ID3 contributes to cerebrospinal fluid seeding and poor prognosis in medulloblastoma

Background : The inhibitor of differentiation (ID) genes have been implicated as promoters of tumor progression and metastasis in many human cancers. The current study investigated the expression and functional roles of ID genes in seeding and prognosis of medulloblastoma. Methods : ID gene expression was screened in human medulloblastoma tissues. Knockdown of ID3 gene was performed in medulloblastoma cells in vitro. The expression of metastasis-related genes after ID3 knockdown was assessed. The effect of ID3 knockdown on tumor seeding was observed in an animal model in vivo. The survival of medulloblastoma patients was plotted according to the ID3 expression levels. Results : Significantly higher ID3 expression was observed in medulloblastoma with cerebrospinal fluid seeding than tumors without seeding. Knockdown of ID3 decreased proliferation, increased apoptosis, and suppressed the migration of D283 medulloblastoma cells in vitro. In a seeding model of medulloblastoma, ID3 knockdown in vivo with shRNA inhibited the growth of primary tumors, prevented the development of leptomeningeal seeding, and prolonged animal survival. High ID3 expression was associated with shorter survival of medulloblastoma patients, especially in Group 4 medulloblastomas. Conclusions : High ID3 expression is associated with medullolbastoma seeding and is a poor prognostic factor, especially in patients with Group 4 tumors. ID3 may represent the metastatic/ aggressive phenotype of a subgroup of medulloblastoma.This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government (MEST) (2012011770) and a grant (no.03-2011-008) from the Seoul National University Hospital Research Fund.Peer Reviewe

Mayo imaging classification is a good predictor of rapid progress among Korean patients with autosomal dominant polycystic kidney disease: results from the KNOW-CKD study

Background Mayo imaging classification (MIC) is a useful biomarker to predict disease progression in autosomal dominant polycystic kidney disease (ADPKD). This study was performed to validate MIC in the prediction of renal outcome in a prospective Korean ADPKD cohort and evaluate clinical parameters associated with rapid disease progression. Methods A total of 178 ADPKD patients were enrolled and prospectively observed for an average duration of 6.2 ± 1.9 years. Rapid progressor was defined as MIC 1C through 1E while slow progressor was defined as 1A through 1B. Renal composite outcome (doubling of serum creatinine, 50% decline of estimated glomerular filtration rate [eGFR], or initiation of renal replacement therapy) as well as the annual percent change of height-adjusted total kidney volume (mHTKV-α) and eGFR decline (mGFR-α) were compared between groups. Results A total of 110 patients (61.8%) were classified as rapid progressors. These patients were younger and showed a higher proportion of male patients. Rapid progressor was an independent predictor for renal outcome (hazard ratio, 4.09; 95% confidence interval, 1.23–13.54; p = 0.02). The mGFR-α was greater in rapid progressors (–3.58 mL/min per year in 1C, –3.7 in 1D, and –4.52 in 1E) compared with that in slow progressors (–1.54 in 1A and –2.06 in 1B). The mHTKV-α was faster in rapid progressors (5.3% per year in 1C, 9.4% in 1D, and 11.7% in 1E) compared with that in slow progressors (1.2% in 1A and 3.8% in 1B). Conclusion MIC is a good predictive tool to define rapid progressors in Korean ADPKD patients

KNOW-Ped CKD (KoreaN cohort study for outcomes in patients with pediatric CKD): Design and methods

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Background The global prevalence of chronic kidney disease (CKD) is increasing. In children, CKD exhibits unique etiologies and can have serious impacts on childrens growth and development. Therefore, an aggressive approach to preventing the progression of CKD and its complications is imperative. To improve the understanding and management of Asian pediatric patients with CKD, we designed and launched KNOW-Ped CKD (KoreaN cohort study for Outcome in patients With Pediatric Chronic Kidney Disease), a nationwide, prospective, and observational cohort study of pediatric CKD with funding from the Korean government. Methods/design From seven major centers, 450 patients <20 years of age with CKD stages I to V are recruited for the comprehensive assessment of clinical findings, structured follow-up, and bio-specimen collection. The primary endpoints include CKD progression, defined as a decline of estimated glomerular filtration rate by 50 %, and a requirement for renal replacement therapy or death. The secondary outcomes include the development of left ventricular hypertrophy or hypertension, impairment of growth, neuropsychological status, behavioral status, kidney growth, and quality of life. Discussion With this study, we expect to obtain more information on pediatric CKD, which can be translated to better management for the patients. Trial registration NCT02165878(ClinicalTrials.gov), submitted on June 11, 2014

Quality of life in patients with diabetic nephropathy: findings from the KNOW-CKD (Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease) cohort

Background Diabetic nephropathy (DN) can affect quality of life (QoL) because it requires arduous lifelong management. This study analyzed QoL differences between DN patients and patients with other chronic kidney diseases (CKDs). Methods The analysis included subjects (n = 1,766) from the KNOW-CKD (Korean Cohort Study for Outcomes in Patients with Chronic Kidney Disease) cohort who completed the Kidney Disease Quality of Life Short Form questionnaire. After implementing propensity score matching (PSM) using factors that affect the QoL of DN patients, QoL differences between DN and non-DN participants were examined. Results Among all DN patients (n = 390), higher QoL scores were found for taller subjects, and lower scores were found for those who were unemployed or unmarried, received Medical Aid, had lower economic status, had higher platelet counts or alkaline phosphatase levels, or used clopidogrel or insulin. After PSM, the 239 matched DN subjects reported significantly lower patient satisfaction (59.9 vs. 64.5, p = 0.02) and general health (35.3 vs. 39.1, p = 0.04) than the 239 non-DN subjects. Scores decreased in both groups during the 5-year follow-up, and the scores in the work status, sexual function, and role-physical domains were lower among DN patients than non-DN patients, though those differences were not statistically significant. Conclusion Socioeconomic factors of DN were strong risk factors for impaired QoL, as were high platelet, alkaline phosphatase, and clopidogrel and insulin use. Clinicians should keep in mind that the QoL of DN patients might decrease in some domains compared with non-DN CKDs

Cinacalcet lowering of serum fibroblast growth factor-23 concentration may be independent from serum Ca, P, PTH and dose of active vitamin D in peritoneal dialysis patients: a randomized controlled study

Background : Elevated serum level of fibroblast growth factor-23 (FGF23) is associated with adverse outcomes in dialyzed patients. Objectives : The CUPID study compared the efficacy of a cinacalcet-based regimen with conventional care (vitamin D and P binders) for achieving the stringent NKF-K/DOQI targets for peritoneal dialysis (PD) patients. Additionally, we analyzed change in FGF23 levels between two treatments to explore the cinacalcet effect in lowering FGF23. Design : Multicenter, open-labeled, randomized controlled study. Setting : Seven university-affiliated hospitals in Korea. Participants : Overall, 66 peritoneal dialysis patients were enrolled. Intervention : Sixty six patients were randomly assigned to treatment with either cinacalcet + oral vitamin D (cinacalcet group, n = 33) or oral vitamin D alone (control group, n = 33) to achieve K/DOQI targets. CUPID included a 4-week screening for vitamin D washout, a 12-week dose-titration, and a 4-week assessment phases. We calculated mean values of iPTH, Ca, P, Ca x P, during assessment phase and final FGF23 to assess the outcome. Main outcome measures : Achievement of >30% reduction of iPTH from baseline (primary) and FGF23 reduction (secondary). Results : 72.7% (n = 24) of the cinacalcet group and 93.9% (n = 31) of the control group completed the study. Cinacalcet group received 30.2 ± 18.0 mg/day of cinacalcet and 0.13 ± 0.32 μg/d oral vitamin D (P < 0.001 vs. control with 0.27 ± 0.18 μg/d vitamin D). The proportion of patients who reached the primary endpoint was not statistically different (48.5% vs. 51.5%, cinacalcet vs. control, P = 1.000). After treatment, cinacalcet group experienced a significant reduction in FGF23 levels (median value from 3,960 to 2,325 RU/ml, P = 0.002), while an insignificant change was shown for control group (from 2,085 to 2,415 RU/ml). The percent change of FGF23 after treatment was also significantly different between the two groups (− 42.54% vs. 15.83%, P = 0.008). After adjustment, cinacalcet treatment was independently associated with the serum FGF23 reduction. Conclusion : Cinacalcet treatment was independently associated with the reduction of FGF23 in our PD patients.The CUPID study was funded by Kyowa Kirin, Korea. However, the funding body had no role in the design, implementation, analysis of the study. Presented at the Kidney Week 2012 of the American Society of Nephrology, San Diego, CA, October 30- November 4, 2012. We thank the Medical Research Collaborating Center (MRCC), Seoul National University Hospital for the statistical advice.Peer Reviewe

Development of predictive score for post-transplant survival based on pre-transplant recipient characteristics

Background : The new kidney allocation system in the United States has introduced longevity matching, which gives priority to allocating the best quality organs to wait-listed candidates with the longest predicted survival for the efficient utilization of organs that are of limited availability. The estimated post-transplant survival (EPTS) score was developed in the United States to risk-stratify all wait-listed patients. However, prognostic indices used in Western countries were derived from data that may be different for Korea and do not necessarily reflect prognostic values for Korean deceased donor kidney transplantation. Prognostic indices for Korean wait-listed candidates therefore need to be developed from Korean data. Methods : We analyzed 6,731 adult solitary kidney transplant patients for candidate risk prediction using the national data from the Korean Network for Organ Sharing (KONOS) and National Health Insurance Data Sharing Service (NHISS). Cox regression analysis was used to model the risk of patient death. Results : The Korean EPTS (K-EPTS) score was developed based on four recipient parameters (age, diabetes mellitus, hepatitis C virus, and duration of dialysis) that showed a significant association with post-transplant survival. K-EPTS scores showed good discrimination (C-statistics: 0.690; 95% confidence interval, 0.666–0.715). Moreover, the ability of the K-EPTS score to discriminate patient survival was better than that of the EPTS according to the criteria of the United Network for Organ Sharing (US-EPTS) score (P<0.001). Conclusions: The K-EPTS score, which was developed based on Korean national data, is expected to contribute to the assessment of recipient prognosis and efficient utilization of deceased donor kidneys