Kidney Week

Abstract: FR-PO0115

Effect of Body Mass Index on CKD Progression in Siblings with Identical Alport Gene Variant: A Matched-Pair Analysis

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

Jan Boeckhaus, MD

• Gross, Oliver, Universitatsmedizin Gottingen, Göttingen, NDS, Germany

Oliver Gross, MD, DrMed

Background

Alport syndrome is a progressive hereditary nephropathy characterized by defects of the glomerular basement membrane. While the genetic variant primarily determines disease severity, secondary hemodynamic factors—such as obesity—could accelerate renal damage. Assessing the independent influence of Body Mass Index (BMI) on renal endpoints is challenging due to genetic confounding factors. This study utilizes a unique sibling matched-pair model to investigate the effect of BMI on albuminuria in patients with identical Alport syndrome genotypes.

Methods

In this retrospective analysis, we identified sibling pairs sharing the exact same pathogenic genetic defect in order to strictly control for genetic variance. The pairs were required to exhibit an intra-pair BMI difference of >8 kg/m² at baseline. Clinical parameters were compared within each sibling pair at baseline and after a defined follow-up period.

Results

In three sibling pairs (N=6 patients), the initial intra-pair BMI difference was 10.8 kg/m² (range: 8.8–12.6). This corresponded to an initial intra-pair difference in albuminuria of +1909 mg/g (range: 235–4677). Over observation periods of 4, 5, and 11 years, the siblings with the higher baseline BMI demonstrated a more pronounced progression of albuminuria. At the time of follow-up, the intra-pair difference in albuminuria was 2,813 mg/g (range 411–5,627), while the intra-pair BMI difference was 14.9 kg/m² (range 9.5–21.2). Over the observation period, the intra-pair difference in eGFR declined from 3.67 ml/min (range -5 to 16; favoring the high-BMI group) to -29 ml/min (range -98 to 14).

Conclusion

In this controlled, genotype-matched sibling analysis, the baseline BMI difference increased from 10.8 to 14.9 and was associated with a higher and accelerated increase in albuminuria and decline in eGFR. These results suggest that an elevated BMI acts as a critical, independent disease modifier in Alport syndrome. Consequently, proactive weight management and targeted BMI reduction could represent fundamental therapeutic strategies to mitigate hyperfiltration and delay the progression in this patient population, regardless of their specific genetic variant.