MMP1 Levels in Kidney Tissue May Be Related to Kidney Interstitial Fibrosis in Fabry Disease

Background: Fabry disease (FD) is a rare disease, linked to the X chromosome and caused by mutations in the GLA gene that leads to complete or partial deficiency of the enzyme α-galactosidase (α-GAL). Loss of this enzyme leads to lysosomal accumulation of glycosphingolipids, especially globotriaosylceramide (gb3), with a broad spectrum of clinical manifestations. Matrix metalloproteinase-1 (MMP-1) is a colagenase responsable for insterstitial remodelling, specifically breaking down collagen type I, II, and III. FD patients could have prominent kidney involvement, with progressively worse of renal function caused by fibrosis. Here, we evaluated the MMP-1 presence in renal tissue. Methods: The study included 6 FD patients diagnosed with the p.G35V missense mutation and 1 control patient. Creatinine and proteinuria levels were evaluated in these patients, and immunohistochemistry for MMP-1 was performed on kidney biopsies. Results: Female patients (n=5) had creatinine levels 0.78 mg/dL (+- 0.10 mg/dL) and proteinuria 322.0 mg/24h (+- 207.2 mg/24h). Male patient (n=1) shows 0.9 mg/dL of creatinine and proteinuria 400.0 mg/24h. Four of them had stage 1 CKD, while the other two had stage 2 CKD. Analysis of the kidney biopsies showed positive immunostaining for MMP-1 in control patient (Figure 1A) and negative immunostaining for MMP-1 in the glomerular capillary walls for all patients with FD (Figure 1B). MMP-1 interstitial positivity was observed in 4 patients; sparse and discrete form in one, discrete focal form in another one and mild multifocal in 2 patients. Furthermore, 2 patients showed MMP-1 positivity in the tubular epithelium and parietal epithelium. All patients with FD had interstitial fibrosis. Conclusion: Patients with FD due to the p.G35V mutation have reduced levels of MMP-1, an enzyme related to interstitial kidney fibrosis, even in stages 1 and 2 of CKD. Funding: Government Support – Non-U.S.Figure 1 - Images showing MMP-1 immunostaining. (A) Control patient. (B) Male patient with FD. The scale bar indicates 50 μm, magnification 200x.