BACKGROUND: Progressive proteinuria and glomerulosclerosis characterize chronic allograft nephropathy. However, the causes are not fully elucidated. Podocytes function to prevent proteinuria; injury to this glomerular cell leads to glomerulosclerosis. The potential role of podocytes in the failing transplanted kidney is unknown. A rat model of kidney transplantation, characterized by proteinuria and glomerulosclerosis, was utilized to examine the potential role of podocytes. METHODS: Archival tissue was examined from allografts (Dark Agouti kidneys transplanted into operationally tolerant Albino Surgery rats), isografts (Dark Agouti) and controls (Dark Agouti: age-matched or after unilateral nephrectomy). The number of podocytes (by WT-1 staining) as well as the podocyte proteins podocin, nephrin and synaptopodin (by immunostaining) were measured at days 0, 2, 6 and at 6 months after transplantation. Changes in these parameters were compared between groups and correlated with urinary protein excretion. RESULTS: At 6 months, podocyte number was reduced in allografted kidneys, accompanied by a decrease in nephrin and synaptopodin, but not podocin staining. Remnant kidneys in the uninephrectomized rats also showed a decreased podocyte number but no change in podocyte protein staining. Podocyte loss in allografts was established on day 6, whereas a decrease in nephrin and synaptopodin was not evident until 6 months. In contrast, podocyte number and protein staining was decreased but not significantly so in remnant and isografted kidneys. CONCLUSION: A decrease in the slit diaphragm proteins, nephrin and synaptopodin, is a component of chronic allograft pathology. Copyright 2009 S. Karger AG, Basel.
BACKGROUND: Progressive proteinuria and glomerulosclerosis characterize chronic allograft nephropathy. However, the causes are not fully elucidated. Podocytes function to prevent proteinuria; injury to this glomerular cell leads to glomerulosclerosis. The potential role of podocytes in the failing transplanted kidney is unknown. A rat model of kidney transplantation, characterized by proteinuria and glomerulosclerosis, was utilized to examine the potential role of podocytes. METHODS: Archival tissue was examined from allografts (Dark Agouti kidneys transplanted into operationally tolerant Albino Surgery rats), isografts (Dark Agouti) and controls (Dark Agouti: age-matched or after unilateral nephrectomy). The number of podocytes (by WT-1 staining) as well as the podocyte proteins podocin, nephrin and synaptopodin (by immunostaining) were measured at days 0, 2, 6 and at 6 months after transplantation. Changes in these parameters were compared between groups and correlated with urinary protein excretion. RESULTS: At 6 months, podocyte number was reduced in allografted kidneys, accompanied by a decrease in nephrin and synaptopodin, but not podocin staining. Remnant kidneys in the uninephrectomized rats also showed a decreased podocyte number but no change in podocyte protein staining. Podocyte loss in allografts was established on day 6, whereas a decrease in nephrin and synaptopodin was not evident until 6 months. In contrast, podocyte number and protein staining was decreased but not significantly so in remnant and isografted kidneys. CONCLUSION: A decrease in the slit diaphragm proteins, nephrin and synaptopodin, is a component of chronic allograft pathology. Copyright 2009 S. Karger AG, Basel.
Authors: Putri A Agustian; Mario Schiffer; Wilfried Gwinner; Irini Schäfer; Katharina Theophile; Friedrich Modde; Clemens L Bockmeyer; Jana Traeder; Ulrich Lehmann; Anika Grosshennig; Hans H Kreipe; Verena Bröcker; Jan U Becker Journal: Am J Pathol Date: 2011-05 Impact factor: 4.307
Authors: Stuart J Shankland; Yuliang Wang; Andrey S Shaw; Joshua C Vaughan; Jeffrey W Pippin; Oliver Wessely Journal: J Am Soc Nephrol Date: 2021-11 Impact factor: 10.121
Authors: Takamoto Ohse; Michael R Vaughan; Jeffrey B Kopp; Ronald D Krofft; Caroline B Marshall; Alice M Chang; Kelly L Hudkins; Charles E Alpers; Jeffrey W Pippin; Stuart J Shankland Journal: Am J Physiol Renal Physiol Date: 2009-12-09
Authors: Jiong Zhang; Jeffrey W Pippin; Michael R Vaughan; Ronald D Krofft; Yoshinori Taniguchi; Paola Romagnani; Peter J Nelson; Zhi-Hong Liu; Stuart J Shankland Journal: Nephron Exp Nephrol Date: 2012-10-25
Authors: Rhea Bhargava; Kayaho Maeda; Maria G Tsokos; Martha Pavlakis; Isaac E Stillman; George C Tsokos Journal: Am J Transplant Date: 2020-07-06 Impact factor: 8.086