Kidney Week

Abstract: TH-OR031

Combination of Changes in eGFR and Albuminuria and the Risk of Major Clinical Outcomes in Type 2 Diabetes Mellitus (T2DM)

Session Information

• Diabetic Kidney Disease Trials: Progress Being Made
  October 25, 2018 | Location: 5A, San Diego Convention Center
  Abstract Time: 04:30 PM - 04:42 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• Jun, Min, The George Institute for Global Health, UNSW Sydney, Newtown, New South Wales, Australia

Min Jun, PhD



Dr. Min Jun is a clinical and health services researcher with a major focus in kidney disease, diabetes and cardiovascular disease epidemiology. He is Senior Research Fellow at the George Institute for Global Health, Australia; Scientia Fellow and Senior Lecturer at the Faculty of Medicine, UNSW Sydney. Min holds a PhD and Master of Science in Medicine in clinical epidemiology (in CKD and AKI) completed at the George Institute for Global Health (Renal and Metabolic Division) and the University of Sydney. He has international postdoctoral training completed in Canada as a NHMRC Early Career Fellow (2013-2016) based at the University of Calgary within the Alberta Kidney Disease Network and the Interdisciplinary Chronic Disease Collaboration, a leading multidisciplinary international research organisation.

• Ohkuma, Toshiaki, The George Institute for Global Health, UNSW Sydney, Newtown, New South Wales, Australia

Toshiaki Ohkuma,

• Perkovic, Vlado, The George Institute for Global Health, Newtown, New South Wales, Australia

Vlado Perkovic,

• Chalmers, John P., The George Institute for Global Health , Camperdown, New South Wales, Australia

John P. Chalmers,

• Woodward, Mark, Johns Hopkins University, Baltimore, Maryland, United States

Mark Woodward,

Group or Team Name

• ADVANCE Collaborative Group

Background

Whether combining changes in eGFR and UACR more accurately predicts outcomes in T2DM compared with assessing either change alone is unknown. We assessed the association between changes in eGFR and UACR and subsequent risk of the composite of major macrovascular and renal events and all-cause mortality in the ADVANCE-ON study.

Methods

We defined eGFR and UACR change (baseline to 2 years) as ≥40% decrease, <40% decrease to <40% increase (minor change; reference) and ≥40% increase. Follow-up for outcomes commenced at the second eGFR or UACR measurement. Cox regression models (adjusted for demographics, ADVANCE randomized treatment, comorbidities and laboratory measurements [including baseline eGFR and UACR]) were used to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) relating changes in eGFR and UACR to the combination endpoint.

Results

Of 8766 patients, from baseline to 2 years, 3% experienced an eGFR decrease ≥40%, 93% experienced a minor change, and 4% experienced an increase ≥40%. For UACR change, the proportions were 29%, 34% and 37%, respectively. 1% experienced both an eGFR decrease ≥40% and a UACR increase ≥40%. Over the next 7.7 years (median), 2191 composite outcome events were recorded. Strong linear associations between eGFR and UACR changes and the subsequent risk of the outcome were observed (p for trend <0.001 for each marker). For eGFR change, the HRs for a decrease ≥40% was 1.59 (95% CI: 1.28-1.97) compared with those with minor change whilst that for an increase ≥40% was 0.82 (0.64-1.04). For UACR change, the HRs were 0.96 (0.85-1.07) for a decrease ≥40% and 1.32 (1.19-1.46) for those with ≥40% increase compared to minor change. Compared to patients with minor changes, patients who experienced an eGFR decrease ≥40% and a UACR increase ≥40% had 2.31 (1.67-3.18) times the risk of the outcome, with evidence of interaction between the 2 markers (p for interaction=0.047).

Conclusion

In patients with T2DM, clinically meaningful decreases in eGFR and increases in UACR over 2 years significantly predicted, independently and in combination, increased risk of major clinical outcomes. Our results suggest that a combined assessment of clinically meaningful changes in both eGFR and UACR compared with separate assessments of the 2 markers may further improve risk stratification in T2DM.

Funding

• Commercial Support – The ADVANCE trial was funded by grants from the National Health and Medical Research Council of Australia and Servier