The contribution of podocytes to chronic allograft nephropathy.
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.


CONCLUSIONS
A decrease in the slit diaphragm proteins, nephrin and synaptopodin, is a component of chronic allograft pathology.
Pippin
Jeffrey
J
Nephrology, University of Washington, Seattle, Wash., USA.
Kumar
Vineeta
V
Stein
Alicia
A
Jablonski
Paula
P
Shankland
Stuart J
SJ
Davis
Connie L
CL
D000818:Animals; D002452:Cell Count; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D016030:Kidney Transplantation / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism / Q000473:pathology*; D011507:Proteinuria / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D014184:Transplantation, Homologous
D008565:Membrane Proteins; D008840:Microfilament Proteins; C503969:Synpo protein, rat; C113267:nephrin; D003404:Creatinine