Background <p>Diabetic nephropathy (DN) remains a major complication of type 2 diabetes mellitus (T2D). Conventional markers such as albuminuria and HbA1c have limited value for early prediction. Plasma glycated CD59 (gCD59), a complement-regulatory protein modified under chronic hyperglycaemia, has emerged as a potential biomarker. This study examined the association of plasma gCD59 with renal function, tubular injury, inflammation, endothelial dysfunction, and complement activation in T2D.</p> Methods <p>A total of 320 adults with T2D were enrolled and classified into microalbuminuria and normoalbuminuria groups (<i>n</i> = 160 each). Plasma gCD59, eGFR, urinary NGAL and KIM-1 (mg/g creatinine), hs-CRP, sICAM-1, sVCAM-1, ApoB, and soluble membrane attack complex (sMAC, ng/mL) were assessed. Hierarchical multivariable logistic regression was performed with sequential adjustment for demographics, diabetes duration, blood pressure, and medication use.</p> Results <p>Patients with microalbuminuria had higher plasma gCD59, NGAL, KIM-1, hs-CRP, sICAM-1/sVCAM-1, ApoB, and sMAC levels, along with lower eGFR (all <i>p</i> &lt; 0.01). Plasma gCD59 correlated with sMAC (<i>r</i> = 0.62), NGAL/KIM-1 (<i>r</i> = 0.58), and HbA1c (<i>r</i> = 0.55). In fully adjusted regression (Model 3), plasma gCD59 (OR: 2.72, 95% CI:1.84–4.03), urinary NGAL (OR:1.57, 95% CI:1.09–2.25), and sMAC (OR:2.31, 95% CI:1.49–3.58) remained independent predictors of microalbuminuria.</p> Conclusion <p>Plasma gCD59 showed strong associations with complement activation, tubular injury, and albuminuria in T2D. When combined with tubular and complement markers, gCD59 may improve early stratification of DN risk. Prospective studies are required to determine temporal and causal relationships and to validate its clinical utility.</p>

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Glycated CD59: an emerging biomarker of diabetic nephropathy associated with microalbuminuria, tubular damage, and complement activation

  • Bhagatsingh Chinta,
  • Sunethri Padma,
  • Ranga Rao Ambati

摘要

Background

Diabetic nephropathy (DN) remains a major complication of type 2 diabetes mellitus (T2D). Conventional markers such as albuminuria and HbA1c have limited value for early prediction. Plasma glycated CD59 (gCD59), a complement-regulatory protein modified under chronic hyperglycaemia, has emerged as a potential biomarker. This study examined the association of plasma gCD59 with renal function, tubular injury, inflammation, endothelial dysfunction, and complement activation in T2D.

Methods

A total of 320 adults with T2D were enrolled and classified into microalbuminuria and normoalbuminuria groups (n = 160 each). Plasma gCD59, eGFR, urinary NGAL and KIM-1 (mg/g creatinine), hs-CRP, sICAM-1, sVCAM-1, ApoB, and soluble membrane attack complex (sMAC, ng/mL) were assessed. Hierarchical multivariable logistic regression was performed with sequential adjustment for demographics, diabetes duration, blood pressure, and medication use.

Results

Patients with microalbuminuria had higher plasma gCD59, NGAL, KIM-1, hs-CRP, sICAM-1/sVCAM-1, ApoB, and sMAC levels, along with lower eGFR (all p < 0.01). Plasma gCD59 correlated with sMAC (r = 0.62), NGAL/KIM-1 (r = 0.58), and HbA1c (r = 0.55). In fully adjusted regression (Model 3), plasma gCD59 (OR: 2.72, 95% CI:1.84–4.03), urinary NGAL (OR:1.57, 95% CI:1.09–2.25), and sMAC (OR:2.31, 95% CI:1.49–3.58) remained independent predictors of microalbuminuria.

Conclusion

Plasma gCD59 showed strong associations with complement activation, tubular injury, and albuminuria in T2D. When combined with tubular and complement markers, gCD59 may improve early stratification of DN risk. Prospective studies are required to determine temporal and causal relationships and to validate its clinical utility.