Renal Progenitor Cells as a Biomarker of Kidney Injury in Fabry Disease

Jessica Ugalde-Altamirano and fellow researchers conducted an open, observational, case-control, single-center study with the goal of demonstrating the presence of renal progenitor cells (RPCs) in urine as a noninvasive early marker for detecting renal damage in patients with Fabry disease (FD). They also hoped to show a correlation between RPC presence, deposition of the lipid globotriaosylceramide (GB3), and the potential association with the level of renal injury. The results were presented at the 61st European Renal Association Congress.

FD is an inherited condition in which a mutation causes a defect in the metabolism of glycosphingolipids, leading to the deposition of GB3 in organs, including the kidneys. Podocytes are most often affected, leading to proteinuria, which can cause a rapid decrease in renal function if it exceeds 0.5 g.

Renal biopsy is the gold standard biomarker, but less invasive biomarkers are starting to gain prominence. RPCs contribute to cellular remodeling, and they express specific markers such as CD133/CD24 and CD106 in the parietal epithelium of Bowman’s capsule; GB3 expresses CD77. If the proliferative response of RPCs becomes dysregulated, detachment and elimination in the urine occurs.

Ugalde-Altamirano’s research group analyzed 75 urine samples from 59 patients, 16 with FD, 11 with Gittelman syndrome, 10 with chronic kidney disease (CKD), and 22 healthy controls. They divided the samples for sediment and microalbuminuria analysis, and separately to isolate RPCs, then classified and quantified the isolated cell types. Positivity points were established using compensation panels with CD3 lymphocyte markers. Next, RPCs were identified through positivity for CD133+/CD24+, CD106+, and CD106– markers. After RPCs were identified, the researchers conducted GB3 marking using CD77+.

There was no or minimal presence of RPCs in the healthy control group, except in two patients who subsequently were found to have bilateral lithiasis and previously unknown hypertension. The Gittelman syndrome group had a higher prevalence of RPCs compared with the control group (P>.05). The FD and CKD groups showed clear RPC positivity as confirmed by biopsy (P<.05). When the level of renal disease was correlated with the presence of proteinuria, differences in the quantity of RPCs were noted (<0.5 g and >0.5 g; P<.05).

The authors wrote, “With these results, we can conclude that [RPCs] may serve as an early biomarker for silent renal injury of various etiologies. Furthermore, if we perform labeling with CD77, we can attribute it to the deposition of GB3 in [FD].”

Source: Ugalde-Altamirano J, Juarez JR, Tubita V, et al. Renal progenitor cells an early non-invasive biomarker of silent kidney injury in Fabry disease. Abstract #2908. Presented at the 61st European Renal Association Congress; May 23-26, 2024; Stockholm, Sweden.