Podocyturia in Fabry disease: a 10-year follow-up

Abstract

Background: Fabry disease (FD) is a rare X-linked disorder of sphingolipid metabolism that results in chronic proteinuric nephropathy. Podocytes are one of the most affected renal cells and play an important role in the development and progression of kidney disease. Detached podocytes found in urine (podocyturia) are considered as a non-invasive early marker of kidney injury; however, the dynamics of podocyte loss remains unknown.

Methods: In this 10-year follow-up study, podocyturia and other renal clinical data were evaluated in 39 patients with FD. From 2009 to 2019, podocyturia was assessed in 566 fresh urine samples from 13 male and 26 female FD patients using immunocytochemical detection of podocalyxin.

Results: Podocyturia (number of podocytes per 100 mL of urine) was found in 311/566 (54.9%) of the samples, more frequently (68.9 ± 21.9% versus 50.6 ± 25.9%; P = 0.035) and with higher values (364 ± 286 versus 182 ± 180 number of podocytes per gram of creatinine (Cr) in urine; P = 0.020) in males compared with females. The mean number of assessed samples for each patient was 14.5 (range 3-40) and the frequency of samples with podocyturia ranged from 0% to 100% (median 57%). Podocyturia was already present in 42.9% of patients <20 years of age and in 89.5% of normoalbuminuric patients. Podocyturia correlated with albuminuria (urine albumin:Cr ratio) (r = 0.20, P < 0.001) and a higher incidence and values of podocyturia were observed in patients with lower estimated glomerular filtration rate.

Conclusions: Our data demonstrated that podocyturia is an early clinical event in the development of nephropathy. In addition, we found podocyturia to be a discontinuous event with wide variability.

Keywords: Fabry disease; albuminuria; biomarkers; immunocytochemistry; podocalyxin; podocyturia; proteinuria; renal function.

Graphical Abstract

FIGURE 1:

Urinary podocalyxin-positive cells (400×) surrounded by urothelial, squamous, and tubular cells (A–F). Bi-nucleated podocalyxin-positive cells (A), a podocalyxin-positive cell with foamy cytoplasm (B), and different sized of cells with variable intensity of podocalyxin staining (C–F).

FIGURE 2:

Correlation between podocyturia (UPodo) and albuminuria (UACR) in Fabry patients.

FIGURE 3:

Frequency of podocyturia in individual Fabry patients included in this study.

FIGURE 4:

Dynamics of podocyturia (UPodo/100 mL) and eGFR for one male and one female Fabry patient.

FIGURE 5:

Podocyturia (UPodo/100 mL) in Fabry patients at different chronic kidney disease (CKD) stages.