e.g., pembrolizumab, ipilimumab) or irAE-specific (e.g., pneumonitis or gastritis). In this review, risk factors and biomarkers to consider before initiating or monitoring ICI are listed with a practical purpose in day-to-day practice. Risk factors are grouped into demographics and social history, medical history, and medication history, tumor-specific and agent-specific risk factors. A higher risk of irAE is associated with age <60 years, high body mass index, women on CTLA4 and men on PD-1/PD-L1 agents, and chronic smokers. Patients with significant kidney (Stage IV-V), cardiac (heart failure, coronary artery disease, myocardial infarction, hypertension), and lung (asthma, pulmonary fibrosis, and chronic obstructive pulmonary disease) are at a higher risk of respective organ-specific irAEs. Pre-existing autoimmune disease and chronic use of certain drugs (proton pump inhibitors, diuretics, anti-inflammatory drugs) also increase the irAE-risk. Biomarkers are categorized into circulating blood counts, cytokines, autoantibodies, HLA genotypes, microRNA, gene expression profiling, and serum proteins. The blood counts and certain protein markers (albumin and thyroid-stimulating hormone) are readily accessible in current practice. High neutrophil-lymphocyte ratio, eosinophil/monocyte/lymphocyte counts; TSH and troponins at diagnosis and drop in the white count and lymphocyte count can predict irAE. Other biomarkers with limited evidence are cytokines, autoantibodies, HLA genotypes, microRNA, and gene expression profiling. With fast-expanding approvals for ICIs in various cancer types, knowledge on risk factors and biomarkers can help providers assess the irAE-risk of their patients. Prospective disease and agent-specific studies are needed to provide further insight on this essential aspect of ICI therapy.

https://www.frontiersin.org/articles/10.3389/fimmu.2022.779691/pdf

Risk Factors and Biomarkers for Immune-Related Adverse Events: A Practical Guide to Identifying High-Risk Patients and Rechallenging Immune Checkpoint Inhibitors

Carbon dots (CDs), comprising crystalline graphitized carbon cores and polymer surface groups, are currently attracting a lot of interest in biological fields owing to their fluorescent properties, high photostability, biocompatibility and low toxicity. In addition, the easy preparation and functionalization of CDs stimulate the development of CDs‐based composite materials with specific functions. Presently, the biological applications of CDs are growing at a remarkable speed, justifying the need for up‐to‐date review articles that capture recent progress in this blossoming field. In this review, breakthroughs in the synthesis, modification, optical properties, toxicology and biocatalytic platforms of CDs are described. Further, recent research related to bioimaging, biosensing, drug delivery, antibacterial, anticancer (photothermal therapy, photodynamic therapy and synergistic therapy) and antiviral therapies involving CDs are discussed in detail. Finally, a perspective on the prospects and challenges of CDs in the fields of biomedicine and biotechnology is provided.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/smsc.202200012

Carbon Dots in Bioimaging, Biosensing and Therapeutics: A Comprehensive Review

Background Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. Methods We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. Results ICPi-AKI occurred at a median of 16 weeks (IQR 8–32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3–10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. Conclusions Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

https://jitc.bmj.com/content/jitc/9/10/e003467.full.pdf

Acute kidney injury in patients treated with immune checkpoint inhibitors.

Background Immune checkpoint inhibitors (ICPi) are a novel and promising anti-cancer therapy There are limited data on the incidence, risk factors and outcomes of acute kidney injury (AKI) in patients receiving ICPi Methods We conducted a cohort study of patients receiving ICPi at our center between 2010 and 2017 via electronic health record The primary outcome was AKI (increase of >50% from baseline serum creatinine (sCr)) Risk factors for AKI were assessed using logistic regression Survival among those with and without AKI was compared using the Kaplan-Meier method Results Among 309 patients on ICPi, 51 (165%) developed AKI (Kidney Disease Improving Global Outcomes (KDIGO) stages 1: 53%, 2: 22%, 3: 25%) AKI was associated with other immune-related adverse events (IRAE) (OR 32, 95% CI 16 to 6; p Conclusion AKI is a common complication in patients receiving ICPi treatment The development of other IRAE and previous diagnosis of hypertension were associated with increased AKI risk AKI was not associated with worse survival Distinguishing kidney IRAE from other causes of AKI will present a frequent challenge to oncology and nephrology practitioners Kidney biopsy should be considered to characterize kidney lesions and guide potential therapy

https://jitc.bmj.com/content/jitc/8/1/e000467.full.pdf

Acute kidney injury associated with immune checkpoint inhibitor therapy: incidence, risk factors and outcomes.

The current treatment paradigm for muscle-invasive bladder cancer (MIBC) consists of cisplatin-based neoadjuvant chemotherapy followed by local definitive therapy, or local definitive therapy alone for cisplatin-ineligible patients. Given that MIBC has a high propensity for distant relapse and is a chemotherapy-sensitive disease, under-utilization of chemotherapy is associated with suboptimal cure rates. Cisplatin eligibility criteria are defined for patients with metastatic bladder cancer by the Galsky criteria, which include creatinine clearance ≥60 ml/min. However, consensus is still lacking regarding cisplatin eligibility criteria in the neoadjuvant, curative MIBC setting, which continues to represent a substantial barrier to the standardization of patient care and clinical trial design. Jiang and colleagues accordingly suggest an algorithm for assessing cisplatin eligibility in patients with MIBC. Instead of relying on an absolute renal function threshold, their algorithm emphasizes a multidisciplinary and patient-centred approach. They also propose mitigation strategies to minimize the risk of cisplatin-induced nephrotoxicity in selected patients with impaired renal function. This new framework is aimed at reducing the inappropriate exclusion of some patients from cisplatin-based neoadjuvant chemotherapy (which leads to under-treatment) and harmonizing clinical trial design, which could lead to improved overall outcomes in patients with MIBC. Many patients with muscle-invasive bladder cancer are currently excluded from cisplatin-based neoadjuvant chemotherapy owing to renal impairment. Here, Jiang and colleagues present an update on cisplatin-induced nephrotoxicity in muscle-invasive bladder cancer and highlight a multidisciplinary and patient-centred approach to treatment decision-making.

Defining cisplatin eligibility in patients with muscle-invasive bladder cancer.

Risk of Acute Kidney Injury After Hypertensive Disorders of Pregnancy: A Population-Based Cohort Study.

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Acute kidney injury associated with immune checkpoint inhibitor therapy: incidence, risk factors and outcomes.

Defining cisplatin eligibility in patients with muscle-invasive bladder cancer.

Risk of Acute Kidney Injury After Hypertensive Disorders of Pregnancy: A Population-Based Cohort Study.