Glomerular disease is the most common cause of endstage renal disease (ESRD), accounting for almost two thirds of cases. In glomerular disease, alterations of po-docytes are of particular importance. Podocyte loss represents a central mediator of glomerular sclerosis. Toxic, genetic, immune, infectious, oxidant, metabolic, hemody-namic, and other mechanisms can all target the podo-cytes. These mechanisms provide new insight into the unique dynamic microenvironment that each individual podocyte inhabits and how it can turn hostile to survival. At the same time, they raise new therapeutic challenges to preserve glomerular function by containing podocyte injury and limiting its spread, both in podo-cytopathies and in other progressive glomerular diseases. Treatment strategies should aim at enhancing podocyte survival. The renin-angiotensin axis blockade, apart from its antifibrotic and intraglomerular hemodynamic effects, has an important role in preventing podocyte loss. However, only long-term observational studies can clarify if many patients will benefit from podocyte-targeted treatment such as abatacept or similar agents.
1. Heraldsson B. A New Era of Podocyte-Targeted Therapy for Proteinuric Kidney Disease. N Eng J Med 2013; 369: 25: 2453-2454.
2. Yadav I, Jhaveri KD. Podocituria: Is there any clinical utility? Indian J Nephrol 2011; 21: 219-220.
3. Dressler GR. The cellular basis of kidney development. Annu Rev Cell Dev Biol 2006; 22: 509-529.
4. Yu D, Petermann A, Kunter U, Rong S, et al. Urinary podocyte loss is a more specific marker of ongoing glomerular damage than proteinuria. J Am Soc Nephrol 2005; 16: 1733-1741.
5. Barisoni L, Schnaper HW, Kop JB. A proposed taxonomy for the podocyropathies: A reassessment of the primary nephritic diseases. Clin J Am Soc Nephrol 2007; 2: 529-542.
6. D' Agati. Podocyte injury can be catching. J Am Soc Nephrol 2011; 22: 1179-1188.
7. Wiggins RC. The spectrum of podocitopathies: a unifying view of glomerular diseases. Kidney Int 2007; 71: 1205-1214.
8. Lemley KV. Protecting podocytes: how good do we need to be? Kidney Int 2012; 81: 9-11.
9. Nagata M, Kriz W. Glomerular damage after uninephrec-tomy in young rats. Mechanical stress on podocytes as a pathway to sclerosis. Kidney Int 1992; 42: 148-160.
10. Fukuda A, Wickman LT, Venkatareddy MP, et al. Angio-tensin II dependent persistent podocyte loss from destabilized glomeruli causes progression of end stage kidney disease. Kidney Int 2012; 81: 40-55.
11. Ichikawa I, Ma J, Motojima M, et al. Podocyte damage po-docytes: autonomous vicious cycle that drives local spread of glomerular sclerosis. Curr Opin Nephrol Hytpertens 2005; 14: 205-210.
12. Peti-Peterdi J, Toma I, Sipos A, et al. Multiphoton imaging of renal regulatory mechanisms. Physiology (Bethesda) 2009; 24: 88-96.
13. Abbate M Zoja C, Morigi M, et al. Transforming growth factor-beta1 is upregulated by podocytes in response to excess intraglomerular passage of proteins. A central pathway in progressive glomerulosclerosis. Am J Path 2002; 161: 2179.
14. Benzing T. Signaling at the slit diaphragm. J Am Soc Nephrol 2004; 15: 1382-1391.
15. Lasagni L, Romagnani P. Glomerular epithelial stem cells, the good, the bad, and the ugly. J Am Soc Nephrol 2010; 21: 1612-1619.
16. Welsh GI, Saleem MA. The podocyte cytoskeleton-key to a functioning glomerulus in health and disease. Nat Rev Nephrol 2012; 8: 14-21.
17. Lemley KV, Lafayette RA, Safai M, et al. Podocytopenia and diseae severity in IgA nephropathy. Kidney Int 2002; 61: 1475-1485.
18. Nakamura T, Ushiyama C, Suzuki S, et al. Urinary podocytes for the assessment of disease activity in lupus nephritis. Am J Med Sci 2000; 320: 112-116.
19. Hara M, Yanagihara T, Kuhara I. Urinary podocytes in primary focal segmental glomerulosclerosis. Nephron 2001 ; 89: 342-347.
20. Hara M, Yanagihara T, Kuhara I, et al. Apical cell membranes are shed into urine from injures podocytes: A nevel phenomenon of podocyte injury. J Am Soc Nephrol 2005; 16: 408-416.
21. Vogelmann SU, Nelson WJ, Meyers BD, et al. Urinary excretion of viable podocyte in health and renal disease. Am J Physiol 2003; 285: F 40-48.
22. Garovic VD, Wagner SJ, Turner ST, et al. Urinary podo-cyte excretion as a marker for preeclampsia. Am J Obstr Gynecol 2007; 196: 320.e1-7.
23. Yu C-C, Fornoni A, Weins A, et al. Abatacept in B7-1 positive proteinuric kidney disease. New Eng J Med 2013; 369: 2416-2423.
24. Reiser J, Mundel P. Danger signaling by glomerular podocytes defines a novel function of inducible B7-1 in the pathogenesis of nephritic syndrome. J Am Soc Nephrol 2004; 15: 2246-2248.
25. Reiser J, von Gersdorff G, Loos M, et al. Induction of B7-1 in podocytes is associated with nephritic syndrome. J Clin Invest 2004; 113: 1390-1397.