TY - JOUR
T1 - Induction of renal tubular cell apoptosis in focal segmental glomerulosclerosis
T2 - Roles of proteinuria and Fas-dependent pathways
AU - Erkan, Elif
AU - Garcia, Clotilde D.
AU - Patterson, Larry T.
AU - Mishra, Jaya
AU - Mitsnefes, Mark M.
AU - Kaskel, Frederick J.
AU - Devarajan, Prasad
PY - 2005
Y1 - 2005
N2 - The hypothesis that apoptosis represents a proximate mechanism by which tubule cells are damaged in FSGS was tested. Thirty kidney biopsy specimens from children with idiopathic early FSGS were studied retrospectively. Unexpected, apoptosis was evident in both proximal and distal tubule cells. There was a significant correlation between the degree of proteinuria and the number of apoptotic cells. Fas protein was detected predominantly in the tubule cells that underwent apoptosis. When compared with patients with other chronic proteinuric states, those with FSGS displayed a proliferation/apoptosis ratio in favor of proliferation in the glomerulus but dramatically in favor of apoptosis in the tubules. When both proteinuria and apoptosis were included in a stepwise logistic regression procedure, only apoptosis was found to predict independently the development of ESRD. Prolonged incubation of cultured Madin-Darby canine kidney (distal/collecting) cells with albumin also resulted in a dose- and duration-dependent induction of apoptosis and activation of the Fas pathway, lending support to the novel finding of distal tubule cell apoptosis in patients with FSGS. The results indicate that an elevated tubule cell apoptosis rate at the time of initial biopsy represents an independent predictor of progression to ESRD in patients with early FSGS.
AB - The hypothesis that apoptosis represents a proximate mechanism by which tubule cells are damaged in FSGS was tested. Thirty kidney biopsy specimens from children with idiopathic early FSGS were studied retrospectively. Unexpected, apoptosis was evident in both proximal and distal tubule cells. There was a significant correlation between the degree of proteinuria and the number of apoptotic cells. Fas protein was detected predominantly in the tubule cells that underwent apoptosis. When compared with patients with other chronic proteinuric states, those with FSGS displayed a proliferation/apoptosis ratio in favor of proliferation in the glomerulus but dramatically in favor of apoptosis in the tubules. When both proteinuria and apoptosis were included in a stepwise logistic regression procedure, only apoptosis was found to predict independently the development of ESRD. Prolonged incubation of cultured Madin-Darby canine kidney (distal/collecting) cells with albumin also resulted in a dose- and duration-dependent induction of apoptosis and activation of the Fas pathway, lending support to the novel finding of distal tubule cell apoptosis in patients with FSGS. The results indicate that an elevated tubule cell apoptosis rate at the time of initial biopsy represents an independent predictor of progression to ESRD in patients with early FSGS.
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U2 - 10.1681/ASN.2003100861
DO - 10.1681/ASN.2003100861
M3 - Article
C2 - 15601749
AN - SCOPUS:20544433886
SN - 1046-6673
VL - 16
SP - 398
EP - 407
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 2
ER -