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Objectives: Thalidomide has various effects, such as immune modulation, anti-angiogenicity, anti-inflammation and anti-proliferation. Moreover, thalidomide modulates the activity of NF-κB, which can up-regulate the expression of downstream genes involved in the pathophysiology of LN. Here we investigated the efficacy of thalidomide monotherapy or thalidomide plus prednisolone (PL) on nephritis in NZB/WF1 mice at different doses and compared both with a combination therapy of MMF plus PL., Methods: Forty-three female NZB/WF1 mice were divided into eight groups (untreated; 1.7, 5 or 10 mg/kg of thalidomide alone; 1.7, 5 or 10 mg/kg of thalidomide plus 1.5 mg/kg of PL and 33.3 mg/kg of MMF plus PL). Proteinuria and histological damage were evaluated. Immune complex deposition and nuclear translocation of NF-κB in kidney tissues were assessed by immunofluorescence staining. Serum concentrations of anti-dsDNA and IgG subclasses were also measured., Results: In comparison with untreated mice, mice treated with 10 mg/kg of thalidomide monotherapy showed a significant decrease in proteinuria and significantly lower glomerular and tubular damage scores, comparable to 5 or 10 mg/kg of thalidomide plus PL or MMF plus PL. Also, treatment with 10 mg/kg of thalidomide significantly decreased immune complex accumulation, reduced the serum concentration of anti-dsDNA, IgG2a and IgG2b and inhibited nuclear translocation of NF-κB in kidney tissues, comparable to standard therapy for LN., Conclusion: These data suggest that thalidomide might play an anti-inflammatory role in the pathophysiology of LN, and it could serve as a complementary therapy to standard induction regimens for refractory LN.

Background: Left atrial (LA) volume index (LAVI) has been considered a stable indicator of diastolic dysfunction and an independent predictor of mortality in patients with end-stage renal disease. To date, however, little is known about the relationship between LA enlargement and the changes in residual renal function (RRF)., Methods: This study was undertaken to investigate the association between LA enlargement and the decline in RRF in 121 incident peritoneal dialysis patients. Within 2 months after the initiation of peritoneal dialysis, LA enlargement was determined by echocardiography and RRF by 24-hour urine collection. Subsequently, RRF was measured every 6 months., Results: The rates of decline in RRF were significantly greater in patients with LA enlargement (LAVI > 32 mL/m(2)) compared with those without LA enlargement (-0.17 ± 0.18 vs -0.07 ± 0.16 mL/min/month/1.73 m(2), P = .002). In a linear mixed model, there was a significant difference in the rates of RRF decline over time between patients with and without LA enlargement (P < .001). Pearson's correlation analysis revealed that there were significant inverse correlations between the rates of the decline in RRF and LAVI (r = -0.22, P = .018). In multiple linear regression analysis adjusted for other risk factors, LAVI was found to be an independent determinant of the rates of decline in RRF (β = -0.026, P = .018)., Conclusions: This study shows that a higher LAVI is independently associated with a more rapid decline in RRF in patients with end-stage renal disease on peritoneal dialysis., (Copyright © 2012 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Glomerulonephritis occurs as a rare form of renal manifestation in Plasmodium falciparum malaria. Herein, we report a case of falciparum malaria-associated IgA nephropathy for the first time. A 49-yr old male who had been to East Africa was diagnosed with Plasmodium falciparum malaria. Microhematuria and proteinuria along with acute kidney injury developed during the course of the disease. Kidney biopsy showed mesangial proliferation and IgA deposits with tubulointerstitial inflammation. Laboratory tests after recovery from malaria showed disappearance of urinary abnormalities and normalization of kidney function. Our findings suggest that malaria infection might be associated with IgA nephropathy.

Background: Endothelial dysfunction, which contributes to atherosclerosis and arteriosclerosis, commonly accompanies end-stage renal disease (ESRD). However, little is known about the role of residual renal function (RRF) in endothelial protection in ESRD patients. This study aimed to investigate the relationship between endothelial function and RRF in patients undergoing peritoneal dialysis (PD)., Methods: This was a cross-sectional study involving 72 prevalent PD patients. Demographic and clinical data were recorded and residual glomerular filtration rate (GFR), Kt/V urea, and serum concentrations of inflammatory markers were measured. Endothelial function was assessed by brachial artery endothelium-dependent vasodilation [flow-mediated dilation (FMD)] to reactive hyperemia following 5 minutes of forearm ischemia., Results: In patients with FMD% above the median value (FMD > 2.41%), residual GFR was significantly higher compared to that in patients with FMD% below the median [1.50 (0 - 9.64) vs 0.48 (0 - 3.89) mL/min/1.73 m(2), P = 0.026]. Correlation analyses revealed that residual GFR (ρ = 0.381, P = 0.001) and total Kt/V urea (γ = 0.408, P < 0.001) were positively correlated with FMD%, whereas PD duration (γ = -0.351, P = 0.003), high-sensitivity C-reactive protein (ρ = -0.345, P = 0.003), pulse pressure (γ = -0.341, P = 0.003), and age (γ = -0.403, P < 0.001) were inversely correlated with FMD%. In contrast, there was no correlation between peritoneal Kt/V urea and FMD%. In multivariate linear regression analysis adjusted for these factors, residual GFR was found to be an independent determinant of FMD% (β = 0.317, P = 0.017)., Conclusion: This study shows that RRF is independently associated with endothelial dysfunction in ESRD patients on PD, suggesting that RRF may contribute to endothelial protection in these patients.

Background: A potential independent association was recently demonstrated between high red blood cell distribution width (RDW) and the risk of all-cause mortality in patients with cardiovascular disease, although the mechanism remains unclear. However, there have been no reports on the relationship between RDW and mortality in acute kidney injury (AKI) patients treated with continuous renal replacement therapy (CRRT). In this study, we assessed whether RDW was associated with mortality in AKI patients on CRRT treatment in the intensive care unit (ICU)., Methods: We enrolled 470 patients with AKI who were treated with CRRT at the Yonsei University Medical Center ICU from August 2007 to September 2009 in this study. We performed a retrospective analysis of demographic, biochemical parameters and patient outcomes. Following CRRT treatment, 28-day all-cause mortality was evaluated., Results: At the initiation of CRRT treatment, RDW level was significantly correlated with white blood cell count, hemoglobin (Hb) and total cholesterol. Patients with high RDW levels exhibited significantly higher 28-day mortality rates than patients with low RDW levels (P < 0.01). Baseline RDW level, Sequential Organ Failure Assessment (SOFA) score, low mean arterial pressure (MAP) and low cholesterol levels were independent risk factors for mortality. In multivariate Cox proportional hazard analyses, RDW at CRRT initiation was an independent predictor for 28-day all-cause mortality after adjusting for age, gender, MAP, Hb, albumin, total cholesterol, C-reactive protein and SOFA score., Conclusion: Our study demonstrates that RDW could be an additive predictor for all-cause mortality in AKI patients on CRRT treatment in the ICU.

Background: Patients with end-stage renal disease (ESRD) have a greatly increased risk of premature cardiovascular disease. Peritoneal dialysis (PD) patients have more atherogenic lipid profiles than haemodialysis patients. In this retrospective cohort study, we evaluated whether statin use is associated with improved mortality in incident PD patients., Methods: The study population included consecutive new PD patients (≥18 years old) from seven PD centres in Korea, between January 2003 and December 2008. The clinical outcome was mortality. A propensity score (PS) comprising demographic, clinical and laboratory variables was used to select a 1:1 matched cohort., Results: Statins were prescribed for 37.8% of incident PD patients. Cumulative survival probabilities for statin user versus non-user were 87 versus 80% and 76 versus 69% at 3 and 5 years, respectively (P = 0.01). Statin prescription was associated with a 41% lower adjusted hazard ratio (HR) of death in the unmatched cohort [95% confidence interval (CI) = 0.42-0.82; P = 0.002]. The protective effect of statins was also observed in a subgroup analysis of patients with diabetic ESRD (HR = 0.53, 95% CI = 0.36-0.80; P = 0.002). After PS matching, the use of statins was also associated with improved survival (HR = 0.55, 95% CI = 0.38-0.79; P = 0.001) in incident PD patients., Conclusions: The use of statins was associated with a reduced risk of all-cause mortality. This association was independent of a history of cardiovascular disease or total cholesterol level. Future randomized clinical trials are warranted to confirm the beneficial effect of statin on PD patients.

Background: Echocardiography is an established technique to estimate the risk for cardiovascular complications in patients with end-stage renal disease (ESRD). An enlarged left atrium (LA) has recently emerged as a marker of adverse cardiovascular outcomes in various pathologic conditions. However, there have been few studies to evaluate its prognostic value in patients with ESRD, particularly those receiving continuous ambulatory peritoneal dialysis (CAPD)., Methods: We conducted an observational cohort study to investigate whether enlarged LA can predict patient outcome in 216 patients with CAPD. Study outcomes were all-cause and cardiovascular mortality., Results: Increased left atrium volume index (LAVI > 32 mL/m(2)) was observed in 99 (45.8%) of the CAPD patients. During the follow-up (26.3 ± 18.6 months), 20 patients (9.3%) died. Kaplan-Meier analysis revealed that the 5-year survival rate was significantly lower in patients with LAVI > 32 mL/m(2) than those with LAVI ≤ 32 mL/m(2) (69 versus 82%, P = 0.024). In multivariate analyses adjusted for echocardiographic parameters and clinical and laboratory data, increased LAVI was an independent predictor of all-cause mortality [hazard ratio (HR) 1.05, 95% confidence interval (CI) 1.01-1.10, P = 0.03] and cardiovascular mortality (HR 1.08, 95% CI 1.02-1.14, P = 0.006). Furthermore, increased LAVI provided the highest predictive value for all-cause mortality [area under the receiver operating characteristic curve (AUC) = 0.766, P < 0.001] and cardiovascular mortality (AUC = 0.836, P < 0.001) among the measured echocardiographic parameters., Conclusions: We showed that increased LAVI predicted adverse outcomes better than other echocardiographic parameters in patients with CAPD.

Background: Statins and angiotensin receptor blockers (ARBs) are known to improve vascular dysfunction in patients with chronic kidney disease. However, these effects have been inconsistent in dialysis patients. Moreover, it is currently unknown whether adding statins to ARBs improves vascular dysfunction better than ARB monotherapy in these patients., Methods: We conducted a prospective open randomized trial to investigate the effects of statin add-on to ARB on vascular protection in 124 nondiabetic patients undergoing peritoneal dialysis (PD). Initially, all patients received 80 mg/day of valsartan for 6 months. Excluding 10 patients who dropped out during this period, patients were randomly assigned to continue ARB treatment alone (n = 57) or to receive 10 mg/day of rosuvastatin (n = 57) added to ARB for the next 6 months. To assess vascular function, endothelium-dependent vasodilation and arterial stiffness were determined by brachial artery flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity (baPWV), respectively., Results: Compared to baseline values, ARB treatment for the first 6 months significantly improved FMD% (2.97 ± 2.64 to 3.57 ± 2.58 %, P < 0.001). In addition, there was a small but significant decrease in baPWV during this period (1691.5 ± 276.3 to 1635.0 ± 278.6 cm/s, P = 0.048). After randomization, add-on treatment further improved FMD% (3.57 ± 2.73 to 4.24 ± 2.77 %, P = 0.003), whereas ARB monotherapy did not (P = 0.02 for between-group difference). Further slight improvement in baPWV (1617.0 ± 280.9 to 1528.9 ± 266.8 cm/s, P = 0.021) was observed only in the combined treatment group (P = 0.28 for between-group difference)., Conclusions: Adding a statin to the ARB was of some help in improving vascular dysfunction more effectively than ARB monotherapy in nondiabetic PD patients. However, whether such limited improvements can lead to better clinical outcomes requires further investigation.

Hyperhomocysteinemia induces oxidative stress and endothelial dysfunction, which share the proposed pathophysiologic mechanisms of contrast-induced nephropathy (CIN). However, no study has investigated the relation between hyperhomocysteinemia and CIN. The aim of the present study was to evaluate the effects of hyperhomocysteinemia on CIN in patients undergoing percutaneous coronary intervention. This was an observational cohort study that included 572 patients who underwent percutaneous coronary intervention. CIN was defined as an absolute ≥0.5 mg/dl or a relative ≥25% increase in the serum creatinine level at 48 hours after the procedure. The incidence of CIN was significantly greater in patients in the third homocysteine tertile (from lowest to highest, 4.7%, 7.3%, and 24.2%, p <0.001). Furthermore, the homocysteine levels were significantly greater in patients with CIN than in those without CIN (16.9 ± 4.9 vs 13.5 ± 4.2 μmol/L, p <0.001). In multiple logistic regression models, hyperhomocysteinemia was an independent risk factor for CIN (per the SD change in the plasma homocysteine level [4.44 μmol/L], odds ratio 1.70, 95% confidence interval 1.07 to 2.71, p = 0.025) after adjusting for major risk factors such as age, diabetes, and baseline cardiac and renal function. In subgroup analyses according to diabetes, acute coronary syndrome, or baseline estimated glomerular filtration rate, significant, graded associations were found between the homocysteine level and the incidence of CIN. In conclusion, hyperhomocysteinemia is independently associated with a greater risk of CIN in patients undergoing percutaneous coronary intervention., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Cardiovascular disease is the main cause of mortality in end-stage renal disease (ESRD) patients. Recent studies have indicated that non-traditional risk factors such as endothelial dysfunction (ED), chronic inflammation and protein-energy wasting (PEW) may contribute significantly to the increased cardiovascular mortality among dialysis patients. To further ascertain this association, we carried out a cross-sectional assessment of nutritional status, inflammatory markers and endothelial dysfunction in peritoneal dialysis (PD) patients., Methods: We measured ED functionally by flow-mediated vasodilatation (FMD) using doppler ultrasonography and biochemically by soluble intercellular adhesion molecule-1 (sICAM-1) in 105 stable PD patients and 32 age- and sex-matched healthy controls. We also simultaneously measured inflammatory markers and performed a subjective global assessment (SGA) of their nutritional status using a seven-point scoring scale. Subjects were subgrouped according to their nutritional and inflammatory status., Results: In PD patients, FMD was markedly lower (9.9 +/- 4.8% vs. 16.4 +/- 4.8%, P < 0.05), and sICAM-1 was significantly higher than those in controls. The malnourished patients had significantly lower FMD (8.4+/-4.6% vs. 10.8+/-4.7%, P <0.05) and higher sICAM-1 than the nourished patients. The inflamed group had significantly lower FMD (7.1 +/- 3.8 vs.11.1 +/- 4.6%, P < 0.05) and higher sICAM-1 than the non-inflamed group. In all PD patients, lean body mass/body weight %, albumin and SGA correlated positively with FMD (r = +0.207, r = +0.224, r = +0.285, P < 0.05). However, age, log high sensitivity C-reactive protein (hsCRP), log IL-6 and sICAM-1 were negatively correlated with FMD (r = -0.275, r = -0.361, r = -0.360, r = -0.271, P < 0.05). A multiple regression analysis showed that log hsCRP was an independent factor affecting FMD. Endothelial function, demonstrated as FMD and sICAM-1 in the nourished PD patients without inflammation, was well preserved compared to other subgroups., Conclusion: Our data suggest that chronic inflammation and PEW are closely linked to ED in PD patients.

Aim: A low-protein diet (LPD) is a conservative treatment in patients with chronic kidney disease (CKD) to improve uremic symptoms and slow the progression of renal dysfunction. However, the deleterious effects of protein restriction on nutritional status have raised concern. We investigated whether ketoanalogs supplementation in CKD patients who had training on LPD retards the progression of CKD and maintains nutritional status., Methods: Data were collected retrospectively from 120 consecutive patients in the CKD stages III and IV. Firstly all patients were restricted to LPD alone for 6 months (LPD alone), and then ketoanalogs of essential amino acids (KA) were supplemented for 6 months., Results: The adequate LPD had not achieved in both periods. The declining slopes of glomerular filtration rate (GFR) during the LPD + KA period were significantly lower than those during the LPD alone period. This improvement in GFR was apparent in both subjects with diabetics and non-diabetic patients. Mean serum total cholesterol levels decreased in LPD + KA compared with LPD alone period. However, serum albumin levels did not change. Responders showed a higher prevalence of diabetes and higher serum albumin levels during the LPD alone period. Multivariate analysis revealed that responsiveness to LPD + KA was independently related to diabetes (p = 0.006) and high serum albumin levels (p = 0.011) in the LPD alone period., Conclusion: KA supplementation on over LPD delayed the progression of CKD without deteriorating nutritional status, and initial serum albumin levels could be an independent factor.

Background: The prevalence of glomerular diseases differs according to geographic area, race, age and indications for a renal biopsy. This study was conducted to evaluate the distribution and changing patterns of renal diseases during the past 20 years in a large patient population in Korea., Methods: Patients aged 16 years or older who underwent a renal biopsy at Severance Hospital in the Yonsei University Health System from 1987 to 2006 were enrolled. All medical records were reviewed retrospectively., Results: In total, 1818 patients (M:F = 1.02:1) were reviewed. Glomerulonephritis (GN) comprised 85.9% of the total biopsied cases. The most common primary GN was IgA nephropathy (IgAN) (28.3%), which was followed by minimal change disease (MCD) (15.5%), membranous nephropathy (MN) (12.3%), focal segmental glomerulosclerosis (FSGS) (5.6%) and membranoproliferative GN (MPGN) (4.0%). The most common secondary GN was lupus nephritis (8.7%). The most common idiopathic nephrotic syndrome was MCD (38.5%), which was followed by MN and IgAN. Among 128 (7.4%) patients who were HBsAg-positive, MN (30.5%) and MPGN (21.1%) were the most common GN. When the incidence rates between 1987-91 and 2002-06 were compared, IgAN increased from 25.6 to 34.5%, while MCD (from 23.2 to 7.0%) and MPGN (from 6.7 to 1.7%) decreased significantly (P < 0.01)., Conclusions: IgAN was the most common primary GN, and MCD was the most common cause of nephrotic syndrome. In the 5-year quartile comparison, the relative frequency of IgAN increased, while the relative frequency of MCD and MPGN decreased significantly during the past 20 years.

Background: Elevated cardiac troponin (cTn) levels have been reported to predict adverse cardiovascular outcomes in asymptomatic ESRD patients. However, the prognostic value of elevated cTn levels associated with sepsis in ESRD patients is unknown. Therefore, this study aimed to elucidate the clinical implications of elevated cTnI levels in ESRD patients with sepsis., Methods: Of the 305 ESRD patients in whom cTnI was measured between January 2003 and December 2005, sepsis developed in 121 patients during follow-up. Based on cTnI levels at the onset of sepsis, patients were classified as elevated cTnI group (ET, n = 50, >0.2 ng/ml) and lower cTnI group (LT, n = 71, < or =0.2 ng/ml). Study endpoints were short- and long-term mortality. Short-term mortality was defined as death occurring within 90 days after sepsis, and patients who survived during this period were followed till death after 90 days., Results: Before sepsis, the median concentration of cTnI was 0.05 (0.01-3.59) ng/ml and it was significantly increased to 0.11 (0.01-22.0) ng/ml when sepsis supervened (P < 0.01). Compared to the LT group, the short-term mortality rate was significantly higher in the ET group (P < 0.05). After adjustment for age, diabetes, serum albumin and CRP levels, presence of shock and previous cardiovascular disease history, the ET group had a greater odds ratio of short-term mortality (OR 5.13, P < 0.01). In addition, the Kaplan-Meier plot for long-term survival revealed a significantly higher mortality rate in the ET group. In a multivariate Cox regression analysis, the elevation of cTnI levels was an independent determinant for long-term mortality (HR 5.90, P < 0.01)., Conclusion: This study showed that elevated cTnI levels were significantly associated with short- and long-term mortality in ESRD patients with sepsis. Therefore, elevated cTnI levels in these patients should not be overlooked and be followed for adverse outcomes.

Background: Peritonitis is the leading cause of technique failure in peritoneal dialysis (PD) patients. Some patients experience recurrent ascites, encapsulating peritoneal sclerosis (EPS), and even death after catheter removal. Little is known, however, about the risk factors for such complications., Methods: The study subjects were 117 patients that had their PD catheter removed due to peritonitis between January 2000 and June 2006. Biochemical and clinical data were reviewed retrospectively. Serum C-reactive protein (CRP) and blood and effluent white blood cell counts (WBC) were measured at baseline and at 72 hours of peritonitis. Based on adverse outcomes, patients were classified into 4 groups: non-complication (NC; n = 73), recurrent ascites (A; n = 26), EPS (E; n = 10), and death directly related to peritonitis (D; n = 8)., Results: Age at PD catheter removal was significantly higher in D group compared to NC group (62.0 +/- 10.6 vs 51.2 +/- 11.5 years, p < 0.05). In addition, mean PD duration was significantly longer in E group compared to NC and A groups (130.5 +/- 48.1 vs 58.8 +/- 42.4 vs 74.8 +/- 47.4 months, p < 0.01). Compared to baseline, effluent WBC was significantly decreased in NC group after 72 hours of peritonitis. In addition, serum CRP level was significantly decreased in NC and A groups, whereas it was significantly increased in D group. Multivariate analyses adjusted for age, PD duration, blood and effluent WBC, serum CRP, and micro-organisms revealed that serum CRP level at 72 hours predicted significantly the development of EPS [odds ratio (OR) 1.15, p < 0.05] and peritonitis-related death (OR 1.18, p < 0.01). In addition, PD duration (per 1 month increase: OR 1.03, p < 0.05) and age at PD catheter removal (per 1 year increase: OR 1.11, p < 0.05) were identified as significant determinants of EPS and peritonitis-related death respectively. Only effluent WBC at 72 hours was significantly associated with the development of ascites (OR 1.27, p < 0.05)., Conclusion: Older patients with long PD duration and those with persistently elevated serum CRP levels were likely to develop complications after peritonitis-related technique failure. Our study suggests that serial measurement of CRP may be helpful in predicting the development of complications after PD catheter removal.

Of a large body of literature reporting clinical outcomes for patients maintained on peritoneal dialysis (PD), most publications have focused on relatively short-term results. Few reports have focused on long-term survival in PD patients. Here, we present our experience with long-term patient outcomes and further analyses of the trends in demographics and clinical outcomes of 2301 end-stage renal disease (ESRD) patients treated with continuous ambulatory PD (CAPD) during a 25-year period (1981 - 2005) at our institute. Outcomes were analyzed for 1656 patients, excluding those younger than 15 years of age at initiation of CAPD, those having less than 3 months' follow-up, or those who had been on hemodialysis or who received a kidney graft before starting CAPD. In the study patients, technique survival at 5 and 10 years was 71.9% and 48.1% respectively. Patient survival was 69.8% and 51.8%. Mean age at the start of PD (50.4 +/- 13.9 years vs. 44.2 +/- 13.9 years, p < 0.01), ESRD incidence as a result of diabetic nephropathy (30.5% vs. 19.5%, p < 0.01), and incidence of cardiovascular comorbidities (26.6% vs. 20.5%, p < 0.01) were all significantly greater in patients who started PD during the second half of the study period (1993 - 2005) as compared with the first half (1981 - 1992). A multivariate analysis adjusting for these changes in demographics and comorbid conditions revealed that PD therapy starting in 1993 - 2005 was associated with a significant reduction in technique failure [hazard ratio (HR): 0.65; p < 0.01] and mortality (HR: 0.68; p < 0.01) as compared with the earlier period. However, in subgroup analyses, technique survival was not observed to be significantly improved in patients with diabetes. In summary, technique and patient survival have significantly improved despite increases in patient age, cardiovascular comorbidity, and ESRD caused by diabetes. Although diabetes, older age, and cardiovascular comorbidities are not factors that are easily modifiable to improve PD outcomes, results at our institution are encouraging in an era of declining PD utilization.

Background: Long-term peritoneal dialysis (PD) is associated with the development of various structural and functional changes to the peritoneal membrane when bioincompatible conventional peritoneal dialysis fluids (PDFs) are used. In this study, we looked at patients that were treated with conventional PDFs and then changed to novel biocompatible PDFs with a neutral pH and a low concentration of glucose degradation products (GDPs) to investigate whether this change could result in the arrest or reversal of peritoneal membrane deterioration., Methods: In an open label, randomized prospective trial, the clinical effects of conventional PDFs and biocompatible PDFs with neutral pH and very low concentration of GDPs were compared in 104 patients equally divided between both study PDFs. Blood and effluent dialysate samples, peritoneal equilibration tests, and adequacy evaluation were undertaken at baseline, 4, 8, and 12 months. The target variables were the ratio of dialysate-to-plasma (D/P) creatinine, peritoneal ultrafiltration, residual renal function, dialysis adequacy indices, and effluent cancer antigen 125 (CA125)., Results: D/P creatinine values were not different in the two groups. Peritoneal ultrafiltration was significantly higher in the low-GDP PDF group than in the conventional PDF group at all follow-up times (4 months: 9.1 +/- 4.3 vs 6.0 +/- 3.0; 8 months: 8.3 +/- 3.4 vs 6.0 +/- 3.0; 12 months: 8.9 +/- 3.3 vs 6.1 +/- 3.3 mL/g dextrose/day; p < 0.05). Peritoneal Kt/V urea values and total weekly Kt/V urea values at 4 months were significantly higher in the low-GDP PDF group than in the conventional PDF group. Residual renal function was not statistically significant. Effluent CA125 levels were significantly higher in the low-GDP PDF group at all follow-up visits (4 months: 37.8 +/- 20.8 vs 22.0 +/- 9.5; 8 months: 41.2 +/- 20.3 vs 25.9 +/- 11.3; 12 months: 40.4 +/- 21.4 vs 28.6 +/- 13.0 U/mL; p < 0.05). Among anuric patients, peritoneal ultrafiltration at 4, 8, and 12 months, total weekly Kt/V at 4 and 8 months, and CA125 levels at all follow-up visits were significantly higher in patients treated with low-GDP PDF than those treated with conventional PDF. However, among anuric patients, D/P creatinine showed no significant differences between the low-GDP PDF group and the conventional PDF group., Conclusion: The use of biocompatible PDFs with neutral pH and low GDP concentration can contribute to improvement of peritoneal ultrafiltration and peritoneal effluent CA125 level, an indicator of peritoneal membrane integrity in PD patients.

Background: The causes of accelerated atherosclerosis in end-stage renal disease (ESRD) patients are unknown, although recent studies have suggested that Chlamydia pneumoniae (Cp) infection and inflammation might be contributing factors. We aimed to evaluate the association of carotid atherosclerosis progression with Cp infection and inflammation in patients undergoing peritoneal dialysis (PD)., Methods: This is a prospective observational study. A total of 52 non-diabetic prevalent PD patients were included. The intima-media thickness of a common carotid artery (CCA-IMT) was measured at baseline and after 36 months by B-mode ultrasonography. Serum antibodies to Cp and inflammatory markers were obtained at the time of initial measurement of the CCA-IMT., Results: CCA-IMT progressors (deltaCCA-IMT > or = 0.015 mm/year) had a higher prevalence of seropositivity for Cp IgA antibody, a higher level of Cp IgA antibodies indices, log IL-(interleukin-)6, and intercellular adhesion molecule-1 (ICAM-1) compared to the non-progressors (deltaCCA-IMT < 0.015 mm/year). On multivariate analysis, Cp IgA index and log IL-6 were independent risk a factors for CCA-IMT progression. Also, Cp IgA index had independent positive correlation with the magnitude of annual deltaCCA-IMT. Cp IgA antibody seropositive patients showed significantly higher mean annual deltaCCA-IMT than seronegative patients. Moreover, patients with both positive Cp IgA antibodies and elevated IL-6 above the median level showed higher deltaCCA-IMT than those with either factor alone., Conclusions: Our data showed that Cp and inflammation were significant risk factors of CCA-IMT change in PD patients. This study strengthens evidence that Cp is involved in the pathogenesis of atherosclerosis and also suggests that the effect of Cp infection under high inflammatory status might be a risk factor for progression of atherosclerosis.

Background: Loss of residual renal function (RRF) contributes to anaemia, inflammation and malnutrition and is also a strong predictor of mortality in continuous ambulatory peritoneal dialysis (CAPD) patients. However, the role of RRF on peritonitis is not yet clearly established. This study aimed to evaluate the effect of RRF on the development of peritonitis., Methods: Study subjects were 204 end-stage renal disease (ESRD) patients who started PD from January 2000 to December 2005. Biochemical and clinical data within 1 month of PD commencement were considered as baseline. To determine risk factors for peritonitis, multivariate Cox regression was performed. Kaplan-Meier analysis and log-rank test were used to examine the difference of peritonitis-free period according to the presence of diabetes and RRF., Results: On univariate analysis based on baseline data in first peritonitis, diabetes was less prevalent and RRF (6.7+/-2.6 vs 4.0+/-2.3 ml/min/1.73 m2, P<0.01), haemoglobin (10.9+/-1.2 vs 10.6+/-1.2 g/dl, P<0.05) and serum albumin level (3.6+/-0.4 vs 3.4+/-0.4 g/dl, P<0.01) were significantly higher in the peritonitis-free group. Kaplan-Meier analysis showed that time to first PD peritonitis episode was significantly longer in the non-diabetic patients (P<0.001) and in patients with higher residual GFR (P<0.001). Multivariate analysis showed that diabetes [hazard ratio(HR) 1.64, P<0.05] and RRF (per 1 ml/min/1.73 m2 increase, HR 0.81, P<0.01) were independent risk factors., Conclusion: Our study revealed that RRF and diabetes were risk factors for peritonitis. These results suggest that preservation of RRF should be viewed as a protective strategy to reduce peritonitis.

Background: Continuous ambulatory peritoneal dialysis (CAPD) is an established treatment for end-stage renal disease (ESRD). We investigated the outcome of CAPD over a period of 25 years at our institution., Methods: CAPD has been performed in 2301 patients in 25 years. After excluding patients with less than 3 months of follow-up and missing data, we evaluated 1656 patients who started peritoneal dialysis between November 1981 and December 2005. Data for sex, age, primary disease, comorbidities, follow-up duration, cause of death, and cause of technique failure were collected. We also examined data for urea kinetic modeling (UKM), beginning in 1990, and peritonitis episodes, including causative organisms, starting in 1992., Results: Compared to incident patients from 1981-1992, mean age and incidence of ESRD caused by diabetic nephropathy increased in patients from 1993 to 2005. Technique survival after 5 and 10 years was 71.9% and 48.1% respectively. Technique survival was significantly higher in patients who started CAPD after 1992 than in those who started before 1992. Peritonitis was the main reason for technique failure. Overall peritonitis rate was 0.38 episodes per patient-year, with a significant downward trend to 0.29 per patient-year over 10 years, corresponding to a decrease in gram-positive peritonitis. Patient survival after 5 and 10 years was 69.8% and 51.8% respectively. Patient survival improved significantly during 1992-2005 compared to 1981-1992 after adjustment for age, gender, diabetes, and cardiovascular comorbidities [hazard ratio (HR) 0.68, p < 0.01]. Subgroup analysis based on UKM revealed that dialysis adequacy did not affect patient survival. However, diabetes (HR 2.78, p < 0.001), older age (per 1 year: HR 1.06; p < 0.001), serum albumin level (per 1 g/dL: increase, HR 0.52; p < 0.05), and cardiovascular comorbidities (HR 2.32, p < 0.01) were identified as significant risk factors., Conclusion: Technique survival has improved due partly to a decrease in peritonitis, which was attributed to a decrease in gram-positive peritonitis. Patient survival has also improved considering increases in aged patients and ESRD caused by diabetes. The mortality rate of CAPD is still high in older, diabetic, malnourished, and cardiovascular diseased patients. A more careful management of higher risk groups will be needed to improve the outcome of CAPD patients in the future.

Information is limited regarding the histological features related to chronic graft dysfunction and failure in patients with IgA nephropathy developing after renal transplantation. The prevalence and significance of glomerular crescents in post-transplant IgAN including recurrent, de novo and transmitted forms (TxIgAN), were studied. Renal morphology was evaluated in 71 patients of TxIgAN, obtained at more than 6 months post-transplant, and compared with regard to the presence (C-TxIgAN) or absence (N-TxIgAN) of glomerular crescents. Crescents were demonstrated in 12 samples of 10 patients (14.1%). The percentages of crescents were from 4.8% to 83.3% (median, 28.6%) in each sample. Ten samples of C-TxIgAN had cellular to fibrocellular crescents, and four of these were associated with diffuse mesangial proliferation. Serum creatinine levels and the frequency of nephrotic range proteinuria at the time of biopsy and the degree of interstitial inflammation were significantly different in the two groups. Graft survival after allograft biopsies was significantly lower in C-TxIgAN (P = 0.0017). Chronic rejection was a major cause of graft loss in N-TxIgAN (31.8%), whereas TxIgAN was the major cause in C-TxIgAN (66.7%). In conclusion, the current study suggests that glomerular crescents are not rare and that they are responsible for chronic graft dysfunction in TxIgAN patients.

Background: In recent years, the rate of peritonitis during continuous ambulatory peritoneal dialysis (CAPD) has been significantly reduced. However, peritonitis remains a major complication of CAPD, accounting for considerable mortality and hospitalization among CAPD patients., Objective: To generate a "center tailored" treatment protocol for CAPD peritonitis by examining the changes of causative organisms and their susceptibilities to antimicrobial agents over the past 10 years., Method: Retrospective review of the medical records of 1015 CAPD patients (1108 episodes of peritonitis) who were followed up from 1992 through 2001., Results: The overall incidence of peritonitis was 0.40 episodes/patient-year. The annual rate of peritonitis and the incidence of peritonitis caused by a single gram-positive organism were significantly higher in 1992 and 1993 compared with those in the rest of the years (p < 0.05). The incidence of peritonitis due to coagulase-negative staphylococcus (CoNS) decreased significantly over time, whereas there was no significant change in the incidence of Staphylococcus aureus (SA)-induced peritonitis. Among CoNS, resistance to methicillin increased from 18.4% in 1992-1993 to 41.7% in 2000-2001 (p < 0.05). In contrast, the incidence of methicillin-resistant SA was not different according to the calendar year. Catheter removal rates were significantly higher in peritonitis due to a single gram-negative organism (16.6%) compared with gram-positive peritonitis (4.8%, p < 0.005). The mortality associated with peritonitis was also higher in gram-negative (3.7%) compared with gram-positive peritonitis (1.4%), but there was no statistical significance. Among single gram-positive organism-induced peritonitis, catheter removal rates were significantly higher in SA (9.3%) than those in CoNS (2.9%, p < 0.01) and other gram-positive organisms (2.9%, p < 0.05). In peritonitis caused by CoNS, the methicillin-resistant group showed significantly higher removal rates than the methicillin-susceptible group (8.2% vs 1.0%, p < 0.01)., Conclusion: The incidence of peritonitis for 2001 decreased to less than half that for 1992, due mainly to a significant decrease in CoNS-induced peritonitis, whereas the proportions of peritonitis due to a single gram-negative organism and methicillin-resistant CoNS increased. These findings suggest that it is necessary to prepare new center-based guidelines for the initial empirical treatment of CAPD peritonitis.

Sclerosing encapsulating peritonitis (SEP) is a rare yet serious complication in patients with continuous ambulatory peritoneal dialysis (CAPD). Incidence and prevalence of this syndrome have been defined in some large populations and a few single-centre experiences, but there is no satisfactory estimate of the comparative incidence of dialysis related SEP. The pathogenesis of SEP still remains uncertain, but there could be various causative factors. The diagnosis of SEP remains based on clinical suspicion confirmed with radiologic and/or pathologic findings. The possible variable etiologies and probable distinct pathways leading to this syndrome may make a uniform therapeutic approach unlikely. To determine the prevalence, etiologic factors, clinical features, effect of dialysis duration, and outcome of SEP in Korea, patients undergoing CAPD who developed SEP were retrospectively studied in five University Hospital dialysis centres with large numbers of CAPD patients in Korea. Out of a total 3888 CAPD studied patients between January 1981 to December 2002 in those five medical centres, 31 cases developed SEP with the overall prevalence 0.8%. There were 15 men and 16 women. The mean age of these patients was 44.0 +/- 9.8 years old. The mean duration of CAPD before SEP was 70.3 +/- 41.9 months (range 9-144 months) and 67.8% of patients (21/31) had been on CAPD more than 4 years. Peritonitis, including one fungal peritonitis, was the main cause of SEP in 25 cases (80.6%). Seventy percent of these cases used beta-blocker and the mean duration of the usage was 61.7 +/- 47.6 months. Seven cases were surgically treated and others were treated conservatively with intermittent total parenteral nutrition. The mortality rate was 25.8%. In conclusion, SEP is a serious life threatening complication of CAPD, and most cases had long-term peritoneal dialysis (PD) duration more than 4 years. To reduce the incidence of SEP, careful monitoring may be needed especially in patients with long-term CAPD and peritonitis.

Background: Pathophysiological causes of the development and progression of diabetic nephropathy are not well known, but the angiotensin-converting enzyme (ACE) gene polymorphism has been proposed to be involved in its development and progression., Methods: The impact of insertion/deletion (I/D) genotypes on the progression of diabetic nephropathy in 239 Korean patients with type 2 diabetes (99 patients with stable renal function, group 1; 140 patients with declining renal function, group 2) was investigated by retrospective review of clinical data., Results: The frequency of the DD genotype was significantly greater in group 2 compared with group 1 (30.7% versus 9.1%; P < 0.05). There were no significant differences in age, blood pressure, hemoglobin A(1c) levels, or lipid profiles among ACE genotype groups. However, the prevalence of retinopathy was significantly greater in patients with the DD genotype (DD, ID, and II, 90.4%, 71.2%, and 70.6%, respectively; P < 0.05). Patients with the DD genotype reached the end point (serum creatinine > 2.0 mg/dL [176.8 micromol/L]) faster than those with the other genotypes (DD, 11.38 +/- 4.08 years; ID, 13.85 +/- 4.04 years; II, 14.04 +/- 4.06 years, respectively; P < 0.05) and took significantly less time to reach dialysis therapy (DD, 13.10 +/- 4.45 years; ID, 16.21 +/- 4.74 years; II, 15.13 +/- 4.09 years, respectively; P < 0.05). In multiple logistic regression analysis, systolic blood pressure and DD genotype showed significant correlations with the progression of diabetic nephropathy. In patients with the DD genotype, the odds ratio was 3.881 (95% confidence interval, 1.564 approximately 9.628; P = 0.003) compared with those with the II genotype., Conclusion: It is suggested that the ACE gene DD genotype might be a significant risk factor for the progression of diabetic nephropathy.

Introduction: Although graft dysfunction has been increasingly reported in post-transplant IgA nephropathy (Tx-IgAN), intragraft morphological changes have been largely overlooked. We evaluated glomerular changes in Tx-IgAN to identify the histological features pertaining to significant proteinuria and therapeutic response to enalapril., Materials and Methods: Fifty-four renal allograft biopsies, diagnosed as Tx-IgAN at a median of 46 months after transplantation, were the subject of the study. In 10 patients, glomerular morphometry was performed. In 14 patients who have been treated with enalapril for more than 12 months, we correlated the therapeutic response to enalapril with allograft histology., Results: No uniform pattern was found in the glomeruli of Tx-IgAN. The glomerular mesangium was mostly indistinct. Interstitial fibrosis was negative or mild in 88.9%. By morphometry, the glomerular tuft areas and mesangial areas were significantly larger in Tx-IgAN than those of the normal native kidney (p < 0.05), but were not different from transplant cases without glomerulonephritis. Proteinuria of >/=1 g/24 h was correlated with glomerulosclerosis, interstitial fibrosis and interstitial inflammation at time of biopsy (p < 0.005). The presence of segmental sclerosis (SS) correlated well with the amount of 24-h proteinuria (p < 0.001). After treatment with enalapril, the amount of proteinuria reduced in 64.3%. Therapeutic response to enalapril tended to be less effective in patients having SS (28.6 versus 71.4%), but this finding did not reach a statistical significance., Conclusions: Significant proteinuria was associated with advanced chronic injury, especially with the presence of SS in Tx-IgAN, but anti-proteinuric effect of enalapril was not affected by graft histology. It remains to be clarified whether glomerular mesangial expansion plays a role in graft dysfunction in a subset of Tx-IgAN showing prominent mesangial changes.

Background: Peritoneal fibrosis is a serious complication in long-term continuous ambulatory peritoneal dialysis (CAPD) patients, but the underlying mechanism is not well understood. Since high glucose activates the p38 mitogen-activated protein kinase (MAPK) pathway in various kinds of cells, and because mesothelial cells are always exposed to high glucose dialysate, we examined the activity and expression of p38 MAPK members in cultured human peritoneal mesothelial cells (HPMCs) under high glucose conditions., Methods: HPMCs were isolated from omentum and subcultured. After serum restriction, HPMCs were exposed to 5.6 mmol/L glucose (low glucose), 5.6 mmol/L glucose + 34.5 mmol/L mannitol (low glucose + mannitol), or 40 mmol/L glucose (high glucose) for 3 minutes to 48 hours with or without SB203580. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were performed to determine mRNA and protein expression, respectively., Results: p38 MAPK and cyclic adenosine monophosphate (cAMP)-responsive element binding protein (CREB) activities and mRNA expressions were significantly increased in HPMCs exposed to high glucose compared to low glucose or low glucose + mannitol after 10 minutes and remain at higher levels to 48 hours (P < 0.05), but total p38 MAPK and CREB protein expressions did not differ. MAPK kinase 3/6 (MKK3/6) activity and mRNA expression were also higher in high glucose cells after 3 minutes (P < 0.05), and fibronectin mRNA expression was significantly increased in HPMCs exposed to high glucose after 2 hours (P < 0.05). In contrast, high glucose significantly inhibited MAPK phosphatase-1 (MKP-1) protein and mRNA expression after 10 minutes (P < 0.05). SB203580 (1 micromol/L) pretreatment for 1 hour significantly reduced high glucose-induced CREB activity and fibronectin mRNA expression by 89% and 75%, respectively (P < 0.05)., Conclusion: p38 MAPK activity was increased in HPMCs exposed to high glucose, in parallel with increased MKK3/6 activity and decreased MKP-1 expression, resulting in CREB activation. This activated p38 MAPK pathway may play a role in the pathogenesis of peritoneal fibrosis.