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      Are Tubular Injury Markers NGAL and KIM-1 Useful in Pediatric Neurogenic Bladder?

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          Abstract

          The lack of early biomarkers of renal damage in children with neurogenic bladder (NB) prompts us to investigate the role of promising proteins: neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). This prospective analysis was conducted on 58 children with NB and 25 healthy children. We assessed urinary levels of NGAL and KIM-1 in both groups. Age, sex, anthropometric measurements, activity assessment, renal function, and urodynamics parameters were analyzed. The differences between the median uNGAL and uKIM-1 in the NB group compared to control were recorded. However, only uNGAL levels were statistically significantly higher. Statistically significant correlation was found between gender, recurrent urinary tract infections, bladder trabeculation, its compliance, activity assessment, and uNGAL. To conclude, elevated levels of uNGAL may be considered a biomarker of tubular injury in children with NB due to MMC in contrast to uKIM-1.

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          Most cited references25

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          Renal tubule injury: a driving force toward chronic kidney disease.

          Renal tubules are the major component of the kidney and are vulnerable to a variety of injuries including hypoxia, proteinuria, toxins, metabolic disorders, and senescence. It has long been believed that tubules are the victim of injury. In this review, we shift this concept to renal tubules as a driving force in the progression of kidney diseases. In response to injury, tubular epithelial cells undergo changes and function as inflammatory and fibrogenic cells, with the consequent production of various bioactive molecules that drive interstitial inflammation and fibrosis. Innate immune-sensing receptors on the tubular epithelium also aggravate immune responses. Necroinflammation, an autoamplification loop between tubular cell death and interstitial inflammation, leads to the exacerbation of renal injury. Furthermore, tubular cells also play an active role in progressive renal injury via emerging mechanisms associated with a partial epithelial-mesenchymal transition, cell-cycle arrest at both G1/S and G2/M check points, and metabolic disorder. Thus, a better understanding the mechanisms by which tubular injury drives inflammation and fibrosis is necessary for the development of therapeutics to halt the progression of chronic kidney disease.
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            Neutrophil gelatinase-associated lipocalin (NGAL) and progression of chronic kidney disease.

            Chronic kidney disease (CKD) has recently assumed epidemic proportion, becoming a troubling emerging cause of morbidity, especially if it progresses to terminal stage (ESRD). The authors aimed to evaluate whether neutrophil gelatinase-associated lipocalin (NGAL), a novel specific biomarker of acute kidney injury, could predict the progression of CKD. Serum and urinary NGAL levels, together with a series of putative progression factors, were evaluated in a cohort of 96 patients (mean age: 57 +/- 16 years) affected by nonterminal CKD (eGFR > or =15 ml/min/1.73 m(2)) of various etiology. Progression of CKD, assessed as doubling of baseline serum creatinine and/or onset of ESRD, was evaluated during follow-up. At baseline, both serum and urinary NGAL were inversely, independently, and closely related to eGFR. After a median follow-up of 18.5 mo (range 1.01 to 20), 31 patients (32%) reached the composite endpoint. At baseline, these patients were significantly older and showed increased serum creatinine, calcium-phosphate product, C-reactive protein, fibrinogen, daily proteinuria, and NGAL levels, whereas eGFR values were significantly lower. Univariate followed by multivariate Cox proportional hazard regression analysis showed that urinary NGAL and sNGAL predicted CKD progression independently of other potential confounders, including eGFR and age. In patients with CKD, NGAL closely reflects the entity of renal impairment and represents a strong and independent risk marker for progression of CKD.
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              Biomarkers for the Early Detection and Prognosis of Acute Kidney Injury.

              AKI is an increasingly common disorder that is strongly linked to short- and long-term morbidity and mortality. Despite a growing heterogeneity in its causes, providing a timely and certain diagnosis of AKI remains challenging. In this review, we summarize the evolution of AKI biomarker studies over the past few years, focusing on two major areas of investigation: the early detection and prognosis of AKI. We highlight some of the lessons learned in conducting AKI biomarker studies, including ongoing attempts to address the limitations of creatinine as a reference standard and the recent shift toward evaluating the prognostic potential of these markers. Lastly, we suggest current gaps in knowledge and barriers that may be hindering their incorporation into care and a full ascertainment of their value.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Role: Academic Editor
                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                27 May 2021
                June 2021
                : 10
                : 11
                : 2353
                Affiliations
                Department of Pediatrics and Nephrology, Medical University of Białystok, 17 Waszyngtona Str, 15-274 Białystok, Poland; iklinped@ 123456umb.edu.pl
                Author notes
                Author information
                https://orcid.org/0000-0002-6912-9502
                Article
                jcm-10-02353
                10.3390/jcm10112353
                8197925
                34071981
                53d22bf0-684d-488c-8014-5d2c8e608158
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 09 May 2021
                : 25 May 2021
                Categories
                Article

                neurogenic bladder,myelomeningocele,markers
                neurogenic bladder, myelomeningocele, markers

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