Open AccessUtility of Genomic Testing after Renal Biopsy
Author(s) -
Susan Murray,
Anthony Dorman,
Katherine A. Benson,
Dervla M. Connaughton,
Caragh Stapleton,
Neil K. Fennelly,
Claire Kennedy,
Ciara Mcdonnell,
Kendrah Kidd,
Sarah Cormican,
Louise Ryan,
Peter Lavin,
Mark A. Little,
Anthony J. Bleyer,
Brendan Doyle,
Gianpiero L. Cavalleri,
Friedhelm Hildebrandt,
Peter J. Conlon
Publication year - 2019
Publication title -
american journal of nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.394
H-Index - 85
eISSN - 1421-9670
pISSN - 0250-8095
DOI - 10.1159/000504869
Subject(s) - medicine , alport syndrome , focal segmental glomerulosclerosis , renal biopsy , kidney disease , thrombotic microangiopathy , pathological , glomerulonephritis , biopsy , kidney , pathology , gastroenterology , disease
Background: Renal biopsy is the mainstay of renal pathological diagnosis. Despite sophisticated diagnostic techniques, it is not always possible to make a precise pathological diagnosis. Our aim was to identify a genetic cause of disease in patients who had undergone renal biopsy and determine if genetic testing altered diagnosis or treatment. Methods: Patients with suspected familial kidney disease underwent a variety of next-generation sequencing (NGS) strategies. The subset of these patients who had also undergone native kidney biopsy was identified. Histological specimens were reviewed by a consultant pathologist, and genetic and pathological diagnoses were compared. Results: Seventy-five patients in 47 families underwent genetic sequencing and renal biopsy. Patients were grouped into 5 diagnostic categories based on pathological diagnosis: tubulointerstitial kidney disease (TIKD; n = 18); glomerulonephritis (GN; n = 15); focal segmental glomerulosclerosis and Alport Syndrome (n = 11); thrombotic microangiopathy (TMA; n = 17); and nonspecific pathological changes (n = 14). Thirty-nine patients (52%) in 21 families (45%) received a genetic diagnosis; 13 cases (72%) with TIKD, 4 (27%) with GN, 6 (55%) with focal segmental glomerulosclerosis/Alport syndrome, and 10 (59%) with TMA and 6 cases (43%) with nonspecific features. Genetic testing resulted in changes in understanding of disease mechanism in 21 individuals (54%) in 12 families (57%). Treatment would have been altered in at least 26% of cases (10/39). Conclusions: An accurate genetic diagnosis can result in changes in clinical diagnosis, understanding of pathological mechanism, and treatment. NGS should be considered as a complementary diagnostic technique to kidney biopsy in the evaluation of patients with kidney disease.