UPDATES IN NEPHROLOGY: BREAKING THE SILENCE
Podocytopathies and Immunosuppressive Agents
The Podocytes: Therapeutic target of proteinuric kidney disease
Abstract
Podocytes have key role in maintaining the blood-urine barrier for high molecular-weight proteins. Proper podocyte function and structure contributes in determining the integrity of the glomerular filtration barrier. In recent years, the understanding of podocytes signalling pathways and the crucial role of genetic predispositions in the pathology of glomerular disorders has widened. Identification of these signalling pathways give support to the hypothesis that immunosuppressive agents directly target glomerular podocytes. Acquired podocytopathies like idiopathic focal segmental glomerulosclerosis and minimal change disease are historically immunologically mediated. Recent evidence shows that the immunosuppressive agents, in addition to the effect on the immune system directly influence the unique structure and function of podocytes. In this context, the actin cytoskeleton of the podocytes and cytokines such as vascular endothelial growth factor play a pivotal role. Several central downstream signalling pathways merge into pathways regulating podocytic actin cytoskeleton and its connection to the slit diaphgram. Podocytes show the characteristic ability to recover from complete effacement and to re-structure interdigitating foot processes and intact slit diaphragms after pharmacological intervention. Drugs directly targeting podocytes include: RAAS blockers, glucocorticoids, calcineurin inhibitors, rituximab, mTOR inhibitors, HMG Co reductase inhibitors, VEGF inhibitors, and PPar y agonists (glitazones). This session will highlight the understanding of relatively therapeutic targets that may open strategies to enhance and stabilize inside-out pathways in podocytes.
