No abstract available.
Glomerulonephritis* ; Humans ; T-Lymphocytes*

Cytomegalovirus(CMV) infection occurs more frequently in renal transplant recipients than in the normal population. But the incidence and severity of CMV infection and antibody positivity are different between countries. We studied the incidence of CMV infection with a long term follow up in renal transplant recipients who were IgG CMV positive and whose donors were also IgG CMV positive preoperatively. We studied the difference and usefulness of various detection methods including IgM CMV antibody by ELISA, shell vial culture, and quantitative dual polymerase chain reaction(PCR). We also studied possible factors that may affect CMV infection and the function of the grafted kidney in CMV infected patients. This study included 36 patients, 20 males and 16 females, who received renal transplantation at Hanyang University Hospital between July, 1994 and March, 1995. IgG and IgM CMV antibodies were detected and shell vial cultures were performed in recipient candidates and donor candidates preoperatively. Postoperatively, we checked IgM CMV and performed shell vial cultures in renal transplant recipients every month after the operation and when CMV infections were suspected. We also performed dual PCR with endpoint titration to quantify the amount of CMV DNA. The total incidence of CMV infection was 30.6% (11 patients among 36 patients). Three patients had CMV disease, and only one patient was severe enough to need gancyclovir therapy. The average onset of infection was 12.9 weeks after the operation(earliest 5weeks-latest 33weeks). In all patients with CMV disease, CMV positivity appeared by all three detection methods. But detection time and duration of positivity were different. The amount of CMV DNA in patients with active CMV disease was higher than those of asymptomatic patients and one patient following antiviral therapy. Age, sex, donor type, HLA matching and rejection did not affect CMV infection. Incidence of CMV infection was higher in patients who were transfused within 3 weeks before the operation(6/8 vs 5/28, p=0.048). Changes of creatinine level from initial outpatient department(OPD) visit to last OPD visit which were corrected by OPD follow up time showed no significant difference between CMV infected and non-infected patients In conclusion, the incidence of CMV infection and disease was relatively low, and the degree of disease severity was mild. In our renal transplant recipients, CMV infection may not be a serious problem. Quantitative dual PCR using end-point titration is a good method to detect CMV infections and monitor the clinical course. Because it is easy to use, detect disease earlier and can quantify the amount of CMV DNA. Among various factors, transfusion affected CMV infection significantly in our patients. In an average of 231 days of OPD follow up time, CMV infected patients showed no impairment of grafted kidney function, but a more long term follow up is needed.
Antibodies ; Creatinine ; Cytomegalovirus Infections* ; Cytomegalovirus* ; DNA ; Enzyme-Linked Immunosorbent Assay ; Female ; Follow-Up Studies ; Ganciclovir ; Humans ; Immunoglobulin G* ; Immunoglobulin M ; Incidence ; Kidney ; Kidney Transplantation ; Male ; Outpatients ; Polymerase Chain Reaction ; Tissue Donors ; Transplantation* ; Transplants

Glucocorticoids are usually given according to a standard dosing protocol regardless of individual difference. We evaluated the pharmacokinetic characteristics of methylprednisolone and the degree of interpatient variation in stable Korean renal transplant recipients during the period of 15-21 days after transplantation. This study included 23 renal transplant recipients, 13 males and 10 females, who received kidneys from living donors with stable graft function and without episode of acute rejection. On the study day at 8 A.M., 16.3mg of ethylprednisolone sodium succinate (i.v.) was administered to each patient instead of usual dose (20mg) of prednisolone (p.o.) after sampling of 7cc of baseline blood and additional blood samples were drawn after starting infusion. Plasma was separated and analyzed for methylprednisolone level using high performance liquid chromatography (HPLC) assay, and parameters for pharmacokinetics were calculated. There was significant interpatient variation in the pharmacokinetics of methylprednisolone in our patients group. There was no significant difference in the pharmacokinetic parameters between patients with and without side effects of steroid. Korean renal transplant recipients had higher volume of distribution than black renal transplant recipients; lower clearance than white renal transplant recipients; longer t1/2 than both black and white renal transplant recipients. Even if the number of patients included in this study was too small to reach conclusion, the differences in the pharmacokinetics of glucocorticoids do not seem to be a significant risk factor for side effects of steroid after transplantation. It may be necessary to individualize the dose of a glucocorticoid to achieve an optimal effect and also we need to establish a new steroid regimen protocol for Korean renal transplant recipients.
Chromatography, Liquid ; Female ; Glucocorticoids ; Humans ; Individuality ; Kidney ; Kidney Transplantation ; Living Donors ; Male ; Methylprednisolone* ; Pharmacokinetics ; Plasma ; Prednisolone ; Risk Factors ; Sodium ; Succinic Acid ; Transplantation* ; Transplants

A new microemulsion formulation of cycloporine(CsA) has been recently used in Korean renal transplants. We compared the clinical effect and the trough levels of microemulsion cyclosporine(M-CsA) as opposed to conventional CsA in soft gelatine capsule(C-CsA). In the study for hospitalized post-operative patients, 58 patients were divided into two groups; the C-CsA(control) group(n=23) received C-CsA, and the M-CsA group(n=28) received M-CsA after transplantation. In the study for stable OPD patients, 32 patients were divided into two groups. The C-CsA(control) group(n=16) did not change the type of CsA and continued C-CsA medication after Sep. 1994, M-CsA group(n=16) switched from C-CsA to M-CsA in Sep. 1995. In postoperative hospitialized patients, mean trough levels were not different between the two groups with CsA dosage (9mg/kg - 5mg/kg), although the M-CsA group had higher trough levels with 10mg/Kg CsA dosage than the control group. In OPD patients, there was no significant change in CsA dosage in both groups during the 6 month period. Mean trough levels, 6 months after conversion, were lower in the M-CsA group than in the control group. In the M-CsA group who received the same dose as a preconversion dose, mean trough levels at 2, 3, 4, 5, 6 months were lower than the preconversion level, although control groups had lower trough levels only at 5 months. Serum creatinine levles were significantly decreased in the M-CsA OPD patients. From these results, we couldn't find a dose saving effect of M-CsA in our patients, it is much desirable to study the pharmacokinetics of M-CsA and C-CsA in Korean renal transplants.
Creatinine ; Cyclosporine* ; Gelatin* ; Humans ; Kidney Transplantation ; Pharmacokinetics ; Transplantation*

PURPOSE: Observational results on seasonal variation of interdialytic weight gain in patients with end-stage renal disease treated with hemodialysis are controversial till now. There has been no report about it for Korean patients. The relation of interdialytic weight gain and climatic factors was studied in one region of Korea. METHODS: From Jan. 2002 to Dec. 2002, fifty patients receiving conventional and regular hemodialysis three times a week in Hanyang University Hospital, Seoul, Korea, where there is distinct seasonal variation in monthly temperature, relatively humidity, and duration of sunshine, were analyzed. For each patient, body weight and blood pressure were measured before and after each dialysis treatment three times per week for one year. The monthly mean values for interdialytic weight gain and blood pressure in relation to the monthly values for climatic factors were then analyzed. RESULTS: The seasonal pattern of interdialytic weight gain was evident throughout the one-year period. The monthly mean temperature was highest in July and lowest in January and mean monthly interdialytic weight gain was lowest in July and highest in December. The difference of mean interdialytic weight gain between July and January was significant (p< 0.05). Interdialytic weight was inversely correlated with monthly mean temperature, mean maximal temperature, and mean minimal temperature(r= -0.721 with p=0.008, r=-0.714 with p=0.009, and r= -0.717 with p=0.009, respectively) but not with mean relatively humidity and duration of sunshine. Mean predialysis systolic and diastolic blood pressure were not related to changes in temperature, relative humidity, and duration of sunshine. CONCLUSION: Interdialytic weight gain in patients with end-stage renal disease treated on hemodialysis was correlated with seasonal variation in temperature, with higher values in the winter and lower values in the summer. It would be better to consider this finding to treat hemodialysis patients.
Blood Pressure ; Body Weight ; Dialysis ; Humans ; Humidity ; Kidney Failure, Chronic ; Korea ; Renal Dialysis* ; Seasons* ; Seoul ; Sunlight ; Weight Gain*

BACKGROUND: The hypotensive effect of the lisinopril, a long acting angiotensin converting enzyme inhibitor, was studied. METHOD: 10mg of lisinopril was administered in 30 hypertensive Korean adults during twelve week after a weeks observation for washout with stepwise increments of the dose according to the patients blood pressure in every two weeks. RESULTS: The supine blood pressures were decreased from 173.3+/-27.9/105.7+/-19.4mmHg to 131.8+/-23.1mmHg/81.4+/-18.7mmHg at the end of twelve weeks durg therapy(P<0.05). The standing blood pressures were also decreased conferrably and to the some lower levels. Hematologic examination and blood chemistry revealed no discernible abnormal findings before and after the treatment. During the period of the study a few probably drug-related symptom such as dry cough and dry mouth developed but not troublesome enough to stop administering. CONCLUSION: Lisinopril 10mg once daily regimen is well tolerated and effective in the treatment of hypertensive patients.
Adult ; Blood Pressure ; Chemistry ; Cough ; Humans ; Hypertension ; Lisinopril* ; Mouth ; Peptidyl-Dipeptidase A

We studied the chronic renal allograft dysfunction in Korean renal transplants from 1 year after transplantation to 5 years. We evaluated renal function by simply using the reciprocal serum creatinine level and sought to find factors affecting the value of the reciprocal serum creatinine and graft survival, and changes of the slope of reciprocal serum creatinine. We also estimated the reciprocal serum creatinine from demographic parameters and routine laboratory results. This study included 114 patients, 87 male and 27 female who underwent renal transplantations and had functioning allografts for more than 18 month after transplantation. The results were as follows. 1) The reciprocal serum creatinine level decreased slowly and linearly. 2) There were many factors related to the reciprocal creatinine, including blood urea nitrogen, serum uric acid level, age of donors, sex of recipients, presence of acute rejecton, age of recipient, serum phosphorus, white cell count in blood, cyclosporine level in blood, hemoglobin level, posttransplantation period. We could derive the estimated reciprocal serum creatinine from data of the patients. 3) The age of the recipient and cyclosporine level at 1 year after transplantation affected the slope of the reciprocal serum creatinine during follow-up time. 4) There were 16 graft loss, including 3 functioning graft loss and 13 graft loss due to chronic allograft dysfunction. 5) Besides creatinine and BUN level at 1 year, higher blood pressure and proteinuria and lower hemoglobin levels at 1 year after transplantation were related to the graft loss from chronic allograft dysfunction. 6) There were more chronic allograft loss in patients who had lower actuarial reciprocal serum creatinine than estimated reciprocal serum creatinine. Because follow-up time was relatively short and there were only mild increases in serum creatinine level in our study, follow up of our patients for a longer-term period is required to find other factors affecting the renal allograft dysfunction.
Allografts* ; Blood Pressure ; Blood Urea Nitrogen ; Cell Count ; Creatinine ; Cyclosporine ; Female ; Follow-Up Studies ; Graft Survival ; Humans ; Kidney Transplantation ; Male ; Phosphorus ; Proteinuria ; Tissue Donors ; Transplants ; Uric Acid

The precise etiology of hemolytic uremic syndrome (HUS) is unknown. However, it has been associated with bacterial (Shigella, Salmonella, E. coli, S. pneumoniae), Bartonella, and viral (coxsackie, ECHO, influenza, varicella. Epstein-Barr) infections and with endotoxemia. Recently, we experienced a case of HUS in a 16-year-old boy who was in the acute phase of an Epstein-Barr virus (EBV) infection. He had typical manifestations of HUS and EBV infection. He also transiently presented disseminated intravascular coagulation. His renal dysfunction recovered by supportive care, including hemodialysis, plasmapheresis, antihypertensive medication and aspirin. We present this case with a review of the literature as the second report of HUS associated with EBV infection.
Adolescence ; Follow-Up Studies ; Hemolytic-Uremic Syndrome/virology* ; Hemolytic-Uremic Syndrome/therapy ; Herpesviridae Infections/diagnosis* ; Herpesvirus 4, Human/isolation & purification* ; Human ; Male ; Renal Dialysis ; Tumor Virus Infections/diagnosis*

OBJECTIVE: Cyclosporine(CsA) and tacrolimus, albeit different in structure, exert immunosuppressive effect by similar mechanism. Although most of clinical manifestations, including nephrotoxicity, are similar in the patients using these drugs, there are some differences including gum hyperplasia, neurotoxicity, and hepatic fibrosis between two drugs. There are several reports about association between reactive oxygen species(ROS) and CsA. In contrast, tacrolimus is known to decrease ROS in central nervous system. Thus, we investigated the possibility of different effects of tacrolimus and CsA on the generation of ROS, on the synthesis and degradation of collagen. METHODS: Experiments were done in primary cultured mesangial cells between 4th and 8th passages. CsA was added to the culture dishes in different concentration(making final CsA concentration of 0, 2, 4, 8 microgram/milliliter) and N-acetylcysteine(NAC) was also added in another mesangial cell culture at 4 microgram/milliliter of CsA concentration; tacrolimus was added in similar pattern(making final tacrolimus concentration of 0, 0.1, 0.2, 0.4 microgram/milliliter, NAC in 0.2 microgram/milliliter of tacrolimus concentration). RESULTS: No significant decrease in viability was noted in both cell groups, but growth retardation was weak in tacrolimus treated cells comparing with CsA treated cells. By flow cytometry, we could find the generation of ROS in CsA treated cells, but not in tacrolimus treated cells. In RT-PCR, there is no significant difference in m-RNA expression for a number of molecules including collagen III, MMP-2, TIMP-2, MT1-MMP in either CsA treated cells or tacrolimus cells. But in zymogram, MMP-2 activities were decreased at higher CsA concentration, then increased with addition of NAC. In tacrolimus cells, MMP2 activity was not changed at 0.1 and 0.2 microgram/milliliter; but, at the concentration of 0.4 microgram/milliliter, changed and not reversed by NAC. MMP-9 activity was similar in both cells. CONCLUSION: We could find ROS generation in CsA treated human mesangial cells, but not in tacrolimus treated cells. We think this difference resulted in the decrease of post-transcriptional MMP-2 activity in CsA treated cells and we also think tacrolimus cells in our experiments were not influenced by ROS. From these results, tacrolimus and CsA are different in the generation of ROS that have some effects in the matrix accumulation in mesangial cells. These result does not mean that tacrolimus is superior to CsA in nephrotoxicity, because nephrotoxicity is similar between two drugs. In conclusion, the mechanisms of nephrotoxicity are different between CsA and tacrolimus.
Central Nervous System ; Collagen ; Cyclosporine* ; Extracellular Matrix* ; Fibrosis ; Flow Cytometry ; Gingiva ; Humans* ; Hyperplasia ; Matrix Metalloproteinase 14 ; Mesangial Cells* ; Oxygen ; Tacrolimus* ; Tissue Inhibitor of Metalloproteinase-2

OBJECTIVE: Treatment with cyclosporine(CsA) for a long-term period may induce renal glomerulosclersosis and interstitial fibrosis. Reactive oxygen species(ROS) seems to be involved in the process of glomerulosclersosis and interstitial fibrosis. We investigated the effect of CsA on the generation of ROS and extracellular matrix accumulation in cultured human mesangial cells. We also studied the relationship between ROS formation and extracellular matrix and the effect of antioxidant on ROS formation and/or extracellular matrix degradation. METHODS: Mesangial cells were treated with varying dose of Cyclosporine(0, 2.5, 5, 7.5 and 10microgram/ mL) and also with cyclosporine(5microgram/mL) plus N- acetylcysteine(1mM). ROS was measured by flow cytometric analysis. mRNA expression of MMP-2, TIMP-2, MT1-MMP and collagen III was assessed by RT-PCR method. MMP-2 activity was measured by gelatin zymography. RESULTS: No significant difference was noted in cell viability with each CsA concentration. CsA inhibited the cell proliferation in a dose dependent manner and induced the expression of ROS. Antioxidant NAC reversed the effect of cyclosporine. CsA had no effect on the mRNA expression of collagen III, MMP-2, TIMP-2, MT1-MMP. However CsA decreased the MMP-2 activity in a dose dependent manner, which was also reversed by NAC. CONCLUSION: Cyclosporine-induced ROS may be associated with the extracellular matrix accumulation, that is glomerulosclersosis and interstitial fibrosis by inhibiting the cell proliferation and by decreasing the degradation of extracellular matrix. Antioxidant, at least in vitro, may prevent some of the adverse effects of CsA on renal function.
Cell Proliferation ; Cell Survival ; Collagen ; Cyclosporine* ; Extracellular Matrix* ; Fibrosis ; Gelatin ; Humans* ; Matrix Metalloproteinase 14 ; Mesangial Cells* ; Oxygen ; RNA, Messenger ; Tissue Inhibitor of Metalloproteinase-2