The Genetics of IgA Nephropathy: Implications for Future Therapies

IgA nephropathy (IgAN), the most prevalent primary glomerulonephritis worldwide, carries a considerable lifetime risk of kidney failure. The etiology of IgAN, however, remains incompletely understood, and effective treatment is lacking. Although the multihit model effectively identifies key steps in IgAN development and, to date, provides the best description of IgAN pathogenesis, it remains under development to fully capture the complexity of immune system dysregulation. Large-scale genome-wide association studies have revealed clues regarding the association between IgAN and genes in both innate and adaptive immune pathways. Hence, genetic investigations may shed light on the aberrant molecular mechanisms, thereby presenting new opportunities for therapeutic advancements. This review discusses the genetic associations that have been robustly connected with IgAN, placing them within the framework of disease mechanism. Altogether, these findings highlight numerous new possibilities for the development of treatments and the road to personalized medicine.