Plasma biomarkers are associated with renal outcomes in individuals with APOL1 risk variants.

G1/G2 variants in the Apolipoprotein L1 (APOL1) gene are associated with end-stage renal disease (ESRD) in people with African ancestry. Plasma biomarkers may have utility for risk stratification in APOL1 high-risk individuals of African ancestry. To evaluate this, we measured tumor necrosis factor receptor 1/2 (TNFR1/2) and kidney injury molecule-1 (KIM1) in baseline plasma specimens from individuals of African ancestry with high-risk APOL1 genotype.

The prognostic importance of duration of AKI: a systematic review and meta-analysis.

Background: Acute kidney injury (AKI), as defined by peak increase in serum creatinine, is independently associated with increased risk of mortality and length of stay. Studies have suggested that the duration of AKI may be an important additional or independent prognostic marker of increased mortality in patients with AKI across clinical settings. We performed a systematic review and meta-analysis of published studies to assess the impact of duration of AKI on outcomes.

Urinary Biomarkers of Kidney Tubular Damage and Risk of Cardiovascular Disease and Mortality in Elders.

Rationale & Objective: Novel urinary biomarkers have enabled earlier detection of kidney tubular damage, but their prognostic value for adverse cardiovascular outcomes is uncertain. We hypothesized that tubular damage, measured by urine α-microglobulin (A1M), amino-terminal propeptide of type III procollagen (PIIINP), and neutrophil gelatinase-associated lipocalin (NGAL), would be associated with higher risks for cardiovascular events and mortality among elders.

Study Design: Case-cohort study.

Identification of Patients Expected to Benefit from Electronic Alerts for Acute Kidney Injury.

Background And Objectives: Electronic alerts for heterogenous conditions such as AKI may not provide benefit for all eligible patients and can lead to alert fatigue, suggesting that personalized alert targeting may be useful. Uplift-based alert targeting may be superior to purely prognostic-targeting of interventions because uplift models assess marginal treatment effect rather than likelihood of outcome.

Design, Setting, Participants, & Measurements: This is a secondary analysis of a clinical trial of 2278 adult patients with AKI randomized to an automated, electronic alert system versus usual care.

Quantification of Urinary Protein Biomarkers of Autosomal Dominant Polycystic Kidney Disease by Parallel Reaction Monitoring.

Purpose: Autosomal dominant polycystic kidney disease (ADPKD) is a life-long disease in which the genes responsible are known, but the pathogenesis of cyst formation and cyst growth are not understood. Cyst growth ultimately leads to end-stage renal failure in most patients. Analysis of the urinary proteome offers the potential to identify proteins that indicate the presence of cysts (and thus provides diagnosis) as well as the rates of cyst growth (providing prognostic information).

Kidney injury biomarkers 5 years after AKI due to pediatric cardiac surgery.

Background: We previously reported that children undergoing cardiac surgery are at high risk for long-term chronic kidney disease (CKD) and hypertension, although postoperative acute kidney injury (AKI) is not a risk factor for worse long-term kidney outcomes. We report here our evaluation of renal injury biomarkers 5 years after cardiac surgery to determine whether they are associated with postoperative AKI or long-term CKD and hypertension.

Methods: Children aged 1 month to 18 years old undergoing cardiopulmonary bypass were recruited to this prospective cohort study.

Biomarkers of AKI Progression after Pediatric Cardiac Surgery.

As children progress to higher stages of AKI, the risk for adverse outcomes dramatically increases. No reliable methods exist to predict AKI progression in hospitalized children. To determine if biomarkers of inflammation and kidney injury can predict AKI progression, we conducted a three-center prospective cohort study of children undergoing cardiopulmonary bypass.

The association of discharge decisions after deceased donor kidney transplantation with the risk of early readmission: Results from the deceased donor study.

Background: Kidney transplant (KT) recipients experience high rates of early (≤30 days) hospital readmission (EHR) after KT, and existing studies provide limited data on modifiable discharge factors that may mitigate EHR risk.

Methods: We performed a retrospective cohort study of 468 adult deceased donor KT recipients transplanted between 4/2010 and 11/2013 at 5 United States transplant centers. We fit multivariable mixed effects models to assess the association of two potentially modifiable discharge factors with the probability of EHR after KT: (i) weekend discharge and (ii) days to first scheduled follow-up.

Development of biomarker combinations for postoperative acute kidney injury via Bayesian model selection in a multicenter cohort study.

Background: Acute kidney injury (AKI) is a frequent complication of cardiac surgery. We sought prognostic combinations of postoperative biomarkers measured within 6 h of surgery, potentially in combination with cardiopulmonary bypass time (to account for the degree of insult to the kidney). We used data from a large cohort of patients and adapted methods for developing biomarker combinations to account for the multicenter design of the study.

Risk of Acute Kidney Injury in Patients Randomized to a Restrictive Versus Liberal Approach to Red Blood Cell Transfusion in Cardiac Surgery: A Substudy Protocol of the Transfusion Requirements in Cardiac Surgery III Noninferiority Trial.

Background: When safe to do so, avoiding blood transfusions in cardiac surgery can avoid the risk of transfusion-related infections and other complications while protecting a scarce resource and reducing costs. This protocol describes a kidney substudy of the Transfusion Requirements in Cardiac Surgery III (TRICS-III) trial, a multinational noninferiority randomized controlled trial to determine whether the risk of major clinical outcomes in patients undergoing planned cardiac surgery with cardiopulmonary bypass is no greater with a restrictive versus liberal approach to red blood cell transfusion.

Objective: The objective of this substudy is to determine whether the risk of acute kidney injury is no greater with a restrictive versus liberal approach to red blood cell transfusion, and whether this holds true in patients with and without preexisting chronic kidney disease.

Phenotyping of Acute Kidney Injury: Beyond Serum Creatinine.

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.

Elevated urinary CRELD2 is associated with endoplasmic reticulum stress-mediated kidney disease.

ER stress has emerged as a signaling platform underlying the pathogenesis of various kidney diseases. Thus, there is an urgent need to develop ER stress biomarkers in the incipient stages of ER stress-mediated kidney disease, when a kidney biopsy is not yet clinically indicated, for early therapeutic intervention. Cysteine-rich with EGF-like domains 2 (CRELD2) is a newly identified protein that is induced and secreted under ER stress.

Group analysis identifies differentially elevated biomarkers with distinct outcomes for advanced acute kidney injury in cardiac surgery.

Aim: To investigate early postoperative biomarkers for risk discrimination of advanced acute kidney injury (AKI).

Materials & Methods: Postoperative plasma biomarkers including NGAL, h-FABP, CK-MB, hsTNT, NT-proBNP, IL-6, IL-10 and VEGF were analyzed using group-based method among 426 patients with AKI after cardiac surgery.

Results: Six patient groups with distinct biomarker patterns were identified.

Biomarker combinations for diagnosis and prognosis in multicenter studies: Principles and methods.

Many investigators are interested in combining biomarkers to predict a binary outcome or detect underlying disease. This endeavor is complicated by the fact that many biomarker studies involve data from multiple centers. Depending upon the relationship between center, the biomarkers, and the target of prediction, care must be taken when constructing and evaluating combinations of biomarkers.

Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine.

Background: Intravenous sodium bicarbonate and oral acetylcysteine are widely used to prevent acute kidney injury and associated adverse outcomes after angiography without definitive evidence of their efficacy.

Methods: Using a 2-by-2 factorial design, we randomly assigned 5177 patients at high risk for renal complications who were scheduled for angiography to receive intravenous 1.26% sodium bicarbonate or intravenous 0.

Association Between High Environmental Heat and Risk of Acute Kidney Injury Among Older Adults in a Northern Climate: A Matched Case-Control Study.

Background: An association between high heat and acute kidney injury (AKI) has been reported in warm climates. However, whether this association generalizes to a northern climate, with more variable temperatures, is unknown.

Study Design: Matched case-control study.

IL-33 deficiency slows cancer growth but does not protect against cisplatin-induced AKI in mice with cancer.

The effect of IL-33 deficiency on acute kidney injury (AKI) and cancer growth in a 4-wk model of cisplatin-induced AKI in mice with cancer was determined. Mice were injected subcutaneously with murine lung cancer cells. Ten days later, cisplatin (10 mg·kg-¹·wk-¹) was administered weekly for 4 wk.

Association of serum albumin levels with kidney function decline and incident chronic kidney disease in elders.

Background: Previous studies in HIV-infected individuals have demonstrated serum albumin to be strongly associated with kidney function decline, independent of urine albumin and inflammatory markers. Lower serum albumin concentrations may be an under-appreciated risk factor for kidney function decline in elders.

Methods: We performed a cohort analysis in the Health Aging and Body Composition Study, a cohort of well-functioning, bi-racial, community-dwelling elders between the age of 70 and 79 years.

Strategies to improve monitoring disease progression, assessing cardiovascular risk, and defining prognostic biomarkers in chronic kidney disease.

Chronic kidney disease (CKD) is a major global public health problem with significant gaps in research, care, and policy. In order to mitigate the risks and adverse effects of CKD, the International Society of Nephrology has created a cohesive set of activities to improve the global outcomes of people living with CKD. Improving monitoring of renal disease progression can be done by screening and monitoring albuminuria and estimated glomerular filtration rate in primary care.

Predictors of Acute Renal Injury Study (PARIS) among HIV-positive individuals: design and methods.

Background: Acute kidney injury (AKI), which is common among HIV-positive individuals, may contribute to the excess burden of chronic kidney disease (CKD) in this patient population; however, conventional clinical methods to detect AKI do not capture kidney injury sufficiently early to prevent irreversible damage. Further, large observational and interventional studies of AKI generally exclude HIV-positive persons in spite of their disproportionate risk.

Methods: The Predictors of Acute Renal Injury Study (PARIS) is a prospective observational cohort study among HIV-positive individuals established to determine the ability of candidate kidney injury biomarkers to predict future hospitalized clinical AKI, to characterize hospitalized subclinical AKI, and to discern the risk of progressive kidney disease following subclinical and clinical AKI.

Performance of Serum Creatinine and Kidney Injury Biomarkers for Diagnosing Histologic Acute Tubular Injury.

Background: 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.

Interleukin-8 and Tumor Necrosis Factor Predict Acute Kidney Injury After Pediatric Cardiac Surgery.

Background: Inflammation is a key component of both acute kidney injury (AKI) and response to cardiopulmonary bypass. Because AKI poses risks to children after cardiac surgery, we investigated the value of inflammatory biomarkers interleukin-8 (IL-8) and tumor necrosis factor alpha (TNFα) for predicting AKI and other complications.

Methods: We enrolled 412 children between the ages of 1 month and 18 years undergoing cardiopulmonary bypass for cardiac surgery.

Relationship of Kidney Injury Biomarkers with Long-Term Cardiovascular Outcomes after Cardiac Surgery.

Clinical AKI, measured by serum creatinine elevation, is associated with long-term risks of adverse cardiovascular (CV) events and mortality in patients after cardiac surgery. To evaluate the relative contributions of urine kidney injury biomarkers and plasma cardiac injury biomarkers in adverse events, we conducted a multicenter prospective cohort study of 968 adults undergoing cardiac surgery. On postoperative days 1-3, we measured five urine biomarkers of kidney injury (IL-18, NGAL, KIM-1, L-FABP, and albumin) and five plasma biomarkers of cardiac injury (NT-proBNP, H-FABP, hs-cTnT, cTnI, and CK-MB).