Kidney Week

Abstract: SA-PO568

Whole Exome Sequencing Identifies a Monogenic Cause of ESRD in 33% of Pediatric Kidney Transplant Patients

Session Information

• Noncystic Mendelian Diseases
  November 04, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Genetic Diseases of the Kidney

• 802 Non-Cystic Mendelian Diseases

Authors

• Mann, Nina, Boston Children's Hospital, Boston, Massachusetts, United States

Nina Mann,

• Shril, Shirlee, Boston Children's Hospital, Boston, Massachusetts, United States

Shirlee Shril,

• Braun, Daniela A., Boston Children's Hospital, Boston, Massachusetts, United States

Daniela A. Braun,

• Tan, Weizhen, Boston Children's Hospital, Boston, Massachusetts, United States

Weizhen Tan,

• van der Ven, Amelie, Boston Children's Hospital, Boston, Massachusetts, United States

Amelie van der Ven,

• Ityel, Hadas, Boston Children's Hospital, Boston, Massachusetts, United States

Hadas Ityel,

• Connaughton, Dervla M., Boston Children's Hospital, Boston, Massachusetts, United States

Dervla M. Connaughton,

• Mane, Shrikant M., Yale University, New Haven, Connecticut, United States

Shrikant M. Mane,

• Amann, Kassaundra, Boston Children's Hospital, Boston, Massachusetts, United States

Kassaundra Amann,

• Spaneas, Leslie D, Boston Children's Hospital, Boston, Massachusetts, United States

Leslie D Spaneas,

• Vakili, Khashayar, Boston Children's Hospital, Boston, Massachusetts, United States

Khashayar Vakili,

• Kim, Heung Bae, Boston Children's Hospital, Boston, Massachusetts, United States

Heung Bae Kim,

• Somers, Michael J., Boston Children's Hospital, Boston, Massachusetts, United States

Michael J. Somers,

• Rodig, Nancy MacDonald, Boston Children's Hospital, Boston, Massachusetts, United States

Nancy MacDonald Rodig,

• Hildebrandt, Friedhelm, Boston Children's Hospital, Boston, Massachusetts, United States

Friedhelm Hildebrandt,

Background

Renal transplantation is the treatment of choice for children with end-stage renal disease (ESRD). Living donation is preferred as it leads to longer graft survival. However, it has been suggested that living related donors (LRDs) are at a higher relative risk for ESRD (Poggio, JASN, advance online publication, 2017). We hypothesized that LRDs may have increased genetic susceptibility to kidney disease and aimed to determine the percentage of pediatric kidney transplant patients in whom a genetic cause of ESRD can be identified.

Methods

Patients who underwent kidney transplantation at Boston Children’s Hospital from 2010 to 2016 were recruited. We performed targeted gene sequencing in 11 individuals and whole exome sequencing (WES) in 49 individuals. When WES was performed, data were analyzed for variants in known and candidate ESRD genes.

Results

60 individuals from 58 families were recruited. 37/60 (62%) patients had congenital anomalies of the kidney and urinary tract (CAKUT), 11/60 (18%) had nephrotic syndrome (NS), and 12/60 (20%) had nephronophthisis (NPHP). We identified a monogenic cause of ESRD in 19/58 (33%) families. Pathogenic mutations were identified in 16% of families with CAKUT, 60% of families with NS, and 64% of families with NPHP. One individual developed insulin-dependent diabetes post-transplantation, which was attributed to steroid use. However, we identified a heterozygous WFS1 mutation in this patient, which can cause impaired glucose regulation and may better explain his clinical picture.

Conclusion

We detected a cause of ESRD in 33% of pediatric patients who undergo renal transplantation. Knowledge of this genetic information can have implications in decision-making for living related donor transplant ascertainment, and may also help to guide future management of transplant patients.

Funding

• Other NIH Support