Defining Disease Modification in IgA Nephropathy: Toward a Paradigm Shift in Management

IgA nephropathy (IgAN) is a rare, chronic, immune-mediated kidney disease characterized by a slow, progressive decline in kidney function. As a disease without an existing cure and a leading cause of chronic kidney disease (CKD) and kidney failure, IgAN requires effective interventions for disease modification. However, identifying interventions as "disease modifying" is challenging in IgAN because of a lack of consensus on the term and uncertainty about suitable markers by which "disease modification" should be defined. This review discusses how "disease modification" could be defined in IgAN, based on the simple premise of the need to preserve nephrons and avoid progression to kidney failure within the patient's lifetime. In addition, how disease modification can be meaningfully assessed (e.g., the impact of an intervention on mortality and kidney failure, estimated glomerular filtration rate [eGFR], urinary protein or albumin, nonvisible [microscopic] hematuria, and markers of underlying IgAN pathology) is examined. Further, the concept of a multifaceted approach to IgAN management is discussed, targeting both the IgAN-specific processes leading to nephron loss and the generic maladaptive responses to IgAN-induced nephron loss.