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

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Abstract

Background

Diagnosis of renal function impairment and deterioration in congenital urinary tract obstruction (UTO) continues to be extremely challenging. Use of renal biomarkers in this setting may favor early renal injury detection, allowing for a reliable choice of optimal therapeutic options and prevention or minimization of definitive renal damage.

Methods

This longitudinal, prospective study analyzed the first-year profile of two serum renal biomarkers: creatinine (sCr) and cystatin C (sCyC); and six urinary renal biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), transforming growth factor beta-1 (TGF-β1), retinol-binding protein (RBP), cystatin C (uCyC), and microalbuminuria (μALB) in a cohort of 37 infants with UTO divided into three subgroups: 14/37 with unilateral hydro(uretero)nephrosis, 13/37 with bilateral hydro(uretero)nephrosis, and 10/37 patients with lower urinary tract obstruction (LUTO), compared with 24 healthy infants matched by gestational age and birth weight.

Results

All urine biomarkers showed significantly higher values at the first month of life (p ≤ 0.009), while NGAL (p = 0.005), TGF-ß1 (p < 0.001), and μALB (p < 0.001) were high since birth compared to controls. Best single biomarker performances were RBP in bilateral hydronephrosis and LUTO subgroups and KIM-1 in unilateral hydronephrosis subgroup. Best biomarker combination results for all subgroups were obtained by matching RBP with TGF-ß1 or KIM-1 and NGAL with CyC ([AUC] ≤ 0.934; sensitivity ≤ 92.4%; specificity ≤ 92.8%).

Conclusions

RBP, NGAL, KIM-1, TGF-ß1, and CyC, alone and especially in combination, are relatively efficient in identifying surgically amenable congenital UTO and could be of practical use in indicating on-time surgery.

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Funding

This study received funds from São Paulo Research Foundation—FAPESP Grant (Reg. N° 2012/50337-9).

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Authors and Affiliations

  1. Pediatric Nephrology Unit, Department of Pediatrics, Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Enéas Carvalho de Aguiar, 647, São Paulo, CEP: 05403-000, SP, Brazil

    Dusan Kostic, Saulo Brasil do Couto, André Henrique Teruaki Kato & Vera Hermina Kalika Koch

  2. Department of Pediatrics, Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

    Glenda Priscila Neves dos Santos Beozzo, Vera Lúcia Jornada Krebs & Werther Brunow de Carvalho

  3. Laboratory of Clinical Investigations (LIM-36)—Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

    Laila Lima & Patricia Palmeira

  4. Department of Obstetrics and Gynecology, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

    Victor Bunduki, Rossana Pulcineli Vieira Francisco & Marcelo Zugaib

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  1. Dusan Kostic
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  12. Vera Hermina Kalika Koch
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Corresponding author

Correspondence to Dusan Kostic.

Ethics declarations

The study protocol was approved by the institution’s Ethics Committee (Reg. N° 0383/11, CAPPesq—HCFMUSP), supported by São Paulo Research Foundation—FAPESP Grant (Reg. N° 2012/50337-9), and was carried out in accordance with the Declaration of Helsinki. A signed informed parental consent form was obtained for each participant.

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The authors have no conflicts of interest to disclose. The results presented in this paper have not been published previously in whole or part, except in abstract format.

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ESM 1

Recruitment dynamics in the period from June 2012 to June 2016. Legend: UH, unilateral hydro (uretero)nephrosis subgroup; BH, bilateral hydro (uretero) nephrosis subgroup; LUTO, low urinary tract obstruction subgroup; PUV, posterior urethral valve. (PDF 280 kb)

ESM 2

Studies of renal biomarker performance for early detection of congenital UTO obstruction that require surgical intervention available in literature. Legend: * 26 with grade III (or higher) hydronephrosis; 36 with grade I and II hydronephrosis; 13 with PUJ obstruction and 11 with VUR. † 14 with unilateral, 13 with bilateral hydronephrosis, 10 with low urinary tract obstruction (LUTO); NR: not reported; sCr: serum creatinine; sCyC: serum cystatin C; RBP: retinol-binding protein; NGAL, neutrophil gelatinase-associated lipocalin; μALB, microalbuminuria; uCyC, urine cystatin C; KIM-1, kidney injury molecule-1; TGF-ß1, transforming growth factor beta-1; AUC: area under curve; sens.: sensibility; spec.: specificity; enz.: enzymatic; BS: before surgery; P: patient; C: control; PUV: posterior urethral valve; VUR: vesicoureteral reflux; PUJ: pelvi-ureteral junction; ELISA: enzyme-linked immunosorbent assay; ACEI: angiotensin-converting-enzyme inhibitor. (PDF 42.7 kb)

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Kostic, D., dos Santos Beozzo, G.P.N., do Couto, S.B. et al. First-year profile of biomarkers for early detection of renal injury in infants with congenital urinary tract obstruction. Pediatr Nephrol 34, 1117–1128 (2019). https://doi.org/10.1007/s00467-019-4195-4

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