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