Physician adjudication of angioedema diagnosis codes in a population of patients with heart failure prescribed angiotensin-converting enzyme inhibitor therapy.

PURPOSE: Our objective was to calculate the positive predictive value (PPV) of the ICD-9 diagnosis code for angioedema when physicians adjudicate the events by electronic health record review. Our secondary objective was to evaluate the inter-rater reliability of physician adjudication. METHODS: Patients from the Cardiovascular Research Network previously diagnosed with heart failure who were started on angiotensin-converting enzyme inhibitors (ACEI) during the study period (July 1, 2006 through September 30, 2015) were included. A team of two physicians per participating site adjudicated possible events using electronic health records for all patients coded for angioedema for a total of five sites. The PPV was calculated as the number of physician-adjudicated cases divided by all cases with the diagnosis code of angioedema (ICD-9-CM code 995.1) meeting the inclusion criteria. The inter-rater reliability of physician teams, or kappa statistic, was also calculated. RESULTS: There were 38 061 adults with heart failure initiating ACEI in the study (21 489 patient-years). Of 114 coded events that were adjudicated by physicians, 98 angioedema events were confirmed for a PPV of 86% (95% CI: 80%, 92%). The kappa statistic based on physician inter-rater reliability was 0.65 (95% CI: 0.47, 0.82). CONCLUSIONS: ICD-9 diagnosis code of 995.1 (angioneurotic edema, not elsewhere classified) is highly predictive of angioedema in adults with heart failure exposed to ACEI.

Comparison of a Kidney Replacement Therapy Risk Score Developed in Kaiser Permanente Northwest vs Estimated Glomerular Filtration Rate in Advanced Chronic Kidney Disease Using Decision Curve Analysis.

INTRODUCTION: Use of kidney replacement therapy (KRT) prediction models for guiding arteriovenous fistula (AVF) referrals in advanced chronic kidney disease (CKD) is unknown. We aimed to compare a hypothetical approach using a KRT prediction model developed in Kaiser Permanente Northwest to estimated glomerular filtration rate (eGFR) for AVF referrals. METHODS: Our retrospective cohort consisted of patients with stage G4 CKD in Kaiser Permanente Northwest followed by nephrology. Two-year KRT risk was calculated at each nephrology visit up to 2 years from entrance into cohort based on a previously published model. We calculated sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) based on several 2-year KRT risk and eGFR cutoffs for outcome of hemodialysis at 18 months. We compared an approach of AVF referral using 2-year KRT risk and eGFR cutoffs using decision curve analysis. RESULTS: Two-year KRT risk better discriminated progression to hemodialysis compared to eGFR < 15 mL/min (AUC 0.60 vs 0.69 at 2-year KRT risk > 20% and 0.69 at 2-year KRT risk > 40%, p = 0.003 and 0.006, respectively) but not to eGFR of 20 mL/min (AUC 0.64, p = 0.16 and 0.19, respectively). Decision curve analysis showed that AVF referral guided by 2-year KRT risk score resulted in higher net benefit compared to eGFR at low thresholds for referral. CONCLUSION: In stage G4 CKD, a 2-year KRT risk model better predicted progression to KRT at 18 months compared to an eGFR of 15 mL/min but not to 20 mL/min and may improve timely referral for AVF placement in patients at lower thresholds for referral.

Predicted risk of renal replacement therapy at arteriovenous fistula referral in chronic kidney disease.

BACKGROUND AND OBJECTIVES: Optimal timing of arteriovenous fistula placement in chronic kidney disease remains difficult and contributes to high central venous catheter use at initial hemodialysis. We tested whether a prediction model for progression to renal replacement therapy developed at Kaiser Permanente Northwest may help guide decisions about timing of referral for arteriovenous fistula placement. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: A total of 205 chronic kidney disease stage 4 patients followed by nephrology referred for arteriovenous fistula placement were followed for up to 2 years. Patients were censored if they died or discontinued Kaiser Permanente Northwest coverage. Survival analyses were performed for overall progression to renal replacement therapy divided by quartiles based on 2-year risk for renal replacement therapy and estimated glomerular filtrate rate at time of referral. RESULTS: By 2 years, 60% progressed to renal replacement therapy and 11% had died. 80% in the highest risk versus 36% in the lowest risk quartile progressed to renal replacement therapy (predicted risk 84% vs 17%). 75% in the lowest estimated glomerular filtrate rate versus 56% in the highest estimated glomerular filtrate rate quartile progressed to renal replacement therapy (mean estimated glomerular filtrate rate 13 mL/min vs 21 mL/min). The hazard ratio was significantly higher for each consecutive higher renal replacement therapy quartile risk while for estimated glomerular filtrate rate, the hazard ratio was only significantly higher for the lowest compared to the highest quartile. The extreme quartile risk ratio was higher for 2-year risk for renal replacement therapy compared to estimated glomerular filtrate rate (4.0 vs 2.4). CONCLUSION: In patients with chronic kidney disease stage 4 referred for arteriovenous fistula placement, 2-year renal replacement therapy risk better discriminated progression to renal replacement therapy compared to estimated glomerular filtrate rate at time of referral.

A Quality Improvement Initiative Targeting Chronic Kidney Disease Metrics Through Increased Urinary Albumin Testing.

INTRODUCTION: Achievement of quality metrics in chronic kidney disease (CKD), specifically urinary albumin testing and angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) use, remained lower in Kaiser Permanente Northwest compared with other Kaiser Permanente regions. We were interested if more frequent testing of urine albumin (ACR) improved CKD quality metrics. METHODS: We implemented a quality improvement project automating ACR testing using an informatics tool in patients with stage 3 CKD linked to an electronic health record (EHR) alert recommending ACEi or ARB initiation in patients with renal indication. RESULTS: At 1 and 2 years after implementation of ACR testing, ACR testing increased from 26.9% prior to implementation to 83% at 1 year and 77% at 2 year after implementation (p < 0.001). However, ACEi or ARB use did not increase significantly (65.8% vs 65.7% vs 66.4%, p = 0.54). There was also no significant change in other quality metrics, including diabetes control, hypertension control, and comanagement of higher-risk CKD patients. DISCUSSION AND CONCLUSION: In patients with stage 3 CKD, increased ACR testing via automated testing linked with EHR alert did not result in an improvement in CKD quality metrics.

Association of Proteinuria with Central Venous Catheter Use at Initial Hemodialysis.

CONTEXT: Central venous catheter (CVC) use is associated with increased mortality and complications in hemodialysis recipients. Although prevalent CVC use has decreased, incident use remains high. OBJECTIVE: To examine characteristics associated with CVC use at initial dialysis, specifically looking at proteinuria as a predictor of interest. DESIGN: Retrospective cohort of 918 hemodialysis recipients from Kaiser Permanente Northwest who started hemodialysis from January 1, 2004, to January 1, 2014. MAIN OUTCOME MEASURES: Multivariable logistic regression was used to examine an association of proteinuria with the primary outcome of CVC use. RESULTS: More than one-third (36%) of patients in our cohort started hemodialysis with an arteriovenous fistula, and 64% started with a CVC. Proteinuria was associated with starting hemodialysis with a CVC (likelihood ratio test, p < 0.001) after adjustment for age, peripheral vascular disease, congestive heart failure, diabetes, sex, race, and length of predialysis care. However, on pairwise comparison, only patients with midgrade proteinuria (0.5-3.5 g) had lower odds of starting hemodialysis with a CVC (odds ratio = 0.39, 95% confidence interval = 0.24-0.65). CONCLUSION: Proteinuria was associated with use of CVC at initial hemodialysis. However, a graded association did not exist, and only patients with midgrade proteinuria had significantly lower odds of CVC use. Our findings suggest that proteinuria is an explanatory finding for CVC use but may not have pragmatic value for decision making. Patients with lower levels of proteinuria may have a higher risk of starting dialysis with a CVC.

Advances of genomic science and systems biology in renal transplantation: a review.

The diagnosis of rejection in kidney transplant patients is based on histologic classification of a graft biopsy. The current "gold standard" is the Banff 97 criteria; however, there are several limitations in classifying rejection based on biopsy samples. First, a biopsy involves an invasive procedure. Second, there is significant variance among blinded pathologists in the interpretation of a biopsy. And third, there is also variance between the histology and the molecular profiles of a biopsy. To increase the positive predictive value of classifiers of rejection, a Banff committee is developing criteria that integrate histologic and molecular data into a unified classifier that could diagnose and prognose rejection. To develop the most appropriate molecular criteria, there have been studies by multiple groups applying omics technologies in attempts to identify biomarkers of rejection. In this review, we discuss studies using genome-wide data sets of the transcriptome and proteome to investigate acute rejection, chronic allograft dysfunction, and tolerance. We also discuss studies which focus on genetic biomarkers in urine and peripheral blood, which will provide clinicians with minimally invasive methods for monitoring transplant patients. We also discuss emerging technologies, including whole-exome sequencing and RNA-Seq and new bioinformatic and systems biology approaches, which should increase the ability to develop both biomarkers and mechanistic understanding of the rejection process.