Ultimately, the common final pathway of any glomerular disease is podocyte effacement, podocyte loss, and, eventually, glomerular scarring. There has been a long-standing debate on the underlying mechanisms for podocyte depletion, ranging from necrosis and apoptosis to detachment of viable cells from the glomerular basement membrane. However, this debate still continues because additional pathways of programmed cell death have been reported in recent years. Interestingly, viable podocytes can be isolated out of the urine of proteinuric patients easily, emphasizing the importance of podocyte detachment in glomerular diseases. In contrast, detection of apoptosis and other pathways of programmed cell death in podocytes is technically challenging. In fact, we still are lacking direct evidence showing, for example, the presence of apoptotic bodies in podocytes, leaving the question unanswered as to whether podocytes undergo mechanisms of programmed cell death. However, understanding the mechanisms leading to podocyte depletion is of particular interest because future therapeutic strategies might interfere with these to prevent glomerular scarring. In this review, we summarize our current knowledge on podocyte cell death, the different molecular pathways and experimental approaches to study these, and, finally, focus on the mechanisms that prevent the onset of programmed cell death.
