Kidney Week

Abstract: TH-PO507

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

Session Information

• Genetic Kidney Diseases: Genotypes and Phenotypes in Cases
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

• Santana, Aline Aparecida, Universidade Federal do Parana, Curitiba, PR, Brazil

Aline Aparecida Santana

• Cunha, Regiane Stafim da, Universidade Federal do Parana, Curitiba, PR, Brazil

Regiane Stafim da Cunha

• Miniskiskosky, Guilherme, Universidade Federal do Parana, Curitiba, PR, Brazil

Guilherme Miniskiskosky

• Gregório, Paulo Cézar, Universidade Federal do Parana, Curitiba, PR, Brazil

Paulo Cézar Gregório, PharmD, PhD

• Hagemann, Rodrigo, Universidade Federal do Parana, Curitiba, PR, Brazil

Rodrigo Hagemann, MD

• Barreto, Fellype, Universidade Federal do Parana, Curitiba, PR, Brazil

Fellype Barreto, MD, PhD

• Stinghen, Andréa Marques, Universidade Federal do Parana, Curitiba, PR, Brazil

Andréa Marques Stinghen, PhD

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.

Figure 1 - Images showing MMP-1 immunostaining. (A) Control patient. (B) Male patient with FD. The scale bar indicates 50 μm, magnification 200x.

Funding

• Government Support – Non-U.S.