Alport’s syndrome: HLA association and kidney graft outcome.

Alport’s Syndrome (AS) is a genetic disease of type IV collagen involving nonhomogeneous patterns of inheritance characterized clinically by the association of progressive hematuric nephritis leading to end stage renal disease (ESRD), hearing loss and/or ophthalmologic abnormalities. Aim of this study was to analyze in a cohort of AS patients (pts) undergoing kidney graft (KG) for ESRD: a) the presence of a possible correlation with HLA allele expression; b) the medium and long term outcome of KG. Among 899 first KG performed at our Center between January 1983 and December 2002, we have selected 24 KG (2.6%) with AS (19 males and 5 females with mean age at the time of transplantation: 23±11.2 years). KG originated from a cadaver donor in 16 cases, from a living-related donor in 8 cases. All transplanted pts with AS had a follow-up period of at least 12 months after KG. Results showed that: i) the frequency of HLA-DRB1*16 allele was significantly increased in AS pts as compared to healthy controls (31.8% vs 5.4%; p<0.05; relative risk:5.2); ii) patient and graft survivals in the AS group were respectively 94.4% and 88.2% at 5 years, 94.4% and 79% at 10 years, and were not different from those of a KG patient control group without AS matched for sex, age, number of HLA mismatches, immunosuppressive regimen. Increased frequency of HLADRB1*16 allele in AS pts may be the expression of a linkage disequilibrium with genes coding for collagen synthesis such as COL11A2 or COL4A5-A3/A4 which are located inside and outside MHC region, respectively. Our data confirm that KG outcome is excellent in AS pts.