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1.
BMC Nephrol ; 20(1): 214, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31185945

RESUMO

BACKGROUND: Many studies have evaluated the usefulness of creatinine- (eGFRcr) and cystatin C-based estimated glomerular filtration rate (eGFRcys) at specific time points in predicting renal outcome. This study compared the performance of both eGFR changing slopes in identifying patients at high risk of end-stage renal disease (ESRD). METHODS: From 2012 to 2017, patients with more than three simultaneous measurements of serum creatinine and cystatin C for 1 year were identified. Rapid progression was defined as eGFR slope < - 5 mL/min/1.73 m2/year. The primary outcome was progression to ESRD. RESULTS: Overall, 1323 patients were included. The baseline eGFRcr and eGFRcys were 39 (27-48) and 38 (27-50) mL/min/1.73 m2, respectively. Over 2.9 years (range, 2.0-3.8 years) of follow-up, 134 subjects (10%) progressed to ESRD. Both the eGFRcr and eGFRcys slopes were associated with a higher risk of ESRD, independently of baseline eGFR (hazard ratio [HR] = 0.986 [0.982-0.991] and HR = 0.988 [0.983-0.993], respectively; all p <  0.001). The creatinine- and cystatin C-based rapid progressions were associated with increased risk of ESRD (HR = 2.22 [1.57-3.13], HR = 2.03 [1.44-2.86], respectively; all p <  0.001). In the subgroup analyses, the rapid progression group, defined on the basis of creatinine levels (n = 503), showed no association between the eGFRcys slope and ESRD risk (p = 0.31), whereas the eGFRcr slope contributed to further discriminating higher ESRD risk in the subjects with rapid progression based on eGFRcys slopes (n = 463; p = 0.003). CONCLUSIONS: Both eGFR slopes were associated with future ESRD risk. The eGFRcr slope was comparable with the eGFRcys slope in predicting kidney outcome.


Assuntos
Creatinina/sangue , Cistatina C/sangue , Taxa de Filtração Glomerular , Falência Renal Crônica , Insuficiência Renal Crônica , Progressão da Doença , Feminino , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Prognóstico , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco
2.
Vascular ; 27(2): 128-134, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30360702

RESUMO

OBJECTIVES: Arteriovenous graft for hemodialysis shows poorer outcomes than arteriovenous fistula, due to frequent stenosis and thrombosis. We investigated arteriovenous graft patency outcomes and prognostic factors for these outcomes. METHODS: We included a single-center cohort of patients receiving arteriovenous graft for hemodialysis access from 2010 to 2014. Demographics, laboratory data, comorbidities, and medications were collected from medical records. Surgical factors related to graft operation including the type and diameter of connected vessels, graft location, and type of operation (elective or emergency) were also recorded. Outcomes included primary and secondary patency. Survival analysis was conducted using the Kaplan-Meier method; univariate and multivariate analyses were used to evaluate the prognostic factors. RESULTS: Data from 225 grafts were analyzed. During the follow-up period (mean: 583 days, range: 1-1717 days), 138 (61%) grafts required intervention and 46 (20%) permanently failed. Primary patency at one, two, and three years was 42%, 20%, and 16%, respectively. Secondary patency at one, two, and three years was 85%, 72%, and 64%, respectively. Multivariate analysis showed that primary patency was negatively associated with increasing age and location of vessel anastomosis (reference-brachiobrachial anastomosis; brachiobasilic - HR, 0.569; 95% CI, 0.376-0.860; p = 0.007; brachioaxillary anastomosis - HR 0.407; 95% CI, 0.263-0.631; p < 0.0001); secondary patency was positively associated with diastolic blood pressure, serum albumin level, and hemoglobin over 10 g/dL. Adverse events other than stenosis or thrombosis, such as infection/inflammation or pseudoaneurysm were observed in approximately 20% of grafts. CONCLUSIONS: Factors associated with diminished primary arteriovenous graft patency included increased patient age and location of vessel anastomosis (brachiobrachial type compared to brachiobasilic or brachioaxillary type); diminished secondary patency was associated with low diastolic blood pressure, low serum albumin, and hemoglobin level under 10 g/dL. Among these factors, diastolic blood pressure, serum albumin, and hemoglobin level may be modifiable and could improve arteriovenous graft patency outcomes.


Assuntos
Derivação Arteriovenosa Cirúrgica/efeitos adversos , Oclusão de Enxerto Vascular/etiologia , Diálise Renal , Trombose/etiologia , Grau de Desobstrução Vascular , Idoso , Feminino , Oclusão de Enxerto Vascular/diagnóstico , Oclusão de Enxerto Vascular/fisiopatologia , Oclusão de Enxerto Vascular/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Trombose/diagnóstico , Trombose/fisiopatologia , Trombose/terapia , Fatores de Tempo , Resultado do Tratamento
3.
J Clin Microbiol ; 56(11)2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30135226

RESUMO

QuantiFERON-TB Gold Plus (QFT-Plus) is a new-generation QuantiFERON-TB Gold In-Tube (QFT-GIT) assay which has two antigen-coated tubes called TB1, which contains long peptides derived from ESAT-6 and CFP-10, and TB2, which contains the same components as TB1 and additional short peptides which potentially stimulate CD8+ T cells through the presentation of major histocompatibility complex class I. This is the first study to compare QFT-Plus and QFT-GIT for use in the diagnosis of latent tuberculosis infection (LTBI) among immunocompromised patients in the Republic of Korea. Among 317 consecutive patients who underwent screening for LTBI before solid organ or hematopoietic stem cell transplantation and tumor necrosis factor alpha inhibitor treatment, LTBI was identified in 92 (29.0%) and 88 (27.8%) patients by QFT-GIT and QFT-Plus, respectively. The rate of concordance between QFT-GIT and QFT-Plus was 93.7% (κ value, 0.860), and the indeterminate rate (3.2%) was similar between QFT-GIT and QFT-Plus. Of 20 (6.3%) samples with discordant results, 11 (55.0%) and 7 (35.0%) were positive by QFT-GIT alone and QFT-Plus alone, respectively, and 2 (15.0%) were indeterminate by each assay. The interferon gamma level in samples with discordant results ranged from 0.39 to 1.10 IU/ml, except for one sample, in which the gamma interferon level was 2.97 IU/ml only in TB2. Conclusively, there was a high degree of agreement between the results of QFT-GIT and QFT-Plus for the screening of immunocompromised patients for LTBI. The reactivity in TB2 contributed substantially to the difference between QFT-GIT and QFT-Plus, particularly in solid organ transplant candidates. The significance of the discrete responses in TB1 and TB2 of QFT-Plus needs to be explored further by means of an immunological and clinical approach in different patient groups and clinical settings.


Assuntos
Hospedeiro Imunocomprometido , Testes de Liberação de Interferon-gama , Tuberculose Latente/diagnóstico , Programas de Rastreamento/métodos , Adolescente , Adulto , Idoso , Feminino , Humanos , Testes de Liberação de Interferon-gama/normas , Tuberculose Latente/epidemiologia , Masculino , Programas de Rastreamento/normas , Pessoa de Meia-Idade , Kit de Reagentes para Diagnóstico , República da Coreia/epidemiologia , Adulto Jovem
4.
Eur J Clin Invest ; 48(6): e12936, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29660832

RESUMO

BACKGROUND: IgA nephropathy (IgAN) is the most frequent primary glomerular disease and the leading cause of end-stage renal disease. We investigated clinicopathologic predictors of renal survival in patients with IgAN with a focus on glomerular filtration rate (GFR) decline slope. MATERIALS AND METHODS: We screened all patients with primary IgAN between 1995 and 2012. Renal progression was defined as doubling of serum creatinine. Using serial serum creatinine levels during the first-year, we calculated the GFR decline slopes. Further, we defined patients in the steepest GFR slope quartile as rapid decliners and those in the second steepest GFR slope quartile as slow decliners. Others were defined as nondecliners. RESULTS: Of 214 participants, baseline GFR was 81 (62, 100) mL/min/1.73 m2 , which was not different among the 3 groups. Rapid decliners and slow decliners had higher levels of urinary protein/creatinine ratio (0.88, 0.89 and 0.58 g/gCr, respectively, P < .001). Five-year renal survival was 76% in rapid decliners, 91% in slow decliners and 100% in nondecliners (P < .001, rapid or slow decliners vs nondecliners). After adjustment for clinicopathologic variables, slow decliners were associated with an 8.8-fold higher risk of progression (P = .011), and rapid decliners were associated with a 10.2-fold increased risk of progression (P = .007) compared with nondecliners. CONCLUSIONS: First-year GFR slope was associated with increased risk of renal progression, independent of proteinuria and histologic findings. Further studies are needed to investigate whether early GFR change can identify high-risk patients who benefit from immunosuppressive treatment in IgAN.


Assuntos
Creatinina/sangue , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/metabolismo , Falência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/metabolismo , Adulto , Creatinina/urina , Progressão da Doença , Intervalo Livre de Doença , Feminino , Glomerulonefrite por IGA/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Estimativa de Kaplan-Meier , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Proteinúria , Insuficiência Renal Crônica/tratamento farmacológico , Estudos Retrospectivos
5.
Clin Transplant ; 32(9): e13372, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30080284

RESUMO

Although various strategies for steroid withdrawal after transplantation have been attempted, there are few reports of the long-term results of steroid withdrawal regimens in kidney transplantation. Earlier, we reported on a 5-year prospective, randomized, single-center trial comparing the safety and efficacy of cyclosporine (CsA) plus mycophenolate mofetil (MMF) with that of tacrolimus (TAC) plus MMF, when steroids were withdrawn 6 months after kidney transplantation in low-risk patients. We now report the 10-year observational data on the study population. We collected data from the database of the Organ Transplantation Center, Samsung Medical Center for 5 years after completion of the original study (TAC group n = 62; CsA group n = 55). The 10-year patient survival, death-censored graft survival, and acute rejection-free survival did not differ between groups (98% vs 96%; P = 0.49, 78% vs 85%; P = 0.75 and 84% vs 76%; P = 0.14 in the TAC group vs CsA group, respectively). In low-risk patients, there was no difference in long-term patient and graft survival between TAC- and CsA-based late steroid withdrawal regimens that included MMF treatment. More long-term randomized clinical trials are needed to clarify the benefits of late steroid withdrawal in kidney transplantation.


Assuntos
Ciclosporina/uso terapêutico , Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Rim/efeitos adversos , Doadores Vivos/provisão & distribuição , Tacrolimo/uso terapêutico , Suspensão de Tratamento/estatística & dados numéricos , Adulto , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/mortalidade , Humanos , Imunossupressores/uso terapêutico , Falência Renal Crônica/mortalidade , Falência Renal Crônica/cirurgia , Testes de Função Renal , Masculino , Complicações Pós-Operatórias , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
6.
Crit Care ; 22(1): 255, 2018 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-30305122

RESUMO

BACKGROUND: Despite aggressive application of continuous renal replacement therapy (CRRT) in critically ill patients with acute kidney injury (AKI), there is no consensus on diuretic therapy when discontinuation of CRRT is attempted. The effect of diuretics on discontinuation of CRRT in critically ill patients was evaluated. METHODS: This retrospective cohort study enrolled 1176 adult patients who survived for more than 3 days after discontinuing CRRT between 2009 and 2014. Patients were categorized depending on the re-initiation of renal replacement therapy within 3 days after discontinuing CRRT or use of diuretics. Changes in urine output (UO) and renal function after discontinuing CRRT were outcomes. Predictive factors for successful discontinuation of CRRT were also analyzed. RESULTS: The CRRT discontinuation group had a shorter duration of CRRT, more frequent use of diuretics after discontinuing CRRT, and greater UO on the day before CRRT discontinuation [day minus 1 (day - 1)]. The diuretics group had greater increases in UO and serum creatinine elevation after discontinuing CRRT. In the CRRT discontinuation group, continuous infusion of furosemide tended to increase UO more effectively. Multivariable regression analysis identified high day - 1 UO and use of diuretics as significant predictors of successful discontinuation of CRRT. Day - 1 UO of 125 mL/day was the cutoff value for predicting successful discontinuation of CRRT in oliguric patients treated with diuretics following CRRT. CONCLUSIONS: Day - 1 UO and aggressive diuretic therapy were associated with successful CRRT discontinuation. Diuretic therapy may be helpful when attempting CRRT discontinuation in critically ill patients with AKI, by inducing a favorable fluid balance, especially in oliguric patients.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Diuréticos/administração & dosagem , Terapia de Substituição Renal/métodos , Idoso , Estudos de Coortes , Estado Terminal/terapia , Diuréticos/metabolismo , Diuréticos/uso terapêutico , Feminino , Furosemida/administração & dosagem , Furosemida/metabolismo , Furosemida/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise de Regressão , Terapia de Substituição Renal/normas , Estudos Retrospectivos , Estatísticas não Paramétricas
7.
Am J Physiol Renal Physiol ; 313(4): F984-F996, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28356286

RESUMO

Preemptive treatment with mesenchymal stem cells (MSCs) can attenuate cisplatin-induced acute kidney injury (AKI). However, it is uncertain whether MSC treatment after the development of renal dysfunction prevents AKI progression or if MSC immunomodulatory properties contribute to MSC therapy. In this study, human umbilical cord blood (hUCB)-derived MSCs were used to compare the effects and mechanisms of early and late MSC therapy in a murine model. After cisplatin injection into C57BL/6 mice, hUCB-MSCs were administered on day 1 (early treatment) or day 3 (late treatment). With early treatment, cisplatin nephrotoxicity was attenuated as evidenced by decreased blood urea nitrogen (BUN) and reduced apoptosis and tubular injury scores on day 3 Early treatment resulted in downregulation of intrarenal monocyte chemotactic protein-1 and IL-6 expression and upregulation of IL-10 and VEGF expression. Flow cytometric analysis showed similar populations of infiltrated immune cells in both groups; however, regulatory T-cell (Treg) infiltration was 2.5-fold higher in the early treatment group. The role of Tregs was confirmed by the blunted effect of early treatment on renal injury after Treg depletion. In contrast, late treatment (at a time when BUN levels were 2-fold higher than baseline levels) showed no renoprotective effects on day 6 Neither the populations of intrarenal infiltrating immune cells (including Tregs) nor cytokine expression levels were affected by late treatment. Our results suggest that early MSC treatment attenuates renal injury by Treg induction and immunomodulation, whereas a late treatment (i.e., after the development of renal dysfunction) does not prevent AKI progression or alter the intrarenal inflammatory micromilieu.


Assuntos
Injúria Renal Aguda/prevenção & controle , Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Imunomodulação , Transplante de Células-Tronco Mesenquimais , Injúria Renal Aguda/imunologia , Animais , Masculino , Camundongos Endogâmicos C57BL , Linfócitos T Reguladores/fisiologia
8.
Surg Endosc ; 31(1): 389-397, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27444840

RESUMO

BACKGROUND: The incidence of metachronous lesions after endoscopic resection (ER) of high-grade dysplasia (HGD) has not been evaluated, and optimal surveillance strategy remains vague. This study aimed to evaluate the incidence and characteristics of metachronous tumors including HGD and early gastric cancer (EGC) arising after ER. PATIENTS: The medical records of 2779 patients with 2981 lesions (445 patients with HGD and 2334 patients with EGC) who underwent ER and surveillance endoscopy at Asan Medical Center between April 1999 and December 2011 were retrospectively reviewed, and clinicopathological features of metachronous tumors were analyzed. RESULTS: Ninety-six metachronous lesions (17 HGD and 79 EGC) occurred in 92 patients during median 42 months of follow-up period (range 26-58 months). The 5-year and 10-year overall cumulative incidences of metachronous tumors were 4.6 and 10.5 %, respectively, and were on steady rise up to 10 years. The 5- and 10-year cumulative incidences of metachronous lesions were 4.1 and 8.4 % in HGD group and 4.7 and 11.3 % in EGC group (P = 0.578), respectively. The size of metachronous tumors was significantly smaller than initial lesion (2.3 vs. 1.9 cm, P = 0.039). Lower third of the stomach was most frequent site for both initial and metachronous lesions (77.1 and 70.8 %, respectively) and age was the significant predicting factor for metachronous tumors. CONCLUSIONS: Cumulative incidence of metachronous tumors after ER of HGD was comparable to the incidence after ER of EGC. Surveillance endoscopy can be considered at least for 10 years, with special attention on the lower third of the stomach.


Assuntos
Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/patologia , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/patologia , Fatores Etários , Detecção Precoce de Câncer , Feminino , Seguimentos , Gastroscopia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/cirurgia , República da Coreia/epidemiologia , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia
9.
Am J Physiol Renal Physiol ; 310(4): F272-83, 2016 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-26661651

RESUMO

Inflammatory process mediated by innate and adaptive immune systems is a major pathogenic mechanism of renal ischemia-reperfusion injury (IRI). There are concerns that organ recipients may be at increased risk of developing IRI after receiving kidneys from elder donors. To reveal the effects of aging on the development of renal IRI, we compared the immunologic micromilieu of normal and postischemic kidneys from mice of three different ages (9 wk, 6 mo, and 12 mo). There was a higher number of total T cells, especially effector memory CD4/CD8 T cells, and regulatory T cells in the normal kidneys of old mice. On day 2 after IRI, the proportion of necrotic tubules and renal functional changes were comparable between groups although old mice had a higher proportion of damaged tubule compared with young mice. More T cells, but less B cells, trafficked into the postischemic kidneys of old mice. The infiltration of NK T cells was similar across the groups. Macrophages and neutrophils were comparable between groups in both normal kidneys and postischemic kidneys. The intrarenal expressions of TNF-α and VEGF were decreased in normal and postischemic kidneys of aged mice. These mixed effects of aging on lymphocytes and cytokines/chemokines were not different between the two groups of old mice. Our study demonstrates that aging alters the intrarenal micromilieu but has small effects on the development of initial renal injury after IRI. Further study investigating aging-dependent differences in the repair process of renal IRI may be required.


Assuntos
Injúria Renal Aguda/imunologia , Injúria Renal Aguda/patologia , Envelhecimento/patologia , Rim/imunologia , Rim/patologia , Traumatismo por Reperfusão/patologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Interleucina-6/biossíntese , Interleucina-6/genética , Testes de Função Renal , Túbulos Renais/patologia , Antígenos Comuns de Leucócito/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Necrose , Peroxidase/metabolismo , Traumatismo por Reperfusão/imunologia , Fator de Necrose Tumoral alfa/biossíntese , Fator A de Crescimento do Endotélio Vascular/biossíntese , Fator A de Crescimento do Endotélio Vascular/genética
10.
J Vasc Surg ; 62(4): 1003-9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26141697

RESUMO

OBJECTIVE: This study identified predictors affecting maturation and patency of autogenous radiocephalic arteriovenous fistulas (RCAVFs). METHODS: We retrospectively reviewed the prospectively collected clinical data of all patients who underwent primary RCAVF creation and evaluated the effect of clinical variables and findings of preoperative duplex ultrasound mapping on primary maturation and patency rates of RCAVFs. RESULTS: From August 2008 to December 2010, 383 vascular access procedures were performed in 371 patients; of these, 331 (86.4%) were autogenous AVFs, 283 (85.5%) were primary first AVFs, and 186 (65.7%) of these were RCAVFs. The primary maturation rate was 88.2% at a mean of 39 ± 24.1 days after the operation. By multiple logistic regression analysis, minimum cephalic vein (CV) diameter >2 mm was an independent predictor of RCAVF maturation (odds ratio, 3.672; 95% confidence interval, 1.394-9.673; P = .008), which was more easily achieved in nondiabetic patients. During the mean follow-up of 47.2 ± 23.1 months, primary patency of RCAVFs was 80.3% at 1 year and 76.5% at 2 years. A Cox proportional hazard model showed diabetes was the only independent risk factor of primary patency (hazard ratio, 2.008; 95% confidence interval, 1.022-3.945; P = .043). Nondiabetic patients with a CV diameter >2 mm had significantly higher primary maturation rate and higher primary patency than diabetic patients with a CV diameter ≤2 mm. CONCLUSIONS: There were different risk factors affecting RCAVF primary maturation and primary patency. A CV with a small-diameter of ≤2 mm combined with diabetes was an independent risk factor of failure not only of primary maturation but also of primary patency in RCAVF.


Assuntos
Derivação Arteriovenosa Cirúrgica , Complicações do Diabetes , Grau de Desobstrução Vascular , Veias/anatomia & histologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Radial , Estudos Retrospectivos , Ultrassonografia Doppler Dupla
11.
Am J Physiol Renal Physiol ; 307(10): F1149-61, 2014 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-25143451

RESUMO

Human umbilical cord blood-derived mesenchymal stem cells (HUCB-MSCs) have been studied in several models of immune-mediated disease because of their unique immunomodulatory properties. We hypothesized that HUCB-MSCs could suppress the inflammatory response in postischemic kidneys and attenuate early renal injury. In 8- to 10-wk-old male C57BL/6 mice, bilateral ischemia-reperfusion injury (IRI) surgery was performed, and 1 × 10(6) HUCB-MSCs were injected intraperitoneally 24 h before surgery and during reperfusion. Renal functional and histological changes, HUCB-MSC trafficking, leukocyte infiltration, and cytokine expression were analyzed. Renal functional decline and tubular injury after IRI were attenuated by HUCB-MSC treatment. PKH-26-labeled HUCB-MSCs trafficked into the postischemic kidney. Although numbers of CD45-positive leukocytes in the postischemic kidney were comparable between groups, the expression of interferon-γ in the postischemic kidney was suppressed by HUCB-MSC treatment. The rapid decrease in intrarenal VEGF after IRI was markedly mitigated by HUCB-MSC treatment. In inflammatory conditions simulated in a cell culture experiment, VEGF secretion from HUCB-MSCs was substantially enhanced. VEGF inhibitor abolished the renoprotective effect of HUCB-MSCs after IRI. Flow cytometry analysis revealed the decreased infiltration of natural killer T cells and increased number of regulatory T cells in postischemic kidneys. In addition, these effects of HUCB-MSCs on kidney infiltrating mononuclear cells after IRI were attenuated by VEGF inhibitor. HUCB-MSCs attenuated renal injury in mice in the early injury phase after IRI, mainly by humoral effects and secretion of VEGF. Our results suggest a promising role for HUCB-MSCs in the treatment of renal IRI.


Assuntos
Injúria Renal Aguda/prevenção & controle , Transplante de Células-Tronco Mesenquimais , Traumatismo por Reperfusão/prevenção & controle , Injúria Renal Aguda/imunologia , Injúria Renal Aguda/metabolismo , Animais , Humanos , Interferon gama/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/metabolismo , Linfócitos T/fisiologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismo
12.
BMC Cancer ; 14: 906, 2014 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-25466872

RESUMO

BACKGROUND: Everolimus was recently introduced as a second-line treatment for renal cell carcinoma (RCC) and many other cancers. Several prospective studies have shown that serum creatinine levels are increased in a significant proportion of patients receiving everolimus. However, data on the occurrence of acute kidney injury (AKI) during everolimus treatment in clinical practice are sparse. Here, we report the incidence, risk factors, and clinical significance of AKI associated with everolimus treatment in patients with cancer. METHODS: We analyzed patients who received everolimus for more than 4 weeks as an anticancer therapy. AKI was defined as increase in creatinine levels from baseline levels greater than 1.5-fold. RESULTS: The majority of the 110 patients enrolled in this analysis had RCC (N=93, 84.5%). AKI developed in 21 (23%) RCC patients; none of the patients (N=17) with other cancers had AKI. Fourteen of 21 cases were considered to be everolimus-associated AKI, in which there were no other nephrotoxic insults other than everolimus at the onset of AKI. The incidence of AKI increased progressively as baseline estimated glomerular filtration rate (eGFR) decreased (10% in subjects with eGFR >90 mL/min/1.73 m2, 17% in subjects with eGFR 60-90 mL/min/1.73 m2, 28% in subjects with eGFR 30-60 mL/min/1.73 m2, and 100% in subjects with eGFR 15-30 mL/min/1.73 m2; P=0.029 for trend). Baseline eGFR was an independent risk factor for the development of everolimus-associated AKI (hazard ratio per 10 mL/min/1.73 m2 increase, 0.70; 95% confidential interval, 049-1.00; P=0.047). Nine of 14 patients with everolimus-associated AKI continued receiving the drug at a reduced dose or after a short-term off period. Administration of the drug was discontinued in four of 14 patients because of progression of an underlying malignancy. Only one patient stopped taking the drug because of AKI. CONCLUSIONS: This paper suggests that AKI is a common adverse effect of everolimus treatment, especially in subjects with impaired renal function. However, the occurrence of AKI did not require the discontinuation of the drug, and the treatment decision should be made via a multidisciplinary approach, including the assessment of the oncological benefits of everolimus and other therapeutic options.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Antineoplásicos/efeitos adversos , Neoplasias Renais/tratamento farmacológico , Sirolimo/análogos & derivados , Injúria Renal Aguda/sangue , Idoso , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/fisiopatologia , Creatinina/sangue , Everolimo , Feminino , Taxa de Filtração Glomerular , Humanos , Incidência , Neoplasias Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Sirolimo/efeitos adversos
13.
Clin Transplant ; 28(6): 699-706, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24654804

RESUMO

Several predictive factors associated with adverse pregnancy outcomes in female renal recipients have been suggested. Our study aimed to determine the most important factor for prediction of adverse pregnancy outcomes in female renal recipients. We studied 41 pregnancies in 29 female renal recipients retrospectively. We reviewed pregnancy outcomes and possible predictive factors including pre-pregnancy serum creatinine (SCr), pre-pregnancy glomerular filtration rate (GFR), pre-pregnancy hypertension, pre-pregnancy proteinuria, transplantation-pregnancy interval and type of immunosuppressants. We defined an adverse pregnancy-related outcomes index (APOI) that included the following conditions: (i) preeclampsia; (ii) fetal growth restriction (FGR); (iii) prematurity before 34 wk of gestation; (iv) fetal loss (v) graft dysfunction during pregnancy or within three months from delivery. The cutoff of pre-pregnancy serum creatinine and GFR was determined by receiver operating characteristics curves for the prediction of each adverse outcome and APOI. Only pre-pregnancy serum creatinine was associated with adverse pregnancy outcome, and 1 mg/dL was determined to be a useful cutoff for the prediction of each adverse outcomes. Pre-pregnancy SCr ≥ 1 mg/dL was associated with 7.7 times increased risk of preeclampsia and 6.9 times increased risk of APOI. Pre-pregnancy serum creatinine is the most powerful predictive factor for adverse pregnancy outcomes, and <1 mg/dL may be used as a screen for successful pregnancy outcome.


Assuntos
Transplante de Rim/efeitos adversos , Complicações na Gravidez/etiologia , Adulto , Creatinina/sangue , Feminino , Seguimentos , Idade Gestacional , Taxa de Filtração Glomerular , Humanos , Imunossupressores/uso terapêutico , Falência Renal Crônica/sangue , Falência Renal Crônica/cirurgia , Testes de Função Renal , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Fatores de Risco
14.
Clin Transplant ; 28(9): 953-60, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24861232

RESUMO

Living-unrelated donors (LURD) have been widely used for kidney transplantation (KT). We retrospectively reviewed 779 patients who underwent living-donor KT from 2000 to 2012, to compare outcomes of 264 KT from LURD and 515 from living-related donors (LRD), and to identify risk factors for living KT. Median follow-up was 67 months. Mean donor age, total human leukocyte antigen (HLA) mismatches, and HLA-DR mismatches were higher, and mean estimated glomerular filtration rate (eGFR) was lower in LURD. Acute rejection (AR)-free survival (p = 0.018) and graft survival (p = 0.025) were lower for LURD than LRD, whereas patient survival rate was comparable. Cox regression analysis showed HLA-DR mismatches (OR 1.75 for one mismatch; OR 2.19 for two mismatches), recipient age ≤ 42 yr, and donor age > 50 yr were significant risk factors for acute rejection. For graft survival, AR and donor eGFR (OR 1.90, p = 0.035) were significant. We also identified significant impact of recipient age > 50 yr and diabetes for patient survival. However, KT from LURD was not a significant risk factor for AR (p = 0.368), graft survival (p = 0.205), and patient survival (p = 0.836). Our data suggest that donor eGFR and donor age are independent risk factors for clinical outcomes of living KT, which can be related with poor outcome of KT from LURD.


Assuntos
Taxa de Filtração Glomerular/fisiologia , Sobrevivência de Enxerto/fisiologia , Falência Renal Crônica/cirurgia , Transplante de Rim , Rim/fisiologia , Doadores Vivos , Adulto , Fatores Etários , Idoso , Feminino , Seguimentos , Teste de Histocompatibilidade , Humanos , Falência Renal Crônica/fisiopatologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
15.
Crit Care ; 18(6): 640, 2014 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-25407928

RESUMO

INTRODUCTION: Although the clinical application of procalcitonin (PCT) as an infection marker in patients with impaired renal function (estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m(2)) has been increasing recently, it is unclear whether PCT is more accurate than C-reactive protein (CRP). We investigated the clinical value of CRP and PCT based on renal function. METHODS: From November 2008 to July 2011, a total of 493 patients who simultaneously underwent CRP and PCT tests were enrolled. The area under the receiver operating characteristic (ROC) curve and characteristics of both markers were analyzed according to infection severity and renal function. RESULTS: In patients with impaired renal function, the area under the ROC curve was 0.876 for CRP and 0.876 for PCT. In patients with infection, CRP levels differed depending on whether the infection was localized, septic, or severely septic, whereas PCT levels were higher in patients with severe sepsis or septic shock. In patients without infection, CRP did not correlate with eGFR, while PCT was negatively correlated with eGFR. CONCLUSION: This study demonstrates that CRP is accurate for predicting infection in patients with impaired renal function. The study suggests that in spite of its higher cost, PCT is not superior to CRP as an infection marker in terms of diagnostic value.


Assuntos
Proteína C-Reativa/metabolismo , Calcitonina/sangue , Precursores de Proteínas/sangue , Insuficiência Renal/sangue , Insuficiência Renal/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/economia , Calcitonina/economia , Peptídeo Relacionado com Gene de Calcitonina , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Precursores de Proteínas/economia , Insuficiência Renal/economia , Sepse/sangue , Sepse/diagnóstico , Sepse/economia
16.
J Korean Med Sci ; 29(1): 76-83, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24431909

RESUMO

Continuous erythropoietin receptor activator (CERA) is an erythropoietin with a long-half life. This study investigated the efficacy of CERA for correcting anemia in Korean patients on dialysis. Patients (≥ 18 yr) who were not receiving any ESAs for more than 8 weeks were randomly assigned to either intravenous CERA once every 2 weeks (n=39) or epoetin beta thrice-weekly (n=41) during a 24-week correction phase. Hemoglobin (Hb) response was defined as increase of Hb by at least 1 g/dL and Hb ≥ 11 g/dL without red blood cell (RBC) transfusion. Median dialysis duration was 1.7 (0.3-20.8) and 1.6 (0.4-13.8) yr in CERA and epoetin beta group, respectively. Hemoglobin response rate of CERA was 79.5% (95% confidence interval [CI], 63.5-90.7). As the lower limit of 95% CI was higher than pre-specified 60% response rate, it can be concluded that CERA corrected anemia (P<0.05). Hb response rate of epoetin beta was 87.8% (95% CI, 73.8-95.9) (P=0.37). Median time to response was 12 weeks in CERA and 10.3 weeks in epoetin beta (P=0.03). It is suggested that once every 2 weeks administration of CERA is effective for correcting anemia in Korean patients on long-term hemodialysis with longer time-to-response than thrice weekly epoetin beta. (ClinicalTrials.gov registry No. NCT00546481).


Assuntos
Anemia/tratamento farmacológico , Eritropoetina/uso terapêutico , Polietilenoglicóis/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Feminino , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Proteínas Recombinantes/uso terapêutico , Diálise Renal , República da Coreia
17.
Medicine (Baltimore) ; 103(26): e38694, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38941432

RESUMO

Schizophrenia (SPR) is the most devastating mental illness that causes severe deterioration in social and occupational functioning, but, the etiology remains unknown. The objective of this study is to explore the genetic underpinnings of novelty seeking behavior in schizophrenic family within the Korean population. By conducting a family-based genome-wide association study, we aim to identify potential genetic markers and variations associated with novelty seeking traits in the context of SPR. We have recruited 27 probands (with SPR) with their parents and siblings whenever possible. DNA was extracted from blood sampling of 58 individuals in 27 families and analyzed in an Illumina core exome single nucleotide polymorphism (SNP) array. A family-based association test (qFAM) was used to derive SNP association values across all chromosomes. Although none of the final 800,000 SNPs reached the genome-wide significant threshold of 8.45 × 10-7, the most significant 4 SNPs were within the 10-5 to 10-7. This study identifies genetic associations between novelty seeking behavior and SPR within families. RAPGEF5 emerges as a significant gene, along with other neuropsychiatric-related genes. Noteworthy genes like DRD4 and COMT did not show associations, possibly due to the focus on schizophrenic family. While shedding light on this complex relationship, larger studies are needed for robust conclusions and deeper mechanistic insights.


Assuntos
Comportamento Exploratório , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Esquizofrenia , Humanos , Esquizofrenia/genética , Masculino , Feminino , República da Coreia/epidemiologia , Projetos Piloto , Adulto , Pessoa de Meia-Idade , Predisposição Genética para Doença , Adulto Jovem
18.
J Korean Med Sci ; 28(10): 1431-4, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24133345

RESUMO

The purpose of the present study was to evaluate the difference in BMI pattern between patients with persistent new-onset diabetes after transplantation (P-NODAT) and without new-onset diabetes after transplantation (N-NODAT) in a retrospective matched case-control (1:3) analysis. Thirty-six patients who developed P-NODAT were identified among 186 adult renal transplant recipients with no evidence of pretransplant diabetes mellitus who underwent kidney transplantation from September 1997 to March 2008 and were treated with a triple regimen including tacrolimus. The controls were selected to match the patients for pretransplant BMI, age at transplantation (± 5 yr), and date of transplantation (± 12 months). Finally, 20 P-NODAT patients and 60 N-NODAT patients were selected. The pre- and posttransplant BMI data were collected every 16 weeks for up to 80 weeks. The clinical characteristics did not differ between the P-NODAT group and N-NODAT group. BMI increased faster in the P-NODAT group than in the N-NODAT group. The mixed-model analysis showed that patients with P-NODAT exhibited a faster increase in BMI. P-NODAT is associated with posttransplant weight gain. The risk of P-NODAT should be considered in patients with rapid weight gain after transplantation.


Assuntos
Diabetes Mellitus Tipo 2/etiologia , Transplante de Rim , Aumento de Peso , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tacrolimo/uso terapêutico , Fatores de Tempo
19.
Am J Kidney Dis ; 60(1): 74-81, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22497793

RESUMO

BACKGROUND: Prophylaxis against contrast-induced acute kidney injury (AKI) in hospitalized patients is underused. We evaluated the impact of a computerized alert program for contrast-induced AKI for hospitalized patients undergoing contrast-enhanced computed tomography (CT). STUDY DESIGN: Quality improvement report. SETTING & PARTICIPANTS: 463 adult inpatients in a single center with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2). QUALITY IMPROVEMENT PLAN: We developed a computer alert program in which the responsible physician was alerted to a patient's risk of contrast-induced AKI in the form of a warning message box and was recommended to consider prophylactic measures for contrast-induced AKI when he or she ordered contrast-enhanced CT for patients with eGFR <60 mL/min/1.73 m(2). The intervention was applied simultaneously to all hospitalized patients from March 18, 2010. The hospital's contrast-induced AKI preventive guidelines included prehydration, posthydration, and oral N-acetylcysteine. OUTCOME & MEASUREMENTS: Use of prophylactic interventions, development of contrast-induced AKI. Contrast-induced AKI was defined as an increase in serum creatinine level (≥0.3 mg/dL or ≥50%) 24-72 hours after contrast medium exposure. RESULTS: 258 adult inpatients with eGFR <60 mL/min/1.73 m(2) were identified as undergoing contrast-enhanced CT before application of the computer alert program (from October 28, 2009, to March 17, 2010), and 205, after its application (from March 18, 2010, to August 5, 2010). Individuals in the postalert group received contrast-induced AKI prophylaxis more often than those in the prealert group (55% vs 25% for total prophylaxis; P < 0.001). The incidence of contrast-induced AKI was lower in the postalert group than in the prealert group (3% vs 10%; P = 0.02). LIMITATIONS: Observation bias; only 61.5% of participants were evaluated for contrast-induced AKI. CONCLUSIONS: Implementation of a computerized alert program in hospitalized patients was followed by increased use of prophylaxis and decreased risk of contrast-induced AKI.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/prevenção & controle , Meios de Contraste/efeitos adversos , Sistemas de Registro de Ordens Médicas , Sistemas de Alerta , Injúria Renal Aguda/diagnóstico por imagem , Injúria Renal Aguda/fisiopatologia , Adulto , Idoso , Computadores , Feminino , Taxa de Filtração Glomerular , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Intensificação de Imagem Radiográfica , Tomografia Computadorizada por Raios X
20.
Scand J Infect Dis ; 44(10): 788-92, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22681387

RESUMO

BACKGROUND: Occult hepatitis B infection (OBI) is the presence of hepatitis B virus (HBV) DNA in serum or hepatic tissue without detectable hepatitis B surface antigen (HBsAg) in serum. Kidney disease patients in the post-renal transplantation period are in a specific situation as a result of the high pre-transplantational risk of HBV infection and post-transplantational immunosuppression. We studied the pre-transplantational prevalence and post-transplantational influence of OBI on kidney transplantation patients. METHODS: We investigated pre-transplantational serum samples of 217 HBsAg-negative patients of post-renal transplant status for the presence of HBV DNA by real-time quantitative polymerase chain reaction. Serologic markers for HBV and hepatitis C virus (HCV) infection as well as liver enzymes were analyzed. RESULTS: We detected HBV DNA in 2.3% (5/217) of HBsAg-negative patients, and the median HBV DNA titer was 33.15 copies/ml (range 30.6-144.6 copies/ml). Among the 5 OBI patients, 2 had hepatitis B surface antibodies (anti-HBs) and 1 had hepatitis B core antibodies (anti-HBc IgG). None of the patients with OBI were co-infected with HCV. There was no evidence of reactivation of OBI during the 36-month (range 27-63 months) follow-up monitoring period after transplantation, in spite of immune suppression to prevent rejection. CONCLUSIONS: The prevalence of occult HBV in the setting of renal transplantation was higher than that in the general population of Korea, and no reactivation of hepatitis B was observed in patients with OBI in the post-renal transplantation period.


Assuntos
Vírus da Hepatite B/isolamento & purificação , Hepatite B/epidemiologia , Transplante de Rim , Transplante , Adulto , DNA Viral/sangue , DNA Viral/isolamento & purificação , Feminino , Hepatite B/virologia , Humanos , Fígado/enzimologia , Masculino , Pessoa de Meia-Idade , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , República da Coreia , Estudos Retrospectivos
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