Variability in estimated glomerular filtration rate and the risk of major clinical outcomes in diabetes: Post hoc analysis from the ADVANCE trial

Min Jun; Katie Harris; Hiddo J L Heerspink; Sunil V Badve; Meg J Jardine; Stephen Harrap; Pavel Hamet; Michel Marre; Neil Poulter; Sradha Kotwal; Martin Gallagher; Vlado Perkovic; John Chalmers; Mark Woodward; ADVANCE Collaborative Group

doi:10.1111/dom.14351

Variability in estimated glomerular filtration rate and the risk of major clinical outcomes in diabetes: Post hoc analysis from the ADVANCE trial

Diabetes Obes Metab. 2021 Jun;23(6):1420-1425. doi: 10.1111/dom.14351. Epub 2021 Mar 4.

Authors

Min Jun^{1

2}, Katie Harris¹, Hiddo J L Heerspink^{1

3}, Sunil V Badve¹, Meg J Jardine⁴, Stephen Harrap⁵, Pavel Hamet⁶, Michel Marre^{7

8

9}, Neil Poulter¹⁰, Sradha Kotwal¹, Martin Gallagher¹, Vlado Perkovic^{1

2}, John Chalmers¹, Mark Woodward^{1

11

12}; ADVANCE Collaborative Group

Affiliations

¹ The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia.
² Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
³ Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, the Netherlands.
⁴ NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia.
⁵ Department of Physiology, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.
⁶ Center de Rechercher, Center Hospitalier de l'Universite de Montreal, Montreal, Quebec, Canada.
⁷ INSERM, UMR S1138, Centre de Recherche des Cordeliers, Paris, France.
⁸ Department of Diabetology, Endocrinology and Nutrition, Assistance Publique-Hôpitaux de Paris, Bichat Hospital, DHU FIRE, Paris, France.
⁹ Université Paris Diderot, Sorbonne Paris Cité, UFR de Médecine, Paris, France.
¹⁰ International Centre for Circulatory Health, Imperial College, London, UK.
¹¹ The George Institute for Global Health, School of Public Health, Imperial College, London, UK.
¹² Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland, USA.

PMID: 33606920
DOI: 10.1111/dom.14351

Abstract

There are limited data on whether estimated glomerular filtration rate (eGFR) variability modifies the risk of future clinical outcomes in type 2 diabetes (T2D). We assessed the association between 20-month eGFR variability and the risk of major clinical outcomes in T2D among 8241 participants in the ADVANCE trial. Variability in eGFR (coefficient of variation [CV_eGFR ]) was calculated from three serum creatinine measurements over 20 months. Participants were classified into three groups by thirds of CV_eGFR : low (≤6.4; reference), moderate (>6.4 to ≤12.1) and high (>12.1). The primary outcome was the composite of major macrovascular events, new or worsening nephropathy and all-cause mortality. Cox regression models were used to estimate hazard ratios (HRs). Over a median follow-up of 2.9 years following the 20-month period, 932 (11.3%) primary outcomes were recorded. Compared with low variability, greater 20-month eGFR variability was independently associated with higher risk of the primary outcome (HR for moderate and high variability: 1.07, 95% CI: 0.91-1.27 and 1.22, 95% CI: 1.03-1.45, respectively) with evidence of a positive linear trend (p = .015). These data indicate that eGFR variability predict changes in the risk of major clinical outcomes in T2D.

Keywords: diabetic nephropathy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Creatinine
Diabetes Mellitus, Type 2* / drug therapy
Diabetes Mellitus, Type 2* / epidemiology
Glomerular Filtration Rate
Humans
Kidney Diseases*
Proportional Hazards Models
Risk Factors

Substances

Creatinine

Grants and funding

The ADVANCE trial was funded by grants from the National Health and Medical Research Council (NHMRC) of Australia and from Servier. MJ is supported by a Scientia Fellowship from the University of New South Wales (Sydney, Australia). MW is supported by a National Health and Medical Research Council of Australia Investigator Grant and Program Grant.