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[45]
progenitor cell source, positioning and differentiation problem . During the embryonic stage, these renal
progenitor cells are located in the renal utricle and S-shaped bodies and retain the ability to differentiate
into both glomerular and tubular epithelial cells. During subsequent development, the number of RPCs
decreases, and at the adult stage, RPCs only account for about 2% of the innate cells in the kidney. As RPCs
of podocyte, only exists in the bowman’s capsule wall, at the same time expressing cells and associated RPCs
differentiation markers.

Podocyte regeneration for repair and functional recovery after kidney damage is of crucial importance. In
the last decade, notable progress has been made in the study of podocyte regeneration. For example, it has
been shown that by enhancing the differentiation capacity of renal precursor cells, podocyte regeneration
[46]
can be enhanced, leading to improved prognosis in chronic kidney disease . In addition, some studies have
[47]
also discussed the effects of specific drugs such as BIO (GSK3 inhibitor) on cell regeneration .
In Fabry disease, the loss of αGalA activity leads to the accumulation of metabolic substrates in podocytes
and other cells, which may affect the normal function and regeneration ability of podocytes. Therefore,
therapeutic strategies targeting podocyte regeneration may have some potential for the treatment of renal
involvement in FD. However, the specific mechanism of the interaction between FD and podocyte
regeneration is not fully understood at present, and further studies are needed to elucidate it.

As research on kidney damage markers advances in both theory and methodology, the evaluation of tissue
damage using non-invasive biomarkers has gained significant attention in recent years. Small molecules,
such as those found in blood and urine tests, are explored, including urine concentrations of dissolved Gb3
in Sertoli cells or the detection of glomerular progenitor cells in urine. At the ERA - EDTA 2024 academic
conference, a study by Ugalde-Altamirano et al. from Spain reported that RPCs detected in urine could
[48]
serve as early non-invasive markers for evaluating kidney damage in Fabry patients . The study
investigated the correlation between RPCs and Gb3 accumulation in relation to the severity of renal tissue
injury. The research involved Fabry disease patients, healthy controls, and chronic kidney disease (CKD)
patients without Fabry disease. RPCs were isolated from urine using specific markers and flow cytometry,
and their association with renal function indicators and the level of proteinuria was analyzed. The study
found that labeled RPCs were difficult to detect in the urine of healthy individuals, while their numbers
significantly increased in the urine of Fabry disease patients and those with biopsy-proven CKD.
Additionally, the number of RPCs correlated with the degree of proteinuria. This research identified, for the
first time, glomerular-specific progenitor cells with Gb3 accumulation in the urine of Fabry patients,
indicating their potential as biomarkers for early kidney injury in this disease. The findings suggest that
therapeutic strategies aimed at podocyte regeneration may emerge as a new direction for future research in
Fabry disease, potentially improving renal prognosis for patients.

CONCLUSION
FD is a lysosomal storage disease that can affect multiple organs and presents diverse and non-specific
clinical manifestations. Among the histological features of renal involvement, podocyte lesions are the most
severely affected. Early ERT can delay disease progression and improve prognosis. The implementation of a
new dynamic monitoring mechanism for podocyte injury, along with the expanded concept of cell repair
and regeneration therapy, combined with comprehensive interdisciplinary symptom management, offers an
optimistic outlook for the prognosis of patients with renal impairment due to FD.