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. 2021 Jul;78(1):48-56.
doi: 10.1053/j.ajkd.2020.10.016. Epub 2020 Dec 14.

Estimated GFR Variability and Risk of Cardiovascular Events and Mortality in SPRINT (Systolic Blood Pressure Intervention Trial)

Rakesh Malhotra  1 , Ronit Katz  2 , Vasantha Jotwani  3 , Adhish Agarwal  4 , Debbie L Cohen  5 , William C Cushman  6 , Areef Ishani  7 , Anthony A Killeen  8 , Dalane W Kitzman  9 , Suzanne Oparil  10 , Vasilios Papademetriou  11 , Chirag R Parikh  12 , Kalani L Raphael  4 , Michael V Rocco  13 , Leonardo J Tamariz  14 , Paul K Whelton  15 , Jackson T Wright Jr  16 , Michael G Shlipak  17 , Joachim H Ix  18
Affiliations

Estimated GFR Variability and Risk of Cardiovascular Events and Mortality in SPRINT (Systolic Blood Pressure Intervention Trial)

Rakesh Malhotra et al. Am J Kidney Dis. 2021 Jul.

Abstract

Rationale and objective: Although low estimated glomerular filtration rate (eGFR) is associated with cardiovascular disease (CVD) events and mortality, the clinical significance of variability in eGFR over time is uncertain. This study aimed to evaluate the associations between variability in eGFR and the risk of CVD events and all-cause mortality.

Study design: Longitudinal analysis of clinical trial participants.

Settings and participants: 7,520 Systolic Blood Pressure Intervention Trial (SPRINT) participants ≥50 year of age with 1 or more CVD risk factors.

Predictors: eGFR variability, estimated by the coefficient of variation of eGFR assessments at the 6th, 12th, and 18-month study visits.

Outcomes: The SPRINT primary CVD composite outcome (myocardial infarction, acute coronary syndrome, stroke, heart failure, or CVD death) and all-cause mortality from month 18 to the end of follow-up.

Analytical approach: Cox models were used to evaluate associations between eGFR variability and CVD outcomes and all-cause mortality. Models were adjusted for demographics, randomization arm, CVD risk factors, albuminuria, and eGFR at month 18.

Results: Mean age was 68 ± 9 years; 65% were men; and 58% were White. The mean eGFR was 73 ± 21 (SD) mL/min/1.73 m2 at 6 months. There were 370 CVD events and 154 deaths during a median follow-up of 2.4 years. Greater eGFR variability was associated with higher risk for all-cause mortality (hazard ratio [HR] per 1 SD greater variability, 1.29; 95% CI, 1.14-1.45) but not CVD events (HR, 1.05; 95% CI, 0.95-1.16) after adjusting for albuminuria, eGFR, and other CVD risk factors. Associations were similar when stratified by treatment arm and by baseline CKD status, when accounting for concurrent systolic blood pressure changes, use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and diuretic medications during follow up.

Limitations: Persons with diabetes and proteinuria > 1 g/d were excluded.

Conclusions: In trial participants at high risk for CVD, greater eGFR variability was independently associated with all-cause mortality but not CVD events.

Keywords: CVD; all-cause mortality; cardiovascular disease; cardiovascular event; eGFR; eGFR variability; estimated glomerular filtration rate; renal function.

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Conflict of interest statement

Peer Review: Received April 27, 2020. Evaluated by 2 external peer reviewers and a statistician, with direct editorial input from an International Editor, who served as Acting Editor-in-Chief. Accepted in revised form October 16, 2020. The involvement of an Acting Editor-in-Chief was to comply with AJKD’s procedures for potential conflicts of interest for editors, described in the Information for Authors & Journal Policies.

Figures

Figure 1.
Figure 1.
Flow chart of study participants.
Figure 2.
Figure 2.
Adjusted spline plots for risk of CVD events and all-cause mortality over the range of eGFR variability. Curves represent adjusted hazard ratio (solid line) and the 95% CI (dashed lines) based on restricted cubic splines with knots at quartiles of eGFR variability. Model adjusted for age, sex, randomization arm, baseline history of CVD, history of heart failure, current smoking status, BMI, LDL, total cholesterol, systolic blood pressure (6m), ACR (6m), eGFR (6m), ACE/ARB (6m), diuretics (6m), and fasting status. CVD, cardiovascular disease; CI, confidence interval; BMI, body mass index; LDL, low-density lipoprotein; ACEI, angiotensin-converting-enzyme inhibitor; ARB, angiotensin II receptor blocker; eGFR, estimated glomerular filtration rate; ACR, albumin-to-creatinine ratio.
See this image and copyright information in PMC

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