Singapore: Diabetes is the leading cause of end-stage kidney disease (ESKD) in many countries (1). The pathophysiological mechanisms underlying the pathogenesis and progression of diabetic kidney disease (DKD) are only partially understood.
According to research published in the Diabetes care Journal, Urine leucine-rich-alpha-2 glycoprotein 1 (LRG1) is a novel protein involved in the pathophysiology of progressive kidney disease with type 2 diabetes (T2D).

The team of researchers studied the association between LRG1 levels and end-stage kidney disease (ESKD).
In animal models, LRG1 is identified as an amplifier of transforming growth factor-β (TGF-β)–induced kidney fibrosis.
The researcher's team, led by Jian-Jun Liu from the Khoo Teck Puat Hospital studied the role of LRG1 in type 2 diabetes individuals regarding its association with the risk of progression to end-stage kidney disease (ESKD).
The study summary is as follows:
There were 1,837 participants with type 2 diabetes and eGFR >30 mL/min/1.73 m2.
Urine LRG1 measurement at baseline (cohort enrolment).
Survival analysis to study the association of urine LRG1 with the risk of ESKD.
The duration of the mean follow-up was 8.6 years.
134 ESKD events were identified (sustained eGFR < 15 ml/min/1.73 m2, dialysis or renal death.
The study participants with urine LRG1 in the highest tertile had a significantly higher risk for ESKD progression.
One SD increment was associated with a 1.53-fold adjusted risk of ESKD.
Urine LRG1 was associated with a rapid decline in kidney function (eGFR decline 5ml/min/1.73 m2 per year or greater) and risk for progression to macroalbuminuria.
To conclude, Urine LRG1 predicts the risk of ESKD progression independently of clinical risk factors in T2D patients. This is a valuable marker to indicate the progression to ESKD.
The participants in the highest tertile of urine LRG1 levels had a significantly higher risk for incident ESKD.
Citation
Jian-Jun Liu et al. 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 2022; dc221611. https://doi.org/10.2337/dc22-1611