Send to

Choose Destination
Nephrol Dial Transplant. 2018 Jul 1;33(7):1189-1196. doi: 10.1093/ndt/gfx255.

Plasma biomarkers improve prediction of diabetic kidney disease in adults with type 1 diabetes over a 12-year follow-up: CACTI study.

Author information

Department of Pediatric Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA.
Barbara Davis Center for Diabetes, University of Colorado Denver, Aurora, CO, USA.
Department of Medicine, Division of Nephrology, and Department of Physiology, University of Toronto, ON, Canada.
Department of Nephrology, University of Colorado Denver, Aurora, CO, USA.



The objective of the study was to determine whether 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.


Participants (n = 527, 53% females) in the Coronary Artery Calcification in T1D (CACTI) Study were examined during 2002-04, at a mean (± standard deviation) age of 39.6 ± 9.0 years with 24.8 years as the median duration of diabetes. Urine albumin-to-creatinine (ACR) and estimated glomerular filtration rate (eGFR) by CKD-EPI (chronic kidney disease epidemiology collaboration) creatinine were measured at the baseline and after mean follow-up of 12.1 ± 1.5 years. Albuminuria was defined as ACR ≥30 mg/g and impaired GFR as eGFR <60 mL/min/1.73 m2. Kidney injury biomarkers (Meso Scale Diagnostics) were measured on stored baseline plasma samples. A principal component analysis (PCA) identified two components: (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.


Component 2 of the PCA was 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 after adjusting for traditional risk factors (age, sex, HbA1c, low-density lipoprotein cholesterol and systolic blood pressure and baseline eGFR/baseline ACR). Only Component 2 of the PCA was associated with incident-impaired GFR (odds ratio 2.08, 95% confidence interval 1.18-3.67, P = 0.01), adjusting for traditional risk factors. The addition of Component 2 to traditional risk factors significantly improved 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).


Plasma kidney injury biomarkers can help predict development of DKD in T1D.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center