Acute kidney injury (AKI) is a common complication in hospitalized patients and is associated with adverse short- and long-term outcomes. AKI is diagnosed by serum creatinine (SCr)-based consensus ...definitions that capture an abrupt decrease in glomerular filtration rate associated with AKI. However, SCr-based AKI definitions lack sensitivity and specificity for diagnosing structural kidney injury. Moreover, AKI is a heterogeneous condition consisting of distinct phenotypes based on its etiology, prognosis, and molecular pathways, and that may potentially require different therapies. SCr-based AKI definitions provide no information on these AKI phenotypes. This review highlights traditional and novel tools that overcome the limitations of SCr-based AKI definitions to improve AKI phenotyping.
Incomplete repair after acute kidney injury can lead to development of chronic kidney disease. To define the mechanism of this response, we compared mice subjected to identical unilateral ...ischemia-reperfusion kidney injury with either contralateral nephrectomy (where tubule repair predominates) or contralateral kidney intact (where tubule atrophy predominates). By day 14, the kidneys undergoing atrophy had more macrophages with higher expression of chemokines, correlating with a second wave of proinflammatory neutrophil and T cell recruitment accompanied by increased expression of tubular injury genes and a decreased proportion of differentiated tubules. Depletion of neutrophils and T cells after day 5 reduced tubular cell loss and associated kidney atrophy. In kidney biopsies from patients with acute kidney injury, T cell and neutrophil numbers negatively correlated with recovery of estimated glomerular filtration rate. Together, our findings demonstrate that macrophage persistence after injury promotes a T cell- and neutrophil-mediated proinflammatory milieu and progressive tubule damage.
Biomarkers of diverse pathophysiologic mechanisms may improve risk stratification for incident or progressive diabetic kidney disease (DKD) in persons with type 2 diabetes. To evaluate such ...biomarkers, we performed a nested case-control study (
=190 cases of incident DKD and 190 matched controls) and a prospective cohort study (
=1156) using banked baseline plasma samples from participants of randomized, controlled trials of early (ACCORD) and advanced (VA NEPHRON-D) DKD. We assessed the association and discrimination obtained with baseline levels of plasma TNF receptor-1 (TNFR-1), TNFR-2, and kidney injury molecule-1 (KIM-1) for the outcomes of incident DKD (ACCORD) and progressive DKD (VA-NEPHRON-D). At baseline, median concentrations of TNFR-1, TNFR-2, and KIM-1 were roughly two-fold higher in the advanced DKD population (NEPHRON-D) than in the early DKD population (ACCORD). In both cohorts, patients who reached the renal outcome had higher baseline levels than those who did not reach the outcome. Associations between doubling in TNFR-1, TNFR-2, and KIM-1 levels and risk of the renal outcomes were significant for both cohorts. Inclusion of these biomarkers in clinical models increased the area under the curve (SEM) for predicting the renal outcome from 0.68 (0.02) to 0.75 (0.02) in NEPHRON-D. Systematic review of the literature illustrated high consistency in the association between these biomarkers of inflammation and renal outcomes in DKD. In conclusion, TNFR-1, TNFR-2, and KIM-1 independently associated with higher risk of eGFR decline in persons with early or advanced DKD. Moreover, addition of these biomarkers to clinical prognostic models significantly improved discrimination for the renal outcome.
Drug-Induced Acute Interstitial Nephritis Moledina, Dennis G; Perazella, Mark A
Clinical journal of the American Society of Nephrology,
12/2017, Letnik:
12, Številka:
12
Journal Article
AbstractObjectiveTo determine whether electronic health record alerts for acute kidney injury would improve patient outcomes of mortality, dialysis, and progression of acute kidney ...injury.DesignDouble blinded, multicenter, parallel, randomized controlled trial.SettingSix hospitals (four teaching and two non-teaching) in the Yale New Haven Health System in Connecticut and Rhode Island, US, ranging from small community hospitals to large tertiary care centers.Participants6030 adult inpatients with acute kidney injury, as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) creatinine criteria.InterventionsAn electronic health record based “pop-up” alert for acute kidney injury with an associated acute kidney injury order set upon provider opening of the patient’s medical record.Main outcome measuresA composite of progression of acute kidney injury, receipt of dialysis, or death within 14 days of randomization. Prespecified secondary outcomes included outcomes at each hospital and frequency of various care practices for acute kidney injury.Results6030 patients were randomized over 22 months. The primary outcome occurred in 653 (21.3%) of 3059 patients with an alert and in 622 (20.9%) of 2971 patients receiving usual care (relative risk 1.02, 95% confidence interval 0.93 to 1.13, P=0.67). Analysis by each hospital showed worse outcomes in the two non-teaching hospitals (n=765, 13%), where alerts were associated with a higher risk of the primary outcome (relative risk 1.49, 95% confidence interval 1.12 to 1.98, P=0.006). More deaths occurred at these centers (15.6% in the alert group v 8.6% in the usual care group, P=0.003). Certain acute kidney injury care practices were increased in the alert group but did not appear to mediate these outcomes.ConclusionsAlerts did not reduce the risk of our primary outcome among patients in hospital with acute kidney injury. The heterogeneity of effect across clinical centers should lead to a re-evaluation of existing alerting systems for acute kidney injury.Trial registrationClinicalTrials.gov NCT02753751.
Toxic nephropathies are a clinically common group of disorders characterized by toxin-induced renal injury that can affect the glomerulus, vasculature, or tubulointerstitium. Various endogenous (eg, ...myoglobin, hemoglobin, monoclonal light chains, and lysozymes) and exogenous toxins (eg, therapeutic drugs, herbal medications, heavy metals, radiocontrast, intoxicants, and environmental exposures) have been implicated. The kidney’s primary role of metabolism and excretion of substances via glomerular filtration and tubular secretion increases its susceptibility to their adverse effects. The structure, dose, metabolic handling, and excretory pathway of the drug/toxin through the kidney determines its nephrotoxic risk. Patient characteristics that impact risk include genetic determinants of drug metabolism, transport and excretion, immune response genes, and comorbid conditions. Clinical manifestations depend on site and severity of renal injury. Toxin-induced tubulointerstitial injury often presents as a decline in renal function and/or solute transport defects and renal solute wasting. Injury is often reversible with limited toxin exposure; however, irreversible renal injury can occur with prolonged exposure. In this Core Curriculum, we will focus on discussing mechanisms of common toxin-induced tubulointerstitial renal injury and review their causes, clinical presentations, diagnosis, and management.
The diagnosis of acute kidney injury (AKI), which is currently defined as an increase in serum creatinine (Scr) concentration, provides little information on the condition’s actual cause. To improve ...phenotyping of AKI, many urinary biomarkers of tubular injury are being investigated. Because AKI cases are not frequently biopsied, the diagnostic accuracy of concentrations of Scr and urinary biomarkers for histologic acute tubular injury is unknown.
Cross-sectional analysis from multicenter prospective cohort.
Hospitalized deceased kidney donors on whom kidney biopsies were performed at the time of organ procurement for histologic evaluation.
(1) AKI diagnosed by change in Scr concentration during donor hospitalization and (2) concentrations of urinary biomarkers (neutrophil gelatinase-associated lipocalin NGAL, liver-type fatty acid-binding protein L-FABP, interleukin 18 IL-18, and kidney injury molecule 1 KIM-1) measured at organ procurement.
Histologic acute tubular injury.
Of 581 donors, 98 (17%) had mild acute tubular injury and 57 (10%) had severe acute tubular injury. Overall, Scr-based AKI had poor diagnostic performance for identifying histologic acute tubular injury and 49% of donors with severe acute tubular injury did not have AKI. The area under the receiver operating characteristic curve (AUROC) of change in Scr concentration for diagnosing severe acute tubular injury was 0.58 (95% CI, 0.49-0.67) and for any acute tubular injury was 0.52 (95% CI, 0.45-0.58). Compared with Scr concentration, NGAL concentration demonstrated higher AUROC for diagnosing both severe acute tubular injury (0.67; 95% CI, 0.60-0.74; P=0.03) and any acute tubular injury (0.60; 95% CI, 0.55-0.66; P=0.005). In donors who did not have Scr-based AKI, NGAL concentrations were higher with increasing severities of acute tubular injury (subclinical AKI). However, compared with Scr concentration, AUROCs for acute tubular injury diagnosis were not significantly higher for urinary L-FABP, IL-18, or KIM-1.
The spectrum of AKI cause in deceased donors may be different from that of a general hospitalized population.
Concentrations of Scr and kidney injury biomarkers (L-FABP, IL-18, and KIM-1) lack accuracy for diagnosing acute tubular injury in hospitalized deceased donors. Although urinary NGAL concentration had slightly higher discrimination for acute tubular injury than did Scr concentration, its overall AUROC was still modest.
False negative SARS-CoV-2 tests can lead to spread of infection in the inpatient setting to other patients and healthcare workers. However, the population of patients with COVID who are admitted with ...false negative testing is unstudied.
To characterize and develop a model to predict true SARS-CoV-2 infection among patients who initially test negative for COVID by PCR.
Retrospective cohort study.
Five hospitals within the Yale New Haven Health System between 3/10/2020 and 9/1/2020.
Adult patients who received diagnostic testing for SARS-CoV-2 virus within the first 96 hours of hospitalization.
We developed a logistic regression model from readily available electronic health record data to predict SARS-CoV-2 positivity in patients who were positive for COVID and those who were negative and never retested.
This model was applied to patients testing negative for SARS-CoV-2 who were retested within the first 96 hours of hospitalization. We evaluated the ability of the model to discriminate between patients who would subsequently retest negative and those who would subsequently retest positive.
We included 31,459 hospitalized adult patients; 2,666 of these patients tested positive for COVID and 3,511 initially tested negative for COVID and were retested. Of the patients who were retested, 61 (1.7%) had a subsequent positive COVID test. The model showed that higher age, vital sign abnormalities, and lower white blood cell count served as strong predictors for COVID positivity in these patients. The model had moderate performance to predict which patients would retest positive with a test set area under the receiver-operator characteristic (ROC) of 0.76 (95% CI 0.70-0.83). Using a cutpoint for our risk prediction model at the 90th percentile for probability, we were able to capture 35/61 (57%) of the patients who would retest positive. This cutpoint amounts to a number-needed-to-retest range between 15 and 77 patients.
We show that a pragmatic model can predict which patients should be retested for COVID. Further research is required to determine if this risk model can be applied prospectively in hospitalized patients to prevent the spread of SARS-CoV-2 infections.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The use of novel biomarkers of acute kidney injury (AKI) in clinical trials may help evaluate treatments for AKI. Here we explore potential applications of biomarkers in simulated clinical trials of ...AKI using data from the TRIBE-AKI multicenter, prospective cohort study of patients undergoing cardiac surgery. First, in a hypothetical trial of an effective therapy at the time of acute tubular necrosis to prevent kidney injury progression, use of an indirect kidney injury marker such as creatinine compared to a new direct biomarker of kidney injury reduces the proportion of true acute tubular necrosis cases enrolled. The result is a lower observed relative risk reduction with the therapy, and lower statistical power to detect a therapy effect at a given sample size. Second, the addition of AKI biomarkers (interleukin-18 and NGAL) to clinical risk factors as eligibility criteria for trial enrollment in early AKI has the potential to increase the proportion of patients who will experience AKI progression and reduce trial cost. Third, we examine AKI biomarkers as outcome measures for the purposes of identifying therapies that warrant further testing in larger, multicenter, multi-country trials. In the hypothetical trial of lower cardiopulmonary bypass time to reduce the risk of postoperative AKI, the sample size required to detect a reduction in AKI is lower if new biomarkers are used to define AKI rather than serum creatinine. Thus, incorporation of new biomarkers of AKI has the potential to increase statistical power, decrease the sample size, and lower the cost of AKI trials.
PDF
