Increased concentrations of soluble CD40 ligand may help to identify type 1 diabetic adolescents and young adults at risk for developing persistent microalbuminuria

被引:18
作者
Chiarelli, F. [1 ]
Giannini, C. [1 ]
Verrotti, A. [1 ]
Mezzetti, A. [2 ]
Mohn, A. [1 ]
机构
[1] Univ G dAnnunzio, Dept Pediat, I-66100 Chieti, Italy
[2] Univ G dAnnunzio, Dept Med, I-66100 Chieti, Italy
关键词
persistent microalbuminuria; CD40; ligand; diabetic nephropathy; type 1 diabetic adolescents and young adults;
D O I
10.1002/dmrr.891
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Recent studies on the pathogenesis of diabetic complications have demonstrated the important role of a number of aberrantly expressed molecules acting together in the development of early diabetic microvascular complications. Soluble CD40 ligand (sCD40L) is supposed to be one of the most likely candidates for both retinopathy and nephropathy. Methods In January 1989, sCD40L was measured in 340 normoalbuminuric diabetic adolescents and Young adults. Participants were examined at baseline and biannually thereafter. sCD40L was measured every 2 years during a 16-year follow-tip period. sCD40L was also measured in parents. Results Over 16 years, 32 out of 340 patients developed persistent microalbuminuria; no patient developed overt diabetic nephropathy. The risk of developing microalbuminuria was higher in children with increased sCD40L at the beginning of the study (using 6 ng/mL as the arbitrary cut-off value) (group A) compared with those with normal sCD40L (group 13). Sex did not influence predictive value, sensitivity, or specificity. sCD40L was not significantly correlated with duration of diabetes. The percentage of offspring with both parents having sCD40L above the mean values was significantly higher in group A than in group B. The odds ratio (OR) for the occurrence of microalbuminuria after adjustment for confounding variables in patients with elevated baseline sCD40L was 4.2 (95% CI, 2.1-10.7). Conclusions Persistently increased sCD40L levels from the onset of diabetes might help to identify those normotensive and normoalbuminuric young patients at increased risk of developing incipient nephropathy later in life. Copyright (c) 2008 John Wiley & Sons, Ltd.
引用
收藏
页码:570 / 576
页数:7
相关论文
共 34 条
[1]   Serum total renin is increased before microalbuminuria in diabetes [J].
Allen, TJ ;
Cooper, ME ;
Gilbert, RE ;
Winikoff, J ;
Skinner, SL ;
Jerums, G .
KIDNEY INTERNATIONAL, 1996, 50 (03) :902-907
[2]  
ANDERSEN AR, 1983, DIABETOLOGIA, V25, P496
[3]   Platelet-derived CD40L -: The switch-hitting player of cardiovascular disease [J].
André, P ;
Nannizzi-Alaimo, L ;
Prasad, SK ;
Phillips, DR .
CIRCULATION, 2002, 106 (08) :896-899
[4]   Enhanced levels of soluble and membrane-bound CD40 ligand in patients with unstable angina -: Possible reflection of T lymphocyte and platelet involvement in the pathogenesis of acute coronary syndromes [J].
Aukrust, P ;
Müller, F ;
Ueland, T ;
Berget, T ;
Aaser, E ;
Brunsvig, A ;
Solum, NO ;
Forfang, K ;
Froland, SS ;
Gullestad, L .
CIRCULATION, 1999, 100 (06) :614-620
[5]   Variants of the CD40 gene but not of the CD40L gene are associated with coronary artery calcification in the Diabetes Heart Study (DHS) [J].
Burdon, KP ;
Langefeld, CD ;
Beck, SR ;
Wagenknecht, LE ;
Carr, JJ ;
Rich, SS ;
Freedman, BI ;
Herrington, D ;
Bowden, DW .
AMERICAN HEART JOURNAL, 2006, 151 (03) :706-711
[6]   The need for early predictors of diabetic nephropathy risk - Is albumin excretion rate sufficient? [J].
Caramori, ML ;
Fioretto, P ;
Mauer, M .
DIABETES, 2000, 49 (09) :1399-1408
[7]   GLOMERULAR HYPERFILTRATION INCREASES THE RISK OF DEVELOPING MICROALBUMINURIA IN DIABETIC CHILDREN [J].
CHIARELLI, F ;
VERROTTI, A ;
MORGESE, G .
PEDIATRIC NEPHROLOGY, 1995, 9 (02) :154-158
[8]   Role of growth factors in the development of diabetic complications [J].
Chiarelli, F ;
Santilli, F ;
Mohn, A .
HORMONE RESEARCH, 2000, 53 (02) :53-67
[9]   Preprocedural level of soluble CD40L is predictive of enhanced inflammatory response and restenosis after coronary angioplasty [J].
Cipollone, F ;
Ferri, C ;
Desideri, G ;
Paloscia, L ;
Materazzo, G ;
Mascellanti, M ;
Fazia, M ;
Iezzi, A ;
Cuccurullo, C ;
Pini, B ;
Bucci, M ;
Santucci, A ;
Cuccurullo, F ;
Mezzetti, A .
CIRCULATION, 2003, 108 (22) :2776-2782
[10]   Enhanced soluble CD40 ligand contributes to endothelial cell dysfunction in vitro and monocyte activation in patients with diabetes mellitus:: effect of improved metabolic control [J].
Cipollone, F ;
Chiarelli, F ;
Davì, G ;
Ferri, C ;
Desideri, G ;
Fazia, M ;
Iezzi, A ;
Santilli, F ;
Pini, B ;
Cuccurullo, C ;
Tumini, S ;
Del Ponte, A ;
Santucci, A ;
Cuccurullo, F ;
Mezzetti, A .
DIABETOLOGIA, 2005, 48 (06) :1216-1224