The ideal blood pressure (BP) target for renoprotection is uncertain in patients with non-diabetic chronic kidney disease (CKD), especially considering the influence exerted by pre-existing proteinuria. In this pooled analysis of landmark trials, we coalesced individual data from 5001 such subjects randomized to intensive versus standard BP targets. We employed multivariable regression to evaluate the relationship between follow-up systolic blood pressure (SBP) and diastolic blood pressure (DBP) on CKD progression (defined as glomerular filtration rate decline by 50% or end-stage renal disease), focusing on the potential for effect modification by baseline proteinuria or albuminuria. The median follow-up was 3.2 years. We found that SBP rather than DBP was the primary predictor of renal outcomes. The optimal SBP target was 110–129 mm Hg. We observed a strong interaction between SBP and proteinuria such that lower SBP ranges were significantly linked with progressively lower CKD risk in grade A3 albuminuria or ≥0.5–1 g/day proteinuria (relative to SBP 110–119 mm Hg, the adjusted HR for SBP 120–129 mm Hg, 130–139 mm Hg, and 140–149 mm Hg was 1.5, 2.3, and 3.3, respectively; all p<0.05). In grade A2 microalbuminuria or proteinuria near 0.5 g/day, a non-significant but possible connection was seen between tighter BP and decreased CKD (aforementioned HRs all <2; all p>0.05), while in grade A1 albuminuria or proteinuria <0.2 g/day no significant association was apparent (HRs all <1.5; all p>0.1). We conclude that in non-diabetic CKD, stricter BP targets <130 mm Hg may help limit CKD progression as proteinuria rises.
- blood pressure
- renal Insufficiency
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Contributors PJDM was the lead author of this study and is primarily responsible for conceptualization/planning, methodology, data acquisition, data curation, investigation, analysis, and writing. EOG supervised the project administration and supported in planning, methodology, analysis, investigation, writing, and review. GS provided support in planning, methodology, writing, and review of this article. All other authors reviewed and helped finalize the paper. AP also provided data access. All authors read and approved the final manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Disclaimer PJDM, GS, ROM, and EOG are employees of the US Department of Veterans Affairs. Opinions expressed in this paper are those of the authors’ and do not necessarily represent the opinion of the Department of Veterans Affairs.
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The study was approved by the Institutional Review Board of the Albany Stratton VA Medical Center in compliance with the Declaration of Helsinki (approval no. 1214452-1).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data may be obtained from a third party and are not publicly available. De-identified, individual participant data (IPD) were obtained from the following sources: Modification of Diet in Renal Disease (MDRD), African American Study of Kidney Disease and Hypertension (AASK), and HALT Progression of Polycystic Kidney Disease (HALT-PKD) trials (study data sets are available from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repository, part of the National Institutes of Health (NIH), at https://repository.niddk.nih.gov/studies/mdrd/https://repository.niddk.nih.gov/studies/aask-trial and https://repository.niddk.nih.gov/studies/halt-pkd/), Systolic Blood Pressure Intervention Trial (SPRINT) (study data sets are available from the National Heart, Lung, and Blood Institute (NHLBI) Data Repository, part of the National Institutes of Health (NIH), at https://biolincc.nhlbi.nih.gov/studies/sprint/), and Ramipril Efficacy In Nephropathy 2 (REIN-2) trial (study data sets are available from the Clinical Research Center for Rare Diseases in the Mario Negri Institute for Pharmacological Research, at http://clintrials.marionegri.it/index.php/main-trials/61.html). IPD obtained from these sources (repository or third party) are not publicly available. As per the data transfer agreements, IPD may not be transferred to other parties. IPD may be requested from the original sources mentioned above, if necessary. Only aggregate or summary data derived from these studies are available in public form.
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