The Utility of Noninvasive Urinary Biomarkers for the Evaluation of Vesicoureteral Reflux in Children.

Vesicoureteral reflux (VUR) is one of the most important disorders encountered in pediatric nephrology due to its frequency and potential evolution to chronic kidney disease (CKD). The aim of our study was to identify noninvasive and easy-to-determine urinary markers to facilitate the diagnosis and staging of VUR. We performed a cross-section study including 39 patients with VUR followed over three years (August 2021-September 2023) and 39 children without urinary disorder (the control group). We measured the urinary concentration of interleukin-6 (IL-6), cathelicidin (LL-37), and neutrophil gelatinase-associated lipocalin (NGAL) in VUR and healthy controls. Moreover, we analyzed the correlation between these biomarkers and the presence of renal scars (RS), reflux nephropathy (RN), and CKD. The NGAL concentrations were significantly higher in patients with VUR than in the controls (p = 0.02). Regarding the severity of the reflux, NGAL/creatinine and LL-37/creatinine were positively correlated with severe reflux (p = 0.04, respectively, p = 0.02). In patients with VUR and RS, LL-37/creatinine was significantly lower (p = 0.01). LL-37/creatinine with an AUC of 0.71 and NGAL/creatinine with an AUC of 0.72 could be acceptable diagnostic tests for severe VUR. In conclusion, urinary IL-6, NGAL, and LL-37 could serve as valuable markers for diagnosing and predicting outcomes in patients with VUR and RN.

Vesicoureteral Reflux and Innate Immune System: Physiology, Physiopathology, and Clinical Aspects.

Vesicoureteral reflux represents one of the most concerning topics in pediatric nephrology due to its frequency, clinical expression with the potential to evolve into chronic kidney disease, and last but not least, its socio-economic implications. The presence of vesicoureteral reflux, the occurrence of urinary tract infections, and the development of reflux nephropathy, hypertension, chronic kidney disease, and finally, end-stage renal disease represent a progressive spectrum of a single physiopathological condition. For the proper management of these patients with the best clinical outcomes, and in an attempt to prevent the spread of uropathogens' resistance to antibacterial therapy, we must better understand the physiopathology of urinary tract infections in patients with vesicoureteral reflux, and at the same time, we should acknowledge the implication and response of the innate immune system in this progressive pathological condition. The present paper focuses on theoretical aspects regarding the physiopathology of vesicoureteral reflux and the interconditionality between urinary tract infections and the innate immune system. In addition, we detailed aspects regarding cytokines, interleukins, antimicrobial peptides, and proteins involved in the innate immune response as well as their implications in the physiopathology of reflux nephropathy. New directions of study should focus on using these innate immune system effectors as diagnostic and therapeutic tools in renal pathology.