Prospective Study on Several Urinary Biomarkers as Indicators of Renal Damage in Children with CAKUT.

PURPOSE: The aim of the study was to investigate urinary levels of monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), ß-2-microglobulin (ß2M), and FAS-ligand (FAS-L) in children with congenital anomalies of kidney and urinary tract (CAKUT) disease at risk of developing glomerular hyperfiltration syndrome. For this reason, we selected patients with multicystic kidney, renal agenesia and renal hypodysplasia, or underwent single nephrectomy. MATERIALS AND METHODS: This prospective, multicentric study was conducted in collaboration between the Pediatric Surgery Unit in Foggia and the Pediatric Nephrology Unit in Bari, Italy. We enrolled 80 children with CAKUT (40 hypodysplasia, 22 agenetic; 10 multicystic; 8 nephrectomy) who underwent extensive urological and nephrological workup. Exclusion criteria were recent urinary tract infections or pyelonephritis, age > 14 years, presence of systemic disease, or hypertension. A single urine sample was collected in a noninvasive way and processed for measuring by enzyme-linked immunosorbent assay urine levels of MCP-1, EGF, ß2M, and FAS-L. As control, urine samples were taken from 30 healthy children.Furthermore, we evaluated the urinary ratios uEGF/uMCP-1 (indicator of regenerative vs inflammatory response) and uEGF/uß2M (indicator of regenerative response vs. tubular damage). RESULTS: These results suggest that urinary levels of MCP-1 are overexpressed in CAKUT patients. Furthermore, our findings clearly demonstrated that both uEGF/uMCP-1 and uEGF/uß2M ratios were significantly downregulated in all patient groups when compared with the control group. CONCLUSION: These findings further support that CAKUT patients may, eventually, experience progressive renal damage and poor regenerative response. The increased urinary levels of MCP-1 in all groups of CAKUT patients suggested that the main factor responsible for the above effects is chronic renal inflammation mediated by local monocytes.

Urinary carbohydrate antigen 19-9/creatinine ratio: A non-invasive marker for follow-up of unilateral ureteropelvic junction obstruction in children.

INTRODUCTION: Ureteropelvic junction obstruction (UPJO) is the most common cause of hydronephrosis in children. One major challenge in the management of UPJO is to select the patients that must be subjected to early obstruction relief. Currently, there is no gold standard for this assessment. Therefore, the aim of the present study was to evaluate the urinary levels of carbohydrate antigen (CA) 19-9 and normalized CA 19-9 (Ca 19-9/Cr ratio) in UPJO patients before and after surgery and compare them with a control group to assess their potential clinical application as an assisting tool in diagnosis of UPJO patients. MATERIAL AND METHODS: From Jan 2013 to Jun 2016, 30 children with history of inguinal hernia, circumcision, hydrocele, and undescended testis as the control group (group 1) and 30 children with unilateral congenital UPJO (group 2) were enrolled in the study. Random CA 19-9 and random creatinine were measured in the voided urine samples of control group and proven congenital UPJO group preoperatively (group 2A) and at 6 months after dismembered pyeloplasty (group 2B). In addition, the random urinary CA 19-9/CR ratio was evaluated as a marker to normalized urinary CA 19-9. DISCUSSION: The urinary CA 19-9/Cr ratio was significantly greater in the UPJO group than in the control group. The urinary CA 19-9 also was more in group 2A than in group 1; however, it was not statistically significant. The urinary CA 19-9/Cr ratio and renal pelvis anteroposterior diameter decreased significantly in the group 2B 6 month after complete relief of obstruction in comparison with group 2A preoperatively. Urinary CA 19-9 also decreased in 2B group though it was not significant. CONCLUSION: Urinary CA 19-9/Cr ratio is suggested as a non-invasive marker that can assist in diagnosis and long-term follow-up of UPJO patients. This ratio is superior to urinary CA 19-9 as it is more strongly correlated with UPJ obstruction.

Determination of the severity of ureteropelvic junction obstruction using urinary epidermal growth factor and kidney injury molecule 1 levels.

AIM: This study aimed to assess the urinary concentrations of epidermal growth factor (EGF) and kidney injury molecule 1 (KIM-1) in patients with hydronephrosis. METHODS: Neonates with a history of prenatal hydronephrosis were enrolled in three groups. Group 1 included neonates with severe obstruction; group 2 included neonates with milder obstruction; and group 3 included neonates with normal findings on postnatal ultrasonography. RESULTS: 59 neonates were enrolled. The EGF: Cr and KIM-1: Cr ratios were significantly higher in group 1 than in group 2 (p = 0.016 and 0.015, respectively). The cut-off values were measured as 16.855 (sensitivity 71%, specificity 77%) and 0.4765 (sensitivity 81%, specificity 71%) for EGF:Cr and KIM-1:Cr ratios, respectively. The values were significantly higher in group 1 than in group 2. CONCLUSIONS: Evaluation of the urinary KIM-1:Cr ratio may help identify neonates with severe obstructive hydronephrosis.