RESUMEN
INTRODUCTION: Congenital chloride diarrhoea (CCD) is an autosomal recessive condition that causes secretory diarrhoea and potentially deadly electrolyte imbalances in infants because of solute carrier family 26 member 3 (SLC26A3) gene mutations. CASE PRESENTATION: A 7-month-old Chinese infant with a history of maternal polyhydramnios presented with frequent watery diarrhoea, severe dehydration, hypokalaemia, hyponatraemia, failure to thrive, metabolic alkalosis, hyperreninaemia, and hyperaldosteronaemia. Genetic testing revealed a compound heterozygous SLC26A3 gene mutation in this patient (c.269_270dup and c.2006 C > A). Therapy was administered in the form of oral sodium and potassium chloride supplements, which decreased stool frequency. CONCLUSIONS: CCD should be considered when an infant presents with prolonged diarrhoea during infancy, particularly in the context of maternal polyhydramnios and dilated foetal bowel loops.
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Diarrea , Diarrea/congénito , Errores Innatos del Metabolismo , Mutación , Transportadores de Sulfato , Humanos , Transportadores de Sulfato/genética , Diarrea/genética , Lactante , Errores Innatos del Metabolismo/genética , Errores Innatos del Metabolismo/diagnóstico , Antiportadores de Cloruro-Bicarbonato/genética , Femenino , Heterocigoto , Masculino , Polihidramnios/genética , Cloruro de Potasio/uso terapéutico , Cloruro de Potasio/administración & dosificación , Pueblos del Este de AsiaRESUMEN
OBJECTIVE: The clinical characteristics, genetic mutation spectrum, treatment strategies and prognoses of 15 children with Dent disease were retrospectively analyzed to improve pediatricians' awareness of and attention to this disease. METHODS: We analyzed the clinical and laboratory data of 15 Chinese children with Dent disease who were diagnosed and treated at our hospital between January 2017 and May 2023 and evaluated the expression of the CLCN5 and OCRL1 genes. RESULTS: All 15 patients were male and complained of proteinuria, and the incidence of low-molecular-weight proteinuria (LMWP) was 100.0% in both Dent disease 1 (DD1) and Dent disease 2 (DD2) patients. The incidence of hypercalciuria was 58.3% (7/12) and 66.7% (2/3) in DD1 and DD2 patients, respectively. Nephrocalcinosis and nephrolithiasis were found in 16.7% (2/12) and 8.3% (1/12) of DD1 patients, respectively. Renal biopsy revealed focal segmental glomerulosclerosis (FSGS) in 1 patient, minimal change lesion in 5 patients, and small focal acute tubular injury in 1 patient. A total of 11 mutations in the CLCN5 gene were detected, including 3 missense mutations (25.0%, c.1756C > T, c.1166T > G, and c.1618G > A), 5 frameshift mutations (41.7%, c.407delT, c.1702_c.1703insC, c.137delC, c.665_666delGGinsC, and c.2200delG), and 3 nonsense mutations (25.0%, c.776G > A, c.1609C > T, and c.1152G > A). There was no significant difference in age or clinical phenotype among patients with different mutation types (p > 0.05). All three mutations in the OCRL1 gene were missense mutations (c.1477C > T, c.952C > T, and c.198A > G). CONCLUSION: Pediatric Dent disease is often misdiagnosed. Protein electrophoresis and genetic testing can help to provide an early and correct diagnosis.
Asunto(s)
Canales de Cloruro , Enfermedad de Dent , Monoéster Fosfórico Hidrolasas , Humanos , Masculino , Niño , Canales de Cloruro/genética , Estudios Retrospectivos , Preescolar , China/epidemiología , Enfermedad de Dent/genética , Enfermedad de Dent/diagnóstico , Monoéster Fosfórico Hidrolasas/genética , Mutación , Proteinuria/genética , Adolescente , Hipercalciuria/genética , Nefrocalcinosis/genética , Nefrolitiasis/genética , Lactante , Pruebas Genéticas , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Mutación Missense , Femenino , Glomeruloesclerosis Focal y Segmentaria/genética , Riñón/patología , Pueblos del Este de AsiaRESUMEN
In this study, we investigated the nephroprotective effects of Umbelliferone (UMB) against cisplatin-induced acute kidney injury (AKI). C57BL/6J mice were treated with cisplatin via a single intraperitoneal injection (25 mg/kg) with or without UMB (40 mg/kg/day) by gavage. Renal function, apoptosis, oxidative stress, inflammation, and mitochondrial function were analyzed to evaluate kidney injury. In vitro, human proximal tubule epithelial cells were treated with cisplatin, with or without UMB, for 24 h. Western blotting and immunohistochemistry were performed to explore the mechanisms underlying the nephroprotective effects of UMB. Cisplatin-induced renal dysfunction, including increases in blood urea nitrogen, serum creatinine, and renal tubular injury indices (NGAL and KIM-1), were significantly attenuated by UMB treatment, along with renal phenotypic changes and renal tubular injury, as evidenced by improved renal histology. Moreover, NRF2 was activated by UMB pretreatment, along with the inhibition of oxidative stress and inflammatory response, as evidenced by decreased levels of antioxidant genes and inflammatory cytokines in cisplatin-induced AKI. Our results demonstrate that UMB can protect against cisplatin-induced nephrotoxicity, which is mediated by the NRF2 signaling pathway via antioxidant and anti-inflammatory activities, suggesting the clinical potential of UMB for the treatment of AKI.