Unmasking the Hidden Burden: Early Renal Microvascular Injury in Prediabetes Using Urinary Biomarkers

Jonas Schneider¹, Anna Fischer², Lukas Weber³

Abstract

Background: Prediabetes is traditionally viewed as a reversible metabolic stage, yet emerging evidence suggests microvascular damage may begin before overt diabetes. Early renal injury remains poorly characterized.

Objective: To assess the prevalence of early renal microvascular dysfunction in prediabetic adults using novel urinary biomarkers.

Methods: A cross-sectional analysis of 624 adults aged 25–55 was conducted between 2022 and 2024. Participants were classified as prediabetic (n = 372) or normoglycemic controls (n = 252). Urinary neutrophil gelatinase-associated lipocalin (uNGAL), kidney injury molecule-1 (KIM-1), and microalbuminuria were quantified. Renal resistive index (RRI) was measured through Doppler ultrasound.

Results: Elevated uNGAL (>20 ng/mL) was found in 46.2% of prediabetic subjects versus 11.5% of controls (p < 0.001). KIM-1 levels were 1.9-fold higher in prediabetics (1.14 ± 0.32 vs 0.60 ± 0.21 ng/mL, p < 0.001). Microalbuminuria prevalence was 18.8% in prediabetics compared with 4.2% in controls (p < 0.001). RRI exceeded 0.70 in 29.3% of prediabetic participants, correlating significantly with HbA1c (r = 0.42). Combining biomarkers (uNGAL + KIM-1) achieved an AUC of 0.87 for early renal injury detection.

Conclusion: Nearly half of prediabetic adults exhibit biomarker evidence of renal microvascular injury, suggesting kidney damage begins earlier than expected. Screening with urinary biomarkers may facilitate earlier intervention.