Kidney Week

Abstract: TH-PO477

Correlation between PKD1 Mutation Type and Height-Adjusted Total Kidney Volume in Chinese Patients with ADPKD: Genotype-Phenotype Analysis

Session Information

• Cystic Kidney Diseases: Clinical Assessment and Therapeutic Directions
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Cystic

Authors

• Liu, Zhiying, Peking University First Hospital, Beijing, Beijing, China

Zhiying Liu, PhD

• Zhang, Jiayi, Peking University First Hospital, Beijing, Beijing, China

Jiayi Zhang, MD

• Qu, Shu, Peking University First Hospital, Beijing, Beijing, China

Shu Qu, MD, PhD

• Li, Mengshi, Peking University First Hospital, Beijing, Beijing, China

Mengshi Li, PhD

• Li, Yang, Peking University First Hospital, Beijing, Beijing, China

Yang Li, MD

• Zhang, Hong, Peking University First Hospital, Beijing, Beijing, China

Hong Zhang, MD, PhD

• Zhou, Xu-jie, Peking University First Hospital, Beijing, Beijing, China

Xu-jie Zhou, MD

Background

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited kidney disease but with allelic and genetic heterogeneity. This study aims to explore the association between PKD1 mutation types and height-adjusted total kidney volume (htTKV) in Chinese ADPKD patients.

Methods

We evaluated genotype-phenotype correlations in 379 subjects with affected ADPKD between August 25, 2017 and April 2, 2024. Patients with complex genotypes (mosaic, digenic, or diallelic) were excluded. We performed regression analysis to examine the effects of age, sex, and mutation type on htTKV natural log scale.

Results

90.5% of the patients got molecularly diagnosed with PKD1 (82.3%, n=312) and PKD2 (7.9%, n=30) in the current study. PKD1 truncating mutations accounts for 67.3% of the patients (Figure 1). Men had more severe disease than women with lower eGFR and larger htTKV (Figure 2, A and B). Patients with nonsense and frameshift mutations showed faster eGFR decline compared to missense mutations (Figure 2C). Patients with PKD1 truncating mutations generally have larger htTKV than non-truncating mutations (P<0.005) (Figure 2D). Allelic effect on htTKV was more significant in splicing, frameshift and nonsense mutation classes (Figure 2E).

Conclusion

In Chinese ADPKD patients, we confirmed that kidney cyst severity differs by mutation types in PKD1. Patients with PKD1 truncating mutations have higher TKV and lower eGFR, particularly frameshift and nonsense mutations. Assessment of mutation types may predict renal prognosis and aid in caring for high-risk ADPKD patients.

Figure 1. Categories of mutation type in PKD1 population.

Figure 2. Sex and allelic effects on ADPKD phenotype in PKD1 population.