BACKGROUND/AIMS: Because there is a lack of effective biomarkers, we aimed to discover proteomic candidate markers for hepatocellular carcinoma (HCC) in cirrhotic patients at the highest-risk of HCC, and to validate the markers. METHODS: We collected tumor tissue from 5 cirrhotics with HCC, and from 5 cirrhotics without HCC, who underwent liver resection or transplantation. These tissue samples were analyzed by 2-dimensional difference gel electrophoresis coupled with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and potential markers were validated at the transcriptional and translational levels. We also performed western blot assays using other blood samples from 10 cirrhotics with HCC and 10 without HCC. RESULTS: Among the 66 distinguishable spots on 2-D gel images, we identified 15 proteins overexpressed more than 1.5 fold in terms of volume ratio in the tumors. Ten of the over-expressed proteins were identified by MALDI-TOF MS; of those, only methionine adenosyltransferase 1 (MAT1), a protein specific for liver, and acyl-CoA dehydrogenase were significantly up-regulated in tumors in further immunoblotting analyses (Ps<0.05). There was no between-pair difference in MAT1 mRNA measured by real-time polymerase chain reaction (P=0.96). However, in western blots of serum samples, distinct MAT1 bands were observed in all 10 HCC patients, but in only 2 of the non-HCC patients. CONCLUSIONS: MAT1 is a potential marker for surveillance in cirrhotic patients with and without prior HCC.
Acyl-CoA Dehydrogenase ; Biomarkers ; Blotting, Western ; Carcinoma, Hepatocellular ; Humans ; Immunoblotting ; Liver ; Liver Cirrhosis ; Mass Spectrometry ; Methionine Adenosyltransferase ; Methionine ; Proteomics ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Two-Dimensional Difference Gel Electrophoresis

PURPOSE: Despite new treatment strategies, anemia remains the most prevalent complication in patients with end-stage renal disease (ESRD). We investigated whether 25-hydroxyvitamin D [25(OH)D3] deficiency was associated with anemia in ESRD patients. MATERIALS AND METHODS: We reviewed the medical records of 410 ESRD patients who had undergone renal transplantation (RTx) at Yonsei University Health System and who had 25(OH)D3 levels measured at the time of RTx. Patients were divided into two groups based on baseline 25(OH)D3 concentrations: group 1, 25(OH)D3 levels <10 ng/mL; and group 2, 25(OH)D3 levels ≥10 ng/mL. RESULTS: Using multivariate regression models, 25(OH)D3, age, and erythrocyte-stimulating agent (ESA) dose were found to be significantly associated with hemoglobin (Hb) levels [25(OH)D3: β=0.263, p<0.001; age: β=0.122, p=0.010; ESA dose: β=-0.069, p=0.005]. In addition, logistic regression analysis revealed that patients in group 1 had a significantly higher risk for developing anemia (Hb level <10 g/dL) compared to group 2 patients, even after adjusting for potential risk factors for anemia (odds ratio=3.857; confidence interval=1.091-13.632; p=0.036). CONCLUSION: 25(OH)D3 deficiency was significantly associated with anemia in patients with ESRD. Randomized controlled trials are needed to determine whether vitamin D supplementation can improve anemia in these patients.
Adult ; Aged ; Anemia/blood/*etiology ; Calcifediol ; Cross-Sectional Studies ; Female ; Hemoglobin A/analysis ; Humans ; Kidney Failure, Chronic/*complications ; Kidney Transplantation ; Male ; Middle Aged ; Odds Ratio ; Prevalence ; Regression Analysis ; Risk Factors ; Vitamin D/analogs & derivatives/blood ; Vitamin D Deficiency/blood/*complications

Primary amyloidosis has unfavorable prognosis, particularly with organ involvement. Here, we report a case of clinical remission of renal amyloidosis after autologous hematopoietic cell transplantation. A 51-year-old female patient visited our hospital due to generalized edema. Initial evaluation showed hyperlipidemia, hypoalbuminemia, and heavy proteinuria, which were consistent with nephrotic syndrome. However, IgM lamda type monoclonal gammopathy was detected in serum and urine electrophoresis studies. Renal biopsy showed Congo red-positive amyloid deposition in mesangial area, glomerular capillary walls, and arterioles and amyloid fibers were confirmed by electron microscopy. Immunohistochemial study of the biopsy tissue demonstrated systemic light-chain amyloidosis (AL amyloidosis). Multiple myeloma was not evident on bone marrow examination. She received autologous hematopoietic cell transplantation after high dose melphalan treatment. Complete remissions were achieved after the treatment, respectively. Our findings suggest the potential role of autologous peripheral blood stem cell transplantation in treatment of AL amyloidosis.
Amyloid ; Amyloidosis* ; Arterioles ; Biopsy ; Bone Marrow Examination ; Capillaries ; Cell Transplantation ; Congo ; Edema ; Electrophoresis ; Female ; Humans ; Hyperlipidemias ; Hypoalbuminemia ; Immunoglobulin M ; Melphalan ; Microscopy, Electron ; Middle Aged ; Multiple Myeloma ; Nephrotic Syndrome ; Paraproteinemias ; Peripheral Blood Stem Cell Transplantation* ; Plaque, Amyloid ; Prognosis ; Proteinuria ; Transplants

Primary amyloidosis has unfavorable prognosis, particularly with organ involvement. Here, we report a case of clinical remission of renal amyloidosis after autologous hematopoietic cell transplantation. A 51-year-old female patient visited our hospital due to generalized edema. Initial evaluation showed hyperlipidemia, hypoalbuminemia, and heavy proteinuria, which were consistent with nephrotic syndrome. However, IgM lamda type monoclonal gammopathy was detected in serum and urine electrophoresis studies. Renal biopsy showed Congo red-positive amyloid deposition in mesangial area, glomerular capillary walls, and arterioles and amyloid fibers were confirmed by electron microscopy. Immunohistochemial study of the biopsy tissue demonstrated systemic light-chain amyloidosis (AL amyloidosis). Multiple myeloma was not evident on bone marrow examination. She received autologous hematopoietic cell transplantation after high dose melphalan treatment. Complete remissions were achieved after the treatment, respectively. Our findings suggest the potential role of autologous peripheral blood stem cell transplantation in treatment of AL amyloidosis.
Amyloid ; Amyloidosis* ; Arterioles ; Biopsy ; Bone Marrow Examination ; Capillaries ; Cell Transplantation ; Congo ; Edema ; Electrophoresis ; Female ; Humans ; Hyperlipidemias ; Hypoalbuminemia ; Immunoglobulin M ; Melphalan ; Microscopy, Electron ; Middle Aged ; Multiple Myeloma ; Nephrotic Syndrome ; Paraproteinemias ; Peripheral Blood Stem Cell Transplantation* ; Plaque, Amyloid ; Prognosis ; Proteinuria ; Transplants

We undertook this study to elucidate whether baseline peritoneal membrane transport characteristics are associated with high mortality in incident automated peritoneal dialysis (APD) patients. This retrospective study includes 117 patients who started APD at Yonsei University Health System from 1996 to 2008 and had a PET within 3 months of APD initiation. High transporters were significantly older and had a higher incidence of cardiovascular disease. Patient survival for years 1, 3, and 5 were 85%, 64%, and 35% for high transporter and 94%, 81%, and 68% for non-high transporter group (P<0.01). Multivariate analysis revealed that age, diabetes, cardiovascular disease, serum albumin level, and residual renal function were independently associated with high mortality in APD patients. In contrast, high transport status was not a significant predictor for mortality in this population when the other covariates were included. Even though high transport was significantly associated with mortality in the univariate analysis, its role seemed to be influenced by other comorbid conditions. These findings suggest that the proper management of these comorbid conditions, as well as appropriate ultrafiltration by use of APD and/or icodextrin, must be considered as protective strategies to improve survival in peritoneal dialysis patients with high transport.
Adult ; Age Factors ; Aged ; Aged, 80 and over ; Automation ; Cardiovascular Diseases/complications ; Diabetes Complications ; Dialysis Solutions/therapeutic use ; Female ; Glomerular Filtration Rate ; Glucans/therapeutic use ; Glucose/therapeutic use ; Humans ; Kidney Failure, Chronic/therapy ; Male ; Middle Aged ; Multivariate Analysis ; Peritoneal Dialysis/*mortality ; Retrospective Studies ; Risk Factors ; Serum Albumin/analysis ; Survival Rate

The study of cancer in patients treated with dialysis in Korea has not been reported. The aim of this study was to investigate the incidence and mortality of cancer among patients on dialysis in Korea. The study subjects were 106 cancer patients (2.3%) out of 4,562 end-stage renal disease (ESRD) patients maintained on hemodialysis (HD) or peritoneal dialysis (PD) at Yonsei University Health System from 1996 to 2005. We excluded patients in whom the diagnosis of cancer preceded dialysis or those who received renal allograft or started dialysis after renal allograft. Seventy- three (69%) of our subjects were male and 33 (31%) were female. The mean age at the time of cancer diagnosis was 57.9+/-11.7 yr. The mean time from the start of dialysis to the diagnosis of cancer was 75.2+/-63.9 months. The most common cancer site was gastrointestinal tract (GIT) (51%) followed by urinary tract (20%), lung (8%), and thyroid (7%). Sixty nine percent of the total mortality was due to cancer. The mean time from diagnosis to death was 2.9+/-2.5 yr. In ESRD patients with cancer, there were no significant differences in mortality rates by dialysis modality. In ESRD patients, the most common cancer was GIT cancer followed by urinary tract cancer. Therefore, careful surveillance of these cancers in ESRD patients is highly recommended.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Kidney Failure, Chronic/*complications/epidemiology/*therapy ; Korea ; Male ; Middle Aged ; Neoplasms/*complications/epidemiology ; *Peritoneal Dialysis ; Registries ; *Renal Dialysis ; Time Factors

PURPOSE: Hyperuricemia is a common complication occurring shortly after kidney transplantation. Although increased uric acid level is a risk factor for cardiovascular disease and mortality, the relationship between uric acid level and graft function after transplantation has been a controversial issue. Therefore, we investigated the effects of uric acid on glomerular filtration rate (GFR) and graft survival in the early periods of kidney transplantation. METHODS: Data were collected from 245 patients who underwent kidney transplantation between 2002 and 2004 at Yonsei University Medical Center. Uric acid level and estimated GFR were measured monthly during the first 6 months and then yearly for 3 years. RESULTS: The mean age of the study population was 40.2+/-11.7 years. The proportion of patients with hyperuricemia (uric acid < or =6.8 mg/dL) showed increment during the 3 year follow up. Increased serum uric acid level showed a negative correlation with estimated GFR during the initial 6 months after transplantation (r=-0.026, p<0.05). In Kaplan-Meier analysis, patients with a mean uric acid level higher than 6.8 mg/dL during the first 6 months showed a lower cumulative graft survival during the consecutive 3 years compared to patients with a uric acid level lower than 6.8 mg/dL (HR 1.7, p=0.003). CONCLUSION: Uric acid levels were associated with the changes of GFR in the initial 6 months of kidney transplantation, and the hyperuricemia during the early stages of transplantation might influence the long term graft survival.
Academic Medical Centers ; Cardiovascular Diseases ; Follow-Up Studies ; Glomerular Filtration Rate ; Graft Survival ; Humans ; Hyperuricemia ; Kaplan-Meier Estimate ; Kidney ; Kidney Transplantation ; Risk Factors ; Transplants ; Uric Acid

A 35-year-old man, previously hepatitis B surface antigen (HBsAg) carrier, presented with gross hematuria and heavy proteinuria that he had been suffering from for 1 month. Serum creatinine was 4.4 mg/dL. Renal biopsy showed pauci-immune crescentic glomerulonephritis. He received plasmapheresis and was treated with high-dose steroids and cyclophosphamide. Lamivudine was started for the prevention of hepatitis B virus (HBV) activation. Serum creatinine and proteinuria were ameliorated one week after the treatment. There was no sign of HBV activation after six months of treatment. We report a case of rapidly progressive glomerulonephritis in a HBV carrier successfully treated with high dose immunosuppressive therapy and prophylactic lamivudine.
Adult ; Biopsy ; Creatinine ; Cyclophosphamide ; Glomerulonephritis ; Hematuria ; Hepatitis ; Hepatitis B ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Humans ; Lamivudine ; Plasmapheresis ; Proteinuria ; Steroids ; Stress, Psychological

PURPOSE: Lower technical survival rate of CAPD compared to hemodialysis is still concerned. We aimed to evaluate the characteristics of long-term CAPD survivors in pre-dialysis and early phase of CAPD for estimating predictive markers for long-term maintenance of CAPD. METHODS: We retrospectively reviewed records of long-term CAPD patients (LT group, >100 months, n=51) and short-term patients (ST group, <50 months, n=102) who were age-sex matched with the LT group in a 2:1 ratio. Clinical characteristics, serial biochemical parameters, Kt/V, and peritoneal equilibrium test (PET) within 1 month and at 1 year of CAPD were analyzed. RESULTS: LT group had lower prevalence of diabetes, higher pre-dialysis serum albumin, creatinine, % LBM at 1 month of CAPD and lower peritonitis rate compared to ST group. However, dialysis adequacy, residual renal function and transport status showed no differences between two groups at 1 month and 1 year of CAPD. In multivariate analysis, diabetes, peritonitis rate and %LBM were independent risk factors for failure of long-term maintenance of CAPD. Moreover, patients with high %LBM were more likely to be in LT group, had longer CAPD maintenance duration, and lower peritonitis rate. In multiple linear regression analysis for risk factors associated with peritonitis, %LBM at 1 month and pre-dialysis serum albumin were independently associated with peritonitis rate. CONCLUSION: The present study revealed that non-diabetic history, higher %LBM and lower peritonitis rate are important predictors of long-term CAPD survival. Also, poor nutritional status assessed by %LBM and serum albumin level was independently associated with high frequency of peritonitis.
Creatinine ; Dialysis ; Humans ; Linear Models ; Malnutrition ; Multivariate Analysis ; Nutritional Status ; Peritoneal Dialysis ; Peritoneal Dialysis, Continuous Ambulatory* ; Peritonitis* ; Prevalence ; Renal Dialysis ; Retrospective Studies ; Risk Factors ; Serum Albumin ; Survival Rate ; Survivors

This study was performed to evaluate the efficacy and toxicity of low-dose paclitaxel/cisplatin chemotherapy in patients with metastatic or recurrent gastric cancer that had failed 5-fluorouracil/platinum-based chemotherapy. Thirty-two patients with documented progression on or within 6 months after discontinuing 5-fluorouracil/platinum-based chemotherapy were enrolled. As a second-line treatment, paclitaxel (145 mg/m2) and cisplatin (60 mg/m2) was administered on day 1 every 3 weeks. Among 32 patients enrolled, 8 (25%) responded partially to paclitaxel/cisplatin, 8 (25%) had stable disease, and 14 (44%) had progressive disease. Two patients (6%) were not evaluable. The median time to progression (TTP) and overall survival for all patients were 2.9 months and 9.1 months, respectively. The most common hematologic toxicity was anemia (47%). Grade 3 neutropenia developed in three patients (9%), but no other grade 3/4 hematologic toxicity occurred. The most common non-hematologic toxicities were emesis (31%) and peripheral neuropathy (38%). Three cases (9%) of grade 3/4 emesis and 2 cases (6%) of grade 3 peripheral neuropathy developed. In conclusion, low-dose paclitaxel and cisplatin chemotherapy showed moderate activity with favorable toxicity profiles. However, relatively short TTP of this regimen warrants the development of more effective paclitaxel-based regimens other than combination with cisplatin in these patients as second-line therapies.
Adenocarcinoma/*drug therapy ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse ; Cisplatin/administration & dosage/adverse effects ; Female ; Fluorouracil/administration & dosage/adverse effects ; Humans ; Leucovorin/administration & dosage/adverse effects ; Male ; Middle Aged ; Organoplatinum Compounds/administration & dosage/adverse effects ; Paclitaxel/administration & dosage/adverse effects ; Stomach Neoplasms/*drug therapy/mortality ; Survival Rate ; Treatment Failure