Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns.

The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) updates the KDIGO 2012 guideline and has been developed with patient partners, clinicians, and researchers around the world, using robust methodology. This update, based on a substantially broader base of evidence than has previously been available, reflects an exciting time in nephrology. New therapies and strategies have been tested in large and diverse populations that help to inform care; however, this guideline is not intended for people receiving dialysis nor those who have a kidney transplant. The document is sensitive to international considerations, CKD across the lifespan, and discusses special considerations in implementation. The scope includes chapters dedicated to the evaluation and risk assessment of people with CKD, management to delay CKD progression and its complications, medication management and drug stewardship in CKD, and optimal models of CKD care. Treatment approaches and actionable guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence and the strength of recommendations which followed the "Grading of Recommendations Assessment, Development, and Evaluation" (GRADE) approach. The limitations of the evidence are discussed. The guideline also provides practice points, which serve to direct clinical care or activities for which a systematic review was not conducted, and it includes useful infographics and describes an important research agenda for the future. It targets a broad audience of people with CKD and their healthcare, while being mindful of implications for policy and payment.

Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus Nephritis.

The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Glomerular Diseases was published in 2021. Since then, the pace of drug development for glomerular diseases has accelerated, due in large part to rapidly accumulating insights into disease pathogenesis from genetic and molecular studies of afflicted patients. To keep the Glomerular Diseases Guideline as current as possible, KDIGO made a commitment to the nephrology community to provide periodic updates, based on new developments for each disease. After the 2021 guideline was published, two novel drugs received regulatory approval for the management of lupus nephritis, leading to the first KDIGO guideline update. Herein, an executive summary of the most important guideline changes from the Lupus Nephritis chapter is provided as a quick reference.

Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated Vasculitis.

In 2021, the Kidney Disease: Improving Global Outcomes (KDIGO) Guideline for the Management of Glomerular Diseases was published. KDIGO is committed to providing the nephrology community with periodic updates, based on new developments for each disease. For patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), avacopan received regulatory approval in late 2021, leading to this KDIGO guideline update. In addition, the evidence supporting a lower-dose glucocorticoid induction regimen or even complete replacement of glucocorticoids has become stronger. Herein, an executive summary of the most important guideline changes from the AAV chapter is provided as a quick reference.

Low-Dose Continuous Kidney Replacement Therapy and Mortality in Critically Ill Patients With Acute Kidney Injury: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: Continuous kidney replacement therapy (CKRT) is preferred when available for hemodynamically unstable acute kidney injury (AKI) patients in the intensive care unit (ICU). The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend a delivered CKRT dose of 20-25mL/kg/h; however, in Japan the doses are typically below this recommendation due to government health insurance system restrictions. This study investigated the association between mortality and dose of CKRT. STUDY DESIGN: Single-center retrospective cohort study. SETTING & PARTICIPANTS: Critically ill patients with AKI treated with CKRT at a tertiary Japanese university hospital between January 1, 2012, and December 31, 2021. EXPOSURE: Delivered CKRT doses below or above the median. OUTCOME: 90-day mortality after CKRT initiation. ANALYTICAL APPROACH: Multivariable Cox regression analysis and Kaplan-Meier analysis. RESULTS: The study population consisted of 494 patients. The median age was 72 years, and 309 patients (62.6%) were men. Acute tubular injury was the leading cause of AKI, accounting for 81.8%. The median delivered CKRT dose was 13.2mL/kg/h. Among the study participants, 456 (92.3%) received delivered CKRT doses below 20mL/kg/h, and 204 (41.3%) died within 90 days after CKRT initiation. Multivariable Cox regression analysis revealed increased mortality in the below-median group (HR, 1.73 [95% CI, 1.19-2.51], P=0.004). Additionally, a significant, inverse, nonlinear association between 90-day mortality and delivered CKRT dose was observed using delivered CKRT dose as a continuous variable. LIMITATIONS: Single-center, retrospective, observational study. CONCLUSIONS: A lower delivered CKRT dose was independently associated with higher 90-day mortality among critically ill patients who mostly received dosing below the current KDIGO recommendations. PLAIN-LANGUAGE SUMMARY: The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend delivering a continuous kidney replacement therapy (CKRT) dose of 20-25mL/kg/h. However, it is not clear if it is safe to use delivered CKRT doses below this recommendation. In this study, over 90% of the patients received CKRT with a delivered dose below the KDIGO recommendation. We divided these patients into 2 groups based on the median delivered CKRT dose. Our findings show that a delivered CKRT dose below the median was associated with increased risk of death within 90 days. These findings show that a lower delivered CKRT dose was independently associated with higher 90-day mortality among critically ill patients who mostly received dosing below current KDIGO recommendations.

Management of adult patients with podocytopathies: an update from the ERA Immunonephrology Working Group.

The histopathological lesions, minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are entities without immune complex deposits which can cause podocyte injury, thus are frequently grouped under the umbrella of podocytopathies. Whether MCD and FSGS may represent a spectrum of the same disease remains a matter of conjecture. Both frequently require repeated high-dose glucocorticoid therapy with alternative immunosuppressive treatments reserved for relapsing or resistant cases and response rates are variable. There is an unmet need to identify patients who should receive immunosuppressive therapies as opposed to those who would benefit from supportive strategies. Therapeutic trials focusing on MCD are scarce, and the evidence used for the 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guideline for the management of glomerular diseases largely stems from observational and pediatric trials. In FSGS, the differentiation between primary forms and those with underlying genetic variants or secondary forms further complicates trial design. This article provides a perspective of the Immunonephrology Working Group (IWG) of the European Renal Association (ERA) and discusses the KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases focusing on the management of MCD and primary forms of FSGS in the context of recently published evidence, with a special emphasis on the role of rituximab, cyclophosphamide, supportive treatment options and ongoing clinical trials in the field.

Acute kidney injury in neonates with hypoxic ischemic encephalopathy based on serum creatinine decline compared to KDIGO criteria.

BACKGROUND: Neonates with hypoxic ischemic encephalopathy receiving therapeutic hypothermia (HIE + TH) are at risk for acute kidney injury (AKI). The standardized Kidney Disease Improving Global Outcomes (KDIGO) criteria identifies AKI based on a rise in serum creatinine (SCr) or reduced urine output. This definition is challenging to apply in neonates given the physiologic decline in SCr during the first week of life. Gupta et al. proposed alternative neonatal criteria centered on rate of SCr decline. This study aimed to compare the rate of AKI based on KDIGO and Gupta in neonates with HIE and to examine associations with mortality and morbidity. METHODS: A retrospective review was performed of neonates with moderate to severe HIE + TH from 2008 to 2020 at a single center. AKI was assessed in the first 7 days after birth by KDIGO and Gupta criteria. Mortality, brain MRI severity of injury, length of stay, and duration of respiratory support were compared between AKI groups. RESULTS: Among 225 neonates, 64 (28%) met KDIGO, 69 (31%) neonates met Gupta but not KDIGO, and 92 (41%) did not meet either definition. Both KDIGO-AKI and GuptaOnly-AKI groups had an increased risk of the composite mortality and/or moderate/severe brain MRI injury along with longer length of stay and prolonged duration of respiratory support compared to those without AKI. CONCLUSIONS: AKI in neonates with HIE + TH was common and varied by definition. The Gupta definition based on rate of SCr decline identified additional neonates not captured by KDIGO criteria who are at increased risk for adverse outcomes. Incorporating the rate of SCr decline into the neonatal AKI definition may increase identification of clinically relevant kidney injury in neonates with HIE + TH.

Continuous Urine Output-Based Alert Identifies Cardiac Surgery-associated Acute Kidney Injury Earlier Than Serum Creatinine: A Prospective and Retrospective Observational Study.

OBJECTIVE(S): Acute kidney injury (AKI) is defined and staged by reduced urine output (UO) and increased serum creatinine (SCr). UO is typically measured manually and documented in the electronic health record, making early and reliable detection of oliguria-based AKI and electronic data extraction challenging. The authors investigated the diagnostic performance of continuous UO, enabled by active drain line clearance-based alerts (Accuryn AKI Alert), compared with AKI stage 2 SCr criteria and their associations with length of stay, need for continuous renal replacement therapy, and 30-day mortality. DESIGN: This study was a prospective and retrospective observational study. SETTING: Nine tertiary centers participated. PARTICIPANTS: Cardiac surgery patients were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 522 patients were analyzed. AKI stages 1, 2, and 3 were diagnosed in 32.18%, 30.46%, and 3.64% of patients based on UO, compared with 33.72%, 4.60%, and 3.26% of patients using SCr, respectively. Continuous UO-based alerts diagnosed stage ≥1 AKI 33.6 (IQR =15.43, 95.68) hours before stage ≥2 identified by SCr criteria. A SCr-based diagnosis of AKI stage ≥2 has been designated a Hospital Harm by the Centers for Medicare & Medicaid Services. Using this criterion as a benchmark, AKI alerts had a discriminative power of 0.78. The AKI Alert for stage 1 was significantly associated with increased intensive care unit and hospital length of stay and continuous renal replacement therapy, and stage ≥2 alerts were associated with mortality. CONCLUSIONS: AKI Alert, based on continuous UO and enabled by active drain line clearance, detected AKI stages 1 and 2 before SCr criteria. Early AKI detection allows for early kidney optimization, potentially improving patient outcomes.

The 2021 KDIGO blood pressure target and the progression of chronic kidney disease: Findings from KNOW-CKD.

BACKGROUND: The 2021 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for the management of blood pressure (BP) in chronic kidney disease (CKD) recommends a target systolic BP of <120 mmHg as this target can provide cardiovascular benefits. However, it remains unclear whether implementing the new BP target could improve kidney outcomes. METHODS: The association between the 2021 KDIGO BP target and CKD progression was examined and compared with the 2012 KDIGO BP target among 1724 participants included in the KoreaN Cohort Study for Outcomes in Patients With CKD. The main exposure was the BP status categorized according to the 2012 or 2021 KDIGO guideline: (1) controlled within the 2021 target, (2) controlled within the 2012 target only, and (3) above both targets. The primary outcome was a composite kidney outcome of ≥50% decline in the estimated glomerular filtration rate from baseline or the initiation of kidney replacement therapy during the follow-up period. RESULTS: Composite kidney outcomes occurred in 650 (37.7%) participants during the 8078 person-years of follow-up (median, 4.9 years). The incidence rates of this outcome were 55, 66.5, and 116.4 per 1000 person-years in BP controlled within the 2021 and 2012 KDIGO targets, and BP above both targets, respectively. In the multivariable cause-specific hazard model, hazard ratios for the composite outcome were 0.76 (95% confidence interval (CI), 0.60-0.95) for BP controlled within the 2021 target and 1.36 (95% CI, 1.13-1.64) for BP above both targets, compared with BP controlled within 2012 target only. CONCLUSION: The newly lowered BP target by the 2021 KDIGO guideline was associated with improved kidney outcome compared with BP target by the 2012 KDIGO guideline.

KDOQI US Commentary on the 2021 KDIGO Clinical Practice Guideline for the Management of Glomerular Diseases.

The KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases represents the first update to this set of recommendations since the initial set of KDIGO guideline recommendations was published in 2012. The pace of growth in our molecular understanding of glomerular disease has quickened and a number of newer immunosuppressive and targeted therapies have been introduced since the original set of guideline recommendations, making such an update necessary. Despite these updates, many areas of controversy remain. In addition, further updates since the publication of KDIGO 2021 have occurred which this guideline does not encompass. With this commentary, the KDOQI work group has generated a chapter-by-chapter companion opinion article that provides commentary specific to the implementation of the KDIGO 2021 guideline in the United States.

Association of eGFR and mortality with use of a joint model: results of a nationwide study in Iceland.

OBJECTIVES: Prior studies on the association of estimated glomerular filtration rate (eGFR) and mortality have failed to include methods to account for repeated eGFR determinations. The aim of this study was to estimate the association between eGFR and mortality in the general population in Iceland employing a joint model. METHODS: We obtained all serum creatinine and urine protein measurements from all clinical laboratories in Iceland in the years 2008-16. Clinical data were obtained from nationwide electronic medical records. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation and categorized as follows: 0-29, 30-44, 45-59, 60-74, 75-89, 90-104 and >104 mL/min/1.73 m2. A multiple imputation method was used to account for missing urine protein data. A joint model was used to assess risk of all-cause mortality. RESULTS: We obtained 2 120 147 creatinine values for 218 437 individuals, of whom 84 364 (39%) had proteinuria measurements available. Median age was 46 (range 18-106) years and 47% were men. Proteinuria associated with increased risk of death for all eGFR categories in persons of all ages. In persons ≤65 years, the lowest risk was observed for eGFR of 75-89 mL/min/1.73 m2 without proteinuria. For persons aged >65 years, the lowest risk was observed for eGFR of 60-74 mL/min/1.73 m2 without proteinuria. eGFR of 45-59 mL/min/1.73 m2 without proteinuria did not associate with increased mortality risk in this age group. eGFR >104 mL/min/1.73 m2 associated with increased mortality. CONCLUSIONS: These results lend further support to the use of age-adapted eGFR thresholds for defining chronic kidney disease. Very high eGFR needs to be studied in more detail with regard to mortality.

HbA1c and beyond.

The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on Diabetes Management in Chronic Kidney Disease from 2020 comes at an opportune time when progress in diabetes technology and therapeutics offers new options to manage the large population of patients with diabetes and chronic kidney disease (CKD) at high risk of poor health outcomes. Management of haemoglobin A1c is important in diabetes, but an enlarging base of evidence from large clinical trials has demonstrated important new treatments offering organ protection and not just glucose management, such as sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists. It is the ambition that the guideline can help to optimize the clinical care of people with diabetes and CKD by integrating new options with existing management strategies based on high-quality evidence. Here, the focus has been on comprehensive care of patients with diabetes and CKD, glycaemic monitoring and targets, antihyperglycaemic therapies in patients with diabetes and CKD, and new developments since the guideline was published offering new opportunities and a wider target population for the new interventions.

Hypothetical intervention of targeted systolic blood pressure control of < 120 mmHg on renal prognosis for persons with stage 3-4 chronic kidney disease: an application of parametric g-formula using health checkup data in Japan.

BACKGROUND: The revised KDIGO guidelines recommend maintaining systolic blood pressure (sBP) < 120 mmHg in patients with chronic kidney disease (CKD), based on cardiovascular and survival benefits. However, the renal benefit of this strategy remains less clear. METHODS: We used data of routine health checkups in Japan. Persons whose estimated glomerular filtration rate (eGFR) was < 60 mL/min/1.73 m2 in 2015 without end-stage disease were followed until 2020. We estimated the 5-year benefit of hypothetical targeted sBP control using parametric g-formula modeling, accounting for both time-fixed and time-varying confounding variables. Four sensitivity analyses, including analysis using a marginal structural model (MSM) and positive control outcome analysis, were also done. RESULTS: We enrolled 28,972 persons with CKD (median age: 54 years, male: 69%, baseline eGFR [median]: 56 mL/min/1.73m2). As compared with the natural course without a targeted intervention, there was no renoprotective effect of targeted sBP control, with a 5-year difference in eGFR of 0.65 mL/min/1.73 m2 (95% confidence interval - 0.42 to 1.65 mL/min/1.73 m2). MSM analysis found a similar result. In contrast, the positive control analysis using the cardiovascular outcome showed that targeted sBP control would reduce the cardiovascular disease incidence by 6.0% over 5 years. CONCLUSIONS: A targeted sBP control strategy maintaining < 120 mmHg may not yield a renoprotective effect for patients with stage 3-4 CKD, although it was expected to offer a cardiovascular benefit. Future research may be warranted in higher-risk populations, such as elderly people or those with more advanced kidney disease.

Acute kidney injury after infant cardiac surgery: a comparison of pRIFLE, KDIGO, and pROCK definitions.

BACKGROUND: KDIGO and pRIFLE classifications are commonly used in pediatric acute kidney injury (AKI). As a novel AKI definition, pROCK considered the high variability of serum creatinine in children. This study aimed to compare the above three definitions for AKI in infants undergoing cardiac surgery. METHODS: We analyzed a clinical cohort of 413 infants undergoing cardiac surgery. AKI was defined and staged according to pRIFLE, KDIGO, and pROCK, respectively. Incidence differences and diagnostic agreement across definitions were assessed. The association between postoperative outcomes and AKI by each definition was investigated. RESULTS: Postoperative AKI was identified in 185 (44.8%), 160 (38.7%), and 77 (18.6%) patients according to pRIFLE, KDIGO, and pROCK, respectively. The agreement between pRIFLE and KDIGO was almost perfect (κ = 0.88), while there was only a slight agreement between pROCK and them. AKI by pROCK was independently associated with adverse outcomes (p = 0.003) and prolonged mechanical ventilation (p = 0.002). CONCLUSIONS: There were considerable differences in AKI incidence and staging among definitions. Compared with pRIFLE and KDIGO, AKI defined by pROCK was significantly reduced and better associated with postoperative adverse outcomes.

The renal angina index accurately predicts low risk of developing severe acute kidney injury among children admitted to a low-resource pediatric intensive care unit.

BACKGROUND: Acute kidney injury (AKI) increases the risk of adverse outcomes. The renal angina index (RAI) has previously been used to predict patients at risk of developing severe AKI (sAKI). METHOD: This single-centre prospective observational study aimed to assess the prevalence of sAKI in PICU as the primary outcome and the duration of mechanical ventilation and PICU stay, RRT need, and mortality as secondary outcomes. The utility of the RAI in predicting day 3 sAKI was also assessed. We enrolled 122 patients aged 1 month to 16 years whose baseline characteristics were collected via questionnaire. RAI was calculated on day 0 with a score of ≥8 being considered positive. sAKI was defined as KDIGO stages 2 and 3. RESULTS: sAKI prevalence was 14.8% and its development was associated with longer duration of mechanical ventilation (p = 0.001) and higher mortality (p = 0.011). A positive Day 0 RAI predicted day 3 sAKI with sensitivity 55.6%, specificity 85.6%, PPV 40.0%, NPV 91.8%, and AUC of 0.77. Exclusion of children older than 5 years improved RAI performance (sensitivity 72.7%, specificity 88.0%, PPV 57.1%, NPV 93.6%, AUC 0.80). A modified RAI based on local AKI risk factors had equivalent performance to RAI (Z - score 0.78 (CI -0.077-0.033), p = 0.435) with sensitivity 72.2%, specificity 80.8%, PPV 39.4%, NPV 94.4% and AUC 0.80. CONCLUSION: The RAI can be an effective tool in ruling out sAKI in patients and a modification of RAI based on population-based risk factors improves the test's sensitivity and NPV.

Effect of dapagliflozin on kidney and cardiovascular outcomes by baseline KDIGO risk categories: a post hoc analysis of the DAPA-CKD trial.

AIMS/HYPOTHESIS: In the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial, dapagliflozin reduced the risks of progressive kidney disease, hospitalised heart failure or cardiovascular death, and death from all causes in patients with chronic kidney disease (CKD) with or without type 2 diabetes. Patients with more severe CKD are at higher risk of kidney failure, cardiovascular events and all-cause mortality. In this post hoc analysis, we assessed the efficacy and safety of dapagliflozin according to baseline Kidney Disease Improving Global Outcomes (KDIGO) risk categories. METHODS: DAPA-CKD was a double-blind, placebo-controlled trial that randomised patients with an eGFR of 25-75 ml min-1 [1.73 m]-2 and urinary albumin/creatinine ratio (UACR) of ≥22.6 and <565.0 mg/mmol (200-5000 mg/g) to dapagliflozin 10 mg/day or placebo. The primary endpoint was a composite of ≥50% reduction in eGFR, end-stage kidney disease (ESKD), and death from a kidney or cardiovascular cause. Secondary endpoints included a kidney composite (≥50% reduction in eGFR, ESKD and death from a kidney cause), a cardiovascular composite (heart failure hospitalisation or cardiovascular death), and death from all causes. We used Cox proportional hazards regression analyses to assess relative and absolute effects of dapagliflozin across KDIGO risk categories. RESULTS: Of the 4304 participants in the DAPA-CKD study, 619 (14.4%) were moderately high risk, 1349 (31.3%) were high risk and 2336 (54.3%) were very high risk when categorised by KDIGO risk categories at baseline. Dapagliflozin reduced the hazard of the primary composite (HR 0.61; 95% CI 0.51, 0.72) and secondary endpoints consistently across KDIGO risk categories (all p for interaction >0.09). Absolute risk reductions for the primary outcome were also consistent irrespective of KDIGO risk category (p for interaction 0.26). Analysing patients with and without type 2 diabetes separately, the relative risk reduction with dapagliflozin in terms of the primary outcome was consistent across subgroups of KDIGO risk categories. The relative frequencies of adverse events and serious adverse events were also similar across KDIGO risk categories. CONCLUSION/INTERPRETATIONS: The consistent benefits of dapagliflozin on kidney and cardiovascular outcomes across KDIGO risk categories indicate that dapagliflozin is efficacious and safe across a wide spectrum of kidney disease severity. TRIAL REGISTRATION: ClinicalTrials.gov NCT03036150. FUNDING: The study was funded by AstraZeneca.

Executive Summary of the KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease.

Infection with the hepatitis C virus (HCV) has adverse liver, kidney, and cardiovascular consequences in patients with chronic kidney disease (CKD), including those on dialysis therapy or with a kidney transplant. Since the publication of the Kidney Disease: Improving Global Outcomes (KDIGO) HCV Guideline in 2018, advances in HCV management, particularly in the field of antiviral therapy and treatment of HCV-associated glomerular diseases, coupled with increased usage of HCV-positive kidney grafts, have prompted a reexamination of the 2018 guideline. As a result, the Work Group performed a comprehensive review and revised the 2018 guidance. This Executive Summary highlights key aspects of the updated guideline recommendations for 3 chapters: Chapter 2: Treatment of HCV infection in patients with CKD; Chapter 4: Management of HCV-infected patients before and after kidney transplantation; and Chapter 5: Diagnosis and management of kidney diseases associated with HCV infection.

Executive summary of the KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease: an update based on rapidly emerging new evidence.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (CKD) represents a focused update of the KDIGO 2020 guideline on the topic. The guideline targets a broad audience of clinicians treating people with diabetes and CKD. Topic areas for which recommendations are updated based on new evidence include Chapter 1: Comprehensive care in patients with diabetes and CKD and Chapter 4: Glucose-lowering therapies in patients with type 2 diabetes (T2D) and CKD. The content of previous chapters on Glycemic monitoring and targets in patients with diabetes and CKD (Chapter 2), Lifestyle interventions in patients with diabetes and CKD (Chapter 3), and Approaches to management of patients with diabetes and CKD (Chapter 5) has been deemed current and was not changed. This guideline update was developed according to an explicit process of evidence review and appraisal. Treatment approaches and guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence, and the strength of recommendations followed the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. Limitations of the evidence are discussed, and areas for which additional research is needed are presented.

Developing an AKI Consensus Definition for Database Research: Findings From a Scoping Review and Expert Opinion Using a Delphi Process.

RATIONALE & OBJECTIVE: The KDIGO (Kidney Disease: Improving Global Outcomes) definition of acute kidney injury (AKI) is frequently used in studies to examine the epidemiology of AKI. This definition is variably interpreted and applied to routinely collected health care data. The aim of this study was to examine this variation and to achieve consensus in how AKI should be defined for research using routinely collected health care data. SOURCES OF EVIDENCE AND STUDY DESIGN: Scoping review via searching Medline and EMBASE for studies using health care data to examine AKI by using the KDIGO creatinine-based definition. An international panel of experts formed to participate in a modified Delphi process to attempt to generate consensus about how AKI should be defined when using routinely collected laboratory data. CHARTING METHODS AND ANALYTICAL APPROACH: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) extension for scoping reviews was followed. For the Delphi process, 2 rounds of questions were distributed via internet-based questionnaires to all participants with a prespecified cutoff of 75% agreement used to define consensus. RESULTS: The scoping review found 174 studies that met the inclusion criteria. The KDIGO definition was inconsistently applied, and the methods for application were poorly described. We found 58 (33%) of papers did not provide a definition of how the baseline creatinine value was determined, and only 34 (20%) defined recovery of kidney function. Of 55 invitees to the Delphi process, 35 respondents participated in round 1, and 25 participated in round 2. Some consensus was achieved in areas related to how to define the baseline creatinine value, which patients should be excluded from analysis of routinely collected laboratory data, and how persistent chronic kidney disease or nonrecovery of AKI should be defined. LIMITATIONS: The Delphi panel members predominantly came from the United Kingdom, the United States, and Canada, and there were low response rates for some questions in round 1. CONCLUSIONS: The current methods for defining AKI using routinely collected data are inconsistent and poorly described in the available literature. Experts could not achieve consensus for many aspects of defining AKI and describing its sequelae. The KDIGO guidelines should be extended to include a standardized definition for how AKI should be defined when using routinely collected data.

Acute kidney injury in critical COVID-19: a multicenter cohort analysis in seven large hospitals in Belgium.

BACKGROUND: Acute kidney injury (AKI) has been reported as a frequent complication of critical COVID-19. We aimed to evaluate the occurrence of AKI and use of kidney replacement therapy (KRT) in critical COVID-19, to assess patient and kidney outcomes and risk factors for AKI and differences in outcome when the diagnosis of AKI is based on urine output (UO) or on serum creatinine (sCr). METHODS: Multicenter, retrospective cohort analysis of patients with critical COVID-19 in seven large hospitals in Belgium. AKI was defined according to KDIGO within 21 days after ICU admission. Multivariable logistic regression analysis was used to explore the risk factors for developing AKI and to assess the association between AKI and ICU mortality. RESULTS: Of 1286 patients, 85.1% had AKI, and KRT was used in 9.8%. Older age, obesity, a higher APACHE II score and use of mechanical ventilation at day 1 of ICU stay were associated with an increased risk for AKI. After multivariable adjustment, all AKI stages were associated with ICU mortality. AKI was based on sCr in 40.1% and UO in 81.5% of patients. All AKI stages based on sCr and AKI stage 3 based on UO were associated with ICU mortality. Persistent AKI was present in 88.6% and acute kidney disease (AKD) in 87.6%. Rapid reversal of AKI yielded a better prognosis compared to persistent AKI and AKD. Kidney recovery was observed in 47.4% of surviving AKI patients. CONCLUSIONS: Over 80% of critically ill COVID-19 patients had AKI. This was driven by the high occurrence rate of AKI defined by UO criteria. All AKI stages were associated with mortality (NCT04997915).

Early diagnosis of kidney injury in a paediatric population: a prospective cohort study (E-DRIP STUDY).

BACKGROUND: Renal Angina Index (RAI) is a bedside tool for risk stratification of patients to predict acute kidney injury (AKI). Kidney biomarkers are better indicators of real-time injury and give us lead time for diagnosing impending AKI. METHODS: We enrolled consecutive children aged 2 months-14 years admitted to a tertiary hospital in northern India over 2 years. RAI was calculated on day 0 (D0) and urinary (u) and plasma (p) neutrophil gelatinase-associated lipocalin (NGAL) were measured within 6 h of admission. Children were followed for the development of severe AKI on day 3 (D3) using Kidney Disease Improving Global Outcomes criteria to define and stage AKI. RESULTS: Of the 253 children enrolled and analysed, 44 (17.4%) developed D3-AKI (stage 1 in 52.2%, stage 2 in 20.5% and stage 3 in 27.3%). Renal angina (RAI ≥ 8) on D0 was present in 66.7% children who developed stage 2/3 D3-AKI vs. 43.5% in children who did not develop D3-AKI /stage 1 AKI (p = 0.065). Area under ROC (AUROC) curve for D0-RAI to predict D3-severe-AKI was 0.66 (95% CI, 0.55-0.77). AUROC curve for uNGAL and pNGAL to predict D3-severe-AKI was 0.62 (95% CI, 0.50-0.74) and 0.48 (95% CI, 0.35-0.61), respectively. The severe AKI group had greater requirement of ventilation and inotropic support with mortality being thrice higher compared to the non-AKI group. CONCLUSION: RAI ≥ 8 and uNGAL had a high negative predictive value but low sensitivity for predicting D3-severe-AKI. pNGAL had a poor predictive value for D3-severe-AKI. A higher resolution version of the Graphical abstract is available as Supplementary information.