DIABETIC kidney disease (DKD) remains a leading cause of kidney failure worldwide, with limited tools available to predict which patients will experience rapid disease progression. While existing research has focused largely on albuminuria and glomerular filtration rate (eGFR), recent evidence highlights the potential of distal tubular biomarkers as prognostic indicators. A recent study within the Veterans Affairs Diabetes in Nephropathy (VA NEPHRON-D) trial investigated whether two such biomarkers, epidermal growth factor (EGF) and uromodulin (UMOD), could predict the progression of DKD. Crucially, the findings reveal that higher urinary levels of both EGF and UMOD are associated with a reduced risk of DKD progression.
The study analysed 1,116 participants with Type 2 diabetes, significant proteinuria (UACR ≥ 300 mg/g), and moderate kidney impairment (eGFR between 30 and 89.9 mL/min/1.73 m²). Researchers employed Cox regression models to examine how baseline and longitudinal levels of urinary EGF and UMOD related to the risk of DKD progression. Additionally, mixed models were used to study changes in biomarker levels over a 12-month period and their association with ongoing eGFR decline.
Over a median follow-up of 2.2 years, 13% (n=144) of participants experienced DKD progression. A two-fold higher baseline level of EGF was linked to a 32% lower risk of progression (adjusted hazard ratio [HR]: 0.68; 95% CI: 0.47–0.99), while the same increase in UMOD was associated with a 15% lower risk (adjusted HR: 0.85; 95% CI: 0.75–0.98). Furthermore, a slower decline in these biomarkers over the first 12 months also correlated with reduced risk, even after adjusting for baseline values.
These findings suggest that urinary EGF and UMOD could be clinically useful biomarkers for identifying patients at lower risk of DKD progression. Incorporating these markers into routine monitoring may help stratify risk more effectively and personalise management plans. However, the study population was predominantly older male veterans, which may limit generalisability. Further research is needed across diverse patient groups and clinical settings before widespread implementation. Nonetheless, the results point toward a promising avenue for enhancing DKD risk assessment in practice.
Reference
Tamargo CL et al. The distal nephron biomarkers associate with diabetic kidney disease progression. JCI Insight. 2025;10(12):e186836.
