Abstract: SA-PO537
Diagnostic Yield Among Patients With Diabetic Nephropathy and/or Hypertension: Genetic Testing in Kidney Transplant Waitlist Patients
Session Information
- Genetic Diseases: Diagnosis
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1102 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Leeser, David Black, Vidant Transplant Center, Greenville, North Carolina, United States
- Kennamer, Karen Elizabeth, Vidant Transplant Center, Greenville, North Carolina, United States
- Kartchner, Laurel, Natera, Inc., Austin, Texas, United States
- Romine, Margaret M., Vidant Transplant Center, Greenville, North Carolina, United States
- Aaron, Ashley E ., Vidant Transplant Center, Greenville, North Carolina, United States
- McLawhorn, Kristel J., Vidant Transplant Center, Greenville, North Carolina, United States
- Jones, Heather, Vidant Transplant Center, Greenville, North Carolina, United States
- Irish, William, Vidant Transplant Center, Greenville, North Carolina, United States
Background
Diabetes and hypertension (HTN) are common causes of end-stage renal disease (ESRD) in the general population. Studies have shown that ESRD often has a genetic cause. Although diabetes and HTN can have a hereditary component in some cases, recommendations for genetic testing in ESRD typically exclude patients with presumed diabetic nephropathy or HTN. We describe a single-center approach to using genetic testing in patients presenting for renal transplant evaluation, including those whose clinical diagnosis was diabetic nephropathy or HTN.
Methods
As part of the initial work-up process, all potential transplant patients were tested to determine cause of original kidney disease, ancestry, diabetes (y/n), and hypertension (y/n). Patients then underwent testing with a panel consisting of >380 genes associated with kidney disease (the RenasightTM test). Positive results included those with pathogenic or likely pathogenic variants, or with the G1 or G2 APOL1 risk alleles. Results were then stratified based on patient clinical diagnosis.
Results
Among the 189 patients tested, 31.7% (n=60) had positive results spanning 14 genes. Six patients were identified as having positive results in >1 gene. At the time of transplant evaluation, diabetic nephropathy or HTN were the most common causes of ESRD. Other causes of ESRD that often are hereditary, such as focal segmental glomerulosclerosis and polycystic kidney disease were highly prevalent among the cohort. Genetic findings were identified in patients whose ESRD was due to diabetic nephropathy (21.7%, 18/83), HTN (34.5%, 19/55), FSGS (66.7%, 6/9), PKD (88.9%, 8/9), and “Other” (27.3%, 9/33).
Conclusion
Despite published protocols excluding genetic testing in patients with presumed diabetic nephropathy, this analysis suggests that patients with ESRD caused by diabetes and/or hypertension may have a high diagnostic yield spanning a wide variety of genetic causes.
Common Positive Genetic Findings
| Clinical Diagnosis (Cause of ESRD) | Diagnostic yield Genes (# patients) |
| Diabetic nephropathy at time of KT evaluation (n=83) | 21.7% (n=18) APOL1 (13), CFH (1), COL4A4 (1), HNF4A (1), PKD2 (1), SLC7A9 (1), TTR (1) |
| HTN at time of KT evaluation (n=55) | 34.5% (n=19) APOL1 (12), COL4A3 (1), COL4A4 (3), COL4A5 (1), GLI3 (1), MC4R (1), PKD1 (1), TTR (2) |
| Focal segmental glomerulosclerosis (FSGS) (n=9) | 66.7% (n=6) APOL1 (6) |
| Polycystic kidney disease (PKD) (n=9) | 88.9% (n=8) APOL1 (1), PKD1 (6), PKD2 (1), TTR (1) |
| Other (n=33) | 27.3% (n=9) APOL1 (6: lupus, covid, cong renal anomaly, IgAN (2), rheumatoid arthritis), COL4A5 (2 GN), FGFR2 (1 solitary kidney), NPHP1 (1 medullary cystic kidney disease), TTR (1) |