RESUMO
Myeloid-related proteins, MRP-8 and -14, which have been identified as molecules that mediate the danger signaling in innate immune response, are also known as the DAMPs (damage associated molecular pattern molecules). The proteins were found in infiltrating macrophages and neutrophils at inflammatory sites. Their expression was correlated with severe forms of glomerulonephritis. Therefore, this study examined whether or not MRP-8 and -14 can be used as biomarkers for identifying severely active lupus nephritis (LN). Total blood leukocyte samples and renal biopsy tissues from a prospective cohort of LN patients were used to determine mRNA and protein expression levels of MRP-8 and -14. The mRNA levels of MRP-8 and -14 in total blood leukocytes were significantly higher in active LN patients than quiescent LN patients and healthy controls. Moreover, the mRNA levels of MRP-8 and -14 in the total blood leukocytes and kidney tissues were significantly correlated with therapeutic response and the mRNA expression levels in the kidney were associated with an early loss of the kidney function. MRP-8 and -14 can be used as non-invasive prognostic biomarkers in patients with LN.
Assuntos
Transportadores de Cassetes de Ligação de ATP/sangue , Calgranulina B/sangue , Rim/metabolismo , Leucócitos/metabolismo , Nefrite Lúpica/sangue , Transportadores de Cassetes de Ligação de ATP/genética , Adulto , Biomarcadores/sangue , Biópsia , Calgranulina B/genética , Estudos Transversais , Humanos , Imuno-Histoquímica , Imunossupressores/uso terapêutico , Rim/efeitos dos fármacos , Rim/patologia , Leucócitos/efeitos dos fármacos , Estudos Longitudinais , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/genética , Estudos Prospectivos , RNA Mensageiro/sangue , Reação em Cadeia da Polimerase em Tempo Real , Índice de Gravidade de Doença , Resultado do Tratamento , Regulação para Cima , Adulto JovemRESUMO
The role of mycophenolate mofetil (MMF) is still controversial in the treatment of cyclophosphamide-resistant proliferative lupus nephritis (PLN). Enteric-coated mycophenolate sodium (EC-MPS) has less gastrointestinal adverse effects than MMF and is, therefore, increasingly utilised in organ transplantation. The aim of this study was to compare the efficacy and safety of EC-MPS versus an extended-course of intravenous cyclophosphamide (ED-IVCY) in resistant-type PLN. Thirty-one, biopsy-proven PLN, patients who failed to respond to an induction of IVCY were enrolled in a prospective, open-labelled, historically controlled study. Patients received 6 month of EC-MPS (720 mg b.i.d.) treatment. The patients in the ED-IVCY group, collected from a database, received a repeated 6-month course of monthly IVCY 0.5-1 g/m(2) of body surface area. Both groups received 0.5-1 mg/kg/day of prednisolone. Primary outcomes were partial or complete responses. A repeated kidney biopsy was performed to evaluate the histological response. No serious adverse events or patient deaths were observed during the study. Both groups had comparable baseline characteristics. At 6 months, the EC-MPS group had a comparable response rate with the ED-IVCY group. There were significantly less adverse events in the EC-MPS group. Repeated biopsies showed significant improvement in the EC-MPS group. EC-MPS provides salutary efficacy and safety in the treatment of resistant-type PLN and can be a suitably alternative treatment to ED-IVCY.
