The evaluation of urinary early kidney injury molecule levels in children with vesicoureteral reflux and ureteropelvic junction obstruction

Kidney injury molecule-1 (Kim-1) is a transmembrane glycoprotein, which has been discovered in renal epithelial cells during acute kidney injury. Clinical studies showed that Kim-1 is over expressed in tubules of patients with focal segmental glomerulosclerosis, IgA nephropathy and membranoproliferative glomerulonephritis and urinary Kim-1 is correlated with the degree of proteinuria, tubular injury and interstitial fibrosis in these patients. Neutrophil gelatinase associated lipocalin (NGAL) is also excreted from renal tubules and is one of the early and sensitive marker of renal injury. In previous studies, increased NGAL levels have been found in acute renal injury, diabetic nephropathy, nephritic syndrome, tubulointerstitial nephritis and IgA nephropathy. There were few studies on urinary Kim-1 and NGAL levels in vesicoureteral reflux (VUR) and ureteropelvic junction obstruction (UPO) in the literature. In this prospective case-control study, we measured urinary Kim-1 / Creatinine and NGAL / Creatinine levels in children with VUR and UPO and compared these results with those of healthy controls. The study included 33 children with VUR and 31children with UPO but with no other systemic illnesses that followed up at Dicle University Hospitals. The control groups (different control groups were recruited for VUR and UPO) included 30 and 31 age and gender matched healthy children. Urine samples of patients were obtained and kept in -80oC until measurements. Thereafter, Kim-1 and NGAL levels of urine samples were measured by ELISA method. Urinary creatinine (Cr) level was measured by standard method and Kim-1/Cr and NGAL/Cr ratios were used for comparison between study groups. Ultrasound, DMSA and VCUG were performed in VUR patients. Ultrasound, DTPA or MAG3, and –in some UPO patients- DMSA were performed in children with UPO. The mean age of VUR patients was 7.5±3.5 (1.5-16) years, and the mean age of UPO patients was 5.2±3.6 (1-12) years. There were unilateral VUR in 19/33 and bilateral VUR in 14/33 children with VUR. Grade 3-5 VUR were detected in 80% of VUR patients. Renal scarring was detected in 36/66 renal unit of VUR patients. In the half of UPO patients who underwent DMSA had renal scarring. Significantly higher urinary Kim-1/Cr levels were found in VUR patients compared with the healthy controls (6.6±9.3 vs. 2.8±6.8, p<0.001). Similarly, VUR patients had significantly higher urinary NGAL/Cr ratio compared with the control group (1801±2161 vs. 558±1143, p<0.001). Bilateral VUR patients had three times urinary Kim-1/Cr and two times NGAL/Cr ratios while compared with the healthy controls. However, no significant differences were found regarding urinary Kim-1/Cr and NGAL/Cr ratios between VUR patients with and without renal scarring (p>0.05). Significantly higher urinary Kim-1/Cr (6.8±8.9 vs. 3.7±7.3, p=0.004) and NGAL/Cr (3309±3549 vs. 696±1228, p<0.001) ratios were found in UPO patients while compared with the healthy subjects. Significant positive correlations were found between urinary Kim-1/Cr between VUR grade and Kim-1/Cr (r=0.467, p=0.007) and NGAL/Cr (r=0.378, p=0.048) with correlation analysis. In conclusion, significantly higher urinary Kim-1 and NGAL excretion were found in children with VUR and UPO compared with the healthy controls. The existence of renal scarring did not affect urinary Kim-1 and NGAL levels in children with VUR. This may be due to different background mechanisms of VUR and renal scarring. Further studies with more patients are needed to clarify the relationships between VUR, UPO, renal scar and urinary early kidney injury molecules.