A targeted multi-omics approach to identify biomarkers associated with rapid eGFR decline in type 1 diabetes
| العنوان: | A targeted multi-omics approach to identify biomarkers associated with rapid eGFR decline in type 1 diabetes |
|---|---|
| المؤلفون: | Christine P. Limonte, Farsad Afshinnia, Niina Sandholm, Subramaniam Pennathur, Tarunveer S. Ahluwalia, Kumar Sharma, Tina Costacou, Jing Zhang, Rachel G. Miller, Loki Natarajan, Manjula Darshi, Andrew N. Hoofnagle, Daniel Montemayor, Carol Forsblom, Trevor J. Orchard, Janet K. Snell-Bergeon, Ian H. de Boer, Erkka Valo, Peter Rossing, Hongping Ye, Per-Henrik Groop |
| المساهمون: | HUS Internal Medicine and Rehabilitation, HUS Abdominal Center, Clinicum, Research Programs Unit, Nefrologian yksikkö, University of Helsinki, Helsinki University Hospital Area, CAMM - Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, Department of Medicine, Per Henrik Groop / Principal Investigator, Medicum |
| المصدر: | Am J Nephrol Limonte, C P, Valo, E, Montemayor, D, Afshinnia, F, Ahluwalia, T S, Costacou, T, Darshi, M, Forsblom, C, Hoofnagle, A N, Groop, P-H, Miller, R G, Orchard, T J, Pennathur, S, Rossing, P, Sandholm, N, Snell-Bergeon, J K, Ye, H, Zhang, J, Natarajan, L, De Boer, I H & Sharma, K 2020, ' A Targeted Multiomics Approach to Identify Biomarkers Associated with Rapid eGFR Decline in Type 1 Diabetes ', American Journal of Nephrology, vol. 51, no. 10, pp. 839-848 . https://doi.org/10.1159/000510830Test |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Oncology, Male, Proteomics, eGFR slope, PROGRESSION, Logistic regression, Kidney Function Tests, METABOLITES, PREDICT, 0302 clinical medicine, Risk Factors, Diabetic Nephropathies, RISK, COMPLICATIONS, 0303 health sciences, Area under the curve, Middle Aged, 3. Good health, Type 1 diabetes, Nephrology, SYSTEMS BIOLOGY, Disease Progression, Population study, Female, RENAL-FUNCTION DECLINE, Glomerular Filtration Rate, Adult, medicine.medical_specialty, NEPHROPATHY, Renal function, Omics, 030209 endocrinology & metabolism, Article, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, medicine, Humans, 030304 developmental biology, business.industry, MICROALBUMINURIA, KIDNEY-DISEASE, medicine.disease, Blood pressure, Diabetes Mellitus, Type 1, ROC Curve, 3121 General medicine, internal medicine and other clinical medicine, Case-Control Studies, Lipidomics, Microalbuminuria, 3111 Biomedicine, business, Biomarkers, Follow-Up Studies |
| الوصف: | Background: Individuals with type 1 diabetes (T1D) demonstrate varied trajectories of estimated glomerular filtration rate (eGFR) decline. The molecular pathways underlying rapid eGFR decline in T1D are poorly understood, and individual-level risk of rapid eGFR decline is difficult to predict. Methods: We designed a case-control study with multiple exposure measurements nested within 4 well-characterized T1D cohorts (FinnDiane, Steno, EDC, and CACTI) to identify biomarkers associated with rapid eGFR decline. Here, we report the rationale for and design of these studies as well as results of models testing associations of clinical characteristics with rapid eGFR decline in the study population, upon which “omics” studies will be built. Cases (n = 535) and controls (n = 895) were defined as having an annual eGFR decline of ≥3 and 2, respectively. Associations of demographic and clinical variables with rapid eGFR decline were tested using logistic regression, and prediction was evaluated using area under the curve (AUC) statistics. Targeted metabolomics, lipidomics, and proteomics are being performed using high-resolution mass-spectrometry techniques. Results: At baseline, the mean age was 43 years, diabetes duration was 27 years, eGFR was 94 mL/min/1.73 m2, and 62% of participants were normoalbuminuric. Over 7.6-year median follow-up, the mean annual change in eGFR in cases and controls was −5.7 and 0.6 mL/min/1.73 m2, respectively. Younger age, longer diabetes duration, and higher baseline HbA1c, urine albumin-creatinine ratio, and eGFR were significantly associated with rapid eGFR decline. The cross-validated AUC for the predictive model incorporating these variables plus sex and mean arterial blood pressure was 0.74 (95% CI: 0.68–0.79; p < 0.001). Conclusion: Known risk factors provide moderate discrimination of rapid eGFR decline. Identification of blood and urine biomarkers associated with rapid eGFR decline in T1D using targeted omics strategies may provide insight into disease mechanisms and improve upon clinical predictive models using traditional risk factors. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f2afe71294ad3a97fe4a4212d4f5d7c8Test https://europepmc.org/articles/PMC7606554Test/ |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f2afe71294ad3a97fe4a4212d4f5d7c8 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |