Abstract
Background: Tubulointerstitial involvement has been reported to have a decisive influence on the progression of IgA nephropathy (IgAN). High levels of urine β2-microglobulin (β2-MG) and retinol-binding protein (RBP) were observed in patients with IgAN with tubulointerstitial lesions. However, their roles in disease progression remain unclear. This study aimed to evaluate the associations of urine β2-MG and RBP with the progression of IgAN.Methods: We retrospectively investigated a cohort of 2,153 patients with IgAN. Clinical and pathological features, outcomes, and urine β2-MG, and RBP at the time of biopsy were collected. The associations, of urine β2-MG and RBP with the composite renal outcome, defined as a decline in estimated glomerular filtration rate (eGFR) of ≥50% from baseline or end-stage renal disease (ESRD), were examined using restricted cubic splines and the Cox proportional hazards models.Results: During a median follow-up of 20.40 months, 140 (6.50%) patients reached the composite renal outcomes. Restricted cubic splines showed that patients with higher urinary β2-MG and RBP levels had worse renal outcomes. The Cox regression analysis revealed that urine β2-MG and RBP were associated with a risk of the composite renal outcome in the multivariate adjusted model [+1 SD for log β2-MG, hazard ratio (HR) = 1.462, 95% CI: 1.136–1.882, p = 0.003; +1 SD for log RBP, HR = 1.972, 95% CI: 1.486–2.617, p = 0.001]. The associations were detectable within patients with baseline eGFR <90 ml/min/1.73 m2 (+1 SD for log β2-MG, HR = 1.657, 95% CI: 1.260–2.180, p < 0.001; +1 SD for log RBP, HR = 1.618, 95% CI: 1.199–2.183, p = 0.002), but not among patients with eGFR ≥90 ml/min/1.73 m2.Conclusion: Higher levels of urine β2-MG and RBP were independent risk factors for renal disease progression in IgAN.
Highlights
IgA nephropathy (IgAN) is the most prevalent type of primary glomerulonephritis globally, defined as prominent IgA deposition in the glomerular mesangial area [1, 2]
The Cox regression analysis revealed that urine β2-MG and retinol-binding protein (RBP) were associated with a risk of the composite renal outcome in the multivariate adjusted model [+1 SD for log β2-MG, hazard ratio (HR) = 1.462, 95% CI: 1.136–1.882, p = 0.003; +1 SD for log RBP, HR = 1.972, 95% CI: 1.486–2.617, p = 0.001]
The associations were detectable within patients with baseline estimated glomerular filtration rate (eGFR)
Summary
IgA nephropathy (IgAN) is the most prevalent type of primary glomerulonephritis globally, defined as prominent IgA deposition in the glomerular mesangial area [1, 2]. It is clinically valuable to find noninvasive biomarkers that predict tubulointerstitial lesions and renal disease progression Both the β2-microglobulin (β2-MG) and retinol-binding protein (RBP) are low-molecular-weight proteins (11.8 and 21 kD, respectively) that are present in low concentrations in the plasma of healthy people and are freely filtered by the normal glomerulus and almost completely reabsorbed and catabolized by cells of the proximal tubules [16, 17]. Increased levels of urine β2-MG and RBP were found in patients with renal tubulointerstitial damage [18,19,20] Their roles in the long-term outcome of IgAN have not been well-assessed. High levels of urine β2-microglobulin (β2-MG) and retinol-binding protein (RBP) were observed in patients with IgAN with tubulointerstitial lesions. Their roles in disease progression remain unclear. This study aimed to evaluate the associations of urine β2-MG and RBP with the progression of IgAN
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