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Abstract: PO1598

Clinical and Genetic Features of Autosomal Dominant Alport Syndrome

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Furlano, Monica, Fundacio Puigvert, Barcelona, Catalunya, Spain
  • Martinez Jimenez, Víctor, Hospital Clinico Universitario Virgen de la Arrixaca, El Palmar, Murcia, Spain
  • Pybus, Marc, Fundacio Puigvert, Barcelona, Catalunya, Spain
  • Domingo Gallego, Andrea, Fundacio Puigvert, Barcelona, Catalunya, Spain
  • Ayasreh, Nadia, Fundacio Puigvert, Barcelona, Catalunya, Spain
  • Benito García, Silvia, Fundacio Puigvert, Barcelona, Catalunya, Spain
  • Arlandis Gallego, Rosa, Hospital General de Castellon, Castellon de la Plana, Valenciana, Spain
  • Ars, Elisabet, Fundacio Puigvert, Barcelona, Catalunya, Spain
  • Torra, Roser, Fundacio Puigvert, Barcelona, Catalunya, Spain
Background

Alport Syndrome is the second most frequent genetic kidney disease, accounting for around 2% of patients with end-stage kidney disease. It is caused by pathogenic variants in COL4A3, COL4A4 and COL4A5 genes. The aim of this study was to evaluate the clinical and genetic spectrum of patients with autosomal dominant Alport syndrome.

Methods

Retrospective cohort study of 82 families (252 patients) with autosomal dominant Alport Syndrome. Clinical, genetic, laboratory and pathological data were collected. Renal survival, estimated glomerular filtration rate (eGFR) decline, genotype-phenotype correlation and extrarenal features were analyzed.

Results

A pathogenic DNA variant in COL4A3 was identified in 106 patients (34 families) while 134 harbored a pathogenic variant in COL4A4 (44 families). Complex/digenic inheritance was observed in 12 patients without clear genotype–phenotype correlation. Overall median renal survival was 67 years [95% CI, 58–73], without significant differences related to gender, causative gene or type of variant (p = 0.85, p = 0.28 and p = 0.81 respectively). Microhematuria was the most common renal manifestation (93%) while extrarenal features were rare. The results of kidney biopsies ranged from normal to focal segmental glomerulosclerosis. Hypertension was common and the age at its diagnosis correlated with age at end-stage kidney disease (p < 0.01). The slope of eGFR decline was -1.66 mL/min/1.73m2 per year (-1.9 to -1.42) for the overall group, with no significant differences between COL4A3 and COL4A4 genes (P=0.60).

Conclusion

This study shows that autosomal dominant Alport Syndrome patients present a wide spectrum of symptoms ranging from asymptomatic to end-stage kidney disease, regardless of the affected gene or type of variant. This broad phenotype contributes to underdiagnosis in clinical practice and makes autosomal dominant Alport Syndrome diagnosis very challenging.

Funding

  • Government Support - Non-U.S.