Long-Read Sequencing in CKD Diagnostics: Breaking Genomic Barriers and Expanding Global Inclusion

Chronic kidney disease (CKD) is a major global health burden, and genetic testing is increasingly used to clarify diagnosis and guide management, particularly in inherited and early-onset disease. Short-read sequencing (SRS), including targeted gene panels, exome sequencing, and genome sequencing, provides diagnostic-grade detection of many exonic single nucleotide variants and small insertions or deletions, but important diagnostic gaps remain in genomic regions that are difficult to resolve with short reads. Long-read sequencing (LRS) addresses several of these limitations by enabling improved detection of structural variants, repeat expansions, and complex or highly homologous loci, and by providing long-range haplotype context. This review focuses on the current and emerging clinical applications of LRS in CKD diagnostics, highlighting scenarios where LRS is most likely to add value beyond SRS, including unresolved suspected monogenic kidney disease and technically challenging genes such as PKD1 and MUC1. We also discuss how improved representation of structural variation and ancestry-specific reference data may reduce uncertainty in variant interpretation for patients who are poorly represented in existing databases. Although routine clinical implementation of LRS is still evolving, ongoing advances in laboratory workflows, bioinformatics pipelines, and reference resources are accelerating translation into nephrology practice.