Being able to predict whether AKI will progress could improve monitoring and care, guide patient counseling, and assist with enrollment into trials of AKI treatment. Using samples from the ...Translational Research Investigating Biomarker Endpoints in AKI study (TRIBE-AKI), we evaluated whether kidney injury biomarkers measured at the time of first clinical diagnosis of early AKI after cardiac surgery can forecast AKI severity. Biomarkers included urinary IL-18, urinary albumin to creatinine ratio (ACR), and urinary and plasma neutrophil gelatinase-associated lipocalin (NGAL); each measurement was on the day of AKI diagnosis in 380 patients who developed at least AKI Network (AKIN) stage 1 AKI. The primary end point (progression of AKI defined by worsening AKIN stage) occurred in 45 (11.8%) patients. Using multivariable logistic regression, we determined the risk of AKI progression. After adjustment for clinical predictors, compared with biomarker values in the lowest two quintiles, the highest quintiles of three biomarkers remained associated with AKI progression: IL-18 (odds ratio=3.0, 95% confidence interval=1.3-7.3), ACR (odds ratio=3.4, 95% confidence interval=1.3-9.1), and plasma NGAL (odds ratio=7.7, 95% confidence interval=2.6-22.5). Each biomarker improved risk classification compared with the clinical model alone, with plasma NGAL performing the best (category-free net reclassification improvement of 0.69, P<0.0001). In conclusion, biomarkers measured on the day of AKI diagnosis improve risk stratification and identify patients at higher risk for progression of AKI and worse patient outcomes.
Background In Central America, an epidemic of chronic kidney disease of unknown cause disproportionately affects young male agricultural workers. Study Design Longitudinal cohort study. Setting & ...Participants 284 sugarcane workers in 7 jobs were recruited from one company in northwestern Nicaragua. Blood and urine samples were collected before and near the end of the 6-month harvest season. Predictors Job category (cane cutter, seeder, seed cutter, agrichemical applicator, irrigator, driver, and factory worker); self-reported water and electrolyte solution intake. Outcomes & Measurements Changes in levels of urinary kidney injury biomarkers normalized to urine creatinine level, including neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), N -acetyl-β- d -glucosaminidase (NAG), and albumin; serum creatinine–based estimated glomerular filtration rate (eGFR). Results Mean eGFR was 113 mL/min/1.73 m2 and <5% of workers had albuminuria. Field workers had increases in NGAL and IL-18 levels that were 1.49 (95% CI, 1.06 to 2.09) and 1.61 (95% CI, 1.12 to 2.31) times as high, respectively, as in non–field workers. Cane cutters and irrigators had the greatest increases in NGAL levels during the harvest, whereas cane cutters and seeders had the greatest increases in IL-18 levels. Electrolyte solution consumption was associated with lower mean NGAL and NAG levels among cane cutters and lower mean IL-18 and NAG levels among seed cutters; however, there was no overall effect of hydration among all workers. On average, workers with the largest increases in NGAL and NAG levels during the harvest had declines in eGFRs of 4.6 (95% CI, 1.0 to 8.2) and 3.1 (95% CI, −0.6 to 6.7) mL/min/1.73 m2 , respectively. Limitations Surrogate exposure measure, loss to follow-up. Conclusions Results are consistent with the hypothesis that occupational heat stress and volume depletion may be associated with the development of kidney disease, and future studies should directly measure these occupational factors. The presence of urine tubular injury markers supports a tubulointerstitial disease that could occur with repeated tubular injury.
Acute kidney injury (AKI) occurs commonly after pediatric cardiac surgery and associates with poor outcomes. Biomarkers may help the prediction or early identification of AKI, potentially increasing ...opportunities for therapeutic interventions. Here, we conducted a prospective, multicenter cohort study involving 311 children undergoing surgery for congenital cardiac lesions to evaluate whether early postoperative measures of urine IL-18, urine neutrophil gelatinase-associated lipocalin (NGAL), or plasma NGAL could identify which patients would develop AKI and other adverse outcomes. Urine IL-18 and urine and plasma NGAL levels peaked within 6 hours after surgery. Severe AKI, defined by dialysis or doubling in serum creatinine during hospital stay, occurred in 53 participants at a median of 2 days after surgery. The first postoperative urine IL-18 and urine NGAL levels strongly associated with severe AKI. After multivariable adjustment, the highest quintiles of urine IL-18 and urine NGAL associated with 6.9- and 4.1-fold higher odds of AKI, respectively, compared with the lowest quintiles. Elevated urine IL-18 and urine NGAL levels associated with longer hospital stay, longer intensive care unit stay, and duration of mechanical ventilation. The accuracy of urine IL-18 and urine NGAL for diagnosis of severe AKI was moderate, with areas under the curve of 0.72 and 0.71, respectively. The addition of these urine biomarkers improved risk prediction over clinical models alone as measured by net reclassification improvement and integrated discrimination improvement. In conclusion, urine IL-18 and urine NGAL, but not plasma NGAL, associate with subsequent AKI and poor outcomes among children undergoing cardiac surgery.
Abstract Background Net fluid and weight loss are used ubiquitously to monitor diuretic response in acute decompensated heart failure research and patient care. However, the performance of these ...metrics has never been evaluated critically. The weight and volume of aqueous fluids such as urine should be correlated nearly perfectly and with very good agreement. As a result, significant discrepancy between fluid and weight loss during the treatment of acute decompensated heart failure would indicate measurement error in 1 or both of the parameters. Methods The correlation and agreement (Bland-Altman method) between diuretic-induced fluid and weight loss were examined in 3 acute decompensated heart failure trials and cohorts: (1) Diuretic Optimization Strategies Evaluation (DOSE) (n = 254); (2) Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) (n = 348); and (3) Penn (n = 486). Results The correlation between fluid and weight loss was modest (DOSE r = 0.55; ESCAPE r = 0.48; Penn r = 0.51; P < .001 for all), and the 95% limits of agreement were wide (DOSE −7.9 to 6.4 kg-L; ESCAPE −11.6 to 7.5 kg-L; Penn −14.5 to 11.3 kg-L). The median relative disagreement ranged from ±47.0% to 63.5%. A bias toward greater fluid than weight loss was found across populations (−0.74 to −2.1 kg-L, P ≤ .002). A consistent pattern of baseline characteristics or in-hospital treatment parameters that could identify patients at risk of discordant fluid and weight loss was not found. Conclusions Considerable discrepancy between fluid balance and weight loss is common in patients treated for acute decompensated heart failure. Awareness of the limitations inherent to these commonly used metrics and efforts to develop more reliable measures of diuresis are critical for both patient care and research in acute decompensated heart failure.
Severe acute kidney injury (AKI) is known to have prognostic value for in-hospital outcomes in malaria. However, little is known about the association of AKI of lesser severity with malarial risk ...factors and outcomes--and such a gap is becoming increasingly relevant with the upsurge in the incidence of AKI due to Plasmodium falciparum malaria and Plasmodium vivax malaria over the last decade. We aimed to identify risk factors of AKI in malaria and assessed in-hospital outcomes stratified by severity of AKI. We performed an observational study of 1,191 hospitalized malaria patients enrolled between 2007 and 2011 in a tertiary care academic center in India. Patients were categorized based on peak serum creatinine into one of three groups: no AKI (<1.6 mg/dL), mild AKI (1.6-3.0 mg/dL), and severe AKI (>3 mg/dL). Plasmodium vivax was the predominant species (61.41%), followed by Plasmodium falciparum (36.41%) and mixed infections with both the species (2.18%). Mild and severe AKI were detected in 12% and 5.6% of patients, respectively. Mild AKI due to Plasmodium vivax (49%) and Plasmodium falciparum (48.5%) was distributed relatively equally within the sample population; however, cases of severe AKI due to Plasmodium falciparum (80%) and Plasmodium vivax (13%) was significantly different (P<0.001). On history and physical examination, risk factors for AKI were age, absence of fever, higher heart rate, lower diastolic blood pressure, icterus, and hepatomegaly. The only laboratory parameter associated with risk of AKI on multivariate analysis was direct bilirubin. Patients with mild and severe AKI had greater organ complications, supportive requirements, longer duration of hospital stay and in-hospital mortality in a dose-dependent relationship, than patients with no AKI. Mild AKI is associated with significant (P<0.05) morbidity compared to no AKI, and future studies should assess strategies for early diagnosis of AKI and prevent AKI progression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background The prevalence of elderly individuals continues to increase over time, as does the incidence of acute kidney injury (AKI). However, it is not known whether age is an important prognostic ...predictor for renal recovery after an episode of AKI. Study Design Systematic review of MEDLINE and EMBASE databases and meta-analysis of pooled data using random-effect models. Setting & Population Adults with AKI, not including kidney transplant recipients. Selection Criteria for Studies Studies published in English between 2000 and 2007 were eligible for this analysis if they met the following inclusion criteria: (1) clear definition of AKI and recovery of kidney function, (2) assessment of kidney function recovery as the primary or secondary outcome, and (3) participant age reported. We contacted the investigators of studies and requested data for recovery of kidney function by patient age. Predictor Patient age of 65 years and older and younger than 65 years. Outcomes Recovery of kidney function defined as independence from dialysis therapy, decrease in serum creatinine level to less than a defined threshold, or return to baseline kidney function. Results We obtained data for recovery of kidney function by age from 17 studies of patients with AKI. Overall, 31.3% of surviving elderly patients did not recover kidney function compared with 26% of younger patients (pooled relative risk, 1.28, 95% confidence interval, 1.06 to 1.55; P < 0.05). The increased risk of nonrecovery in the elderly remained greater in several subgroups examined through sensitivity analyses, including those stratified by type of dialysis support, time of assessment of recovery (short versus long term), and definition of renal recovery. Limitations There was significant heterogeneity among studies with respect to comorbid factors, definition of AKI, and study design. Conclusions There is impaired recovery of kidney function after AKI in aged individuals. Future studies should be cognizant of “age” as a potential effect modifier in the prognosis after AKI, and clinical trials should focus on improving outcomes in the elderly cohort.
Aims/hypothesis
Higher plasma concentrations of tumour necrosis factor receptor (TNFR)-1, TNFR-2 and kidney injury molecule-1 (KIM-1) have been found to be associated with higher risk of kidney ...failure in individuals with type 2 diabetes in previous studies. Whether drugs can reduce these biomarkers is not well established. We measured these biomarkers in samples of the CANVAS study and examined the effect of the sodium–glucose cotransporter 2 inhibitor canagliflozin on these biomarkers and assessed whether the early change in these biomarkers predict cardiovascular and kidney outcomes in individuals with type 2 diabetes in the CANagliflozin cardioVascular Assessment Study (CANVAS).
Methods
Biomarkers were measured with immunoassays (proprietary multiplex assay performed by RenalytixAI, New York, NY, USA) at baseline and years 1, 3 and 6. Mixed-effects models for repeated measures assessed the effect of canagliflozin vs placebo on the biomarkers. Associations of baseline levels and the early change (baseline to year 1) for each biomarker with the kidney outcome were assessed using multivariable-adjusted Cox regression.
Results
In total, 3523/4330 (81.4%) of the CANVAS participants had available samples at baseline. Each doubling in baseline TNFR-1, TNFR-2 and KIM-1 was associated with a higher risk of kidney outcomes, with corresponding HRs of 3.7 (95% CI 2.3, 6.1;
p
< 0.01), 2.7 (95% CI 2.0, 3.6;
p
< 0.01) and 1.5 (95% CI 1.2, 1.8;
p
< 0.01), respectively. Canagliflozin reduced the level of the plasma biomarkers with differences in TNFR-1, TNFR-2 and KIM-1 between canagliflozin and placebo during follow-up of 2.8% (95% CI 3.4%, 1.3%;
p
< 0.01), 1.9% (95% CI 3.5%, 0.2%;
p
= 0.03) and 26.7% (95% CI 30.7%, 22.7%;
p
< 0.01), respectively. Within the canagliflozin treatment group, each 10% reduction in TNFR-1 and TNFR-2 at year 1 was associated with a lower risk of the kidney outcome (HR 0.8 95% CI 0.7, 1.0;
p
= 0.02 and 0.9 95% CI 0.9, 1.0;
p
< 0.01 respectively), independent of other patient characteristics. The baseline and 1 year change in biomarkers did not associate with cardiovascular or heart failure outcomes.
Conclusions/interpretation
Canagliflozin decreased KIM-1 and modestly reduced TNFR-1 and TNFR-2 compared with placebo in individuals with type 2 diabetes in CANVAS. Early decreases in TNFR-1 and TNFR-2 during canagliflozin treatment were independently associated with a lower risk of kidney disease progression, suggesting that TNFR-1 and TNFR-2 have the potential to be pharmacodynamic markers of response to canagliflozin.
Graphical abstract
Serum creatinine is not an ideal marker of renal function in patients with acute kidney injury (AKI). Previous studies demonstrated that urinary IL-18 is increased in human AKI. Thus, whether urine ...IL-18 is an early diagnostic marker of AKI was investigated. A nested case-control study was performed within the Acute Respiratory Distress Syndrome (ARDS) Network trial. AKI was defined as an increase in serum creatinine by at least 50% within the first 6 d of ARDS study enrollment. A total of 400 urine specimens that were collected on study days 0, 1, and 3 of the ARDS trial were available from 52 case patients and 86 control patients. The data were analyzed in a cross-sectional manner and according to the time before development of AKI. The median urine IL-18 levels were significantly different at 24 and 48 h before AKI in case patients as compared with control patients. On multivariable analysis, urine IL-18 values predicted development of AKI 24 and 48 h later after adjustment for demographics, sepsis, Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) III score, serum creatinine, and urine output. Urine IL-18 levels of >100 pg/ml are associated with increased odds of AKI of 6.5 (95% confidence interval 2.1 to 20.4) in the next 24 h. On diagnostic performance testing, urine IL-18 demonstrates an area under the receiver operating characteristic curve of 73% to predict AKI in the next 24 h. The urine IL-18 values were also significantly different between survivors and nonsurvivors (P < 0.05), and on multivariable analysis, the urine IL-18 value on day 0 is an independent predictor of mortality. Urinary IL-18 levels can be used for the early diagnosis of AKI. Urine IL-18 levels also predict the mortality of patients who have ARDS and are in the intensive care unit.
Random assignment to intensive blood pressure (BP) lowering (systolic BP<120mmHg) compared to a less intensive BP target (systolic BP<140mmHg) in the Action to Control Cardiovascular Risk in Diabetes ...BP (ACCORD-BP) trial resulted in a more rapid decline in estimated glomerular filtration rate (eGFR). Whether this reflects hemodynamic effects or intrinsic kidney damage is unknown.
Longitudinal analysis of a subgroup of clinical trial participants.
A subgroup of 529 participants in ACCORD-BP.
Urine biomarkers of tubular injury (kidney injury molecule 1, interleukin 18 IL-18), repair (human cartilage glycoprotein 39 YKL-40), and inflammation (monocyte chemoattractant protein 1) at baseline and year 2.
Changes in eGFR from baseline to 2 years.
We compared changes in biomarker levels and eGFRs across participants treated to an intensive versus less intensive BP goal using analysis of covariance.
Of 529 participants, 260 had been randomly assigned to the intensive and 269 to the standard BP arm. Mean age was 62±6.5 years and eGFR was 90mL/min/1.73m2. Baseline clinical characteristics, eGFRs, urinary albumin-creatinine ratios (ACRs), and urinary biomarker levels were similar across BP treatment groups. Compared to less intensive BP treatment, eGFR was 9.2mL/min/1.73m2 lower in the intensive BP treatment group at year 2. Despite the eGFR reduction, within this treatment group, ACR was 30% lower and 4 urinary biomarker levels were unchanged or lower at year 2. Also within this group, participants with the largest declines in eGFRs had greater reductions in urinary IL-18 and YKL-40 levels. In a subgroup analysis of participants developing incident chronic kidney disease (sustained 30% decline and eGFR<60mL/min/1.73m2; n=77), neither ACR nor 4 biomarker levels increased in the intensive treatment group, whereas the level of 1 biomarker, IL-18, increased in the less intensive treatment group.
Few participants with advanced baseline chronic kidney disease. Comparisons across treatment groups do not represent comparisons of treatment arms created solely through randomization.
Among a subset of ACCORD-BP trial participants, intensive BP control was associated with reductions in eGFRs, but not with an increase in injury marker levels. These findings support that eGFR decline observed with intensive BP goals in ACCORD participants may predominantly reflect hemodynamic alterations.
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