Antihypertensive Medication Use and Change in Kidney Function in Elderly Adults: A Marginal Structural Model Analysis

Michelle C. Odden, Oregon State University
Ira B. Tager, University of California, Berkeley
Mark J. van der Laan, University of California, Berkeley
Joseph A.C. Delaney, University of Florida
Carmen A. Peralta, University of California, San Francisco
Ronit Katz, University of Washington
Mark J. Sarnak, Tufts Medical Center
Bruce M. Psaty, University of Washington
Michael G. Shlipak, University of California, San Francisco

Abstract

Background: The evidence for the effectiveness of antihypertensive medication use for slowing decline in kidney function in older persons is sparse. We addressed this research question by the application of novel methods in a marginal structural model.

Methods: Change in kidney function was measured by two or more measures of cystatin C in 1,576 hypertensive participants in the Cardiovascular Health Study over 7 years of follow-up (1989-1997 in four U.S. communities). The exposure of interest was antihypertensive medication use. We used a novel estimator in a marginal structural model to account for bias due to confounding and informative censoring.

Results: The mean annual decline in eGFR was 2.41 ± 4.91 mL/min/1.73 m². In unadjusted analysis, antihypertensive medication use was not associated with annual change in kidney function. Traditional multivariable regression did not substantially change these estimates. Based on a marginal structural analysis, persons on antihypertensives had slower declines in kidney function; participants had an estimated 0.88 (0.13, 1.63) ml/min/1.73 m² per year slower decline in eGFR compared with persons on no treatment. In a model that also accounted for bias due to informative censoring, the estimate for the treatment effect was 2.23 (-0.13, 4.59) ml/min/1.73 m² per year slower decline in eGFR.

Conclusion: In summary, estimates from a marginal structural model suggested that antihypertensive therapy was associated with preserved kidney function in hypertensive elderly adults. Confirmatory studies may provide power to determine the strength and validity of the findings.