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Urinary angiotensinogen antedates the development of stage 3 CKD in patients with type 1 diabetes mellitus.
Physiol Rep 2019; 7(19):e14242PR

Abstract

We examined if urinary angiotensinogen (uAOG), a marker of intrarenal renin-angiotensin system activity, antedates stage 3 chronic kidney disease (CKD) using samples from participants in the Diabetes Control and Complications Trial (DCCT) and later in the Epidemiology of Diabetes Intervention and Complications (EDIC) trial. In a nested case-control design, cases were matched at the outcome visit (eGFR less than 60, 21-59 mL/min per 1.73 m2) on age, gender, and diabetes duration, with controls: eGFR (95, 75-119, mL/min per 1.73 m2 .) Additionally, in an exploratory analysis progressive renal decline (PRD), defined as eGFR loss >3.5 mL/min per 1.73m2 /year, was evaluated using only data from EDIC because no progressions were observed during DCCT. At the EDIC visit, which antedated the GFR outcome visit by 2 years (range 1-7years) the median uAOG/creatinine was markedly higher in cases than in controls (13.9 vs. 3.8 ng/mg P = 0.003) whereas at the DCCT visit, which antedated the GFR outcome by 17 to 20 years it was not (2.75 vs. 3.16 ng/mg, respectively). The Odds Ratio for uAOG and CKD stage 3 development was significant after adjusting for eGFR, HbA1c, and systolic blood pressure 1.82 (1.00-3.29) but no longer significant when Albumin Excretion Ratio (AER) was included 1.21 (0.65-2.24).In the PRD analysis, uAOG/creatinine was sixfold higher in participants who experienced PRD than in those who did not (26 vs. 4.0 ng/mg, P = 0.003). The Odds Ratio for uAOG and PRD was significant after adjusting for eGFR, HbA1c, and systolic blood pressure 2.48 (1.46-4.22) but no longer significant when AER was included 1.32 (0.76-2.30). In people with type1 diabetes, a robust increase in uAOG antedates the development of stage 3 CKD but is not superior to AER in predicting this renal outcome. Increased uAOG moreover is associated with PRD, an index of progression to End Stage Kidney Disease (ESKD).

Authors+Show Affiliations

Northwestern University Feinberg School of Medicine, Chicago, Illinois.Northwestern University Feinberg School of Medicine, Chicago, Illinois.Northwestern University Feinberg School of Medicine, Chicago, Illinois.Northwestern University Feinberg School of Medicine, Chicago, Illinois.Northwestern University Feinberg School of Medicine, Chicago, Illinois.Northwestern University Feinberg School of Medicine, Chicago, Illinois.Northwestern University Feinberg School of Medicine, Chicago, Illinois.George Washington University, Rockville, Maryland.George Washington University, Rockville, Maryland.National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona.Northwestern University Feinberg School of Medicine, Chicago, Illinois.Northwestern University Feinberg School of Medicine, Chicago, Illinois.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31605461

Citation

Ba Aqeel, Sheeba, et al. "Urinary Angiotensinogen Antedates the Development of Stage 3 CKD in Patients With Type 1 Diabetes Mellitus." Physiological Reports, vol. 7, no. 19, 2019, pp. e14242.
Ba Aqeel S, Ye M, Wysocki J, et al. Urinary angiotensinogen antedates the development of stage 3 CKD in patients with type 1 diabetes mellitus. Physiol Rep. 2019;7(19):e14242.
Ba Aqeel, S., Ye, M., Wysocki, J., Sanchez, A., Khattab, A., Lores, E., ... Batlle, D. (2019). Urinary angiotensinogen antedates the development of stage 3 CKD in patients with type 1 diabetes mellitus. Physiological Reports, 7(19), pp. e14242. doi:10.14814/phy2.14242.
Ba Aqeel S, et al. Urinary Angiotensinogen Antedates the Development of Stage 3 CKD in Patients With Type 1 Diabetes Mellitus. Physiol Rep. 2019;7(19):e14242. PubMed PMID: 31605461.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Urinary angiotensinogen antedates the development of stage 3 CKD in patients with type 1 diabetes mellitus. AU - Ba Aqeel,Sheeba, AU - Ye,Minghao, AU - Wysocki,Jan, AU - Sanchez,Alejandro, AU - Khattab,Ahmed, AU - Lores,Enrique, AU - Rademaker,Alfred, AU - Gao,Xiaoyu, AU - Bebu,Ionut, AU - Nelson,Robert G, AU - Molitch,Mark, AU - Batlle,Daniel, AU - ,, PY - 2019/07/22/received PY - 2019/08/28/revised PY - 2019/08/29/accepted PY - 2019/10/13/entrez PY - 2019/10/13/pubmed PY - 2019/10/13/medline KW - biomarkers KW - chronic kidney disease KW - diabetes KW - hypertension KW - renin angiotensin system KW - urinary angiotensinogen SP - e14242 EP - e14242 JF - Physiological reports JO - Physiol Rep VL - 7 IS - 19 N2 - We examined if urinary angiotensinogen (uAOG), a marker of intrarenal renin-angiotensin system activity, antedates stage 3 chronic kidney disease (CKD) using samples from participants in the Diabetes Control and Complications Trial (DCCT) and later in the Epidemiology of Diabetes Intervention and Complications (EDIC) trial. In a nested case-control design, cases were matched at the outcome visit (eGFR less than 60, 21-59 mL/min per 1.73 m2) on age, gender, and diabetes duration, with controls: eGFR (95, 75-119, mL/min per 1.73 m2 .) Additionally, in an exploratory analysis progressive renal decline (PRD), defined as eGFR loss >3.5 mL/min per 1.73m2 /year, was evaluated using only data from EDIC because no progressions were observed during DCCT. At the EDIC visit, which antedated the GFR outcome visit by 2 years (range 1-7years) the median uAOG/creatinine was markedly higher in cases than in controls (13.9 vs. 3.8 ng/mg P = 0.003) whereas at the DCCT visit, which antedated the GFR outcome by 17 to 20 years it was not (2.75 vs. 3.16 ng/mg, respectively). The Odds Ratio for uAOG and CKD stage 3 development was significant after adjusting for eGFR, HbA1c, and systolic blood pressure 1.82 (1.00-3.29) but no longer significant when Albumin Excretion Ratio (AER) was included 1.21 (0.65-2.24).In the PRD analysis, uAOG/creatinine was sixfold higher in participants who experienced PRD than in those who did not (26 vs. 4.0 ng/mg, P = 0.003). The Odds Ratio for uAOG and PRD was significant after adjusting for eGFR, HbA1c, and systolic blood pressure 2.48 (1.46-4.22) but no longer significant when AER was included 1.32 (0.76-2.30). In people with type1 diabetes, a robust increase in uAOG antedates the development of stage 3 CKD but is not superior to AER in predicting this renal outcome. Increased uAOG moreover is associated with PRD, an index of progression to End Stage Kidney Disease (ESKD). SN - 2051-817X UR - https://www.unboundmedicine.com/medline/citation/31605461/Urinary_angiotensinogen_antedates_the_development_of_stage_3_CKD_in_patients_with_type_1_diabetes_mellitus L2 - https://doi.org/10.14814/phy2.14242 DB - PRIME DP - Unbound Medicine ER -