Urinary Podocyte Loss Is Increased in Patients with Fabry Disease and Correlates with Clinical Severity of Fabry Nephropathy

Abstract

Chronic kidney disease is a major complication of Fabry disease. Podocytes accumulate globotriaosylceramide inclusions more than other kidney cell types in Fabry patients. Podocyte injury occurs early in age, and is progressive. Since injured podocytes detach into the urine (podocyturia), we hypothesized that podocyturia would increase in Fabry patients and correlate with clinical severity of Fabry nephropathy. Urine specimens from 39 Fabry patients and 24 healthy subjects were evaluated for podocyturia. Most of the Fabry patients and many healthy subjects had podocyturia. The number of podocytes per gram of urine creatinine (UPodo/g Cr) was 3.6 fold greater in Fabry patients (3,741 ± 2796; p = 0.001) than healthy subjects (1,040 ± 972). Fabry patients with normoalbuminuria and normoproteinuria had over 2-fold greater UPodo/g Cr than healthy subjects (p = 0.048). UPodo/gCr was inversely related to eGFR in male patients (r = -0.69, p = 0.003). UPodo/gCr was directly related to urine protein creatinine ratio (r = 0.33; p = 0.04) in all Fabry patients. These studies confirm increased podocyturia in Fabry disease, even when proteinuria and albuminuria are absent. Podocyturia correlates with clinical severity of Fabry nephropathy, and potentially may be of prognostic value.

Globotriaosylsphingosine (Lyso‐Gb3) as a biomarker for cardiac variant (N215S) Fabry disease

“…It has been previously shown that the renal disease course in N215S FD subtype of both male and female follows a rather slow progression compared to males with classical FD (Thomas et al 2015). Progression of renal involvement in FD is multifactorial but the reasons for a more indolent course in N215S FD subtype remain poorly understood (Najafian et al 2011;Fall et al 2016). Furthermore, there was evidence of subclinical brain involvement in the form of white matter changes on brain MRI.…”

α‐Galactosidase A‐deficient rats accumulate glycosphingolipids and develop cardiorenal phenotypes of Fabry disease

“…Patients are found to have glomerular disease and proteinuria resulting from GSL-laden podocytes that eventually detach (32). Proximal and distal tubule abnormalities also develop (33)(34)(35)(36).…”

Bedside Stereomicroscopy of Fabry Kidney Biopsies: An Easily Available Method for Diagnosis and Assessment of Sphingolipid Deposits

“…Progressive damage of the glomerular filtration barrier plays an important role in the development of albuminuria/proteinuria and focal and segmental glomerular sclerosis in general, leading to progressive organ failure in kidney diseases, including Fabry disease [1,2,6]. In particular, the role of podocyte damage has been highlighted in Fabry nephropathy, and early structural and functional damage as well as podocyturia have been linked to podocyte Gb3 deposits and clinical disease in Fabry disease [7,8]. For assessment of disease severity and renal effect of enzyme replacement therapy, histopathologic examination of glomerular, tubulointerstitial and vascular kidney biopsy compartments is pivotal.…”