External Validation of an Electronic Health Record-Based Diagnostic Model for Histological Acute Tubulointerstitial Nephritis.

BACKGROUND: Accurate diagnosis of acute tubulointerstitial nephritis (AIN) often requires a kidney biopsy. We previously developed a diagnostic statistical model for predicting biopsy-confirmed AIN by combining four laboratory tests after evaluating over 150 potential predictors from the electronic health record. Here, we validate this diagnostic model in two biopsy-based cohorts at Johns Hopkins Hospital (JHH) and Yale, which were geographically and temporally distinct from the development cohort, respectively. METHODS: We analyzed patients who underwent kidney biopsy at JHH and Yale University (2019-2023). We assessed discrimination (AUC) and calibration using previously derived model coefficients and recalibrated the model using an intercept correction factor that accounted for differences in baseline prevalence of AIN between development and validation cohorts. RESULTS: We included 1982 participants: 1454 at JHH and 528 at Yale. JHH (5%) and Yale (17%) had lower proportions of biopsies with AIN than the development set (23%). The AUC was 0.73 (0.66-0.79) at JHH and 0.73 (0.67-0.78) at Yale, similar to the development set (0.73 (0.64-0.81)). Calibration was imperfect in validation cohorts, particularly at JHH, but improved with application of an intercept correction factor. The model increased AUC of clinicians' prebiopsy suspicion for AIN by 0.10 to 0.77 (0.71-0.82). CONCLUSIONS: An AIN diagnostic model retained discrimination in two validation cohorts but needed recalibration to account for local AIN prevalence. The model improved clinicians' ability to predict AIN.

Early, Individualized Recommendations for Hospitalized Patients With Acute Kidney Injury: A Randomized Clinical Trial.

Importance: Acute kidney injury (AKI) is a common complication during hospitalization and is associated with adverse outcomes. Objective: To evaluate whether diagnostic and therapeutic recommendations sent by a kidney action team through the electronic health record improve outcomes among patients hospitalized with AKI compared with usual care. Design, Setting, and Participants: Randomized clinical trial conducted at 7 hospitals in 2 health systems: in New Haven, Bridgeport, New London, and Waterbury, Connecticut, and Westerly, Rhode Island; and in Baltimore, Maryland. Hospitalized patients with AKI were randomized between October 29, 2021, and February 8, 2024. Final follow-up occurred February 22, 2024. Intervention: An alert about AKI was sent to the kidney action team, consisting of a study physician and study pharmacist, which sent personalized recommendations through the electronic health record in 5 major categories (diagnostic testing, volume, potassium, acid base, and medications) within 1 hour of AKI detection. The note was immediately visible to anyone with access to the electronic health record. Randomization to the intervention or usual care occurred after the recommendations were generated, but the note was only delivered to clinicians of patients randomized to the intervention group. Main Outcomes and Measures: The primary outcome was a composite outcome consisting of AKI progression to a higher stage of AKI, dialysis, or mortality occurring while the patient remained hospitalized and within 14 days from randomization. Results: Of the 4003 patients randomized (median age, 72 years [IQR, 61-81 years), 1874 (47%) were female and 931 (23%) were Black patients. The kidney action team made 14 539 recommendations, with a median of 3 (IQR, 2-5) per patient. The primary outcome occurred in 19.8% of the intervention group and in 18.4% in the usual care group (difference, 1.4%, 95% CI, -1.1% to 3.8,% P = .28). Of 6 secondary outcomes, only 1 secondary outcome, rates of recommendation implementation, significantly differed between the 2 groups: 2459 of 7270 recommendations (33.8%) were implemented in the intervention group and 1766 of 7269 undelivered recommendations (24.3%) were implemented in the usual care group within 24 hours (difference, 9.5%; 95% CI, 8.1% to 11.0%). Conclusions and Relevance: Among patients hospitalized with AKI, recommendations from a kidney action team did not significantly reduce the composite outcome of worsening AKI stage, dialysis, or mortality, despite a higher rate of recommendation implementation in the intervention group than in the usual care group. Trial Registration: ClinicalTrials.gov Identifier: NCT04040296.

The ASSESS-AKI Study found urinary epidermal growth factor is associated with reduced risk of major adverse kidney events.

Biomarkers of tubular function such as epidermal growth factor (EGF) may improve prognostication of participants at highest risk for chronic kidney disease (CKD) after hospitalization. To examine this, we measured urinary EGF (uEGF) from samples collected in the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) Study, a multi-center, prospective, observational cohort of hospitalized participants with and without AKI. Cox proportional hazards regression was used to investigate the association of uEGF/Cr at hospitalization, three months post-discharge, and the change between these time points with major adverse kidney events (MAKE): CKD incidence, progression, or development of kidney failure. Clinical findings were paired with mechanistic studies comparing relative Egf expression in mouse models of kidney atrophy or repair after ischemia-reperfusion injury. MAKE was observed in 20% of 1,509 participants over 4.3 years of follow-up. Each 2-fold higher level of uEGF/Cr at three months was associated with decreased risk of MAKE (adjusted hazards ratio 0.46, 95% confidence interval: 0.39-0.55). Participants with the highest increase in uEGF/Cr from hospitalization to three-month follow-up had a lower risk of MAKE (adjusted hazards ratio 0.52; 95% confidence interval: 0.36-0.74) compared to those with the least change in uEGF/Cr. A model using uEGF/Cr at three months combined with clinical variables yielded moderate discrimination for MAKE (area under the curve 0.73; 95% confidence interval: 0.69-0.77) and strong discrimination for kidney failure at four years (area under the curve 0.96; 95% confidence interval: 0.92-1.00). Accelerated restoration of Egf expression in mice was seen in the model of adaptive repair after injury, compared to a model of progressive atrophy. Thus, urinary EGF/Cr may be a biomarker of distal tubular health, with higher concentrations and increased uEGF/Cr post-discharge independently associated with reduced risk of MAKE in hospitalized patients.

Epidemiology and Clinical Outcomes of Community-Acquired Acute Kidney Injury in the Emergency Department: A Multisite Retrospective Cohort Study.

RATIONALE & OBJECTIVE: The prevalence of community-acquired acute kidney injury (CA-AKI) in the United States and its clinical consequences are not well described. Our objective was to describe the epidemiology of CA-AKI and the associated clinical outcomes. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 178,927 encounters by 139,632 adults at 5 US emergency departments (EDs) between July 1, 2017, and December 31, 2022. PREDICTORS: CA-AKI identified using KDIGO (Kidney Disease: Improving Global Outcomes) serum creatinine (Scr)-based criteria. OUTCOMES: For encounters resulting in hospitalization, the in-hospital trajectory of AKI severity, dialysis initiation, intensive care unit (ICU) admission, and death. For all encounters, occurrence over 180 days of hospitalization, ICU admission, new or progressive chronic kidney disease, dialysis initiation, and death. ANALYTICAL APPROACH: Multivariable logistic regression analysis to test the association between CA-AKI and measured outcomes. RESULTS: For all encounters, 10.4% of patients met the criteria for any stage of AKI on arrival to the ED. 16.6% of patients admitted to the hospital from the ED had CA-AKI on arrival to the ED. The likelihood of AKI recovery was inversely related to CA-AKI stage on arrival to the ED. Among encounters for hospitalized patients, CA-AKI was associated with in-hospital dialysis initiation (OR, 6.2; 95% CI, 5.1-7.5), ICU admission (OR, 1.9; 95% CI, 1.7-2.0), and death (OR, 2.2; 95% CI, 2.0-2.5) compared with patients without CA-AKI. Among all encounters, CA-AKI was associated with new or progressive chronic kidney disease (OR, 6.0; 95% CI, 5.6-6.4), dialysis initiation (OR, 5.1; 95% CI, 4.5-5.7), subsequent hospitalization (OR, 1.1; 95% CI, 1.1-1.2) including ICU admission (OR, 1.2; 95% CI, 1.1-1.4), and death (OR, 1.6; 95% CI, 1.5-1.7) during the subsequent 180 days. LIMITATIONS: Residual confounding. Study implemented at a single university-based health system. Potential selection bias related to exclusion of patients without an available baseline Scr measurement. Potential ascertainment bias related to limited repeat Scr data during follow-up after an ED visit. CONCLUSIONS: CA-AKI is a common and important entity that is associated with serious adverse clinical consequences during the 6-month period after diagnosis. PLAIN-LANGUAGE SUMMARY: Acute kidney injury (AKI) is a condition characterized by a rapid decline in kidney function. There are many causes of AKI, but few studies have examined how often AKI is already present when patients first arrive to an emergency department seeking medical attention for any reason. We analyzed approximately 175,000 visits to Johns Hopkins emergency departments and found that AKI is common on presentation to the emergency department and that patients with AKI have increased risks of hospitalization, intensive care unit admission, development of chronic kidney disease, requirement of dialysis, and death in the first 6 months after diagnosis. AKI is an important condition for health care professionals to recognize and is associated with serious adverse outcomes.

Evaluation of Plasma Biomarkers to Predict Major Adverse Kidney Events in Hospitalized Patients With COVID-19.

RATIONALE & OBJECTIVE: Patients hospitalized with COVID-19 are at increased risk for major adverse kidney events (MAKE). We sought to identify plasma biomarkers predictive of MAKE in patients hospitalized with COVID-19. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: A total of 576 patients hospitalized with COVID-19 between March 2020 and January 2021 across 3 academic medical centers. EXPOSURE: Twenty-six plasma biomarkers of injury, inflammation, and repair from first available blood samples collected during hospitalization. OUTCOME: MAKE, defined as KDIGO stage 3 acute kidney injury (AKI), dialysis-requiring AKI, or mortality up to 60 days. ANALYTICAL APPROACH: Cox proportional hazards regression to associate biomarker level with MAKE. We additionally applied the least absolute shrinkage and selection operator (LASSO) and random forest regression for prediction modeling and estimated model discrimination with time-varying C index. RESULTS: The median length of stay for COVID-19 hospitalization was 9 (IQR, 5-16) days. In total, 95 patients (16%) experienced MAKE. Each 1 SD increase in soluble tumor necrosis factor receptor 1 (sTNFR1) and sTNFR2 was significantly associated with an increased risk of MAKE (adjusted HR [AHR], 2.30 [95% CI, 1.86-2.85], and AHR, 2.26 [95% CI, 1.73-2.95], respectively). The C index of sTNFR1 alone was 0.80 (95% CI, 0.78-0.84), and the C index of sTNFR2 was 0.81 (95% CI, 0.77-0.84). LASSO and random forest regression modeling using all biomarkers yielded C indexes of 0.86 (95% CI, 0.83-0.89) and 0.84 (95% CI, 0.78-0.91), respectively. LIMITATIONS: No control group of hospitalized patients without COVID-19. CONCLUSIONS: We found that sTNFR1 and sTNFR2 are independently associated with MAKE in patients hospitalized with COVID-19 and can both also serve as predictors for adverse kidney outcomes. PLAIN-LANGUAGE SUMMARY: Patients hospitalized with COVID-19 are at increased risk for long-term adverse health outcomes, but not all patients suffer long-term kidney dysfunction. Identification of patients with COVID-19 who are at high risk for adverse kidney events may have important implications in terms of nephrology follow-up and patient counseling. In this study, we found that the plasma biomarkers soluble tumor necrosis factor receptor 1 (sTNFR1) and sTNFR2 measured in hospitalized patients with COVID-19 were associated with a greater risk of adverse kidney outcomes. Along with clinical variables previously shown to predict adverse kidney events in patients with COVID-19, both sTNFR1 and sTNFR2 are also strong predictors of adverse kidney outcomes.

Prognostic Significance of Urinary Biomarkers in Patients Hospitalized With COVID-19.

RATIONALE & OBJECTIVE: Acute kidney injury (AKI) is common in patients with coronavirus disease 2019 (COVID-19) and associated with poor outcomes. Urinary biomarkers have been associated with adverse kidney outcomes in other settings and may provide additional prognostic information in patients with COVID-19. We investigated the association between urinary biomarkers and adverse kidney outcomes among patients hospitalized with COVID-19. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Patients hospitalized with COVID-19 (n=153) at 2 academic medical centers between April and June 2020. EXPOSURE: 19 urinary biomarkers of injury, inflammation, and repair. OUTCOME: Composite of KDIGO (Kidney Disease: Improving Global Outcomes) stage 3 AKI, requirement for dialysis, or death within 60 days of hospital admission. We also compared various kidney biomarker levels in the setting of COVID-19 versus other common AKI settings. ANALYTICAL APPROACH: Time-varying Cox proportional hazards regression to associate biomarker level with composite outcome. RESULTS: Out of 153 patients, 24 (15.7%) experienced the primary outcome. Twofold higher levels of neutrophil gelatinase-associated lipocalin (NGAL) (HR, 1.34 [95% CI, 1.14-1.57]), monocyte chemoattractant protein (MCP-1) (HR, 1.42 [95% CI, 1.09-1.84]), and kidney injury molecule 1 (KIM-1) (HR, 2.03 [95% CI, 1.38-2.99]) were associated with highest risk of sustaining primary composite outcome. Higher epidermal growth factor (EGF) levels were associated with a lower risk of the primary outcome (HR, 0.61 [95% CI, 0.47-0.79]). Individual biomarkers provided moderate discrimination and biomarker combinations improved discrimination for the primary outcome. The degree of kidney injury by biomarker level in COVID-19 was comparable to other settings of clinical AKI. There was evidence of subclinical AKI in COVID-19 patients based on elevated injury biomarker level in patients without clinical AKI defined by serum creatinine. LIMITATIONS: Small sample size with low number of composite outcome events. CONCLUSIONS: Urinary biomarkers are associated with adverse kidney outcomes in patients hospitalized with COVID-19 and may provide valuable information to monitor kidney disease progression and recovery.

Overview of acute kidney manifestations and management of patients with COVID-19.

Since the start of the COVID-19 pandemic, several manifestations of kidney involvement associated with infection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have been described, including proteinuria, hematuria, and acute kidney injury. A growing body of literature has explored the risk factors and pathogenesis of COVID-19-associated acute kidney injury (AKI), including direct and indirect mechanisms, as well as early postdischarge outcomes that may result from various manifestations of kidney involvement. In this review, we explore the current state of knowledge of the epidemiology of COVID-19-associated AKI, potential mechanisms and pathogenesis of AKI, and various management strategies for patients in the acute setting. We highlight how kidney replacement therapy for patients with COVID-19-associated AKI has been affected by the increasing demand for dialysis and how the postacute management of patients, including outpatient follow-up, is vitally important. We also review what is presently known about long-term kidney outcomes after the initial recovery from COVID-19. We provide some guidance as to the management of patients hospitalized with COVID-19 who are at risk for AKI as well as for future clinical research in the setting of COVID-19 and the significance of early identification of patients at highest risk for adverse kidney outcomes.

Results from the TRIBE-AKI Study found associations between post-operative blood biomarkers and risk of chronic kidney disease after cardiac surgery.

Patients undergoing cardiac surgery are placed under intense physiologic stress. Blood and urine biomarkers measured peri-operatively may help identify patients at higher risk for adverse long-term kidney outcomes.We sought to determine independent associations of various biomarkers with development or progression of chronic kidney disease (CKD) following cardiac surgery. In this sub-study of the prospective cohort -TRIBE-AKI Study, we evaluated 613 adult patients undergoing cardiac surgery in Canada in our primary analysis and tested the association of 40 blood and urinary biomarkers with the primary composite outcome of CKD incidence or progression. In those with baseline estimated glomerular filtration rate (eGFR) over 60 mL/min/1.73m2, we defined CKD incidence as a 25% reduction in eGFR and an eGFR under 60. In those with baseline eGFR under 60 mL/min/1.73m2, we defined CKD progression as a 50% reduction in eGFR or eGFR under 15. Results were evaluated in a replication cohort of 310 patients from one study site in the United States. Over a median follow-up of 5.6 years, 172 patients developed the primary outcome. Each log increase in basic fibroblast growth factor (adjusted hazard ratio 1.52 [95% confidence interval 1.19, 1.93]), Kidney Injury Molecule-1 (1.51 [0.98, 2.32]), N-terminal pro-B-type natriuretic peptide (1.19 [1.01, 1.41]), and tumor necrosis factor receptor 1 (1.75 [1.18, 2.59]) were associated with outcome after adjustment for demographic factors, serum creatinine, and albuminuria. Similar results were noted in the replication cohort. Although there was no interaction by acute kidney injury in continuous analysis, mortality was higher in the no acute kidney injury group by biomarker tertile. Thus, elevated post-operative levels of blood biomarkers following cardiac surgery were independently associated with the development of CKD. These biomarkers can provide additional value in evaluating CKD incidence and progression after cardiac surgery.

Rationale and design of the Kidney Precision Medicine Project.

Chronic kidney disease (CKD) and acute kidney injury (AKI) are common, heterogeneous, and morbid diseases. Mechanistic characterization of CKD and AKI in patients may facilitate a precision-medicine approach to prevention, diagnosis, and treatment. The Kidney Precision Medicine Project aims to ethically and safely obtain kidney biopsies from participants with CKD or AKI, create a reference kidney atlas, and characterize disease subgroups to stratify patients based on molecular features of disease, clinical characteristics, and associated outcomes. An additional aim is to identify critical cells, pathways, and targets for novel therapies and preventive strategies. This project is a multicenter prospective cohort study of adults with CKD or AKI who undergo a protocol kidney biopsy for research purposes. This investigation focuses on kidney diseases that are most prevalent and therefore substantially burden the public health, including CKD attributed to diabetes or hypertension and AKI attributed to ischemic and toxic injuries. Reference kidney tissues (for example, living-donor kidney biopsies) will also be evaluated. Traditional and digital pathology will be combined with transcriptomic, proteomic, and metabolomic analysis of the kidney tissue as well as deep clinical phenotyping for supervised and unsupervised subgroup analysis and systems biology analysis. Participants will be followed prospectively for 10 years to ascertain clinical outcomes. Cell types, locations, and functions will be characterized in health and disease in an open, searchable, online kidney tissue atlas. All data from the Kidney Precision Medicine Project will be made readily available for broad use by scientists, clinicians, and patients.

High-Sensitivity Cardiac Troponin, Natriuretic Peptide, and Long-Term Risk of Acute Kidney Injury: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Cardiac markers such as high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B natriuretic peptide (NTproBNP) are predictors of developing acute kidney injury (AKI) during hospitalization for surgery or revascularization. However, their associations with the long-term risk of AKI in the general population are uncharacterized. METHODS: We conducted a prospective cohort study in 10 669 participants of the Atherosclerosis Risk in Communities Study (visit 4, 1996-1998, mean age, 63 years, 56% female, 22% black race) to examine the association of plasma concentrations of hs-cTnT and NTproBNP with the incident hospitalization with AKI. We used multivariable Cox regression analysis to estimate hazard ratios (HRs). RESULTS: During follow-up, 1907 participants had an incident hospitalization with AKI. Participants with higher concentrations of hs-cTnT had a higher risk of hospitalization with AKI in a graded fashion (adjusted HR, 1.88 [95%CI , 1.59-2.21] for ≥14 ng/L, 1.36 [1.18-1.57] for 9-13 ng/L, and 1.16 [1.03-1.30] for 5-8 ng/L compared to <5 ng/L). The graded association was also observed for NTproBNP (HR, 2.27 [1.93-2.68] for ≥272.7 pg/mL, 1.67 [1.45-1.93] for 142.4-272.6 pg/mL, and 1.31 [1.17-1.47] for 64.0-142.3 pg/mL compared to <64.0 pg/mL). The addition of hs-cTnT and NTproBNP to a model with established predictors significantly improved 10-year risk prediction for hospitalization with AKI (Δc-statistic, 0.015 [95%CI, 0.006-0.024]). CONCLUSIONS: In middle-aged to older black and white adults in the community, higher concentrations of hs-cTnT and NTproBNP were robustly associated with an increased risk of hospitalization with AKI. These results suggest the usefulness of hs-cTnT and NT-proBNP to identify people at risk of AKI in the general population.

Higher Prevalence of Concurrent Thrombocytopenia in Patients Receiving Continuous Renal Replacement Therapy in the Cardiac Intensive Care Unit.

INTRODUCTION: Thrombocytopenia (TCP) is a common finding in patients receiving continuous renal replacement therapy (CRRT). OBJECTIVE: The purpose of this study was to assess the nature of TCP in patients receiving CRRT. METHODS: This is a single-center case-control observational study of 795 patients involving over 166,950 h of delivered CRRT at Johns Hopkins Hospital. Concurrent TCP in patients receiving CRRT was defined as a decrease in platelet count of ≥50% any time within 72 h of initiation of CRRT with strict exclusion criteria. RESULTS: There was a higher incidence of TCP in the cardiac intensive care unit (CICU) (22.5%) compared to medical ICU (MICU) (13.1%). Using logistic regression, the odds of developing concurrent TCP in patients receiving CRRT was 2.46 (95% CI 1.32-3.57, p < 0.05) times higher in the CICU compared with the MICU. There was no difference in the incidence of severe or profound TCP or timing of acute TCP between the CICU and MICU. CONCLUSION: Safe delivery of dialysis care in the ICU is paramount and creating awareness of potential risks such as concurrent TCP in patients receiving CRRT should be part of this care.

Serum magnesium, bone-mineral metabolism markers and their interactions with kidney function on subsequent risk of peripheral artery disease: the Atherosclerosis Risk in Communities Study.

BACKGROUND: Few studies have investigated the association of magnesium levels with incident peripheral artery disease (PAD) despite emerging evidence of magnesium contributing to vascular calcification. Moreover, no data are available on whether the magnesium-PAD relationship is independent of or modified by kidney function. METHODS: A cohort of 11 839 participants free of PAD in the Atherosclerosis Risk in Communities Study at Visit 2 (1990-92) was studied. We investigated the association of serum magnesium and other bone-mineral metabolism markers [calcium, phosphorus, intact parathyroid hormone (iPTH) and intact fibroblast growth factor-23] with incident PAD using multivariable Cox proportional hazards regression. RESULTS: Over a median of 23 years, there were 471 cases of incident PAD. The hazard ratio for incident PAD in Quartile 1 (<1.5 mEq/L) versus Quartile 4 (>1.7 mEq/L) of magnesium was 1.96 (95% confidence interval 1.40-2.74) after adjustment for potential confounders. Lower magnesium levels were associated with greater incidence of PAD, particularly in those with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (n = 11 606). In contrast, the association was largely flat in those with eGFR <60 mL/min/1.73 m2 (n = 233) with P-for-interaction 0.03. Among bone-mineral metabolism markers, only higher iPTH showed an interaction with kidney function (P-for-interaction 0.01) and iPTH >65 pg/mL was significantly related to PAD only in those with eGFR <60 mL/min/1.73 m2. CONCLUSIONS: Lower magnesium was independently associated with incident PAD, but this association was significantly weaker in those with reduced kidney function. In contrast, higher iPTH levels were particularly related to PAD risk in this clinical population.

Early Prediction of Acute Kidney Injury in the Emergency Department With Machine-Learning Methods Applied to Electronic Health Record Data.

STUDY OBJECTIVE: Acute kidney injury occurs commonly and is a leading cause of prolonged hospitalization, development and progression of chronic kidney disease, and death. Early acute kidney injury treatment can improve outcomes. However, current decision support is not able to detect patients at the highest risk of developing acute kidney injury. We analyzed routinely collected emergency department (ED) data and developed prediction models with capacity for early identification of ED patients at high risk for acute kidney injury. METHODS: A multisite, retrospective, cross-sectional study was performed at 3 EDs between January 2014 and July 2017. All adult ED visits in which patients were hospitalized and serum creatinine level was measured both on arrival and again with 72 hours were included. We built machine-learning-based classifiers that rely on vital signs, chief complaints, medical history and active medical visits, and laboratory results to predict the development of acute kidney injury stage 1 and 2 in the next 24 to 72 hours, according to creatinine-based international consensus criteria. Predictive performance was evaluated out of sample by Monte Carlo cross validation. RESULTS: The final cohort included 91,258 visits by 59,792 unique patients. Seventy-two-hour incidence of acute kidney injury was 7.9% for stages greater than or equal to 1 and 1.0% for stages greater than or equal to 2. The area under the receiver operating characteristic curve for acute kidney injury prediction ranged from 0.81 (95% confidence interval 0.80 to 0.82) to 0.74 (95% confidence interval 0.74 to 0.75), with a median time from ED arrival to prediction of 1.7 hours (interquartile range 1.3 to 2.5 hours). CONCLUSION: Machine learning applied to routinely collected ED data identified ED patients at high risk for acute kidney injury up to 72 hours before they met diagnostic criteria. Further prospective evaluation is necessary.

An unusual cause of metabolic alkalosis: hiding in plain sight.

BACKGROUND: Sodium bicarbonate, in the form of baking soda, is widely used as a home remedy, and as an additive for personal and household cleaning products. Its toxicity has previously been reported following oral ingestion in the setting of dyspepsia. However, its use as a non-ingested agent, like a toothpaste additive, has not been reported as a potential cause of toxicity. CASE PRESENTATION: We are reporting a case of an 80-year-old woman who presented with chronic metabolic alkalosis and hypokalemia secondary to exogenous alkali exposure from baking soda as a toothpaste additive, which might have represented an underreported ingestion of the substance. CONCLUSIONS: Considering that one teaspoon of baking soda provides approximately 59 m-equivalents (mEq) of bicarbonate, specific questioning on its general use should be pursued in similar cases of chloride resistant metabolic alkalosis.

Additional prognostic value of toe-brachial index beyond ankle-brachial index in hemodialysis patients.

BACKGROUND: Ankle-brachial index (ABI), the first-line diagnostic test for peripheral artery disease, can be falsely elevated when ankle arteries are incompressible, showing a J-shaped association with mortality. In this situation, toe-brachial index (TBI) is the recommended test. However, whether TBI provides additional prognostic information beyond ABI in patients on hemodialysis is unknown. METHODS: In this retrospective cohort study of 247 Japanese prevalent hemodialysis patients (mean age 66.8 [SD 11.6] years), we evaluated mortality (116 deaths over a median follow-up of 5.2 years) related to quartiles of ABI and TBI, as well as three categories of low ABI (≤0.9), normal/high ABI (> 0.9) + low TBI (≤0.6), and normal/high ABI + normal TBI (> 0.6) using multivariable Cox models. RESULTS: ABI showed a J-shaped association with mortality (adjusted hazard ratio 2.72 [95% CI, 1.52-4.88] in the lowest quartile and 1.59 [95% CI, 0.87-2.90] in the highest quartile vs. the second highest). Lower TBI showed a potentially dose-response association with mortality (e.g., adjusted hazard ratios 2.63 [95% CI, 1.36-5.12] and 2.89 [95% CI, 1.49-5.61] in the lowest two quartiles vs. the highest). When three categories by both ABI and TBI were analyzed, those with low ABI (≤0.9) experienced the highest risk followed by normal/high ABI (> 0.9) + low TBI (≤0.6). Among patients with normal/high ABI (> 0.9), the increased mortality risk in individuals with low TBI (≤0.6) compared to those with normal TBI (> 0.6) were significant (adjusted hazard ratio 1.84 [95% CI, 1.12-3.02]). CONCLUSIONS: Lower TBI was independently associated with mortality in patients on hemodialysis and has the potential to classify mortality risk in patients with normal/high ABI. Our results support the importance of evaluating TBI in addition to ABI in this clinical population.

The COVID-19 nephrology compendium: AKI, CKD, ESKD and transplantation.

The pandemic of coronavirus disease 2019 (CoVID-19) has been an unprecedented period. The disease afflicts multiple organ systems, with acute kidney injury (AKI) a major complication in seriously ill patients. The incidence of AKI in patients with CoVID-19 is variable across numerous international studies, but the high incidence of AKI and its associated worse outcomes in the critical care setting are a consistent finding. A multitude of patterns and mechanisms of AKI have been elucidated, and novel strategies to address shortage of renal replacement therapy equipment have been implemented. The disease also has had consequences on longitudinal management of patients with chronic kidney disease and end stage kidney disease. Kidney transplant recipients may be especially susceptible to CoVID-19 as a result of immunosuppression, with preliminary studies demonstrating high mortality rates. Increased surveillance of disease with low threshold for testing and adjustment of immunosuppression regimen during acute periods of illness have been recommended.

Assessing the health of the nephron in acute kidney injury: biomarkers of kidney function and injury.

PURPOSE OF REVIEW: Serum creatinine and urine output continue to be the mainstays of diagnosis of acute kidney injury, though both of these measures have significant limitations, especially in acutely hospitalized patients. Biomarkers in both blood and urine have been studied extensively in the research setting and are on the verge of clinical practice to improve diagnosis of AKI. RECENT FINDINGS: Blood and urine biomarkers can be localized to specific areas or functions within the nephron. Biomarkers can help to characterize glomerular or tubular function; glomerular, tubular, or interstitial injury; inflammation; or repair. Further, biomarkers can improve diagnosis of AKI in various clinical settings including acute interstitial nephritis, acute tubular injury, and hepatorenal syndrome, and cardiorenal syndrome. SUMMARY: Biomarkers are becoming more prevalent in both research and getting close to clinical use. Both blood and urine biomarkers can help to localize impairment in nephron health by either location or function within the nephron and among various causes of AKI.

Indoxyl sulfate is associated with mortality after AKI - more evidence needed!

Patients who develop acute kidney injury (AKI) have significantly higher short-term outcomes including in-hospital mortality. The development of AKI has been associated with long-term consequences including progression to chronic kidney disease (CKD) and higher rates of cardiovascular disease (CVD) and mortality. In recent years there has been a growing push for the discovery of novel methods to diagnose AKI at earlier stages, and for an improvement in risk stratification and prognosis following AKI.Wang and colleagues assessed the association of total serum indoxyl sulfate (IS) levels, a protein bound uremic toxin, with 90-day mortality after hospital-acquired AKI (HA-AKI). These authors found that serum IS levels were significantly elevated in patients with HA-AKI (2.74 ± 0.75 µg/mL) compared to healthy subjects (1.73 ± 0.11 µg/ml, P < 0.001) and critically ill patients (2.46 ± 0.35 µg/ml, P = 0.016).The mechanisms of this relationship remain unclear, with a limited understanding of cause-specific mortality associated with either the high or low-IS group. One limitation of this current study is an understanding of the acceptable or expected higher level in IS during episodes of AKI. IS levels remained persistently elevated at day 7 compared to ß2-microglobulin and serum creatinine which were both lower at 7 days. It is unclear, however, if levels of ß2-microglobulin and serum creatinine were lower for other reasons, such as if any patients with AKI required dialysis.This work provides an important addition to the field of AKI research, specifically in the evaluation of readily measurable biomarkers and outcomes after AKI. Moving forward, further validation in studies of acute kidney injury are needed to develop a better understanding of IS levels at the time of AKI diagnosis and trends during the course of AKI.

Predictors of Renal Outcomes in Sclerotic Class Anti-Neutrophil Cytoplasmic Antibody Glomerulonephritis.

BACKGROUND: The prognostic value of the anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis (GN) classification has been demonstrated in several cohorts with sclerotic class having the worst renal outcome. Relevant published data on factors predicting outcomes in sclerotic ANCA GN is limited. METHODS: Sclerotic ANCA GN patients were recruited from 5 centers worldwide for this retrospective cohort study. We describe the clinical characteristics of this cohort and evaluate predictors of 1-year glomerular filtration rate (GFR) and end-stage renal disease (ESRD). Kidney function at 12 months as measured by Modification of Diet in Renal Disease estimated GFR (eGFR) was modeled by simple and multiple linear regression analyses. We used Cox proportional hazards regression modeling to evaluate ESRD-free survival. RESULTS: Of the 50 patients, 92% were Caucasian and 60% male with a mean age of 61 years. While 72% had renal limited disease, 82% were MPO ANCA positive. Kidney biopsies contained a median of 20 (interquartile range [IQR] 15-34) glomeruli with 96% showing moderate to severe interstitial fibrosis. Overall, 96% of patients received immunosuppressive drug therapy and 16% received plasmapheresis. Treatment response was achieved in all but 1 patient. The median (IQR) eGFR at entry was 14.5 (9-19) mL/min/1.73 m2. Over a median (IQR) follow-up of 33.5 (17-82) months, 26 patients reached ESRD. Ten patients died with 6 of the deaths occurring within the first year of diagnosis. The hazard of progression to ESRD was significantly higher in those with lower GFR at study entry (p = 0.003) and with higher degree of tubular atrophy (p = 0.043). CONCLUSIONS: Renal recovery is rare among sclerotic ANCA GN patients requiring dialysis at entry and 12% of patients died in the first year. Entry GFR and tubular atrophy were significant predictors of GFR at 12 months and renal survival in patients with sclerotic class ANCA GN.