Decrease in eGFR associated with future risk of renal and CV events in patients with T2DM

The relationship between eGFR slope and subsequent risk of vascular outcomes and all-cause mortality in type 2 diabetes: the ADVANCE-ON study

Literature - Oshima M, Jun M, Ohkuma T et al., - Diabetologia 2019, 62:1988–1997,

Introduction and methods

Diabetic kidney disease can lead to end-stage kidney disease (ESKD), CVD and premature death [1-4]. Kidney function declines more rapidly in patients with diabetes compared to people without diabetes [5-7]. For the prevention of adverse long-term outcomes, early recognition of diabetic kidney disease progression is necessary.

Meta-analyses have shown that a 30% and 40% decline in eGFR is associated with risks of ESKD mortality in people with and without diabetes [8,9]. However, the percentual decline in these studies was calculated from only two measurements. Thus, the trajectory of eGFR over time was not assessed. The current study aimed to determine the prognostic value of eGFR slope in predicting the risk of clinical outcomes in patients with T2DM.

This study is a post hoc analysis of 8879 participants aged 65.6 ± 6.3 years (mean ± SD) from the large randomized controlled trial ADVANCE and its post-trial follow-up ADVANCE-ON. ADVANCE evaluated the effect of BP-lowering and intensive blood glucose-lowering treatment on vascular outcomes in patients with T2DM. The eGFR slope of each participant was calculated based on three eGFR measurements at 4, 12 and 24 months after randomization (slope ascertainment period). eGFR data of the first 4 months were excluded, because of the acute fall in eGFR known to occur after initiation of RAAS-inhibiting medication.

The primary outcome was the composite of major renal events (chronic dialysis, kidney transplantation, or death from renal disease), major macrovascular events (myocardial infarction, stroke or CV death) and all-cause mortality.

Main results

  • Mean eGFR was 75 ± 17 mL/min/1.73m² at baseline. Mean annual change in eGFR was -0.63 ± 1.75 ml/ min/1.73m².
  • During a median follow-up of 7.6 years, starting after the 20-months eGFR slope ascertainment period, a substantial decrease in eGFR (lowest 25% of slopes, <-1.63) was associated with higher risk of the primary outcome (HR=1.30, 95% CI 1.17-1.43, P<0.001), compared to a stable eGFR (middle 50%, -1.63 to 0.33). A substantial increase in eGFR (highest 25%, >0.33) had no effect on the risk of the primary outcome (HR=0.96, 95% CI 0.86-1.07, P<0.42).
  • Greater annual declines in eGFR were associated with higher risks of study outcomes, compared to no change in eGFR (0 mL/min/1.73m²). Those with eGFR slopes of -3 mL/min/1.73m² per year showed a higher risk of the primary outcome (HR: 1.37, 95%CI: 1.20-1.56).
  • The components of the primary outcomes also showed elevated risk for those with slopes of -3 mL/min/1.73m² per year: HR: 6.14 (95%CI: 3.60-10.49) for major renal events, HR: 1.25 (95%CI:1.06-1.48) for major macrovascular events and HR: 1.54 (95%CI: 1.31-1.81) for all-cause mortality.
  • A significant linear association was found between the estimated eGFR slope and the risk of the primary outcome (P for linear trend <0.001, P for quadratic effect: 0.18).


This post hoc analysis of ADVANCE and ADVANCE-ON data showed that a decrease in eGFR of 3 mL/min/1.73m² per year over 20 months was associated with clinical outcomes in patients with T2DM. This suggests that eGFR slope monitoring over time has the potential to identify T2DM patients at high risk of renal events, vascular events and all-cause mortality.


1. Australian Institute of Health and Welfare (2018) Deaths from diabetes. Available from Accessed 15 Oct 2018

2. Tuttle KR, Bakris GL, Bilous RW et al (2014) Diabetic kidney disease: a report from an ADA Consensus Conference. Diabetes Care 37(10):2864–2883.

3. The United States Renal Data System (2017) 2017 USRDS annual data report: Epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD

4. Ninomiya T, Perkovic V, de Galan BE et al (2009) Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes. J AmSoc Nephrol 20(8):1813–1821.

5. Hobeika L, Hunt KJ, Neely BA, Arthur JM (2015) Comparison of the rate of renal function decline in nonproteinuric patients with and without diabetes. Am J Med Sci 350(6):447–452.

6. Zoppini G, Targher G, Chonchol M et al (2012) Predictors of estimated GFR decline in patients with type 2 diabetes and preserved kidney function. Clin J Am Soc Nephrol 7(3):401–408.

7. Warren B, Rebholz CM, Sang Yet al (2018) Diabetes and trajectories of estimated glomerular filtration rate: a prospective cohort analysis of the Atherosclerosis Risk in Communities study. Diabetes Care 41(8):1646–1653.

8. Coresh J, Turin TC, Matsushita K et al (2014) Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality. JAMA 311(24):2518–2531.

9. Lambers Heerspink HJ, Tighiouart H, Sang Y et al (2014) GFR decline and subsequent risk of established kidney outcomes: a meta-analysis of 37 randomized controlled trials. Am J Kidney Dis 64(6):860–866.

Find this article online at Diabetologia

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