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Background. Mitochondrial dysfunction plays an important role in the pathogenesis and progression of diabetic nephropathy (DN). We study the relation between urinary and intra-renal mitochondrial deoxyribonucleic acid (mtDNA) levels and renal dysfunction in DN. Methods. We recruited 92 patients with biopsy-proven DN. Urinary sediment, urinary supernatant and intra-renal mtDNA levels were measured and compared with baseline renal biopsy, kidney scarring and renal function decline in the subsequent 24 months. Results. mtDNA could be detected in all urine supernatant, urine sediment and renal biopsy specimens. There was a modest but statistically significant inverse correlation between urinary supernatant and intra-renal mtDNA levels (r =-0.453, P = 0.012). Urinary supernatant mtDNA level had modest but statistically significant correlations, inversely with estimated glomerular filtration rate (r =-0.214, P = 0.04), and positively with interstitial fibrosis (r = 0.300, P = 0.005). Intra-renal mtDNA had significant inverse correlation with interstitial fibrosis (r =-0.537, P = 0.003). However, there was no significant relation between renal function decline and urinary supernatant, urinary sediment or intra-renal mtDNA levels. Conclusions. mtDNA is readily detectable in urinary supernatant and kidney tissue, and their levels correlate with renal function and scarring in DN. Further studies are needed to determine the accuracy of urinary supernatant mtDNA level as a prognostic indicator of DN, as well as its role in other kidney diseases. [ABSTRACT FROM AUTHOR]

Background. The response to recombinant hepatitis B vaccine remains suboptimal among the dialysis population. [ABSTRACT FROM PUBLISHER]

Background. Shortening behaviour during peritoneal dialysis training can be easily measured, and likened to the skipping behaviour in haemodialysis subjects, although its effect on peritoneal dialysis outcomes is now well understood. We studied the clinical impact of failing to adhere to a peritoneal dialysis training programme among incident dialysis patients.Methods. This study included 159 consecutive inception peritoneal dialysis patients in a single centre from September 1999 through November 2002. We evaluated the effects of behavioural compliance quantified by the per cent time arriving late for scheduled peritoneal dialysis training. The patients were categorized by whether they arrived late in >20% of their peritoneal dialysis training sessions.Results. Of the 159 incident peritoneal dialysis patients (mean age 57 ± 13 years) who attended peritoneal dialysis training, 70 subjects (44%) arrived late in >20% of the sessions. They were younger by 5 years than patients who arrived late ≤20%. Mean peritonitis-free time for subjects who arrived late for training in >20% the of sessions was 30.9 months, as compared with 41.8 months in subjects with ≤20% late attendance behaviour (log rank test, P = 0.038). Multivariable Cox proportional hazards analysis showed that late attendance behaviour and baseline serum albumin were the only independent risk factors for the time to a first peritonitis after adjustment for diabetes mellitus and relevant coexisting medical factors. Late arrival in >20% of the peritoneal dialysis training sessions was associated with >50% increased likelihood of subsequent peritonitis, with an adjusted risk ratio of 1.56 (95% confidence interval, 1.02–2.39; P = 0.04).Conclusion. These findings show that the behavioural measure of late attendance for peritoneal dialysis training has a crucial role in predicting peritonitis. It may therefore represent a practical strategy for identifying poor adherence or predicting medical outcomes. [ABSTRACT FROM AUTHOR]

Background. Chronic utilization of a bio-incompatible peritoneal dialysis (PD) solution with acidic pH and a high content of glucose degradation product (GDP) has been implicated as a contributing cause of peritoneal failure. We compared a newly formulated solution of neutral pH and low levels of GDP to a standard PD solution.Methods. Fifty new PD patients were randomized to a conventional lactate-buffered fluid (control) and a pH neutral, lactate-buffered, low GDP solution (balance). Patients were followed for 12 months. Serum samples were assayed for C-reactive protein (CRP). PD effluent was collected and assayed for cancer antigen-125 (CA125) and hyaluronan (HA). Clinical end points were the residual renal function and dialysis adequacy indices.Results. After 52 weeks of treatment, PD fluid CA125 rose from 2.45 ± 0.96 to 14.30 ± 2.17 U/ml (P < 0.001), and HA declined from 2.26 ± 0.60 to 1.45 ± 0.32 μg/ml (P = 0.07) in the balance group. The balance group had a higher PD fluid CA-125 (14.30 ± 2.17 vs 7.36 ± 2.23 U/ml, P = 0.007), lower HA (1.45 ± 0.32 vs 2.55 ± 0.32 μg/ml, P = 0.007), and lower serum CRP level (1.77 ± 0.42 vs 7.73 ± 2.42 mg/l, P = 0.026) than the control group at 52 weeks. There was no difference in dialysis adequacy indices, ultrafiltration volume, urine output, residual renal function, peritonitis rate or need of hospitalization in 1 year.Conclusion. As compared to conventional PD solution, the use of balance, a neutral pH, low GDP solution resulted in a superior profile of PDE mesothelial cell marker and a lower degree of systemic inflammation, and the difference was maintained for 1 year. It remains to be determined whether these effects could result in better long-term clinical outcome. [ABSTRACT FROM AUTHOR]

Background. Previous studies have shown that messenger RNA (mRNA) expression of target genes is increased in the urinary sediment of patients with active lupus. We study the effect of immunosuppressive therapy on the urinary gene expression profile in patients with active lupus nephritis.Method. We recruited nine patients with active systemic lupus erythematosus (SLE) and renal disease, and required corticosteroid, with or without cytotoxic treatment. They were followed for 6 months, urine samples were collected at 0, 4, 12 and 24 weeks and gene expression profile was determined by polymerase chain reactions. The pattern of gene expression was compared to clinical parameters of therapeutic response.Results. Amongst the target genes studied, there was a progressive decline in the urinary expression of T-bet, interleukin (IL)-10, transforming growth factor-beta (TGF-β), monocyte chemoattractant protein-1 (MCP-1), and interferon-gamma (IFN-γ) after immunosuppressive treatment, although the change of IFN-γ was not statistically significant. The time course of their urinary expression was parallel to the systemic activity as reflected by the systemic lupus erythematosus disease activity index (SLEDAI). Throughout the study period, the SLEDAI score correlated significantly with the expressions of IFN-γ (r = 0.43, P = 0.009), T-bet (r = 0.40, P = 0.016), TGF-β (r = 0.51, P = 0.002) and MCP-1 (r = 0.38, P = 0.022). The anti-double strand(anti-ds)DNA antibody titer correlated significantly with the expressions of IFN-γ (r = 0.45, P = 0.009), T-bet (r = 0.37, P = 0.034), IL-10 (r = 0.59, P<0.001), TGF-β (r = 0.44, P = 0.010) and MCP-1 (r = 0.49, P = 0.004). On the other hand, the expression level of IL-2, IL-4, IL-12, IL-18 and GATA-3 remained static throughout the study period.Conclusions. The mRNA expression of T-bet, IL-10, TGF-β, MCP-1, and probably IFN-γ in the urinary sediment of patients with active lupus nephritis improves with successful immunosuppressive therapy, and the change in gene expression profile is in phase with the clinical disease activity. Measurement of urinary mRNA expression of target genes may be a potential non-invasive tool for the monitoring of lupus disease activity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background. Clinical outcomes among patients on peritoneal dialysis (PD) might not be linked to medical factors alone. We studied the clinical impact of various social factors among patients on PD.Methods. In a cohort of 102 consecutive patients who started PD in a single centre between 2003 and 2004, we evaluated the effects of social factors on the development of peritonitis and risk of hospitalization after initiation of PD.Results. Of 102 incident PD patients, 35 subjects (34.3%) were referred to nephrologists more than 3 months before dialysis initiation. During 85.7 patient-years of observation (median follow-up, 10.7 months), four subjects died and six underwent kidney transplantation. Patients receiving social security assistance and those younger than 40 years fared worse than others in terms of their risk of peritonitis. Mean peritonitis-free time for subjects who were on social security assistance was 2.7 months, and for those who were not, 16.4 months (P = 0.045). In the Cox proportional hazards analysis, need for social security assistance and illiteracy were the only statistically significant factors associated with the time to a first peritonitis, after adjustment for social characteristics and relevant coexisting medical factors. Dependence on social security assistance prior to PD was associated with a >2-fold increased likelihood of peritonitis, with an adjusted risk ratio of 2.69 (95% confidence interval, 1.10 to 6.54; P = 0.029). The total number of hospitalization days was similar between those who received social security assistance and those who did not: 17.4±14.6 days (range, 4–50 days) vs 17.9±14.0 days (range, 0–60 days) (P = 0.89).Conclusions. Our results confirm that socioeconomic status is closely associated with the rate of peritonitis among PD patients. The long-term reliability of these social predictors remains to be validated. [ABSTRACT FROM AUTHOR]

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- (TGF-), monocyte chemotactic protein-1 (MCP-1) and collagen IV between disease groups and controls. Urinary TGF- mRNA expression correlated significantly with estimated glomerular filtration rate (r?= -0.412, P = 0.029) and the degree of tubulointerstitial scarring (r = 0.418, P = 0.024). Urinary MCP-1 expression correlated with the degree of glomerulosclerosis (r = 0.450, P = 0.014), but not tubulointerstitial scarring. Urinary MCP-1 expression correlated with its corresponding level by enzyme-linked immunosorbent assay (ELISA) (r = 0.650, P<0.001), but TGF- expression did not correlate with its ELISA level. Urinary TGF- gene expression correlated with its intra-renal expression in glomeruli (r = 0.701, P<0.001) and tubulointerstitium (r = 0.573, P = 0.001) by immunohistochemistry, while urinary MCP-1 gene expression correlated with its staining in glomeruli (r = 0.576, P = 0.001) but not tubulointerstitium. After 12 months, there was a significant inverse correlation between the rate of renal function decline and urinary expression of connective tissue growth factor (r = -0.471, P = 0.010) and collagen I (r = -0.399, P = 0.032), but not TGF- or MCP-1.Conclusions. Amongst the target genes examined, the mRNA expression of TGF- in urinary sediment correlated with renal function, the degree of histological damage and intra-renal level in patients with chronic kidney diseases. Measurement of TGF- mRNA expression in urine may be a useful non-invasive tool for assessing the severity of renal damage in patients with chronic kidney diseases. [ABSTRACT FROM AUTHOR]

In this article, the authors report on the importance of peritoneal dialysis catheter insertion by nephrologists. The main aim of the practice is to provide timely and effective catheter insertion without unduly long waiting times or delay. The next important concern is the feasibility and safety of peritoneal access creation by nephrologists. A table is also presented in support of the article.

Background. After prolonged peritoneal dialysis (PD) and exposure to a non-physiological dialysis solution, peritoneal mesothelial cells undergo the epithelial-to-mesenchymal transition. In other biological systems, bone morphogenic protein-7 (BMP-7) is a key factor that controls this process. However, the role of BMP-7 in peritoneal physiology has not been studied. Methods. We studied the peritoneal transport characteristics of 50 consecutive new PD patients at 4 and 52 weeks after PD. Peritoneal permeability will be determined by the standard peritoneal equilibration test (PET). BMP-7 in PD effluent (PDE) at mRNA and protein level at 4 weeks was quantified. Results. At 4 weeks, the mRNA expression of BMP-7 in PDE significantly correlated with peritoneal transport characteristics, including the dialysate-to-plasma creatinine ratio at 4 h (D/P4) (r = 0.422, P = 0.015) and mass transfer area coefficient (MTAC) of creatinine (r = 0.457, P = 0.008). The PDE BMP-7 level by ELISA also had marginal correlation with D/P4 (r = 0.287, P = 0.072) and MTAC creatinine (r = 0.287, P = 0.073), although the result did not reach statistical significance. For the subgroup of patients who remained free of peritonitis, the PDE BMP-7 level by ELISA had significant correlation with the change in D/P4 (r = 0.441, P = 0.017) and MTAC creatinine in 52 weeks (r = 0.415, P = 0.025). The PDE BMP-7 level remained independently associated with the change in peritoneal transport adjusting for age, sex, serum C-reactive protein and PDE transforming growth factor-beta level. In patients who had peritonitis during the study period, the PDE BMP-7 level did not affect the change in peritoneal transport. Conclusion. We find that the peritoneal BMP-7 level correlates with peritoneal transport characteristics, and a high PDE BMP-7 level is associated with a gradual increase in peritoneal transport parameters with time. It remains unclear, however, whether this effect is beneficial, and the therapeutic role of exogenous BMP-7 on peritoneal transport requires a further study. [ABSTRACT FROM AUTHOR]

Background. Cytokine gene polymorphisms have been associated with poor outcomes after renal transplantation such as chronic allograft nephropathy (CAN), graft rejection (GR) and graft failure (GF), but the effects of these polymorphisms are still controversial. We therefore conducted a systematic review, with individual patient data (IPD) where possible, to determine the association between cytokine polymorphisms (TGF-β1, TNF-α and IL-10) and outcomes after renal transplantation. Methods. Five investigators were willing to participate and provided IPD. The outcomes of interest were GF, GR and CAN. Subjects with at least one of these were classified as having poor outcomes. Heterogeneity of gene effects was assessed. Multiple logistic regression was applied to assess gene effects, adjusting for clinical variables such as HLA matching and age. Results. One-thousand and eighty-seven subjects were included in the IPD meta-analysis. Pooled results showed no evidence of heterogeneity and indicated that the strongest variables determining poor outcomes are HLA mismatching (OR = 1.6–1.8 for ≥3 HLA-A, -B, -DR mismatches compared with those with <3 mismatches) and age (OR = 1.2–1.4 for age 45 years or more). Incremental information on risk of a poor outcome is provided by the TGF-β1c10 polymorphism (OR = 1.5, P = 0.034, 95% CI: 1.0–2.2 for TC genotype compared to TT genotype). Haplotypes of TGF-β1 at c10 and c25 were inferred and the C-C haplotype was a marker of a poor outcome (OR = 1.3, P = 0.177, 95% CI: 1.0–2.3). Three polymorphisms of the IL-10 gene at −1082, −819, −592 are in strong linkage disequilibrium with each other (correlation coefficients: 0.6–1) and inferred haplotypes between these three loci show some association, with ACC increasing the risk of poor events com- pared to GCC (OR = 1.3, P = 0.044, 95% CI: 0.9–1.6). Conclusion. Pooled results to date suggest possible association between both the TGF-β1 c10 polymorphism and a 3-SNP-haplotype of IL-10 and poor outcomes in renal transplantation, but this needs to be confirmed in larger studies. [ABSTRACT FROM AUTHOR]

Background. Diabetic patients often have reduced insulin requirements when they progress to renal failure. Since peritoneal dialysis (PD) solution contains glucose, the insulin requirement of these patients often increases after commenced on PD. However, the change in insulin requirement has not been studied systematically. Methods. We study 60 consecutive patients (32 male) with diabetic nephropathy newly started on PD. Their insulin requirement before and 6 months after initiation of dialysis is compared. Clinical factors affecting insulin requirement are explored. Results. All patients received a standard 6 l/day dialysis exchange. The mean age was 60.3 ± 8.9 years. Twelve patients did not require insulin before PD; four of them were started on insulin 6 months after dialysis. The average dosages of insulin 6 months before and after PD were 0.27 ± 0.28 and 0.37 ± 0.29 unit/kg/day, respectively (paired t-test, P r = −0.307, P = 0.017) and haemoglobin level (r = 0.284, P = 0.028), but not with body mass index (BMI). The change in insulin dosage correlates with the number of 2.5% dialysis cycle required per day (r = 0.433, P = 0.001), but not with peritoneal transport status or BMI. In patients who did not receive hypertonic exchange, the dosage of insulin increased by 1.5 ± 11.1 unit/day. Each extra 2.5% 2 l exchange results in a 7.5 unit/day (95%CI 3.2–11.8, P = 0.001) increase in insulin requirement. Conclusion. Diabetic patients have a minimal increase in insulin requirement after initiation of PD per se, but the dosage of insulin increased markedly after exposure to hypertonic glucose solution. Our result provides a basis for the dosage adjustment of insulin in diabetic patients newly commenced on PD. [ABSTRACT FROM AUTHOR]