Bjornstad P, et al. - Whether or not plasma biomarkers of kidney injury improve the prediction of diabetic kidney disease (DKD) in adults with type 1 diabetes (T1D) over a period of 12 years. Findings suggest that plasma kidney injury biomarkers could assist in predicting the development of DKD in T1D.

Methods

• During 2002–04, researchers examined participants (n = 527, 53% females) in the Coronary Artery Calcification in T1D (CACTI) Study.
• The mean (± standard deviation) age of participants was 39.6 ± 9.0 years with 24.8 years as the median duration of diabetes.
• At the baseline and after mean follow-up of 12.1 ± 1.5 years, researchers measured urine albumin-to-creatinine (ACR) and estimated glomerular filtration rate (eGFR) by CKD-EPI (chronic kidney disease epidemiology collaboration) creatinine.
• They defined albuminuria as ACR ≥30 mg/g and impaired GFR as eGFR <60 mL/min/1.73 m².
• Stored baseline plasma samples were assessed for kidney injury biomarkers (Meso Scale Diagnostics).
• Two components were identified with a principal component analysis (PCA): (i) kidney injury molecule-1, calbindin, osteoactivin, trefoil factor 3 and vascular endothelial growth factor; and (ii) β-2 microglobulin, cystatin C, neutrophil gelatinase-associated lipocalin and osteopontin that were used in the multivariable regression analyses.

Results

• After adjusting for traditional risk factors (age, sex, HbA1c, low-density lipoprotein cholesterol and systolic blood pressure and baseline eGFR/baseline ACR), component 2 of the PCA was noted to be associated with increase in log modulus ACR [β ± standard error (SE): 0.16 ± 0.07, P=0.02] and eGFR (β ± SE: -2.56 ± 0.97, P=0.009) over a period of 12 years .
• Adjusting for traditional risk factors, only Component 2 of the PCA was noted to be associated with incident-impaired GFR (odds ratio 2.08, 95% confidence interval 1.18–3.67, P=0.01).
• The addition of Component 2 to traditional risk factors led to a significant improvement in C-statistics and net-reclassification improvement for incident-impaired GFR (ΔAUC: 0.02 ± 0.01, P=0.049, and 29% non-events correctly reclassified, P < 0.0001).