Leucine-rich α-2-glycoprotein 1 can be a novel angiogenic mediator in autosomal dominant polycystic kidney disease

Abstract Objectives In the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD), hypoxia-associated angiogenesis is increasingly considered a significant mechanism. We aimed to assess serum and urine leucine-rich α-2-glycoprotein 1 (LRG1) levels and their correlation with vascular endothelial growth factor A (VEGF-A), hypoxia-inducible factor 1-alpha (HIF-1α), and disease severity to explore LRG1’s role as a biochemical marker in ADPKD-related angiogenesis. Methods The study involved 67 ADPKD patients and 25 healthy controls. The ADPKD-I group comprised 40 patients with an estimated glomerular filtration rate (eGFR, mL/min/1.73 m 2 ) >60, and the ADPKD-II group comprised 27 patients with an eGFR <60. Height-adjusted total kidney volume (hTKV) was calculated from magnetic resonance (MR) images. Serum levels of LRG1, VEGF-A, HIF-1α, and urine LRG1 levels were assayed by ELISA, and urinary albumin levels were measured by the immunoturbidimetric method. Urine LRG and albumin levels were calculated by normalizing the urine creatinine ratio. Results The levels of serum LRG1 were remarkably higher only in the ADPKD-II group compared to controls (p<0.025). Serum HIF-1α and VEGF-A levels were significantly elevated in both ADPKD-I and ADPKD-II groups compared to controls (p = 0.039, p = 0.029, p<0.001, and p<0.001, respectively); however, there was no notable difference between two groups. Urinary LRG1 and albumin excretion levels were notably higher in both ADPKD groups than in controls but the highest in the ADPKD-II group. In the ADPKD-I group, urine LRG1 correlated positively with urinary albumin excretion (r = 0.338, p = 0.038). Conclusions LRG1 may serve as a mediator in the crosstalk between hypoxia and angiogenesis in patients with ADPKD. Additionally, urinary LRG1 levels could potentially reflect disease severity.