Yildiz Bilal, Kural Nurdan, Colak Omer, Ak Ilknur, Akcar Nevbahar
Department of Pediatrics Faculty of Medicine, University of Osmangazi, Eskisehir, Turkey.
Clin Physiol Funct Imaging. 2008 Mar;28(2):107-12. doi: 10.1111/j.1475-097X.2007.00783.x. Epub 2007 Dec 18.
Mechanisms of compensatory renal growth (CRG) still remain a mystery. Various growth factors, including growth hormone, insulin-like growth factor-1 (IGF-1) have been implicated in different forms of CRG.
To investigate the serum levels of IGF-1, vascular endothelial growth factor (VEGF - role in vascular remodelling), matrix metalloproteinase-9 (MMP-9 - essential for normal nephrogenesis) and correlation of renal function in patients with unilateral nephrectomized, agenesis and hypoplasic kidney.
Thirty patients were included in this study. In group I, there were 10 patients with unilateral nephrectomy, while in group II, there were 10 patients with unilateral agenesis. As for group III, there were 10 patients with unilateral hypoplastic kidney. The serum levels of IGF-1, IGF-binding protein-3 (IGFBP-3), VEGF and MMP-9 were studied in all the cases. Clearance of creatinin (Ccr) and protein excretion were examined in the 24 h urine. CRG was determined with ultrasonography and scintigraphy. Twenty-six control subjects were also studied.
The levels of IGF-1, IGFBP-3, VEGF and MMP-9 were significantly higher in patients than in the control subjects (P < 0.001). Ccr and protein excretion levels were different in study groups than in those of the control group (P < 0.01). There were positive correlations between the serum levels of IGF-1 with IGFBP-3; IGF-1 with MMP-9; IGFBP-3 with MMP-9 (r = 0.825, P = 0.0001; P < 0.001 r = 0.611; P < 0.001 r = 0.585, respectively). There were negative correlations between GFR and the serum levels of IGF-1, IGFBP-3 and MMP-9 (P < 0.01 r = -0.708; P = 0.002 r = -0.803; P < 0.05 r = -0.442, respectively). Furthermore, there were positive correlations between proteinuria and the serum levels of IGF-1, IGFBP-3 and MMP-9 (P = 0.039 r = 0.600; P < 0.05 r = 0.456; P < 0.05 r = 0.424).
Increased IGF-1, IGFBP-3, VEGF and MMP-9 were observed in CRG in the follow-up period. IGF-1 and MMP-9 seemed to have increased in patients with CRG in defiance of the development of fibrosis. Moreover, IGF-1 and MMP-9 seem to be associated with reduced renal function and proteinuria.
代偿性肾生长(CRG)的机制仍是一个谜。多种生长因子,包括生长激素、胰岛素样生长因子-1(IGF-1),已被认为与不同形式的CRG有关。
研究单侧肾切除、肾缺如和肾发育不全患者血清中IGF-1、血管内皮生长因子(VEGF,在血管重塑中的作用)、基质金属蛋白酶-9(MMP-9,对正常肾发生至关重要)的水平以及肾功能的相关性。
本研究纳入30例患者。第一组有10例单侧肾切除患者,第二组有10例单侧肾缺如患者。第三组有10例单侧肾发育不全患者。研究了所有病例的血清IGF-1、IGF结合蛋白-3(IGFBP-3)、VEGF和MMP-9水平。检测24小时尿肌酐清除率(Ccr)和蛋白排泄量。通过超声和闪烁扫描测定CRG。还研究了26名对照受试者。
患者的IGF-1、IGFBP-3、VEGF和MMP-9水平显著高于对照受试者(P < 0.001)。研究组的Ccr和蛋白排泄水平与对照组不同(P < 0.01)。血清IGF-1与IGFBP-3、IGF-1与MMP-9、IGFBP-3与MMP-9之间存在正相关(r分别为0.825,P = 0.0001;P < 0.001,r = 0.611;P < 0.001,r = 0.585)。肾小球滤过率(GFR)与血清IGF-1、IGFBP-3和MMP-9水平之间存在负相关(P < 0.01,r = -0.708;P = 0.002,r = -0.803;P < 0.05,r = -0.442)。此外,蛋白尿与血清IGF-1、IGFBP-3和MMP-9水平之间存在正相关(P = 0.039,r = 0.600;P < 0.05,r = 0.456;P < 0.05,r = 0.424)。
在随访期CRG患者中观察到IGF-1、IGFBP-3、VEGF和MMP-9升高。IGF-1和MMP-9在CRG患者中似乎不顾纤维化的发展而升高。此外,IGF-1和MMP-9似乎与肾功能降低和蛋白尿有关。