Dataset Information

Serum Uromodulin Predicts Less Coronary Artery Calcification and Diabetic Kidney Disease Over 12 Years in Adults With Type 1 Diabetes: The CACTI Study.

ABSTRACT:

Objective

Novel biomarkers are needed to better predict coronary artery calcification (CAC), a marker of subclinical atherosclerosis, and diabetic kidney disease (DKD) in type 1 diabetes. We evaluated the associations between serum uromodulin (SUMOD [a biomarker associated with anti-inflammatory and renal protective properties]), CAC progression, and DKD development over 12 years.

Research design and methods

Participants (n = 527, 53% females) in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study were examined during 2002-2004, at a mean age of 39.6 ± 9.0 years and a median duration of diabetes of 24.8 years. Urine albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) determined by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation were measured at baseline and after a mean follow-up period of 12.1 ± 1.5 years. Elevated albumin excretion was defined as ACR ?30 mg/g, rapid GFR decline (>3 mL/min/1.73 m²/year), and impaired GFR as eGFR <60 mL/min/1.73 m². SUMOD was measured on stored baseline plasma samples (Meso Scale Discovery). CAC was measured using electron beam computed tomography. CAC progression was defined as a change in the square root-transformed CAC volume of ?2.5.

Results

Higher baseline SUMOD level conferred lower odds of CAC progression (odds ratio 0.68; 95% CI 0.48-0.97), incident elevated albumin excretion (0.37; 0.16-0.86), rapid GFR decline (0.56; 0.35-0.91), and impaired GFR (0.44; 0.24-0.83) per 1 SD increase in SUMOD (68.44 ng/mL) after adjustment for baseline age, sex, systolic blood pressure, LDL cholesterol, and albuminuria/GFR. The addition of SUMOD to models with traditional risk factors also significantly improved the prediction performance for CAC progression and incident DKD.

Conclusions

Higher baseline SUMOD level predicted lower odds of both CAC progression and incident DKD over 12 years in adults with type 1 diabetes.

SUBMITTER: Bjornstad P

PROVIDER: S-EPMC6341281 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Publications

Serum Uromodulin Predicts Less Coronary Artery Calcification and Diabetic Kidney Disease Over 12 Years in Adults With Type 1 Diabetes: The CACTI Study.

Bjornstad Petter P Wiromrat Pattara P Johnson Richard J RJ Sippl Rachel R Cherney David Z I DZI Wong Randy R Rewers Marian J MJ Snell-Bergeon Janet K JK

Diabetes care 20181127 2

<h4>Objective</h4>Novel biomarkers are needed to better predict coronary artery calcification (CAC), a marker of subclinical atherosclerosis, and diabetic kidney disease (DKD) in type 1 diabetes. We evaluated the associations between serum uromodulin (SUMOD [a biomarker associated with anti-inflammatory and renal protective properties]), CAC progression, and DKD development over 12 years.<h4>Research design and methods</h4>Participants (<i>n</i> = 527, 53% females) in the Coronary Artery Calcifi ...[more]

PMID: 30482755

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Project description:BackgroundThe 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.MethodsParticipants (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.ResultsComponent 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).ConclusionsPlasma kidney injury biomarkers can help predict development of DKD in T1D.

Project description:Background and objectivesVascular calcification (VC) is common in CKD, but little is known about its prognostic effect on patients with nondialysis CKD. The prevalence of VC and its ability to predict death, time to hospitalization, and renal progression were assessed.Design, setting, participants, & measurementsThe Study of Mineral and Bone Disorders in CKD in Spain is a prospective, observational, 3-year follow-up study of 742 patients with nondialysis CKD stages 3-5 from 39 centers in Spain from April to May 2009. VC was assessed using Adragao (AS; x-ray pelvis and hands) and Kauppila (KS; x-ray lateral lumbar spine) scores from 572 and 568 patients, respectively. The primary end point was death. Secondary outcomes were hospital admissions and appearance of a combined renal end point (beginning of dialysis or drop >30% in eGFR). Factors related to VC were assessed by logistic regression analysis. Survival analysis was assessed by Cox proportional models.ResultsVC was present in 79% of patients and prominent in 47% (AS≥3 or KS>6). Age (odds ratio [OR], 1.05; 95% confidence interval [95% CI], 1.02 to 1.07; P<0.001), phosphorous (OR, 1.68; 95% CI, 1.28 to 2.20; P<0.001), and diabetes (OR, 2.11; 95% CI, 1.32 to 3.35; P=0.002) were independently related to AS≥3. After a median follow-up of 35 months (interquartile range=17-36), there were 70 deaths (10%). After multivariate adjustment for age, smoking, diabetes, comorbidity, renal function, and level of phosphorous, AS≥3 but not KS>6 was independently associated with all-cause (hazard ratio [HR], 2.07; 95% CI, 1.07 to 4.01; P=0.03) and cardiovascular (HR, 3.46; 95% CI, 1.27 to 9.45; P=0.02) mortality as well as a shorter hospitalization event-free period (HR, 1.14; 95% CI, 1.06 to 1.22; P<0.001). VC did not predict renal progression.ConclusionsVC is highly prevalent in patients with CKD. VC assessment using AS independently predicts death and time to hospitalization. Therefore, it could be a useful index to identify patients with CKD at high risk of death and morbidity as previously reported in patients on dialysis.

Dataset Information

Serum Uromodulin Predicts Less Coronary Artery Calcification and Diabetic Kidney Disease Over 12 Years in Adults With Type 1 Diabetes: The CACTI Study.

Objective

Research design and methods

Results

Conclusions

Publications

Serum Uromodulin Predicts Less Coronary Artery Calcification and Diabetic Kidney Disease Over 12 Years in Adults With Type 1 Diabetes: The CACTI Study.

Similar Datasets

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