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The kallikrein-kinin system (KKS) serves as the physiologic counterbalance to the renin-angiotensin system. This study was conducted to examine the changes in the expression of KKS components in podocytes under diabetic conditions and to elucidate the functional role of bradykinin (BK) in diabetes-associated podocyte apoptosis. Thirty-two rats were injected with either diluent (n = 16, C) or with streptozotocin intraperitoneally (n = 16, DM), and 8 rats from each group were treated with BK infusion for 6 weeks. Immortalized mouse podocytes were cultured in media containing 5.6 mmol/l glucose (NG), NG + 10(-7) mol/l AII (AII), or 30 mmol/l glucose (HG) with or without 10(-8) mol/l BK. Urinary albumin excretion was significantly higher in DM rats, and this increase was ameliorated by BK. Not only kininogen, kallikrein, and BK B1- and B2-receptor expression but also BK levels were significantly decreased in DM glomeruli and in cultured podocytes exposed to HG. The changes in the expressions of apoptosis-related molecules and the increase in the number of apoptotic cells in DM glomeruli as well as in HG- and AII-stimulated podocytes were significantly abrogated by BK. The suppressed KSS within podocytes under diabetic condition was associated with podocyte apoptosis, suggesting that BK may be beneficial in preventing podocyte loss in diabetic nephropathy.

Background: Fungal peritonitis (FP) is an uncommon but serious complication of peritoneal dialysis (PD) and is associated with high morbidity and mortality. Although previous studies have demonstrated that abdominal pain and catheter in situ are associated with mortality in FP patients, the effect of early catheter removal on mortality remains largely unexplored. In this study, therefore, we not only determine the risk factors for mortality but also investigate the effect of immediate catheter removal on mortality in PD patients with FP., Patients and Methods: This retrospective study was conducted on 94 episodes of FP in 1926 patients that underwent PD at Yonsei University Health System from January 1992 to December 2008. Data including demographic characteristics, laboratory and clinical findings, management, and outcome were collected from medical records., Results: Among a total of 2361 episodes of peritonitis, there were 94 episodes of FP in 92 patients, which accounted for 4.0% of all peritonitis episodes and occurred in 4.8% of patients. Mean age of patients was 52.1 years and mean duration of PD before contracting FP was 46.1 months. The presenting symptoms included turbid dialysate (93.6%), abdominal pain (84.0%), and fever (66.0%). Intestinal obstruction was complicated in 39 episodes (41.5%). 75% of FP was caused by Candida species, among which Candida albicans was the most common pathogen, accounting for 41.5% of all episodes of FP. The PD catheter was removed within 24 hours in 39 patients (41.5%), whereas catheter removal was performed between 2 and 9 days after the diagnosis of FP in 42 patients (44.7%). 27 patients (28.7%) died as a result of FP, 59 patients (62.8%) required a change to hemodialysis, and PD was resumed in 8 episodes (8.5%). In addition, the mortality rate was significantly higher in patients with delayed catheter removal (13/41, 31.7%) compared to patients with catheter removal within 24 hours (5/39, 12.8%) (p < 0.01). Multivariate logistic regression analysis revealed that delayed catheter removal, the presence of intestinal obstruction, and higher white blood cell counts in the blood and in the PD effluent were independently associated with mortality in FP patients., Conclusion: These results suggest that immediate catheter removal (i.e., within 24 hours after the diagnosis of FP) is mandatory in PD patients with FP.

Background: Left ventricular (LV) geometric patterns have never been evaluated as independent risk factors for renal disease progression (RDP). We investigated the risk factors for RDP in type 2 diabetic nephropathy patients, especially focusing on the effects of LV geometric patterns., Methods: This was a single-center retrospective cohort study. Type 2 diabetic nephropathy patients who underwent echocardiography for routine checkup were recruited. Baseline laboratory data within 1 month from the time of echocardiography and clinical and follow-up laboratory data were collected by retrospective reviews., Results: A total of 150 patients (90 men, mean age 62.9 years) were enrolled. Distributions of the patients according to LV geometric patterns were as follows: normal 21 (14.0%), concentric remodeling 18 (12.0%), concentric hypertrophy 70 (46.7%) and eccentric hypertrophy 41 (27.3%). During the study period (30.1 ± 19.4 months), RDP developed in 53 of 150 patients (35.3%). On univariate analysis, use of erythropoiesis-stimulating agent, hemoglobin, serum creatinine, estimated glomerular filtration rate (eGFR), serum albumin, log-transformed 24-hour urine protein, LV mass index and eccentric hypertrophy were strong predictors of renal outcomes. RDP-free survival was significantly decreased in the eccentric hypertrophy group (p=0.001, vs. other groups) according to Kaplan-Meier analysis. On multivariate analysis, eGFR, eccentric hypertrophy and hemoglobin levels were significant predictors of renal outcome., Conclusion: Anemia and eccentric hypertrophy may be considered as important risk factors for RDP. Multicenter prospective trials should be needed to validate the effect of LV geometric patterns on RDP.

Renal involvement in Churg-Strauss syndrome (CSS) is not uncommon, but nephrotic syndrome is rarely reported in patients with CSS. A 25-year-old woman with a long history of bronchial asthma presented to our hospital with a chief complaint of generalized edema. Laboratory studies revealed normocytic normochromic anemia, marked eosinophilia, positive anti-neutrophil cytoplasmic antibody, hypoalbuminemia, and hypercholesterolemia. Urinalysis showed heavy proteinuria (4+) without significant casts. The 24-hour urinary protein excretion was 6.5 g with a selective index of 0.35. Echocardiography and X-ray of the paranasal sinuses suggested restrictive cardiomyopathy and maxillary sinusitis, respectively. Diagnoses of CSS and nephrotic syndrome were made on the basis of clinical and laboratory findings. Renal biopsy was performed, and pathologic findings revealed focal segmental glomerulosclerosis with mesangiolysis. The patient's clinical symptoms and proteinuria improved markedly after combined treatment with corticosteroids and cyclophosphamide. Herein, we report a case of nephrotic syndrome in a patient with CSS.

Background: Previous studies have demonstrated that AST-120 (Kremezin((R))), a well-known oral adsorbent, inhibits the progression of diabetic (DM) and non-DM chronic kidney disease along with a decrease in oxidative stress. This study was undertaken to investigate whether AST-120 could reduce oxidative stress and ameliorate the development of nephropathy in experimental DM rats with normal renal function., Methods: Rats were injected with diluent (C, n = 16) or 65 mg/kg streptozotocin intraperitoneally (DM, n = 16), and eight rats from each group were treated with chow containing 5% AST-120. After 3 months, plasma advanced oxidation protein products (AOPP) and total malondialdehyde (MDA) levels, 24-h urinary albumin excretion, and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) excretion were determined by ELISA. Glomerular endothelial nitric oxide synthase (eNOS), subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (gp91phox, p47phox and p22phox), and fibronectin (FN) mRNA and protein expressions were determined by real-time PCR and western blot, respectively. In addition, dichlorodihydrofluorescein diacetate (DCF-DA) staining was performed to detect glomerular reactive oxygen species (ROS) production., Results: Compared to the C group, 24-h urinary albumin excretion was significantly higher in the DM group (P < 0.01), and AST-120 treatment significantly reduced albuminuria in DM rats (P < 0.05). Glomerular eNOS, gp91phox, p47phox and FN expression were significantly increased in DM rats compared to C rats, and these increases in DM glomeruli were significantly abrogated by AST-120 treatment (P < 0.05). The increases in plasma AOPP and MDA levels as well as renal oxidative stress in DM rats, assessed by DCF-DA staining and urinary 8-OHdG excretion rates, were also significantly attenuated by AST-120 treatment (P < 0.05)., Conclusion: In conclusion, the renoprotective effects of AST-120 in DM nephropathy seem to be associated with the amelioration of enhanced oxidative stress and FN expression under diabetic conditions.

Background: Metabolic syndrome is associated with higher morbidity and mortality in the general population, but the corresponding effects in patients on dialysis have not been clearly defined. In this study, we prospectively investigated the effect of metabolic syndrome and its individual components on outcome in non-diabetic peritoneal dialysis (PD) patients. Method. The study subjects included 106 stable non-diabetic PD patients who had been on PD for >3 months. We measured baseline characteristics, blood pressure, fasting blood glucose, lipid profiles and high-sensitivity CRP (hsCRP), and defined metabolic syndrome using the modified National Cholesterol Education Program (Adult Treatment Panel III) criteria. Mortality, technical failure and hospitalization were evaluated during the follow-up period., Results: Metabolic syndrome was present in 50 patients (47.2%), and these showed higher baseline hsCRP levels (0.67; 95% CI: 0.50-0.94 versus 1.78 mg/dl; 95% CI: 1.21-2.57; P < 0.001). Patients with metabolic syndrome experienced significantly lower 5-year survival rates than patients without (90% versus 67%, P = 0.02), although these groups did not differ in peritonitis rates, technical failure or hospitalization. A Cox proportional hazards analysis identified the following as predictors of mortality: metabolic syndrome (RR: 3.39; 95% CI: 1.16-9.94; P = 0.02), baseline albumin (RR: 0.06; 95% CI: 0.01-0.30; P = 0.001) and baseline hsCRP levels (RR: 1.14; 95% CI: 1.07-1.22; P < 0.001)., Conclusion: Metabolic syndrome is prevalent and is a risk factor influencing long-term survival in non-diabetic 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: Uric acid (UA) is known to play a pathogenic role in chronic kidney disease (CKD). However, its effect in end-stage renal disease (ESRD) has not yet been elucidated. We explored the prevalence of hyperuricaemia and the relationship between UA and residual renal function (RRF) in peritoneal dialysis (PD) patients., Methods: The subjects of this study were 134 PD patients who started dialysis at the Yonsei University Health System between January 2000 and December 2005. Timed urine collections were performed within 1 month of PD commencement and at 6-month intervals thereafter. The slope of decline of RRF over time was calculated by linear regression analysis of serial urinary urea and creatinine clearances for each patient. Biochemical and clinical data at the time of initial urine collection were considered as baseline., Results: At baseline, 32.8% of the PD patients had hyperuricaemia (UA >or=7.0 mg/dl). A significant majority of patients with hyperuricaemia were diabetic (P = 0.02). Hypertensive patients had a higher UA level (P = 0.002) compared to normotensive patients. The overall reduction rate of RRF in hyperuricaemic patients was significantly higher than in the normouricaemic group (P = 0.001). In the multiple linear regression analysis, hyperuricaemia and history of DM showed a significant negative correlation with the reduction rate of RRF after adjusting for demographic data, comorbid conditions, body mass index, baseline RRF and medications (P = 0.001)., Conclusions: Hyperuricaemia is common among PD patients and is significantly associated with the rate of decline of RRF.

Metabolic syndrome is associated with an increased risk of diabetes and cardiovascular disease. Although some data suggest that the prevalence of metabolic syndrome is higher in patients undergoing peritoneal dialysis (PD), the factors related to this increased risk are not well elucidated. We therefore examined whether peripheral white blood cell (WBC) count is correlated with the risk of metabolic syndrome in nondiabetic PD patients. We enrolled 104 nondiabetic PD patients without current infections or chronic inflammatory diseases. Complete blood cell count, anthropometry, blood pressure, fasting glucose, insulin, and lipid profiles were measured. Metabolic syndrome was defined in accordance with the National Cholesterol Education Program (Adult Treatment Panel III) criteria. Metabolic syndrome was present in 49 patients (47.1%). Patients with metabolic syndrome had a higher WBC count and high-sensitivity C-reactive protein level. As the number of metabolic syndrome components increased, WBC count increased significantly. White blood cell count was significantly positively correlated with body mass index, insulin, homeostasis model assessment of insulin resistance, and triglyceride and negatively correlated with high-density lipoprotein cholesterol. The risk of metabolic syndrome increased significantly with a higher WBC count, resulting in an adjusted odds ratio of 1.65 (per 10(3)/muL increase, P = .002). These findings demonstrate that metabolic syndrome is prevalent among nondiabetic PD patients and that WBC count is strongly associated with metabolic syndrome and its components.