Urine leucine-rich α-2 glycoprotein 1 (LRG1) predicts the risk of progression to end-stage kidney disease in patients with type 2 diabetes

OBJECTIVE: Leucine-rich a-2 glycoprotein 1 (LRG1) was recently identified as an amplifier of transforming growth factor-b (TGF-b)–induced kidney fibrosis in animal models. We aimed to study whether urine LRG1 is associated with risk of progression to end-stage kidney disease (ESKD) in individuals wi...

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Main Authors: Liu, Jian-Jun, Liu, Sylvia, Wang, Jiexun, Pek, Sharon L. T., Lee, Janus, Gurung, Resham L., Ang, Keven, Shao, Yi Ming, Tavintharan, Subramaniam, Tang, Wern Ee, Sum, Chee Fang, Lim, Su Chi
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2023
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Online Access:https://hdl.handle.net/10356/172167
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-1721672023-11-28T02:43:30Z Urine leucine-rich α-2 glycoprotein 1 (LRG1) predicts the risk of progression to end-stage kidney disease in patients with type 2 diabetes Liu, Jian-Jun Liu, Sylvia Wang, Jiexun Pek, Sharon L. T. Lee, Janus Gurung, Resham L. Ang, Keven Shao, Yi Ming Tavintharan, Subramaniam Tang, Wern Ee Sum, Chee Fang Lim, Su Chi Lee Kong Chian School of Medicine (LKCMedicine) Admiralty Medical Center, Singapore Saw Swee Hock School of Public Heath, NUS Science::Medicine LRG1 Protein End Stage Renal Disease OBJECTIVE: Leucine-rich a-2 glycoprotein 1 (LRG1) was recently identified as an amplifier of transforming growth factor-b (TGF-b)–induced kidney fibrosis in animal models. We aimed to study whether urine LRG1 is associated with risk of progression to end-stage kidney disease (ESKD) in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 1,837 participants with type 2 diabetes and estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 were recruited from a regional hospital and a primary care facility. Association of urine LRG1 with risk of ESKD (progres-sion to sustained eGFR <15 mL/min/1.73 m2, dialysis, or death resulting from renal causes) was assessed by survival analyses. RESULTS: During a median follow-up of 8.6 (interquartile range 5.8–9.6) years, 134 incident ESKD events were identified. Compared with those in the lowest tertile, participants with baseline urine LRG1 in the highest tertile had a 1.91-fold (95% CI 1.04–3.50) increased risk of progression to ESKD, after adjustment for cardiorenal risk factors, including eGFR and albuminuria. As a continuous variable, 1 SD incre-ment in urine LRG1 was associated with a 1.53-fold (95% CI 1.19–1.98) adjusted risk of ESKD. Of note, the association of urine LRG1 with ESKD was independent of plasma LRG1. Moreover, urine LRG1 was associated with rapid kidney function decline and progression to macroalbuminuria, two common pathways leading to ESKD. CONCLUSIONS: Urine LRG1, a TGF-b signaling modulator, predicts risk of progression to ESKD in-dependently of clinical risk factors in patients with type 2 diabetes, suggesting that it may be a novel factor involved in the pathophysiological pathway leading to kidney disease progression. National Medical Research Council (NMRC) This work was funded by a Singapore National Medical Research Council Clinician Scientist Individual Research grant (MOH-000066) and Khoo Teck Puat Hospital Science Translational and Applied Research grants (18203 and 20201). S.C.L. was partly supported by a Clinician Scientist Award–Investigator (INV/0020/2017) and an Open Fund–Large Collaborative grant (OFLCG/001/2017) from the Singapore National Medical Research Council. 2023-11-28T02:43:30Z 2023-11-28T02:43:30Z 2023 Journal Article Liu, J., Liu, S., Wang, J., Pek, S. L. T., Lee, J., Gurung, R. L., Ang, K., Shao, Y. M., Tavintharan, S., Tang, W. E., Sum, C. F. & Lim, S. C. (2023). Urine leucine-rich α-2 glycoprotein 1 (LRG1) predicts the risk of progression to end-stage kidney disease in patients with type 2 diabetes. Diabetes Care, 46(2), 408-415. https://dx.doi.org/10.2337/dc22-1611 0149-5992 https://hdl.handle.net/10356/172167 10.2337/dc22-1611 36516193 2-s2.0-85147047508 2 46 408 415 en MOH-000066 18203 20201 INV/0020/2017 OFLCG/001/2017 Diabetes Care © 2023 by the American Diabetes Association. All rights reserved.
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
LRG1 Protein
End Stage Renal Disease
spellingShingle Science::Medicine
LRG1 Protein
End Stage Renal Disease
Liu, Jian-Jun
Liu, Sylvia
Wang, Jiexun
Pek, Sharon L. T.
Lee, Janus
Gurung, Resham L.
Ang, Keven
Shao, Yi Ming
Tavintharan, Subramaniam
Tang, Wern Ee
Sum, Chee Fang
Lim, Su Chi
Urine leucine-rich α-2 glycoprotein 1 (LRG1) predicts the risk of progression to end-stage kidney disease in patients with type 2 diabetes
description OBJECTIVE: Leucine-rich a-2 glycoprotein 1 (LRG1) was recently identified as an amplifier of transforming growth factor-b (TGF-b)–induced kidney fibrosis in animal models. We aimed to study whether urine LRG1 is associated with risk of progression to end-stage kidney disease (ESKD) in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 1,837 participants with type 2 diabetes and estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 were recruited from a regional hospital and a primary care facility. Association of urine LRG1 with risk of ESKD (progres-sion to sustained eGFR <15 mL/min/1.73 m2, dialysis, or death resulting from renal causes) was assessed by survival analyses. RESULTS: During a median follow-up of 8.6 (interquartile range 5.8–9.6) years, 134 incident ESKD events were identified. Compared with those in the lowest tertile, participants with baseline urine LRG1 in the highest tertile had a 1.91-fold (95% CI 1.04–3.50) increased risk of progression to ESKD, after adjustment for cardiorenal risk factors, including eGFR and albuminuria. As a continuous variable, 1 SD incre-ment in urine LRG1 was associated with a 1.53-fold (95% CI 1.19–1.98) adjusted risk of ESKD. Of note, the association of urine LRG1 with ESKD was independent of plasma LRG1. Moreover, urine LRG1 was associated with rapid kidney function decline and progression to macroalbuminuria, two common pathways leading to ESKD. CONCLUSIONS: Urine LRG1, a TGF-b signaling modulator, predicts risk of progression to ESKD in-dependently of clinical risk factors in patients with type 2 diabetes, suggesting that it may be a novel factor involved in the pathophysiological pathway leading to kidney disease progression.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Liu, Jian-Jun
Liu, Sylvia
Wang, Jiexun
Pek, Sharon L. T.
Lee, Janus
Gurung, Resham L.
Ang, Keven
Shao, Yi Ming
Tavintharan, Subramaniam
Tang, Wern Ee
Sum, Chee Fang
Lim, Su Chi
format Article
author Liu, Jian-Jun
Liu, Sylvia
Wang, Jiexun
Pek, Sharon L. T.
Lee, Janus
Gurung, Resham L.
Ang, Keven
Shao, Yi Ming
Tavintharan, Subramaniam
Tang, Wern Ee
Sum, Chee Fang
Lim, Su Chi
author_sort Liu, Jian-Jun
title Urine leucine-rich α-2 glycoprotein 1 (LRG1) predicts the risk of progression to end-stage kidney disease in patients with type 2 diabetes
title_short Urine leucine-rich α-2 glycoprotein 1 (LRG1) predicts the risk of progression to end-stage kidney disease in patients with type 2 diabetes
title_full Urine leucine-rich α-2 glycoprotein 1 (LRG1) predicts the risk of progression to end-stage kidney disease in patients with type 2 diabetes
title_fullStr Urine leucine-rich α-2 glycoprotein 1 (LRG1) predicts the risk of progression to end-stage kidney disease in patients with type 2 diabetes
title_full_unstemmed Urine leucine-rich α-2 glycoprotein 1 (LRG1) predicts the risk of progression to end-stage kidney disease in patients with type 2 diabetes
title_sort urine leucine-rich α-2 glycoprotein 1 (lrg1) predicts the risk of progression to end-stage kidney disease in patients with type 2 diabetes
publishDate 2023
url https://hdl.handle.net/10356/172167
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