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. 2025 Feb 4;14(3):218.
doi: 10.3390/cells14030218.

Telomere Length, Oxidative Stress, and Kidney Damage Biomarkers in Fabry Nephropathy

Tina Levstek  1   2 , Erazem Bahčič  1 , Bojan Vujkovac  3 , Andreja Cokan Vujkovac  3 , Tine Tesovnik  2 , Žiga Iztok Remec  2 , Vanja Čuk  2 , Katarina Trebušak Podkrajšek  1   2
Affiliations

Telomere Length, Oxidative Stress, and Kidney Damage Biomarkers in Fabry Nephropathy

Tina Levstek et al. Cells. .

Abstract

Fabry nephropathy is a life-threatening complication of Fabry disease characterized by complex and incompletely understood pathophysiological processes possibly linked to premature aging. We aimed to investigate leukocyte telomere length (LTL), oxidative stress, and kidney damage biomarkers in relation to kidney function. The study included 35 Fabry patients and 35 age and sex-matched control subjects. Based on the estimated slope of the glomerular filtration rate, the patients were divided into two groups. Relative LTL was quantified by qPCR, urinary biomarkers 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) by UHPLC-MS/MS, and kidney damage biomarkers by flow cytometry. There was no statistically significant difference in LTL between Fabry patients and controls. However, a significant difference was observed in male patients compared to their matched control subjects (p = 0.013). Oxidative stress biomarkers showed no differences between patients and controls, while significant differences were observed in urinary IGFBP7, EGF, and OPN levels between Fabry patients with stable kidney function and those with progressive nephropathy (FDR = 0.021, 0.002, and 0.013, respectively). Significant differences were also observed in plasma levels of cystatin C, TFF3, and uromodulin between patients with progressive nephropathy and controls (all FDR = 0.039). Along with these biomarkers (FDR = 0.007, 0.017, and 0.010, respectively), NGAL also exhibited a significant difference between the two patient groups (FDR = 0.017). This study indicates accelerated telomere attrition, which may be related to disease burden in males. Furthermore, analyses of urinary oxidative stress markers revealed no notable disparities between the different kidney function groups, indicating their limited utility. However, promising differences were found in some biomarkers of kidney damage in urine and plasma.

Keywords: Fabry disease; aging; biomarker; kidney damage; nephropathy; oxidative stress; telomere length.

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Conflict of interest statement

T.L. received travel and accommodation funding from Chiesi. B.V. received speaker fees and consultancy honoraria from Sanofi-Genzyme, Takeda Pharmaceuticals, Amicus, Chiesi, Swixx, and Eleva. A.C.V. received speaker fees and travel and accommodation funding from Sanofi-Genzyme and Takeda Pharmaceuticals. K.T.P. received travel and accommodation funding from Sanofi Genzyme and speaker fees from Takeda Pharmaceuticals.

Figures

Figure 1
Figure 1
Comparison of leukocyte telomere length (TL) between (a) control subjects and Fabry patients, (b) control subjects and male Fabry patients, and (c) control subjects and female Fabry patients.
Figure 2
Figure 2
Comparison of leukocyte telomere length (TL) between (a) control subjects and Fabry patients with stable kidney function (FD-SKF) and (b) control subjects and Fabry patients with progressive nephropathy (FD-NN).
Figure 3
Figure 3
Comparison of urinary 8-OHdG levels between (a) control subjects and Fabry patients, (b) control subjects and Fabry patients with stable kidney function (FD-SKF), and (c) control subjects and Fabry patients with progressive nephropathy (FD-NN).
Figure 4
Figure 4
Comparison of urinary MDA levels between (a) control subjects and Fabry patients, (b) control subjects and Fabry patients with stable kidney function (FD-SKF), and (c) control subjects and Fabry patients with progressive nephropathy (FD-NN).
Figure 5
Figure 5
Correlation between urinary concentration of (a) 8-OHdG or (b) MDA and relative leukocyte telomere length (TL).
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