Women with Alport syndrome: risks and rewards of kidney donation.

Insights gained during the last 30 years of research in Alport syndrome have influenced the way potential related kidney donors for Alport patients with end-stage renal disease (ESRD) are assessed. Awareness of Alport syndrome among clinicians and families has increased greatly, so the disease is more likely to be suspected in patients with haematuria and in kindreds with renal disease. Widespread application of electron microscopy, immunohistochemistry and molecular genetics has enhanced diagnostic accuracy, with the result that we are more likely to know which patients and families truly have Alport syndrome. We have learned that Alport syndrome is primarily an X-linked disorder (∼80% of families) and that only ∼10% of affected males represent de novo mutations, meaning that the mother of a boy with Alport syndrome is most likely a heterozygous carrier. Over 95% of heterozygous women with X-linked Alport syndrome (XLAS) exhibit haematuria, so detection of affected women in XLAS kindreds is a straightforward process [1]. Finally, it has been demonstrated that, contrary to the conventional wisdom of the 1980s and 1990s, heterozygous females with XLAS carry a substantial risk of developing chronic renal failure and ESRD [1]. It has been the practice in our transplant centre to counsel carriers with XLAS against kidney donation, based in part on the paucity of long-term outcome data in carriers who have undergone nephrectomy [2]. In this issue of NDT, Gross and colleagues describe six mothers with Alport syndrome who donated kidneys to their children with the disease [3]. Five mothers with XLAS donated to their sons and one mother who was a carrier of autosomal recessive Alport syndrome (ARAS) donated to her daughter. Renal function declined 25–60% in four of the six donors over 2–14 years of observation following nephrectomy, al-