Background: Alport syndrome (AS) is caused by mutations in α3/α4/α5 (IV) collagen genes, whose severity determines the progression of AS. Post-transplant outcome is good, though anti-GBM glomerulonephritis occurs in 3-5% of recipients, clustering in patients with a severe mutation.

Aim: to assess whether the severity of the underlying AS mutation (COL4A5/A4/A3 genes) affects graft and patient's outcome after transplantation, including the occurrence of anti-GBM nephritis.

Methods: Retrospective analysis including AS patients with an identified mutation transplanted between 1971 and 2014. Severe mutations included truncating, splice-site and non-sense mutations. Missense mutations and in-frame deletions were considered non-severe.

Results: 73 patients (81% male) had received 93 kidney grafts: COL4A5=57, COL4A3=9, COL4A4=6, heterozygous composite COL4A3 and A4=1. Forty-one patients had a severe mutation (COL4A5:30, COL4A3:6, COL4A4:5) and 32 had a non-severe mutation (COL4A5:27, COL4A3:4; COL4A4:1). Patient survival was similar in patients with severe and non-severe mutations (89% vs 84% at 5 years, 83% vs 75 % at 10, 15 and 20 years (p=0.46). Graft survival was not affected by the severity of mutation (77% vs 63% at 5 years, 60% vs 55 % at 10 years, 55% vs 55% at 15 years, and 55% vs 50% at 20 years (p=0.65). Post-transplant cardiovascular, infectious, neoplastic complications and acute rejection rate were similar in both groups. Anti-GBM glomerulonephritis occurred in one patient with truncating COL4A5 mutation 6 years after transplantation, with crescents and linear IgG deposits leading rapidly to graft loss. Three years after retransplantation, recurrence of anti-GBM nephritis led again to graft loss. Out of 48 grafts biopsies, linear IgG deposits without glomerular lesion were observed in 4 grafts (severe COL4A5 mutation:2, severe COL4A4 mutation:1, missense COL4A5 mutation:1)

Conclusion: Anti-GBM nephritis occurred in only 1,4 % of AS patients and in 2.4 % of the subgroup with a severe mutation, which is lower than generally thought. Anti-GBM nephritis may manifest later than previously reported and recurs in a subsequent graft.

CITATION INFORMATION: Gillion V, Dahan K, Goffin E, Cosyns J.-P, Jadoul M, De Meyer M, Mourad M, Pirson Y, Kanaan N. Graft Loss from Anti-GBM Nephritis: A Rare Event in Alport Syndrome, Even with a Severe COL4A5/A4/A3 Mutation. Am J Transplant. 2017;17 (suppl 3).

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