Abstract: FR-PO0124
Environmental Factors Drive the Risk for Kidney Failure in Autosomal Dominant Alport Syndrome: Evidence from Monozygotic Twins Raised Apart
Session Information
- Hereditary Glomerular and Tubulointerstitial Kidney Diseases
October 23, 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
- Boeckhaus, Jan, Universitatsmedizin Gottingen, Göttingen, NDS, Germany
- Gross, Oliver, Universitatsmedizin Gottingen, Göttingen, NDS, Germany
Background
Heterozygous autosomal COL4A3/4 variants have a global prevalence of 1:100. Lifetime risk for kidney failure is estimated to less than 3%. Our study investigates the hypothesis that these variants represent modifiable risk factors.
Methods
Our study offers a rare opportunity to directly compare the impact of lifestyle factors in identical twins, who grew up under vastly different conditions.
Results
The monozygotic twins carry a heterozygous missense variant in the COL4A3 gene.
As todders, 50 years ago, the twins (I.2 and I.3) were placed in a children's home due to familial alcohol-related problems. Only I.2 was adopted; he had to change name and place of residence, resulting in a complete loss of contact with his biological family. I.3, however, was forced to return to his difficult home environment. Their life trajectories have remained - and continue to be - different with regard to their educational and professional backgrounds, body weight, and lifestyle.
Both have developed hearing loss and have started RAS-blockade around age 45.
I.3 became dialysis-dependent with just above 50 years of age. In contrast, I.2’s kidney function has remained stable with an eGFR >90 ml/min (G1A2). The children of the healthier twin, II.1 and II.2, carry the heterozygous COL4A3 variant. II.1, with a BMI of 42, already exhibits nephrotic-range proteinuria, her leaner brother presents with microalbuminuria only. Again, as observed in the parental generation, kidney status correlates more with enviromental factors than with genetics.
Conclusion
According to our data, heterozygous COL4A3/4 variants should be regarded as modifiable risk factors rather than as a matter of genetic destiny. The extent to which kidney failure in carriers of heterozygous COL4A3/4 variants is "dominantly" determined by environmental factors should raise our awareness of these common "risk variants" and lead to proactive, long-term care from time of early diagnosis.