A systematic review of statistical methodology used to evaluate progression of chronic kidney disease using electronic healthcare records

BACKGROUND: Electronic healthcare records (EHRs) are a useful resource to study chronic kidney disease (CKD) progression prior to starting dialysis, but pose methodological challenges as kidney function tests are not done on everybody, nor are tests evenly spaced. We sought to review previous research of CKD progression using renal function tests in EHRs, investigating methodology used and investigators’ recognition of data quality issues. METHODS AND FINDINGS: We searched for studies investigating CKD progression using EHRs in 4 databases (Medline, Embase, Global Health and Web of Science) available as of August 2021. Of 80 articles eligible for review, 59 (74%) were published in the last 5.5 years, mostly using EHRs from the UK, USA and East Asian countries. 33 articles (41%) studied rates of change in eGFR, 23 (29%) studied changes in eGFR from baseline and 15 (19%) studied progression to binary eGFR thresholds. Sample completeness data was available in 44 studies (55%) with analysis populations including less than 75% of the target population in 26 studies (33%). Losses to follow-up went unreported in 62 studies (78%) and 11 studies (14%) defined their cohort based on complete data during follow up. Methods capable of handling data quality issues and other methodological challenges were used in a minority of studies. CONCLUSIONS: Studies based on renal function tests in EHRs may have overstated reliability of findings in the presence of informative missingness. Future renal research requires more explicit statements of data completeness and consideration of i) selection bias and representativeness of sample to the intended target population, ii) ascertainment bias where follow-up depends on risk, and iii) the impact of competing mortality. We recommend that renal progression studies should use statistical methods that take into account variability in renal function, informative censoring and population heterogeneity as appropriate to the study question.