Relation of Serum and Urine Renal Biomarkers to Cardiovascular Risk in Patients with Type 2 Diabetes Mellitus and Recent Acute Coronary Syndromes (From the EXAMINE Trial)
Section snippets
Methods
The design11 and primary results12 of EXAMINE have been previously published. In brief, EXAMINE was a global, multicenter, trial of adult patients with T2DM (glycated hemoglobin levels 6.5% to 11.0%) and recent ACS (within 15 to 90 days before randomization) who were randomly assigned to alogliptin, a dipeptidyl peptidase (DPP)-4 inhibitor, or matching placebo in 1:1 double-blinded fashion. Both treatment arms received standard of care for T2DM and secondary CV protection. Patients deemed
Results
Of the 5,380 patients enrolled in EXAMINE, all patients had a calculated CKD-EPI eGFR, 5,213 (97%) had serum Cystatin C values, 4,875 (91%) had uKIM-1/Cr, 4,962 (92%) had uNGAL/Cr, 4,049 (75%) had urine protein/Cr ratio, and 3,135 (58%) had an albumin/Cr ratio measured at randomization (median 44 days from qualifying ACS) and available for analysis.
EXAMINE enrolled older adults (mean age, 61 years) who were predominantly men (68%) and White (73%). Patients commonly had co-morbid hypertension
Discussion
In a large, well-characterized cohort of patients with T2DM, 4 urinary biomarkers and 1 serum renal biomarker measured early after index ACS were robustly associated with risk of subsequent CV events and death in step-wise manner, independent of baseline eGFR. The highest quartiles of these renal biomarkers informing various axes of renal function identified patients who face the highest risks of major adverse CV events (18% to 25% at 2 years). However, when tested together, only serum Cystatin
Disclosures
Muthiah Vaduganathan: Research support from the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst | The Harvard Clinical and Translational Science Center (NIH/NCATS Award UL 1TR002541), and serves on advisory boards for AstraZeneca, Bayer AG, and Baxter Healthcare.
William B. White: Research support from National Institutes of Aging (RO1 AG 0220902) and Chair of the EXAMINE steering committee with personal fees from Takeda Development Center from 2010 to 2016.
David
Acknowledgments
EXAMINE was supported by Takeda Development Center, North America, Deerfield, IL, USA. We would like to thank the 898 site investigators and the patients of EXAMINE for their participation in the trial.
References (28)
- et al.
Longitudinal progression trajectory of GFR among patients with CKD
Am J Kidney Dis
(2012) - et al.
Factors other than glomerular filtration rate affect serum cystatin C levels
Kidney Int
(2009) Comprehensive medical evaluation and assessment of comorbidities
Diabetes Care
(2017)- et al.
Predicting adverse outcomes after myocardial infarction among patients with diabetes mellitus
Circ Cardiovasc Qual Outcomes
(2016) - et al.
Liraglutide and renal outcomes in type 2 diabetes
N Engl J Med
(2017) - et al.
Canagliflozin and cardiovascular and renal events in type 2 diabetes
N Engl J Med
(2017) - et al.
Empagliflozin and progression of kidney disease in type 2 diabetes
N Engl J Med
(2016) - et al.
Biomarkers of renal injury and function: diagnostic, prognostic and therapeutic implications in heart failure
Eur Heart J
(2016) - et al.
Urinary biomarkers and risk of ESRD in the atherosclerosis risk in communities study
Clin J Am Soc Nephrol
(2015) - et al.
Association of urinary KIM-1, L-FABP, NAG and NGAL with incident end-stage renal disease and mortality in American Indians with type 2 diabetes mellitus
Diabetologia
(2015)
Kidney biomarkers and decline in eGFR in patients with type 2 diabetes
Clin J Am Soc Nephrol
EXamination of cArdiovascular outcoMes with alogliptIN versus standard of carE in patients with type 2 diabetes mellitus and acute coronary syndrome (EXAMINE): a cardiovascular safety study of the dipeptidyl peptidase 4 inhibitor alogliptin in patients with type 2 diabetes with acute coronary syndrome
Am Heart J
Alogliptin after acute coronary syndrome in patients with type 2 diabetes
N Engl J Med
Alogliptin after acute coronary syndrome in patients with type 2 diabetes
N Engl J Med
Cited by (0)
Source of Support: The EXAMINE trial was supported by Takeda Development Center Americas.