Glomerular disease: looking beyond pathology

Abstract

The National Institute of Diabetes and Digestive and Kidney Diseases-supported Kidney Research National Dialogue asked the scientific community to formulate and prioritize research objectives aimed at improved understanding of kidney function and disease progression. Over the past 2 years, 1600 participants posted almost 300 ideas covering all areas of kidney disease. An overriding theme that evolved through these discussions is the need to move beyond pathology to take advantage of basic science and clinical research opportunities to improve diagnostic classification and therapeutic options for people with primary glomerular disease. High-priority research areas included focus on therapeutic targets in glomerular endothelium and podocytes, regenerating podocytes through developmental pathways, use of longitudinal phenotypically defined disease cohorts to improve classification schemes, identifying biomarkers, disease-specific therapeutics, autoantibody triggers, and changing the clinical research culture to promote participation in clinical trials. Together, these objectives provide a path forward for improving clinical outcomes of glomerular disease.

Keywords: GN; autoantibodies; endothelium; glomerulosclerosis; inflammation; nephrotic syndrome; podocytes; translational and clinical research.

Figure 1.

This figure depicts the integration of research areas and approaches needed to move beyond pathology to further the understanding of GN progression and regression to identify new targets to improve clinical outcomes. Although traditional pathology has defined current clinical approaches, new approaches are needed. Basic research on the podocyte and its interaction with the endothelial cell and the immune system to produce a disordered inflammatory response can be coupled with translational work in glomerular disease biomarkers. Joining these findings with the role of autoantibodies and various circulating factors will enhance ongoing clinical studies and point to new targets to reduce or reverse progression. Combining clinical phenotypes with new definitions of pathology, genotypic, proteomic, metabolomic, and social–environmental interactions will lead to new collaborations of basic and clinical scientists, who will integrate this new knowledge to identify new routes for intervention. Patient participation in these long-term endeavors is crucial to move us to the goal of better clinical outcomes.