Plasma Biomarkers Predict Diabetic Kidney Disease (DKD) in Adults with Type 1 Diabetes (T1D) over a 12-Year Follow-up: Cacti Study

Presentation Number: OR09-2
Date of Presentation: April 4th, 2017

Petter Bjornstad*1, Richard J Johnson2, Laura Pyle3, Rachel Sippl4, Randy Wong4, Marian Rewers1 and Janet K Snell-Bergeon5
1University of Colorado School of Medicine, Aurora, CO, 2University of Colorado, 3University of Colorado Anschutz Medical Campus, Aurora, CO, 4Barbara Davis Center for Diabetes, 5Barbara Davis Center for Diabetes, Aurora, CO


OBJECTIVE: To determine whether plasma biomarkers of kidney injury predict progression of DKD in adults with T1D.

METHODS: Participants (n=527, 53% females) in the prospective Coronary Artery Calcification in Type 1 Diabetes (CACTI) study were examined during 2002-04, at mean age 39.6 ± 9.0 years and median duration of diabetes 24.8 years (Q1=19.1, Q3=32.1 years). Urine albumin-to-creatinine (ACR) and estimated GFR (eGFR) by CKD-EPI creatinine were measured at the baseline and after mean follow-up of 12.1 ± 1.5 years. Albuminuria was defined as ACR ≥ 30mg/g and impaired GFR as eGFR <60ml/min/1.73m2. Kidney injury biomarkers (Kidney Injury Panels 3 and 5, Meso Scale Diagnostics) were measured on stored baseline plasma samples. Due to the pleiotropic and synergistic effects of the kidney injury biomarkers, a principal component analysis (PCA) was performed to evaluate the overall kidney injury burden. A PCA identified two components: 1) kidney injury molecule-1, calbindin, osteoactivin, trefoil factor-3 and vascular endothelial growth factor; and 2) β-2 microglobulin, cystatin C, neutrophil gelatinase-associated lipocalin and osteopontin that explained 61% of the total variance and were used in the multivariable regression analyses. Glutathione S-transferase alpha loaded meaningfully (factor load ≥ 0.40) on component 1 and 2 and were thus excluded. Uromodulin did not meaningfully load on either component, and was examined separately. A composite score (range 0–4) was derived from component 2 by assigning a score of 1 for each biomarker value ≥75th percentile. Participants were stratified into 3 groups; those with a composite score of 0 (n=268), those with a score 1-2 (n=172) and those with a score 3-4 (n=87).

RESULTS: Only component 2 of the PCA was associated with incident albuminuria (OR 2.15 95% CI: 1.21–3.82, p=0.009) and incident impaired GFR (OR 2.65, 1.50-4.66, p=0.0008), adjusting for age, sex, HbA1c, LDL-cholesterol and systolic blood pressure. Participants with 3-4 component 2 biomarkers ≥75th percentile had greater risk of albuminuria (OR 6.41, 95% CI 1.40-29.24, p=0.02) and impaired GFR (OR 11.05, 95% CI 3.10-39.37, p=0.0002) compared to those with 0 biomarkers ≥75th percentile, in adjusted models. Higher uromodulin concentrations predicted lower risk of albuminuria (OR 0.29, 95% CI: 0.12-0.69, p=0.005) and impaired GFR (OR 0.37, 95%: 0.19-0.71, p=0.003), per 1 SD (138.7 mcg/mg), in the multivariable models.

CONCLUSIONS: Urine kidney injury biomarkers can help predict development of DKD in adults with T1D.


Nothing to Disclose: PB, RJJ, LP, RS, RW, MR, JKS