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Kidney Week

Abstract: FR-PO999

Factors Regulating the Severity in Male X-Linked Alport Syndrome: Study of 367 Cases

Session Information

Category: Genetic Diseases of the Kidney

  • 1002 Genetic Diseases of the Kidney: Non-Cystic

Authors

  • Yamamura, Tomohiko, Kobe University Graduate School of Medicine, Kobe, Japan
  • Nozu, Kandai, Kobe University Graduate School of Medicine, Kobe, Japan
  • Nagano, China, Kobe University Graduate School of Medicine, Kobe, Japan
  • Horinouchi, Tomoko, Kobe University Graduate School of Medicine, Kobe, Japan
  • Nakanishi, Keita, Kobe University Graduate School of Medicine, Kobe, Japan
  • Minamikawa, Shogo, Kobe University Graduate School of Medicine, Kobe, Japan
  • Kaito, Hiroshi, Kobe University Graduate School of Medicine, Kobe, Japan
  • Shima, Yuko, Wakayama Medical University, Wakayama City, Japan
  • Nakanishi, Koichi, Graduate School of Medicine, University of the Ryukyus, Nishihara-cho, Japan
  • Iijima, Kazumoto, Kobe University Graduate School of Medicine, Kobe, Japan
Background

X-linked Alport syndrome (XLAS) is a hereditary disease caused by mutations of COL4A5 gene. Affected males generally develop end-stage renal disease (ESRD) in early or middle adulthood. It has been reported some factors such as genotype or ACEI treatment affect renal prognosis. However, comprehensive analysis for the influence of factors regulating the severity using large-scale data has not been reported.

Methods

We conducted a retrospective study of 367 male patients in 231 families who were genetically diagnosed with XLAS at our institute. We collected clinical data from medical records and constructed renal survival curve. These curves were compared depending on the following differences in clinicopathological or genetic features; presence of hearing loss, findings of α5 staining positivity on glomerular basement membrane, treatment with ACEI/ARB and genotype. Regarding genotype, renal survival curve was constructed on not only each mutation type but also dividing all genotypes into two groups of truncating and non-truncating variants.

Results

The median age of our cohort was 12yrs. 149 cases reached ESRD and the median renal survival period was 33yrs. Ocular changes were detected in 6.1% and hearing loss was 34%. There was a significant difference in the median renal survival period between cases with (27yrs, n=94) and without hearing loss (55yrs, n=134) (P=0.0116), α5 staining positive (>60yrs, n=54) and negative (28yrs, n=75) (P=0.0052), treated by ACEI/ARB (43yrs, n=112) and not treated (28yrs, n=72) (P=0.0079). The median renal survival period of each mutation type was 18yrs (nonsense mutation, n=29), 21yrs (large rearrangement, n=14), 25yrs (splicing variant, n=57), 26yrs (small rearrangement, n=62) and 40yrs (missense mutation, n=196). In addition, there was a significant difference between cases with truncating (20yrs, n=102) and non-truncating variants (39yrs, n=241) (p<0.0001).

Conclusion

It was shown that the renal prognosis of male XLAS was regulated by various factors. In particular, treatment with ACEI/ARB dramatically improved renal prognosis. In addition, we also showed that the strong genotype-phenotype correlation was observed not only among mutation types but also, and for the first time, between cases with truncating and non-truncating variants.