Deletion of the epidermal growth factor receptor in renal proximal tubule epithelial cells delays recovery from acute kidney injury

被引:131
作者
Chen, Jianchun [1 ]
Chen, Jian-Kang [1 ]
Harris, Raymond C. [1 ,2 ]
机构
[1] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA
[2] Dept Vet Affairs, Nashville, TN USA
基金
美国国家卫生研究院;
关键词
bone; dialysis; hemodialysis; parathyroid hormone; renal osteodystrophy; ISCHEMIA-REPERFUSION INJURY; STEM-CELLS; EARLY PHASE; RAT-KIDNEY; REGENERATION; FAILURE; ACTIVATION; HYPERTROPHY; MECHANISMS; REPAIR;
D O I
10.1038/ki.2012.43
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
100201 [内科学]; 100221 [泌尿外科学];
摘要
Abnormalities of bone mineral metabolism and vascular calcification are prevalent in patients with kidney failure. Clinical management is based on biochemical targets, in particular parathyroid hormone (PTH) concentrations, but this has many limitations including high biological variation. A possible alternative is bone-specific alkaline phosphatase (ALP); therefore, we evaluated the biological variation of this marker in patients undergoing hemodialysis. Bone ALP was measured in non-fasting serum samples taken twice a week over a 6-week period in 22 stable hemodialysis patients and 12 healthy volunteers. The within-individual coefficients of variance were calculated and used to derive the critical difference required to be certain that an observed change was significant. The coefficient of variance for bone ALP was significantly higher in hemodialysis patients compared to healthy individuals. Seven samples were required to estimate the homeostatic set point of bone ALP, within 10%, in a hemodialysis patient. The concentration of serial bone ALP measurements would need to change by 36% between any two measurements before it can be considered a significant change. Since the biological variation of bone ALP is less than half that reported for PTH, our study provides further support for the use of bone ALP as an alternative marker of bone mineral metabolism in the setting of chronic kidney disease-mineral and bone disorder. Kidney International (2012) 82, 100-105; doi:10.1038/ki.2012.77; published online 28 March 2012
引用
收藏
页码:45 / 52
页数:8
相关论文
共 37 条
[1]
MECHANISMS OF ISCHEMIC ACUTE-RENAL-FAILURE [J].
BONVENTRE, JV .
KIDNEY INTERNATIONAL, 1993, 43 (05) :1160-1178
[2]
DISPARATE MECHANISMS FOR HYPOXIC CELL INJURY IN DIFFERENT NEPHRON SEGMENTS - STUDIES IN THE ISOLATED PERFUSED RAT-KIDNEY [J].
BREZIS, M ;
SHANLEY, P ;
SILVA, P ;
SPOKES, K ;
LEAR, S ;
EPSTEIN, FH ;
ROSEN, S .
JOURNAL OF CLINICAL INVESTIGATION, 1985, 76 (05) :1796-1806
[3]
S6 kinase 1 knockout inhibits uninephrectomy- or diabetes-induced renal hypertrophy [J].
Chen, Jian-Kang ;
Chen, Jianchun ;
Thomas, George ;
Kozma, Sara C. ;
Harris, Raymond C. .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2009, 297 (03) :F585-F593
[4]
Role of EGF receptor activation in angiotensin II-induced renal epithelial cell hypertrophy [J].
Chen, Jianchun ;
Chen, Jian-Kang ;
Neilson, Eric G. ;
Harris, Raymond C. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2006, 17 (06) :1615-1623
[5]
EGFR Signaling Promotes TGFβ-Dependent Renal Fibrosis [J].
Chen, Jianchun ;
Chen, Jian-Kang ;
Nagai, Kojiro ;
Plieth, David ;
Tan, Mingqi ;
Lee, Tang-Cheng ;
Threadgill, David W. ;
Neilson, Eric G. ;
Harris, Raymond C. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2012, 23 (02) :215-224
[6]
Role of mammalian target of rapamycin signaling in compensatory renal hypertrophy [J].
Chen, JK ;
Chen, JC ;
Neilson, EG ;
Harris, RC .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2005, 16 (05) :1384-1391
[7]
Function of Akt/PKB signaling to cell motility, invasion and the tumor stroma in cancer [J].
Chin, Y. Rebecca ;
Toker, Alex .
CELLULAR SIGNALLING, 2009, 21 (04) :470-476
[8]
Renal ischemia-reperfusion injury and adenosine 2A receptor-mediated tissue protection: role of macrophages [J].
Day, YJ ;
Huang, L ;
Ye, H ;
Linden, J ;
Okusa, MD .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2005, 288 (04) :F722-F731
[9]
Origin of new cells in the adult kidney: results from genetic labeling techniques [J].
Duffield, Jeremy S. ;
Humphreys, Benjamin D. .
KIDNEY INTERNATIONAL, 2011, 79 (05) :494-501
[10]
Erlotinib (Tarceva): An update on the clinical trial program [J].
Herbst, RS .
SEMINARS IN ONCOLOGY, 2003, 30 (03) :34-46