Regression methods for investigating risk factors of chronic kidney disease outcomes: the state of the art

Abstract

BackgroundChronic kidney disease (CKD) is a progressive and usually irreversible disease. Different types of outcomes are of interest in the course of CKD such as time-to-dialysis, transplantation or decline of the glomerular filtration rate (GFR). Statistical analyses aiming at investigating the association between these outcomes and risk factors raise a number of methodological issues. The objective of this study was to give an overview of these issues and to highlight some statistical methods that can address these topics.MethodsA literature review of statistical methods published between 2002 and 2012 to investigate risk factors of CKD outcomes was conducted within the Scopus database. The results of the review were used to identify important methodological issues as well as to discuss solutions for each type of CKD outcome.ResultsThree hundred and four papers were selected. Time-to-event outcomes were more often investigated than quantitative outcome variables measuring kidney function over time. The most frequently investigated events in survival analyses were all-cause death, initiation of kidney replacement therapy, and progression to a specific value of GFR. While competing risks were commonly accounted for, interval censoring was rarely acknowledged when appropriate despite existing methods. When the outcome of interest was the quantitative decline of kidney function over time, standard linear models focussing on the slope of GFR over time were almost as often used as linear mixed models which allow various numbers of repeated measurements of kidney function per patient. Informative dropout was accounted for in some of these longitudinal analyses.ConclusionsThis study provides a broad overview of the statistical methods used in the last ten years for investigating risk factors of CKD progression, as well as a discussion of their limitations. Some existing potential alternatives that have been proposed in the context of CKD or in other contexts are also highlighted.

Elevated blood pressure is not associated with accelerated glomerular filtration rate decline in the general non-diabetic middle-aged population

“…36 The intraindividual variation in the GFR measurements calculated from this subset was lower than in most previous studies and indicates a low level of measurement error. 25,37 The repeated followup measurements were included in the linear mixed models and allowed adjustment for intraindividual variation in the analyses.…”

Association of glomerular DNA damage and DNA methylation with one-year eGFR decline in IgA nephropathy

“…eGFR was calculated using the following equation: eGFR (ml/min/1.73 m 2 ) = 194 × serum creatinine (−1.094) × age (−0.287) × 0.739 (if female) 27 . The slope of eGFR decline over one year was calculated by standard linear models using the data of eGFR at biopsy, 6 months and one year after biopsy as reported previously 28 . Hypertension was defined as systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg or if the patient indicated the use of antihypertensive drugs.…”

Rationale, description and baseline findings of a community-based prospective cohort study of kidney function amongst the young rural population of Northwest Nicaragua

“…Therefore, we chose to measure within-person change in eGFR, which is inherently independent of between-person factors. Assuming that the main drivers of the within-person measurement error in the eGFR are constant, and if calculated across a number of time points, then eGFR decline at the level of the individual will be less affected by factors that are not related to the progressive kidney damage of interest [12–14]. …”