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Randomized Controlled Trial
. 2022 May;79(5):677-687.e1.
doi: 10.1053/j.ajkd.2021.07.024. Epub 2021 Sep 17.

Kidney Disease, Hypertension Treatment, and Cerebral Perfusion and Structure

Manjula Kurella Tamura  1 , Sarah Gaussoin  2 , Nicholas M Pajewski  2 , Greg Zaharchuk  3 , Barry I Freedman  4 , Stephen R Rapp  5 , Alexander P Auchus  6 , William E Haley  7 , Suzanne Oparil  8 , Jessica Kendrick  9 , Christianne L Roumie  10 , Srinivasan Beddhu  11 , Alfred K Cheung  11 , Jeff D Williamson  12 , John A Detre  13 , Sudipto Dolui  14 , R Nick Bryan  15 , Ilya M Nasrallah  14 ; SPRINT Research Group
Collaborators, Affiliations
Randomized Controlled Trial

Kidney Disease, Hypertension Treatment, and Cerebral Perfusion and Structure

Manjula Kurella Tamura et al. Am J Kidney Dis. 2022 May.

Abstract

Rationale & objective: The safety of intensive blood pressure (BP) targets is controversial for persons with chronic kidney disease (CKD). We studied the effects of hypertension treatment on cerebral perfusion and structure in individuals with and without CKD.

Study design: Neuroimaging substudy of a randomized trial.

Setting & participants: A subset of participants in the Systolic Blood Pressure Intervention Trial (SPRINT) who underwent brain magnetic resonance imaging studies. Presence of baseline CKD was assessed by estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR).

Intervention: Participants were randomly assigned to intensive (systolic BP <120 mm Hg) versus standard (systolic BP <140 mm Hg) BP lowering.

Outcomes: The magnetic resonance imaging outcome measures were the 4-year change in global cerebral blood flow (CBF), white matter lesion (WML) volume, and total brain volume (TBV).

Results: A total of 716 randomized participants with a mean age of 68 years were enrolled; follow-up imaging occurred after a median 3.9 years. Among participants with eGFR <60 mL/min/1.73 m2 (n = 234), the effects of intensive versus standard BP treatment on change in global CBF, WMLs, and TBV were 3.38 (95% CI, 0.32 to 6.44) mL/100 g/min, -0.06 (95% CI, -0.16 to 0.04) cm3 (inverse hyperbolic sine-transformed), and -3.8 (95% CI, -8.3 to 0.7) cm3, respectively. Among participants with UACR >30 mg/g (n = 151), the effects of intensive versus standard BP treatment on change in global CBF, WMLs, and TBV were 1.91 (95% CI, -3.01 to 6.82) mL/100 g/min, 0.003 (95% CI, -0.13 to 0.13) cm3 (inverse hyperbolic sine-transformed), and -7.0 (95% CI, -13.3 to -0.3) cm3, respectively. The overall treatment effects on CBF and TBV were not modified by baseline eGFR or UACR; however, the effect on WMLs was attenuated in participants with albuminuria (P = 0.04 for interaction).

Limitations: Measurement variability due to multisite design.

Conclusions: Among adults with hypertension who have primarily early kidney disease, intensive versus standard BP treatment did not appear to have a detrimental effect on brain perfusion or structure. The findings support the safety of intensive BP treatment targets on brain health in persons with early kidney disease.

Funding: SPRINT was funded by the National Institutes of Health (including the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; the National Institute on Aging; and the National Institute of Neurological Disorders and Stroke), and this substudy was funded by the National Institutes of Diabetes and Digestive and Kidney Diseases.

Trial registration: SPRINT was registered at ClinicalTrials.gov with study number NCT01206062.

Keywords: Hypertension; albuminuria; blood pressure (BP); cerebral perfusion; chronic kidney disease (CKD); intensive BP control; magnetic resonance imaging (MRI); neuroimaging; white matter injury; white matter lesions.

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Conflict of interest statement

Financial Disclosure: Dr. Kurella Tamura has received an honorarium from the American Federation for Aging Research outside the submitted work. Dr. Oparil reports grants and support from NIH/National Heart, Lung and Blood Institute (NHLBI) during the conduct of the study and outside the submitted work, has received personal fees from Preventric Diagnostics, CinCor, and currently serves as Editor-in-Chief for Current Hypertension Reports. Dr. Auchus reports grants from the University of Mississippi Medical Center during the conduct of the study. Dr. Roumie reports grants from the NIH during the conduct of the study. Dr. Beddhu reports grants from NHLBI and NIDDK during the conduct of the study, support from Bayer, Boehringer Ingelheim, Novo Nortis, and UpToDate outside the submitted work. Dr. Zaharchuk reports grants from the NIH during the conduct of the study. Dr. Freedman reports grants from the NIH during the conduct of the study. Dr. Williamson reports grants from the NIH, Biogen and Alzheimer’s Association outside the submitted work. Dr. Nasrallah reports grants from NIH during the conduct of the study and fees from Biogen outside the submitted work. The remaining authors declare that they have no relevant financial interests.

Figures

Figure 1.
Figure 1.
Flowchart for inclusion of participants
Figure 2.
Figure 2.
Effect of intensive versus standard BP treatment on change in cerebral blood flow (Panel A), white matter lesion volume (Panel B), and total brain volume (Panel C), by baseline estimated glomerular filtration rate and urine albumin to creatinine ratio. Note: Units are expressed as ml/100 g/min for cerebral blood flow, asinh (cm3) for white matter lesion volume, and cm3 for total brain volume.
See this image and copyright information in PMC

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