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Background. Lamivudine is a potent inhibitor of hepatitis B virus replication. Little has been reported about the efficacy and safety of lamivudine in the treatment of chronic hepatitis B in the setting of renal transplantation. Methods. Two patients were treated for chronic hepatitis B with lamivudine and subsequently underwent renal transplantation. Four other patients were treated with lamivudine for reactivation of hepatitis B after renal transplantation. Chronic hepatitis B was proven histologically in all the patients. The doses of lamivudine ranged from 100 to 150 mg/day. Hepatic enzyme and viral markers were monitored. Results. Lamivudine was well tolerated for a median duration of 8 months (range, 4-14 months) without significant side effects. Viral replication was suppressed, as evidenced by negative conversion of serum hepatitis B virus DNA in all the patients. Hepatic enzyme was also normalized. Modification of doses of immunosuppressant regimen was not required in using lamivudine in all patients. One patient experienced acute rejection and responded to solumedrol pulse therapy with normalization of graft function. Normal graft function was maintained in other patients while they were treated with lamivudine. Conclusion. Lamivudine was a safe and effective therapy for activated hepatitis B in renal transplant recipients in the short term.

of fibrinogen, and possibly factor VII, in CAPD patients. Background. This study was performed to evaluate the relationship between serum albumin and plasma Key words: albumin, CAPD, factor VII, fibrinogen concentration of haemostatic factors and the eVect of raising serum albumin on haemostatic factors synthesized in the liver in CAPD patients. Methods. We measured blood levels of albumin, fib- Introduction rinogen, factor II, factor VII, protein C, free protein S, plasminogen, a2-antiplasmin and antithrombin III Hypoalbuminaemia, a major adverse prognostic factor in 103 CAPD patients and 30 normal controls. Twenty- in dialysis patients, is known to be strongly associated two patients with albumin

Lipoprotein(a) [Lp(a)], an independent risk factor for atherosclerotic cardiovascular disease in the general population, is known to be elevated in patients with renal disease accompanied by hypoalbuminemia such as nephrotic syndrome and end-stage renal disease. In this study, the role of hypoalbuminemia in the elevation of serum Lp(a) was investigated in 20 continuous ambulatory peritoneal dialysis (CAPD) patients with serum albumin below 3.5 g/dL. The patients were divided into two groups. In group 1 (n = 10), fasting serum Lp(a) and albumin were measured before, after repeated infusion of 20% albumin 100 mL three times per week for 2 weeks, and 4 weeks after withdrawal of albumin infusion. In group 2 (n = 10), serum albumin and Lp(a) were measured similarly without albumin infusion. C-reactive protein was monitored in both group as an indicator of acute-phase reactant. Serum Lp(a) was also measured in 20 age- and sex-matched normal controls. Apolipoprotein(a) [apo(a)] phenotype was determined in all the subjects. CAPD patients as a whole (n = 20; median, 70.2 mg/dL; interquartile range, 45.0 to 86.2 mg/dL) had higher serum Lp(a) than normal controls (n = 20; median, 9.9 mg/dL; interquartile range, 2.4 to 24.3 mg/dL) (P < 0.0001), although the distribution of apo(a) phenotype was similar. Serum albumin in group 1 increased from 2.6 ± 0.5 g/dL to 3.5 ± 0.6 g/dL (P < 0.0005) at the end of repeated infusion of albumin, whereas serum Lp(a) decreased from 73.7 mg/dL (range, 43.2 to 89.0 mg/dL) to 25.6 mg/dL (range, 10.7 to 71.7 mg/dL) (P < 0.01). Four weeks after withdrawal of albumin infusion, serum albumin decreased again to 2.9 ± 0.5 g/dL (P < 0.001), whereas serum Lp(a) increased to 65.2 mg/dL (range, 43.3 to 106.0 mg/dL) (P < 0.05). Serum albumin in group 2 was 2.8 ± 0.6 g/dL, 3.0 ± 0.4 g/dL, and 2.9 ± 0.7 g/dL, respectively. The change of serum Lp(a) was not significant (67.0 mg/dL [range, 46.8 to 84.8 mg/dL], 62.8 mg/dL [range, 45.1 to 81.0 mg/dL], and 63.0 mg/dL [range, 44.7 to 74.0 mg/dL]). C-reactive protein was stable during the study period in both groups. These findings support the hypothesis that hypoalbuminemia is one of the important trigger factors in the elevation of serum Lp(a) in CAPD patients.

Malnutrition is known to be highly associated with morbidity and mortality in dialysis patients. Malnutrition may begin to develop in patients with chronic renal failure(CRF) before they need dialysis. In this study, the nutritional status of patients with moderate to severe CRF on unrestricted diet was evaluated.We measured dietary protein intake (DPI, g/kg/day) in 64 patients with CRF and 42 normal controls(N). Nutritional indices such as serum albumin(SA, g/dl), transferrin(TF, mg/dl), prealbumin(PA, mg/dl) and insulin-like growth factor-1(IGF-1, ng/ml) were measured to evaluate the visceral proteins, and creatinine-height index(C-H, g/d/m) to evaluate the somatic proteins.Mean DPI was 0.80 +/- 0.27(S.D) in CRF and 1.07 +/- 0.30 in N(p0.0001). DPI was lower than 0.6 in 15 CRF patients(23%). Serum albumin, transferrin and C-H were significantly lower in CRF patients than in N(p0.01). In patients with CRF, nutritional indices were significantly worse with lower DPI(0.6 g/kg/d, n = 15) than higher DPI(0.6 g/kg/d, n = 49)(SA 2.9 +/- 0.7 vs. 3.6 +/- 0.8, p0.005; TF 147 (134-179) vs. 220(182-264), p0.0005; PA 24 +/- 8 vs. 32 +/- 9, p0.001; IGF-1 123 (66-261) vs. 226(140-344), p0.05; C-H 0.52 +/- 0.15 vs. 0.87 +/- 0.23, p0.0001). CRF patients with nephrotic range proteinuria (3.5 g/d, n = 19) had lower SA (2.8 +/- 0.6 vs. 3.8 +/- 0.8, p0.0001) and PA(27 +/- 9 vs. 32 +/- 9, p0.05). CRF patients with diabetes mellitus (n = 20) showed worse nutrition than non-diabetic patients(SA 2.8 +/- 0.6 g/dl vs. 3.8 +/- 0.8 g/dl, p0.0001; TF 176 mg/dl(148-214) vs. 220 mg/dl(175-266), p0.05; PA 24 +/- 10 mg/dl vs. 33 +/- 8 mg/dl, p0.0005; IGF-1 138 ng/ml(69-269) vs 231 ng/ml(140-364), p0.05; C-H 0.66 +/- 0.23 vs. 0.85 +/- 0.5, p0.005).A significant protein malnutrition prevails in patients with pre-dialysis CRF on unrestricted diet, especially with low protein intake. The effort to detect and correct malnutrition should be made in patients with CRF even before initiation of maintenance dialysis.

ObjectiveTo evaluate the distribution pattern of apolipoprotein(a) [Apo(a)] phenotypes in Koreans and the effect of dialysis modality on serum lipoprotein(a) [Lp(a)] concentration according to apo(a) phenotype in patients with end-stage renal disease (ESRO).DesignCross-sectional study.SettingA university hospital. Participants: 153 normal controls, 99 hemodialysis (HO) patients and 82 continuous ambulatory peritoneal dialysis (CAPO) patients.Main Outcome MeasuresFasting serum Lp(a), lipids, and apo(a) phenotypes were measured.ResultsThe frequencies of the subjects with apo(a) phenotypes of high-molecular weight only, including S3, S4, or S5 or null type were 95.4% of control, 100% of HO patients, and 95.1% of CAPO patients. The frequent apo(a) phenotypes in Koreans consisted of S4, S4S5, S5, and S5S5 isoforms. Significant difference was found in serum Lp(a) concentration among controls and HO and CAPO patients [median (interquartile range): 0.05 g/L, (0.01 0.19); 0.19g/L, (0.10 0.35); 0.63g/L, (0.28 0.90), p< 0.001]. Lp(a) levels in CAPO patients were significantly higher than in HO patients for all four common apo(a) isoforms found in Korean subjects. CAPO patients had higher total and LOL cholesterol levels, and higher ApoB levels than H O patients. Significant differences were found in serum albumin levels between controls and HO and CAPO patients (44 ± 3 g/L, 40 ± 4 g/L, 32 ± 7 g/L, respectively, p < 0.05). There were significant inverse correlations between serum albumin and Lp(a) (r = -0.33, p < 0.01), total cholesterol (r = -0.31, p < 0.01), LOL (r = -0.39, p < 0.01) or ApoB (r = -0.35, p < 0.01) in ESRO patients. A significant positive correlation was found between serum albumin and ApoA1 (r = 0.24, p < 0.01).ConclusionThese findings indicate that Koreans have mainly high -molecular weight apo(a) phenotypes and serum Lp(a) is elevated in CAPO patients compared to HO patients for common apo(a) phenotypes, which may contribute to the frequent cardiovascular mortality in CAPO patients.

We sought to investigate the clinical courses of renal transplant recipients with plasma BK viral loads10(4) copies/mL.A single-center retrospective review was performed of 88 kidney transplant patients in whom high BK viremia (defined as plasma BKV load10(4) copies/mL) was detected more than once from January 1, 2004, to December 31, 2011.At the time of transplantation, the mean recipient and donor ages were 44.5 ± 11.1 and 43.9 ± 11.3 years, respectively, and 59 subjects (67.0%) were male. The median times to first BK positivity and high BK viremia after transplantation were 44 and 136 days, respectively. Within 3 months after transplantation, we detected, 56 cases of high BK viremia (63.6%). The mean duration of high BK viremia was 8.2 ± 7.7 months. When plasma BKV load was first4 logs, the mean log BKV load was 5.50 ± 1.11 log copies/mL, which rose to a maximum of 5.82 ± 1.11. At these times, mean serum creatinine concentrations were 1.67 ± 0.79 and 2.64 ± 2.78 mg/dL, respectively. There were 31 cases (35%) of biopsy-proven BK nephropathy patients among 51 (58%) biopsies. Treatment modalities included discontinuation or dose reduction of mycophenolic acid drugs (n = 68) and switch from tacrolimus to cyclosporine (n = 9), cidofovir (n = 9), and leflunomide (n = 3). Based on the serum creatinine elevation after high BK viremia, patients were divided into group 1 (n = 27; 30.1%), whose maximal creatinine change was 0.5 mg/dL, and group 2, with a greater alteration. On multivariate logistic regression analysis, the maximal plasma BK viral load was significantly associated with a greater serum creatinine elevation (P .001).High BK viremia mostly occurred within 3 months after kidney transplantation. About 30% of renal allograft recipients with high BK viremia maintained stable renal function. Maximal plasma BK viral load was the only independent risk factor for high serum creatinine elevation.

Summary: Lipocortin-1 (LC-1), a Ca++-dependent phospholipid binding protein, is believed to be involved in anti-inflammatory actions of glucocorticoids. to prove the hypothesis that steroid-resistant glomerulonephritis would show increased expression of LC-1, we evaluated the expression of LC-1 in various types of glomerulonephritis. Frozen samples of seven normal kidneys and 30 kidney biopsy tissues were stained with indirect immunofluorescent method. In the normal tissues, minimal change disease (n=9), lupus nephritis (n=5) and IgA nephropathy (n=6), glomeruli did not stain for LC-1. Positive reactions for LC-1 were observed along the peripheral capillary walls in all five patients with membranous nephropathy with out hepatitis B surface antigen (HBsAg). In the patients with membranous nephropathy (MN) who also had chronic liver disease and HBsAg (n=3), only weak reactions for LC-1 were found along the capillary walls and mesangial area in 1 patient. Patients with membranoproliferative glomerulonephritis (n=2) showed positive reactions for LC-1 along the capillary walls. Fourteen patients with minimal change disease or lupus nephritis were treated with prednisolone. Ten patients showed substantial reduction of proteinuria, but four patients did not; however, staining for LC-1 was not negative in the kidney tissues of both steroid-responsive and steroid-resistant patients. These findings suggest that LC-1 does not mediate the action of glucocorticoids in human glomerulonephritis.

Objective To evaluate and compare the pharmacokinetics and tolerability of a single oral dose of mirodenafil in volunteer patients with severe renal impairment and healthy volunteers. Methods and materials This open-label, single-dose, parallel group clinical study enrolled a total 12 volunteers (6 healthy volunteers and 6 volunteer patients with severe renal impairment). Each volunteer was orally administered 50 mg mirodenafil and serial blood samples were obtained after drug administration to determine the plasma concentration of mirodenafil using LC-MS/MS. The measured individual plasma concentrations were used to calculate the pharmacokinetic parameters using noncompartmental methods. Tolerability was also assessed using measurements of vital signs, clinical chemistry tests, and interviews. Results All of the volunteers completed the study with no serious adverse events (AEs). A total of 4 AEs were reported, but all were of mild or moderate intensity and not considered to be related to the study drug. The geometric mean (95% CI) of the terminal half-life (t1/2β) and the apparent clearance (CL/F) values of mirodenafil were 2.2 (1.4 - 3.4) h and 127.2 (95.1 - 170.2) l/h in the volunteer patients, and 3.0 (2.1 - 4.4) h and 136.1 (74.4 - 249.2) l/h in the healthy volunteers, respectively. The geometric mean of the AUC0-t of the volunteer patients was 8% higher and the geometric mean for clearance was 7% lower compared with the healthy volunteers. However, the geometric mean of the Cmax of the volunteer patients was 38% higher than that of the healthy volunteers. Conclusions A single oral 50-mg dose of mirodenafil was well tolerated. Exposure (AUC0-t) to mirodenafil was similar in both healthy volunteers and volunteer patients with severe renal impairment and healthy volunteers.

Routine DMSA scintigraphy, ultrasound (US) of the kidney, intravenous pyelography (IVP) and voiding cystoureterography (VCU) were performed in 27 consecutive adult women with recurrent acute pyelonephritis (APN) during a 12-month follow-up. Both planar and single photon emission computed tomography (SPECT) images were obtained for DMSA scan. DMSA scans were repeated in those patients with abnormal initial scan. DMSA-SPECT showed normal findings in 2, single renal cortical detect (RCD) in 9 and multiple RCD in 16 (including nonvisualization in 2). Of the 11 kidneys with normal findings or single RCD on DMSA-SPECT, only 1 (9%) showed vesicoureteral reflux (VUR) on VCU (grade I). A large proportion of those with multiple RCDs showed abnormal findings on IVP (44%, 7/16), US (38%, 6/16) or VCU (31%, 5/16); 63% in any of these three studies. 5 of 6 patients with VUR had multiple RCDs on DMSA-SPECT, and 3 of these 5 showed no abnormality on IVP or US. 7 patients who needed other managements besides initial standard antibiotic treatment had multiple RCDs on DMSA-SPECT. 15 normal women were also studied and showed normal DMSA-SPECT, US and IVP, in all cases. Follow-up DMSA-SPECT was done in 16 patients (7 with single RCD, 9 with multiple RCD). All 7 patients with single RCD showed improvement, in those with multiple RCDs improvement was observed in 2, no change in 7 on follow-up studies. We conclude: (1) DMSA-SPECT is a useful initial diagnostic tool in adult women with recurrent APN to identify patients who need more extensive radiological studies. (2) The multiple RCDs on DMSA-SPECT indicate irreversible tissue damage in most adult women with recurrent APN.

The role of spleen tyrosine kinase (Syk) in high glucose-induced intracellular signal transduction has yet to be elucidated. We investigated whether Syk is implicated in high glucose-induced transforming growth factor-β1 (TGF-β1) up-regulation in cultured human proximal tubular epithelial cells (HK-2 cell). High glucose increased TGF-β1 gene expression through Syk, extracellular signal-regulated kinase (ERK), AP-1 and NF-κB. High glucose-induced AP-1 DNA binding activity was decreased by Syk inhibitors and U0126 (an ERK inhibitor). Syk inhibitors suppressed high glucose-induced ERK activation, whereas U0126 had no effect on Syk activation. High glucose-induced NF-κB DNA binding activity was also decreased by Syk inhibitors. High glucose increased nuclear translocation of p65 without serine phosphorylation of IκBα and without degradation of IκBα, but with an increase in tyrosine phosphorylation of IκBα that may account for the activation of NF-κB. Both Syk inhibitors and Syk-siRNA attenuated high glucose-induced IκBα tyrosine phosphorylation and p65 nuclear translocation. Depletion of p21-activated kinase 2 (Pak2) by transfection of Pak2-siRNA abolished high glucose-induced Syk activation. In summary, high glucose-induced TGF-β1 gene transcription occurred through Pak2, Syk and subsequent ERK/AP-1 and NF-κB pathways. This suggests that Syk might be implicated in the diabetic kidney disease.

Background Arterial blood gas analysis (ABGA) is a useful test that estimates the acid–base status of patients. However, numerically reported test results make rapid interpretation difficult. To overcome this problem, we have developed an algorithm that automatically interprets ABGA results, and assessed the validity of this algorithm for applications in clinical laboratory services. Methods The algorithm was developed based on well-established guidelines using three test results (pH, PaCO2 and [HCO3−]) as variables. Ninety-nine ABGA test results were analysed by the algorithm. The algorithm's interpretations and the interpretations of two representative web-based ABGA interpretation programs were compared with those of two experienced clinicians. Results The concordance rates between the interpretations of each of the two clinicians and the algorithm were 91.9% and 97.0%, respectively. The web-based programs could not issue definitive interpretations in 15.2% and 25.3% of cases, respectively, but the algorithm issued definitive interpretations in all cases. Of the 10 cases that invoked disagreement among interpretations by the algorithm and the two clinicians, half were interpreted as compensated acid–base disorders by the algorithm but were assessed as normal by at least one of the two clinicians. In no case did the algorithm indicate a normal condition that the clinicians assessed as an abnormal condition. Conclusions The interpretations of the algorithm showed a higher concordance rate with those of experienced clinicians than did two web-based programs. The algorithm sensitively detected acid–base disorders. The algorithm may be adopted by the clinical laboratory services to provide rapid and definitive interpretations of test results.

Atherosclerotic cardiovascular disease is the major cause of morbidity and mortality in solid organ transplant recipients. Endothelin-1 (ET-1) is implicated in the pathogenesis of atherosclerosis and is one of the potential therapeutic targets. This study was conducted to evaluate the effect of mycophenolic acid (MPA), an immunosuppressant for the transplant recipients, on tumor necrosis factor-alpha (TNF-alpha)-induced ET-1 production in aortic endothelial cells.In cultured human aortic endothelial cells, TNF-alpha increased ET-1 through AP-1 and NF-kappaB, whereas MPA attenuated it by reducing both AP-1 and NF-kappaB DNA-binding activities. TNF-alpha increased ET-1 via c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), but not extracellular signal-regulated kinase. N-acetylcysteine that downregulated TNF-alpha-induced reactive oxygen species (ROS) inhibited JNK activation, but not p38 MAPK. N-acetylcysteine, SP600125 (JNK inhibitor) and SB203580 (p38 MAPK inhibitor) attenuated TNF-alpha-induced DNA-binding activities of both AP-1 and NF-kappaB. MPA inhibited JNK and p38 MAPK activations as well as ROS generation. N-acetylcysteine, SP600125, SB203580 and MPA had no effect on either TNF-alpha-induced IkappaBalpha degradation or p65 nuclear translocation, but attenuated p65 Ser276 phosphorylation.MPA attenuated TNF-alpha-induced ET-1 production through inhibitions of ROS-dependent JNK and ROS-independent p38 MAPK that regulated NF-kappaB as well as AP-1. These findings suggest that MPA could have an effect of amelioration of atherosclerosis.

Background/Aims: Accurate measurement of glomerular filtration rate (GFR) is critical for the management of kidney transplant recipients. Comparison of creatinine and cystatin C in renal transplant recipients gave conflicting results. We aimed to compare the performance of creatinine- and cystatin C-based equations and creatinine clearance in 102 early postoperative Korean renal transplant patients. Methods: We measured 51Cr-EDTA clearance using a 2-compartment model and considered this the reference GFR. Then, we estimated GFR using 13 creatinine- and 7 cystatin C-based equations. Serum creatinine value was calibrated to isotope-dilution mass spectrometry (IDMS). Results: The mean reference GFR was 76.77 ± 17.01 ml/min/1.73 m2. The IDMS-traceable MDRD (IDMS-MDRD) equation had the highest accuracy (94.12 within 30% of the reference; 99.02 within 50% of the reference) with a bias of 0.33 ml/min/1.73 m2 and a precision of 12.57 ml/min/1.73 m2. The Mayo Clinic equation also performed well (92.16% within 30% of the reference; 99.02% within 50% of the reference; bias: –0.19 ml/min/1.73 m2). As for cystatin C-based equations, the Filler equation had the least bias (0.03 ml/min/1.73 m2) but low accuracy (78.43% within 30% of the reference). Conclusions: We conclude that the IDMS-MDRD equation provided the best estimate of GFR in our early postoperative Korean renal transplant patients.

SUMMARY: Aim: To describe the clinical features and to identify factors related to development of acute kidney injury in acute hepatitis A patients. Methods: The study and control groups consisted of 21 and 425 patients who did or did not develop acute kidney injury, respectively, after acute hepatitis A from January 1997 to May 2007. Results: There were 13 men and eight women; their mean age at diagnosis was 28.8 ± 8.2 years in the study group. Peak values for renal and liver function impairment consisted of a median serum creatinine of 4.6 mg/dL (range, 1.5–15.3 mg/dL) on day 6 (range, days 1–20) and a median total bilirubin of 10.7 mg/dL (range, 2.6–57.5 mg/dL) on day 8 (range, day 1–19). Serum creatinine concentrations returned to baseline level by a median of 16 days and total bilirubin levels returned to normal by a median of 62 days. Six of 21 (29%) patient underwent haemodialysis. Renal biopsies performed in two patients showed acute tubular necrosis and interstitial nephritis, respectively. Logistic regression analysis showed that a lower haematocrit, the presence of coagulopathy and high C-reactive protein concentration on admission, and higher peak bilirubin value during the illness were associated with development of acute kidney injury. Conclusion: Acute hepatitis A should be considered in the differential diagnosis of patients with acute kidney injury, even without fulminant hepatic failure. A lower haematocrit, the presence of coagulopathy and high C-reactive protein level at presentation, and higher peak bilirubin level during the illness were associated with development of acute kidney injury in acute hepatitis A patients.

Background: The ratio of bioimpedance in the right leg (rl-RBI) may be helpful in adjusting dry body weight (DBW) in new hemodialysis (HD) patients. Methods: rl-RBI was calculated as follows: rl-RBI = impedance at 50 kHz/impedance at 500 kHz, as measured by bioimpedance spectroscopy (BIS). Theoretically, rl-RBI is inversely related to extracellular water. A reference range of rl-RBI was obtained from 137 chronic but stable HD patients already achieving DBW. In 34 new HD patients (females:males = 16:18; age 49 ± 12 years), DBW(s) were stepwise adjusted under the guidance of rl-RBI by modifying the amount of ultrafiltration. Results: The target range of rl-RBI was defined as 1.106–1.150. rl-RBI before the first HD was 1.115 ± 0.027. At the study endpoint, when the target range of rl-RBI was achieved, pretibial pitting edema and pulmonary edema were resolved without any episode of muscle cramping or intradialytic hypotension. Along with an increase in rl-RBI, pre-HD blood pressure tended to decrease at systole (p = 0.072) and diastole (p = 0.005). The cardiothoracic ratio also decreased significantly (p = 0.004). Conclusion: The measurement of rl-RBI by BIS is worthy of further evaluation as an objective and applicable index for determining DBW in new HD patients.

Hemodialysis (HD) and continuous venovenous hemodiafiltration (CVVHDF) have been adopted as forms of renal replacement therapy (RRT) in patients with acute renal failure (ARF). Although CVVHDF has many advantages, previous studies reported no definite improvement in survival rate compared to HD.In this retrospective study, 148 intensive care unit patients underwent HD (70 males, 25 females; mean age 45 +/- 17 years) or CVVHDF (42 males, 11 females; mean age 52 +/- 18 years). The severity of illness was estimated at the initiation of RRT and on the third day of RRT and presented using the APACHE III scoring system. The number of organ failures was checked at the initiation of RRT.The survival rate was 46% in the HD group and 21% in the CVVHDF group (p = 0.002). CVVHDF was applied to the more severely ill patients, who had longer periods using a ventilator (p = 0.002) and/or vasopressor (p0.001), higher numbers of organ failures (p0.001) and higher initial APACHE III scores (p0.001). Among patients with APACHE III scores103, the survival rate was 13% in the CVVHDF group and 0% in the HD group. In patients with kidney failure and failure of two other organs, the survival rate was 9% in the HD group and 36% in the CVVHDF group (p = 0.035).The mortality rate in the CVVHDF group was higher than that in the HD group, which may have been because CVVHDF was applied to the more severely ill patients. In contrast, CVVHDF may give a chance of survival to patients with APACHE III scores103 and may be more useful than HD in patients with failure of three or more organs.

Background: The competition between STAT1 and Smad3 for a limiting amount of the nuclear protein p300, a transcriptional coactivator, was suggested to be a mechanism for the antagonism between interferon-γ (IFN-γ) and transforming growth factor-β1 (TGF-β1). We investigated the effect of TGF-β1 on IFN-γ-induced HLA-DR production in cultured human glomerular endothelial cells (HGECs), and the involvement of p300 in this process. Methods: Cell surface expression of HLA-DR and mRNA levels of HLA-DR and class II transactivator (CIITA), the master regulator of HLA-DR gene transcription, were measured by cellular ELISA and Northern blot, respectively. The levels of STAT1 and Smad3 protein were analyzed by Western blot. Nuclear binding activity of STAT1 was assessed by electrophoretic mobility shift assay. Results: IFN-γ increased the cell surface expression of HLA-DR along with increases in the mRNA levels of CIITA and HLA-DR, while these stimulatory effects of IFN-γ were down-regulated by TGF-β1. IFN-γ increased phosphorylation of STAT1 and this activation was not inhibited by TGF-β1. IFN-γ increased binding of p-STAT1 to p300, while TGF-β1 increased binding of Smad3 to p300. TGF-β1-induced Smad3 binding to p300 was inhibited by IFN-γ, whereas IFN-γ-induced p-STAT1 binding to p300 was not inhibited by TGF-β1. IFN-γ increased DNA binding activity of STAT1. Inhibition of interaction between STAT1 and p300 by addition of anti-p300 antibody to nuclear extract down-regulated DNA binding activity of STAT1. In contrast, TGF-β1 did not inhibit IFN-γ-induced STAT1 binding to DNA. Conclusions: TGF-β1 down-regulated IFN-γ-induced CIITA and HLA-DR expression in HGECs. Though there was an antagonism between IFN-γ and TGF-β1, the competition for p300 between p-STAT1 and Smad3 was not the mechanism for it.

Leukocyte adhesion to mesothelium is an important step during peritonitis, which is mediated by adhesion molecules including vascular cell adhesion molecule-1 (VCAM-1). We investigated the effect of exogenous nitric oxide (NO) on VCAM-1 expression in cultured human peritoneal mesothelial cells and its signal transduction pathway. Mesothelial cells were exposed to tumor necrosis factor-alpha (TNF-alpha) in the presence or absence of NO donors, 3-morpholino-sydnonimine (SIN-1) and nitroprusside (NP). VCAM-1 mRNA and protein expression were measured by Northern blot analysis and flow cytometry. Nuclear factor-kappaB (NF-kappaB) binding activity was determined by electrophoretic mobility shift assay. Both SIN-1 and NP inhibited the TNF-alpha induced VCAM-1 mRNA expression in a dose dependent manner (0.25-2 mM). SIN-1 also suppressed the cell surface expression of VCAM-1 molecule. Furthermore, SIN-1 and NP inhibited the VCAM-1 mRNA expression induced by interleukin-1beta or lipopolysaccharide as well. NF-kappaB inhibitor, PDTC dose dependently inhibited the TNF-alpha induced VCAM-1 mRNA expression. SIN-1 inhibited the TNF-alpha- induced NF-kappaB binding activity. Analogue of cGMP (8-bromo-cGMP) had no significant effect on TNF-alpha-induced VCAM-1 mRNA expression and guanylate cyclase inhibitor (ODQ) also had no significant influence on the inhibitory effect of SIN-1. These results suggest that exogenous NO inhibits VCAM-1 expression via suppression of NF-kappaB through a cGMP-independent pathway.

Oxidative stress is known to be implicated in the pathogenesis of atherosclerotic cardiovascular disease. Many studies have demonstrated that hormone replacement therapy (HRT) has beneficial effects on oxidation injury in postmenopausal women with normal renal function. In this study, we examined the effects of HRT on plasma malondialdehyde (MDA) level and total antioxidant capacity (TAC) in postmenopausal hemodialysis women.We randomly assigned 70 postmenopausal women on maintenance hemodialysis into either a HRT group or a control group. Oral conjugated estrogen (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) was given daily for 12 weeks in HRT group. Plasma MDA, TAC, albumin, uric acid and C-reactive protein (CRP) were measured before, 4 and 12 weeks after the start of medication in the HRT group. In the control group, the same parameters were measured without HRT.There was no difference in baseline values between the two groups. In the control group (n = 32), all these parameters showed no change at 4 and 12 weeks. HRT decreased MDA from 1.32 (0.55-1.88) microM to 1.08 (0.44-1.50) microM (p0.001) at 4 weeks and to 1.11 (0.50-1.37) microM (p0.001) at 12 weeks (n = 33). TAC was not changed at 4 weeks, however, it decreased from 1.59 (1.27-2.00) mM to 1.45 (1.08-1.65) mM (p0.05) at 12 weeks. The albumin, uric acid and CRP levels were not changed significantly after HRT.These results suggest that HRT has a favorable effect on oxidative stress in postmenopausal women with ESRD as in the general population.

Purpose: To determine the size range of lacrimal glands calculated from Brain CT angiography. Methods: A retrospective review of 107 CT scans of 214 orbits was performed. Aquaris Intuition Viewer software was used to calculate the volumes. Results: The mean volume of the lacrimal gland was 0.655 cm in right orbits and 0.595 cm in left orbits, 0.616 cm in men and 0.625 cm in women. There was a significant difference between right and left (p = 0.012) but no difference between men and women (p = 0.725). Linear regression analyses revealed that there was an inverse relationship between gland volume and age (Pearson r = -0.433, p < 0.001). Conclusions: This is the first study to report the normal volume range of Korean lacrimal glands as measured by CT scans. A difference was detected in the volume between right and left lacrimal glands. The volume of the lacrimal gland decreased with age, and there were no gender differences. J Korean Ophthalmol Soc 2014;55(10):1413-1417

Increased coagulation factors found in dialysis patients may explain in part the high prevalence of thrombotic cardiovascular disease. Several studies showed low-dose warfarin is effective in decreasing coagulation factors and preventing thrombosis without increasing the risk of bleeding. To evaluate the effects of fixed low-dose warfarin therapy on thrombogenesis in continuous ambulatory peritoneal dialysis (CAPD) patients, 76 CAPD patients were assigned randomly to treatment and disease control groups. The treatment group received 2 mg of warfarin daily for 12 months. International normalized ratio (INR) of the prothrombin time and plasma levels of factor VII, D-dimer, von Willebrand factor (vWF), and plasminogen activator inhibitor-1 (PAI-1) were measured before and 3, 6, and 12 months after the start of medication. The same parameters were measured in 30 healthy volunteers at the beginning of the study and in the disease control group during the study period. Of 76 patients, 60 completed the study. Deaths from atherosclerotic cardiovascular disease (cerebral infarction or acute myocardial infarction) occurred in 1 patient in the treatment group (n = 29) and 3 in the disease control group (n = 31), which was not statistically significant. No major bleeding occurred during the study period. With administration of warfarin, there was a small increase in INR in the treatment group. CAPD patients at baseline had significantly higher plasma factor VII, D-dimer, vWF, and PAI-1 levels than normal controls. Warfarin therapy lowered plasma factor VII and D-dimer levels. No change was seen in vWF and PAI-1 levels. In the disease control group, these hemostatic factors showed no change during the study period. There was a negative correlation between serum albumin and INR in the treatment group during the study period. Fixed low-dose warfarin was effective in partially reversing the thrombogenic coagulation profile in CAPD patients without a big increase in the risk of bleeding.

Previous studies have demonstrated that enalapril and verapamil seem to attenuate the cyclosporine nephrotoxicity. However, the mechanisms have not been completely understood, especially on molecular events. The aim of this study was to examine the effect of individual or combined treatment on osteopontin, TGF-beta, endothelin-1 and procollagen alpha 1(I) mRNA expressions. Enalapril (50 mg/L in drinking water) and verapamil (0.5 mg/kg/day, subcutaneously), alone or in combination, were administered to rats with chronic cyclosporine nephrotoxicity (cyclosporine, 25 mg/kg/day, subcutaneously) (n = 5 each). Five rats treated with olive oil vehicle were used as control. After 4 weeks, biochemical parameters were measured, and renal cortical mRNA levels were evaluated by Northern blot analysis. Cyclosporine reduced renal creatinine clearance significantly and induced renal cortical osteopontin, TGF-beta, endothelin-1 and procollagen alpha 1(I) gene expressions around 13.5 +/- 1.3, 2.4 +/- 0.2, 1.5 +/- 0.1, 1.9 +/- 0.1 folds, respectively. Individual treatment with enalapril or verapamil significantly suppressed the osteopontin and TGF-beta mRNA expression, but not endothelin-1 and procollagen alpha 1(I). Combined treatment also inhibited the osteopontin and TGF-beta mRNA expression but there was no difference between combined and individual treatment. In conclusion, enalapril or verapamil significantly blunted the cyclosporine-induced osteopontin and TGF-beta gene expressions. However, combined treatment did not show any additive effect.

Background. Elevated plasma fibrinogen is an important risk factor for coronary artery disease in the general population and patients with chronic renal failure. High plasma fibrinogen may trigger thrombus formation in arteriovenous fistulas. We performed a prospective, cohort study to evaluate the association of plasma fibrinogen concentration with vascular access failure in patients undergoing long-term haemodialysis. Methods. Between September 1989 and October 1995, 144 patients underwent a vascular access operation. In March 1997, 102 patients (56 M, 46 F) who had been followed up for more than 18 months (median; 37 months, range; 18-102 months) were included in the study. The median age of the patients was 52 years (range; 19--78 years). In 35 patients, renal disease was secondary to diabetes mellitus. The type of vascular access was a polytetrafluoroethylene (PTFE) graft in 17 patients. Seventy-seven patients received recombinant human erythropoietin (r-HuEPO) therapy during the follow-up period. Plasma fibrinogen, albumin, total cholesterol, hematocrit, platelets and creatinine were measured at the time of operation. Vascular access failure was defined as the occurrence of complications requiring transluminal angioplasty, thrombolytic therapy or surgical repair. Results. Thirty-eight patients had at least one vascular access failure and the incidence was 0.3 (range; 0-2.4) episodes per patient-year. The survival rate of vascular access was 78% (native fistula; 80%, PTFE graft; 71%) after 12 months and 70% (native fistula; 73%, PTFE graft; 51%) after 24 months. Older age, a PTFE graft, r-HuEPO therapy, higher hematocrit, lower albumin and higher fibrinogen levels were significantly associated with vascular access failure, whereas gender, diabetes mellitus, total cholesterol and platelet count were not. Plasma fibrinogen was inversely correlated with albumin (r = - 0.38, P = 0.001). The cumulative vascular access survival was significantly lower in patients with high plasma fibrinogen levels (≥460 mg/dl) compared with patients with low levels (

This study was performed to investigate the interrelation between blood albumin level and D-dimer (a marker of intravascular coagulation) and von Willebrand factor (vWF; a marker of endothelial injury) levels or platelet aggregation. Blood levels of albumin, D-dimer, vWF, and C-reactive protein (CRP) and the threshold aggregating concentration (TAC) of ristocetin were measured in 64 continuous ambulatory peritoneal dialysis (CAPD) patients and compared with 36 healthy controls. Twenty-two CAPD patients with albumin levels less than 3.0 g/dL were divided into experimental and disease-control groups. In the experimental group, levels were measured before and after repeated infusions of 20% albumin, 100 mL/d for 7 days. The same parameters were measured in the disease-control group that did not receive the albumin infusion. CAPD patients had higher D-dimer and vWF levels than the healthy controls. There were inverse correlations between albumin and D-dimer (r = -0.48; P < 0.001), vWF (r = -0.29; P < 0.05), or logCRP (r = -0.44; P < 0.001) in CAPD patients. There were positive correlations between logCRP and D-dimer (r = 0.38; P < 0.01) and between logCRP and vWF (r = 0.32; P = 0.01) in CAPD patients. No change was seen in D-dimer, vWF, and CRP levels in either group. The TAC of ristocetin in the 18 CAPD patients was not different from that in the 11 healthy controls (0.55 +/- 0.09 v 0.65 +/- 0.07 mg/mL). There was a correlation between albumin level and TAC in the CAPD patients (r = 0.59; P < 0.01). TAC increased from 0.50 +/- 0.09 to 0.62 +/- 0.13 mg/mL (123% +/- 17%; P < 0.05; n = 6) at the end of the repeated albumin infusions in the experimental group, whereas it did not change in the control group. CRP level did not change in either group. The results of this study indicate that hypoalbuminemia increases platelet aggregability. The observation that the albumin infusion was not associated with changes in D-dimer and vWF despite the inverse correlations suggests that these relationships may be secondary to other factors, such as inflammation.

To evaluate the therapeutic effect of recombinant human alpha-interferon (alpha-IFN) on hepatitis B virus associated glomerulonephritis (HBV-GN) and the relationship between the seroconversion of viral antigens and the change of proteinuria, the hepatitis B viral markers and urinary protein were monitored during alpha-IFN treatment in 8 male adult patients who (1) were positive in serum HBsAg and HBeAg, (2) had chronic hepatitis, (3) had persistent proteinuria1 g/day, and (4) showed glomerulonephritis on kidney biopsy. alpha-IFN was given at a dose of 3 million units, subcutaneously, three times a week for 6 months. Kidney biopsy specimens showed membranoproliferative glomerulonephritis (MPGN) in 4 patients, mesangial proliferative glomerulonephritis (MesPGN) in 2, and membranous glomerulonephritis (MGN) in 2 patients. Seven of the 8 patients received a 6-month course of alpha-IFN therapy; 1 patient with MGN quitted therapy 2 months after the initial dose because of side effects. In 5 of the 7 patients who received a 6-month therapy, serum HBeAg disappeared, and anti-HBe appeared during the therapy. In 2 of these 5 patients, HBeAg reappeared, in 1 during alpha-IFN therapy and in 1 9 months after the last dose of alpha-IFN. The hepatitis B viral markers of the patient who received a 2-month therapy did not change. HBs antigenemia persisted in all patients. In all 4 patients with MPGN, serum HBeAg was transiently or persistently converted to negative, but the proteinuria persisted. Both patients with MesPGN showed remission of proteinuria; however, only 1 patient had seroconversion of HBeAg. In 2 patients with MGN, proteinuria persisted. In conclusion, alpha-IFN at the doses given was not effective in MPGN type of HBV-GN. Improvement of proteinuria was achieved in MesPGN patients without disappearance of HBs antigenemia which is the finding against the possible role of HBsAg in the pathogenesis of this type of HBV-GN.

Malnutrition in haemodialysis patients is associated with an increased cardiovascular mortality. Lipoprotein(a) (Lp(a)) is an independent risk factor for atherosclerotic cardiovascular disease. To evaluate the relationship between atherogenic lipid profile and serum albumin in haemodialysis patients we measured fasting serum Lp(a), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), triglyceride (TG), apoprotein A-I (ApoA-I), apoprotein B (ApoB) and albumin in 101 haemodialysis patients and in 46 healthy subjects as a control. The haemodialysis patients were divided into two groups on the basis of the level of serum albumin: group I, serum albumin or = 4.0 g/dl. Haemodialysis patients as a whole (n = 101, 17.1 mg/dl (10.3-30.9)) had higher serum Lp(a) than normal subjects (n = 46, 10.5 mg/dl (3.3-24)) (P < 0.05). Lp(a) in group I (n = 38, 27.1 mg/dl (14.6-35.0)) was significantly higher than in group II (n = 63, 14.5 mg/dl (7.7-21.7), P < 0.005) and normal subjects (P < 0.0005). However, serum Lp(a) level of group II was not different from those of normal subjects. There was a significant inverse correlation between serum Lp(a) and albumin concentration (rs = -0.26, P < 0.01). TC, TG, HDL-C, ApoA-I, ApoB, TC/HDL-C, and ApoA-I/ApoB ratios were not different between group I and group II. No correlation was found between albumin and TC, TG, HDL-C, TC/HDL-C, and ApoA-I/ApoB ratios. These results suggest that Lp(a) could be responsible for an increased cardiovascular mortality in haemodialysis patients with malnutrition.

A new staging system for multiple myeloma (MM) has utilized serum concentrations of beta2-microglobulin (Sbeta2M) and albumin as important prognostic factors for survival. Since Sbeta2M is an indicator of glomerular filtration rate, we compared the prognostic values of Sbeta2M and 24-hr urinary creatinine clearance (Ccr) in patients with MM. We retrospectively reviewed the records of 170 MM patients from January 1996 to November 2003 whose 24-hr urinary Ccr was available at the time of diagnosis. We found that pretreatment Sbeta2M was inversely related to Ccr (Spearman's correlation coefficient=-0.787). In univariate analysis, the hazard ratio (HR) of death was 1.043 (p0.001) for Sbeta2M and 0.985 (p0.001) for Ccr. Multivariate analysis showed that Sbeta2M (HR 1.030, p=0.010) and Ccr (HR 0.993, p=0.059) were significant prognostic factors in patients' survival. In conclusion, 24-hr urinary Ccr may be utilized for staging of patients with MM.

In the new staging system of multiple myeloma (MM) by South West Oncology Group (SWOG), the concentration of serum β2 microglobulin (β2m) and serum albumin were focused as the most important prognostic factors for survival. However, serum concentration of β2m has been known as an indicator of glomerular filtration rate. The aim of this study was to compare the prognostic value of the level of β2m with that of creatinine clearance (Ccr) in patients with multiple myeloma. Retrospectively, from January 1, 1996 to November 30, 2003, we reviewed 176 MM patients (M: F 110:66 mean age: 58.5±11.0) whose 24-hour urinary creatinine clearance was available at the time of diagnosis. We collected clinical data such as hemoglobin, serum creatinine, calcium, albumin, β2m, creatinine clearance before chemotherapies, and patients’ survival time. Pretreatment β2m was inversely related to Ccr (Spearman’s correlation coefficient = −0.781, P We could propose another new staging system with β2m replaced by Ccr in SWOG staging system. The stages were defined as: stage 1, Ccr ≥ 80ml/min; stage 2, 50< Ccr In conclusion, Ccr could be more important prognostic factor than the level of β2m in patients of MM and we propose that Ccr should be reassessed as the component of staging system of MM.