Kidney Week

Abstract: TH-PO494

Variants Involving Podocyte and Extracellular Matrix Proteins in Alport Syndrome: A Case Series

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

• Lujinschi, Stefan Nicolaie, Institutul Clinic Fundeni, Bucuresti, Romania

Stefan Nicolaie Lujinschi

• Obrisca, Bogdan, Institutul Clinic Fundeni, Bucuresti, Romania

Bogdan Obrisca, MD, PhD

• Sorohan, Bogdan, Institutul Clinic Fundeni, Bucuresti, Romania

Bogdan Sorohan, MD

• Rusu, Elena-Emanuela, Institutul Clinic Fundeni, Bucuresti, Romania

Elena-Emanuela Rusu, MD, PhD

• Jurubita, Roxana Adriana, Institutul Clinic Fundeni, Bucuresti, Romania

Roxana Adriana Jurubita, MD

• Ismail, Gener, Institutul Clinic Fundeni, Bucuresti, Romania

Gener Ismail, MD, PhD

Background

Caused by mutations of type IV collagen genes (COL4), Alport syndrome (AS) displays a wide phenotype. Recent studies have highlighted AS as one of the leading causes of focal and segmental glomerulosclerosis (FSGS). There is a growing body of evidence favoring the modifier role of variants involving podocyte and extracellular matrix proteins in AS.

Methods

We conducted a retrospective case series study including 6 patients with COL4 mutations and simultaneous variants involving podocyte or non-collagen basement membrane proteins, aiming to describe the influence of such variants on the phenotypic spectrum of AS.

Results

We identified 8 different COL4A3 and COL4A4 variants. Two patients had multiple COL4 variants: one had digenic AS and the other had 2 different COL4A3 variants. There were 5 variants of uncertain significance (VUS), 2 pathogenic and one likely-pathogenic variant. All the variants were heterozygous. There were 7 variants involving podocyte and extracellular matrix proteins, including: LAMA5, LAMB2, NUP107, NPHS2, MYO1E and PLCE1. All the variants were heterozygous VUS. Four patients had nephrotic syndrome or nephrotic range proteinuria, one had nephritic syndrome and one had acute tubulointerstitial nephritis. Only 2 patients had hearing loss. Four patients had a family history of kidney disease. Only 2 subjects developed end-stage kidney disease (at 29 and 39 years old respectively). There were 2 cases of FSGS and one case of thin basement membrane disease on kidney biopsy (3/6 patient). Five patients received renin-angiotensin system inhibitors. Only 2 patients were treated with sodium-glucose transport protein 2 inhibitors. Both experienced an important drop in proteinuria (82% and 88% respectively) when compared to baseline. Three patients received immunosuppression, all having nephrotic syndrome.

Conclusion

Although mutations of podocyte and extracellular matrix proteins do not usually cause genetic nephrotic syndrome in heterozygous form, the presence of such variants influenced the phenotype of patients with AS followed in our clinic, as most of them presented with nephrotic syndrome or nephrotic range proteinuria.