Treatment Effect Heterogeneity in Acute Kidney Injury Incidence Following Intravenous Antihypertensive Administration for Severe Blood Pressure Elevation During Hospitalization

Lama Ghazi; Xinyuan Chen; Michael O Harhay; Liangyuan Hu; Aditya Biswas; Aldo J Peixoto; Fan Li; F Perry Wilson

doi:10.1053/j.ajkd.2024.09.011

Treatment Effect Heterogeneity in Acute Kidney Injury Incidence Following Intravenous Antihypertensive Administration for Severe Blood Pressure Elevation During Hospitalization

Am J Kidney Dis. 2024 Nov 21:S0272-6386(24)01081-3. doi: 10.1053/j.ajkd.2024.09.011. Online ahead of print.

Authors

Lama Ghazi¹, Xinyuan Chen², Michael O Harhay³, Liangyuan Hu⁴, Aditya Biswas⁵, Aldo J Peixoto⁶, Fan Li⁷, F Perry Wilson⁸

Affiliations

¹ Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: lghazi@uab.edu.
² Department of Mathematics and Statistics, Mississippi State University, Mississippi State, MS, USA. Electronic address: xchen@math.msstate.edu.
³ Clinical Trials Methods and Outcomes Lab, Palliative and Advanced Illness Research Center (PAIR), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁴ Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ, USA.
⁵ Department of Internal Medicine, Clinical and Translational Research Accelerator, Yale University, New Haven, CT, USA.
⁶ Section of Nephrology, Yale School of Medicine, Yale University, New Haven, Connecticut, USA.
⁷ Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA; Center for Methods in Implementation and Prevention Science, Yale School of Public Health, New Haven, CT, USA.
⁸ Department of Internal Medicine, Clinical and Translational Research Accelerator, Yale University, New Haven, CT, USA; Section of Nephrology, Yale School of Medicine, Yale University, New Haven, Connecticut, USA.

PMID: 39580068
DOI: 10.1053/j.ajkd.2024.09.011

Abstract

Rationale & objective: Severe hypertension (sHTN) that develops after hospital admission is prevalent in 10% of patients admitted for reasons other than HTN. sHTN is commonly treated with intravenous (IV) antihypertensives and is associated with a greater risk of acute kidney injury (AKI). Our goal was to explore whether there is heterogeneity in IV antihypertensives' effect on AKI incidence among patients who develop sHTN during hospitalization.

Study design: Heterogeneity of treatment effect analysis.

Settings & participants: Patients who developed sHTN, systolic blood pressure (BP) >180, or diastolic BP >110 mmHg during hospitalization and did not have kidney failure.

Exposure: Treatment with IV antihypertensives within 3 hours of BP elevation.

Outcome: Time to develop AKI.

Analytical approach: An accelerated failure time Bayesian Additive Regression Trees (BART) model to capture the association between the time to develop AKI and predictors. Individual treatment effects estimated for each participant using a counterfactual outcome framework and these estimates were used to identify patient characteristics associated with treatment effect heterogeneity in response to IV antihypertensives.

Results: We included 11,951 patients who developed sHTN, 741 were treated with IV antihypertensives, and 11,210 were not, of which 18% and 13% developed AKI, respectively. Most patients would have been harmed from IV antihypertensive treatment except for a small subset of 317 patients who were White, had an SBP on admission ≥156 mmHg, an eGFR ≥70.7 ml/min/1.73m², and a serum bicarbonate <21.7 mmol/L.

Limitations: Data-driven, hypothesis-generating approach. Findings were not validated with external data sources.

Conclusion: These exploratory findings suggest that most patients who develop sHTN will not benefit from IV antihypertensive treatment. Future studies should assess for heterogeneity when identifying treatment options, if any are needed, for sHTN.

Keywords: acute kidney injury; antihypertensive medications; heterogeneity of treatment effect; hypertension; inpatient.