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  • 1
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    Biobanking for glomerular diseases: a study design and protocol for KOrea Renal biobank NEtwoRk System TOward NExt-generation analysis (KORNERSTONE)
    Springer Science and Business Media LLC ; 2020
    In:  BMC Nephrology Vol. 21, No. 1 ( 2020-12)
    Details
    In: BMC Nephrology, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2020-12)
    Abstract: Glomerular diseases, a set of debilitating and complex disease entities, are related to mortality and morbidity. To gain insight into pathophysiology and novel treatment targets of glomerular disease, various types of biospecimens linked to deep clinical phenotyping including clinical information, digital pathology, and well-defined outcomes are required. We provide the rationale and design of the KOrea Renal biobank NEtwoRk System TOward Next-generation analysis (KORNERSTONE). Methods The KORNERSTONE, which has been initiated by Korea Centres for Disease Control and Prevention, is designed as a multi-centre, prospective cohort study and biobank for glomerular diseases. Clinical data, questionnaires will be collected at the time of kidney biopsy and subsequently every 1 year after kidney biopsy. All of the clinical data will be extracted from the electrical health record and automatically uploaded to the web-based database. High-quality digital pathologies are obtained and connected in the database. Various types of biospecimens are collected at baseline and during follow-up: serum, urine, buffy coat, stool, glomerular complementary DNA (cDNA), tubulointerstitial cDNA. All data and biospecimens are processed and stored in a standardised manner. The primary outcomes are mortality and end-stage renal disease. The secondary outcomes will be deterioration renal function, remission of proteinuria, cardiovascular events and quality of life. Discussion Ethical approval has been obtained from the institutional review board of each participating centre and ethics oversight committee. The KORNERSTONE is designed to deliver pioneer insights into glomerular diseases. The study design allows comprehensive, integrated and high-quality data collection on baseline laboratory findings, clinical outcomes including administrative data and digital pathologic images. This may provide various biospecimens and information to many researchers, establish the rationale for future more individualised treatment strategies for glomerular diseases. Trial registration NCT03929887 .
    Type of Medium: Online Resource
    ISSN: 1471-2369
    URL: Article
    DOI: 10.1186/s12882-020-02016-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2041348-8
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  • 2
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    Clinical implications of changes in metabolic syndrome status after kidney transplantation: a nationwide prospective cohort study
    Oxford University Press (OUP) ; 2023
    In:  Nephrology Dialysis Transplantation ( 2023-05-26)
    Details
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), ( 2023-05-26)
    Abstract: Metabolic syndrome (MetS) is prevalent in patients with end-stage kidney disease, and kidney transplantation is expected to modify the metabolic status. However, whether changes in metabolic status at the time of transplantation affect recipient outcomes remains unclear. Methods We analyzed 4187 recipients registered in a nationwide prospective cohort from 2014 to 2020. MetS was defined as the presence of three or more components of the metabolic syndrome. Patients were classified based on the pre- and post-transplant MetS status: MetS-free, MetS-developed, MetS-recovered and MetS-persistent. Study outcomes were occurrence of death-censored graft loss and a composite of cardiovascular events and death. Results Among recipients without pre-transplant MetS, 19.6% (419/2135) developed post-transplant MetS, and MetS disappeared in 38.7% (794/2052) of the recipients with pre-transplant MetS. Among the four groups, the MetS-developed group showed the worst graft survival rate, and the MetS-persistent group had a poorer composite event-free survival rate. Compared with the MetS-free group, the MetS-developed group was associated with an increased risk of graft loss [adjusted hazard ratio (aHR) 2.35; 95% confidence interval (CI) 1.17–4.98] and the risk of graft loss increased with increasing numbers of dysfunctional MetS components. MetS-persistent was associated with increased risks of cardiovascular events and death (aHR 2.46; 95% CI 1.12–5.63), but changes in the number of dysfunctional MetS components was not. Conclusion Kidney transplantation significantly alters the metabolic status. Newly developed MetS after transplantation was associated with an increased risk of graft loss, whereas persistent MetS exposure before and after transplantation was associated with increased risks cardiovascular events and patient survival.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    URL: Article
    DOI: 10.1093/ndt/gfad115
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1465709-0
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  • 3
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    P0502BIOBANKING FOR GLOMERULAR DISEASES: A STUDY DESIGN AND PROTOCOL FOR KOREA RENAL BIOBANK NETWORK SYSTEM TOWARD NEXT-GENERATION ANALYSIS (KORNERSTONE)
    Oxford University Press (OUP) ; 2020
    In:  Nephrology Dialysis Transplantation Vol. 35, No. Supplement_3 ( 2020-06-01)
    Details
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 35, No. Supplement_3 ( 2020-06-01)
    Abstract: Glomerular diseases, a set of debilitating and complex disease entities, are related to mortality and morbidity. To gain insight into pathophysiology and novel treatment targets of glomerular disease, various types of biospecimens linked to deep clinical phenotyping including clinical information, digital pathology, and well-defined outcomes are required. We provide the rationale and design of the KOrea Renal biobank NEtwoRk System TOward Next-generation analysis (KORNERSTONE). Method The KORNERSTONE, which has been initiated by Korea Centres for Disease Control and Prevention, is designed as a multi-centre, prospective cohort study and biobank for glomerular diseases. Clinical data, questionnaires will be collected at the time of kidney biopsy and subsequently every one year after kidney biopsy. All of the clinical data will be extracted from the electrical health record and automatically uploaded to the web-based database. High-quality digital pathologies are obtained and connected in the database. Various types of biospecimens are collected at baseline and during follow-up: serum, urine, buffy coat, stool, glomerular complementary DNA (cDNA), tubulointerstitial cDNA. All data and biospecimens are processed and stored in a standardised manner. The primary outcomes are mortality and end-stage renal disease. The secondary outcomes will be deterioration renal function, remission of proteinuria, cardiovascular events and quality of life. Disussion Ethical approval has been obtained from the institutional review board of each participating centre and ethics oversight committee. The KORNERSTONE is designed to deliver pioneer insights into glomerular diseases. The study design allows comprehensive, integrated and high-quality data collection on baseline laboratory findings, clinical outcomes including administrative data and digital pathologic images. This may provide various biospecimens and information to many researchers, establish the rationale for future more individualised treatment strategies for glomerular diseases. Conclusion In conclusion, we describe the objectives and clinical protocol for the KORNERSTONE. As the first large-scale glomerulonephropathy cohort study with the integration of clinical data, biospecimens and digital pathologic images in Korea, the KORNERSTONE will help to clarify the natural course, complication profiles, and novel treatment targets of the Asian population with glomerular disease.
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    URL: Article
    DOI: 10.1093/ndt/gfaa142.P0502
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 4
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    Renoprotective effects of a novel cMet agonistic antibody on kidney fibrosis
    Springer Science and Business Media LLC ; 2019
    In:  Scientific Reports Vol. 9, No. 1 ( 2019-09-17)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2019-09-17)
    Abstract: Hepatocyte growth factor (HGF) and its receptor, cMet, activate biological pathways necessary for repair and regeneration following kidney injury. Because HGF is a highly unstable molecule in its biologically active form, we asked whether a monoclonal antibody (Ab) that displays full agonist activity at the receptor could protect the kidney from fibrosis. We attempted to determine whether the cMet agonistic Ab might reduce fibrosis, the final common pathway for chronic kidney diseases (CKD). A mouse model of kidney fibrosis disease induced by unilateral ureteral obstruction was introduced and subsequently validated with primary cultured human proximal tubular epithelial cells (PTECs). In kidney biopsy specimens from patients with CKD, cMet immunohistochemistry staining showed a remarkable increase compared with patients with normal renal functions. cMet Ab treatment significantly increased the levels of phospho-cMet and abrogated the protein expression of fibrosis markers such as fibronectin, collagen 1, and αSMA as well as Bax2, which is a marker of apoptosis triggered by recombinant TGF-β1 in PTECs. Remarkably, injections of cMet Ab significantly prevented kidney fibrosis in obstructed kidneys as quantified by Masson trichrome staining. Consistent with these data, cMet Ab treatment decreased the expression of fibrosis markers, such as collagen1 and αSMA, whereas the expression of E-cadherin, which is a cell-cell adhesion molecule, was restored. In conclusion, cMet-mediated signaling may play a considerable role in kidney fibrosis. Additionally, the cMet agonistic Ab may be a valuable substitute for HGF because it is more easily available in a biologically active, stable, and purified form.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-019-49756-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2615211-3
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  • 5
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    cMet agonistic antibody attenuates apoptosis in ischaemia‐reperfusion–induced kidney injury
    Wiley ; 2020
    In:  Journal of Cellular and Molecular Medicine Vol. 24, No. 10 ( 2020-05), p. 5640-5651
    Details
    In: Journal of Cellular and Molecular Medicine, Wiley, Vol. 24, No. 10 ( 2020-05), p. 5640-5651
    Abstract: Acute kidney injury (AKI) is a very common complication with high morbidity and mortality rates and no fundamental treatment. In this study, we investigated whether the hepatocyte growth factor (HGF)/cMet pathway is associated with the development of AKI and how the administration of a cMet agonistic antibody (Ab) affects an AKI model. In the analysis using human blood samples, cMet and HGF levels were found to be significantly increased in the AKI group, regardless of underlying renal function. The administration of a cMet agonistic Ab improved the functional and histological changes after bilateral ischaemia‐reperfusion injury. TUNEL‐positive cells and Bax/Bcl‐2 ratio were also reduced by cMet agonistic Ab treatment. In addition, cMet agonistic Ab treatment significantly increased the levels of PI3K, Akt and mTOR. Furthermore, after 24 hours of hypoxia induction in human proximal tubular epithelial cells, treatment with the cMet agonistic Ab also showed dose‐dependent antiapoptotic effects similar to those of the recombinant HGF treatment. Even when the HGF axis was blocked with a HGF‐blocking Ab, the cMet agonistic Ab showed an independent dose‐dependent antiapoptotic effect. In conclusion, cMet expression is associated with the occurrence of AKI. cMet agonistic Ab treatment attenuates the severity of AKI through the PI3K/Akt/mTOR pathway and improves apoptosis. cMet agonistic Ab may have important significance for the treatment of AKI.
    Type of Medium: Online Resource
    ISSN: 1582-1838 , 1582-4934
    URL: Issue
    URL: Article
    DOI: 10.1111/jcmm.v24.10
    DOI: 10.1111/jcmm.15225
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2076114-4
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  • 6
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    The Role of TNF Superfamily Member 13 in the Progression of IgA Nephropathy
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Journal of the American Society of Nephrology Vol. 27, No. 11 ( 2016-11), p. 3430-3439
    Details
    In: Journal of the American Society of Nephrology, Ovid Technologies (Wolters Kluwer Health), Vol. 27, No. 11 ( 2016-11), p. 3430-3439
    Abstract: TNF superfamily member 13 (TNFSF13) has been identified as a susceptibility gene for IgA nephropathy in recent genetic studies. However, the role of TNFSF13 in the progression of IgA nephropathy remains unresolved. We evaluated two genetic polymorphisms (rs11552708 and rs3803800) and plasma levels of TNFSF13 in 637 patients with IgA nephropathy, and determined the risk of ESRD according to theses variable. Neither of the examined genetic polymorphisms associated with a clinical outcome of IgA nephropathy. However, high plasma levels of TNFSF13 increased the risk of ESRD. To explore the causal relationship and underlying mechanism, we treated B cells from patients ( n =21) with or without recombinant human TNFSF13 (rhTNFSF13) and measured the expression of IgA and galactose-deficient IgA (GdIgA) using ELISA and flow cytometry. Treatment with rhTNFSF13 significantly increased the total IgA level among B cells, and TNFSF13 receptor blockade abrogated this increase. Furthermore, the absolute levels of GdIgA increased with rhTNFSF13 treatment, but the total IgA-normalized levels did not change. Both RNA sequencing and quantitative PCR results showed that rhTNFSF13 did not alter the expression of glycosyltransferase enzymes. These results suggest that high plasma TNFSF13 levels associate with a worse prognosis of IgA nephropathy through the relative increase in GdIgA levels.
    Type of Medium: Online Resource
    ISSN: 1046-6673 , 1533-3450
    URL: Article
    DOI: 10.1681/ASN.2015060677
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 2029124-3
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  • 7
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    Effect of pretransplant dialysis vintage on clinical outcomes in deceased donor kidney transplant
    Springer Science and Business Media LLC ; 2022
    In:  Scientific Reports Vol. 12, No. 1 ( 2022-10-21)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-10-21)
    Abstract: The waiting time for deceased donor kidney transplants (DDKT) is increasing. We evaluated DDKT prognosis according to the pretransplant dialysis vintage. A total of 4117 first-time kidney transplant recipients were enrolled from a prospective nationwide cohort in Korea. DDKT recipients were divided into tertiles according to pretransplant dialysis duration. Graft failure, mortality, and composite were compared between DDKT and living donor kidney transplant (LDKT) recipients. Pretransplant dialysis vintage was longer annually in DDKT recipients. In the subdistribution of the hazard model for the competing risk, the first tertile did not show an increased risk of graft failure compared with LDKT recipients; however, the second and third tertile groups had an increased risk of graft failure compared to LDKT recipients (adjusted hazard ratio [aHR] 3.59; 95% confidence interval [CI] 1.69–7.63; P   〈  0.001; aHR 2.37; 95% CI 1.06–5.33; P  = 0.037). All DDKT groups showed a significantly higher risk of patient death than LDKT, with the highest risk in the third tertile group (aHR 11.12; 95% CI 4.94–25.00; P   〈  0.001). A longer pretransplant dialysis period was associated with a higher risk of the composite of patient death and graft failure in DDKT recipients. DDKT after a short period of dialysis had non-inferior results on graft survival compared with LDKT.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-022-20003-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2615211-3
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  • 8
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    Urinary cMet as a prognostic marker in immunoglobulin A nephropathy
    Wiley ; 2020
    In:  Journal of Cellular and Molecular Medicine Vol. 24, No. 19 ( 2020-10), p. 11158-11169
    Details
    In: Journal of Cellular and Molecular Medicine, Wiley, Vol. 24, No. 19 ( 2020-10), p. 11158-11169
    Abstract: The prediction of prognosis in patients with immunoglobulin A nephropathy (IgAN) is challenging. We investigated the correlation between urinary cMet (ucMet) levels and clinical parameters and examined the effects of cMet agonistic antibody (cMet Ab) in an in vitro IgAN model. Patients diagnosed with IgAN (n = 194) were divided into three groups representing undetectable (Group 1), below‐median (Group 2) and above‐median (Group 3) levels of ucMet/creatinine (ucMet/Cr). Stained kidney biopsy samples were graded according to cMet intensity. Primary‐cultured human mesangial cells were stimulated with recombinant tumour necrosis factor (TNF)‐α and treated with cMet Ab. Our results showed that ucMet/Cr levels positively correlated with proteinuria ( P   〈  .001). During the follow‐up, patients in Group 3 showed a significantly lower probability of complete remission (CR; uPCr  〈  300 mg/g) than those in groups 1 and 2, after adjusting for blood pressure, estimated glomerular filtration rate, and proteinuria, which influence clinical prognosis (HR 0.60, P  = .038); moreover, ucMet/Cr levels were also associated with glomerular cMet expression. After TNF‐α treatment, the proliferation of mesangial cells and increased interleukin‐8 and intercellular adhesion molecule‐1 expression were markedly reduced by cMet Ab in vitro. In conclusion, ucMet/Cr levels significantly correlated with proteinuria, glomerular cMet expression, and the probability of CR. Further, cMet Ab treatment alleviated the inflammation and proliferation of mesangial cells. Hence, ucMet could serve as a clinically significant marker for treating IgAN.
    Type of Medium: Online Resource
    ISSN: 1582-1838 , 1582-4934
    URL: Issue
    URL: Article
    DOI: 10.1111/jcmm.v24.19
    DOI: 10.1111/jcmm.15636
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2076114-4
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  • 9
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    Evaluating anti-thymocyte globulin induction doses for better allograft and patient survival in Asian kidney transplant recipients
    Springer Science and Business Media LLC ; 2023
    In:  Scientific Reports Vol. 13, No. 1 ( 2023-08-02)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2023-08-02)
    Abstract: Anti-thymocyte globulin (ATG) is currently the most widely prescribed induction regimen for preventing acute rejection after solid organ transplantation. However, the optimal dose of ATG induction regimen in Asian kidney recipients is unclear. Using the Korean Organ Transplantation Registry, we performed a retrospective cohort study of 4579 adult patients who received renal transplantation in South Korea and divided them into three groups according to the induction regimen: basiliximab group (n = 3655), low-dose ATG group (≤ 4.5 mg/kg; n = 467), and high-dose ATG group ( 〉  4.5 mg/kg; n = 457). We applied the Toolkit for Weighting and Analysis of Nonequivalent Groups (TWANG) package to generate high-quality propensity score weights for intergroup comparisons. During four-year follow-ups, the high-dose ATG group had the highest biopsy-proven acute rejection rate (basiliximab 20.8% vs. low-dose ATG 22.4% vs. high-dose ATG 25.6%; P  〈  0.001). However, the rates of overall graft failure (4.0% vs. 5.0% vs. 2.6%; P  〈  0.001) and mortality (1.7% vs. 2.8% vs. 1.0%; P  〈  0.001) were the lowest in the high-dose ATG group. Our results show that high-dose ATG induction ( 〉  4.5 mg/kg) was superior to basiliximab and low-dose ATG induction in terms of graft and patient survival in Asian patients undergoing kidney transplant.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-023-39353-6
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2615211-3
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  • 10
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    Dominant predictors of early post-transplant outcomes based on the Korean Organ Transplantation Registry (KOTRY)
    Springer Science and Business Media LLC ; 2022
    In:  Scientific Reports Vol. 12, No. 1 ( 2022-05-24)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-05-24)
    Abstract: Data for Asian kidney transplants are very limited. We investigated the relative importance of prognostic markers in Asian kidney transplants by using Korean Organ Transplantation Registry (KOTRY) cohort. Prediction models were developed by data-driven variable selection approach. The relative importance of the selected predictors was measured by dominance analysis. A total of 4854 kidney transplant donor-recipient pairs were analyzed. Overall patient survival rates were 99.8%, 98.8%, and 91.8% at 1, 3, and 5 years, respectively. Death-censored graft survival rates were 98.4%, 97.0%, and 95.8% at 1, 3, and 5 years. Biopsy-proven acute rejection free survival rates were 90.1%, 87.4%, and 87.03% at 1, 3, and 5 years. The top 3 dominant predictors for recipient mortality within 1 year were recipient cardiovascular disease history, deceased donor, and recipient age. The dominant predictors for death-censored graft loss within 1 year were acute rejection, deceased donor, and desensitization. The dominant predictors to acute rejection within 1 year were donor age, HLA mismatched numbers, and desensitization. We presented clinical characteristics of patients enrolled in KOTRY during the last 5 years and investigated dominant predictors for early post-transplant outcomes, which would be useful for clinical decision-making based on quantitative measures.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-022-12302-5
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2615211-3
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