Defining Baseline Creatinine for Identification of Acute Kidney Injury in Population-based Laboratory Databases - A Danish Nationwide Cohort Study

Background: The baseline creatinine level is central in the KDIGO criteria of acute kidney injury (AKI), but baseline creatinine is often inconsistently defined or unavailable in AKI research. We examined the rate, characteristics, and 30-day mortality of AKI in five AKI cohorts created using different definitions of baseline creatinine. Methods: This nationwide cohort study included all individuals aged ≥18 in Denmark with a creatinine measurement in year 2017. Applying the KDIGO criteria, we created four AKI cohorts using four different baseline definitions (most recent, mean, or median value of outpatient creatinine 365-8 days before, or median value 90-8 days before if available otherwise median value 365-91 days before) and one AKI cohort not using a baseline value. AKI rate and the distribution of age, sex, baseline creatinine, and comorbidity was described for each AKI cohort, and the 30-day all-cause mortality was estimated using the Kaplan-Meier method. Results: The study included 2,095,850 adults with at least one creatinine measurement in 2017. The four different baseline definitions identified between 61,189 and 62,597 AKI episodes. The AKI rate in these four cohorts was 13-14 per 1,000 person-years, and 30-day all-cause mortality was 17-18%. The cohort created without using a baseline creatinine included 37,659 AKI episodes, corresponding to an AKI rate of 8.2 per 1,000 person-years, and a 30-day mortality of 23%. All five cohorts were similar regarding age, sex, and comorbidity. Conclusions: In a population-based setting with available outpatient baseline creatinine, different baseline creatinine definitions revealed comparable AKI cohorts, while the lack of a baseline creatinine when defining AKI led to a smaller AKI cohort with a higher mortality. These findings underscore the importance of availability and consistent use of an outpatient baseline creatinine, in particular in studies of community-acquired AKI.

Validation study of canine urine cortisol measurement with the Immulite 2000 Xpi cortisol immunoassay

We report here validation of the Immulite 2000 Xpi cortisol immunoassay (Siemens; with kit lot numbers <550) for measurement of urine cortisol in dogs, with characterization of the precision (CV), accuracy (spiking-recovery [SR] bias), and observed total error (TEo = bias + 2CV) across the reportable range. Linearity assessed by simple linear regression was excellent. Imprecision, SR bias, and TEo increased markedly with decreasing urine cortisol concentration. Interlaboratory comparison studies determined range-based (RB) bias and average bias (AB). The 3 biases (SR, RB, and AB) and resulting TEo differed markedly. At 38.6 and 552 nmol/L (1.4 and 20 μg/dL), between-run CVs were 10% and 4.5%, respectively, and TEoRB were ~30% and 20%, respectively, similar to observations in serum in another validation study. These analytical performance parameters should be considered for urine cortisol:creatinine ratio (UCCR) result interpretation, given that, for any hypothetical errorless urine creatinine measurement, the error % on UCCR mirrors the error % on urine cortisol. Importantly, there is no commonly used interpretation threshold for UCCR, given that UCCR varies greatly depending on measurement methods and threshold computation. To date, there is no manufacturer-provided quality control material (QCM) with target values for urine cortisol with an Immulite; for Liquicheck QCM (Bio-Rad), between-run imprecision was ~5% for both QCM levels. Acceptable QC rules are heavily dependent on the desired total allowable error (TEa) for the QCM system, itself limited by the desired clinical TEa.

EXPRESS: Drug dosing using estimated Glomerular Filtration Rate: Misclassification due to metamizole interference in a creatinine assay

The estimated glomerular filtration rate is a rather important measurement for patients under intensive care, since they often receive several drugs, and impaired renal function may result in misleading dosing. The estimated glomerular filtration is derived from mathematical models using serum creatinine, a measurement that suffers interference of some drugs, such as metamizole. The study intented to evaluate the impact on patient stratification for dose adjustment of two antimicrobials (meropenem and vancomycin) caused by metamizole interference in creatinine measurement by dry chemistry. A cross-sectional study was conducted with a group of 108 hospitalized patients under metamizole prescriptions at fixed intervals. Serum creatinine levels were determined by enzymatic dry chemistry and Jaffé assays and the estimated glomerular filtration rate was calculated through the CKD-EPI equation. Patients were stratified in groups according to their estimated glomerular filtration rate for drug dosing of vancomycin and meropenem. As expected, creatinine values were significantly lower in measurements performed by the dry chemistry method in comparison to Jaffé assay (p<0.0001) when patients are under metamizole treatment. A significant bias (-40.3%) was observed between those two methods, leading to a significant difference (p<0.0001) in patient classification according to renal function using the CKD-EPI equation for dosing adjustment. Thus, during the validity of metamizole treatment, the stratification for drug dosing by the estimated glomerular filtration rate is not reliable if the creatinine measurement is done through dry chemistry. Clinical and laboratory staff must be aware of these limitations and cooperate to optimize pharmacotherapy.

Vancomycin Associated Acute Kidney Injury: A Longitudinal Study in China

Background: Vancomycin-associated acute kidney injury (VA-AKI) is a recognizable condition with known risk factors. However, the use of vancomycin in clinical practices in China is distinct from other countries. We conducted this longitudinal study to show the characteristics of VA-AKI and how to manage it in clinical practice.Patients and Methods: We included patients admitted to hospital, who received vancomycin therapy between January 1, 2016 and June 2019. VA-AKI was defined as a patient having developed AKI during vancomycin therapy or within 48 h following the withdrawal of vancomycin therapy.Results: A total of 3719 patients from 7058 possible participants were included in the study. 998 patients were excluded because of lacking of serum creatinine measurement. The incidence of VA-AKI was 14.3%. Only 32.3% (963/2990) of recommended patients performed therapeutic drug monitoring of vancomycin. Patients with VA-AKI were more likely to concomitant administration of cephalosporin (OR 1.55, 95% CI 1.08–2.21, p = 0.017), carbapenems (OR 1.46, 95% CI 1.11–1.91, p = 0.006) and piperacillin-tazobactam (OR 3.12, 95% CI 1.50–6.49, p = 0.002). Full renal recovery (OR 0.208, p = 0.005) was independent protective factors for mortality. Compared with acute kidney injury stage 1, AKI stage 2 (OR 2.174, p = 0.005) and AKI stage 3 (OR 2.210, p = 0.005) were independent risk factors for fail to full renal recovery.Conclusion: Lack of a serum creatinine measurement for the diagnosis of AKI and lack of standardization of vancomycin therapeutic drug monitoring should be improved. Patient concomitant with piperacillin-tazobactam are at higher risk. Full renal recovery was associated with a significantly reduced morality.

The Association Between Estimated Glomerular Filtration Rate and Hospitalization for Fatigue: A Population-Based Cohort Study

Background: Fatigue is a pervasive symptom among patients with chronic kidney disease (CKD) that is associated with several adverse outcomes, but the incidence of hospitalization for fatigue is unknown. Objective: To explore the association between estimated glomerular filtration rate (eGFR) and incidence of hospitalization for fatigue. Design: Population-based retrospective cohort study using a provincial administrative dataset. Setting: Alberta, Canada. Patients: People above age 18 who had at least 1 outpatient serum creatinine measurement taken in Alberta between January 1, 2009, and December 31, 2016. Measurements: The first outpatient serum creatinine was used to estimate GFR. Hospitalization for fatigue was identified using International Classification of Diseases, Tenth Revision (ICD-10) code R53.x. Methods: Patients were stratified by CKD category based on their index eGFR. We used negative binomial regression to determine if there was an increased incidence of hospitalization for fatigue by declining kidney function (reference eGFR ≥ 60 mL/min/1.73m2). Estimates were stratified by age, and adjusted for age, sex, socioeconomic status, and comorbidity. Results: The study cohort consisted of 2 823 270 adults, with a mean age of 46.1 years and median follow-up duration of 6.0 years; 5 422 hospitalizations for fatigue occurred over 14 703 914 person-years of follow-up. Adjusted rates of hospitalization for fatigue increased with decreasing kidney function, across all age strata. The highest rates were seen in adults on dialysis (adjusted incident rate ratios 24.47, 6.66, and 3.13 for those aged 18 to 64, 65 to 74, and 75+, respectively, compared with eGFR ≥ 60 mL/min/1.73m2). Limitations: Fatigue hospitalization codes have not been validated; reference group limited to adults with at least 1 outpatient serum creatinine measurement; remaining potential for residual confounding. Conclusions: Declining kidney function was associated with increased incidence of hospitalization for fatigue. Further research into ways to address fatigue in the CKD population is warranted. Trial Registration: Not applicable (not a clinical trial).

The validity of Dutch health claims data for identifying patients with chronic kidney disease: a hospital-based study in the Netherlands

Background Health claims data may be an efficient and easily accessible source to study chronic kidney disease (CKD) prevalence in a nationwide population. Our aim was to study Dutch claims data for their ability to identify CKD patients in different subgroups. Methods From a laboratory database, we selected 24 895 adults with at least one creatinine measurement in 2014 ordered at an outpatient clinic. Of these, 15 805 had ≥2 creatinine measurements at least 3 months apart and could be assessed for the chronicity criterion. We estimated the validity of a claim-based diagnosis of CKD and advanced CKD. The estimated glomerular filtration rate (eGFR)-based definitions for CKD (eGFR &lt; 60 mL/min/1.73 m2) and advanced CKD (eGFR &lt; 30 mL/min/1.73 m2) satisfying and not satisfying the chronicity criterion served as reference group. Analyses were stratified by age and sex. Results In general, sensitivity of claims data was highest in the population with the chronicity criterion as reference group. Sensitivity was higher in advanced CKD patients than in CKD patients {51% [95% confidence interval (CI) 47–56%] versus 27% [95% CI 25–28%]}. Furthermore, sensitivity was higher in young versus elderly patients. In patients with advanced CKD, sensitivity was 72% (95% CI 62–83%) for patients aged 20–59 years and 43% (95% CI 38–49%) in patients ≥75 years. The specificity of CKD and advanced CKD was ≥99%. Positive predictive values ranged from 72% to 99% and negative predictive values ranged from 40% to 100%. Conclusion When using health claims data for the estimation of CKD prevalence, it is important to take into account the characteristics of the population at hand. The younger the subjects and the more advanced the stage of CKD the higher the sensitivity of such data. Understanding which patients are selected using health claims data is crucial for a correct interpretation of study results.

Real-world data on adjuvant bisphosphonate use in a breast cancer center in Mexico.

e12544 Background: Results from the Early Breast Cancer Trials Collaborative Group (EBCTCG) meta-analysis published in 2015 showed a significant reduction in risk of distant recurrence, bone recurrence and a 10-year breast cancer mortality reduction1. Moreover, Cancer Care Ontario and ASCO issued a guideline regarding the use of adjuvant bisphosphonates (AB) in breast cancer postmenopausal patients2. While these data are compelling, we have no information to support the implementation of this recommendation at Hospital San José’s Breast Cancer Center (HSJBCC). Methods: A retrospective analysis was performed to evaluate our compliance to the current recommendations for AB administration from 2015 through 2019. Inclusion criteria were based on the ASCO guidelines and comprised invasive breast cancer, postmenopausal status and early or locally advanced stage. Furthermore, in AB-treated patients we assessed the percentage of baseline calcium and creatinine measurement, prior dental evaluation, and concurrent calcium and vitamin-D supplementation during AB use. Results: A total of 106 patients met the inclusion criteria. Within the 4-year timeframe, AB was prescribed to 28/106 (26%) patients. Stratifying by year, we observed an increase of AB use rate from 4% in 2015 to 32% in 2019. Moreover, we observed a 93% baseline calcium and creatinine measurement, a 60% prior dental evaluation, and a 43% concurrent calcium and vitamin-D supplementation in the AB-treated population. Conclusions: HSJBCC recommendation for AB use is less than expected in the evaluated eligible patients in the 4-year timeframe. Despite an increase in our compliance to current ASCO guidelines it is not yet the standard of care at HSJBCC. Based on these results, we are currently planning a quality improvement initiative to undertake our low percentage of AB usage. [Table: see text]