Abstract: TH-PO0111
Rapid Long-Read Sequencing in Thrombotic Microangiopathy to Triage Therapy in a Low-Resource Setting
Session Information
- Integrative Genomics and Multi-Omics in Noncystic Genetic Kidney Disease
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)
Authors
- Wongboonsin, Janewit, Mahidol University Faculty of Medicine Siriraj Hospital, Bangkok, Thailand
- Srithongkul, Thatsaphan, Mahidol University Faculty of Medicine Siriraj Hospital, Bangkok, Thailand
- Sampson, Matt G., Boston Children's Hospital, Boston, Massachusetts, United States
- Chawanasuntorapoj, Ratana, Mahidol University Faculty of Medicine Siriraj Hospital, Bangkok, Thailand
Background
The diagnostic evaluation of thrombotic microangiopathy (TMA) is complex and requires specialized assays and genetic tests that often take weeks to months to complete. In current practice of resourceful countries, C5 inhibitors are frequently initiated empirically before these data are available, but this strategy carries substantial financial burden.
Methods
We employed rapid targeted long-read sequencing to assess complement-mediated kidney disease genes in three patients who presented with TMA of unclear etiology and were suspected of having atypical hemolytic uremic syndrome (aHUS). Results were available within one week and were used to guide subsequent clinical management.
Results
In the first two cases, Shiga toxin–negative TMA and malignant hypertension-associated TMA, rapid sequencing revealed no pathogenic or likely pathogenic variants. These findings supported discontinuation of empiric therapeutic plasma exchange (TPE) and continuation of conservative management. Both patients experienced hematologic resolution of TMA and improvement in kidney function after 2 weeks. In the third case, rapid sequencing identified a loss-of-function variant in CD46, leading to cessation of TPE and the initiation of a philanthropic access process for C5 inhibitor therapy. While awaiting approval, the patient exhibited spontaneous renal recovery and did not ultimately require therapy. Knowing the genetic information upfront allow these three cases to be managed upfront conservatively.
Conclusion
Our findings suggest that rapid genomic testing can be used a diagnostically and economically effective tool to guide therapeutic use of C5 inhibitors in patients presenting with TMA of unclear etiology. Extending the ability to use rapid sequencing in resource-limiting settings hold promise in democratizing the use of these valuable therapies globally.
| Case 1 | Case 2 | Case 3 | |
| Sex | Female | Female | Male |
| Age | 70 | 34 | 22 |
| Syndrome | Infectious diarrhea, Shiga toxin negative | Malignant hypertension | Influenza A infection |
| Peak creatinine (mg/dL) | 4 | 3.1 | 10.4 |
| RRT | Yes | No | Yes |
| Plasmaphresis | Yes | No | Yes |
| Biopsy | Not performed | Acute on chronic TMA | Acute TMA (previous biopsy) |
| Genetic test | Negative | Negative | CD46 loss of function |
| Discharge Cr | 2.4 (day 23) | 2 (day 12) | 2.3 (day 16) |
| Follow up Cr | 1.2 (week 4) | 1.6 (week 8) | 0.9 (week 2) |
Funding
- Government Support – Non-U.S.