The Study Of Serum And Urine (TIMP-2)·(IGFBP7),NGAL And L-FABP As Markers Of Renal Injury Induced By Unilateral Ureteral Calculi

Objective:To investigate the expression levels of tissue inhibitors of metalloproteinase-2(TIMP-2),insulin-like growth factor binding protein7(IGFBP7),neutrophil gelatinase associated lipocalin(NGAL),liver-type fatty acid binding protein(L-FABP)in serum and urine samples;And to value their clinical applications of the early diagnosis of uretaral calculi associated renal injury,predicting the prognosis of kidney and guiding treatment of ureteral calculi.Materials and methods:We measured the serum creatinine(Scr),serum and urine TIMP-2,IGFBP7,NGAL and L-FABP levels in 20 healthy people as baseline.52 patients without underlying disease,ranging from 18 to 50 years old,diagnosed as incipient unilateral ureteral stones,were well documented their degrees of hydronephrosis,sizes and locationes of ureteral stones.They were all accepted ureteroscopy holmium laser lithotripsy(URHL)to relieve the obstruction.We detected and analyzed the values of Scr,TIMP-2,IGFBP7,NGAL and L-FABP in serum and urine samples in each patient just on the day before operation,together with their values on the first day,the 3nd day,the 7th day and the 3nd month after operation.Split glomerular filtration rate(GFR)was evaluated by 99Tc-diethylene triamine penta acetic acid(99Tcm-DTPA)renal dynamic imaging within 3 days before operation and the 3nd months after operation.The correlation between these biomarkers and clinical data were analyzed.All statistical analysis was performed by using SPSS 20.0.Results:(1)There was no significant difference of the serum creatinine,serum(TIMP-2)·(IGFBP7)and serum L-FABP level between ureteral calculi patients and healthy people(all P>0.05).(2)The urine(TIMP-2)·(IGFBP7),urine L-FABP,serum and urine NGAL levels of preoperative and postoperative samples from the ureteral calculi patients were significantly higher than those of healthy people(all P<0.01).The urine level of(TIMP-2)·(IGFBP7)decreased in the first day after ureteral stones were removed,its level decreased obviously in the first 3 days after surgery and no longer declined in the 7th day after operation;however,it was still higher than that of healthy people at 3nd month after operation(P<0.01);Urine L-FABP level gradually declined in the 1st day,3nd day,7th day,3nd month postoperatively;its level declined most rapidly in first 3 days postoperatively,but it was still higher than health samples in 3nd month(P<0.01).Serum and urine NGAL levels gradually declined in the 1st day,3nd day,7th day,3nd month postoperatively,and also its level was still higher than health samples in 3nd month(all P<0.01).(3)The urine(TIMP-2)·(IGFBP7),urine L-FABP,serum and urine NGAL level were positively correlated with the degree of hydronephrosis(r=0888,0.871,0.865 and 0.671,respectively;all P<0.01).However,urine(TIMP-2)·(IGFBP7),urine L-FABP,serum and urine NGAL was found no significant correlation with location and size of the ureteral stones(all P>0.05).The urine(TIMP-2)·(IGFBP7),urine L-FABP,serum and urine NGAL level were positively correlated with the decreased GFR of the affected kidney within the first 3 days and at the 3nd month postoperatively(r=0.571,0.606,0.655,0.671,0.497,0.572,0.515 and 0.602,respectively;all P<0.01).The urine(TIMP-2)·(IGFBP7),urine L-FABP,serum and urine NGAL level were negatively correlated with the GFR of the affected kidney within the first 3 days preoperatively and at 3 months postoperatively(all P<0.01).(4)The degree of hydronephrosis was negatively correlated with the GFR of the affected kidney before and after operation(r=-0.892 and-0.922,respectively;all P<0.01).No significant correlation was obtained between the stone location and its size with the GFR of the affected kidney(all P>0.05).Conclusion:The urine(TIMP-2)·(IGFBP7),urine L-FABP,serum and urine NGAL levels of the patients with ureteral calculus are significantly higher than those of healthy people.Their expression levels decreased gradually after calculus removed within 3 months;among them,urine(TIMP-2)·(IGFBP7)declines most rapidly,urine L-FABP takes the second place,serum and urine NGAL decrease slowest.The preoperative urine(TIMP-2)·(IGFBP7),urine L-FABP,serum,urine NGAL level,may predict postoperative GFR decline degree of the affected kidney.These biomarkers may be used to early diagnosis ureteral calculus associated renal injury and may play a role in determining therapeutic schedule and the best time of operation for patients with ureteral calculus.