Potential Novel Biomarkers of Obstructive Nephropathy in Children with Hydronephrosis

Abstract

Obstructive nephropathy (ON) secondary to the congenital hydronephrosis (HN) is one of the most common causes of chronic kidney disease in children. Neither currently used imaging techniques nor conventional laboratory parameters are sufficient to assess the onset and outcome of this condition; hence, there is a need to prove the usefulness of newly discovered biomarkers of kidney injury in this respect. The purpose of the study was to assess the urinary excretion of alpha-GST, pi-GST, NGAL, and KIM-1 and the serum level of NGAL in children with congenital unilateral hydronephrosis secondary to ureteropelvic junction obstruction. The results were evaluated in relation to severity of HN, the presence of ON, relative function of an obstructed kidney, and the presence of proteinuria. The study comprised 45 children with HN of different grades and 21 healthy controls. Urinary and serum concentrations of biomarkers were measured using specific ELISA kits. Urinary biomarker excretions were expressed as a biomarker/creatinine (Cr) ratio. Patients with the highest grades of HN showed significantly increased values of all measured biomarkers, whereas those with the lowest grades of HN displayed only significant elevation of urinary alpha-GST and the serum NGAL. Urinary NGAL positively correlated with percentage loss of relative function of an obstructed kidney in renal scintigraphy. In patients with proteinuria, significantly higher urinary alpha-GST excretion was revealed as compared to those without this symptom. The ROC curve analysis showed the best diagnostic profile for urinary alpha-GST/Cr and NGAL/Cr ratios in the detection of ON. In conclusion, the results of the study showed that urinary alpha-GST and NGAL are promising biomarkers of ON. Ambiguous results of the remaining biomarkers, i.e., urinary pi-GST and KIM-1, and serum NGAL level may be related to a relatively small study group. Their utility in an early diagnosis of ON should be reevaluated.

Ethanol extract of Nigella sativa has antioxidant and ameliorative effect against nickel chloride-induced hepato-renal injury in rats

“…Alternatively, it could be suggestive of the onset of kidney diseases. Certain isoforms of GST are elevated at the early stage and during the progression of kidney diseases [62,63]. The increase in renal GST observed in this study may also be due to NiCl 2 -induced damage to renal tubules.…”

Roles Played by Biomarkers of Kidney Injury in Patients with Upper Urinary Tract Obstruction

“…The serum or urine NGAL level is a clinically useful biomarker of various types of AKI, including AKI after kidney transplantation [ 42 ], contrast medium-induced AKI [ 43 ], and AKI in critical care settings [ 44 ]. In children with UUTO, urine NGAL levels are significantly higher in bladder urine and/or renal pelvic urine compared to controls, correlate inversely with worsening obstruction, and decrease after surgery ( Table 1 ) [ 26 , 36 , 45 , 46 , 47 , 48 , 49 ]. The AUC-ROC value for UUTO in children is 0.61–0.90 for bladder urine NGAL [ 26 , 36 , 45 , 46 , 47 , 48 ].…”

“…In children with UUTO, urine NGAL levels are significantly higher in bladder urine and/or renal pelvic urine compared to controls, correlate inversely with worsening obstruction, and decrease after surgery ( Table 1 ) [ 26 , 36 , 45 , 46 , 47 , 48 , 49 ]. The AUC-ROC value for UUTO in children is 0.61–0.90 for bladder urine NGAL [ 26 , 36 , 45 , 46 , 47 , 48 ]. In adults with UUTO, the urine NGAL level increases in those with obstructive nephropathy (AUC-ROCs of 0.70 for bladder urine and 0.76 for renal pelvic urine) and decreases after relief of the obstruction [ 23 , 50 , 51 ].…”

“…In adults with UUTO, the urine NGAL level increases in those with obstructive nephropathy (AUC-ROCs of 0.70 for bladder urine and 0.76 for renal pelvic urine) and decreases after relief of the obstruction [ 23 , 50 , 51 ]. Serum NGAL levels are significantly higher than in controls [ 45 , 50 ]. However, the use of NGAL as a biomarker of kidney injury induced by UUTO has several limitations.…”

Utility of urinary organic anion transporter 5 as an early biomarker of obstructive nephropathy

“…Creatinine is a poorly reliable indicator of the renal status because it only assesses glomerular filtration rate and functional changes, disregarding the subclinical situations. At present, an array of peptides and proteins are studied and evaluated as potential biomarkers of renal injury for the early detection of this pathology 4‐7 …”