Modeling mortality risk in hemodialysis patients using laboratory values as time-dependent covariates

Document Type


Peer Reviewed


Publication Date


NLM Title Abbreviation

Am J Kidney Dis

Journal/Book/Conference Title

American Journal of Kidney Diseases

PubMed ID


DOI of Published Version


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End Page



Proportional hazards analyses assume that the magnitude of mortality risk for a predictor variable remains proportional over time. In a time-dependent model, the explanatory variable violates this assumption, and repeat observations are required to accommodate the change in risk that occurs over time. Using a retrospective cohort design, we tested the following laboratory values for a time-by-covariate interaction: hematocrit (HCT), serum albumin (ALB), and serum creatinine (CR). A random sample of 4,083 hemodialysis patients whose specimens were analyzed in a central laboratory over a 3-year period served as the study group. Using the baseline observation, we discovered significant probability values for the interaction terms TIME*CR (P = 0.013) and TIME*ALB (P < 0.01). The beta coefficient for TIME*HCT was not significant, indicating that the proportional hazard assumption was not violated by this covariate. Based on these results, we fitted a multivariate regression model containing two time-dependent covariates (CR and ALB) using a data structure that incorporated repeat observations of these laboratory values. Patients with high ALB levels experienced the lowest mortality risk. Similarly, serum CR levels were higher in long-term survivors. This analysis verifies the clinical importance of monitoring ALB and CR levels over time and the hazard of using a single laboratory observation to make long-term projections. Additionally, the predictive values of the time-dependent covariates ALB and CR affirm the significance of nutritional approaches directed toward maintaining visceral and somatic protein content throughout renal replacement therapy.


Adult, Cohort Studies, Creatinine/blood, Diabetes Mellitus, Type 1/epidemiology, Diabetes Mellitus, Type 2/epidemiology, Female, Hematocrit, Humans, Kidney Failure, Chronic/blood/diagnosis/mortality/therapy, Male, Multivariate Analysis, Predictive Value of Tests, Proportional Hazards Models, Renal Dialysis/mortality, Retrospective Studies, Risk Factors, Serum Albumin/analysis, Time Factors

Published Article/Book Citation

American Journal of Kidney Diseases, 28:5 (1996) pp.741-746.

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