Prevalence and Genetic Spectrum of Inherited Kidney Diseases

BACKGROUND: Inherited Kidney Disease (IKD) significantly contributes to CKD in children, adolescents, and adults. However, large-scale research on the prevalence of IKD in a Chinese population is currently lacking. To address this gap, we use exome sequencing (ES) to thoroughly investigate the prevalence and disease spectrum of IKD in a Chinese population. METHODS: ES was conducted on 290 patients with kidney disease of unknown etiology from two centers. Genetic test results were interpreted following the American College of Medical Genetics and Genomics (ACMG) guidelines and the criteria for Variants of Uncertain Significance (VUS). Clinical data were integrated to establish a definitive diagnosis. RESULTS: 290 patients from 261 families were included in this study. Diagnostic variants were identified in 82 families, yielding a diagnostic rate of 31% (82/261). Six genes (PKD1, PKD2, COL4A3, COL4A4, COL4A5, and UMOD) accounted for 50% (41/82) of diagnosed cases. Ciliopathies were the most common subtype, followed by tubulopathies, collagenopathies, and podocytopathies. The diagnostic rate was higher in the age groups of ≤20 years and ≥41 years, at 63% and 39%, respectively. Among 51 biopsied patients, glomerular lesions (34/51) were the most common pathological type, followed by tubulointerstitial lesions (11/51). Of the 14 genetic diagnoses, 12 (86%) were consistent with histopathologic findings. CONCLUSIONS: A molecular genetic diagnosis was achieved in 31% of selected Chinese families. Genetic and clinical diagnosis complement each other, highlighting the application value of genetic testing in the diagnosis of IKD.