Abstract: FR-PO624
LOANing a Kidney: Role of Whole Exome Sequencing (WES) in Diagnosis of Microscopic Hematuria in Potential Kidney Donors
Session Information
- Trainee Case Reports - IV
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Reports
- 1802 Transplantation: Clinical
Authors
- Virmani, Sarthak, Yale School of Medicine, New Haven, Connecticut, United States
- Dahl, Neera K., Yale School of Medicine, New Haven, Connecticut, United States
Introduction
Kidney donors with microscopic hematuria present a particular challenge to transplant clinics, with some advocating for donor kidney biopsies. Only those with no glomerular lesions by biopsy are deemed to be suitable donors. We used WES instead of a more invasive kidney biopsy to determine a donor’s eligibility for transplant. Subsequent confirmatory testing in her sibling, the recipient, led to an unexpected finding.
Case Description
A 62-year-old French Canadian woman was referred to our transplant center for evaluation as a potential kidney donor to her 60-year-old younger sister with ESRD from biopsy proven FSGS. Years earlier, their mother had also developed ESRD of unknown etiology. Routine evaluation of the donor showed microscopic hematuria. Further inquiry revealed a long-standing history of microscopic hematuria in at least 3 other first degree family members. This prompted WES of the potential donor. An autosomal recessive homozygous variant (cA740G) in the INVS gene, associated with nephronophthisis was found. This variant was classified a variant of unknown significance (VUS).
Her sister, the potential recipient, was also found to have the same homozygous mutation. However, in addition to his mutation, a likely pathogenic frameshift variant in the COL4A4 gene (P1235fs) was also found to be present. This led to a reformed diagnosis of autosomal dominant Later Onset Alport Nephropathy (LOAN) in the proposed recipient and cleared her sister for donation.
Discussion
COL4A4 mutations can differentiate the patients with familial microscopic hematuria into benign familial hematuria or LOAN presenting histologically as FSGS. About 25 % of patients above the age of 50 with COL4A3/A4 mutation, who are labelled as having thin basement membrane nephropathy, have been found to have proteinuria, hematuria, hypertension and progression to ESRD making this differentiation imprortant. This case highlights the importance of WES in differentiating various familial microscopic hematuria syndromes and helps obviate the need for renal biopsies, especially in patients being considered for transplant.