Oversight on the Bioethical Compliance of National R&D Projects or Research Personnel

BACKGROUND: Oversight on the bioethical compliance of national R&D projects or research personnel is currently conducted exclusively by IRB (Institutional Review Board) within the relevant research institute. Considering current state of affairs in Korea, there is an imperative to establish a national oversight system for bioethical compliance, conduct comprehensive oversight on bioethical compliance of national R&D projects, and enhance subject protection system. METHODS: We examined opinions from researchers and IRB personnels regarding ethical oversight system on R&D projects. Additionally, we looked at IRB assessment by KAIRB (Korea Association of Institutional Review Board) in order to identify status and problems with current IRB system in Korea. Assessment was also done for four other countries (US, UK, Germany, Singapore) through in-person visits as well as surveys in writing for a total of 6 months (2012.12.1~2013.5.31). The research comprised of two aspects: system management and R&D project audit. Based on this, we examined current status and problems of the existing system in Korea and made recommendations for improvement. RESULTS: Regulatory objectives and backgrounds of biomedical researches are different from each country due to different characteristics of bioethical oversight system. This shows that each country sets up its own regulations and procedures to fit each situation. Bioethical compliance oversight system greatly varied between the countries. From this study, it can be seen that improvement of existing procedures and oversight system or establishment of new ones are essential in Korea. CONCLUSION: In terms of system management, a dedicated government organization need to be established for bioethical compliance, subject protection, IRB inspection, training, evaluation, and certification of systems, and also support for IRB e-system. Regarding R&D project oversight, it is essential to confirm IRB review results before start of a research, to conduct a review on ethical aspects of research plans, and to carry out continued oversight on bioethical compliance through interim reports.

Hypoxia Induces Connective Tissue Growth Factor (CTGF) in Cultured Tubular Cells / 대한신장학회잡지

BACKGROUND: Connective tissue growth factor (CTGF) is demonstrated to mediate the fibrotic effect of TGF-beta1 and to stimulate cell proliferation and matrix production. In the present study, we examined the effect of hypoxia on CTGF gene expression in cultured mouse tubular cell (MTC). METHODS: Quiescent cultures of MTC were exposed to hypoxia (1% O2) or normoxia in serum-free medium. The effects on hypoxia-induced CTGF expression were evaluated by Northern blot and real- time PCR. The role of MAP kinase was assessed using specific biochemical inhibitors. RESULTS: ELISA revealed that TGF-beta in conditioned medium by MTC exposed to hypoxia was maximally greater at 24 hours (41.16+/-6.31 ng/mL) than medium from normoxic cultures (15.742.92 ng/mL). Hypoxia caused a significant increase in CTGF mRNA expression in MTC (p<0.05). The steady-state level of CTGF mRNA was maximally up regulated by 3-fold within 4 hours as compared with the cells cultured under the normoxic condition. The induction of CTGF was not blocked by either JNK or ERK inhibitor, whereas an inhibitor of p38 MAP kinase reduced the hypoxia-induced stimulation of CTGF (p<0.05). Although hypoxia stimulated TGF-beta production, neutralizing anti-TGF-beta1 antibody did not abolish the hypoxia-induced CTGF mRNA expression. CONCLUSION: These data indicate that hypoxia up-regulates CTGF gene expression, and that p38 MAP kinase plays a role in hypoxic-stimulation of CTGF in cultured renal tubular cells. In addition, hypoxia induces CTGF mRNA expression via a TGF-beta1-independent mechanism.

Mycophenolate Mofetil Therapy in Severe Membranous Nephropathy and Diffuse Proliferative Lupus Nephritis: Clinical Observation / 대한신장학회잡지

OBJECTIVE: Although cyclophosphamide (CYC) is effective for the treatment of diffuse proliferative lupus nephritis (DPLN) and severe membranous nephropathy (MN), it has serious adverse effects. Therefore, we evaluated our clinical observations with mycophenolate mofetil (MMF) for empirical treatment of DPLN and severe MN. METHODS: Seventeen patients with biopsy proven severe MN (n=8) and DPLN (n=9) received MMF for > or = 6 months as primary treatment (n=9) or subsequent maintenance therapy after CYC treatment (n=8). Treatment outcome was evaluated by random urine protein/creatinine ratio (UP/Cr) and serum creatinine (sCr) at the start and at 12 months and compared by the Wilcoxon signed-rank test. RESULTS: Overall, the mean (+/-SD) UP/Cr decreased in both MN (6.48+/-3.03 vs. 1.31+/-1.22, p= 0.016) and DPLN (3.77+/-2.34 Vs 0.83+/-0.53, p=0.043) patients. No significant change in serum Cr was detected in both MN and DPLN patients. Adverse events included nausea/abdominal discomfort (n=1) and menstrual irregularity (n=1). CONCLUSION: Short term empirical treatment with MMF in the majority of patients with severe MN and DPLN was well tolerated and effective in decrease of proteinuria and stabilization of renal function. Controlled clinical trials are necessary to define the role of MMF in the treatment of severe MN and DPLN.

Effect of N-Acetylcysteine in Prevention of Contrast-Induced Nephropathy after Coronary Angiography

BACKGROUND AND OBJECTIVES: Contrast-induced nephropathy (CIN) is associated with increased morbidity and mortality in coronary angiography. Although the mechanism is unclear, N-acetylcysteine (NAC) is known to protect against CIN. Preliminary studies with NAC have found conflicting results for the prevention of CIN in patients undergoing coronary angiography. This study was designed to evaluate the efficacy and safety of NAC for the prevention of CIN in patients undergoing coronary angiography. SUBJECTS AND METHODS: 48 patients with chronic renal insufficiency (mean [+/-SD] serum creatinine concentration, 2.06+/-0.56 mg/dL), who were undergoing coronary angiography with a nonionic, low-osmolar contrast agent, were prospectively studied. Patients were randomly assigned to receive either the antioxidant, NAC (600 mg orally twice daily), and 0.45% saline intravenously (n=25), before and after administration of contrast agents, or saline only (n=23). The renal function parameters were assessed 48 hour before and after radiocontrast media administration. RESULTS: 14 of the 48 patients (29%) showed an increase in the 0.5 mg/dL serum creatinine concentration after 48 hours of contrast media administration: 4 of the 25 patients in the NAC group (16%) and 10 of the 23 in the control group (43%; p=0.036; relative risk, 0.37; 95% confidence interval, 1.04 to 7.79). In the NAC group, the mean serum creatinine concentration insignificantly increased (p=0.54), from 2.2+/-0.8 to 2.3+/-0.9 mg/dL, after 48 hours of contrast media administration; whereas, in the control group, the mean serum creatinine concentration significantly increased (p=0.011), from 1.9+/-0.4 to 2.2+/-0.8 mg/dL. The absolute change in serum creatinine concentration was significantly greater in the control than the NAC group (p=0.044). CONCLUSION: Prophylactic oral administration of the antioxidant NAC, along with hydration, prevents the decrease in the renal function induced by a nonionic, low-osmolality contrast agent in patients with chronic renal insufficiency.

Tuberculous Abscess of the Graft in a Renal Transplant Recipient after Chronic Rejection: Case Report / 대한이식학회지

Tuberculosis is a significant opportunistic infection often found in transplant recipients. Although not common, tuberculosis has been known to develop in higher incidence among transplant recipients than in the general population. The diagnosis and treatment of the tuberculosis in transplant recipients are more complicated because of the side effects of antituberculous agents, their interaction with immunosuppressive drugs, and the higher incidence of atypical presentations with extrapulmonary disease. The patient in this report had no evidence of tuberculous infection anywhere through the body before the transplant. The course of disease was continuously devastating despite active antituberculosis therapy. Only after the transplant nephrectomy, patient's general condition improved. The authors report a patient with tuberculous abscess, developed in a renal allograft after chronic rejection.

Candida Polyarthritis in a Renal Transplant Patient / 대한이식학회지

Candidal infection has been known to cause significant morbidity and mortality in renal transplant patients. Type of immunosuppressive regimens, prolonged antibiotics therapy, metabolic derangement such as diabetes and corticosteroid use, the long-term use of indwelling urinary and intravenous catheters are important predisposing factors in the development of candidal infection. Septic arthritis caused by Candida species is relatively uncommon, occurring most frequently as a complication of disseminated candidiasis. Although several drugs are available for the treatment of Candida arthritis, intravenous amphotericin B therapy has been shown to most consistently result in successful treatment. We report herein successful outcome of treatment with amphotericin B for septic arthritis due to C. albicans after a successful second renal transplant.

Clinical Trial Evaluating Efficacy and Safety of Recombinant Human Erythropoietin(Espogen(R)) in Dialysis Patients / 대한신장학회잡지

We conducted a multicenter clinical trial to evaluate the efficacy and safety of recombinant human erythropoietin(Espogen(R), LG Chemical Ltd.) in the anemic patients of chronic renal failure undergoing dialysis. The patients were end-stage renal disease who were undergoing hemodialysis or peritonea1 dialysis for 3 months or longer and they had less than 8g/dL of hemoglobin and more than 100ng/mL of serum ferritin. Hemodialysis patients were administered 150unit/kg/week of recombinant human erythropoietin as initial dose, and peritoneal dialysis patients 50unitAg, twice per week. We examined hemoglobin value every other week and adjusted the dose in order to maintain hemoglobin level as 10-llg/dL. We enrolled 64 patients and analysed 54 cases in the final. 96.3% (52/54) of patients showed increase by more than 1.0g/dL and the others in- crease by more than 0.5g/dL. Baseline hemoglobin, hematocrit were 7.11+/-0.85g/dL, 21.3+/-2.6% and final level were 10.42+/-1.31g/dL, 31.9+/-3.5%(p=0.0001), respectively. Reticulocyte was increased after 2 weeks of administration from 0.90+/-0.74% to 2.45+/-0.84% The adverse effects included hypertension, headache, increased potassium and phosphate level so required regular monitoring. Therefore we showed that Es-pogen was effective in correcting the anemia of chronic renal failure and didn't have any particular adverse effects.

Changes of Serum Leptin Concentration Shortly after Start of Peritoneal Dialysis / 대한신장학회잡지

Elevated serum leptin concentration can contribute to anorexia and poor nutrition in patients with chronic renal failure, since leptin is elevated in chronic renal failure patients with or without dialysis, especially in chronic ambulatory peritoneal dialysis(CAPD) patients. The aim of this study to find whether leptin can be removed by peritoneal dialysis(PD) and to analyze factors that can affect serum leptin concentration after start of CAPD by observing the changes of serum leptin shortly after start of CAPD and their correlations with body mass index(BMI), serum insulin concentration and residual renal function(Creatinine clearance+Urea clearance/2). Twenty patients who started CAPD during the observation periods were studied. Serum leptin concentration was measured before start of CAPD, 3-5 days and 1, 3 months after start of CAPD by RIA method. Simultaneously, body weight, serum insulin concentration and residual renal function were measured. Removal of leptin was assessed by measuring dialysate leptin concentration divided by average serum leptin concentration before and after peritoneal equilibration test(PET) to compensate for the circardian rhythm of leptin. Leptin was eliminated by PD with dialysate to serum ratio of leptin to be 0.16+/-0.07 which was comparable to removal of beta2-microglobulin(0.14+/-0.06). The mean serum leptin concentration did not decrease after 3-5 days of CAPD(8.4+/-13.1-->11.9+/-18.0) despite its removal by PD and increased markedly 189%, 260% of basal serum leptin concentration on 1 month and 3 months after start of PD, respectively. Correlation coefficients(Spearmann's) between changes of serum leptin concentration and changes of BMI, serum insulin concentration, residual renal function were 0.267(P>0.05, n=20), 0441(P>0.05, n= 16), 0.706(P>0.05, n=8) respectively. Leptin was removed by peritoneal dialysis. Serum leptin concentration did not decrease in 5 days after start of PD despite its removal by PD, and increased markedly 3 months after start of PD. We could not find significant correlation between changes of serum leptin concentration and changes of BMI. Factors other than fat mass gain can stimulate leptin increase shortly after start of PD.