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Kidney Week

Abstract: TH-PO480

Genotype-Phenotype Correlations in Alport Syndrome: A Single-Center Experience

Session Information

Category: Genetic Diseases of the Kidneys

  • 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Lujinschi, Stefan Nicolaie, Fundeni Clinical Institute, Bucharest, Romania
  • Obrisca, Bogdan, Fundeni Clinical Institute, Bucharest, Romania
  • Sorohan, Bogdan, Fundeni Clinical Institute, Bucharest, Romania
  • Jurubita, Roxana Adriana, Fundeni Clinical Institute, Bucharest, Romania
  • Vornicu, Alexandra, Fundeni Clinical Institute, Bucharest, Romania
  • Ismail, Gener, Fundeni Clinical Institute, Bucharest, Romania
Background

Alport syndrome is a common and heterogeneous genetic kidney disease, oftentimes leading to end-stage kidney disease (ESKD). Due to the growing availability of genetic testing, understanding the interplay between genetic and clinical features has become essential for individualized prognostication.

Methods

This is a single-center, retrospective study that included 36 adults with type IV collagen mutations. Our scope was to describe how genetic features influence renal survival, i.e., the age at renal replacement therapy initiation.

Results

A total of 28 different mutations were identified, out of which 8 had not been previously described. Mutations affecting each of the type IV collagen α chains were equally prevalent (33.3%). Six patients had multiple mutations. One patient had mutations involving all α chains. Five patients also had mutations involving podocyte and glomerular basement membrane proteins, but with no significant differences regarding proteinuria and renal survival. Most patients had a family history of kidney disease (71%). The most prevalent clinical picture was nephritic syndrome (64%), followed by isolated hematuria (24%). One third of the subjects had extrarenal manifestations, such as hearing loss (28.6%) and eye abnormalities (7.1%). There were no significant differences in laboratory findings at diagnosis between patients with COL4A3, COL4A4 and COL4A5 mutations. Eighteen patients presented with (41.6%) or later developed (8.3%) ESKD at a median age of 25.5 years old (IQR, 21.5-37.25). Six patients underwent kidney transplant. Overall kidney survival was 40.55 years (95% CI, 35.55-45.55). COL4A4 group displayed a significantly better renal survival when compared to COL4A3 (p=0.027). Hearing loss was associated with a significantly poorer renal prognosis (p<0.001). For a subgroup where follow-up data were available (44.4%), the 5-year renal survival was 68.6% and in patients with multiple mutations, a lower renal survival at 27 months was noticed (p=0.014).

Conclusion

In our study, COL4A3 mutations, presence of multiple mutations and a personal history of hearing loss were associated with a poorer renal prognosis.