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Review
. 2020 Sep 18;11(9):1091.
doi: 10.3390/genes11091091.

Biomarkers of Fabry Nephropathy: Review and Future Perspective

Tina Levstek  1 , Bojan Vujkovac  2 , Katarina Trebusak Podkrajsek  1   3
Affiliations
Review

Biomarkers of Fabry Nephropathy: Review and Future Perspective

Tina Levstek et al. Genes (Basel). .

Abstract

Progressive nephropathy is one of the main features of Fabry disease, which largely contributes to the overall morbidity and mortality burden of the disease. Due to the lack of specific biomarkers, the heterogeneity of the disease, and unspecific symptoms, diagnosis is often delayed. Clinical presentation in individual patients varies widely, even in patients from the same family carrying the same pathogenic GLA variant. Therefore, it is reasonable to anticipate that additional genomic, transcriptomic, proteomic, and metabolomics factors influence the manifestation and progression of the disease. The aim of this article is to provide an overview of nephropathy in Fabry patients and the biomarkers currently used in the diagnosis and follow-up. Current biomarkers are associated with late signs of kidney damage. Therefore, there is a need to identify biomarkers associated with early stages of kidney damage that would enable early diagnosis, which is crucial for effective treatment and prevention of severe irreversible complications. Recent advances in sequencing and -omics technologies have led to several studies investigating new biomarkers. We will provide an overview of the novel biomarkers, critically evaluate their clinical utility, and propose future perspectives, which we believe might be in their integration.

Keywords: Fabry disease; Fabry nephropathy; biomarkers; epigenomics; genomics; metabolomics; nephropathy; proteomics; transcriptomics.

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Conflict of interest statement

B.V. received honoraria, travel, and accommodation funding from Sanofi Genzyme, Shire (now part of Takeda), and Greenovation Biotech GmbH and is a member of the EU Advisory Board of Fabry Registry sponsored by Sanofi Genzyme. K.T.P. received research, travel, and accommodation funding from Sanofi Genzyme and honoraria from Shire (now part of Takeda).

Figures

Figure 1
Figure 1
Birefringent Maltese cross in the urine sediment of Fabry patient when viewed under a polarized microscope (magnification 400×). Figure courtesy of Mravljak M; Department of Internal Medicine, General Hospital Slovenj Gradec.
Figure 2
Figure 2
Kidney biopsy with electron microscopy with typical lamelar inclusions in a 27-year old Fabry male patient with normal kidney function (eGFR 102 mL/min/1.73 m2), normoalbuminuria (ACR 12 mg/g), but high levels of podocyturia (UPod 2.420/g creatinine). Diffuse and numerous myeloid inclusions in podocyte cytoplasm (black arrow) with presence of vacuoles in the cytoplasm of podocytes (white arrow) are evident. Figure courtesy of Pleško J and Kojc N; Institute of Pathology, Ljubljana Medical Faculty.
See this image and copyright information in PMC

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