Background While lupus nephritis (LN) is more common with higher severity and mortality in children than in adult-onset disease, data regarding long-term outcome of childhood-onset LN is rare. ...Methods Long-term renal outcome and their treatment were assessed in 57 Korean childhood-onset LN patients diagnosed between 1999 and 2020 from a tertiary single center in Korea. Results Median age at diagnosis of LN was 14.5 (range 7.8–17.8) years. Median follow-up period was 135 (30–266) months. 26.3% (15/57) of patients progressed to chronic kidney disease (CKD) stage 3–5 (CKD stage 3: 6 patients, stage 4: 1 patient, stage 5: 8 patients). 10-year renal survival was 100% in patients diagnosed after 2011, compared to 80.3% in patients diagnosed before 2011 (p=0.049). Comparing the two eras, there were no clear difference between the laboratory finding at diagnosis, the drug used, and the cumulative dose of cyclophosphamide or hydroxychloroquine, except that primary renal response rate was higher at the latter era (55.2% vs 82.1%, p=0.029), and the diagnosis age was slightly younger in the earlier era (median 13.5 vs 14.6, p=0.056). Hydroxychloroquine use was significantly associated with maintaining renal estimated glomerular filtration rate (eGFR) higher than 60ml/min/m2 at 10 years (95.2% vs 77.2%), and 20 years (68.6% vs 16.1%), respectively (p= 0.033). Conclusions Early diagnosis and timely adequate treatment, and the use of hydroxychloroquine are important in the long-term kidney prognosis of childhood-onset LN.
Diabetic nephropathy (DN) is a major healthcare challenge. It occurs in up to 50% of those living with diabetes, is a major cause of end‐stage kidney disease (ESKD) that requires treatment with ...dialysis or renal transplantation, and is associated with significantly increased cardiovascular morbidity and mortality. DN is a clinical syndrome characterized by persistent albuminuria and a progressive decline in renal function, but it is increasingly recognized that the presentation and clinical course of kidney disease in diabetes is heterogeneous. The term diabetic kidney disease (DKD) is now commonly used to encompass the spectrum of people with diabetes who have either albuminuria or reductions in renal function. In this article, the clinical presentation and approach to diagnosis of DKD will be discussed, as will its prognosis. The general principles of management of DKD will also be reviewed with reference to current international guidelines.
Abstract
INTRODUCTION
Medulloblastoma (MB) is the most common malignant brain tumor in children. Although accumulated research suggests that cancer stem-like cells may play a key role in ...medullolastoma tumorigenesis, the molecular mechanisms of proliferation still remain elusive and further investigation can provide a novel application for therapeutic target in MB patients.
METHODS
The expression of MELK and EZH2 was detected by tissue microarray analysis with 88 MBs and its association with prognosis was identified. Co-location of MELK and EZH2 in MB CSCs and tissues was studied by using confocal and immunostaining. Immunoblotting analysis following co-immunoprecipitation was performed to check the interaction between MELK and EZH2. Through the loss-of-function study by siRNA, CSCs-drived tumor growth was detected. Then we studied the targeted treatment of MB with MELK and EZH2 inhibitor in vivo to confirm the molecular basis of MELK and EZH2.
RESULTS
>MELK and EZH2 co-located in the nuclei of MB CSCs and MB with extensive nodularity and large cell/anaplastic differed the staining levels as measured using microarray analysis when compared with the other two subgroups. The proportion of MELK positive staining cells was the potential indicator for the survival. MELK bound and phosphorylated EZH2 and its methylation was induced by EZH2 in MB, which regulated the proliferation of CSCs. MELK and EZH2 depletion by siRNA or treatment of inhibitors attenuated the MB CSCs-derived tumor growth in vivo.
CONCLUSION
Interaction between MELK and EZH2 is essential for MB CSCs-drived tumor proliferation, thereby identifying a potential therapeutic strategy for MB patients.
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