Nephrogenesis, Renal Function, and Biomarkers in Preterm Newborns.

BACKGROUND: The survival of premature newborns increased in the last decades due to advances in neonatal care. The physiology of this group is still under investigation, once the incomplete organogenesis entails functional particularities that are not yet clarified by current clinical knowledge. The immature kidneys are especially susceptible to acute injury with potential long-term impacts. Current diagnostic parameters of acute kidney injury are limited among the preterm population. The commonly used serum creatinine protein constitutes a poor biomarker to predict early lesions as it is susceptible to several factors, including muscle mass and gestational age. OBJECTIVE: The present review explores the evidence on nephrogenesis, renal function, and acute kidney injury in neonatology, as well as studies on renal function biomarkers and their potential application for diagnosis, follow-up, and prognosis in preterm newborns. RESULTS: Premature newborns reach full-term gestational age with reduced number and quality of nephrons. Consequently, the glomerular filtration rate and tubular function become impaired and are proportional to the gestational age. Despite having a high incidence among the pediatric population, acute kidney injury is still underdiagnosed and poorly managed due to the absence of proper, sensible, and non-invasive biomarkers. Although cystatin C, NGAL, and KIM-1, are promising urinary markers, current literature remains inconsistent. CONCLUSION: Further research is needed to properly identify and standardize sensible and specific urinary biomarkers to better assess kidney function in preterm newborns.

Biomarkers of renal function in preterm neonates at 72 h and 3 weeks of life

Abstract Objective: Serum levels of creatinine in neonates are quite variable and suffer interference from the immature kidney and maternal creatinine concentration. The aim of this study was to measure novel biomarkers of glomerular and tubular function in healthy preterm neonates at 72 h and 3 weeks of life. Methods: Urine samples were collected in 40 preterm neonates with 28-34 incomplete weeks of gestational age. None of the participants had comorbidities, malformations and infections. The samples were collected at 72 h of life and at 3 weeks after birth. Measurements of Calbindin, Collagen IV, FABP1, αGST, IP-10, KIM-1, Osteoactivin, Renin, TFF-3, TIMP-1, α-1-Microglobulin, Albumin, Clusterin, Cystatin C, EGF, Lipocalin-2/NGAL and Osteopontin were performed using panels 1 and 2 of multiplex kits of kidney injury. Data were analyzed using the software GraphPad Prism version 6.0. Results: The preterm neonates included 55% of males with gestational age of 30 ± 1 weeks. The most frequent maternal condition associated with preterm birth was preeclampsia (80%). Molecules related to glomerular function showed a significant increase in the concentrations obtained at 3 weeks of life compared to 72 h of life. Markers related to tubular injury (KIM-1 and NGAL) also showed an increase. On the other hand, cystatin C did not change. Conclusion: The elevation of molecules related to glomerular function indicates an increase of glomerular filtration rate from 72 h up until 3 weeks of life, which was not clearly detected with the measurement of cystatin C.

Biomarkers of renal function in preterm neonates at 72h and 3weeks of life.

OBJECTIVE: Serum levels of creatinine in neonates are quite variable and suffer interference from the immature kidney and maternal creatinine concentration. The aim of this study was to measure novel biomarkers of glomerular and tubular function in healthy preterm neonates at 72h and 3 weeks of life. METHODS: Urine samples were collected in 40 preterm neonates with 28-34 incomplete weeks of gestational age. None of the participants had comorbidities, malformations and infections. The samples were collected at 72h of life and at 3 weeks after birth. Measurements of Calbindin, Collagen IV, FABP1, αGST, IP-10, KIM-1, Osteoactivin, Renin, TFF-3, TIMP-1, α-1-Microglobulin, Albumin, Clusterin, Cystatin C, EGF, Lipocalin-2/NGAL and Osteopontin were performed using panels 1 and 2 of multiplex kits of kidney injury. Data were analyzed using the software GraphPad Prism version 6.0. RESULTS: The preterm neonates included 55% of males with gestational age of 30±1 weeks. The most frequent maternal condition associated with preterm birth was preeclampsia (80%). Molecules related to glomerular function showed a significant increase in the concentrations obtained at 3 weeks of life compared to 72h of life. Markers related to tubular injury (KIM-1 and NGAL) also showed an increase. On the other hand, cystatin C did not change. CONCLUSION: The elevation of molecules related to glomerular function indicates an increase of glomerular filtration rate from 72h up until 3 weeks of life, which was not clearly detected with the measurement of cystatin C.

Fluconazole prophylaxis in preterm infants: a systematic review

ABSTRACT Objective: This article aims to review the use of antifungal prophylaxis with intravenous fluconazole in premature newborns and the occurrence of Invasive Candidiasis. Methods: This is a systematic review with search at databases: PubMed, Capes Portal, Virtual Health Library (BVS - Biblioteca Virtual em Saúde)/Lilacs, Scopus and Cochrane. The keywords used were: "Antifungal", "Candida" "Fluconazole prophylaxis" and "Preterm infants". Results: Invasive Candidiasis was evaluated in all the twelve items. In eleven of them, there was a statistically significant difference between the groups receiving prophylactic fluconazole, with lower frequency of Invasive Candidiasis, compared to placebo or no prophylaxis group. Colonization by Candida species was also evaluated in five studies; four of them presented statistically lower proportion of colonization in patients with Fluconazole prophylaxis, compared to placebo or no drugs. In one study, there was a significant difference, favoring the use of fluconazole, and reduction of death. Conclusion: Studies indicate the effectiveness of prophylaxis with fluconazole, with reduction in the incidence of colonization and invasive fungal disease. The benefits of prophylaxis should be evaluated considering the incidence of candidiasis in the unit, the mortality associated with candidiasis, the safety and toxicity of short and long-term medication, and the potential for development of resistant pathogens.

Fluconazole prophylaxis in preterm infants: a systematic review.

OBJECTIVE: This article aims to review the use of antifungal prophylaxis with intravenous fluconazole in premature newborns and the occurrence of Invasive Candidiasis. METHODS: This is a systematic review with search at databases: PubMed, Capes Portal, Virtual Health Library (BVS - Biblioteca Virtual em Saúde)/Lilacs, Scopus and Cochrane. The keywords used were: "Antifungal", "Candida" "Fluconazole prophylaxis" and "Preterm infants". RESULTS: Invasive Candidiasis was evaluated in all the twelve items. In eleven of them, there was a statistically significant difference between the groups receiving prophylactic fluconazole, with lower frequency of Invasive Candidiasis, compared to placebo or no prophylaxis group. Colonization by Candida species was also evaluated in five studies; four of them presented statistically lower proportion of colonization in patients with Fluconazole prophylaxis, compared to placebo or no drugs. In one study, there was a significant difference, favoring the use of fluconazole, and reduction of death. CONCLUSION: Studies indicate the effectiveness of prophylaxis with fluconazole, with reduction in the incidence of colonization and invasive fungal disease. The benefits of prophylaxis should be evaluated considering the incidence of candidiasis in the unit, the mortality associated with candidiasis, the safety and toxicity of short and long-term medication, and the potential for development of resistant pathogens.