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Kidney Week

Abstract: PO1269

Phenotypic Heterogeneity in Type IV Collagen-Associated Nephropathy: The Cystic Phenotype

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic

Authors

  • Zeni, Letizia, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy
  • Mazza, Cinzia, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy
  • Toso, Diego, Universita degli Studi di Brescia, Brescia, Lombardia, Italy
  • Econimo, Laura, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy
  • Cortinovis, Roberta, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy
  • Dordoni, Chiara, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy
  • Savoldi, Gianfranco, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy
  • Scolari, Francesco, Universita degli Studi di Brescia, Brescia, Lombardia, Italy
  • Izzi, Claudia, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, Lombardia, Italy
Background

Exome sequencing (ES) revealed mutations (mut) in type IV collagen (COL4) genes in patients (pt) diagnosed with other forms of chronic kidney disease (CKD), supporting the concept of spectrum of phenotypes for COL4-Nephropathy. Unexpectedly, some pt with CKD presenting with cystic phenotype were identified with COL4-Nephropathy by ES.

Methods

The retrospective study included 130 pt referred to outpatient clinic of genetic kidney diseases of ASST Spedali Civili of Brescia from 2002 to 2021 and diagnosed with COL4-Nephropathy. Based on the presence of multiple and bilateral renal cysts on imaging (fig1), a group of pt with cystic phenotype was selected (27/130;21%).

Results

Among cystic group (CG), diagnosis was based on genetic test (gt) and kidney biopsy in 10/27 pt, whereas it was ‘biopsy-proven only’ in 7 pt, gt-based in 3 pt and clinically in 7 pt. Fifteen pt underwent gt (fig2): heterozygous mut in COL4A3 and COL4A4 were detected in 9 and 3 cases, respectively; 1 patient showed mut in COL4A5 and 2 pt had a digenic pattern. At baseline, comparison between CG to non-CG showed lower eGFR (70[IQR 35;91] vs 91[IQR 74;114] mL/min/1.73m2 p<0,001) and higher proteinuria (1.1vs0.38g/24 hrs), although the statistical significance was not reached for proteinuria (p=0.058). At last censoring, data confirmed a lower eGFR (26[IQR 7;55] vs 86[IQR 44;104]) and a tendency (p=0.0545) of greater proteinuria in CG. Prevalence of arterial hypertension, CKD (defined as eGFR < 60) and ESKD was higher in CG.

Conclusion

The study contributes to expand the emerging phenotypic heterogeneity of COL4-Nephropathy and suggests that cystic phenotype could predict progression of kidney disease.