B NEUEN1,2, M WELDEGIORGIS1,2, W HERRINGTON3, T OKHUMA1,4, M SMITH5,6, M WOODWARD1,2,7
1The George Institute For Global Health, Sydney, Australia, 2The George Institute for Global Health, University of Oxford, Oxford, United Kingdom, 3Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom, 4Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, 5Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom, 6NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom, 7Department of Epidemiology, John Hopkins University, Baltimore, USA
Aim: To assess the association between combined changes in urinary albumin:creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) with clinical outcomes in a general population.
Background: Changes in UACR/eGFR have separately been used as surrogate endpoints for chronic kidney disease (CKD) progression in randomized trials. It is unclear whether combined changes in UACR/eGFR predict kidney outcomes better than either alone.
Methods: We analysed data from the United Kingdom Clinical Practice Research Datalink to calculate changes in UACR/eGFR over a three-year period (≥30% increase, stable or ≥30% decrease). The primary outcome was advanced CKD (sustained eGFR <30 mL/min/1.73m2); secondary outcomes included end-stage kidney disease, cardiovascular disease and all-cause mortality. Associations between changes in UACR/eGFR (individually and in combination) with clinical outcomes were assessed using multivariable Cox regression. Discrimination statistics were calculated to assess the prognostic value of combined exposure changes.
Results: 91,319 participants were studied with a mean eGFR of 72.6 mL/min/1.73m2 and median UACR of 9.7 mg/g, of whom 70,957 (77.7%) had diabetes. Over a median follow-up of 2.9 years, 2,541 people progressed to advanced CKD. Compared to stable values, hazard ratios (HR) for a ≥30% increase in UACR and ≥30% decrease in eGFR were 1.78 (95% CI 1.59-1.98) and 7.53 (95% CI 6.70-8.45), respectively. The HR for combined change in UACR/eGFR was 15.15 (95% CI 12.43-18.46). Combined changes in UACR/eGFR improved the discrimination of advanced CKD better than either alone.
Conclusion: In a large-scale general population, combined increases in UACR and decreases in eGFR were strongly associated with risk of advanced CKD. Further assessment of combined changes in UACR/eGFR as an alternative endpoint for kidney failure in trials of CKD progression is warranted.
Dr Brendon Neuen is an academic nephrology registrar and NHMRC Postgraduate Scholar at The George Institute for Global Health. His research focuses on the cardiovascular and kidney protective effects of SGLT2 inhibition in people with diabetic kidney disease, having trained on the landmark CANVAS and CREDENCE trials. He is also involved in analyses of large-scale observational studies using routinely collected data, both in Australia and the UK. He graduated in medicine at James Cook University with 1st Class Honours and an Academic Medal and holds a Masters in Global Health from Oxford University, where he was a Clarendon Scholar.