The effects of periodontitis on the metabolic syndrome and cancer

학위논문 (박사)-- 서울대학교 대학원 : 치의과학과, 2014. 2. 배광학.본 연구는 국가 대표표본 조사인 제4차 국민건강영양조사(KNHANES)에 참여한 대한민국 성인에서 대사증후군과 치주염 사이의 연관성을 확인하고, 종합병원에 내원한 암환자의 치주질환을 평가하여 암과 치주질환과의 연관성 여부를 조사하기 위한 목적으로 시행되었다. 국민건강영양조사에 참여한 19세 이상의 성인 총 7,178명을 대상으로 대사증후군 연구를 시행하였다. 대사증후군은 NCEP ATP III (National Cholesterol Education Program Adult Treatment Panel III) 정의를 따랐으며, 복부비만의 기준은 대한비만학회의 제안을 기초로 하였다. 치주상태는 지역사회치주지수(Community Periodontal Index)를 이용하여 평가하고, 사회인구학적 요인과 구강건강상태, 보건행태 및 구강보건행태를 보정하여 다변량 로지스틱 회귀분석을 시행하였다. 모든 분석은 복합표본설계를 고려하였고, 연령, 성별, 현재흡연상태에 따른 하위집단분석을 수행하였다. 다변량 로지스틱 회귀분석 결과 대사증후군과 치주염 간 유의한 연관성을 보였다. 모든 혼동변수를 보정한 후 지역사회치주지수 3 이상을 보인 치주염 그룹과 대사증후군 그룹 사이의 오즈비(odds ratio)는 1.55(1.32–1.83)였다. 하위집단분석 결과 40세 이상의 대상에서 대사증후군과 치주염이 유의한 연관성을 보였고, 보정된 오즈비는 여성과 흡연자군에서 남성 및 비흡연자군에 비해 더 크게 나타났다. 2010년 5월부터 2012년 2월까지 한국원자력의학원에 내원한, 암으로 진단받은 후 암 치료를 시행하기 이전이며, 본 연구에 대한 설명을 듣고 참여에 동의한 57명의 환자를 대상으로 자기기입식 설문조사와 의무기록지 조사, 치주조직 검사를 실시하고, 임상적 치주조직 부착상실 정도가 가장 큰 부위에서 치은열구액을 채취하여 여섯 가지 치주질환 병원균 분석을 시행하였다. 폐암과 식도암 및 기타부위 암의 세 군으로 암종을 분류하여, 암종 별 치주염 정도의 차이는 카이제곱 검정법으로 분석하였고, 3.0 mm 이상의 치주낭 깊이를 가진 부위의 치주낭 깊이 평균 및 각 병원균량의 암종 간 차이는 Kruskal-Wallis 비모수 검정으로 분석한 결과, 치주염 심도는 암종 간 유의한 차이가 없었으나(p>0.05), 식도암 환자군에서 Treponema denticola의 양이 다른 암종에 비하여 더 많이 관찰되었다(p=0.042). 결론적으로, NCEP-ATP III 진단기준을 사용한 대사증후군과 치주염은 유의하게 연관되어 있었고, 치주염 심도는 암종 간 유의한 차이가 없었으나, 식도암 환자군에서 Treponema denticola의 양이 더 많이 관찰되었다.I. 서 론 II. 연구배경 III. 연구방법 IV. 연구성적 V. 고 안 VI. 결 론 참고문헌 영문초록Docto

Cystatin C is Better than Serum Creatinine for Estimating Glomerular Filtration Rate to Detect Osteopenia in Chronic Kidney Disease Patients

PURPOSE: Recent studies have reported that loss of bone mass is associated with renal function decline and increased fracture risks in chronic kidney disease (CKD) patients. The aim of this study was to investigate the best estimated glomerular filtration rate (eGFR) equation to detect osteopenia in CKD patients. MATERIALS AND METHODS: This was a cross-sectional study, and 780 patients aged 50 years or above were classified into normal bone mass or osteopenia groups according to the -1.0 of T-scores at total hip and femur neck. Comparisons of area under the receiver operating characteristic (ROC) curves (AUC) were performed to investigate significant differences among three eGFR formulas: Modification of Diet in Renal Disease, CKD-Epidemiology Collaboration (EPI) creatinine, and CKD-EPI cystatin C (CKD-EPI-Cys). RESULTS: The mean age was 61 years old and the proportion of females was 37.3%. The total hip osteopenia group showed lower CKD-EPI-Cys eGFR levels (osteopenia group, 33.3±19.0 mL/min/1.73 m²; normal group, 48.1±26.2 mL/min/1.73 m², p<0.001). In multiple logistic regression analysis, CKD-EPI-Cys eGFR was independently associated with osteopenia at the total hip (per 1 mL/min/1.73 m² increase, odds ratio 0.98, 95% confidence interval 0.97-0.99, p=0.004) after adjusting for confounding variables. ROC curve analyses indicated that CKD-EPI-Cys shows the largest AUC for osteopenia at the total hip (AUC=0.678, all p<0.01) and the femur neck (AUC=0.665, all p<0.05). CONCLUSION: Decreased renal function assessed by CKD-EPI-Cys equation correlates with osteopenia better than creatinine-based methods in CKD patients, and the CKD-EPI-Cys formula might be a useful tool to assess skeletal-related event risks.ope

Periostin-Binding DNA Aptamer Treatment Ameliorates Peritoneal Dialysis-Induced Peritoneal Fibrosis

Peritoneal fibrosis is a major complication in peritoneal dialysis (PD) patients, which leads to dialysis discontinuation. Periostin, increased by transforming growth factor β1 (TGF-β1) stimulation, induces the expression of extracellular matrix (ECM) genes. Aberrant periostin expression has been demonstrated to be associated with PD-related peritoneal fibrosis. Therefore, the effect of periostin inhibition by an aptamer-based inhibitor on peritoneal fibrosis was evaluated. In vitro, TGF-β1 treatment upregulated periostin, fibronectin, α-smooth muscle actin (α-SMA), and Snail expression and reduced E-cadherin expression in human peritoneal mesothelial cells (HPMCs). Periostin small interfering RNA (siRNA) treatment ameliorated the TGF-β1-induced periostin, fibronectin, α-SMA, and Snail expression and restored E-cadherin expression in HPMCs. Similarly, the periostin-binding DNA aptamer (PA) also attenuated fibronectin, α-SMA, and Snail upregulation and E-cadherin downregulation in TGF-β1-stimulated HPMCs. In mice treated with PD solution for 4 weeks, the expression of periostin, fibronectin, α-SMA, and Snail was significantly increased in the peritoneum, whereas E-cadherin expression was significantly decreased. The thickness of the submesothelial layer and the intensity of Masson's trichrome staining in the PD group were significantly increased compared to the untreated group. These changes were significantly abrogated by the intraperitoneal administration of PA. These findings suggest that PA can be a potential therapeutic strategy for peritoneal fibrosis in PD patients.ope

Change of Nutritional Status Assessed Using Subjective Global Assessment Is Associated With All-Cause Mortality in Incident Dialysis Patients

Subjective global assessment (SGA) is associated with mortality in end-stage renal disease (ESRD) patients. However, little is known whether improvement or deterioration of nutritional status after dialysis initiation influences the clinical outcome. We aimed to elucidate the association between changes in nutritional status determined by SGA during the first year of dialysis and all-cause mortality in incident ESRD patients. This was a multicenter, prospective cohort study. Incident dialysis patients with available SGA data at both baseline and 12 months after dialysis commencement (n = 914) were analyzed. Nutritional status was defined as well nourished (WN, SGA A) or malnourished (MN, SGA B or C). The patients were divided into 4 groups according to the change in nutritional status between baseline and 12 months after dialysis commencement: group 1, WN to WN; group 2, MN to WN; group 3, WN to MN; and group 4, MN to MN. Cox proportional hazard analysis was performed to clarify the association between changes in nutritional status and mortality. Being in the MN group at 12 months after dialysis initiation, but not at baseline, was a significant risk factor for mortality. There was a significant difference in the 3-year survival rates among the groups (group 1, 92.2%; group 2, 86.0%; group 3, 78.2%; and group 4, 63.5%; log-rank test, P < 0.001). Multivariate Cox regression analysis revealed that the mortality risk was significantly higher in group 3 than in group 1 (hazard ratio [HR] 2.77, 95% confidence interval [CI] 1.27-6.03, P = 0.01) whereas the mortality risk was significantly lower in group 2 compared with group 4 (HR 0.35, 95% CI 0.17-0.71, P < 0.01) even after adjustment for confounding factors. Moreover, mortality risk of group 3 was significantly higher than in group 2 (HR 2.89, 95% CI 1.22-6.81, P = 0.02); there was no significant difference between groups 1 and 2. The changes in nutritional status assessed by SGA during the first year of dialysis were associated with all-cause mortality in incident ESRD patients.ope

Delta neutrophil index is an independent predictor of mortality in septic acute kidney injury patients treated with continuous renal replacement therapy

BACKGROUND: Delta neutrophil index (DNI), representing an elevated fraction of circulating immature granulocytes in acute infection, has been reported as a useful marker for predicting mortality in patients with sepsis. The aim of this study was to evaluate the prognostic value of DNI in predicting mortality in septic acute kidney injury (S-AKI) patients treated with continuous renal replacement therapy (CRRT). METHOD: This is a retrospective analysis of consecutively CRRT treated patients. We enrolled 286 S-AKI patients who underwent CRRT and divided them into three groups based on the tertiles of DNI at CRRT initiation (high, DNI > 12.0%; intermediate, 3.6-12.0%; low, < 3.6%). Patient survival was estimated with the Kaplan-Meier method and Cox proportional hazards models to determine the effect of DNI on the mortality of S-AKI patients. RESULTS: Patients in the highest tertile of DNI showed higher Acute Physiology and Chronic Health Evaluation II score (highest tertile, 27.9 ± 7.0; lowest tertile, 24.6 ± 8.3; P = 0.003) and Sequential Organ Failure Assessment score (highest tertile, 14.1 ± 3.0; lowest tertile, 12.1 ± 4.0; P = 0.001). The 28-day mortality rate was significantly higher in the highest tertile group than in the lower two tertile groups (P < 0.001). In the multiple Cox proportional hazard model, DNI was an independent predictor for mortality after adjusting multiple confounding factors (hazard ratio, 1.010; 95% confidence interval, 1.001-1.019; P = 0.036). CONCLUSION: This study suggests that DNI is independently associated with mortality of S-AKI patients on CRRT.ope

Glycemic Control Modifies Difference in Mortality Risk Between Hemodialysis and Peritoneal Dialysis in Incident Dialysis Patients With Diabetes: Results From a Nationwide Prospective Cohort in Korea

Although numerous studies have tried to elucidate the best dialysis modality in end-stage renal disease patients with diabetes, results were inconsistent and varied with the baseline characteristics of patients. Furthermore, none of the previous studies on diabetic dialysis patients accounted for the impact of glycemic control. We explored whether glycemic control had modifying effect on mortality between hemodialysis (HD) and peritoneal dialysis (PD) in incident dialysis patients with diabetes. A total of 902 diabetic patients who started dialysis between August 2008 and December 2013 were included from a nationwide prospective cohort in Korea. Based on the interaction analysis between hemoglobin A1c (HbA1c) and dialysis modalities for patient survival (P for interaction = 0.004), subjects were stratified into good and poor glycemic control groups (HbA1c< or ≥8.0%). Differences in survival rates according to dialysis modalities were ascertained in each glycemic control group after propensity score matching. During a median follow-up duration of 28 months, the relative risk of death was significantly lower in PD compared with HD in the whole cohort and unmatched patients (whole cohort, hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.47-0.90, P = 0.01; patients with available HbA1c [n = 773], HR = 0.64, 95% CI = 0.46-0.91, P = 0.01). In the good glycemic control group, there was a significant survival advantage of PD (HbA1c <8.0%, HR = 0.59, 95% CI = 0.37-0.94, P = 0.03). However, there was no significant difference in survival rates between PD and HD in the poor glycemic control group (HbA1c ≥8.0%, HR = 1.21, 95% CI = 0.46-2.76, P = 0.80). This study demonstrated that the degree of glycemic control modified the mortality risk between dialysis modalities, suggesting that glycemic control might partly contribute to better survival of PD in incident dialysis patients with diabetes.ope

Low Mitochondrial DNA Copy Number is Associated With Adverse Clinical Outcomes in Peritoneal Dialysis Patients

Mitochondrial dysfunction may play an important role in abnormal glucose metabolism and systemic inflammation. We aimed to investigate the relationship between mitochondrial DNA (mtDNA) copy number and clinical outcomes in peritoneal dialysis (PD) patients. We recruited 120 prevalent PD patients and determined mtDNA copy number by PCR. Primary outcome was all-cause mortality, whereas secondary outcomes included cardiovascular events, technical PD failure, and incident malignancy. Cox proportional hazards analysis determined the independent association of mtDNA copy number with outcomes. The mean patient age was 52.3 years; 42.5% were men. The mean log mtDNA copy number was 3.30 ± 0.50. During a follow-up period of 35.4 ± 19.3 months, all-cause mortality and secondary outcomes were observed in 20.0% and 59.2% of patients, respectively. Secondary outcomes were significantly lower in the highest mtDNA copy number group than in the lower groups. In multiple Cox analysis, the mtDNA copy number was not associated with all-cause mortality (lower two vs highest tertile: hazard ratio [HR] = 1.208, 95% confidence interval [CI] = 0.477-3.061). However, the highest tertile group was significantly associated with lower incidences of secondary outcomes (lower two vs highest tertile: HR [95% CI] = 0.494 [0.277-0.882]) after adjusting for confounding factors. The decreased mtDNA copy number was significantly associated with adverse clinical outcomes in PD patients.ope

Which Biomarker is the Best for Predicting Mortality in Incident Peritoneal Dialysis Patients: NT-ProBNP, Cardiac TnT, or hsCRP?: A Prospective Observational Study

Although numerous previous studies have explored various biomarkers for their ability to predict mortality in end-stage renal disease (ESRD) patients, these studies have been limited by retrospective analyses, mostly prevalent dialysis patients, and the measurement of only 1 or 2 biomarkers. This prospective study was aimed to evaluate the association between 3 biomarkers and mortality in incident 335 ESRD patients starting continuous ambulatory peritoneal dialysis (CAPD) in Korea. According to the baseline NT-proBNP, cTnT, and hsCRP levels, the patients were stratified into tertiles, and cardiovascular (CV) and all-cause mortalities were compared. Additionally, time-dependent ROC curves were constructed, and the net reclassification index (NRI) and integrated discrimination improvement (IDI) of the models with various biomarkers were calculated. We found the upper tertile of NT-proBNP was significantly associated with increased risk of both CV and all-cause mortalities. However, the upper tertile of hsCRP was significantly related only to the high risk of all-cause mortality even after adjustment for age, sex, and white blood cell counts. Moreover, NT-proBNP had the highest predictive power for CV mortality, whereas hsCRP was the best prognostic marker for all-cause mortality among these biomarkers. In conclusions, NT-proBNP is a more significant prognostic factor for CV mortality than cTnT and hsCRP, whereas hsCRP is a more significant predictor than NT-proBNP and cTnT for all-cause mortality in incident peritoneal dialysis patients.ope

Vitamin D deficiency is an independent risk factor for urinary tract infections after renal transplants

Vitamin D deficiency is frequently found in patients with renal transplants (RTxs). Because vitamin D plays indispensable roles in the immune system, there may be an association between vitamin D deficiency and infection in these patients, but this has not been fully elucidated. Therefore, this study investigated the impact of pre-RTx vitamin D deficiency on urinary tract infection (UTI) development after RTx.We measured 25-hydroxyvitamin D3 (25(OH)D3) levels in 410 patients 2 weeks before they underwent RTx. Vitamin D deficiency was defined as 25(OH)D3 <10 ng/mL. The primary outcome was UTI occurrence after RTx. Cox proportional hazard analysis determined whether vitamin D deficiency was independently associated with UTI.The mean 25(OH)D3 level was 12.8 ± 6.9 ng/mL, and 171 patients (41.7%) were vitamin D deficient. During a median follow-up duration of 7.3 years, the UTI incidence was significantly higher in vitamin D-deficient patients (52 patients, 30.4%) compared with vitamin D-nondeficient patients (40 patients, 16.7%) (P = 0.001). Moreover, multivariate Cox proportional hazard analysis showed that vitamin D deficiency was an independent predictor of UTI after RTx (hazard ratio 1.81, 95% confidence interval 1.11-2.97, P = 0.02).Vitamin D deficiency was an independent risk factor for UTI after RTx; hence, determining 25(OH)D3 levels might help to predict infectious complications after RTx.ope

Preoperative Low Serum Bicarbonate Levels Predict Acute Kidney Injury After Cardiac Surgery

Acute kidney injury (AKI) after cardiac surgery is a common and serious complication. Although lower than normal serum bicarbonate levels are known to be associated with consecutive renal function deterioration in patients with chronic kidney injury, it is not well-known whether preoperative low serum bicarbonate levels are associated with the development of AKI in patients who undergo cardiac surgery. Therefore, the clinical implication of preoperative serum bicarbonate levels on AKI occurrence after cardiac surgery was investigated. Patients who underwent coronary artery bypass or valve surgery at Yonsei University Health System from January 2013 to December 2014 were enrolled. The patients were divided into 3 groups based on preoperative serum bicarbonate levels, which represented group 1 (below normal levels) 24 mEq/L. The primary outcome was the predicated incidence of AKI 48 hours after cardiac surgery. AKI was defined according to Acute Kidney Injury Network criteria. Among 875 patients, 228 (26.1%) developed AKI within 48 hours after cardiac surgery. The incidence of AKI was higher in group 1 (40.9%) than in group 2 (26.5%) and group 3 (19.5%) (P < 0.001). In addition, the duration of postoperative stay in a hospital intensive care unit (ICU) was longer for AKI patients and for those in the low-preoperative-serum-bicarbonate-level groups. A multivariate logistic regression analysis showed that low preoperative serum bicarbonate levels were significantly associated with AKI even after adjustment for age, sex, hypertension, diabetes mellitus, operation type, preoperative hemoglobin, and estimated glomerular filtration rate. In conclusion, low serum bicarbonate levels were associated with higher incidence of AKI and prolonged ICU stay. Further studies are needed to clarify whether strict correction of bicarbonate levels close to normal limits may have a protective role in preventing further AKI development.ope