The Role of Kidney Biopsy in Fabry Disease
Abstract
:1. Introduction
2. The Kidney Biopsy in the Diagnosis of Fabry Disease
2.1. Algoritm of Diagnosis of Fabry Disease
2.2. Diagnostic Finding on Kidney Biopsy in FD
2.3. The Histological Scoring
2.4. The Overlapping Diseases and Misdiagnosis
2.5. The Use of Kidney Biopsy in the Definition of VUS Pathogenicity and in the Female Patients
3. The Kidney Biopsy in Monitoring
4. Kidney Biopsy and Evaluation of Disease Progression
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Conflicts of Interest
Abbreviations
FD | Fabry disease |
Gb3 | Globotriaosylceramide |
Lyso-Gb3 | Globotriaosylsphingosine |
VUS | Variants of uncertain significance |
XCI | X-chromosome inactivation |
LM | Light microscopy |
IF | Immunofluorescence |
EM | Electron microscopy |
H&E | Hematoxylin and eosin |
PAS | Periodic acid-Schiff |
GBM | Glomerular basement membrane |
ECM | Extracellular matrix |
ISGFN | International Study Group of Fabry Nephropathy |
MCD | Minimal change disease |
IgAN | IgA nephropathy |
DIP | Drug-induced phospholipidosis |
NPS | Nail–patella syndrome |
ESRD | End-stage renal disease |
NPLRD | Nail–patella-like renal disease |
GL-3 | Globotriaosylceramide |
FPW | Foot process width |
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Fabry Disease | Nail–Patella Syndrome | Niemann-Pick Disease Types A/B and C | |
---|---|---|---|
Gene | GLA | LMX1B | NPC1-NPC2 |
Clinical features | Neuropathic pain Hypertrophic cardiomyopathy Cornea verticillata Gastrointestinal symptoms Hypohidrosis Angiokeratoma | Skeletal abnormalities (kneecap, iliac, patellae) Nail abnormalities Ocular (glaucoma) Neurological issues | Jaundice Hepatosplenomegaly Neurological issues (supranuclear vertical gaze palsy, cerebellar ataxia) Gelastic cataplexy |
Renal involvement | Hematuria Proteinuria CKD | Hematuria (30–50 cases) Proteinuria ESRD (5% of patients) | Rare Hematuria Proteinuria CKD |
Kidney biopsy findings | Myeloid bodies are widespread in all renal cellular compartments | Minor modifications Moth-eaten GBM (electron-lucent regions thickened GBM) Deposition of curvilinear type III collagen fibrils on GBM | Foamy podocyte’s cytoplasm on LM lamellar bodies in podocytes on EM |
Study/Reference | Histopathological Findings | Clinical Prognostic Correlation |
---|---|---|
Fogo et al., 2010 [21] (ISGFN) | Semi-quantitative histological scoring of fibrosis, sclerosis, vascular changes | Used for risk stratification and prognosis assessment |
Najafian et al., 2011 [44] | Progressive podocyte injury and Gb3 accumulation on EM | Associated with worsening renal function and proteinuria |
Weidemann et al., 2013 [17] | Renal fibrosis on LM | Marker of disease progression and resistance to therapy |
Tøndel et al., 2015 [13] | Podocyte foot process effacement on EM | Early marker of nephropathy, even before proteinuria onset |
Mauer et al., 2017 [43] | Reduction of Gb3 inclusion in podocyte on EM with treatment | Correlates with improved renal outcomes in treated patients |
Rusu et al., 2022 [30] | Glomerular sclerosis on LM | Predicts kidney disease progression and mortality |
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Capelli, I.; Martano, L.; Berti, G.M.; Vischini, G.; Lerario, S.; Donadio, V.; Incensi, A.; Aiello, V.; Ciurli, F.; Fabbrizio, B.; et al. The Role of Kidney Biopsy in Fabry Disease. Biomedicines 2025, 13, 767. https://doi.org/10.3390/biomedicines13040767
Capelli I, Martano L, Berti GM, Vischini G, Lerario S, Donadio V, Incensi A, Aiello V, Ciurli F, Fabbrizio B, et al. The Role of Kidney Biopsy in Fabry Disease. Biomedicines. 2025; 13(4):767. https://doi.org/10.3390/biomedicines13040767
Chicago/Turabian StyleCapelli, Irene, Laura Martano, Gian Marco Berti, Gisella Vischini, Sarah Lerario, Vincenzo Donadio, Alex Incensi, Valeria Aiello, Francesca Ciurli, Benedetta Fabbrizio, and et al. 2025. "The Role of Kidney Biopsy in Fabry Disease" Biomedicines 13, no. 4: 767. https://doi.org/10.3390/biomedicines13040767
APA StyleCapelli, I., Martano, L., Berti, G. M., Vischini, G., Lerario, S., Donadio, V., Incensi, A., Aiello, V., Ciurli, F., Fabbrizio, B., Chilotti, S., Mignani, R., Pasquinelli, G., & La Manna, G. (2025). The Role of Kidney Biopsy in Fabry Disease. Biomedicines, 13(4), 767. https://doi.org/10.3390/biomedicines13040767