NGAL may serve as a sensitive biomarker of early tubular injury in Fabry disease, including before overt nephropathy, and may provide complementary, noninvasive tools for detecting and monitoring renal involvement.
In male Fabry disease patients, elevated NGAL strongly correlated with the presence of Fabry nephropathy.
In female Fabry disease patients, urine NGAL was increased regardless of nephropathy status, while plasma NGAL rose mainly in those with reduced eGFR.
Tubular dysfunction and damage may precede detectable glomerular filtration rate decline in Fabry disease.
Urinary and plasma NGAL reflect distinct aspects of renal dysfunction in Fabry nephropathy.
NGAL was identified as a potentially sensitive biomarker of early tubular injury in Fabry disease, detectable before overt nephropathy.
Fabry disease is caused by pathogenic variants in the GLA gene resulting in α-galactosidase A deficiency and accumulation of Gb3/lyso-Gb3 in renal cells including podocytes and renal tubular cells.
Fabry disease is a rare inherited condition where a faulty gene causes a critical enzyme to be missing or not work properly, leading to a harmful fatty substance building up in cells throughout the body, including in the kidneys. Kidney damage in Fabry disease can affect two main areas: the filtering units (glomeruli, involving specialized cells called podocytes) and the tiny tubes (tubules) that process filtered fluid. This research suggests that damage to the tubules — and the scarring it causes — may actually begin before the commonly used kidney function test (eGFR) shows a measurable decline, meaning kidney injury could be underdetected using standard monitoring alone. This study examined a protein called NGAL (neutrophil gelatinase-associated lipocalin), which can be measured in urine or blood and signals kidney injury. Among 33 Fabry disease patients, the researchers found that NGAL behaved differently depending on sex. In males, high NGAL levels were strongly linked to having established kidney disease. In females, urine NGAL was elevated even in those who did not yet show signs of kidney disease by standard measures, while blood NGAL only rose when kidney function (eGFR) was clearly reduced. This pattern suggests that in women with Fabry disease, tubular damage and early scarring may be occurring silently, before it shows up on routine tests. This research suggests that measuring NGAL — particularly in urine — could serve as an early warning signal for kidney damage in Fabry disease patients, potentially allowing for earlier intervention. Because it is a simple, noninvasive test (urine or blood sample), it could complement existing tools and reduce the need for kidney biopsies to assess the type and extent of kidney involvement. These findings highlight the importance of monitoring both tubular and glomerular health separately in Fabry disease, and that standard kidney function tests alone may miss early but significant kidney injury, especially in female patients.
Ivanova M, Dao J, Svarny L, Nguyen E, Ponnam S, Goker-Alpan O. (2026). NGAL as a Biomarker of Tubular Injury and Glomerular Dysfunction in Fabry Nephropathy.. Cells. https://doi.org/10.3390/cells15191797