Dataset Information

Medical records-based chronic kidney disease phenotype for clinical care and "big data" observational and genetic studies.

ABSTRACT: Chronic Kidney Disease (CKD) represents a slowly progressive disorder that is typically silent until late stages, but early intervention can significantly delay its progression. We designed a portable and scalable electronic CKD phenotype to facilitate early disease recognition and empower large-scale observational and genetic studies of kidney traits. The algorithm uses a combination of rule-based and machine-learning methods to automatically place patients on the staging grid of albuminuria by glomerular filtration rate ("A-by-G" grid). We manually validated the algorithm by 451 chart reviews across three medical systems, demonstrating overall positive predictive value of 95% for CKD cases and 97% for healthy controls. Independent case-control validation using 2350 patient records demonstrated diagnostic specificity of 97% and sensitivity of 87%. Application of the phenotype to 1.3 million patients demonstrated that over 80% of CKD cases are undetected using ICD codes alone. We also demonstrated several large-scale applications of the phenotype, including identifying stage-specific kidney disease comorbidities, in silico estimation of kidney trait heritability in thousands of pedigrees reconstructed from medical records, and biobank-based multicenter genome-wide and phenome-wide association studies.

SUBMITTER: Shang N

PROVIDER: S-EPMC8044136 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Medical records-based chronic kidney disease phenotype for clinical care and "big data" observational and genetic studies.

Shang Ning N Khan Atlas A Polubriaginof Fernanda F Zanoni Francesca F Mehl Karla K Fasel David D Drawz Paul E PE Carrol Robert J RJ Denny Joshua C JC Hathcock Matthew A MA Arruda-Olson Adelaide M AM Peissig Peggy L PL Dart Richard A RA Brilliant Murray H MH Larson Eric B EB Carrell David S DS Pendergrass Sarah S Verma Shefali Setia SS Ritchie Marylyn D MD Benoit Barbara B Gainer Vivian S VS Karlson Elizabeth W EW Gordon Adam S AS Jarvik Gail P GP Stanaway Ian B IB Crosslin David R DR Mohan Sumit S Ionita-Laza Iuliana I Tatonetti Nicholas P NP Gharavi Ali G AG Hripcsak George G Weng Chunhua C Kiryluk Krzysztof K

NPJ digital medicine 20210413 1

Chronic Kidney Disease (CKD) represents a slowly progressive disorder that is typically silent until late stages, but early intervention can significantly delay its progression. We designed a portable and scalable electronic CKD phenotype to facilitate early disease recognition and empower large-scale observational and genetic studies of kidney traits. The algorithm uses a combination of rule-based and machine-learning methods to automatically place patients on the staging grid of albuminuria by ...[more]

PMID: 33850243

Similar Datasets

Project description:Epidemiological studies demonstrate an association between migraine and chronic kidney disease (CKD), while the genetic basis underlying the phenotypic association has not been investigated. We aimed to help avoid unnecessary interventions in individuals with migraine through the investigation of phenotypic and genetic relationships underlying migraine, CKD, and kidney function. We first evaluated phenotypic associations using observational data from UK Biobank (N = 255,896). We then investigated genetic relationships leveraging genomic data in European ancestry for migraine (Ncase/Ncontrol = 48,975/540,381), CKD (Ncase/Ncontrol = 41,395/439,303), and two traits of kidney function (estimated glomerular filtration rate [eGFR, N = 567,460] and urinary albumin-to-creatinine ratio [UACR, N = 547,361]). Observational analyses suggested no significant association of migraine with the risk of CKD (HR = 1.13, 95% CI = 0.85-1.50). While we did not find any global genetic correlation in general, we identified four specific genomic regions showing significant for migraine with eGFR. Cross-trait meta-analysis identified one candidate causal variant (rs1047891) underlying migraine, CKD, and kidney function. Transcriptome-wide association study detected 28 shared expression-trait associations between migraine and kidney function. Mendelian randomization analysis suggested no causal effect of migraine on CKD (OR = 1.03, 95% CI = 0.98-1.09; P = 0.28). Despite a putative causal effect of migraine on an increased level of UACR (log-scale-beta = 0.02, 95% CI = 0.01-0.04; P = 1.92 × 10-3), it attenuated to null when accounting for both correlated and uncorrelated pleiotropy. Our work does not find evidence supporting a causal association between migraine and CKD. However, our study highlights significant biological pleiotropy between migraine and kidney function. The value of a migraine prophylactic treatment for reducing future CKD in people with migraine is likely limited.

Project description:Evaluating appropriate methodologies for imputation of missing outcome data from electronic medical records (EMRs) is crucial but lacking for observational studies. Using US EMR in people with type 2 diabetes treated over 12 and 24 months with dipeptidyl peptidase 4 inhibitors (DPP-4i, n = 38,483) and glucagon-like peptide 1 receptor agonists (GLP-1RA, n = 8,977), predictors of missingness of disease biomarker (HbA1c) were explored. Robustness of multiple imputation (MI) by chained equations, two-fold MI (MI-2F) and MI with Monte Carlo Markov Chain were compared to complete case analyses for drawing inferences. Compared to younger people (age quartile Q1), those in age quartile Q3 and Q4 were less likely to have missing HbA1c by 25-32% (range of OR CI: 0.55-0.88) at 6-month follow-up and by 26-39% (range of OR CI: 0.50-0.80) at 12-month follow-up. People with HbA1c ≥ 7.5% at baseline were 12% (OR CI: 0.83, 0.93) and 14% (OR CI: 0.77, 0.97) less likely to have missing data at 6-month follow-up in the DPP-4i and GLP-1RA groups, respectively. All imputation methods provided similar HbA1c distributions during follow-up as observed with complete case analyses. The clinical inferences based on absolute change in HbA1c and by proportion of people reducing HbA1c to a clinically acceptable level (≤ 7%) were also similar between imputed data and complete case analyses. MI-2F method provided marginally smaller mean difference between observed and imputed data with relatively smaller standard error of difference, compared to other methods, while evaluating for consistency through artificial within-sample analyses. The established MI techniques can be reliably employed for missing outcome data imputations in large EMR-based relational databases, leading to efficiently designing and drawing robust clinical inferences in pharmaco-epidemiological studies.Supplementary informationThe online version contains supplementary material available at 10.1007/s41666-022-00119-w.

Dataset Information

Medical records-based chronic kidney disease phenotype for clinical care and "big data" observational and genetic studies.

Publications

Medical records-based chronic kidney disease phenotype for clinical care and "big data" observational and genetic studies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets