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Although immunoassays are the most widely used protein measurement method, aptamer-based methods such as the SomaScan platform can quantify up to 7000 proteins per biosample, creating new opportunities for unbiased discovery. However, there is limited research comparing the consistency of biomarker-disease associations between immunoassay and aptamer-based platforms. In a substudy of the TRIBE-AKI cohort, preoperative and postoperative plasma samples from 294 patients with previous immunoassay measurements were analyzed using the SomaScan platform. Inter-platform Spearman correlations (rs) and biomarker-AKI associations were compared across 30 preoperative and 34 postoperative immunoassay-aptamer pairs. Possible factors contributing to inter-platform differences were examined including target protein characteristics, immunoassay, and SomaScan coefficients of variation, other assay characteristics, and sample storage time. The median rs was 0.54 (interquartile range [IQR] 0.34-0.83) in postoperative samples and 0.41 (IQR 0.21-0.69) in preoperative samples. We observed a trend of greater rs in biomarkers with greater concentrations; the Spearman correlation between the concentration of protein and the inter-platform correlation was 0.64 in preoperative pairs and 0.53 in postoperative pairs. Of proteins measured by immunoassays, we observed significant biomarker-AKI associations for 13 proteins preop and 24 postop; of all corresponding aptamers, 8 proteins preop and 12 postop. All proteins significantly associated with AKI as measured by SomaScan were also significantly associated with AKI as measured by immunoassay. All biomarker-AKI odds ratios were significantly different (P < 0.05) between platforms in 14% of aptamer-immunoassay pairs, none of which had high (rs > 0.50) inter-platform correlations. Although similar biomarker-disease associations were observed overall, biomarkers with high physiological concentrations tended to have the highest-confidence inter-platform operability in correlations and biomarker-disease associations. Aptamer assays provide excellent precision and an unprecedented coverage and promise for disease associations but interpretation of results should keep in mind a broad range of correlations with immunoassays. [ABSTRACT FROM AUTHOR]

Children undergoing a cardiac surgical procedure are at increased risk for acute kidney injury (AKI). Novel biomarkers are needed to improve risk stratification of AKI after cardiac surgery. We enrolled children aged 1 month to 18 years old from July 2007 to December 2010 undergoing cardiopulmonary bypass. Three United States Food and Drug Administration-approved plasma biomarkers of cardiac stretch, N-terminal pro B-type natriuretic peptide (NTproBNP), inflammation (ST2), or fibrosis (galectin-3), were measured preoperatively and postoperatively within 6 hours of cardiac surgery. All analyses were stratified by age (<2 or ≥2 years old) to account for changing biomarker distributions during childhood and due to a significant interaction between biomarker and age for galectin-3 and NTproBNP (P <.05). Postoperatively, AKI, defined by a doubling of baseline serum creatinine, was diagnosed in 51 of 194 children <2 years and in 28 of 201 children ≥2 years. After multivariable adjustment, for children <2 years, none of the biomarkers were independently associated with AKI, whereas for children ≥2 years, the highest tertile of preoperative galectin-3 and NTproBNP as well as the postoperative galectin-3 and ST2 were associated with AKI. Preoperative plasma galectin-3 and NTproBNP and the first postoperative galectin-3 and ST2 levels were independently associated with AKI in children ≥2 years old. The performance of cardiac biomarkers after cardiac surgical procedure is affected by age, and research is required to develop biomarkers for children <2 years old. [ABSTRACT FROM AUTHOR]

Approximately 10% to 20% of children are readmitted after congenital heart surgery. Very little is known about biomarkers as predictors of risk of unplanned readmission after pediatric congenital heart surgery. Novel cardiac biomarker ST2 may be associated with risk of unplanned readmission. ST2 concentrations are believed to reflect cardiovascular stress and fibrosis. Our objective was to explore the relationship between pre- and postoperative ST2 biomarker levels and risk of readmission within 1 year after congenital heart surgery. We prospectively enrolled pediatric patients aged < 18 years who underwent at least 1 congenital heart operation at Johns Hopkins Hospital from 2010 to 2014. Plasma samples were collected immediately before surgery and at the end of bypass. We used Kaplan-Meier survival analysis and multivariable Cox regression models to adjust for variables used in The Society of Thoracic Surgeons Congenital Heart Surgery Database mortality risk model. Of our cohort of 145 patients, we found 39 children with readmissions within 365 days. The median time to unplanned readmission was 54 days (interquartile range, 10-153). Kaplan-Meier analysis demonstrated a significant difference across terciles of pre- and postoperative ST2 biomarker levels. After adjustment, elevated serum levels of ST2 measured preoperatively and postoperatively were associated with increased risk of readmission (hazard ratio, 2.5-3.7; all P <.05). Elevated levels of ST2 are significantly associated with increased risk of unplanned readmission within 1 year after pediatric congenital heart surgery. Novel serum biomarker ST2 can be used for risk stratification or estimating postsurgical prognosis. [ABSTRACT FROM AUTHOR]

Background: Cardiac surgery induces hemodynamic stress on the myocardium, and this process can be associated with significant post-operative morbidity and mortality. Soluble suppression of tumorigenicity 2 (sST2) and galectin-3 (gal-3) are biomarkers of myocardial remodeling and fibrosis; however, their potential association with post-operative changes is unknown.Methods: We measured peri-operative plasma sST2 and gal-3 levels in two prospective cohorts (TRIBE-AKI and NNE) of over 1800 patients who underwent cardiac surgery. sST2 and gal-3 levels were evaluated for association with a composite primary outcome of cardiovascular event or mortality over median follow-up periods of 3.4 and 6.0 years, respectively, for the two cohorts. Meta-analysis of hazard ratio estimates from the cohorts was performed using random effects models.Results: Cohorts demonstrated event rates of 70.2 and 66.8 per 1000 person-years for the primary composite outcome. After adjustment for clinical covariates, higher post-operative sST2 and gal-3 levels were significantly associated with cardiovascular event or mortality [pooled estimate HRs: sST2 1.29 (95% CI 1.16, 1.44); gal-3 1.26 (95% CI 1.09, 1.46)]. These associations were not significantly modified by pre-operative congestive heart failure or AKI.Conclusions: Higher post-operative sST2 and gal-3 values were associated with increased incidence of cardiovascular event or mortality. These two biomarkers should be further studied for potential clinical utility for patients undergoing cardiac surgery. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the association between preoperative biomarker levels and 365-day readmission or mortality after pediatric congenital heart surgery. Children aged 18 years or younger undergoing congenital heart surgery (n = 145) at Johns Hopkins Hospital from 2010 to 2014 were enrolled in the prospective cohort. Novel biomarkers suppression of tumorgenicity 2, galectin-3, N-terminal prohormone brain natriuretic peptide, and glial fibrillary acidic protein were measured. The composite study endpoint was unplanned readmission within 365 days after discharge or mortality either in hospital during the surgical admission or within 365 days after discharge. A clinical model based on covariates used in The Society of Thoracic Surgeons Congenital Heart Surgery Database mortality risk model and an augmented model using the clinical model in conjunction with a novel biomarker panel were evaluated. Readmission or mortality within 365 days of surgery occurred among 39 pediatric patients (27%). The clinical model alone resulted in a c-statistic of 0.719 (95% confidence interval, 0.63 to 0.81). The clinical model in conjunction with the log-transformed biomarkers improved the c-statistic to 0.805 (95% confidence interval, 0.73 to 0.88). The addition of biomarkers resulted in a significant improvement to the clinical model alone (P value = 0.035). Novel biomarkers may add predictive value when assessing the likelihood of 365-day readmission or mortality after pediatric congenital heart surgery. After adjusting for clinical and novel biomarkers, preoperative and postoperative suppression of tumorgenicity 2 remained associated with 365-day readmission or mortality. Currently, The Society of Thoracic Surgeons clinical congenital mortality risk model can be applied to identify children with increased risk of repeat hospitalizations and postdischarge mortality and may inform preventative care interventions that aim to reduce these adverse events. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a common complication of cardiac surgery. Postprocedural AKI is a risk factor for 30-day readmission. We sought to examine the association of AKI and kidney injury biomarkers with readmission after cardiac surgery. Patients alive at discharge who underwent cardiac surgery from the Translational Research Investigating Biomarker Endpoints-AKI cohort were enrolled from six medical centers in the United States and Canada. AKI duration was defined as the total number of days AKI was present during index admission (no AKI, 1–2, 3–6, and 7+ days). Preoperative and postoperative urinary levels were collected for interleukin-18, neutrophil gelatinase–associated lipocalin, kidney injury molecule-1, liver-fatty-acid-binding protein, cystatin C, microalbumin, creatinine, and albumin-to-creatinine ratio. Readmission and death events were identified through US (Medicare) and Canadian administrative databases at 30 days and 365 days after discharge. Of 968 patients 15.9% were readmitted or died within 30 days of discharge and 35.9% were readmitted or died within 365 days. AKI duration of 3 to 6 days was significantly associated with 30-day readmission or death (adjusted odds ratio, 1.82%; 95% confidence interval, 1.08–3.05). Patients with AKI duration ≥ 7 days had increased odds of readmission or death at both 30 days (adjusted odds ratio, 2.49%; 95% confidence interval, 1.15–5.43) and 365 days (adjusted odds ratio, 3.67%; 95% confidence interval, 1.73–7.79). Urinary biomarkers had no association with readmission and death. AKI duration ≥ 3 days, and not kidney biomarkers, was strongly associated with readmission or death. These clinical outcomes are potentially due to cardiovascular or hemodynamic causes rather than intrinsic injury to the kidney parenchyma. [ABSTRACT FROM AUTHOR]

Background Hospital readmission within 30 days is associated with higher risks of complications, death, and increased costs. Accurate statistical models to stratify the risk of 30-day readmission or death after cardiac surgery could help clinical teams focus care on those patients at highest risk. We hypothesized biomarkers could improve prediction for readmission or mortality. Methods Levels of ST2, galectin-3, N-terminal pro-brain natriuretic peptide, cystatin C, interleukin-6, and interleukin-10 were measured in samples from 1,046 patients discharged after isolated coronary artery bypass graft surgery from eight medical centers, with external validation in 1,194 patients from five medical centers. Thirty-day readmission or mortality were ascertained using Medicare, state all-payer claims, and the National Death Index. We tested and externally validated the clinical models and the biomarker panels using area under the receiver-operating characteristics (AUROC) statistics. Results There were 112 patients (10.7%) who were readmitted or died within 30 days after coronary artery bypass graft surgery. The Society of Thoracic Surgeons augmented clinical model resulted in an AUROC of 0.66 (95% confidence interval: 0.61 to 0.71). The biomarker panel with The Society of Thoracic Surgeons augmented clinical model resulted in an AUROC of 0.74 (bootstrapped 95% confidence interval: 0.69 to 0.79, p < 0.0001). External validation of the model showed limited improvement with the addition of a biomarker panel, with an AUROC of 0.51 (95% confidence interval: 0.45 to 0.56). Conclusions Although biomarkers significantly improved prediction of 30-day readmission or mortality in our derivation cohort, the external validation of the biomarker panel was poor. Biomarkers perform poorly, much like other efforts to improve prediction of readmission, suggesting there are many other factors yet to be explored to improve prediction of readmission. [ABSTRACT FROM AUTHOR]

Background Novel cardiac biomarkers including soluble suppression of tumorigenicity 2, galectin-3, and the N-terminal prohormone of brain natriuretic peptide may be associated with long-term adverse outcomes after cardiac surgery. We sought to measure the association between cardiac biomarker levels and 1-year hospital readmission or mortality. Methods Plasma biomarkers from 1,047 patients discharged alive after isolated coronary artery bypass graft surgery from 8 medical centers were measured in a cohort from the Northern New England Cardiovascular Disease Study Group between 2004 and 2007. We evaluated the association between preoperative and postoperative biomarkers and 1-year readmission or mortality using Kaplan-Meier estimates and Cox proportional hazards modeling, adjusting for covariates used in The Society of Thoracic Surgeons 30-day readmission model. Results The median follow-up time was 365 days. After adjustment for established risk factors, above-median levels of postoperative galectin-3 (median 10.35 ng/mL; hazard ratio, 1.40; 95% confidence interval, 1.08 to 1.80; p = 0.010) and N-terminal prohormone of brain natriuretic peptide (median = 15.21 ng/mL, hazard ratio, 1.42; 95% confidence interval, 1.07 to 1.87; p = 0.014) were each significantly associated with 1-year readmission or mortality. Conclusions In patients undergoing cardiac surgery, novel cardiac biomarkers were associated with readmission or mortality independent of established risk factors. Measurement of these biomarkers may improve our ability to identify patients at highest risk for readmission or mortality before discharge. This will also allow resource allocation accordingly, while implementing strategies for personalized medicine based on the biomarker profile of the patient. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. We collected blood both preoperatively and postoperatively (within 6 hours post-surgery) and measured plasma IL-8 and TNFα. Results IL-8 and TNFα did not predict AKI in children <2 years, but were strongly associated with AKI in children ≥2 years. There were significant associations between biomarker levels and age (<2 or ≥2 years). In children ≥2 years, patients in the highest tertile of preoperative IL-8 and postoperative TNFα had 4.9-fold (95% CI: 1.8-13.2) and 3.3-fold (95% CI: 1.2-9.0) higher odds of AKI compared with those in the lowest tertile. Children <2 years with higher biomarker levels also had higher odds of AKI, but the difference was not significant. We also found that postoperative TNFα levels were significantly higher in patients with longer hospital stays, and that both postoperative IL-8 and TNFα levels were significantly higher in patients with longer ventilation lengths. There was no evidence that biomarker levels mediated the association between AKI and length of ventilation; they appear to be independent predictors. Conclusions Preoperative IL-8 and postoperative TNFα are significantly associated with higher odds of AKI and greater lengths of hospital stays and ventilator use in children 2 years and older. [ABSTRACT FROM AUTHOR]

Background Monocyte chemotactic protein-1 (MCP-1; chemokine C-C ligand-2 [CCL-2]) is upregulated in ischemia-reperfusion injury and is a promising biomarker of inflammation in cardiac operations. Methods We measured preoperative and postoperative plasma MCP-1 levels in adults undergoing cardiac operations to evaluate the association of perioperative MCP-1 levels with acute kidney injury (AKI) and death in Translational Research Investigating Biomarker Endpoints in AKI (TRIBE-AKI), a prospective, multicenter, observational cohort. Results Of the 972 participants in the study, AKI developed in 329 (34%), and severe AKI developed in 45 (5%). During a median follow-up of 2.9 years (interquartile range, 2.2 to 3.5 years), 119 participants (12%) died. MCP-1 levels were significantly higher in those who developed AKI and died than in those without AKI and death. Participants with a preoperative MCP-1 level in the highest tertile (>196 pg/mL) had an increased AKI risk than those in the lowest tertile (<147 pg/mL; odds ratio [OR], 1.43l; 95% confidence interval [CI], 1.00 to 2.05). The association appeared similar but was not significant for the severe AKI outcome (OR, 1.48; 95% CI, 0.62 to 3.54). Compared with participants with preoperative MCP-1 level in the lowest tertile, those in the highest tertile had higher adjusted risk of death (hazard ratio, 1.82; 95% CI, 1.40 to 2.38). Similarly, participants in the highest tertile had a higher adjusted risk of death (hazard ratio, 1.95; 95% CI, 1.09–3.49) than those with a postoperative MCP-1 level in the lowest tertile. Conclusions Higher plasma MCP-1 is associated with increased AKI and risk of death after cardiac operations. MCP-1 could be used as a biomarker to identify high-risk patients for potential AKI prevention strategies in the setting of cardiac operations. [ABSTRACT FROM AUTHOR]

Background Acute kidney injury (AKI) is a common complication after cardiac surgery. While AKI severity is known to be associated with increased risk of short-term outcomes, its long-term impact is less well understood. Methods Adult patients undergoing isolated coronary artery bypass graft surgery at eight centers were enrolled into the Northern New England biomarker registry (n = 1,610). Patients were excluded if they had renal failure (n = 15) or died during index admission (n = 38). Severity of AKI was defined using the Acute Kidney Injury Network (AKIN). We linked our cohort to national Medicare and state all-payer claims to ascertain readmissions and to the National Death Index to ascertain survival. Kaplan-Meier and multivariate Cox proportional hazards modeling was conducted for time to readmission and death over 5 years. Results Within 5 years, 513 patients (33.8%) had AKI with AKIN stage 1 (29.9%) and stage 2 to 3 (3.9%). There were 620 readmissions (39.9%) and 370 deaths (23.8%). After adjustment, stage 1 AKI patients had a 31% increased risk of readmission (95% confidence interval [CI]: 1.10 to 1.57), whereas stage 2 or 3 patients had a 98% increased risk (95% CI: 1.41 to 2.78) compared with patients having no AKI. Relative to patients without AKI, stage 1 patients had a 56% increased risk of mortality (95% CI: 1.14 to 2.13), whereas stage 2 or 3 patients had a 3.5 times higher risk (95% CI: 2.16 to 5.60). Conclusions Severity of AKI using the AKIN stage criteria is associated with a significantly increased risk of 5-year readmission and mortality. Our findings suggest that efforts to reduce AKI in the perioperative period may have a significant long-term impact on patients and payers in reducing mortality and health care utilization. [ABSTRACT FROM AUTHOR]

Background: Worsening renal function (WRF) is a common endpoint in decompensated heart failure clinical trials because of associations between WRF and adverse outcomes. However, WRF has not universally been identified as a poor prognostic sign, challenging the validity of WRF as a surrogate endpoint. Our aim was to describe the associations between changes in creatinine and adverse outcomes in a clinical trial of decongestive therapies.Methods and Results: We investigated the association between changes in creatinine and the composite endpoint of death, rehospitalization or emergency room visit within 60 days in 301 patients in the Diuretic Optimization Strategies Evaluation (DOSE) trial. WRF was defined as an increase in creatinine >0.3 mg/dL and improvement in renal function (IRF) as a decrease >0.3 mg/dL. When examining linear changes in creatinine from baseline to 72 hours (the coprimary endpoint of DOSE), increasing creatinine was associated with lower risk for the composite outcome (HR = 0.81 per 0.3 mg/dL increase, 95% CI 0.67-0.98, P = .026). Compared with patients with stable renal function (n = 219), WRF (n = 54) was not associated with the composite endpoint (HR = 1.17, 95% CI = 0.77-1.78, P = .47). However, compared with stable renal function, there was a strong relationship between IRF (n = 28) and the composite endpoint (HR = 2.52, 95% CI = 1.57-4.03, P < .001).Conclusion: The coprimary endpoint of the DOSE trial, a linear increase in creatinine, was paradoxically associated with improved outcomes. This was driven by absence of risk attributable to WRF and a strong risk associated with IRF. These results argue against using changes in serum creatinine as a surrogate endpoint in trials of decongestive strategies. [ABSTRACT FROM AUTHOR]

Background: Renal dysfunction (RD) is a potent risk factor for death in patients with cardiovascular disease. This relationship may be causal; experimentally induced RD produces findings such as myocardial necrosis and apoptosis in animals. Cardiac transplantation provides an opportunity to investigate this hypothesis in humans.Methods and Results: Cardiac transplantations from the United Network for Organ Sharing registry were studied (n = 23,056). RD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m(2). RD was present in 17.9% of donors and 39.4% of recipients. Unlike multiple donor characteristics, such as older age, hypertension, or diabetes, donor RD was not associated with recipient death or retransplantation (age-adjusted hazard ratio [HR] = 1.00, 95% confidence interval [CI] 0.94-1.07, P = .92). Moreover, in recipients with RD the highest risk for death or retransplantation occurred immediately posttransplant (0-30 day HR = 1.8, 95% CI 1.54-2.02, P < .001) with subsequent attenuation of the risk over time (30-365 day HR = 0.92, 95% CI 0.77-1.09, P = .33).Conclusions: The risk for adverse recipient outcomes associated with RD does not appear to be transferrable from donor to recipient via the cardiac allograft, and the risk associated with recipient RD is greatest immediately following transplant. These observations suggest that the risk for adverse outcomes associated with RD is likely primarily driven by nonmyocardial factors. [ABSTRACT FROM AUTHOR]

Background Acute kidney injury is a risk factor for death in cardiac surgical patients. Plasma cystatin C and creatinine have different temporal profiles in the postoperative setting, but the associations of simultaneous changes in both filtration markers compared with change in only one marker with prognosis after hospital discharge are not well described. Methods This is a longitudinal study of 1,199 high-risk adult cardiac surgical patients in the TRIBE-AKI (Translational Research Investigating Biomarker Endpoints for Acute Kidney Injury) Consortium who survived hospitalization. We examined in-hospital peak changes of cystatin C and creatinine in the 3 days after cardiac operations. We evaluated associations of these filtration markers with death, adjusting for demographics, operative characteristics, medical comorbidities, preoperative estimated glomerular filtration rate, preoperative urinary albumin-to-creatinine ratio, and site. Results During the first 3 days of hospitalization, nearly twice as many patients had a 25% or higher rise in creatinine (30%) compared with a 25% or higher peak rise in cystatin C (15%). The risk of death was higher in those with elevations in cystatin C (adjusted hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.4 to 2.37) or creatinine (adjusted HR, 1.90; 95% CI, 1.32 to 2.72) compared with patients who experienced a postoperative decrease in either filtration marker. Patients who had simultaneous elevations of 25% or higher in cystatin C and creatinine were at similar adjusted risk for 3-year mortality (HR, 1.79; 95% CI, 1.03 to 3.1) as those with a 25% or higher increase in cystatin C alone (HR, 2.2; 95% CI, 1.09 to 4.47). Conclusions Elevations in creatinine postoperatively are more common than elevations in cystatin C. However, elevations in cystatin C appeared to be associated with a higher risk of death after hospital discharge. [ABSTRACT FROM AUTHOR]

Kidney involvement is common in coronavirus disease-2019 (COVID-19), and our understanding of the effects of COVID-19 on short- and long-term kidney outcomes has evolved over the course of the pandemic. Initial key questions centered on the spectrum and degree of acute kidney injury (AKI) in patients hospitalized with severe COVID-19. Investigators worldwide have explored the association between COVID-19-associated AKI and short-term outcomes, including inpatient mortality and disease severity. Even as treatments evolved, vaccinations were developed, and newer viral variants arose, subsets of patients were identified as at continued high risk for major adverse kidney outcomes. In this review, we explore key topics of continued relevance including the following: (1) a comparison of COVID-19-associated AKI with AKI developing in other clinical settings; (2) the ongoing controversy over kidney tropism in the setting of COVID-19 and the potential for competitive binding of the severe acute respiratory syndrome coronavirus 2 virus with angiotensin converting enzyme-2 to prevent viral cell entry; and (3) the identification of high-risk patients for adverse outcomes to inform long-term outpatient management. Patients at particularly high risk for adverse kidney outcomes include those with APOL1 high-risk genotype status. Biomarkers of injury, inflammation, tubular health, and repair measured in both the blood and urine may hold prognostic significance. [ABSTRACT FROM AUTHOR]

Objective Cardiac surgery is a major cause of acute kidney injury. In this setting, receipt of blood transfusions seems to be associated with a higher risk of acute kidney injury, as measured using serum creatinine values. We examined this association further by using urinary biomarkers of kidney injury. Methods A total of 1210 adults underwent cardiac surgery and were divided into 3 groups on the basis of the receipt of intraoperative packed red blood cell units: no blood (n = 894), 2 or less packed red blood cell units (n = 206), and more than 2 packed red blood cell units (n = 110). Acute kidney injury was defined as (1) doubling of serum creatinine from the preoperative value; (2) first postoperative urinary interleukin-18 in the fifth quintile; and (3) first postoperative urinary neutrophil gelatinase-associated lipocalin in the fifth quintile. We determined the relative risk for acute kidney injury outcome according to packed red blood cell units group after adjusting for 12 preoperative and surgical variables. By using the Sobel test for mediation analysis, we also evaluated the role of biomarkers in causing acute kidney injury through alternative pathways. Results Acute kidney injury was more common in those who received more than 2 packed red blood cell units. In patients receiving more than 2 packed red blood cell units, the adjusted relative risks were 2.3 (95% confidence interval, 1.2-4.4, P .01), 1.36 (95% confidence interval, 1.0-1.9, P .05), and 1.34 (95% confidence interval, 1.0-1.8, P .06) for doubling of serum creatinine, urinary interleukin-18 in the fifth quintile (>60 pg/mL), and urinary neutrophil gelatinase-associated lipocalin in the fifth quintile (>102 ng/mL), respectively. Furthermore, the effect of packed red blood cell units transfusion on acute kidney injury was partially mediated by interleukin-18. Conclusions Receipt of 2 or more packed red blood cell units during cardiac surgery is associated with a greater risk of acute kidney injury defined by serum creatinine and kidney injury biomarkers. [ABSTRACT FROM AUTHOR]

Background. Acute kidney injury (AKI) after pediatrie cardiac operations is associated with poor outcomes and is difficult to predict. We conducted a prospective study to evaluate whether preoperative brain natriuretic peptide (BNP) levels predict postoperative AKI among children undergoing cardiac operations. Methods. This was a three-center, prospective study (2007-2009) of 277 children undergoing cardiac operations (n = 121, aged <2 years) with available preoperative BNP values. Preoperative BNP was measured and categorized into tertiles. The performance of BNP was evaluated alone and in combination with clinical factors. AKI was defined as doubling of serum creatinine or need for acute dialysis. Results. Postoperative AKI occurred in 165 children (60%), with 118 cases (43%) being mild and 47 cases (17%) severe. Preoperative BNP was not associated with increased risk of mild or severe postoperative AKI and did not significantly improve AKI risk prediction when added to clinical models. Preoperative BNP was, however, associated with several clinical outcomes, including length of stay and mechanical ventilation. The results were similar when the analysis was repeated in the subset of children younger than 2 years of age or when the association of postoperative BNP and AKI was evaluated. Conclusions. Preoperative BNP levels did not predict postoperative AKI in this cohort of children undergoing cardiac operations. Both preoperative and postoperative BNP levels are associated with postoperative outcomes. Clinical Trial Registration at Clinicaltrials.gov as NCT00774137. [ABSTRACT FROM AUTHOR]

Background. Acute kidney injury (AKI) is a serious complication of cardiac operations for which there remains no specific therapy. Animal data and several observational studies suggest that statins prevent AKI, but the results are not conclusive, and many studies are retrospective in nature. Methods. We conducted a multicenter prospective cohort study of 625 adult patients undergoing elective cardiac operations. All patients were taking statins and were grouped according to whether statins were continued or held in the 24 hours before operation. The primary outcome was AKI as defined by a doubling of serum creatinine or dialysis. The secondary outcome was the peak level of several kidney injury biomarkers. The results were adjusted for demographic and clinical factors. Results. Continuing (vs holding) a statin before operation was not associated with a lower risk of AKI, as defined by a doubling of serum creatinine or dialysis (adjusted relative risk [RR] 1.09; 95% confidence interval [CI] 0.44, 2.70). However, continuing a statin was associated with a lower risk of elevation of the following AKI biomarkers: urine interleukin-18, urine neutrophil gelatinase-associated lipocalin, urine kidney injury molecule-I, and plasma neutrophil gelatinase-associated lipocalin (adjusted RR 0.34; 95% CI 0.18, 0.62), (adjusted RR 0.41; 95% CI 0.22, 0.76), (adjusted RR 0.37; 95% CI 0.20, 0.76), (adjusted RR 0.62; 95% CI 0.39, 0.98), respectively. Conclusions. Statins may prevent kidney injury after cardiac operations, as evidenced by lower levels of kidney injury biomarkers. [ABSTRACT FROM AUTHOR]

Background. Of patients undergoing cardiac surgery in the United States, 15% to 20% are re-hospitalized within 30 days. Current models to predict readmission have not evaluated the association between severity of postoperative acute kidney injury (AKI) and 30-day readmissions. Methods. We collected data from 2,209 consecutive patients who underwent either coronary artery bypass or valve surgery at 7 member hospitals of the Northern New England Cardiovascular Disease Study Group Cardiac Surgery Registry between July 2008 and December 2010. Administrative data at each hospital were searched to identify all patients readmitted to the index hospital within 30 days of discharge. We defined AKI stages by the AKI Network definition of 0.3 or 50% increase (stage 1), twofold increase (stage 2), and a threefold or 0.5 increase if the baseline serum creatinine was at least 4.0 (mg/dL) or new dialysis (stage 3). We evaluate the association between stages of AKI and 30-day readmission using multivariate logistic regression. Results. There were 260 patients readmitted within 30 days (12.1%). The median time to readmission was 9 (interquartile range, 4 to 16) days. Patients not developing AKI after cardiac surgery had a 30-day read-mission rate of 9.3% compared with patients developing AKI stage I (16.1%), AKI stage 2 (21.8%), and AKI stage 3 (28.6%, p < 0.001). Adjusted odds ratios for AKI stage 1 (1.81; 1.35, 2.44), stage 2 (2.39; 1.38, 4.14), and stage 3 (3.47; 1.85 to 6.50). Models to predict readmission were significantly improved with the addition of AKI stage (c-statistic 0.65, p = 0.001) and net reclassification rate of 14.6% (95% confidence interval: 5.05% to 24.14%, p = 0.003). Conclusions. In addition to more traditional patient characteristics, the severity of postoperative AKI should be used when assessing a patient's risk for readmission. [ABSTRACT FROM AUTHOR]

A 62-year-old man with cirrhosis secondary to hepatitis C and chronic alcohol abuse was admitted to the intensive care unit with hematemesis and mental status changes. Physical examination showed ascites and stigmata of chronic liver disease. Blood pressure was noted as 87/42 mm Hg and laboratory studies showed a serum creatinine level of 0.8 mg/dL, an estimated glomerular filtration rate of 84 mL/min/1.73 m2 calculated using the Modification of Diet in Renal Disease Study equation, a serum sodium level of 123 mEq/L, a total serum bilirubin level of 4.3 mg/dL, and an international normalization ratio of 1.6. The patient was resuscitated with packed red blood cells and fresh-frozen plasma and bleeding was controlled. However, on the third day of admission, creatinine level increased to 1.5 mg/dL. Examination of urine sediment showed 1 to 5 bilirubin-stained granular casts per high-powered field and a few renal tubular epithelial cells. The urine sodium level was 21 mEq/L and the fractional excretion of sodium was 0.43%. [Copyright &y& Elsevier]

Background: Differentiation of HF-induced renal dysfunction (RD) from irreversible intrinsic kidney disease is challenging, likely related to the multifactorial pathophysiology underlying HF-induced RD. In contrast, HF-induced liver dysfunction results in characteristic laboratory abnormalities. Given that similar pathophysiologic factors are thought to underlie both conditions, and that the liver and kidneys share a common circulatory environment, patients with laboratory evidence of HF-induced liver dysfunction may also have a high incidence of potentially reversible HF-induced RD. Methods and Results: Hospitalized patients with a discharge diagnosis of HF were reviewed (n = 823). Improvement in renal function (IRF) was denned as a 20% improvement in estimated glomerular filtration rate (eGFR). An elevated international normalized ratio (INR; odds ratio [OR] 2.8; P < .001), bilirubin (BIL; OR 2.2; P < .001), aspartate aminotransferase (AST; OR 1.8; P = .004), and alanine aminotransferase (ALT; OR 2.1; P = .001) were all significantly associated with IRF. Among patients with baseline RD (eGFR ≤45 mL min-1 1.73 m-2), associations between liver dysfunction and IRF were particularly strong (INR: OR 5.7 [P < .001]; BIL: OR 5.1 [P < .001]; AST: OR 2.9 [P = .005]; ALT: OR 4.8 [P < .001]). Conclusions: Biochemical evidence of mild liver dysfunction is associated with reversible RD in decompensated HF patients. In the absence of methodology to directly identify HF-induced RD, signs of HF-induced dysfunction of other organs may serve as an accessible method by which HF-induced RD is recognized. [ABSTRACT FROM AUTHOR]

Summary: Members of the 18 glycosyl hydrolase (GH 18) gene family have been conserved over species and time and are dysregulated in inflammatory, infectious, remodeling, and neoplastic disorders. This is particularly striking for the prototypic chitinase-like protein chitinase 3-like 1 (Chi3l1), which plays a critical role in antipathogen responses where it augments bacterial killing while stimulating disease tolerance by controlling cell death, inflammation, and remodeling. However, receptors that mediate the effects of GH 18 moieties have not been defined. Here, we demonstrate that Chi3l1 binds to interleukin-13 receptor α2 (IL-13Rα2) and that Chi3l1, IL-13Rα2, and IL-13 are in a multimeric complex. We also demonstrate that Chi3l1 activates macrophage mitogen-activated protein kinase, protein kinase B/AKT, and Wnt/β-catenin signaling and regulates oxidant injury, apoptosis, pyroptosis, inflammasome activation, antibacterial responses, melanoma metastasis, and TGF-β1 production via IL-13Rα2-dependent mechanisms. Thus, IL-13Rα2 is a GH 18 receptor that plays a critical role in Chi3l1 effector responses. [Copyright &y& Elsevier]

Progressive disruption of renal tubular integrity in the setting of increased cellular proliferation and apoptosis is a feature of autosomal dominant polycystic kidney disease (ADPKD). Here we evaluated the effect of these processes on the expression of Lcn2 (NGAL) and interleukin (IL)-18, markers of tubular injury, in rodent models and in the cyst fluid and urine of patients with ADPKD. Two mouse models where Pkd2 was inactivated, which resulted in early- or adult-onset cysts, were used to evaluate NGAL levels. Further, the Han:SPRD rat model of polycystic disease was used to study IL-18 levels. In four annual serial urine samples collected from 107 patients with ADPKD in the Consortium for Radiologic Imaging for the Study of Polycystic Kidney Disease (CRISP) study, NGAL and IL-18 excretion rates were determined in conjunction with measures of total kidney volume and estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease equation. Kidneys from affected mice and rats showed prominent expression of NGAL and IL-18/IL-18R, respectively, in epithelial cells lining kidney cysts. In human ADPKD cyst fluid, both NGAL and IL-18 were elevated. In CRISP patients, the mean percentage increase in total kidney volume was 5.4/year and the mean decline in eGFR 2.4 ml/min/year. The trend of increased mean urine NGAL and IL-18 over 3 years was statistically significant; however, there was no association between tertiles of IL-18 or quartiles of NGAL and change in total kidney volume or eGFR over this period. Thus, urinary NGAL and IL-18 excretion is mildly and stably elevated in ADPKD, but does not correlate with changes in total kidney volume or kidney function. This may be due, in part, to the lack of communication between individual cysts and the urinary collecting system in this disorder. [ABSTRACT FROM AUTHOR]

Objective: The study objective was to examine the utility of using proteinuria in preoperative risk stratification for acute kidney injury. Acute kidney injury is a common and important complication for patients undergoing cardiac surgery. Proteinuria, which reflects structural damage to the glomeruli or renal tubules, may aid the prediction of acute kidney injury. Methods: The urine albumin to creatinine ratio and dipstick proteinuria concentration were prospectively measured in 1159 patients undergoing cardiac surgery. The cohort was organized into 4 clinical risk categories based on the preoperative urine albumin to creatinine ratio: 10 mg/g or less (≤1.1 mg/mmol), 11 to 29 mg/g (1.2–3.3 mg/mmol), 30 to 299 mg/g (3.4–33.8 mg/mmol), and 300 mg/g or greater (≥33.9 mg/mmol). The primary outcome was postoperative acute kidney injury, defined by the Acute Kidney Injury Network stage I criterion (serum creatinine increase ≥ 50% or ≥ 0.3 mg/dL; 26.5 μmol/L). Results: An increase in the incidence of acute kidney injury was noted across the urine albumin to creatinine ratio categories. Adding the urine albumin to creatinine ratio to the clinical model to predict acute kidney injury improved the area under the curve from 0.67 to 0.70 (P < .001), and the continuous net reclassification improvement was 29% (P < .001). The urine albumin to creatinine ratio was also independently associated with the risk of in-hospital dialysis and intensive care unit and hospital lengths of stay. Surgery status and preoperative glomerular filtration rate were effect modifiers; the association was stronger among those undergoing elective surgery and those with an estimated glomerular filtration rate of 45 mL/min/1.73 m2 or greater. Conclusions: Preoperative proteinuria provides graded stratification risk for acute kidney injury and is an independent predictor of other outcomes in patients undergoing cardiac surgery. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) duration after cardiac surgery is associated with poor survival in a dose-dependent manner. However, it is not known what perioperative risk factors contribute to prolonged AKI and delayed recovery. We sought to identify perioperative risk factors that predict duration of AKI, a complication that effects short and long-term survival. Methods: We studied 4,987 consecutive cardiac surgery patients from 2002 through 2007. Acute kidney injury was defined as a 0.3 or greater (mg/dL) or 50% or greater increase in serum creatinine from baseline. Duration of AKI was defined by the number of days AKI was present. Stepwise multivariable negative binomial regression analysis was conducted using perioperative risk factors for AKI duration. The c-index was estimated by Kendall''s tau. Results: Acute kidney injury developed in 39% of patients with a median duration of AKI at 3 days and ranged from 1 to 108 days. Patients without AKI had a duration of 0 days. Independent predictors of AKI duration included baseline patient and disease characteristics, and operative and postoperative factors. Prediction for mean duration of AKI was developed using coefficients from the regression model and externally validated the model on 1,219 cardiac surgery patients in a separate cardiac surgery cohort (Translational Research Investigating Biomarker Endpoints-AKI). The c-index was 0.65 (p < 0.001) for the derivation cohort and 0.62 (p < 0.001) for the validation cohort. Conclusions: We identified and externally validated perioperative predictors of AKI duration. These risk factors will be useful to evaluate a patient''s risk for the tempo of recovery from AKI after cardiac surgery and subsequent short and long-term survival. The levels of awareness created by working with these risk factors have implications regarding positive changes in processes of care that have the potential to decrease the incidence and mitigate AKI. [Copyright &y& Elsevier]

Acute kidney injury (AKI) after cardiac surgery confers a significant increased risk of death. Several risk models have been developed to predict postoperative kidney failure after cardiac surgery. This systematic review evaluated the available risk models for AKI after cardiac surgery. Literature searches were performed in the Web of Science/Knowledge, Scopus, and MEDLINE databases for articles reporting the primary development of a risk model and articles reporting validation of existing risk models for AKI after cardiac surgery. Data on model variables, internal or external validation (or both), measures of discrimination, and measures of calibration were extracted. The systematic review included 7 articles with a primary development of a prediction score for AKI after cardiac surgery and 8 articles with external validation of established models. The models for AKI requiring dialysis are the most robust and externally validated. Among the prediction rules for AKI requiring dialysis after cardiac surgery, the Cleveland Clinic model has been the most widely tested thus far and has shown high discrimination in most of the tested populations. A validated score to predict AKI not requiring dialysis is lacking. Further studies are required to develop risk models to predict milder AKI not requiring dialysis after cardiac surgery. Standardizing risk factor and AKI definitions will facilitate the development and validation of risk models predicting AKI. [ABSTRACT FROM AUTHOR]

Background Serum creatinine is a delayed marker of acute kidney injury (AKI). Our purpose is to discover and validate novel early urinary biomarkers of AKI after cardiac surgery. Study Design Diagnostic test study. Setting & Participants Children undergoing cardiopulmonary bypass surgery. The test set included 15 participants with AKI and 15 matched controls (median age, 1.5 year) of 45 participants without AKI. The validation set included 365 children (median age, 1.9 year). Index Tests Biomarkers identified using proteomic profiling: α1-microglobulin, α1-acid glycoprotein, and albumin. Reference Test AKI, defined as ≥50% increase in serum creatinine level from baseline within 3 days of surgery. Results Proteomic profiling using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) showed 3 protein peaks that appeared consistently within 2 hours in children who developed AKI after cardiopulmonary bypass surgery. The proteins were identified as a1-microglobulin, a1-acid glycoprotein, and albumin. Using clinical assays, results were confirmed in a test set and validated in an independent prospective cohort. In the validation set, 135 (37%) developed AKI, in whom there was a progressive increase in urinary biomarker concentrations with severity of AKI. Areas under the curve for urinary a1-microglobulin, a1-acid glycoprotein, and albumin at 6 hours after cardiac surgery were 0.84 (95% CI, 0.79-0.89), 0.87 (95% CI, 0.83-0.91), and 0.76 (95% CI, 0.71-0.81), respectively. Participants with increasing quartiles of biomarkers showed increasing lengths of hospital stays and durations of AKI (P < 0.001). Limitations Single-center study of children with normal kidney function at recruitment. The SELDI-TOF MS technique has limited sensitivity for the detection of proteins greater than the 20-kDa range. Conclusions Urinary α1-microglobulin, α1-acid glycoprotein, and albumin represent early, accurate, inexpensive, and widely available biomarkers of AKI after cardiac surgery. They also offer prognostic information about the duration of AKI and length of hospitalization after cardiac surgery. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) after cardiac surgery is associated with worse outcomes. However, it is not known how adverse long-term consequences vary according to the duration of AKI. We sought to determine the association between duration of AKI and survival. Methods: Medical records of 4,987 cardiac surgery patients from 2002 through 2007 with serum creatinine (SCr) collection at a medical center in northern New England were reviewed. Acute kidney injury was defined as at least a 0.3 (mg/dL) or at least a 50% increase in SCr from baseline and further classified into AKI Network stages. Duration of AKI was defined by the number of days AKI was present and categorized as no AKI and AKI for 1 to 2, 3 to 6, and at least 7 days. Results: Thirty-nine percent of patients exhibited AKI. Long-term survival was significantly different by AKI duration (p < 0.001). The proportion of patients with AKI duration, adjusted hazard ratio, and 95% confidence interval for mortality (no AKI as referent) were as follows: 1 to 2 days (18%; adjusted hazard ratio, 1.66; 95% confidence interval, 1.32 to 2.09), 3 to 6 days (11%; adjusted hazard ratio, 1.94; 95% confidence interval, 1.51 to 2.49), ≥7 days (9%; adjusted hazard ratio, 3.40; 95% confidence interval, 2.73 to 4.25). This graded relationship of duration of AKI with long-term mortality persisted when patients who died during hospitalization were excluded from analysis (p < 0.001). Propensity-matched analysis confirmed results. Conclusions: The duration of AKI after cardiac surgery is directly proportional to long-term mortality. This AKI dose-dependent effect on long-term mortality helps to close the gap between association and causation, whereby AKI stages and AKI duration have important implications for patient care and can aid clinicians in evaluating the risk of in-hospital and postdischarge death. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is common in hospitalized patients. The impact of AKI on long-term outcomes is controversial.Study Design: Systematic review and meta-analysis.Setting& Participants: Persons with AKI.Selection Criteria For Studies: MEDLINE and EMBASE databases were searched from 1985 through October 2007. Original studies describing outcomes of AKI for patients who survived hospital discharge were included. Studies were excluded from review when participants were followed up for less than 6 months.Predictor: AKI, defined as acute changes in serum creatinine level or acute need for renal replacement therapy.Outcomes: Chronic kidney disease (CKD), cardiovascular disease, and mortality.Results: 48 studies that contained a total of 47,017 participants were reviewed; 15 studies reported long-term data for patients without AKI. The incidence rate of mortality was 8.9 deaths/100 person-years in survivors of AKI and 4.3 deaths/100 patient-years in survivors without AKI (rate ratio [RR], 2.59; 95% confidence interval, 1.97 to 3.42). AKI was associated independently with mortality risk in 6 of 6 studies that performed multivariate adjustment (adjusted RR, 1.6 to 3.9) and with myocardial infarction in 2 of 2 studies (RR, 2.05; 95% confidence interval, 1.61 to 2.61). The incidence rate of CKD after an episode of AKI was 7.8 events/100 patient-years, and the rate of end-stage renal disease was 4.9 events/100 patient-years.Limitations: The relative risk for CKD and end-stage renal disease after AKI was unattainable because of lack of follow-up of appropriate controls without AKI.Conclusions: The development of AKI, defined as acute changes in serum creatinine level, characterizes hospitalized patients at increased risk of long-term adverse outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Acute kidney injury (AKI) occurs frequently after nonmyeloablative hematopoietic cell transplantation (HCT). The severity of AKI after nonmyeloablative HCT has association with short-term mortality. However, the long-term effect of AKI on survival after nonmyeloablative HCT is not known. We performed a retrospective analysis of patients who underwent an HLA matched nonmyeloablative HCT between 1997 and 2006. Patients were followed for a median of 36 (range: 3-99) months. AKI occurring up to day 100 was defined as a >2-fold increase in serum creatinine or requirement of dialysis. Of the 358 patients who were included in the analysis, 200 (56%) had AKI, 158 (44%) had no AKI. Overall, 158 patients (43%) died during follow-up. After controlling for potential confounders, the adjusted hazard ratio for overall mortality associated with AKI was 1.57 (95 % confidence interval [CI] 1.2-2.3; P = .0006). The adjusted hazards ratio of nonrelapse mortality (NRM) associated with AKI was 1.72 (95% CI 0.9-3.1; P = .07). AKI is an independent predictor of overall mortality after nonmyeloablative HCT. This finding reiterates the importance of identifying preventative strategies in nonmyeloablative HCT for attenuating incidence and severity of AKI. [Copyright &y& Elsevier]

Acute renal failure independently predicts mortality after myeloablative allogeneic hematopoietic cell transplant. Background. Patients undergoing myeloablative allogeneic hematopoietic cell transplantation (HCT) have a high incidence of acute renal failure (ARF). However, it is unclear if ARF is independently associated with mortality after this procedure. Methods. We performed meta-analysis of published reports on ARF after myeloablative allogeneic HCT. Four databases (MEDLINE, Cochrane Library, PubMed, Web of Science) and hand searching of conference proceedings were used to identify the studies. ARF was defined as the doubling of serum creatinine occurring within the first 100 days after HCT. The absolute and the relative risks for death after ARF were calculated for every study. The combined relative risk was calculated using the random effects model. Also, multivariate analysis of patient level data was performed on patients from The University of Colorado to establish independent association between ARF and mortality. Results. One thousand two hundred and eleven patients were included in the meta-analysis from the 6 published reports in the literature. The overall incidence of ARF varied from 42% to 84% in these studies. On combining the studies by random-effects model, the relative risk of death after ARF was 2.22 (95%CI 1.38–3.5, P< 0.001). The analysis of patient level data from the University of Colorado demonstrated increasing mortality with worsening grades of ARF. After controlling for various demographic and clinical variables with logistic regression, patients who required dialysis had a 6.8-fold higher association with mortality. Conclusion. ARF appears to independently influence mortality after myeloablative allogeneic HCT. Future studies should be aimed at interventions that can reduce the incidence and severity of ARF with this procedure. [ABSTRACT FROM AUTHOR]

Renal dysfunction in allogeneic hematopoietic cell transplantation. Background. Allogeneic hematopoietic cell transplantation (HCT), formerly called bone marrow transplantation, can potentially cure various malignant and non-malignant diseases, but it is associated with a high risk of toxicity. We have previously shown an overall 21% incidence of severe acute renal failure in patients undergoing autologous HCT. The present study evaluated renal dysfunction in patients undergoing allogeneic HCT. Methods. The clinical course of 88 adult patients who received allogeneic HCT at the University of Colorado Health Science Center was analyzed. Renal dysfunction was classified as follows: Grade 0 = normal renal function; Grade 1 =>25% decrement in GFR but twofold increase in serum creatinine; Grade 3 =>twofold increase in serum creatinine and need for dialysis. Results. Of the 88 patients, 81 (92%) patients had some degree of renal dysfunction (Grade 1, 20 patients; Grade 2, 32 patients; Grade 3, 29 patients). Severe nephrotoxicity (Grade 2 and Grade 3 renal dysfunction) was associated with significantly higher frequencies of sepsis, hepatic toxicity and hepatic veno-occlusive disease (VOD), and lung toxicity. The overall mortality rate at the end of 6 months was 58%. Grade 3 renal dysfunction was associated with a significantly increased risk of mortality (82.6%). Conclusion. A 92% incidence of renal dysfunction in allogeneic HCT patients was found. Lung and liver toxicities were significantly correlated with developing renal dysfunction, and the mortality rates for patients with Grade 3 renal failure exceeded 80%. [ABSTRACT FROM AUTHOR]

This Commentary discusses concepts related to the development of the point-of-care (POC) diagnostic system and its advantages and disadvantages. Also discussed are the patient, provider, and financial outcomes that ought to be evaluated before the POC test becomes available for clinical use. [ABSTRACT FROM AUTHOR]

Background & Aims Acute kidney injury (AKI) is a common complication in patients with cirrhosis that increases mortality. The most common causes of AKI in these patients are prerenal azotemia, acute tubular necrosis (ATN), and hepatorenal syndrome; it is important to determine the etiology of AKI to select the proper treatment and predict patient outcome. Urine biomarkers could be used to differentiate between patients with ATN and functional causes of AKI. We performed a systematic review and meta-analysis of published studies to determine whether urine levels of interleukin (IL)18 and lipocalin 2 or neutrophil gelatinase-associated lipocalin (NGAL) are associated with the development of ATN in patients with cirrhosis. Methods We searched MEDLINE, Scopus, ISI Web of Knowledge, and conference abstracts through December 31, 2015, for studies that assessed urine biomarkers for detection of acute kidney injury in patients with cirrhosis or reported an association between urine biomarkers and all-cause mortality in these patients. We included only biomarkers assessed in 3 or more independent studies, searching for terms that included urine biomarkers, cirrhosis, NGAL, and IL18. We calculated the pooled sensitivities and specificities for detection and calculated the area under the receiver operating characteristic curve (AUC) values using a bivariate logistic mixed-effects model. We used the χ 2 test to assess heterogeneity among studies. Results We analyzed data from 8 prospective studies, comprising 1129 patients with cirrhosis. We found urine levels of the markers discriminated between patients with ATN and other types of kidney impairments, with AUC values of 0.88 for IL18 (95% confidence interval [CI], 0.79–0.97) and 0.89 for NGAL (95% CI, 0.84–0.94). Urine levels of IL18 identified patients who would die in the hospital or within 90 days (short-term mortality) with an AUC value of 0.76 (95% CI, 0.68–0.85); NGAL identified these patients with the same AUC (0.76; 95% CI, 0.71–0.82). Conclusions In a systematic review and meta-analysis, we found that urine levels of IL18 and NGAL from patients with cirrhosis discriminate between those with ATN and other types of kidney impairments, with AUC values of 0.88 and 0.89, respectively. Urine levels of IL18 and NGAL identified patients with short-term mortality with an AUC value of 0.76. These biomarkers might be used to determine prognosis and select treatments for patients with cirrhosis. [ABSTRACT FROM AUTHOR]

A response by M. Zappitelli and colleagues to a letter to the editor on their article "Early postoperative serum cystatin C predicts severe acute kidney injury following pediatric cardiac surgery" in the 2011 issue is presented.

Objective Acute kidney injury is common after cardiac surgery and associated with postoperative mortality. Perioperative cardiac biomarkers may predict acute kidney injury and mortality. We evaluated whether cardiac biomarkers were associated with severe acute kidney injury, defined as a doubling in serum creatinine or requiring renal replacement therapy during hospital stay after surgery, and mortality. Methods In a prospective multicenter cohort of adults undergoing cardiac surgery, we measured the following biomarkers in preoperative and postoperative banked plasma: high-sensitivity troponin T, cardiac troponin I, creatine kinase-MB, and N-terminal prohormone of brain natriuretic peptide. Results In the patients who were discharged alive, severe acute kidney injury occurred in 37 of 960 (3.9%), and 43 of 960 (4.5%) died within 1 year of follow-up. N-terminal prohormone of brain natriuretic peptide was the only preoperative biomarker that was independently associated with severe acute kidney injury (with log transformation, adjusted odds ratio, 1.4; 95% confidence interval, 1.0-1.9). Biomarkers measured within 6 hours of surgery (day 1) were all associated with severe acute kidney injury. Preoperative N-terminal prohormone of brain natriuretic peptide was also independently associated with 1-year mortality (with log transformation, adjusted odds ratio, 1.7; 95% confidence interval, 1.2-2.2). Patients in the highest tertile for N-terminal prohormone of brain natriuretic peptide preoperatively (>1006.4 ng/L) had marked increases in their risk for 1-year mortality (adjusted odds ratio, 27.2; 95% confidence interval, 3.5-213.5). Day 1 N-terminal prohormone of brain natriuretic peptide was associated with mortality independently of change in serum creatinine from preoperative baseline. Conclusions Of the studied biomarkers, N-terminal prohormone of brain natriuretic peptide was the only preoperative biomarker independently associated with severe acute kidney injury and mortality. Early increases in postoperative cardiac biomarkers were associated with severe acute kidney injury after cardiac surgery. Future research should focus on whether interventions that lower N-terminal prohormone of brain natriuretic peptide can affect postoperative outcomes. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Biomarkers For The Diagnosis and Risk Stratification of Acute Kidney Injury: A Systematic Review" by S. G. Coca, R. Yalavarthy and J. Concato in a previous issue.

Acute kidney injury may increase the risk for chronic kidney disease and end-stage renal disease. In an attempt to summarize the literature and provide more compelling evidence, we conducted a systematic review comparing the risk for CKD, ESRD, and death in patients with and without AKI. From electronic databases, web search engines, and bibliographies, 13 cohort studies were selected, evaluating long-term renal outcomes and non-renal outcomes in patients with AKI. The pooled incidence of CKD and ESRD were 25.8 per 100 person-years and 8.6 per 100 person-years, respectively. Patients with AKI had higher risks for developing CKD (pooled adjusted hazard ratio 8.8, 95% CI 3.1-25.5), ESRD (pooled adjusted HR 3.1, 95% CI 1.9-5.0), and mortality (pooled adjusted HR 2.0, 95% CI 1.3-3.1) compared with patients without AKI. The relationship between AKI and CKD or ESRD was graded on the basis of the severity of AKI, and the effect size was dampened by decreased baseline glomerular filtration rate. Data were limited, but AKI was also independently associated with the risk for cardiovascular disease and congestive heart failure, but not with hospitalization for stroke or all-cause hospitalizations. Meta-regression did not identify any study-level factors that were associated with the risk for CKD or ESRD. Our review identifies AKI as an independent risk factor for CKD, ESRD, death, and other important non-renal outcomes. [ABSTRACT FROM AUTHOR]

Background: Contrast-associated acute kidney injury (CA-AKI) associates with an increased relative risk for serious adverse outcomes. However, the magnitude of this risk and the incidence of clinically significant CA-AKI derived from analyses of large cohorts with prospective assessment of CA-AKI and subsequent outcomes are unknown.Objectives: This study sought to characterize the relative risk for and incidence of serious adverse outcomes following the development of CA-AKI and to explore whether CA-AKI mediates the association of pre-angiography estimated glomerular filtration rate with adverse outcomes.Methods: Among 4,418 participants in the PRESERVE (Prevention of Serious Adverse Outcomes Following Angiography) trial with comprehensive baseline and outcome data, we assessed whether CA-AKI was associated with the 90-day outcome comprising death, need for dialysis, or persistent impairment in kidney function. We calculated the incidence of clinically significant CA-AKI (i.e., proportion of patients who developed CA-AKI and the 90-day outcome) and examined whether CA-AKI was a mediator of the association of baseline kidney function with the 90-day outcome.Results: CA-AKI was associated with an increased relative risk for 90-day death, need for dialysis, or persistent kidney impairment (odds ratio: 3.93; 95% confidence interval: 2.82 to 5.49; p < 0.0001). The incidence of clinically significant CA-AKI was 1.2% (53 of 4,418 patients). CA-AKI was not a mediator of the association of pre-angiography estimated glomerular filtration rate with the primary outcome.Conclusions: Whereas CA-AKI is associated with an increased relative risk of serious, adverse 90-day outcomes, the incidence of clinically significant CA-AKI is very low. CA-AKI does not mediate the association of the pre-angiography estimated glomerular filtration rate with these outcomes. [ABSTRACT FROM AUTHOR]

Background: It is widely believed that a reduced cardiac index (CI) is a significant contributor to renal dysfunction in patients with heart failure (HF). However, recent data have challenged this paradigm.Objectives: This study sought to determine the relationship between CI and renal function in a multicenter population of HF patients undergoing pulmonary artery catheterization (PAC).Methods: Patients undergoing PAC in either the randomized or registry portions of the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial were included (n = 575). We evaluated associations between CI and renal function across multiple subgroups and assessed for nonlinear, threshold, and longitudinal relationships.Results: There was a weak but significant inverse correlation between CI and estimated glomerular filtration rate (eGFR), such that higher CI was paradoxically associated with worse eGFR (r = -0.12; p = 0.02). CI was not associated with blood urea nitrogen (BUN) or the BUN to creatinine ratio. Similarly, no associations were observed between CI and better renal function across multiple subgroups defined by indications for PAC or hemodynamic, laboratory, or demographic parameters. A nonlinear or threshold effect could not be identified. In patients with serial assessments of renal function and CI, we were unable to find within-subject associations between change in CI and eGFR using linear mixed modeling. Neither CI nor change in CI was lower in patients developing worsening renal function (p ≥ 0.28).Conclusions: These results reinforce evidence that reduced CI is not the primary driver for renal dysfunction in patients hospitalized for HF, irrespective of the degree of CI impairment or patient subgroup analyzed. [ABSTRACT FROM AUTHOR]