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Early prediction of outcomes has major potential implications regarding the management of dialysis-related peritonitis. The outcomes of 565 consecutive episodes of peritonitis complicating peritoneal dialysis between August 2001 and July 2005 were evaluated in relation to the dialysate cell counts. Discriminatory power, based on the area under the receiver-operating characteristic (ROC) curves, of the cell counts was assessed. The findings then were validated externally in a cohort of 217 peritonitis episodes from another dialysis unit. During the study period, 565 episodes of peritonitis were included for analysis, 465 of which had treatment success defined as complete resolution of peritonitis without the need for Tenckhoff catheter removal. Of the remaining 100 episodes (treatment failure), 70 required Tenckhoff catheter removal and 30 had peritonitis-related death. The peritoneal dialysate total white blood cell count on day 3 of peritonitis predicted treatment failure independent of standard risk factors, and it had a higher area under the ROC curve than the dialysate white cell count on day 1 (0.80 versus 0.58; P0.0001). Using a peritoneal dialysate white count cut pointor = 1090/mm3 on day 3, the sensitivity was 75% and the specificity was 74% for the prediction of treatment failure (defined as catheter loss or peritonitis-related death). In multiple logistic regression analyses, peritoneal dialysate white countor = 1090/mm3 on day 3 was an independent prognostic marker for treatment failure after adjustment for conventional risk factors (hazard ratio 9.03; 95% confidence interval 4.40 to 18.6; P0.0001). Number of years on peritoneal dialysis; diabetes; gram-negative organisms; and Pseudomonas, fungal, or Mycobacterium species were other independent risk factors that were predictive of treatment failure. Findings from an independent validation set of peritonitis (217 episodes after exclusion of Mycobacterium and fungal causes) also favored the peritoneal dialysate white count on day 3, as compared with day 1 and day 2, to predict treatment failure. Area under the ROC curve for the white counts on day 3 was 0.98 (95% confidence interval 0.95 to 0.99) in the validation set. This study demonstrated and cross-validated the superiority of peritoneal dialysate white cell count on day 3 to predict outcomes of dialysis-related peritonitis. These results call attention to the value of validating prognostic factors of peritonitis complicating peritoneal dialysis.

SUMMARY: Background: Lupus nephritis is characterized by intra-renal inflammation. Patients with systemic lupus erythematosus (SLE) showed abnormal T-cell expression of RANTES (regulated upon activation, normal T cell expressed) and its level in their serum. The authors studied the mRNA expression of RANTES in the urinary sediment of lupus patients. Methods: The authors studied 88 lupus patients, who were classified into active, remission and non-renal SLE groups according to the disease activity, 29 non-SLE and 10 healthy controls. Lupus activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Urinary mRNA expression of RANTES was studied by real-time quantitative polymerase chain reaction. Results: The expression of RANTES in urinary sediment was significantly elevated in active group (P

Previous studies showed that angiotensin-receptor blocker (ARB) therapy decreased proteinuria and possibly slowed the rate of renal function decline in patients with chronic proteinuric nephropathies. We performed a double-blind, randomized, placebo-controlled, multicenter study on the ARB valsartan in the treatment of patients with immunoglobulin A (IgA) nephropathy.From 6 centers, we recruited 109 patients with IgA nephropathy who had either: (1) proteinuria with protein greater than 1 g/d and serum creatinine level less than 2.8 mg/dL (250 micromol/L), or (2) serum creatinine level of 1.4 to 2.8 mg/dL (120 to 250 micromol/L) regardless of degree of proteinuria. Patients were randomly assigned to administration of either valsartan, 80 mg/d (titrated up to 160 mg/d for blood pressure control), or placebo for 104 weeks. Additional antihypertensive therapy was allowed to achieve a target blood pressure of 140/90 mm Hg. The primary end point was doubling of serum creatinine level or dialysis-dependent renal failure. Secondary outcomes included change in proteinuria and decrease in glomerular filtration rate (GFR).There were 54 patients in the treatment group and 55 patients in the placebo group. Baseline clinical characteristics were similar between groups, although the treatment group had a marginally greater baseline GFR (87 +/- 36 versus 78 +/- 38 mL/min/1.73 m2 [1.45 +/- 0.60 versus 1.30 +/- 0.63 mL/s/1.73 m2];P = 0.29) and less proteinuria (protein, 1.8 +/- 1.2 versus 2.3 +/- 1.7 g/d; P = 0.21) than the placebo group. Average blood pressures during the study were 92.7 +/- 10.6 mm Hg in the treatment group and 100.9 +/- 9.1 mm Hg in the placebo group (P0.001). During the study period, 4 patients in the placebo group and 1 patient in the treatment group reached the primary end point (log-rank test, P = 0.18). Proteinuria decreased significantly in the treatment group (protein, 1.8 +/- 1.2 to 1.2 +/- 1.2 g/d; P = 0.03), but did not change in the placebo group. With multiple linear regression models, valsartan treatment resulted in a 33.0% decrease in proteinuria (95% confidence interval, 10.9 to 55.1) after adjusting for other confounding factors. There was a significant decrease in mean rate of GFR decrease in the valsartan-treated group (-5.62 +/- 6.79 mL/min/y [-0.09 +/- 0.11 mL/s/y]) compared with the placebo group (-6.98 +/- 6.17 mL/min/y [-0.12 +/- 0.10 mL/s/y]) throughout the study period after adjustment for average blood pressure and proteinuria (P = 0.014).Valsartan significantly decreases proteinuria and slows renal deterioration in patients with IgA nephropathy after adjustment for confounding factors, notably blood pressure. The long-term benefit of valsartan needs to be confirmed with additional studies.

Mononuclear cells play a cardinal role in the pathogenesis of systemic lupus erythematosus (SLE). A high urine cytology score has been reported to be associated with lupus nephritis in relapse. The objective of this study was to examine the urinary mononuclear cell population of patients with lupus nephritis, and explore its correlation with lupus disease activity. We studied 12 patients with active lupus nephritis, 17 patients with lupus nephritis in remission, 12 SLE patients with no history of renal disease and 13 healthy subjects. Clinical disease activity was quantified by the SLE Disease Activity Index (SLEDAI). Mononuclear cell species in the urinary sediment were examined by immunocytochemistry. Patients with active lupus nephritis had significantly more mononuclear cells in the urinary sediment. The number of + cell was significantly elevated in the active lupus nephritis than the others ( P < 0.001), while there was no significant difference in the number of + and + cell among patient groups. The total urinary mononuclear cell correlated significantly with the overall SLEDAI score ( r = 0.58, P < 0.001) as well as the renal score ( r = 0.57, P < 0.001). The number of urinary +, but not + or +, cell significantly correlated with the overall SLEDAI score ( r = 0.46, P = 0.003) as well as the renal score ( r = 0.40, p < 0.011). In nine patients with renal biopsy, the histological activity index correlated with the total urinary mononuclear cell ( r = 0.75, P = 0.02), + ( r = 0.69, P = 0.04) and + cell ( r = 0.69, P = 0.04). We conclude that urinary mononuclear cell was markedly elevated in patients with active lupus, and the urinary mononuclear cell count correlated significantly with the SLEDAI score and histological activity. + and + cells are the major component of urinary mononuclear cell in SLE patients and their number correlates with lupus disease activity.

Background: Previous studies found that transforming growth factor-β (TGF-β) induces mesothelial production of connective tissue growth factor (CTGF), which may be downstream mediators of TGF-β. Since high dose TGF-β induces apoptosis of peritoneal mesothelial cells (PMC), we study the effect of CTGF blockade in the system of TGF-β-induced PMC apoptosis. Method: We examined the effect of TGF-W in primary culture of rat peritoneal mesothelial cells (PMC). PMC apoptosis was studied by flow cytometry. The effect of CTGF was blocked by antibody and short-interfering RNA (siRNA). Expression of apoptotic gene was studied by real-time polymerase chain reaction. Result: In cultured unstimulated rat PMC, there is a low but definite incidence of spontaneous apoptosis. Stimulation with TGF-β 50 pg/ml induces an upregulation of apoptotic gene BAX expression and a downregulation of anti-apoptotic gene BCL-2L expression, and a 4-fold increase in PMC apoptosis. The effect of TGF-β-induced PMC apoptosis was partly prevented by antibody against CTGF, and completely abolished by CTGF-specific siRNA, while CTGF-blockade by siRNA had no effect on PMC necrosis. CTGF silencing by siRNA prevented the down-regulation of BCL-2L expression induced by TGF-β, had no effect on the BAX expression. Conclusion: Our results indicate that CTGF is an important downstream mediator of TGF-β-induced PMC apoptosis.

Objective We hypothesized that patients with hepatitis B virus infection and cirrhosis are more susceptible to peritonitis as a complication of peritoneal dialysis (PD). Methods A retrospective study was carried out to compare peritonitis rates between cirrhotic and non-cirrhotic patients with hepatitis B virus infection. Results Between 1994 and 2004, 25 PD patients with hepatitis B cirrhosis and 36 patients with hepatitis B without cirrhosis were included for analysis. Mean follow-up duration was 52 months. Subjects with hepatitis B cirrhosis consisted of more males and had higher total body weight. No cirrhotic patients (20 of them being Child–Pugh class A, 2 class B, and 3 class C) had undergone portosystemic shunting or liver transplantation. Cirrhotic patients had slightly higher bilirubin concentration than the non-cirrhotic group (22 ± 50 vs 9 ± 4 μmol/L, p = 0.16). There was no difference in median peritonitis-free survival between cirrhotic and non-cirrhotic patients (40 vs 37 months, p = 0.64 by log-rank test). The average peritonitis rate was 1 episode every 19.2 patient-months in the cirrhotic group and 1 episode every 20.5 patient-months in the non-cirrhotic group. Time to first peritonitis did not differ between the two groups with respect to gram-negative organisms ( p = 0.88) or gram-positive organisms ( p = 0.52). Cirrhotic patients had more frequent Streptococcus species peritonitis, which accounted for 13% of all peritonitis episodes, as opposed to 2% among the non-cirrhotic patients ( p = 0.01). Overall treatment response rate and outcome did not differ between patients with and patients without cirrhosis. Conclusions Peritonitis-free survival of cirrhosis patients infected by hepatitis B virus compares favorably with that in patients without cirrhosis. The presence of liver cirrhosis does not appear to compromise PD outcome.

OBJECTIVE Systemic lupus erythematosus (SLE) is characterized by the aberrant activation of T lymphocytes. Since T-bet and GATA-3 are the principal transcription factors for the differentiation of type-1 and type-2 helper T lymphocytes, respectively, we studied their mRNA expression in the urinary sediment of SLE patients and compared this with their urinary and intra-renal protein expression. METHODS We studied 100 SLE patients and 10 healthy subjects. Urinary mRNA expression of T-bet and GATA-3 were studied by the real-time quantitative polymerase chain reaction. Intra-renal and urinary expressions of T-bet and GATA-3 were studied by immunohistochemistry and western blotting, respectively. RESULTS The urinary mRNA and protein expressions of T-bet were significantly higher in SLE patients with active nephritis than those with inactive disease (mRNA: P < 0.001; protein: P = 0.004). The urinary mRNA expression of T-bet correlated with the SLE disease activity index (SLEDAI) score (r = 0.55, P < 0.001) and the histological activity index (r = 0.48, P = 0.03). On the other hand, the urinary mRNA and protein expressions of GATA-3 were significantly lower in SLE patients with active nephritis (mRNA: P < 0.001; protein: P = 0.006), and GATA-3 mRNA expression inversely correlated with the SLEDAI score (r = 0.38, P < 0.001). For the 22 SLE patients with kidney biopsy, tubular expressions of T-bet and GATA-3 significantly correlated with the histological activity index (T-bet: r = 0.57, P = 0.006; GATA-3: r = -0.79, P < 0.001). CONCLUSIONS Patients with active lupus nephritis have increased T-bet and depressed GATA-3 expression in the urinary sediment and kidney tissue, indicating a predominant Th1 type of T-lymphocyte activation.

Vascular endothelial growth factor (VEGF) plays a pivotal role in the capillary endothelial cell growth and proliferation and has known effects on glomerular microvascular permeability. Because certain VEGF polymorphisms are correlated with alterations in VEGF expression, we hypothesized that VEGF genetic polymorphisms may affect the renal survival and progression of primary IgA nephropathy.The study population consisted of 195 biopsy-proven IgA nephropathy patients at our center between 1984 and 2004. VEGF genotype polymorphism at -2578 positions was determined from peripheral blood leukocytes DNA using polymerase chain reaction methodologies. The primary end point was kidney survival as measured by the time interval from renal biopsy to end-stage renal disease or the requirement of renal replacement therapy.In total, we studied 119 women (61%) and 76 men (39%), with a mean age of 35 +/- 10 yr at the time of renal biopsy. Observed genotype frequency was 55.6%, 38.8%, and 5.1% for CC, CA, and AA genotypes respectively. Baseline characteristics did not differ significantly between three genotype groups for patient age, sex, prevalence of hypertension, degree of proteinuria, initial serum creatinine concentration, and the histological grading. After a median follow-up period of 11 yr, doubling of the baseline serum creatinine occurred in 107 of them; 99 patients reached end-stage renal disease requiring renal replacement therapy with a median renal survival of 88 months. The kidney survival in the CC genotype subgroup was similar to that of the CA/AA genotype subgroup during the first 2 yr but became worse than the latter thereafter (log-rank test P = 0.023). The kidney survival rates at the end of 6 yr were 76.8% in the CA genotype, 67.0% in the CC, and 50.0% in the AA genotype groups. Unadjusted hazard ratio of developing end-stage renal disease was 2.65 (95% CI, 1.16 to 6.06) for the CC group as compared to the CA/AA group. The influence of VEGF genotype upon renal survival, however, was not significant after multivariate Cox regression analysis.Our preliminary results raise the concern that the CC genotype of the VEGF promoter at -2578 position might be associated with increased risk of renal progression in patients with IgA nephropathy.

Podocyte slit diaphragm plays an important role in the control of glomerular permeability. We hypothesize that studying the gene expression profile of podocyte in urinary sediment may provide diagnostic and prognostic information on acquired proteinuric diseases.We studied 28 patients who required kidney biopsy for acquired proteinuric diseases (diabetic glomerulosclerosis, 9 cases; IgA nephropathy, 10 cases; minimal change disease, 5 cases; membranous nephropathy, 5 cases). We also studied 10 cases of diabetic microalbuminuria and 9 healthy controls. The mRNA expressions of nephrin (NephRNA), podocin (PodRNA) and synaptopodin (SynRNA) in urinary sediment were measured by real time quantitative PCR. After recruitment, all patients were followed for at least 12 months.There were significant differences in the NephRNA and PodRNA in the urinary sediment between diagnosis groups (p0.005). On the other hand, SynRNA was only marginally significant between diagnosis groups (p0.05). Although statistically significant, the degree of proteinuria had only modest correlations with the urinary expression of nephrin. After a median follow up for 23 months, there was a significant correlation between the rate of decline in renal function and NephRNA (r=0.559, p=0.001) and PodRNA (r=0.530, p=0.002), but not SynRNA (r=0.054, p=NS). The correlation remained statistically significant after multivariate analysis to adjust for the degree of proteinuria and initial renal function.Urinary mRNA expression of podocyte markers, such as nephrin and podocin, are significantly different between proteinuric disease categories. Further, NephRNA and PodRNA correlated with the rate of decline in renal function. Our results suggest that urinary podocyte gene expression may be a useful non-invasive tool which provides additional information for the management of proteinuric diseases.

Background Corynebacterium species are part of the normal skin flora. The incidence of nosocomial infections caused by Corynebacterium species have increased substantially over the past two decades. However, the clinical course of Corynebacterium peritonitis complicating peritoneal dialysis remains unclear. Method We reviewed all the Corynebacterium peritonitis in our dialysis unit from 1995 to 2002. During this period, there were 1485 episodes of peritonitis recorded; 27 (1.8%) of which were caused by Corynebacterium species. Results The underlying renal diagnosis and prevalence of comorbid conditions of the 27 patients were similar to our whole dialysis population. The bacteria isolated were resistant to penicillin in 8 cases (29.6%). Three cases (11.1%) had concomitant exit-site infection. The overall primary response rate was 74.1%; the complete cure rate was 37.0%. Episodes that received vancomycin as initial antibiotic had a marginally higher primary response rate (9 in 10 vs 11 in 17 episodes, P = 0.2) and complete cure rates (7 in 10 vs 3 in 17 episodes, P = 0.12) than the episodes that received cephalosporins, although neither of the differences was statistically significant. Thirteen cases (48.1%) had recurrent peritonitis after antibiotic therapy, 8 of which had the recurrent episode at least 30 days after stopping antibiotics (median 54 days, range 43-60 days). Eight recurrent cases (61.5%) were successfully cured by another 3 week course of intra-peritoneal vancomycin. Conclusions Recurrent Corynebacterium peritonitis is common after a 2 week course of antibiotics. Recurrent Corynebacterium peritonitis may be delayed up to 2 months after the antibiotic is stopped. Recurrent peritonitis can usually be cured with a 3 week course of intra-peritoneal vancomycin, which is probably the preferred antibiotic regimen for Corynebacterium peritonitis.

Central nervous system toxicity following administration of beta-lactam antibiotics, of which penicillin is the prototype, is a potential cause of morbidity and mortality. In recent years, important advances have been made in the pathogenesis of antibiotic-related neurotoxicity. This review focuses on the experimental and clinical aspects of neurotoxicity caused by beta-lactam antibiotics. The purpose is to provide an update on the pathogenesis, mechanism, and clinical manifestations of the neurotoxicity, along with an overview of the relationship between antibiotic structure and convulsive action. In particular, some of the prevailing ideas about pathogenesis are highlighted, including theories of the mechanism of pathogenicity. A better understanding of antibiotic-related neurotoxicity, as derived from animal models and human clinical experience, would be of value in facilitating more efficient and safer use of antimicrobial compounds.

BackgroundMicroalbuminuria is a marker of systemic endothelial dysfunction. We hypothesize that peritoneal albumin excretion in peritoneal dialysis (PD) patients, which is conceptually analogous to microalbuminuria in nonuremic patients, can predict cardiovascular disease in new PD patients.MethodWe studied peritoneal albumin excretion in 43 new PD patients. They were then followed prospectively for the development of cardiovascular events. All-cause mortality and duration of hospitalization for cardiovascular diseases were also recorded.ResultThe average duration of follow-up was 26.5 ± 17.6 months. During the follow-up period, 15 patients developed cardiovascular events. Event-free survival at 36 months was 81.4% and 53.6% for low (ConclusionAlthough the sample size of our present study is small and does not have adequate statistical power, we conclude that peritoneal albumin excretion may be an important predictor of cardiovascular disease. Further studies are needed to examine the role of dialysate albumin excretion as a means of cardiovascular risk stratification in PD patients.

Objective: We studied the etiology, clinical features and outcome of patients with bacterial meningitis from an urban Chinese city over a 10-years period. Methods: We reviewed the files of all persons aged 15-years old or above diagnosed with community-acquired bacterial meningitis from a regional hospital. The clinical findings, relevant laboratory and imaging results as well as outcome were recorded in cases with microbiological evidence of meningitis. Neurosurgical and pediatric patients were excluded. Results: Sixty-five patients between the ages of 15 and 86 years of age (mean 52 years) were identified of whom 18 (28%) died. The four most common causes were Mycobacteria tuberculosis (46%), Streptococcus pneumoniae (11%), Streptococcus suis (9%) and Klebsiella pneumoniae (8%). Neisseria meningitidis and Haemophilus influenzae were rare pathogens. The annual incidence of community-acquired bacterial meningitis was 1.27/100,000 adults. Delay in treatment was associated with a poorer prognosis (p Conclusion: The causative organisms found in this region of China differ from that reported from Europe and the US; tuberculous meningitis is the most common cause of bacterial meningitis.

Abnormal potassium metabolism may contribute to the increased cardiac morbidity and mortality seen in dialysis patients. We studied the pattern of serum potassium levels in a cohort of Chinese peritoneal dialysis (PD) patients.We studied serum potassium levels of 266 PD patients during 3 consecutive clinic visits. Dialysis adequacy, residual renal function, and nutritional status also were assessed. Patients were followed up for 33.7 +/- 20.7 months.Mean serum potassium level was 3.9 +/- 0.5 mEq/L (mmol/L). Five patients (1.9%) had an average serum potassium level less than 3 mEq/L (mmol/L), whereas 54 patients (20.3%) had a serum potassium level less than 3.5 mEq/L (mmol/L). Serum potassium levels correlated with overall Subjective Global Assessment score (r = 0.276; P0.001) and serum albumin level (r = 0.173; P = 0.005) and inversely with Charlson comorbidity score (r = -0.155; P = 0.011). There was no correlation between serum potassium level and daily PD exchange volume, total Kt/V, urine volume, or residual glomerular filtration rate. By means of multivariate analysis with Cox proportional hazard model to adjust for confounders, serum potassium level was an independent predictor of actuarial patient survival. PD patients with hypokalemia (serum potassium3.5 mEq/L [mmol/L]) had significantly worse actuarial survival (hazard ratio, 1.79; 95% confidence interval, 1.12 to 2.85; P = 0.015) than those without hypokalemia after adjusting for confounding factors.Hypokalemia is common in Chinese PD patients. Serum potassium level was associated with nutritional status and severity of coexisting comorbid condition. Furthermore, hypokalemia was an independent predictor of survival in PD patients. Additional studies may be needed to investigate the benefit of potassium supplementation for PD patients with hypokalemia.

Toxic nephropathy is an important cause of reversible renal injury. This article focuses on the nephrotoxicity of several new therapeutic compounds. Selective cyclooxygenase-2 inhibitor is associated with sodium retention, hypertension, ankle edema, and acute renal failure. The incidence of renal complication is similar to conventional nonsteroidal anti-inflammatory drugs. Bisphosphonates, especially when used in high dose for prolonged duration, can cause toxic acute tubular necrosis and renal failure. Pamidronate is also associated with a specific form of collapsing focal segmental glomerulosclerosis similar to one found in patients with human immunodeficiency virus (HIV) infection. Acyclic nucleoside phosphonate, a new group of antiviral agents, can cause Fanconi-like syndrome and progressive renal impairment. On the other hand, indinavir, a potent protease inhibitor for the treatment of HIV infection, can cause crystalluria, renal stone, acute tubular obstruction and chronic interstitial nephritis. Intravenous immune globulin and hydroxyethyl starch, a new plasma expander, are associated with acute renal failure with characteristic renal histology known as osmotic nephrosis. In short, physicians should be cautious about possible renal toxicity during the use of any new therapeutic agents.

Cytokine transforming growth factor (TGF) is involved in regulation of tissue repair after injury. More recently, TGF-beta1 codon 10 gene polymorphism has been shown to be associated with circulating TGF-beta levels. We tested whether TGF-beta1 genotype polymorphism was predictive of renal allograft function decline.The study population consisted of 129 consecutive cadaveric or living related renal transplant recipients at our center between 1985 and 2001. The recipient TGF-beta1 genotype polymorphism was determined from peripheral blood leucocytes DNA. The primary endpoint was rate of glomerular filtration rate decline between the first year and the third year of transplant.Baseline glomerular filtration rate as estimated by MDRD study equation at 1 year measured 50+/-17 mL/min/1.73 m2. At the end of the 3-year follow-up period, 52 patients (40%) experienced biopsy-confirmed acute rejections. Frequency and severity of allograft rejection did not differ with TGF-beta genotypes. However, the decline in glomerular filtration rate was significantly greater in Leu/Leu (TT) than Leu/Pro (CT) recipients, 6.3+/-16.9 mL/min/1.73 m2 versus 0.1+/-10.2 mL/min/1.73 m2, p=0.04.Our results demonstrate that recipient TGF-beta1 codon 10 Leu/Leu homozygosity is a potential risk factor of kidney allograft function decline.

Background. The degree of renal scarring in kidney biopsy is an important prognostic factor in patients with chronic kidney diseases. We hypothesize that gene expression in the urinary sediment reflects the degree of renal damage. Methods. We studied 29 patients with chronic kidney disease who underwent kidney biopsy (12 immunoglobulin-A nephropathy and 17 glomerulosclerosis) and 10 healthy controls. The mRNA expressions of a panel of target genes in urinary sediment were measured by real-time quantitative polymerase chain reaction. The results were compared with the degree of histological damage and renal function decline. Results. There were significant differences in the urinary expression of transforming growth factor-b (TGF-b), monocyte chemotactic protein-1 (MCP-1) and collagen IV between disease groups and controls. Urinary TGF-b mRNA expression correlated significantly with estimated glomerular filtration rate (r ¼ � 0.412, P ¼ 0.029) and the degree of tubulointerstitial scarring (r ¼ 0.418, P ¼ 0.024). Urinary MCP-1 expression correlated with the degree of glomerulosclerosis (r ¼ 0.450, P ¼ 0.014), but not tubulointerstitial scarring. Urinary MCP-1 expression correlated with its corresponding level by enzyme-linked immunosorbent assay (ELISA) (r ¼ 0.650, P

Acidosis is a classic uremic toxin that causes protein catabolism, mainly by selective breakdown of skeletal muscle protein. However, the importance of acidosis is often overlooked in dialysis patients. In the presence of acidosis, there is activation of the ubiquitin-proteasome machinery as well as the branched-chain keto acid dehydrogenase, resulting in catabolism of muscle protein. Acidosis acts synergistically with other catabolic factors, such as inflammatory cytokines and insulin resistance, in inducing protein catabolism. There is ample laboratory evidence showing that correction of acidosis prevents the up-regulation of the ubiquitin-proteasome machinery and reduces protein degradation. Randomized control trials further show that acidosis in dialysis patients can be treated successfully by a higher dialysate bicarbonate or lactate concentration, or by oral bicarbonate supplement. Correction of mild acidosis in dialysis patients is effective in improving nutritional status and reducing the duration of hospitalization.

Background Peritonitis is a serious complication of peritoneal dialysis (PD). We studied the efficacy of imipenem / cilastatin monotherapy in the treatment of PD-related peritonitis. Methods We performed an open-label, randomized control study comparing imipenem / cilastatin monotherapy (treatment group) versus cefazolin plus ceftazidime (control group) in the treatment of PD peritonitis. The result was further compared to a historic group treated with cefazolin plus netilmycin. Outcome measures were primary response rate at day 10 and complete cure rate. Results We enrolled 51 patients in the treatment group, 51 in the control group, and identified 96 in the historic group. The primary response rate to the assigned antibiotics was 49.0%, 51.0%, and 49.0% for the treatment, control, and historic groups, respectively ( p = 0.97). The primary response rate allowing for change in antibiotic was 82.4%, 90.2%, and 82.3%, respectively, for the three groups ( p = 0.41). The complete cure rate was 72.5%, 80.4%, and 82.3%, respectively ( p = 0.60). Tenckhoff catheter removal was needed in 6 cases in the treatment group, 6 cases in the control group, and 13 cases in the historic group ( p = 0.90). Conclusions We concluded that monotherapy of imipenem / cilastatin has similar efficacy compared to the two standard regimens of cefazolin plus ceftazidime or netilmycin in the treatment of PD peritonitis.

Hydrothorax complicating continuous ambulatory peritoneal dialysis (CAPD) appears in approximately 2% of all patients. Recent advances in minimally invasive surgery have revolutionized the treatment strategy of this condition.Hydrothorax in CAPD is most commonly secondary to a pleuro-peritoneal communication. Thoracocentesis with biochemical analysis of pleural fluid is the first-line investigation. In uncertain cases, or when there is a clinical need to demonstrate the anatomy of the communication, an imaging approach such as peritoneal scintigraphy is required. Cessation of peritoneal dialysis is indicated if diagnosis of the complication is confirmed. For half of the cases, a conservative approach allows reinstitution of CAPD, presumably because of spontaneous resolution of the leakage. A small-volume exchange is a feasible alternative for children. In patients who failed conservative treatment, video-assisted thoracoscopic pleurodesis or diaphragmatic repair or both allows most of them to continue with CAPD. Chemical pleurodesis is probably indicated for those who failed conservative treatment in centers without video-assisted thoracoscopic support. Currently, only a minority of patients will require open thoracotomy.Once hydrothorax secondary to pleuro-peritoneal communication is confirmed in CAPD patients, temporary cessation of peritoneal dialysis remains the first-line treatment. Current evidence shows that video-assisted thoracoscopic pleurodesis or repair should be the treatment of choice in patients who failed conservative management.

Genetic polymorphism of VEGF: Impact on longitudinal change of peritoneal transport and survival of peritoneal dialysis patients. Background Vascular endothelial growth factor (VEGF) plays a pivotal role in the peritoneal angiogenesis and hyperpermeability in patients on peritoneal dialysis. We hypothesis that VEGF genetic polymorphism may affect the longitudinal change of peritoneal transport and clinical outcome of peritoneal dialysis patients. Methods We studied 135 consecutive new peritoneal dialysis patients. VEGF genetic polymorphism at –1154 and –2578 positions were determined by polymerase chain reaction (PCR) methodologies. Standard peritoneal test and dialysis adequacy and transport test (DATT) were performed at the initiation of peritoneal dialysis. After 12 months, DATT was repeated in 83 patients. In 35 patients, VEGF production in vivo was determined by its levels in serum and peritoneal dialysis effluent, and mRNA expression in peritoneal dialysis effluent. Patients were followed for 19.4 ± 8.5 months for survival study. Results There was no relation between VEGF genotype and baseline peritoneal transport group. The changes in 24-hour dialysate-to-plasma (D/P) creatinine after 12 months were 0.028 ± 0.159, -0.013 ± 0.137, and 0.141 ± 0.231 for CC, CA, and AA genotype at –2578 position, respectively [one-way analysis of variance (ANOVA), P = 0.028]. The AA genotype had significantly higher increase in 24-hour D/P creatinine than the other genotypes. Similar results were found with the genotype at -1154 position, which had marked linkage disequilibrium with the genotype at –2578 position. Actuarial patient survival was 90.3% and 74.9% at 24 months for CC and CA/AA genotypes at –2578 position, respectively (P = 0.036). After correcting for confounding covariates, the adjusted hazard ratio of death was 3.04 (95% CI, 1.10 to 8.36) for the CA/AA group as compared to CC group. Although baseline serum VEGF level was higher in patients with CC genotype than those with CA/AA genotype at –2578 position (541.5 ± 322.8 pg/mL vs. 298.8 ± 209.4 pg/mL, P = 0.012), VEGF mRNA expression in peritoneal dialysis effluent was significantly lower in patients with CC genotype (1.82 ± 2.77 vs 4.48 ± 3.28, P = 0.021). VEGF protein level in peritoneal dialysis effluent was also marginally lower in patients with CC genotype, although the difference was not significant. Genotype at –1154 position was not associated with VEGF production in vivo or patient survival. Conclusion We conclude that in peritoneal dialysis patients, the AA genotype of VEGF promoter at –2578 position was associated with progressive increase in peritoneal transport. The CA/AA genotype at –2578 position was also associated with an excess mortality. Our finding also suggests that systemic and local peritoneal VEGF production may be differentially regulated.

Neurological complications of antibiotics are relatively common in renal failure. Central nervous system neurotoxicity due to penicillin and beta-lactam antibiotics is best documented with fewer accounts of ototoxicity, peripheral nerve toxicity and neuromuscular blockade. In the context of risk stratification, the goal of this review is to explore the mosaic of factors in renal impairment that may contribute to susceptibility to antibiotic neurotoxicity. Improved knowledge of the pathogenesis of these formidable adverse events among the renal failure subjects should help prevent antibiotic neurotoxicity in the future.

The proportion of end-stage renal disease patients on continuous ambulatory peritoneal dialysis (CAPD) has increased by twofold in Hong Kong over last two decades, accounting for 80% of the entire dialysis population. Our encouraging outcome results—a 2-year actuarial patient survival of 83%, and a 2-year technique survival of 72.8%—further testify to the success of CAPD in our territory. A relatively constant successful outcome has been achieved despite an increasing prevalence of diabetes mellitus and an aging population. The present review postulates the reasons behind our success. Apart from reimbursement policy, technique-related factors, and center effects, inherent patient factors—including baseline survival advantage of Chinese patients, genetic difference, cardiovascular risk factors, and possibly lower dialysis volume requirement and compliance—are thought to be contributory. As for the future, more efforts are needed to further improve the technique survival rate and the nutritional status, psychosocial well-being, and rehabilitation of CAPD patients. Judicious assessment of peritoneal dialysis adequacy and preservation of residual renal function should be constantly exercised to tailor treatment to the needs of Chinese CAPD patients.

Animal models have been the mainstay of experimental means to study chronic renal failure. An ideal experimental animal model provides a stable uremic milieu to allow experimental manipulation. The model should be technically simple to produce and have a reproducible degree of glomerular filtration rate reduction. There should also be close mimicry of human chronic renal failure without additional (unwanted) physiologic changes. This review article outlines the various choices of animal models in relation to the aforementioned criteria, with particular emphasis on their advantages and shortcomings. In principle, reduction of renal mass is undertaken in these models, after which adaptive changes take place in the remaining/remnant kidney. The glomerular changes, in proportion to the number of nephrons resected or damaged, are characterized by growth as well as hyperfunction. To date, the five-sixths nephrectomy model has remained the state-of-the-art prototype, although it must be acknowledged that no single animal model can ever duplicate the original condition of human kidney disease. It is in this context that a thorough understanding of each animal model allows the most effective modeling strategy in biomedical research. Insofar as the ideal animal model does not exist, researchers should use the biologic and biochemical diversity among the models to experimental advantage. It is expected, with good reason, that the differences can tell us as much as the similarities. Attention to selection of appropriate animal models is important to further advance the nephrology research frontier. [ Hong Kong J Nephrol 2003; 5(2):57-64]

Basal peritoneal permeability has a major impact on the outcome of peritoneal dialysis (PD) patients, but the determinant of this is unknown. Early evidence suggests that peritoneal permeability is affected by nitric oxide (NO) activity. Recently, a gene polymorphism of the endothelial NO synthase (ENOS) gene was identified that is associated with circulating nitrate levels.We performed a cross-sectional study to examine the relationship between ENOS4(a/b) gene polymorphism and basal peritoneal function in 86 Chinese incident PD patients. ENOS genotypes for variable number tandem repeats in intron 4 (a/b) were identified by polymerase chain reaction. Patients were classified into 2 groups according to results of a basal peritoneal equilibration test (PET) performed within 2 months of dialysis therapy: group A consisted of patients with low (L)/L average (LA) PET results, and group B consisted of those with H and HA PET results.Group A (L/LA) had a significantly greater prevalence of ENOS aa/ab genotype than group B (H/HA; 30% versus 12%; P0.05). Frequencies of the ENOS a allele also were greater in group A (L/LA) than group B (H/HA) (16% versus 6%; P = 0.03). ENOS genotype remained an independent predictor for peritoneal transport after adjustment for sex, body weight, and prevalence of diabetes by multivariate analysis (adjusted odds ratio, 3.3; confidence interval, 1.1 to 3.7; P = 0.03). Subjects with the aa/ab genotype had significantly lower mass transfer area coefficients (7.35 +/- 3.4 versus 9.48 +/- 5.21 mL/min; P = 0.023) and dialysate-plasma creatinine ratios at 4 hours (0.55 +/- 0.13 versus 0.62 +/- 0.14; P = 0.048) than those with the bb genotype.ENOS4(a/b) gene polymorphism is associated with basal peritoneal permeability in uremic Chinese patients.

Hydrothorax as a result of pleuroperitoneal communication occurs in approximately 2% of continuous ambulatory peritoneal dialysis (CAPD) patients. Although our understanding of its mechanisms is incomplete, it is apparent that the key to successful therapy is obliteration of a transdiaphragmatic route of dialysate leakage (pleuroperitoneal communication), possibly coupled with reduction of intra-abdominal pressure. This review corroborated the findings from 10 major population-based case series in which 60 of the 104 cases (58%) were able to resume long-term peritoneal dialysis (PD). Temporary interruption of PD alone was successful in half of them. As compared to this conservative approach, as well as chemical pleurodesis via intercostal chest drain, video-assisted thoracoscopic intervention (including direct pleurodesis and diaphragmatic repair) has shown a promising role. Efficacy of thoracoscopic treatment has been confirmed by several case series from various centers and the demonstration of a success rate in excess of 90%. With accumulating experience using the thoracoscopic technique, it remains to be seen whether this mode of treatment will obviate the traditional closed pleurodesis.

Acidosis causes malnutrition in peritoneal dialysis (PD) patients. The effect of oral bicarbonate in PD patients with Kt/V

Objective Lupus nephritis is characterized by intrarenal inflammation and lymphocyte activation. In the present study, the expression of cytokine genes in the urinary sediment of patients with systemic lupus erythematosus (SLE) was examined. Methods We studied 3 SLE patient groups (25 with active lupus nephritis [active group], 25 with inactive SLE and previous renal involvement [remission group], 20 with inactive SLE and no history of renal involvement [nonrenal SLE group]) and 2 control groups (10 patients with noninflammatory renal diseases [non-SLE group] and 10 healthy volunteers [healthy group]). Cytokine gene expression in the urinary sediment was studied by real-time quantitative polymerase chain reaction. Results Expression of interferon-γ (IFNγ) in urinary sediment was significantly higher in the active group than in all other groups (P < 0.001 by Kruskal-Wallis test). Among the SLE patient groups, there was a close correlation between IFNγ expression and the overall SLE Disease Activity Index (SLEDAI) score (Spearman's r = 0.590, P < 0.001) and the SLEDAI renal score (r = 0.642, P < 0.001). Urinary expression of interleukin-2 (IL-2) in the active group was significantly higher than that in the healthy group (P = 0.046) but not in the remission or nonrenal SLE groups. There was no difference in the levels of IL-4 expression among the SLE groups. Conclusion We found a predominance of Th1 cytokine in the urinary sediment of patients with active lupus nephritis. Measurement of cytokine gene expression in urinary sediment may be a useful noninvasive tool for assessing the severity of renal involvement in SLE.

Association of transforming growth factor-beta (TGF-β) T869C (Leu 10Pro) gene polymorphisms with type 2 diabetic nephropathy in Chinese.IntroductionTransforming growth factor-β (TGF-β) is known to play a pivotal role in the regulation of extracellular matrix (ECM) accumulation. Since diabetic nephropathy (DMN) is characterized by basement membrane thickening and mesangial expansion, control of ECM deposition is believed to be important in the pathogenesis of the disease. Recently, TGF-β T869C (Leu 10Pro) gene polymorphism has been identified which may be associated with circulating TGF-β levels.MethodsIn order to examine the relationship between TGF-β gene polymorphism with DMN in Chinese, we carried out a case-control study, which recruited 123 Chinese type 2 diabetic patients with an average duration of diabetes for 12 years. A total of 58 patients who developed DMN (micro- or macroalbuminuria, with or without renal impairment) were compared with 65 diabetic patients without DMN despite similar duration of disease (normoalbuminuric and creatinine

We have previously reported the experimental use of genetically engineered Escherichia coli with microencapsulation to lower nitrogenous waste. Concern has surfaced, nonetheless, about safety of genetically engineered product. The purpose of this study is to explore the alternative use of probiotics in removal of plasma urea. After repeated cycles of exposure of Lactobacillus delbrueckii in urea-rich medium under anaerobic environment, the organisms were demonstrated to lower plasma urea concentration in vitro. Suspension of Lactobacillus in uremic plasma reduced the urea nitrogen levels from 51.5 +/- 5.2 mg/dL to 44.3 +/- 3.9 mg/dL (P = 0.02) after 24 hours. With microencapsulation of Lactobacillus (inside semipermeable alginate-polylysine-alginate polymeric membrane), further lowering of urea nitrogen levels was achieved (35.4 +/- 0.8 mg/dL, P = 0.03) at 24 hours. These preliminary data show that expression of certain enzymes could be induced in Lactobacillus delbrueckii and thus capable of lowering plasma urea. Further studies and molecular analysis would be indicated to explore and refine the techniques.

We compared the Bergstrom's and Randerson's formula for PNA determination, and compared the normalization of PNA by ideal body weight (IBW) and standard body weight (SBW) as estimated by the Watson's formula. METHODS. We studied 208 Chinese PD patients. Two 24-h dialysate and urine collections were performed six months apart. Protein nitrogen appearance was determined by the Randerson's formula (PNA-Rand) and Bergstrom's formula (PNA-Berg), the latter used as the gold standard. PNA-Berg was normalized with IBW and SBW, denoted as NPNA-IBW and NPNA-Watson respectively. The change of PNA over six months, denoted as APNA-Rand and APNA-Berg, were calculated. The results were compared by the Bland and Altman's method.At zero month, the average PNA-Berg was 61.8 +/- 14.8 g/day, and the average PNA-Rand was 58.1 +/- 14.5 g/day. The value of PNA-Rand was consistently lower than the corresponding PNA-Berg. The bias of PNA-Rand was -3.7g/day. The limits of agreement were -9.2 to +1.8 g/day. When NPNA-Watson was compared to NPNA-IBW, the bias of NPNA-Watson, using NPNA-IBW as gold standard, was 0.01 g/kg/day; the limits of agreement were -0.22 to +0.23 g/kg/day. The difference between NPNA-Watson and NPNA-IBW correlated with the body mass index (r = -0.820, p0.001) and body weight (r = -0.834, r0.001). After six month, there was a significant reduction in urine protein loss. However, total protein loss was only slightly reduced (7.3 +/- 3.0 to 6.9 +/- 2.8 g/day, p = 0.029). The correlation between APNA-Berg and APNA-Rand remained excellent (r = 0.983, p0.001). The bias of APNA-Rand was +0.3 g/day; the limits of agreement were -4.7 to +5.2 g/day.Ideal body weight that is validated for specific ethnic group, rather than the Watson's formula, should be used for normalization of PNA. Although the Randerson's formula under-estimates PNA when compared to the Bergstrom's formula, it is a reliable method for serial PNA monitoring because dialysate protein loss is stable in most patients.

Background. Plasma level of plasminogen activator inhibitor (PAI)-1 is genetically determined by a polymorphism in the promoter region, involving two alleles, 4G and 5G. Plasma PAI-1 concentrations are higher in subjects homozygous for the 4G allele than other genotypes (5G/5G and 4G/5G). Such genetic variation in fibrinolytic system may affect the long-term renal transplant outcome. Methods. We determined PAI-1 4G/5G-promoter genotype polymorphism among our renal transplant recipients between 1985 and 2001. Primary event was defined as doubling of baseline serum-creatinine level. Results. Over a median period of 79 months, 130 patients with 132 kidney grafts were assessed. Baseline clinical variables were comparable among three genotype groups. There was no association between primary event and PAI-1 genotype among the entire cohort. However, among subjects with prior acute rejection episodes, those homozygous for 4G had significantly higher risk of serum creatinine doubling than the other two genotypes (relative risk 2.45, 95% confidence interval 1.19–5.04). PAI-1 genotype does not predict primary events in patients without rejection (relative risk 0.57, 95% confidence interval 0.07–4.17). Conclusions. PAI-1 4G/5G-promoter polymorphism modulates the risk of renal transplant outcomes after acute rejection(s). Recipients homozygous for PAI-1 4G allele have a higher risk of progressive renal damage after acute rejection episode(s). PAI-1 promoter polymorphisms are potentially important determinants of renal response to rejection.

Purpose Because polymicrobial peritonitis is believed to be caused by bowel perforation in peritoneal dialysis patients, surgical exploration is often recommended. However, there is recent evidence that antibiotic therapy may be a safe alternative. Methods We studied 140 consecutive episodes of dialysis-related polymicrobial peritonitis from January 1995 to June 2001. All episodes were treated primarily with intraperitoneal antibiotics. When there was no response, the Tenckhoff catheter was removed, usually after about 10 days of treatment. Laparotomy was performed only when there was clinical suspicion of surgical pathology. Results Ninety patient-episodes (64%) responded to antibiotics alone by day 10; 56 patients (40%) had complete cure with no relapse in 4 months. Nine patients (6%) died within 2 days. Laparotomy was performed in 8 patients who did not respond by day 10, but only 3 had underlying surgical disease (strangulated hernia, ischemic colitis, and colonic cancer). In a multivariate logistic regression analysis, age and the presence of fungus, anaerobes, or Pseudomonas species in the dialysis fluid were independent predictors of poor primary response; and presence of fungus was the only independent predictor of failure to cure in 4 months. Conclusion Most patients with dialysis-related polymicrobial peritonitis responded to antibiotic therapy, and surgical exploration was needed only in a few patients. A careful examination of isolated organisms may help in identifying patients who need Tenckhoff catheter removal or surgical intervention.

We identified 60 cases of tuberculous peritonitis during the past 12 years at our health care center. Most of the patients had severe underlying medical conditions, such as cirrhosis, renal failure, diabetes mellitus, and malignancy. Abnormal chest radiograph findings, ascitic fluid lymphocytosis, and biochemical findings for exudates could only identify 33%, 37%, and 53% of the cases, respectively. On the other hand, peritoneal biopsy allowed early definitive diagnosis for 9 patients. Thirty-one patients died, 26 of whom died < or =6 weeks after their initial presentation, often before the result of mycobacterial culture was available. Only 8 patients died of advanced disease after antituberculous therapy was started. Univariate analysis showed that advanced age, underlying diagnosis, and delayed initiation of therapy were associated with higher mortality rates. Standard antituberculous chemotherapy is highly effective. However, conventional microbiologic diagnostic methods are slow and not sensitive enough for establishing a diagnosis of tuberculous peritonitis.

Dialysis adequacy and transport test (DATT) is an accurate method to classify peritoneal transport type for continuous ambulatory peritoneal dialysis (CAPD) patients with a regimen of four exchanges of 2 L/d. We examined the accuracy of DATT for the characterization of peritoneal transport type in patients with a regimen of three exchanges of 2 L/d, which is the standard CAPD regimen in Hong Kong Chinese. We studied 189 adult Chinese CAPD patients with a prescription of three exchanges of 2 L/d. Patients who had a peritonitis episode within the previous 30 days were excluded. Standard peritoneal equilibration test (PET) and DATT were performed on consecutive days. Correlation coefficients between dialysate-to-plasma ratios of creatinine (D/P) obtained for the PET and the DATT was 0.698 (P0.001). Peritoneal transport type was classified according to the reported D/P creatinine reference values obtained from the PET at 4 hours. When the result was compared with the transport type classified by the DATT result using the linear regression formula derived, the Cohen kappa was 0.433 (95% confidence interval, 0.329 to 0.537), which could be regarded as a moderate level of agreement. For classification of the low transporters, the specificity of DATT was 90.1%, and sensitivity was 72.3%. For classification of the high transporters, the specificity of DATT was 96.6%, and sensitivity was 57.1%. DATT and PET had a reasonable agreement in the classification of peritoneal transport type for Chinese CAPD patients receiving a daily schedule of three exchanges of 2 L/d. Although DATT may be less accurate for CAPD patients with three daily exchanges, it remains a specific method to identify low and high transporters.

Published guidelines suggest that after an episode of severe peritonitis that requires Tenckhoff catheter removal, peritoneal dialysis can be resumed after a minimum of 3 wk. However, the feasibility of resuming peritoneal dialysis after Tenckhoff catheter removal remains unknown. One hundred patients were identified with peritonitis that did not respond to standard antibiotic therapy in a specific center. Their clinical course was reviewed; in all of them, Tenckhoff catheters were removed and reinsertion was attempted at least 4 wk later. In 51 patients, the Tenckhoff catheter was successfully reinserted and peritoneal dialysis was resumed (success group). In the other 49 patients, reinsertion failed and the patient was put on long-term hemodialysis (fail group). The patients were followed for 18.5 +/- 16.8 mo. The overall technique survival was 30.8% at 24 mo. In the success group, 11 patients were changed to long-term hemodialysis within 8 mo after their return to continuous ambulatory peritoneal dialysis. In the fail group, 18 of the 20 deaths occurred within 12 mo after conversion to long-term hemodialysis. After resuming peritoneal dialysis, there was a significant decline in net ultrafiltration volume (0.38 +/- 0.16 to 0.21 +/- 0.19 L; P = 0.03) and a trend of rise in dialysate-to-plasma ratios of creatinine at 4 h (0.664 +/- 0.095 to 0.725 +/- 0.095; P = 0.15). Forty-five patients (88.2%) required additional dialysis exchanges or hypertonic dialysate to compensate for the loss of solute clearance or ultrafiltration, although there was no significant change in dialysis adequacy or nutritional status. It was concluded that after an episode of severe peritonitis that required Tenckhoff catheter removal, only a small group of patients could return to peritoneal dialysis. An early assessment of peritoneal function after Tenckhoff catheter reinsertion may be valuable.

Metabolic complications are common with tacrolimus therapy. Recent evidence suggests that there is ethnical variability in the side-effect profile of tacrolimus. We performed an open-label study to examine the metabolic profile of tacrolimus-based immunosuppressive therapy in 10 consecutive adult Chinese patients after cadaveric renal transplantation. One case withdrew because of parvovirus infection. The mean age of the remaining nine cases was 33 +/- 2.9 yr. Mean tacrolimus whole blood trough level at 0 and 12 months were 11.4 +/- 1.8 and 7.0 +/- 0.7 ng/mL, respectively. The dosage at corresponding time points were 0.31 +/- 0.001 and 0.10 +/- 0.003 mg/kg, respectively. We found no difference in lipid profile, blood pressure control, and most importantly, fasting glucose level, before and I yr after tacrolimus therapy. Standard 75-g oral glucose tolerance test and whole blood HbAlc level were normal in all patients. Our preliminary data suggest good short-term safety among Chinese renal transplantation recipients after tacrolimus-based immunosuppressants, with a very low incidence of hyperglycemia, hypertension and dyslipidemia. The long-term implications and the underlying explanation for this ethnical difference require further investigations.

Histologic low-grade chronic renal lesions in 144 adults with primary immunoglobulin A (IgA) nephropathy were correlated with clinical parameters of disease progression over a median follow-up of 93 months. Using chronicity-based histologic grading, 50, 59, and 35 patients were glomerular grade (GG) 1a, GG1b, and GG2; 83 and 61 patients were tubulointerstitial grade (TIG) 1 and TIG2; and 25 patients had hyaline arteriolosclerosis. On follow-up, GG and TIG were predictive of disease progression by impairment of renal function, development of hypertension, and significant proteinuria (>1 g/d). Hyaline arteriolosclerosis correlated only with the development of hypertension. Histologic lesions GG1a or TIG1 predicted a significant low risk for disease progression compared with other renal lesions, regardless of the renal manifestation at the time of biopsy. Combined GG1a, TIG1, and isolated hematuria at the time of biopsy enhanced the sensitivity to determine early IgA nephropathy and to define a nonearly cohort with a higher risk of disease progression appropriate for recruitment into clinical therapeutic trials within realistic time frames. The significant risk of progression in other low-grade lesions, such as GG1b or TIG2, suggests that the point of no return in IgA nephropathy may occur much earlier than perceived and that delayed biopsy in these patients no longer may be justified.

To investigate the clinical course and outcome of peritoneal dialysis-associated peritonitis secondary to Gordonia species.We reviewed all Gordonia peritonitis episodes occurring in a single dialysis unit from 1994 to 2013.During the study period, four episodes of Gordonia peritonitis were recorded. All were male patients. One patient responded to vancomycin therapy. One patient had refractory peritonitis despite vancomycin, but responded to imipenem and amikacin combination therapy. One patient had relapsing peritonitis and required catheter removal. The fourth patient had an elective Tenckhoff catheter exchange. No patient died of peritonitis. Causative organism was not fully identified until 7 to 18 days of peritonitis.Gordonia species is increasingly recognized to cause serious infections. In patients undergoing peritoneal dialysis, Gordonia peritonitis should be considered in case of refractory Gram-positive bacilli peritonitis, especially when the exact organism could not be identified one week after the onset of peritonitis. A close liaison with a microbiologist is needed for a timely diagnosis.

Background. The clinical benefits of using icodextrin during acute peritonitis in peritoneal dialysis are uncertain. On the premise that high glucose concentration might jeopardize the peritoneal defense during peritonitis, icodextrin administration during acute peritonitis could have the potential to improve the peritonitis outcome whilst improving ultrafiltration. Methods. We conducted a single-center, open-label, randomized controlled trial in which 53 adult continuous ambulatory peritoneal dialysis patients underwent randomization to receive either icodextrin or original glucose-based dialysis solution. The primary outcome measure was the peritoneal dialyzate white cell count on Day 3. Secondary outcome measures comprised the need of additional hypertonic exchanges, fluid control as denoted by changes in body weight, and the clinical outcome of peritonitis including 30-day and 120-day all-cause mortality. Results. Between icodextrin and control treatment groups, there were no statistically significant differences in the peritoneal dialyzate white cell count on day (1829 versus 987/mm 3 , P = 0.13). There was neither improvement in primary cure rate (31.8 versus 32.3%, P = 1.00), nor was there any change in 120-day mortality after icodextrin use (13.6 versus 12.9%, P = 1.00). However, requirement of hypertonic dialysis exchange was much more frequent in the control group than in those randomized to icodextrin (35.5 versus 0%, P= 0.001). Body weight did not change significantly in the icodextrin group, but body weight in the control group increased from 63.3±14.5 kg at baseline to 64.2±14.2 kg at Day 5 (P= 0.0002) and 65.2± 14.1 kg at Day 10 (P< 0.0001). Conclusions. As compared with glucose-based peritoneal dialysis solution, use of icodextrin achieved better ultrafiltration and fluid control during acute peritonitis complicating continuous ambulatory peritoneal dialysis, although we found no evidence of a worthwhile clinical benefit on peritonitis resolution. (ClinicalTrial.gov number, NCT0104446 [ClinicalTrial.gov].).

Minimal change nephropathy is a common cause of primary nephrotic syndrome in adults. However, there are few studies of its clinical course, response to treatment, and long-term outcome.Retrospective cohort study.340 consecutive adult patients with nephrotic syndrome and biopsy-proven minimal change nephropathy treated in a university hospital from 1984 until 2004.Treatment response groups: primary steroid resistance, frequent relapse (≥4 relapses within 1 year), infrequent relapse (≥1 relapse but not frequent relapse), and no relapse (reference group); disease pattern.Medical problems after diagnosis; patient survival; renal survival.Median time to remission was 10 (IQR, 8-12) weeks; 179 (52.6%) had no relapse, 42 (12.4%) had infrequent relapses, 86 (25.3%) were frequent relapsers or steroid dependent, and 33 (9.7%) had primary steroid resistance. After a median follow-up of 174.7 (IQR, 119.7-235.0) months, 32 patients developed end-stage renal disease and 62 died (25 after progression to end-stage renal disease). Cox regression analysis showed that age and treatment response groups were the independent predictors of patient survival. Compared to the no-relapse group, the infrequent-relapse group had significantly better patient survival (adjusted HR, 0.19; 95% CI, 0.08-0.44; P0.001), whereas the primary-steroid-resistance group had significantly worse patient survival (adjusted HR, 5.87; 95% CI, 1.83-18.85; P0.001). Renal survival was excellent except in the primary-steroid-resistance group.Retrospective study.A substantial proportion of adult patients with minimal change nephropathy continue to have disease flares more than 10 years after the initial presentation, and medical problems after diagnosis are common.

In the general population, metabolic syndrome (MES) is associated with cardiovascular risk. However, the definition of MES and its prognostic implication among patients undergoing peritoneal dialysis (PD) remain controversial.We studied 329 prevalent PD patients from April 2008 to April 2011 and compared four sets of diagnostic criteria: the original World Health Organization (WHO) criteria, the International Diabetes Federation (IDF) criteria, the original National Cholesterol Education Program (NCEP) criteria, and the modified NCEP criteria. Nutritional status, body composition, and arterial pulse-wave velocity were measured. Patients were followed for 31.7 ± 15.5 months.Among the 329 patients, 175 (53.2%) fulfilled the WHO criteria, 177 (53.8%) the IDF criteria, 199 (60.5%) the original NCEP criteria, and 218 (66.3%) the modified NCEP criteria. The agreement among the four sets of criteria was fair to moderate (Cohen κ=0.35-0.58). Patients with MES defined by all four criteria had higher adipose tissue mass than the others, although the difference in adipose tissue mass was most pronounced with the IDF criteria (MES versus no MES, 18.2 ± 7.9 versus 10.7 ± 5.9 kg; P0.001). Patients with MES, as defined by the IDF criteria, were hospitalized longer than those without MES (3.82 [interquartile range, 0.00-12.61] versus 1.07 [interquartile range, 0.00-6.43]) days per year of follow-up; P=0.01). Overall survival, cardiovascular survival, or technique survival did not differ between patients with and without MES, irrespective of the diagnostic criteria after adjustment for diabetic status.In patients undergoing PD, overall survival, cardiovascular survival, and technique survival did not differ between patients with and without MES, irrespective of diabetic status and diagnostic criteria. Further studies are needed to establish a new definition or clinical scoring system for risk stratification of PD patients.

Aging kidneys undergo structural and functional changes that resemble chronic kidney disease. The management of older adults with chronic kidney disease is complicated by the presence of many other comorbid conditions, frailty and sometimes conflicting treatment priorities that arise from other medical conditions. For those elderly patients with more coexisting diseases and functional impairment, an individualised patient-centred care approach is more appropriate. The benefits of recommended drug intervention and dialysis therapy can be highly variable in older adults and definitely differ from those younger patients.

Countries in Asia vary significantly in culture and socioeconomic status. Dialysis costs and reimbursement structures are significant factors in decisions about the rates and modalities of renal replacement therapy. From our survey of Asian nephrologists conducted in 2001, a number of observations can be made. In many developing countries, the annual cost of continuous ambulatory peritoneal dialysis (CAPD) is greater than the per-capita gross national income (GNI). The median cost of a 2-L bag of peritoneal dialysis (PD) fluid is around US$5. The absolute cost of PD fluid among countries with significant differences in per-capita GNI actually varies very little. Thus, most renal failure patients can be expected to have problems accessing PD therapy in developing countries in Asia. In countries with unequal reimbursement policies for PD versus hemodialysis, a lack of incentive to prescribe PD also exists. Automated PD is nearly non existent in many developing countries in Asia. Some possible ways to reduce the cost barriers to PD in those countries include • individual governments providing more public funding for treating dialysis patients; • dialysate-producing companies reducing the cost of their products; • physicians using appropriately smaller exchange volumes (3 x 2 L) in some Asian patients with smaller body sizes and with residual renal function; and • reducing the complication rate for PD (for example, peritonitis) thereby reducing the costs required for treatment and hospitalization.

Previous studies have suggested that the cross-sectional relationship observed between total solute clearance (Kt/V) and dietary protein intake (DPI) in patients undergoing dialysis is possibly mathematical in origin. A cross-sectional study on 242 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) was performed to determine the differential effects of dialysis adequacy and residual renal function (RRF) on actual dietary intake. All patients underwent a 7-d food frequency questionnaire to quantify daily dietary protein, calorie (DCI), and other nutrient intake, subjective global assessment (SGA), and collection of 24-h dialysate and urine for total (PD and renal) Kt/V and RRF. Patients were categorized into three groups: I ( n = 94), total Kt/V ≥1.7 and GFR >0.5 ml/min per 1.73 m 2 ; II ( n = 58), total Kt/V ≥1.7 but GFR 2 ; and III ( n = 90), total Kt/V versus 62% versus 42% of group I versus II versus III patients were well nourished according to SGA ( P = 0.004). DPI (1.23 [0.47] versus 1.12 [0.49] versus 0.99 [0.40] g/kg per d; P = 0.002) and DCI (27.3 [8.9] versus 23.8 [8.6] versus 23.0 [8.2] kcal/kg per d; P = 0.002) showed significant decline across the three groups. Intake of other nutrients, including carbohydrate, fat, fatty acids, and cholesterol was higher for group I compared with groups II and III. Adjusting for age, gender, weight, and diabetes, every 1 ml/min per 1.73 m 2 increase in GFR was associated with a 0.838-fold increase in DCI (95% confidence interval to interval, 0.279 to 1.397; P = 0.003) and a 0.041-fold increase in DPI (95% confidence interval, 0.009 to 0.072; P = 0.012), whereas every 0.25-unit increase in total (PD and renal) Kt/V was associated with a 0.570-fold increase in DCI (95% confidence interval, 0.049 to 1.092; P = 0.032) and a 0.052-fold increase in DPI (95% confidence interval, 0.023 to 0.081; P = 0.001). Greater small-solute clearances are associated with better dietary intake and better nutrition. The study confirmed significant and independent effect of RRF, but not PD solute clearance, on actual DPI, DCI, and other nutrient intake in patients on CAPD.

The renin-angiotensin system is important in the control of hemodynamic status and pathogenesis of macrovascular disease, which is a major cause of morbidity and mortality in patients with type 2 diabetes with nephropathy. Serum angiotensin-converting enzyme (ACE) and angiotensinogen (Atg) levels are related to their respective gene polymorphisms. Seventy patients with type 2 diabetes with overt nephropathy (serum creatinine >/= 1.5 mg/dL) were studied. Serum ACE activity was measured by the spectrophotometric method. ACE deletion/insertion (D/I) and Atg M235T genotypes were determined by polymerase chain reaction. Patients with and without macroangiopathy were compared. Those with macroangiopathy had increased ACE activity (median, 60.9 U/L; range, 37.9 to 100 U/L versus without macroangiopathy, 47.9 U/L; range, 11.2 to 84.5 U/L; P = 0.01) and prevalence of ACE DD/DI genotypes (DD/DI:II: with macroangiopathy, 61%:39% versus without macroangiopathy, 34%:66%; P = 0.03). Multivariate analysis using age; sex; duration of diabetes; glycemic, blood pressure, and lipid level control; serum creatinine level; and presence of the ACE D allele showed that presence of the D allele (P = 0.03; odds ratio, 1.8; confidence interval, 1.1 to 3.1) and serum creatinine level (P = 0.0007) were independent risk factors for macroangiopathy. Association of the D allele became insignificant after serum ACE activity was included in the analysis in which only serum ACE activity (P = 0.004) and serum creatinine level (P = 0.01) were independent risk factors. Neither Atg M235T nor its synergistic effect with the ACE D allele showed an association with macroangiopathy. In conclusion, the ACE D allele is associated with macroangiopathy in Chinese patients with type 2 diabetes with nephropathy. The association is dependent on its effect on serum ACE activity, which is an independent risk factor for the development of macroangiopathy.