A Hitchhiker’s Guide to Precision Medicine in Glomerulonephritis

Purpose Glomerulonephritis (GN) comprises a heterogeneous group of immune-mediated kidney diseases and is the third leading cause of kidney failure. Although increasing clinical trials in this area have led to new therapeutic options, selecting the right treatment for the right patient remains challenging. We review current precision medicine initiatives that integrate deep clinical phenotyping with genomics and multi-omics approaches to identify pathway-specific therapies and refine risk stratification. We also discuss how these strategies may reshape clinical trial design and treatment selection in GN. Sources of Information Literature was identified through PubMed and Google Scholar from inception to 2026. Patient perspectives were informed by engagement with patient partners. Methods Search terms included “precision medicine”, “nephrology”, and “glomerulonephritis”. Key Findings Advances in genetics, multi-omics profiling, and large collaborative cohorts have revealed molecularly distinct subtypes within GN, enabling biomarker-guided diagnosis, improved risk stratification, and targeted therapy. Initiatives such as the Kidney Precision Medicine Project and the Nephrotic Syndrome Study Network (NEPTUNE) integrate kidney tissue, blood, urine, and clinical data to identify actionable biological pathways. The NEPTUNE Match initiative aims to align patients with clinical trials most likely to benefit them based on their molecular profiles. Disease-specific examples, including PLA2R antibody monitoring in membranous nephropathy and proof-of-concept studies in focal segmental glomerulosclerosis, highlight the potential of precision medicine approaches that can translate into clinical care. Genetic variation at the human leukocyte antigen (HLA) locus may represent a shared risk factor across GN subtypes. Incorporating sex- and gender-based analyses into precision frameworks will be essential to ensure appropriate risk stratification and therapeutic selection. Importantly, patient-centered initiatives demonstrate high levels of engagement and willingness to participate in precision medicine research. Collectively, these findings support a paradigm shift toward personalized GN management. Limitations A systematic review was not conducted, and our search was restricted to English-language articles.