First-year profile of biomarkers for early detection of renal injury in infants with congenital urinary tract obstruction

Kostić, Dušan; Beozzo, Glenda Priscila Neves Dos Santos; Couto, Saulo B.; A, Kato; Lima, Larissa; Palmeira, Patrícia; Krebs, Vera Lúcia Jornada; Bunduki, Victor; Francisco, Rossana Pulcineli Vieira; Zugaib, Marcelo; Carvalho, Werther Brunow de; Koch, Vera H.

doi:10.1007/s00467-019-4195-4

Cited by 9 publications

(5 citation statements)

References 46 publications

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“…Kostic et al . [ 36 ] found NGAL to be a better marker for bilateral HDN and LUTO in patients with congenital urinary tract obstruction (UPJO, UVJO, and LUTO). A high specificity (>90%) but less sensitivity (<75%) for NGAL and uCysC was observed in their study.…”

Section: Discussionmentioning

confidence: 99%

Role of Urinary Biomarkers (Transforming Growth Factor β1, Neutrophil Gelatinase-Associated Lipocalin, and Cystatin C) as a Prognostic Factor of Renal Outcome in the Posterior Urethral Valve

Sharma,

Panda,

Ratan

et al. 2024

Journal of Indian Association of Pediatric Surgeons

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Background: The urinary biomarker response precedes the appearance of any renal structural or functional derangement. Transforming growth factor-β1 (TGF-β1), neutrophil gelatinase associated lipocalin (NGAL), and Cystatin C (CysC) can act as the early prognostic markers in posterior urethral valve (PUV) patients. Aim: To compare the urinary levels of TGF-β1, NGAL, and CysC between PUV cases and age matched controls and to correlate these with renal structural and functional parameters. Materials and Methods: This prospective study included children with PUV diagnosed using the standard investigations and an equal number of age-matched controls with nonurological problems. For the study subjects, the urinary samples were collected at three different time points (pre- and postoperatively at 3 and 6 months), whereas for controls, only single-voided samples were studied. The urinary levels of TGF-β1, NGAL, and CysC were estimated by the standardized techniques using the ELISA kits. Statistical methods were used to drive the comparisons between cases and controls. Results: Fifteen children with a median age of 10 (5–48) months were enrolled in each of the two groups. The mean uTGF-β1 in the case group was significantly higher at all three time points (43.20 ± 6.13 pg/ml, 43.33 ± 11.89 pg/ml and 40.71 ± 9.01 pg/ml) as compared to the control group (29.12 ± 8.31 pg/ml) (P ≤ 0.001). The median uNGAL in the case group was also higher (17.78 ng/ml, 2.35 ng/ml and 2.536 ng/ml) as compared to the control group (1.31 ng/ml). However, the difference was significant only preoperatively (P = 0.02). The median uCysC in case group was similarly higher (0.347 μg/ml, 0.439 μg/ml, and 0.382 μg/ml) than the control group (0.243 μg/ml) (P > 0.05). Serum creatinine in the case group (0.49 mg/dl) showed no significant rise above that of control (0.24 mg/dl). A cutoff value of uTGF-β1 = 36.55 pg/ml (P < 0.001), uNGAL = 0.879 ng/ml (P = 0.02), and uCysC = 0.25 μg/ml (P = 0.22) was found to be associated with renal damage in PUV. A significant correlation was found between uNGAL and S. creatinine at 3 months (r = 0.43, P = 0.017) and 6 months (r = 0.47, P = 0.08). Conclusion: The elevated uTGF-β1, a decline in uNGAL and an increase in uCysC suggests ongoing inflammation, improvement in hydronephrosis and a prolonged proximal tubular dysfunction in PUV patients, respectively.

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Section: Discussionmentioning

confidence: 99%

Role of Urinary Biomarkers (Transforming Growth Factor β1, Neutrophil Gelatinase-Associated Lipocalin, and Cystatin C) as a Prognostic Factor of Renal Outcome in the Posterior Urethral Valve

Sharma,

Panda,

Ratan

et al. 2024

Journal of Indian Association of Pediatric Surgeons

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“…We were able to find 4 recent studies advocating uNGAL as a promising factor effectively identifying surgical cases. The median age of patients ranged from 3 to 20 months at the time of inclusion (21)(22)(23)(24). However, small sample size and different patterns of obstruction in the compared subgroups were the drawbacks frequently.…”

Section: Discussionmentioning

confidence: 99%

Urine Biomarkers Combined With Ultrasound for the Diagnosis of Obstruction in Pediatric Hydronephrosis

et al. 2022

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Introduction: To establish the efficacy of ultrasound (US) combined with urine biomarkers in differentiating patients who require surgical management from those who do not, avoiding invasive investigations.Materials and Methods: From February 2019 to February 2021, all pediatric patients who presented with hydronephrosis were selected for the study. All renal units (RU) were evaluated by US, and fresh frozen voided urine samples were collected at the time of inclusion. Hydronephrosis grade was evaluated by the Society for Fetal Urology (SFU) and an alternative grading system (AGS). Patients who had high-grade hydronephrosis on US were referred to renal scan (RS) or intervention, when there was an increase of dilatation in subsequent follow-up images. Fresh frozen urine from the control group with no history of renal diseases and no renal anomalies on US was collected. We compared differences of US parameters combined with urine biomarkers between surgically and non-surgically managed patients and between the groups of patients when they were stratified by different RS findings and analyzed whether urinary biomarkers give any additional value to US. Instead of the anterior–posterior diameter (APD), we used its ratio with mid-parenchymal thickness. The additional efficacy of biomarkers to US was calculated when the US component was derived to a cumulative APD/mid-parenchymal ratio.Results: Sixty-four patients with hydronephrosis were prospectively included in the study accounting for a total of 81 patient visits and 162 RUs evaluated. A control group of 26 patients was collected. The mean age at inclusion in the hydronephrosis group was 43.7(±45.5) months, and a mean age in a control group was 61.2(±41.3) months. The cumulative APD/mid-parenchymal ratio combined with urinary albumin, β2 microglobulin (β2-M), and urinary neutrophil gelatinase-associated lipocalcin may have a better performance in the prediction of surgical intervention than the cumulative APD/mid-parenchymal ratio alone (p = 0.1). The best performance to detect the increased tissue transit time and obstructive curve on RS was demonstrated by the β2-M creatinine ratio. An increased cumulative APD/mid-parenchymal ratio with biomarkers together had a fairly good sensitivity and specificity for detection of DRF < 40%.Conclusions: According to our data, the APD/mid-parenchymal ratio alone has good efficacy in prediction of surgery and abnormal RS findings especially when combined with urine biomarkers.

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“…Proteinuria is a common marker in nephrology that is used to assess kidney damage. Several studies have identified proteinuria as a negative prognostic marker for renal outcome in PUV patients [ 36 , 62 , 66 , 67 ]. Some studies have shown that urinary markers of inflammation and fibrotic remodelling can predict renal outcome.…”

Section: Prognostic Factors For Chronic Kidney Disease Developmentmentioning

confidence: 99%

“…Some studies have shown that urinary markers of inflammation and fibrotic remodelling can predict renal outcome. Transforming growth factor-β (TGF-β) is a marker of fibrosis, and is elevated in patients with an unfavourable renal outcome [ 67 , 68 , 69 ]. Monocyte chemotactic protein (MCP-1) recruits macrophages and is thus a marker of inflammation.…”

Section: Prognostic Factors For Chronic Kidney Disease Developmentmentioning

confidence: 99%

Chronic Kidney Disease in Boys with Posterior Urethral Valves–Pathogenesis, Prognosis and Management

Klaus

Lange-Sperandio

2022

Biomedicines

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Posterior urethral valves (PUV) are the most common form of lower urinary tract obstructions (LUTO). The valves can be surgically corrected postnatally; however, the impairment of kidney and bladder development is irreversible and has lifelong implications. Chronic kidney disease (CKD) and bladder dysfunction are frequent problems. Approximately 20% of PUV patients will reach end-stage kidney disease (ESKD). The subvesical obstruction in PUV leads to muscular hypertrophy and fibrotic remodelling in the bladder, which both impair its function. Kidney development is disturbed and results in dysplasia, hypoplasia, inflammation and renal fibrosis, which are hallmarks of CKD. The prognoses of PUV patients are based on prenatal and postnatal parameters. Prenatal parameters include signs of renal hypodysplasia in the analysis of fetal urine. Postnatally, the most robust predictor of PUV is the nadir serum creatinine after valve ablation. A value that is below 0.4 mg/dl implies a very low risk for ESKD, whereas a value above 0.85 mg/dl indicates beneficial kidney outcome. Experimental urinary markers such as MCP-1 and TGF-β, as well as microalbuminuria, indicate progression to CKD. Until now, prenatal intervention may improve survival but yields no renal benefit. The management of PUV patients includes control of bladder dysfunction and CKD treatment to slow down progression by controlling hypertension, proteinuria and infections. In kidney transplantation, aggressive bladder management is essential to ensure optimal graft survival.

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First-year profile of biomarkers for early detection of renal injury in infants with congenital urinary tract obstruction

Cited by 9 publications

References 46 publications

Role of Urinary Biomarkers (Transforming Growth Factor β1, Neutrophil Gelatinase-Associated Lipocalin, and Cystatin C) as a Prognostic Factor of Renal Outcome in the Posterior Urethral Valve

Role of Urinary Biomarkers (Transforming Growth Factor β1, Neutrophil Gelatinase-Associated Lipocalin, and Cystatin C) as a Prognostic Factor of Renal Outcome in the Posterior Urethral Valve

Urine Biomarkers Combined With Ultrasound for the Diagnosis of Obstruction in Pediatric Hydronephrosis

Chronic Kidney Disease in Boys with Posterior Urethral Valves–Pathogenesis, Prognosis and Management

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