Urinary exosomal miR-146a as a marker of albuminuria, activity changes and disease flares in lupus nephritis.

BACKGROUND: Urinary exosomes, especially microRNAs (miRNAs) packaged within, are ideal sources of renal damage markers. We investigated the association between exosomal miR-146a, (anti-inflammatory regulator) and disease activity, proteinuria and systemic lupus erythematosus (SLE) flares over a 36-month follow-up period. METHODS: We isolated urinary exosomes from 41 SLE patients, 27 with lupus nephritis (LN) and 20 healthy controls, and exosomal miR-146a, quantified by the real-time quantitative polymerase chain reaction (RT-qPCR), was correlated with histological features in 13 renal biopsies. We also analysed the association between the exosomal miR-146a and TRAF6 axis. RESULTS: Exosomal miR-146a showed an inverse association with circulating C3 and C4 complement components, proteinuria, and with histological features such as chronicity index. This marker was able to identify LN with an AUC of 0.82 (p = 0.001). Basal exosomal miR-146a was associated with disease activity and proteinuria changes and was an independent marker of 36-month follow-up flares (OR 7.08, p = 0.02). Pathway analysis identified IRAK1 and TRAF6 as miR-146a target genes. Finally, in vitro experiments suggested that miR-146a exerts a protective effect through negative regulation of inflammation by suppressing IRAK1 and TRAF6. CONCLUSIONS: Urinary exosomal miR-146a levels are correlated with lupus activity, proteinuria and histological features, discriminating patients with LN and being a good baseline marker of SLE flares. We have identified a relevant biological miR-146a-TRAF6 axis association in LN renal fibrosis progression.

Crizotinib and renal insufficiency: a case report and review of the literature.

A 69 year old man with idiopathic chronic kidney disease was diagnosed with relapsing EGFR negative, ALK positive lung adenocarcinoma, and treated with chemotherapy and antiangiogenic treatment, under which his renal insufficiency worsened. During second line crizotinib treatment, further worsening of the renal function was seen, with very clear correlation with crizotinib withdrawal and rechallenge. No further drug causes for the worsening blood creatinine values were detected.

Advancing in the management of chronic kidney disease: the results of implementing a quick resolution consultation.

BACKGROUND: Currently, chronic kidney disease (CKD) is understood as global important public health problem, a situation that requires a new approach. OBJECTIVES: To show the results obtained after implementing a quick resolution consultation for CKD management. METHODS: Results were analysed during 6 month time period. RESULTS: A total of 9.61% of received proposals were referred to primary care without in-person visits. In addition, 28.05% of patients were initially evaluated through high resolution clinics and 62.33% were directly referred to other clinics. From the initial 28.05% mentioned, once evaluated, treatment adjusted and informed about the disease, 70% were referred over to primary care for monitoring and the remaining 30% were given specialist appointments. As a consequence, 70.65% of patients were selected for monitoring by nephrology from all proposals received, and 29.35% for primary care monitoring. We observed a significant decrease in the delay until the first medical appointment. CONCLUSIONS: Quick resolution consultations demonstrated to be an efficient tool for CKD management. Its implementation allowed both low consumption of health care resources, selected patients with high risk of progressive cardiovascular disease for long term monitoring, and offered not only an initial evaluation and adjustment of treatment with information provided to those who would be monitored by primary care, but also diminished primary care delays significantly.