Unraveling the Genetic Architecture of Kidney Diseases: From Mechanisms to Precision Medicine

Kidney diseases, including chronic kidney disease (CKD) and acute kidney injury (AKI), represent a major global public health burden. These diseases cause significant morbidity and mortality. Their clinical presentation and progression are highly heterogeneous. This variation arises from a complex interplay of environmental, clinical, and genetic factors. Over the past decade, genomic technologies have undergone significant advancements. These advances have revolutionized our understanding of the genetic basis of renal pathologies. Monogenic kidney diseases, such as Autosomal dominant polycystic kidney disease (ADPKD) and Alport syndrome, have been well-characterized. The genetic architecture of more common, complex CKD is now being studied through large-scale genome-wide association studies (GWAS). These studies have identified many susceptibility loci and have revealed novel biological pathways in disease pathogenesis. However, moving from genetic discovery to mechanistic understanding, and ultimately to new diagnostic tools and therapies, remains a critical challenge and a central goal for the nephrology community.

The purpose of this Research Topic is to assemble cutting-edge research and reviews that highlight the role of genetic variation in kidney diseases. We seek to bridge the gap between genetic discovery and clinical application. Our goal is to provide a platform for studies that identify novel genetic risk factors, functionally characterize these variants, and explore their utility in risk prediction, diagnosis, and patient stratification. We aim to integrate genetic information with other omics data (transcriptomics, proteomics) and clinical parameters to drive the field toward precision nephrology. We encourage submissions addressing the genetic basis of understudied nephropathies, interactions between genetic predisposition and environmental triggers, and the development of polygenic risk scores for common kidney traits. By highlighting diverse methodologies and findings, this collection will be a comprehensive resource for researchers and clinicians. We hope it will foster collaboration and speed the translation of genetic insights into improved patient outcomes.

Specific themes:
• Monogenic and Syndromic Kidney Diseases: Discovery of new causative genes, genotype-phenotype correlations, and modifying factors in diseases like ADPKD, Alport syndrome, Congenital Anomalies of the Kidney and Urinary Tract (CAKUT), and podocytopathies.
• Genetics of Complex Kidney Traits: High-throughput sequencing (Whole exome sequencing, whole genome sequencing) studies for CKD, AKI, diabetic nephropathy, IgA nephropathy, and lupus nephritis, focusing on diverse populations.
• Functional Validation and Mechanistic Insights: Studies using in vitro and in vivo models (e.g., cell lines, organoids, animal models) to elucidate the functional consequences of genetic variants identified in human studies.
• Integrative Multi-Omics and Translational Applications: Research that combines genetics with transcriptomic, epigenetic, or proteomic data to uncover disease pathways. This includes work on the development and validation of polygenic risk scores (PRS) for risk prediction. We also welcome studies on drug repurpose based on genetic evidence.

Types of manuscript:
Types of manuscripts: We are interested in a variety of manuscript types to ensure a dynamic discussion. Original Research articles presenting new findings are welcome. Review and Mini-Review articles that summarize current knowledge and propose new directions are highly encouraged. We also invite submissions of Methodology articles that describe innovative analytical or experimental approaches in renal genetics. Perspective and Opinion pieces that challenge existing paradigms or propose novel hypotheses are welcomed to stimulate scholarly debate. Case reports must adhere to the relevant journal guidelines, including submitting variants to public databases and complying with the Case Report guideline (CARE) guidelines, as detailed in this journal's Instructions for Authors.