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Weekly Rewind: Thin Basement Membrane Disease

By Beatrice Concepcion posted 03-23-2018 13:17

Thin Basement Membrane Disease

ASN Communities Weekly Rewind

Beatrice Concepcion, MD, FASN

Introduction and Background
A 45 year old white male wishes to donate a kidney. He has a history of persistent hematuria with no proteinuria and a normal blood pressure. Kidney biopsy revealed thin basement membrane nephropathy (TBMN). He has no family history of kidney disease, hearing loss or lenticonus.

Would you allow this man to donate a kidney?

The discussion focused on two issues:

How does one definitively exclude Alport syndrome (including carrier states) in this potential donor?
There was an enlightening discussion regarding findings of immunofluorescence staining for type IV collagen subchains in various forms of Alport syndrome. Although immunostaining can aid in the diagnosis of X-linked, autosomal recessive (AR) and carrier states of X-linked Alport, COL IV immunostaining is normal in carriers of AR or autosomal dominant (AD) Alport syndrome. Genetic analysis is therefore advised. A study by Voskarides et al was cited to aid in the discussion of the renal implications of COL4A3/COL4A4 mutations in the setting of thin basement membranes and so-called benign familial hematuria. In this study of Cypriot families, mutation carriers were shown to have a predisposition for CKD and ESRD with advancing age. Presence of such mutations therefore, at least in this population, is not at all consistent with a “benign” course.

“Primum non nocere” versus informed consent and donor autonomy
There were differing opinions on whether or not this patient should be allowed to donate. On one hand, due to the possibility of a carrier state of Alport syndrome and the unknown post-donation risk associated with this, one should not allow him to proceed. On the other hand, given that this patient has no other risk factors (normal blood pressure, no proteinuria, absence of a family history) and is in his 40’s, post-donation risk may be reasonable and he should therefore be allowed to donate if he so chooses, after appropriate and extensive counseling. Additional information may sway the decision towards one or the other. If genetic testing reveals COL IV alpha chain mutations or the patient’s birth weight is found to have been less than 2.5 kg, then he should not proceed with donation due to the uncertainty that after a unilateral nephrectomy, he will have only minimal risk of developing overt renal disease for the remainder of his life.

A carrier state of Alport syndrome is possible in potential donors with thin basement membrane nephropathy and normal COL IV immunostaining. Genetic testing should be highly considered in these individuals and those found to have COL IV alpha chain mutations should be discouraged from donating.

Read the whole discussion here