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Purpose: This study was undertaken to investigate the effects of gamma linolenic acid (GLA) on inflammation and extracellular matrix (ECM) synthesis in mesan gial and tubular epithelial cells under diabetic conditions. Materials and Methods: Sprague-Dawley rats were intraperitoneally injected with either a diluent [n=16, control (C)] or streptozotocin [n=16, diabetes (DM)], and eight rats each from the control and diabetic groups were treated with evening primrose oil by gavage for three months. Rat mesangial cells and NRK-52E cells were exposed to medium containing 5.6 mM glucose and 30 mM glucose (HG), with or without GLA (10 or 100 µM). Intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), and fibronectin (FN) mRNA and protein ex pression levels were evaluated. Results: Twenty-four-hour urinary albumin excretion was significantly increased in DM compared to C rats, and GLA treatment significantly reduced albuminuria in DM rats. ICAM-1, MCP-1, FN mRNA and protein expression levels were significantly higher in DM than in C kidneys, and these increases were significantly abrogated by GLA treatment. In vitro, GLA significantly inhibited increases in MCP-1 mRNA expression and protein levels un der high glucose conditions in HG-stimulated mesangial and tubular epithelial cells (p

Purpose Smoking reportedly exerts deleterious effects on renal function; however, its effects on histology have not been clarified in patients with IgA nephropathy (IgAN). Materials and methods Renal histology was evaluated in a cohort of 397 patients diagnosed with IgAN according to smoking status and dose in relation to renal function. Results Among the study cohort, which was predominantly male (88.5%), 52 patients (13%) were current smokers. These current smokers demonstrated more frequent hypertension and higher serum creatinine levels than non/ex-smokers at the time of diagnosis, which was apparent with increased smoking dose. The percentages of global glomerulosclerosis and arteriolar hyalinosis increased with increased smoking dose, whereas tubulointerstitial fibrosis or arterial intimal thickening did not. Glomerular mesangial alpha-smooth muscle actin expression were similar between current and non/ex-smokers matched for age, gender, hypertension, and histologic severity, although the number of glomerular CD68+ cells was significantly fewer in smokers. Initial serum creatinine level, estimated glomerular filtration rate (eGFR), and global glomerulosclerosis were found to be risk factors of serum creatinine doubling in both smokers and non/ex-smokers by univariate analysis during a mean follow-up of 3.8 years. Conclusion In addition to dose dependent renal functional decline and hypertension, smoking contributes to renal disease progression by eliciting microvascular injury in IgAN patients.

Purpose Continuous renal replacement therapy (CRRT) has been established for critically ill acute kidney injury (AKI) patients. In addition, some centers consist of a specialized CRRT team (SCT) with physicians and nurses. To our best knowledge, however, ona a few studies have yet been carried out on the superiority of SCT management. Materials and Methods A total of 551 patients, who received CRRT between January 2008 and March 2009, were divided into two groups based on the controller of CRRT. The impact of the CRRT management on 28-day mortality was compared between two groups by Kaplan-Meier curve and Cox analysis. Results During the study period, the number of filters used, down-time per day, and intensive care unit length of day were significantly higher in non-SCT group than in SCT group (6.2 hrs vs. 5.0 hrs, p=0.042; 5.0 hrs vs. 3.8 hrs, p

Purpose This study aimed to elucidate whether stone removal by extracorporeal shock wave lithotripsy (ESWL) is associated with delayed chronic kidney disease (CKD) progression. Materials and Methods We conducted a retrospective analysis of 131 nephrolithiasis patients with stage 3 and 4 CKD. We collected baseline clinical and laboratory data, kidney stone characteristics, and history of receiving ESWL. We classified study patients into two groups according to whether they underwent ESWL or not (Non-ESWL group vs. ESWL group). We initially compared annual estimated glomerular filtration rate (eGFR) changes of Non-ESWL group with those of ESWL group before undergoing ESWL. In the next step, we sought to compare annual eGFR changes in the same patients before and after ESWL. Finally, we compared annual eGFR changes between success and failure groups among patients undergoing ESWL. Results The mean age of the patients was 62 years and 72.5% were male. The mean observation period was 3.2 years. Non-ESWL group and ESWL group before undergoing ESWL showed similar annual eGFR changes (-1.75±6.5 vs. -1.63±7.2 mL/min/1.73 m2/year, p=0.425). However, eGFR declined slower after undergoing ESWL than before ESWL (annual eGFR changes, -0.29±6.1 vs. -1.63±7.2 mL/min/1.73 m2/year, p

Purpose: In patients with diabetic end stage renal disease (ESRD), glycated albumin (GA) reflects recent glycemic control more accurately than glycated hemoglo bin (HbA1c). We evaluated the relationship between GA and average blood glucose (AG) level and developed an estimating equation for translating GA values into easier-to-understand AG levels. Materials and Methods: A total of 185 ESRD patients, including 154 diabetic and 31 non-diabetic participants, were enrolled (108 hemodialysis, 77 peritoneal dialysis). Patients were asked to perform fourpoint daily self-monitoring of capillary blood glucose (SMBG) at least three consecutive days each week for four weeks. Serum levels of GA, HbA1c and other biochemical parameters were checked at baseline, as well as at 4 and 8 weeks. Results: Approximately 74.3±7.0 SMBG readings were obtained from each participant and mean AG was 169.1±48.2 mg/dL. The correlation coefficient between se rum GA and AG levels (r=0.70, p

Sclerosing encapsulating peritonitis (SEP) is a rare but serious complication in patients with continuous ambulatory peritoneal dialysis (CAPD), and is characterized by a progressive, intra-abdominal, inflammatory process resulting in the formation of sheets of new fibrous tissue, which cover, bind, and constrict the viscera, thereby compromising the motility of the bowel. No satisfactory estimate is available on the comparative incidence of dialysis related SEP and the pathogenesis of SEP still remains uncertain. Although recent therapeutic approaches have reported varying degrees of success, an efficient measure to detect, at an early stage, patients at risk for SEP would be beneficial and a standardized treatment regimen to prevent the illness is urgently needed. This study aimed to evaluate the clinical features of SEP and to identify the possible risk factors for the development of SEP in CAPD patients. We retrospectively reviewed by questionnaire SEP cases among CAPD patients from 7 university hospital dialysis centers in Korea, including Yonsei University, Ajou University, Catholic University, Inha University, Kyungpook University, Seoul National University and Soonchunhyang University, from January 1981 to December 2002. Out of a total of 4,290 CAPD patients in these centers, 34 cases developed SEP with an overall prevalence of 0.79%. The male to female ratio was 17:17. The median age of these patients was 44.5 years (range 19 - 66). The median duration of CAPD before SEP was 64 months (9 - 144) and 68% of patients (23/34) had been on CAPD for more than 4 years. Peritonitis (including two fungal cases) was the main cause of catheter removal in SEP (27 cases, 79%). Seventy-five percent of the cases (15/20) were administered β-blocker for a mean duration of 85 months (26 - 130). Among 10 cases with available peritoneal equilibration test (PET) data, 8 showed high transporter characteristics, and the remaining 2 were high average. Eighteen cases were diagnosed by clinical and radiologic methods, and 16 were surgically diagnosed. Eleven cases were surgically treated and the others were treated conservatively with intermittent total parenteral nutrition (TPN). The overall mortality rate was 24%. SEP is a serious, life threatening complication of CAPD. Most cases had a PD duration of more than 4 years, a history of severe peritonitis, and high transporter characteristics in PET. Therefore, to reduce the incidence of SEP, careful monitoring and treatment, including early catheter removal in patients with severe peritonitis, should be considered for long-term CAPD patients with the above characteristics.

The aim of this study was to evaluate the evolution of lupus activity in end-stage renal disease (ESRD) patients due to lupus nephritis and to determine the long-term prognosis. We reviewed the clinical courses of 45 patients with ESRD due to systemic lupus erythematosus (SLE). We analyzed the course of SLE following the onset of ESRD, with special attention to the clinical and serological manifestations, survival time on dialysis, and renal transplantation outcome. Disease activity was measured using the SLE Disease Activity Index (SLEDAI). Of the 45 patients, 21 patients were being treated with hemodialysis (HD), 11 were undergoing peritoneal dialysis (PD), and 13 underwent transplantation. Duration of follow- up was 53 +/- 29 months. The SLEDAI score on commencement of renal replacement therapy was not significantly different among the 3 groups (HD: 4.2 +/- 4.2, PD: 4.3 +/- 2.3, Transplant: 3.2 +/- 1.9). However, disease activity scored by follow-up maximal SLEDAI during dialysis or transplantation showed a significant increase after peritoneal dialysis (HD: 5.0 +/- 3.6, PD: 7.4 +/- 3.7, Transplant: 2.2 +/- 1.7, p < 0.05). When the individual changes in the maximal SLEDAI score were considered, a significant increase was apparent after peritoneal dialysis (p < 0.05), but not after either hemodialysis or renal transplantation. There was no significant difference in cumulative survival rate, and also in technique or graft survival rates of the 3 groups. Among the variables tested, follow-up maximal SLEDAI score was the only significant factor associated with patient survival (odds ratio: 1.15, p < 0.05). The incidence (36% versus 19%) of high disease activity was greater, but not significantly, in the peritoneal dialysis group, as compared to the hemodialysis group. Clinical activity of SLE was apparent in 65% of patients in the first year of dialysis, but none showed any activity after the third year of dialysis. We found that although lupus disease activity declined after patients progressed to ESRD, lupus disease activity still affected patients' survival. An incremental increase in postdialysis lupus activity was not uncommon, especially during the first one year of dialysis. During the follow-up period, maximal SLEDAI score increased significantly after peritoneal dialysis. However, the long-term prognosis was not significantly different according to the treatment modality.

Maintenance of healthy endothelium is essential to vascular homeostasis, and preservation of endothelial cell function is critical for transplant allograft function. Damage of microvascular endothelial cells is now regarded as a characteristic feature of acute vascular rejection and chronic allograft nephropathy, which is an important predictor of graft loss and is often associated with transplant vasculopathy. In this review, we will discuss the role of microvascular endothelium, in renal allograft dysfunction, particularly as it relates to markers of endothelial dysfunction and endothelial repair mechanisms. We also discuss the potential for therapies targeting endothelial dysfunction and transplant graft vasculopathy.

Previously, we reported that high glucose enhanced cytokine-induced nitric oxide (NO) production by rat mesangial cells (MCs), and that the enhanced expression of the iNOS pathway may promote extracellular matrix accumulation by MCs. The present study was designed to examine whether the iNOS pathway is pathologically altered in experimental diabetic nephropathy, and whether therapy with angiotensin converting enzyme (ACE) inhibitor (imidapril: I) or angiotensin II type I receptor (AT1) blocker (L-158,809: L), ameliorates these changes. Male Sprague-Dawley rats were injected with diluent (control: C) or streptozotocin. At sacrifice after 4, 8 and 12 weeks, rats underwent either a 4 hour placebo or an intraperitoneal lipopolysaccharide (LPS, 2 mg/kg) challenge. Systolic blood pressure (SBP) and urinary protein excretion (UPE) increased significantly in diabetic (D) rats compared with C. The basal expression of glomerular iNOS mRNA was increased in D rats compared with that of C rats, by reverse- transcription (RT)-polymerase chain reaction (PCR), whereas there was no significant difference in the level of protein by Western blot analysis. Upon LPS stimulation, the iNOS mRNA and protein expression was significantly elevated in D rats. In D rats, this up-regulation, of LPS-stimulated iNOS expression, was equally ameliorated both by I and L in mRNA and protein levels. From immunohistochemistry (IHC), there was a negative staining for the iNOS within the glomeruli of five C rats without LPS treatment, but one of four rats, with LPS treatment, showed minimal iNOS staining in the glomeruli. In D rats, the glomerular mesangium and podocytes were positive for iNOS in each of three out of five rats with, and without, LPS treatment. In conclusion, LPS-stimulated glomerular iNOS expression was enhanced in diabetic pnephropathy, and the activation of angiotensin II may play a role in this enhancement.

Focal segmental glomerulosclerosis (FSGS) is an important cause of nephrotic syndrome and end-stage renal disease. FSGS recurrence after renal transplantation has a potentially detrimental course leading to the loss of renal function. In order to establish FSGS recurrence rates and evaluate the course of the disease on living-related-donor renal transplantation in ethnic Korean adults (> or = 18 years), we reviewed our experiences of 27 kidney transplantations with FSGS over the last 15 years. Of the 27 renal allografts, 13 were found to have recurrent FSGS by graft biopsy. In comparison with background data upon patients with and without recurrence of FSGS, the donor age of patients with recurrent FSGS was significantly higher than that of those without recurrence (median, 39 years vs 26, p < 0.05). In terms of, age at transplantation, length of dialysis period, and mode of dialysis no differences were found between recurrent and nonrecurrent cases. The graft survival rate of recipients from a kidney donor of age less than 40 years was significantly higher than that of recipients from a kidney donor of age more than 40 years, at 5 and 10 years, respectively (87% vs 33%, 41% vs 0%, p < 0.05). The association between clinical variables and recurrence was assessed by multiple logistic regression analysis, and donor age was found to be a risk factor of FSGS recurrence (p

In order to investigate cytokine productions in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), we studied the production of interleukin (IL)-1 beta, -6 and interferon (IFN)-gamma by cultured peripheral blood mononuclear cells (PBMC) in peritonitis-free CAPD patients. The correlation of cytokine production with plasma parathyroid hormone (PTH) and albumin levels was also evaluated. While the release of IL-1 beta was not markedly different from controls release of IL-6 from 24-hour cultured PBMCs was significantly greater than that of controls, (Mean +/- S.D., IL-6: 2186.8 +/- 1217.9 pg/ml, vs 1516.3 +/- 767.9, p0.05). The addition of lipopolysaccharide (LPS, 10 micrograms/ml, significantly stimulated IL-1 beta and -6 production of PBMCs in CAPD patients and controls, compared to an unstimulated condition. The LPS-induced IL-1 beta production was also not markedly different from controls, whereas LPS-induced IL-6 production was significantly higher than controls (IL-6: 13,220.7 +/- 7177.4 vs 7411.4 +/- 1236.9, p0.05). However, the percentage increases of IL-6 production stimulated with LPS in CAPD patients were not significantly different from controls (p0.05). No difference of baseline IFN-gamma was detected between CAPD patients controls, but phytohemagglutinin (PHA, 10 micrograms/ml)-stimulated IFN-gamma release was significantly higher in CAPD patients than controls (2425.9 +/- 1565.0 pg/ml vs 1364.0 +/- 755.1, p0.05). There was no significant correlation between PTH and, IL-1 beta, serum albumin level and LPS-stimulated IL-6 production (r = 0.54, p0.05). In conclusion, CAPD seems to partly induce activation of PBMCs with an enhanced release of IL-6 and IFN-gamma, and CAPD patients with higher serum albumin levels tend to show higher IL-6 production in immune response.

The aim of this study was to elucidate the effects of anti-hypertensive drugs, nifedipine, furosemide, hydrochlorothiazide, captopril, and atenolol on DNA synthesis and proliferation of cultured rat aortic smooth muscle cells induced by fetal calf serum. Aortic smooth muscle cells from Sprague-Dawley rats were isolated, cultured, and seeded in multi-well plates. When confluent, cells were cultured in a conditioned medium without fetal calf serum. After 72 hours, cells were cultured in the medium retaining 10% fetal calf serum with or without anti-hypertensive drugs by increasing the concentration between 10(-8) and 10(-4) M. DNA synthesis was assessed by [3H]-thymidine uptake and proliferation by cell numbers using a hemocytometer. Nifedipine at a concentration of 10(-5) M and 5 x 10(-5) M inhibited serum-induced DNA synthesis significantly by 50.8% and 86.6%, respectively (p < 0.05). The results of cell numbers paralleled those of 3H-thymidine incorporation. Serum-induced DNA synthesis was also reduced by 32.6% at the highest dose of furosemide (10(-4) M), but there was no statistical significance. Hydrochlorothiazide, captopril, and atenolol did not show anti-proliferative effect throughout any of the doses. In conclusion, among the various anti-hypertensive drugs, nifedipine seems to be most beneficial in view of its direct inhibitory effect on DNA synthesis and proliferation of smooth muscle cells, as well as for its anti-hypertensive effect.

Renal osteodystrophy has become a frequent complication in patients with chronic renal failure (CRF), and various histologic forms such as high turnover, low turnover and mixed bone disease have been demonstrated. The only reliable method for distinguishing patients with high turnover from those with low turnover bone disease is bone histomorphometric study, but its clinical utility is restricted. Because of its invasive nature, efforts have been made to predict indirectly the type and severity of this metabolic bone disease by serum assays. In this cross-sectional study, we measured total and regional (head, arms, trunk, ribs, legs, spine and pelvis) bone mineral densities (BMD) by dual X-ray absorptiometry (DXA) in patients with variable degrees of CRF and correlated them with various bone markers. Decreased BMDs were detected in various skeletal sites (trunk and pelvis) in the patients' group. Total BMD Z score was lower in predialysis CRF patients than in the control subjects. Decreased BMD Z scores on weight-bearing bone were pronounced at L1 lumbar vertebra, femur trochanter, femur neck and Ward's triangle. Positive linear correlations were found between creatinine clearance and trunk, ribs, pelvis, and spine BMDs. There were inverse linear correlations between total BMD and total BMD Z score and alkaline phosphatase (AP), urine deoxypyridinoline (U-DPD) in the patients' group. There were no correlations between regional and total BMD, total BMD Z score and serum calcium, ionized calcium, and serum phosphate. There were inverse linear correlations between BUN, creatinine and bone-specific alkaline phosphatase in the predialysis CRF group. We evaluated the correlations between intact parathyroid hormone (i-PTH) and biochemical and other bone markers. There was statistically significant linear correlation between i-PTH and AP. Other bone markers have no significant correlations with i-PTH. Our results demonstrated that there is significant bone loss in patients with CRF before the start of dialysis and also regional variations of BMDs in predialysis CRF patients. DXA is a useful method for evaluating regional and total BMDs and provides information about diverse regional skeletal changes. AP, i-PTH and U-DPD can predict BMD of predialysis CRF patients.

In order to investigate the anti-proliferative effect of 3-hydroxy-3-methylglutaryl coenzyme. A reductase inhibitor, we evaluated the effects of lovastatin on DNA replication and the proliferation of rat mesangial and aortic smooth muscle cells, both of which were mesenchymal origin cells. Proliferations were determined by measuring [3H]thymidine uptake, and counting the number of cells. Growth-arrested mesangial and aortic smooth muscle cells were exposed to platelet-derived growth factor (PDGF), endothelin (ET) and angiotensin II (Ang II) to stimulate mitogenesis. All agents exhibited dose-dependent stimulation of [3H] thymidine uptake. PDGF was more potent than the others. Ang II increased [3H] thymidine uptake without demonstrable mitogenic activity. Lovastatin inhibited PDGF (10 ng/ml in mesangial cell, 25 ng/ml in smooth muscle cell)-, ET (10(-7)M)- and Ang II (10(-7)M)-induced [3H] thymidine uptake significantly in a dose-dependent manner in both cells. The increase of cell number in response to PDGF and ET treatment were also inhibited at 10 microM of lovastatin. The inhibitory effect of lovastatin was largely overcome in the presence of exogenous mevalonate at 200 microM, with 75.5% restoration from lovastatin-induced inhibition on PDGF-induced [3H] thymidine uptake in mesangial cells (77.8% in aortic smooth muscle cells). However, the addition of cholesterol did not prevent inhibition by lovastatin. In conclusion, lovastatin had an inhibitory effect on mesangial and aortic smooth muscle cell proliferation, and mevalonate was essential for DNA replication in both types of cells. Lovastatin may reduce glomerular and atherosclerotic injury through an anti-proliferative effect on mesangial and vascular smooth muscle cells, in addition to lowering circulating lipids.

We have done cross sectional and prospective studies to determine the prevalence and the clinical significance of antibodies to the hepatitis C virus (Anti-HCV) in 54 hemodialysis (HD) patients and 227 continuous ambulatory peritoneal dialysis (CAPD) patients. Fifteen patients (27.8%) were anti-HCV (+) among the HD group, and twelve patients (5.3%) were anti-HCV (+) among the CAPD group. In the HD group, the positivity of anti-HCV correlated with the duration of HD, but there was no significant correlation with the history of transfusion, the amount of transfusion and abnormal alanine aminotransferase (ALT). At the follow-up study in 164 cases (HD 50 cases, CAPD 114 cases) after 6 months, one of 14 anti-HCV (+) CAPD patients was converted to anti-HCV (-) and two of 35 anti-HCV (-) HD patients were converted to anti-HCV (+). In conclusion, the prevalence of anti-HCV was significantly higher in HD patients compared to CAPD patients, and the positivity for anti-HCV in HD patients correlated with the duration of HD. A regular follow-up of anti-HCV and isolation of anti-HCV (+) HD patients with a separate machine may be needed to prevent the transmission of the hepatitis C virus during hemodialysis.

To investigate the effect of nutritional status of continuous ambulatory peritoneal dialysis (CAPD) patients on the development of peritonitis, a cross-sectional study of the nutritional status of 79 CAPD patients and a retrospective study on the incidence of peritonitis in these patients were done. The incidences of peritonitis were compared according to the nutritional status of these patients on CAPD. Protein-caloric malnutrition assessed by a score system based on triceps skinfold thickness, mid-arm circumference, serum albumin level and relative body weight was demonstrated in 27 patients (34%) among 79 total CAPD patients. The incidence of peritonitis was significantly higher in poor nutritional status patients, with 1.09 +/- 0.86/patient-year, than that in normal nutritional status patients with 0.64 +/- 0.72/patient-year (p less than 0.05). In patients with the same nutritional status, patients using Dianeal solution had a trend of a lower incidence of peritonitis than those using Peritosol solution. In conclusion, the nutritional status and possibly the type of CAPD solution may influence CAPD peritonitis as risk factors.