Genotoxicity evaluation in chronic renal patients undergoing hemodialysis and peritoneal dialysis, using the micronucleus test

Patients with chronic renal disease have an increased incidence of cancer. It is well known that long periods of hemodialysis treatment are linked to DNA damage due to oxidative stress. This genotoxic effect may cause the loss of chromosome fragments, or even entire chromosomes, which form micronuclei after cell division, and can be detected by the micronucleus test. In the present case-control study, we evaluated the genotoxic effect of hemodialysis treatment in 20 patients undergoing hemodialysis, and 20 subjected to peritoneal dialysis, matched for gender and age with 40 controls. Genetic damage was assessed by examining the frequency of micronuclei in 2000 exfoliated buccal cells per individual. Our results revealed that patients undergoing hemodialysis treatment have a significantly higher frequency of micronucleated cells (MNC; 5.60 +/- 5.31) compared to control subjects (1.50 +/- 2.01, p < 0.01). Interestingly, the same was not observed for the peritoneal dialysis patients who showed no significant differences in MNC (2.85 +/- 2.96) frequency compared to control individuals (3.25 +/- 3.85). In addition, we evaluated the possible association between creatine levels, smoking, alcohol intake, age, duration of treatment, and incomes of the individuals (separately analyzed according to their gender) and the frequency of micronuclei. The results reported here indicate that the duration of treatment is the only factor associated with increased MNC frequency among hemodialysis patients (Spearman coefficient of 0.414, p = 0.01). The number of MNC found in individuals with six years or less of treatment was significantly lower (2.91 +/- 2.74) compared to patients with seven or more years of treatment (8.89 +/- 5.96, p < 0.05). Overall, peritoneal dialysis may be a safer choice of treatment, but further studies need to be performed to investigate the risks and benefits of both treatments.     

Arteriovenous hemofiltration as an adjuvant therapy in peritoneal dialysis and hemodialysis in a patient with terminal renal failure]

In the uraemic patient regularly treated with peritoneal dialyses occurring peritonitis caused a decrease of ultrafiltration and transfer abilities of the peritoneum. Other symptoms dangerous for life also appeared: uraemic pericarditis and significant overhydration. Peritoneal dialyses lost its effectiveness. Therefore they were supplemented by arterio-venous haemofiltration. Haemofiltration was also conducted at the beginning of haemodialysis treatment, which was initially unregular. Application of haemofiltration enabled the patient to survive during the time of waiting for regular haemodialyses. It may be useful to consider such a treatment, when the adequacy of proper renal substitutive management of uraemia by other methods is impossible to obtain.     

Predictors and prevalence of latent tuberculosis infection in patients receiving long-term hemodialysis and peritoneal dialysis

Background

Tuberculosis is a common infectious disease in long-term dialysis patients. The prevalence of latent tuberculosis infection (LTBI) in this population is unclear, particularly in those receiving peritoneal dialysis (PD). This study investigated the prevalence of LTBI in patients receiving either hemodialysis (HD) or PD to determine predictors of LTBI and indeterminate results of interferon-gamma release assay.

Methods

Patients receiving long-term (≥3 months) HD or PD from March 2011 to February 2012 in two medical centers were prospectively enrolled. QuantiFERON-Gold in tube (QFT) test was used to determine the status of LTBI after excluding active tuberculosis. The LTBI prevalence was determined in patients receiving different dialysis modes to obtain predictors of LTBI and QFT-indeterminate results.

Results

Of 427 patients enrolled (124 PD and 303 HD), 91 (21.3%) were QFT-positive, 316 (74.0%) QFT-negative, and 20 (4.7%) QFT-indeterminate. The prevalence of LTBI was similar in the PD and HD groups. Independent predictors of LTBI were old age (OR: 1.034 [1.013–1.056] per year increment), TB history (OR: 6.467 [1.985–21.066]), and current smoker (OR: 2.675 [1.061–6.747]). Factors associated with indeterminate QFT results were HD (OR: 10.535 [1.336–83.093]), dialysis duration (OR: 1.113 [1.015–1.221] per year increment), anemia (OR: 8.760 [1.014–75.651]), and serum albumin level (OR: 0.244 [0.086–0.693] per 1 g/dL increment).

Conclusion

More than one-fifth of dialysis patients have LTBI. The LTBI prevalence is similar in PD and HD patients but is higher in the elderly, current smokers, and those with prior TB history. Such patients require closer follow-up. Repeated or alternative test may be required for malnutrition patients who received long length of HD.     

Effect of continuous ambulatory peritoneal dialysis on a British renal unit.

Experience in the use of continuous ambulatory peritoneal dialysis (CAPD) for the treatment of end stage renal failure in Nottingham was reviewed. During six years 150 patients aged from 11 to 73 received this type of treatment. At three years patient actuarial survival was 69% and CAPD technique survival was 41%. Although CAPD was satisfactory as a first treatment for many patients, its long term use was possible in only a few. Actuarial survival of patients who changed to haemodialysis was 64% at one year after the change, suggesting that unsuccessful CAPD increased the risk of death. Hospital haemodialysis was the only suitable form of treatment for most patients in whom CAPD had been abandoned. British renal units have adopted CAPD to a much greater extent than those in Europe, but care in the selection of patients is necessary to reduce mortality, and many patients may eventually need hospital haemodialysis. Greater numbers of hospital haemodialysis places will probably have to be made available to meet this extra demand.     

Cytology of peritoneal fluid from patients on continuous ambulatory peritoneal dialysis

Peritoneal fluids from 41 patients on continuous ambulatory peritoneal dialysis (CAPD) were examined. The patients were divided into a short-term group (18 patients with CAPD up to one year) and a long-term group (23 patients with CAPD for one to seven years). Peritoneal fluids from a control group, consisting of ten nondialysis patients with ascites, were also examined. The cellular background of the peritoneal fluids and, in particular, the morphology of the mesothelial cells were studied. The following were found to be significantly increased in the CAPD groups: background lymphocytes, mesothelial exfoliation in three-dimensional clusters, mesothelial nuclear size and the number of mesothelial nucleoli. All of these features increased slightly with an increased duration of the dialysis. These findings emphasize that peritoneal dialysis of any duration can induce significantly atypical changes in mesothelial cells.     

Proteomic analysis in peritoneal dialysis patients with different peritoneal transport characteristics

Peritoneal membranes can be categorized as high, high average, low average, and low transporters, based on the removal or transport rate of solutes. In this study, we used proteomic analysis to determine the differences in proteins removed by different types of peritoneal membranes. Peritoneal transport characteristics in patients who received peritoneal dialysis therapy were assessed by a peritoneal equilibration test. Two-dimensional differential gel electrophoresis technology followed by quantitative analysis was performed to study the variation in protein expression from peritoneal dialysis effluents (PDE) among different groups. Proteins were identified by MALDI-TOF-MS/MS analyses. Further validation in PDE or serum was performed utilizing ELISA analysis. Proteomics analysis revealed ten protein spots with significant differences in intensity levels among different groups, including vitamin D-binding protein, complement C3, apolipoprotein-A1, complement factor C4A, haptoglobin, alpha-1 antitrypsin, immunoglobulin kappa light chain, alpha-2-microglobulin, retinol-binding protein 4 and transthyretin. The levels of vitamin D-binding protein, complement C3, and apolipoprotein-A1 in PDE derived from different groups were greatly varied (P < 0.05). However, no significant difference was found in the serum levels of these proteins among different groups (P > 0.05 for all groups). This study provides a novel overview of the differences in PDE proteomes of four types of peritoneal membranes. Vitamin D-binding protein, complement C3, and apolipoprotein-A1 showed enhanced expression in PDE of patients with high transporter.     

Impact of continuous ambulatory peritoneal dialysis on treatment of renal failure in patients aged over 60.

Thirty eight patients aged over 60 with end stage renal disease were treated by continuous ambulatory peritoneal dialysis for up to three years. Most of these patients, because of their age or coexisting diseases, had been considered to be unsuitable for haemodialysis by the criteria used before the advent of continuous ambulatory peritoneal dialysis in 1980. Actuarial patient survival at one and two years was 72% and 61% respectively, and only two patients were permanently transferred to haemodialysis. Twenty one of the 23 survivors were fully rehabilitated, the remaining two being partially disabled but living at home. Continuous ambulatory peritoneal dialysis permits more liberal selection of patients with end stage renal disease for renal replacement treatment with excellent survival and rehabilitation and without overburdening scarce hospital haemodialysis facilities.     

Continuous ambulatory peritoneal dialysis: experience with 22 unselected patients with renal failure.

The present study describes our experience with CAPD in an unselected group of patients presenting with endstage renal failure. Twenty-three consecutive patients were offered CAPD, in-center, and home hemodialysis. Twenty-two patients selected CAPD, including 14 patients more than 60 years of age, four patients with diabetes, and one with multiple myeloma. CAPD training was performed in an out-of-hospital office facility. One patient returned to hemodialysis following the development of resistant Pseudomonas peritonitis, two patients died of a myocardial infarction, and one patient died with a GI bleed. The other 18 patients are doing well. Assessment of 17 patients maintained on therapy for four months or more revealed that the patients are less depressed, less organic, and have fewer physical symptoms than previously reported for a comparable group of patients maintained on hemodialysis for a similar period of time. In conclusion, CAPD can be successfully employed, at least for the initial months of therapy, to treat the vast majority of patients with endstage renal disease. CAPD training and follow-up care can be provided in an out-of-hospital office facility.     

Activity of some lysosomal enzymes in peritoneal macrophages of patients with end-stage renal failure treated by intermittent peritoneal dialysis.

Acid phosphatase, beta-D-Glucuronidase and N-acetyl-beta-D-glucosaminidase were assessed cytochemically in peritoneal macrophages obtained from 50 patients with end-stage renal failure treated by intermittent peritoneal dialysis and from 30 control subjects with normal renal function. A statistically significant increase in beta-D-glucuronidase activity accompanied by a decrease in acid phosphatase activity were observed in peritoneal macrophages of dialysed patients, as compared with the control group. In patients with dialysis-associated peritonitis, the activity of N-acetyl-beta-D-glucosaminidase was significantly higher than that observed in the same patients during the complication-free period of the treatment.     

Effect of glucose concentration on peritoneal inflammatory cytokines in continuous ambulatory peritoneal dialysis patients

OBJECTIVE: It is known that glucose concentrations of peritoneal dialysis solutions are detrimental to the peritoneal membrane. In order to determine the effect of glucose concentration on cytokine levels of peritoneal fluid of continuous ambulatory peritoneal dialysis (CAPD) patients, a cross-sectional study was performed. METHODS: Nine non-diabetic CAPD patients participated in two 8-h dwell sessions of overnight exchanges in consecutive days, with 1.36% and 3.86% glucose containing peritoneal dialysis solutions (Baxter-Eczacibas). Peritoneal dialysis fluid tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 levels were measured. RESULTS: TNF-alpha levels after 1.36% and 3.86% glucose used dwells were 23+/-14 pg/ml and 28+/-4 pg/ml, respectively (p=0.78). The IL-6 levels were 106+/-57 pg/ml and 115+/-63 pg/ml (p=0.81), respectively. CONCLUSION: In our in vivo study we found that the glucose concentration of the conventional lactate-based CAPD solution has no effect on basal IL-6 and TNF-alpha levels of peritoneal fluid. Further in vivo studies with non-lactate-based CAPD solutions are needed in order to determine the effect of glucose concentration per se on cytokine release.     

The effect of hemodialysis,peritoneal dialysis and renal transplantation on nutritional status and serum micronutrient levels in patients with end-stage renal disease; Multicenter, 6-month period,longitudinal study

PurposeNutritional status and micronutrient levels of end stage renal disease (ESRD) patients may vary depending on the mode of renal replacement therapy (RRT). We aimed to compare the effects of hemodialysis, peritoneal dialysis (PD) and renal transplantation (RT) on micronutrient levels and nutritional status in ESRD patients.Patients and MethodsA total of 77 ESRD patients who had not received RRT were included in this prospective longitudinal study. All ESRD patients underwent a blood serum analysis that assessed the micronutrients such as selenium, copper, zinc, chromium, retinol, thiamine and vitamin B6 as well as a nutritional status assessment. After the baseline assessments and the initiation of RRT was accomplished, all patients were followed for 6 months.ResultsThe study showed significant improvements in subjective global assessment scores (percentage increases in score A were 26.6 and 36.6; p = 0.039 and p = 0.001; respectively), mid-arm circumference and the skin-fold thicknesses (p < 0.001, p < 0.001; respectively) in the RT and hemodialysis groups. The examinations at sixth month revealed a significant increase in body weight (4.8 kg; p = 0.002) and albumin levels (0.6 g/dL; p < 0.001) in only RT group. Zinc, thiamin and vitamin B6 were the most deficient micronutrients (44.1 %, 24.7 % and 35.1 %; respectively) in ESRD patients. There was a significant increase in selenium and retinol levels (p = 0.020 and p < 0.001; respectively) but a significant decrease in thiamin levels (p = 0.041) in RT patients. A significant increase in retinol levels (p = 0.028) and a significant decrease in thiamin levels (p = 0.022) was observed in the hemodialysis patients. However, no significant change in micronutrient levels was observed in the PD patients.ConclusionThe results support the recommendation that ESRD patients should be supplemented with water-soluble vitamins, especially thiamine and vitamin B6, and trace elements, especially zinc. RT appears to be superior to other modes of RRT when examining SGA score, anthropometric measurements, albumin and micronutrient levels.     

Speciation of chromium in plasma and liver tissue of endstage renal failure patients on continuous ambulatory peritoneal dialysis

This work is a first attempt to determine the speciation of Cr in human plasma. With the aid of in vitro and in vivo⁵¹Cr-labeled experiments, it was possible to develop the necessary biochemical techniques for the separation of the plasma proteins. Further work will use real samples, taking care to avoid contamination of the various fractions and to preserve the original binding of the Cr to the specific plasma compounds. In a first attempt on the distribution of Cr over the different organelles of liver tissue, work will be restricted to in vivo labeled experiments with rats. The procedure to do the speciation work seems so elaborate that it may be impossible ever to achieve the contemplated speciation of Cr in human liver tissue by subcellular fractionation.     

Continuous ambulatory peritoneal dialysis and renal transplantation: a five year experience.

Continuous ambulatory peritoneal dialysis is a new and increasingly popular method of routine dialysis, but its effect on renal transplantation is uncertain. A non-randomised comparison was made of the outcome of grafting in patients who had been treated before transplantation with continuous ambulatory peritoneal dialysis with that in patients treated with haemodialysis. During the five years, 1979-84, after continuous ambulatory peritoneal dialysis was introduced to Newcastle upon Tyne 220 patients have received transplants after either continuous ambulatory peritoneal dialysis (61 patients) or haemodialysis (159 patients). During follow up no significant differences occurred in survival of patients or grafts between the two treatment groups. One year after transplantation the percentages of survivors who had received continuous ambulatory peritoneal dialysis and haemodialysis were 88% and 91% respectively, and overall graft survival was 66% and 72%, respectively. A multiple regression model was used to allow for differences among patients--for example, duration of dialysis and number of preoperative transfusions--on the survival of grafts. When only first cadaver grafts were considered (in 152 patients) graft survival (non-immunological failures excluded) was not significantly different between the patients treated with continuous ambulatory peritoneal dialysis and haemodialysis. Continuous ambulatory peritoneal dialysis is not a risk factor in renal transplantation, and its continued use in treatment of potential renal graft recipients is recommended.     

Use of the Deane prosthesis in patients on long-term peritoneal dialysis

The Deane peritoneal prosthesis has been used successfully in the treatment of 21 patients with chronic renal failure who were maintained on peritoneal dialysis for periods of up to 20 months. All patients were dialyzed for 24 hours twice weekly. While the prosthesis was still in place, transplantation was carried out in seven patients and laparotomy in three. The prosthesis was also used temporarily whenever a permanent peritoneal catheter (Tenckhoff''s) failed because of infection; it was used until the signs of infection disappeared, then the permanent catheter could be replaced safely. From a total of 1136 dialyses 36 positive cultures were reported. Clinical peritonitis was found on only four occasions.     

Mesenchymal stroma cells in peritoneal dialysis effluents from patients

Mesenchymal stroma cells (MSCs) have potential as an emerging cell therapy for treating many different diseases, but discovery of the practical sources of MSCs is needed for the large-scale clinical application of this therapy. This study was to identify MSCs in peritoneal dialysis (PD) effluents that were discarded after PD. The effluents were collected from patients who were on the dialysis for less than 1 month. Adherent cells from the effluents were isolated by incubation in serum-containing medium in plastic culture dishes. Cell surface markers were determined by a flow cytometric analysis, and the in vitro differentiation to chondrocytes, osteocytes or adipocytes was confirmed by staining with a specific dye. After four passages, these isolated cells displayed the typical morphology of mesenchymal cells in traditional 2-D cultures, and were grown to form spherical colonies in 3-D collagen cultures. Flow cytometric analysis revealed that the unsorted cells from all of seven patient samples showed robust expression of typical mesenchymal marker CD29, CD44, CD73, CD90 and CD166, and the absence of CD34, CD79a, CD105, CD271, SSEA-4, Stro-1 and HLA-DR. In differentiation assays, these cells were induced in vitro to chondrocytes, osteocytes or adipocytes. In conclusion, this preliminary study suggests the presence of MSCs in the “discarded” PD effluents. Further characterization of the phenotypes of these MSCs and evaluation of their therapeutic potential, particularly for the prevention of PD failure, are needed.