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Cited by 48Chronic Kidney Disease and DiabetesDiabetes Treatment and ManagementBlood Pressure and Hypertension Studies

Long-term effects of intensive glycemic and blood pressure control and fenofibrate use on kidney outcomes

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Mottl, Amy K., Buse, John B., Ismail-Beigi, Faramarz, Sigal, Ronald J., Pedley, Carolyn F., Papademetriou, Vasilios, Simmons, Debra L., Katz, Lois +2 more·2018·Clinical Journal of the American Society of Nephrology
DOI 10.2215/cjn.06200518PMC PMC6237052
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Abstract

Visual Abstract Export Background and objectives In people with type 2 diabetes, aggressive control of glycemia, BP, and lipids have resulted in conflicting short-term (<5 years) kidney outcomes. We aimed to determine the long-term kidney effects of these interventions. Design, setting, participants, & measurements The Action to Control Cardiovascular Risk in Diabetes (ACCORD) was a multifactorial intervention study in people with type 2 diabetes at high risk for cardiovascular disease (n=10,251), to examine the effects of intensive glycemic control (hemoglobin A1c <6.0% versus 7%–7.9%), BP control (systolic BP <120 mm Hg versus <140 mm Hg) or fenofibrate versus placebo added to simvastatin on cardiovascular events and death. The glycemia trial lasted 3.7 years and participants were followed for another 6.5 years in ACCORDION, the ACCORD Follow-On Study. The post hoc primary composite kidney outcome was defined as incident macroalbuminuria, creatinine doubling, need for dialysis, or death by any cause. Cox proportional hazards regression estimated the effect of each intervention on the composite outcome and individual components. In secondary outcome analyses, competing risk regression was used to account for the risk of death in incident kidney outcomes. Analyses were adjusted for sociodemographics, randomization groups, and clinical factors. Results There were 988 cases of incident macroalbuminuria, 954 with doubling of creatinine, 351 requiring dialysis, and 1905 deaths. Hazard ratios (HRs) for the composite outcome with intensive glycemic, BP control, and fenofibrate use compared with standard therapy were 0.92 (95% confidence interval [95% CI], 0.86 to 0.98), 1.16 (95% CI, 1.05 to 1.28), and 1.16 (95% CI, 1.06 to 1.27). Multivariable, secondary outcome analyses showed that in the glycemia trial, only macroalbuminuria was significantly decreased (HR, 0.68; 95% CI, 0.59 to 0.77). In the BP and lipid trials, only creatinine doubling was affected (HR, 1.64; 95% CI, 1.30 to 2.06 and HR, 2.00; 95% CI, 1.61 to 2.49, respectively). Conclusions In people with type 2 diabetes at high risk for cardiovascular disease, intensive glycemic control may result in a long-term reduction in macroalbuminuria; however, intensive BP control and fenofibrates may increase the risk for adverse kidney events.

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  • A target HbA1c ≤6.0% probably increased all-cause mortality.

    “Two studies comparing a target HbA1c of # 6.0% to higher HbA1c targets (standard glycemic control) found that the lower HbA1c target probably increased all-cause mortality (Supplementary Table S13 240,242,255 )”

    From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [255]

    The Materials and Methods section says the ACCORD glycemia trial, which targeted HbA1c <6.0% versus 7.0%–7.9%, was stopped early after excess mortality in the intensive group. But this paper’s long-term Results report virtually identical all-cause mortality in the two groups (952 versus 953 deaths; adjusted HR 1.00, 95% CI 0.91–1.10), so it does not support an increased risk over the full follow-up. (LLM, conf=0.85)

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Authors
Mottl, A. K., Buse, J. B., Ismail-Beigi, F., Sigal, R. J., Pedley, C. F., Papademetriou, V., Simmons, D. L., Katz, L., Mychaleckyj, J. C., & Craven, T. E.
Affiliations
  • University of North Carolina at Chapel Hill (US)
  • University of Calgary (CA)
  • Atrium Health Wake Forest Baptist (US)
  • United States Department of Veterans Affairs (US)
  • Veterans Health Administration (US)
  • VA NY Harbor Healthcare System (US)
  • University of Virginia (US)
  • Wake Forest University Health Sciences (US)
Corresponding author
Mottl, Amy K.
ORCID
Venue
Clinical Journal of the American Society of Nephrology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2018-10-25
Volume
13
Issue
11
Pages
1693-1702
ISSN
  • 1555-9041 (ISSN-L)
  • 1555-905X
DOI
10.2215/cjn.06200518
PMC
PMC6237052
OpenAlex
W2898602921
Cited by
48
References
11
Citations by year
2026: 5 · 2025: 6 · 2024: 6 · 2023: 7 · 2022: 5 · 2021: 5 · 2020: 5 · 2019: 7 · 2018: 1
FWCI
3.69
Type
journal article
Language
en
Open access
Locations
  • Clinical Journal of the American Society of Nephrology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • UNC Libraries
Funders
  • National Institutes of Health (n01hc95183-23-0-0, n01hc95180-24-0-1, n01hc95184-24-0-1, n01hc95181-23-0-1, n01hc95182-23-0-1, n01hc95178-28-0-1, n01hc95179-25-0-0)
  • National Heart, Lung, and Blood Institute (HHSN268201100027C, N01 HC095184, N01 HC095182, N01 HC095181, Y01 HC001010, N01-HC-095183, N01 HC095178, N01 HC095180, Y01 HC009035, N01 HC095179)
Topics
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
Keywords
type 2 diabetes, tight glycemic control, blood pressure control, fenofibrate, renal outcomes, macroalbuminuria, dialysis, mortality, ACCORD, lipid-lowering therapy, cardiovascular risk reduction, competing risk regression, long-term follow-up, HbA1c, systolic blood pressure, simvastatin
MeSH terms
Adult, Aged, Albuminuria, Antihypertensive Agents, Hypolipidemic Agents, Blood Pressure, Creatinine, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Female, Glomerular Filtration Rate, Renal Dialysis, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Kidney Failure, Chronic, Male, Middle Aged, Fenofibrate, Time Factors, Simvastatin

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