High Glucose Induces MCP-1 Expression in Cultured Human Mesangial Cells Partly Via Tyrosine Kinase-AP-1 Pathway / 대한신장학회잡지

Infiltration of circulating monocytes into glomeruli has been implicated in the pathogenesis of glomerular injury in many human and experimental forms of glomerulonephritis. Monocyte chemoattractant protein-1(MCP-1), a potent chemokine with considerable specificity for monocytes, can be up-regulated by various cytokines and growth factors in mesangial cells. Glomerular infiltration of monocytes has been reported in diabetic nephropathy as well. However, effect of high glucose on MCP-1 expression in human mesangial cells has not been known well. We investigated the effect of high glucose on MCP-1 expression and its signal transduction pathway. Human mesangial cells were conditioned with glucose(5-60 mM) or mannitol chronically for up to 5 days. Expression of MCP-1 mRNA and protein was measured by Northern blot analysis and ELISA respectively. To examine the role of transcription factor AP-1 or NF-KB, electrophoretic mobility shift assay(EMSA) was performed. Glucose induced MCP-1 mRNA expression in a time and dose dependent manner. MCP-1 protein in cell culture supernant was also increased. Equivalent concentrations of mannitol had no significant effect. EMSA revealed that glucose increased the AP-1 binding activity in a time and dose dependent manner but not NF-B. Inhibitor of AP-1, curcumin(7.5- 15 muM) dose dependently suppressed the induction of MCP-1 mRNA by high glucose. Tyrosine kinase inhibitors such as genistein(12.5-50 muM) and herbimycin A(0.1-1 muM) inhibited the high glucose-induced MCP-1 mRNA expression in a dose dependent manner and also suppressed the high glucose-induced AP-1 binding activity. In summary, high glucose induces mesangial MCP-1 expression partly via tyrosine kinase-AP-1 pathway.

A Case of Persistent Anemia in a Renal Transplant Patient - Parvovirus B19 Infection / 대한신장학회잡지

We report an unexplained anemia that persisted for 4 months in a renal transplant patient who was receiving immunosuppression therapy that included prednisolone, tacrolimus, and azathioprine. A bone marrow biopsy demonstrated pure erythroid hypoplasia and occasional giant pronormoblasts with intranuclear inclusions, characteristic of a parvovirus B19 infection. Both the serum and bone marrow cells were positive for a parvovirus B19 DNA polymerase chain reaction. The anemia resolved 6 weeks after the administration of IV immunoglobuln. But, 4 months later, refractory anemia developed and persisted despite treatment with IV immunoglobulin. However, the patient showed rapid improvement after tacrolimus was switched to cyclosporin A. A parvovirus B19 infection should be included in the differential diagnosis of renal transplant recipients who present with an anemia associated with low reticulocytes; and clinicians should be awared that tacrolimus may impair the clearance of a parvovirus B19 infection.

Two Cases of Combined Liver-kidney Transplantation in Patients with End Stage Renal Diseases Associated with Hepatitis B Related Liver Cirrhosis / 대한신장학회잡지

We here report two cases of combined liver-kidney transplantation in patients with both end stage renal disease and hepatitis B related liver cirrhosis. The first case was a 55-year-old man with hepatitis B related liver cirrhosis and chronic renal failure, who received cadaveric liver and kidney transplantation. Immunosuppressants were cyclosporine, prednisolone, and mycophenolate mofetil. Clinical course was uneventful except for hemolytic anemia due to alloimmunization that occurs after ABO-mismatched solid organ transplantation. Hemoglobin level became stable after plasmapheresis. His renal and hepatic function is maintained up to the present time. The second case was a 42-year-old man with nephrotic syndrome and liver cirrhosis. The patient underwent living related-combined liver-kidney transplantation. Donors were his son and brother. Blood type of the patient and donors were identical and the result of HLA crossmatch was negative. On the 14th postoperative day, stenosis at anastomotic site of hepatic artery was detected. After balloon angioplasty hepatic function was normalized. At 8 months after the transplantation, the patient is stable without adverse events.

The Clinical Outcomes of Coronary Stenting and Coronary Artery Bypass Grafting in ESRD Patients with Ischemic Heart Disease / 대한신장학회잡지

The purpose of this study was firstly, to evaluate the efficacy of coronary stenting in ESRD patients compared with non uremic patients and secondly, to compare the perioperative mortality of coronary artery bypass grafting(CABG) in ESRD patients with that in non-uremic patients exhibiting a similar degree of left ventricular function. We examined the clinical restenosis of coronary stenting and 30 day mortality rate after CABG in this retrospective, case-controlled study. The case histories of twenty-five ESRD patients with ischemic heart disease(IHD) and twenty-five non-uremic IHD patients matched for age, sex, ejection fraction and number of implanted stents, who had undergone first, elective, primarily successful coronary stenting were reviewed. The case of histories of another sixteen ESRD patients with IHD and sixteen non-uremic IHD patients matched for age, sex, ejection fraction and number of grafted vessels, who had undergone first elective CABG were also reviewed. Clinical restenosis developed in nine of the twenty-five ESRD patients and in eight of the twenty-five non-uremic patients after coronary stenting within follow up periods of 16.9+/-14.5 months and 17.6+/-14.6 months, respectively. There was no significant difference in the cumulative clinical restenosis free curves between the two groups(p=0.79). Three out of sixteen for the ESRD patients and one out of sixteen for the non-uremic patients died in 30 days after CABG, follow up periods being 11.3+/-9.6 months and 11.1+/-8.9 months, respectively. The perioperative mortality did not differ between the two groups(p=0.28). We conclude that coronary stenting in ESRD patients is as effective as in non-uremic patients regarding initial coronary revascularization and perioperative mortality rate of CABG in ESRD patients is not significantly higher compared with non-uremic patients when Left ventricular function is matched.

A Case of Idiopathic Fibrillary Glomerulonephritis / 대한신장학회잡지

A 17-year-old girl was admitted to our hospital due to mild generalized edema. Laboratory tests revealed a serum creatinine was 0.7mg/dL, protein/albumin 6.7/3.5g/dL, cholesterol 190mg/dL, hemoglobin 10.0g/dL, and 24 hour urinary protein 4,40mg/day. Chest X-ray and renal ultrasound were normal. There were no clinical or serologic evidences of paraproteinemia, cryoglobulinemia, light chain disease or systemic lupus erythematosus. Renal biopsy showed membranoproliferative glomerulonephritis-like pattern with lobular accentuation, hypercellularity and diffuse GBM thickening by light microscope. Congo red staining was negative. Granular IgG and C3 deposits were found along the glomerular capillary wall and mesangium by immunofluorescence microscope. Ultrastructurally, abundant subendothelial and mesangial fibrillary deposits were found associated with thickening and wrinkling of GBM. These fibrils, measured about 20-30nm in diameter, were nonbranching and randomly arranged without either periodicity or an organized structure. These findings were compatible with those of fibrillary glomerulonephritis. Thus we report a case of idiopathic fibrillary glomerulonephritis, which is a rare cause of nephrotic syndrome.

Clinical Significance and Prognostic Factors of IgA Nephropathy Developed in Renal Allograft / 대한신장학회잡지

Recently IgA nephropathy(IgAN) in transplanted kidney have been reported a more grave prognosis of the disease, which account for progressive allograft loss as 12-16%. But, the studies for the clinical significance and the prognostic factors of IgAN developed in transplanted kidney were not sufficient. We analyzed the frequency and the prognostic factors of IgAN developed in patients who underwent Kidney transplantation(KT) between January 1990 and October 1998. Total 231 renal biopsies was done. IgAN was diagnosed in 31 cases, and it was 13.4% of total cases and 24.4% of cases that acute rejection(AR) were excluded. After the 3 patients of IgAN was excluded due to combined AR, 28 patients were followed. The allograft dysfunction, which defined as serum creatinine at last follow-up was above 2.0 mg/dL, was observed in 10 patients(35.7%) and 4 patients(14.3%) of them had graft failure and restarted hemodialysis. The serum crcatinine and creatinine clearance at renal biopsy were significantly correlated with allograft dysfunction, also interstitial fibrosis, tubular atrophy and vascular fibrous intima1 thickening showed similar correlation with prognosis. In conclusion, when allograft dysfunction was developed, IgAN in transplanted kidney should be considered and if the evidences of elevated serurn creatinine and decresed creatinine clearence at biopsy, severe interstitial fibrosis and tubular atrophy, severe vascular fibrous intimal thickening were present, more closer follow-up and careful treatment should be taken.

Clinical Analysis on REnal Transplants at Asan Medical Center / 대한신장학회잡지

From June 1990 to December 1998, 792 kidney transplantations were performed at Asan Medical Center. 436 cases(55M) were from living-related donors, 139 cases(17.6%) were from living-unrelated donors and 217 cases(27.4%) were from cadaveric donors. The results of the trasnplantation were analyzed according to the various factors known to influence the outcome of transplantation. In living transplants, the overall patients survival rate was 98.2% at 1 year and 95.8% at 5 years, the corres-ponding allograft survival rate was 96.9 and 86.1N. In cadaveric transplants, the overall patients survival rate was 94.3% at 1 year and 94.3% at 5 years, the corresponding allograft survival rate was was 90.296 and 84.8%. In living transplants, donor age(>50yrs), recipient age(>50yrs), ABO compatability, pretrans-plant blood transfusion, diabetic history had no effect on allograft survival rate. But HLA DR cornpa-tability, serum creatinine(2.5mg/dL) at discharge and rejection history had effect on allograft survival(p50yrs), recipient age(>50yrs), ABO compatability, HLA DR match, diabetic history, pretransplant transfusion had no effect on allograft survival. But serum creatinine at discharge(>2.5mg/dL) and posttransplant rejection had effect on allograft survival.

Difference of Pertoneal Solute Transport in CAPD Patients with and without Diabetes Mellitus: Measurement by Personal Dialysis Capacity(PDC) Test / 대한신장학회잡지

Using PDC test, peritoneal function in CAPD patients was compared between diabetes and non- diabetes. PDC test were performed in 12 diabetic and 11 nondiabetic CAPD patients. Urea, creatinine, and albumin were measured in each dialysate effluent. Blood urea nitrogen, creatinine, glucose, albumin, and sodium were measured in blood sample at the start and the end of the study. Area parameter(Ao/d x), hydraulic conductance(LpS), final absorption rate (JVAR), large pore fluid flux(JVr.), urea generation rate(UGR), creatinine generation rate (CGR), protein nitrogen appearance/protein catabolic rate(PNA/PCR), residual renal Ccr, total Ccr(PD Ccr+renal Ccr), water removal via PD, total ultrafiltration, and PD clearance of urea, creatinine, vitamin B12 b2 microglobulin, and albumin were calculated. In diabetic patients(n=12), serum albumin was lower in patients on CAPD for less 6 months than patients on CAPD for more 15 months. But total ultrafiltration was lower in patients on CAPD for more 15 months. In non-diabetics(n=ll), protein loss across the peritoneum was lower in patients on CAPD for more 15 months. Other PDC parameters were not different in diabetic and non-diabetic patients according to CAPD duration. In patients on CAPD for less 6 months, serum albumin and PNA/PCR were lower in diabetics than non-diabetics.

Hyperfiltration Affecting the Outcome of Living-related Renal Allograft / 대한신장학회잡지

It is well known that immunologic factors like rejection episode and HLA missmatch influence allograft loss and prognosis. However, non-immu- nologic factors such as glomerular hyperfiltration may also have an effect on the survival of the allograft. We measured relative kidney function(dkRF) by DMSA scan, GFR(dGFR) using EDTA and CCr dCCr) by 24-hour urine collection in donors of 70 adult living-related renal allografts engrafted at a single center between December 1992 and January 1994 as a donor work-up before transplantation, and calculated donated kidney GFR(dkGFR=dGFRxdkRF) and CCr(dkCCr=dkCCrxdkRF). We observed graft function for 5 years and analyzed the prognostic factors for the graft. Graft dysfunction was defined as the increase of serum creatinine 5 years after transplantation more than 1.5 times of stabilized serum creatinine at 3 months after transplantation. 1) Sixty patients were followed up for 5 years. Graft dysfunction was observed in 22 patients(37%) and maintenance renal replacement therapy was required in 9(15%) of them. 2) Of the non-immunologic factors, donor age was older in patients with graft dysfunction(51 +/- 12 years) than those without it(34 +/- 11 years, p<0.01), but dkGFR(54.1 +/- 12.2ml/min vs. 58.5 +/- 11.9mVmin), dkCCr(44.8 +/- 14.3mVmin vs. 50.74 13.4ml/min) and the ratio of body surface area(recipient/donor, 0.964 0.14 vs. 0.990.12) were not different in the two groups. Age of recipients and occurrence of graft glomerulopathy also were not different in the two groups. The episode of acute rejection was more frequent in patients with graft dysfunction(32%, 7/ 22) than those without it(3%, 1/38, p<0.01), but the degree of HLA missmatch was not different. In multivariate analysis, donor age(p<0.01) and the episode of acute rejection(p<0.05) were independent factors affecting graft dysfunction. 3) Donor age was older(52 +/- 12 vs. 3814 years, p<0.01) and the episode of acute rejection was more frequent(56%, 5/9 vs. 696, 3/51, p<0.01) in 9 patients with graft loss than those without it. However, dkGFR, dkCCr, body surface area ratio, recipient age, occurrence of glomerulopathy and HLA missmatch were not different. In multivariate analysis, donor age(p<0.05) and the experience of acute rejection(p<0.01) were independent factors affecting graft loss. We therefore conclude that donor age is more important as non-immunologic prognostic factors in graft dysfunction than GFR of the donated kidney and the difference in body mass between recipient and donor.

A Case of Vancomycin Resistant Enterococci(VRE) Peritonitis in a Patient on CAPD / 대한신장학회잡지

Peritonitis is a major complication of continuous ambulatory peritoneal dialysis and it remains the leading cause of patient droupout. VRE is a very serious pathogen because it is difficult to eradicate due to very limited effective antibiotics and because there is a possibility of transfer of this resistance to other gram-positive organisms including Staphylo-coccus aureus. We experienced a case of CAPD peritonitis by VRE, which was treated with high dose ampicillin and streptomycin without removal of CAPD catheter. We report our experience of CAPD peritonitis caused by VRE and review the literature.

Changing Patterns of Salmonella Infection & Changes In Antimicrobial Resistance of Salmonella strains Isolated in 1987-1995 / 대한내과학회지

OBJECTIVES: Salmonellosis is one of the most common bacterial infections in the Korea. The incidence of salmonellosis has changed dramatically. The incidence of typhoid fever tends to decrease as environmental & personal sanitations improve, whereas that of nontyphoid salmonellae have markedly increased. Antimicrobial resistance is increasing in Salmonella strains. Increasing emergence in multiple-drug resistant Sallmonella strains has important clinical & public implications for populations at risk and the treatment of invasive salmonellosis is complicated by the increasing resistance among Salmonella strains to commonly used antimicrobial agents. This study is performed to fine out the pattern and the antimicrobial susceptibility of isolated Salmonella strains and the clinical charateristics of Salmonella infection. METHODS: We reviewed medical records of all patients with culture-confirmed Salmonella infection in Kyung Hee University Hospital for the period January 1987 through December 1995. RESULTS: 1) The mean age of the patients was 31.0 years and the ratio of male to female was 1.03:1. 2) The frequency of isolation of specific serogroups is ordered as followings : serogroup B(47.9%), serogroup D(23.3%), S. typhi(16.2%), serogroup C(9.6%), serogroup E(1.8%), serogroup A(1.2%). 3) The sites of isolation were as follows : stool(68.6%), blood(24.0%), pus(3.5%), urine(2.2%), bone marrow(2.2%), bile juice(0.4%), ascites(0.4%), CSF(0.2%), sputum(0.2%). 4) The isolation rate of resistant strains of specific serogroups was as follows in order : serogroup B(52.4%), serogroup C(33.3%), serogroup E(25%), serogroup D(9.8%), S. typhi(4.2%), serogroup A(0%). 5) The frequency of animicrobial resistance in Salmonella strains to tested 8 antimicrobial agents was as follows : ampicillin(28.8%), carbenicillin(28.1%), chloramphenicol(16.4%), kanamycin(5.9%), trimethoprim-sulfamethoxazole(5.3%), cephalothin(2.3%), gentamicin(0.9%), amikacin(0.5%). 6) The most of antimicrobial-resistant Salmonella(95.0% of resistant strains) has multiple drug resiatance. 7) The frequency of clinical manifestations of nontyphoid salmonellosis was as follows : enterocolitis(80.1%), bacteremia without focal infection(13.1%), focal infection(6.8%). 8) The clinical variables statistically significant between resistant and sensitive Salmonella infection are frequency of bacteremia and duration of admission. CONCLUSION: Different serogroups of Salmonella isolates reveal the different frequency & pattern in antimicrobial resistance. The frequency of antimicrobial resistance for Salmonella isolates is markely increased during recent 9 years. In preparation for the future outbreaks of multiresistant sallmonellosis, nationwide studies should be carried out periodically to monitor effectively trends in the antimicrobial resistance of Salmonella and the development of effective and practical alternative therapy for resistant salmonellosis is clearly needed.

1 case of imported Plasmodium vivax malaria with delayed manifestations due to inadequate chemoprophylaxis / 대한내과학회지

Malaria is the world's most important parasitic infec tion. Although it has been eradicated from temperate zones including Korea , increasing numbers of travellers visit tropical malarious countries and imported malaria becomes important medical problem in the developed countries. In Korea with increasing travellers to malaria endemic area, the incidence of imported malaria shows rising tendency same as the developed countries. It beco mes important to provide general personal protective me asures and chemoprophylaxis to trevellers, when employed in appropriate manner, that can be highly effective in preventing malaria . We recently experienced a case of imported Plasmodium vivax malaria with delayed mani festations due to inadequate chemoprophylaxis. A 53- year-old woman with history of trevel to East Africa 4 months ago and chief complaint of fever was diagnosed as tertian malaria. She had irregularly taken prophylatic antimalarial during travel and had not taken it after return but should have taken it at least 4 weeks after return.

A Case of Infective Endocarditis with Mycotic Aneurysms / 대한내과학회지

Cerebral mycotic aneurysms have been noted in 2-10% of cases of bacterial endocarditis and account for 2.5-6.2% of all intracerebral aneurysms. Mycotic aneurysms were reported to occur more frequently in the course of acute endocarditis rather than late in the course of subacute disease. Symptomatic mycotic aneurysms are now uncommon. Early or late hemorrhage correlates better with the presence of pyogenic arteritis and uncontrolled S, aureus infection. Early cerebral hemorrhage is usually associated with S. aureus arteritis, is not amenable to surgery, and carries a high mortality. Control of the infection dramatically decreases the risk of embolism in infective endocarditis patients. Recurrent emboli are not common after adequate antimicrobial treatment of the underlying infection. Recently, we experienced a case of infective endocarditis in which angiographically demonstrated mycotic aneurysm had been resolved with adequate antibiotic therapy.