Utility of Genomic Testing after Renal Biopsy.

Murray SL1,2, Dorman A3,4, Benson KA5, Connaughton DM6,7, Stapleton CP5, Fennelly NK3, Kennedy C6, McDonnell CA6, Kidd K8, Cormican SM6, Ryan LA6, Lavin P9, Little MA10, Bleyer AJ8, Doyle B3, Cavalleri GL5, Hildebrandt F7, Conlon PJ6,11.

Author information

1: Department of Nephrology and Transplantation, Beaumont Hospital, Dublin, Ireland, susanmurray@beaumont.ie.
2: Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland, susanmurray@beaumont.ie.
3: Department of Pathology, Beaumont Hospital, Dublin, Ireland.
4: Department of Pathology, Royal College of Surgeons in Ireland, Dublin, Ireland.
5: Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
6: Department of Nephrology and Transplantation, Beaumont Hospital, Dublin, Ireland.
7: Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
8: Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
9: Department of Nephrology, Tallaght Hospital, Dublin, Ireland.
10: Trinity Health Kidney Centre, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland.
11: Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.

Abstract

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.