Evaluating TIMP-2 and IGFBP-7 as a predictive tool for kidney injury in ureteropelvic junction obstruction

ABSTRACT A major challenge in the management of ureteropelvic junction obstruction (UPJO) is the selection of patients who would benefit from surgical treatment. Tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) indicate renal cell stress and are associated with cell cycle arrest. The [TIMP-2] [IGFBP7] ratio (Nephrocheck®) has been recently applied in patients in intensive care units patients to predict the development of acute kidney injury. In this study, we evaluated the performance of these biomarkers performance to distinguishing obstructive hydronephrosis (HN) from non-obstructive HN. Materials and Methods: Consecutive patients with UPJO were enrolled in this study. Urinary [TIMP-2] [IGFBP7] and clinical characteristics (hydronephrosis grade, differential renal function, and drainage half-time) were measured in the following groups: 26 children with obstructive HN at initial diagnosis (group 1A) and after six months of dismembered pyeloplasty (group 1B); 22 children with non-obstructive HN (group 2), and 26 children without any urinary tract condition, as the control group (group 3). Results: Comparing the initial samples, [TIMP-2] [IGFBP7] had higher levels in the HN groups and lower levels in the control group; however, no difference was observed between the HN groups (obstructive vs. non-obstructive). After six months of follow-up, patients who underwent dismembered pyeloplasty showed stability in the urinary concentration of [TIMP-2] [IGFBP7]. All patients with [TIMP-2] [IGFBP7] higher than 1.0 (ng/mL)2/1000 had diffuse cortical atrophy on ultrasonography. Conclusions: We showed that urinary levels of urinary [TIMP-2] [IGFBP7] are higher in children with HN than controls. Nephrocheck® is not reliable in predicting the need for surgical intervention for pediatric patients with UPJO.

Coexistence of proangiogenic potential and increased MMP-9, TIMP-1, and TIMP-2 levels in the plasma of patients with critical limb ischemia / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The objective of this study was to assess the angiogenic potential expressed as a quotient of vascular endothelial growth factor A (VEGF-A), as an indicator of proangiogenic activity, and the circulating receptors (soluble VEGF receptor protein R1 (sVEGFR-1) and sVEGFR-2), as indicators of the effect of angiogenic inhibition, depending on the concentrations of matrix metalloproteinase 2 (MMP-2) and MMP-9 and their tissue inhibitor 1 (TIMP-1) and TIMP-2 in the plasma of patients with lower extremity artery disease (LEAD). These blood parameters in patients with intermittent claudication (IC) and critical limb ischemia (CLI) were compared for select clinical and biochemical features. Stimulation of angiogenesis in the plasma of individuals with LEAD was evident as indicated by the significant increase in VEGF-A concentration along with reduced inhibition depending on circulating receptors sVEGFR-1 and sVEGFR-2. Critical ischemia was associated with higher VEGF-A, MMP-9, TIMP-1, and TIMP-2 concentrations than in the case of IC.