On ‘Incidence of renal failure and nephroprotection by RAAS inhibition in heterozygous carriers of X-chromosomal and autosomal recessive Alport mutations’

Abstract

To the Editor: Familial microscopic hematuria has been of interest to us for over 25 years. In 2007, we published a study (which was the largest at that time) on 82 patients with heterozygous mutations in the COL4A3/A4 genes where a significant percentage of patients, starting with microscopic hematuria and thin basement membrane nephropathy, went on to develop FSGS with the addition of proteinuria and progressive renal failure. In all, 19.5% of patients developed end-stage kidney disease.1 This publication was commented on by Prof C Kashtan and established convincingly, for the first time, the significant risk for late-onset renal failure in COL4A3/COL4A4 mutation carriers and also established that thin basement membrane nephropathy is not always a benign condition. Further publications strengthened these data.2, 3 The article by Temme et al.4 ignores all these published data and describes similar findings in a small group of 29 COL4A3/COL4A4 mutation carriers pooled from several European centers. It also reconfirms, in 188 COL4A5 female heterozygous mutation carriers, that 15.4% of such X-linked Alport syndrome carriers may also develop end-stage kidney disease.