NGAL as a Biomarker of Tubular Injury and Glomerular Dysfunction in Fabry Nephropathy

Fabry disease (FD) is an X-linked lysosomal disorder caused by pathogenic variants in the GLA gene, resulting in α-galactosidase A deficiency and accumulation of Gb3/lyso-Gb3 (globotriaosylceramide/globotriaosylsphingosine) in cells, including podocytes and renal tubular cells. While podocyte damage drives glomerular dysfunction, tubular dysfunction leads to atrophy and fibrosis, often preceding a detectable decline in glomerular filtration rate (eGFR). Neutrophil gelatinase-associated lipocalin (NGAL) is a marker of renal injury, with urinary and plasma NGAL reflecting distinct aspects of renal dysfunction; however, their clinical value in Fabry nephropathy (FN) remains poorly defined. We explored the clinical relevance of NGAL in distinguishing tubular atrophy from glomerular podocytopathy. Thirty-three FD patients were categorized into groups without and with FN using eGFR. In males, elevated NGAL strongly correlated with FN. In females, urine NGAL was increased regardless of nephropathy status, while plasma NGAL rose mainly in those with reduced eGFR. This pattern suggests that tubular damage and early tubulointerstitial fibrosis (TIF) may precede glomerular impairment in female patients. Conclusions: Tubular damage may precede glomerular dysfunction in FD, and NGAL may serve as a sensitive biomarker of early tubular injury, including before overt nephropathy. NGAL may provide complementary, noninvasive tools for detecting and monitoring renal involvement in Fabry disease.