Table 3.

Crude and adjusted association of baseline biomarker or change at 6 mo with eGFR decline in participants of the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) trial

BiomarkerUnadjusted HR (95% CI)P ValueAdjusted HR (95% CI)P Value
Baseline
 Cystatin C2.37 (2.17 to 2.60)<0.0011.66 (1.41 to 1.96)<0.001
 uKIM-1/Cr1.22 (1.14 to 1.31)<0.0010.97 (0.85 to 1.10)0.61
 uNGAL/Cr1.28 (1.21 to 1.34)<0.0011.03 (0.94 to 1.14)0.55
Change from baseline to 6 mo
 uKIM-1/Cr1.08 (1.00 to 1.16)0.051.05 (0.98 to 1.12)0.15
 uNGAL/Cr1.06 (1.01 to 1.11)0.011.07 (1.02 to 1.12)0.004
  • eGFR decline was defined as 50% decrease in eGFR from baseline, stage 5 CKD eGFR<15 ml/min per 1.73 m2, dialysis, or both eGFR<15 ml/min per 1.73 m2 and dialysis. Time from randomization to eGFR decline was fit using the Cox proportional hazards model with stratification per treatment and with adjustment for nine predictors: age, sex, race, ethnicity, historical hypertension, systolic BP, hemoglobin A1c, Chronic Kidney Disease Epidemiology Collaboration eGFR, and baseline proteinuria. All missing values of predictors were estimated through the Markov Chain Monte Carlo method with imputation. Subjects with eGFR decline within 180 d (6 mo) are excluded for the models of biomarker change over 6 mo (n=32). The base model for the change in biomarkers includes the nine traditional predictors plus the baseline biomarker concentration. SDs for baseline biomarkers: Cystatin C±0.38, uKIM-1/Cr±0.90, uNGAL/Cr±157.50. SD for change from baseline to 6 mo: uKIM-1/Cr±1.25 and uNGAL/Cr±263.71. HR, hazard ratio; 95% CI, 95% confidence interval; uKIM-1/Cr, urinary kidney injury molecule–1–to-creatinine; uNGAL/Cr, urinary neutrophil gelatinase-associated lipocalin–to-creatinine.