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Am J Kidney Dis. 2018 Oct 2. pii: S0272-6386(18)30879-5. doi: 10.1053/j.ajkd.2018.07.015. [Epub ahead of print]

Effects of Intensive Blood Pressure Lowering on Kidney Tubule Injury in CKD: A Longitudinal Subgroup Analysis in SPRINT.

Author information

1
Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, San Diego, CA; Imperial Valley Family Care Medical Group, El Centro, CA.
2
Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
3
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN.
4
Division of Nephrology, Department of Medicine, Mayo Clinic, Jacksonville, FL.
5
Division of Nephrology & Hypertension, Department of Internal Medicine, University of Utah; Medical Service, Veterans Affairs Salt Lake City Healthcare System, Salt Lake City, UT.
6
Division of Nephrology & Hypertension, Department of Medicine, University of Colorado, Denver, CO.
7
Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA.
8
Division of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, CT.
9
Division of General Internal Medicine, San Francisco VA Medical Center, San Francisco, CA; Kidney Health Research Collaborative, San Francisco VA Medical Center and University of California, San Francisco, CA.
10
Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, San Diego, CA; Division of Preventive Medicine, Department of Family Medicine and Public Health, University of California San Diego, San Diego, CA; Nephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, CA. Electronic address: joeix@ucsd.edu.

Abstract

BACKGROUND:

Random assignment to the intensive systolic blood pressure (SBP) arm (<120mmHg) in the Systolic Blood Pressure Intervention Trial (SPRINT) resulted in more rapid declines in estimated glomerular filtration rates (eGFRs) than in the standard arm (SBP<140mmHg). Whether this change reflects hemodynamic effects or accelerated intrinsic kidney damage is unknown.

STUDY DESIGN:

Longitudinal subgroup analysis of clinical trial participants.

SETTINGS & PARTICIPANTS:

Random sample of SPRINT participants with prevalent chronic kidney disease (CKD) defined as eGFR<60mL/min/1.73m2 by the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation at baseline.

OUTCOMES & MEASUREMENTS:

Urine biomarkers of tubule function (β2-microglobulin [B2M], α1-microglobulin [A1M]), and uromodulin), injury (interleukin 18, kidney injury molecule 1, and neutrophil gelatinase-associated lipocalin), inflammation (monocyte chemoattractant protein 1), and repair (human cartilage glycoprotein 40) at baseline, year 1, and year 4. Biomarkers were indexed to urine creatinine concentration and changes between arms were evaluated using mixed-effects linear models and an intention-to-treat approach.

RESULTS:

978 SPRINT participants (519 in the intensive and 459 in the standard arm) with prevalent CKD were included. Mean age was 72±9 years and eGFR was 46.1±9.4mL/min/1.73m2 at baseline. Clinical characteristics, eGFR, urinary albumin-creatinine ratio, and all 8 biomarker values were similar across arms at baseline. Compared to the standard arm, eGFR was lower by 2.9 and 3.3mL/min/1.73m2 in the intensive arm at year 1 and year 4. None of the 8 tubule marker levels was higher in the intensive arm compared to the standard arm at year 1 or year 4. Two tubule function markers (B2M and A1M) were 29% (95% CI, 10%-43%) and 24% (95% CI, 10%-36%) lower at year 1 in the intensive versus standard arm, respectively.

LIMITATIONS:

Exclusion of persons with diabetes, and few participants had advanced CKD.

CONCLUSIONS:

Among participants with CKD in SPRINT, random assignment to the intensive SBP arm did not increase any levels of 8 urine biomarkers of tubule cell damage despite loss of eGFR. These findings support the hypothesis that eGFR declines in the intensive arm of SPRINT predominantly reflect hemodynamic changes rather than intrinsic damage to kidney tubule cells.

KEYWORDS:

CKD progression; Chronic kidney disease (CKD); blood pressure (BP); eGFR decline; estimated glomerular filtration rate (eGFR); hemodynamics; hypertension; intensive BP control; kidney tubule cell; renal perfusion; tubular injury; urinary biomarkers; urine

PMID:
30291012
DOI:
10.1053/j.ajkd.2018.07.015

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