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.     

Cancer in patients receiving dialysis.

The incidence of cancer and related mortality was studied in 1651 patients from six dialysis centres in England over 10 years. The only type of cancer for which there was a significant excess was non-Hodgkin''s lymphoma (four cases observed against an expected incidence of 0.15 (p < 0.001); three deaths against an expected 0.1 (p < 0.001)). This excess could not be attributed to either subsequent transplantation or treatment with immunosuppressive drugs. Since immunodepression is a feature of chronic renal failure, these observations together with those on patints treated with immunosuppressive drugs suggest that immunosuppression favours the development of non-Hodgkin''s lymphoma. Studies in which it is concluded that patients receiving dialysis show an excess of other types of cancer have certain shortcomings; the unusual opportunities for detecting cancer in such patients may account for some of the reported excess.     

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.     

Bactericidal activity of human peritoneal macrophages from patients undergoing peritoneal dialysis

Peritoneal macrophages (PM) play an essential role in the pathogenesis of bacterial peritonitis, the main complication of peritoneal dialysis (PD). We determined the antibacterial activity of PM from 31 PD patients using gram-positive (Staphylococcus aureus, Staphylococcus epidermidis) and gram-negative (Escherichia coli, Pseudomonas aeruginosa) test organisms. In an 8-hour test assay, PM revealed the highest antibacterial activity against E. coli [median bactericidal index (Bi) = 5.46 representing 0.74 log growth inhibition compared to controls] and the lowest against P. aeruginosa (Bi = 1.63, 0.21 log growth inhibition, p less than 0.05). The antibacterial activity against S. aureus (Bi = 1.99, 0.3 log growth inhibition) and S. epidermidis (Bi = 2.0, 0.31 log growth inhibition) was within this range. When compared to peripheral blood polymorphonuclear leukocytes, PM reached only 4% (S. aureus) and 8.1% (E. coli) of their antibacterial activity (p less than 0.05). Using E. coli as a test organism, PM isolated after a 4-hour dialysis period revealed the highest antibacterial activity when compared to PM isolated after longer dialysis periods (p less than 0.05). Increasing the duration of PD to 6 and 8 h subsequently decreased the antibacterial activity of PM, suggesting that unphysiologic concentrations of toxic metabolites in the peritoneal effluent might have a harmful influence on PM functions.     

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.     

Phospholipids profiling and outcome of peritoneal dialysis patients

Abstract

Objectives: To investigate phospholipids (PLs) biomarkers in predicting outcome of patients undergoing peritoneal dialysis (PD).

Materials and methods: Twenty PD patients were followed using baseline plasma PLs with an improved online two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry system.

Results: Significant differences were observed in eight PL species with sphingomyelin (SM) and glycerophosphocholine between technical survival (n=15) and failure patients (n?=?5). Cox regression showed SM 21:0 (adjusted HR 13.7, 95% CI 2.42–77.88, p?=?0.003) was independently associated with patients technical failure.

Conclusions: PD failure patients had different plasma PLs profiling as compared with survival patients. Elevated plasma SM 21:0 level may potentially serve as a biomarker of PD patients at risk for adverse outcomes.     

Long-term outcomes of patients receiving drug-eluting stents

Background

We sought to establish the long-term safety of drug-eluting stents compared with bare-metal stents in a usual care setting.

Methods

Using data from a prospective multicentre registry, we compared rates of death and of death or repeat revascularization during 3 years of follow-up of 6440 consecutive patients who underwent angioplasty with either drug-eluting or bare-metal stents between Apr. 1, 2003, and Mar. 31, 2006.

Results

Drug-eluting stents were inserted in 1120 patients and bare-metal stents in 5320. The drug-eluting stents were selected for patients who had a greater burden of comorbid illness, including diabetes mellitus (32.8% v. 20.8% in the bare-metal group, p < 0.001) and renal disease (7.4% v. 5.0%, p = 0.001). At 1-year follow-up, the drug-eluting stents were associated with a mortality of 3.0%, as compared with 3.7% with the bare-metal stents (adjusted odds ratio [OR] 0.62, 95% confidence interval [CI] 0.46–0.83). The rate of the composite outcome of death or repeat revascularization was 12.0% for the drug-eluting stents and 15.8% for the bare-metal stents (adjusted OR 0.40, 95% CI 0.33–0.49). In the subgroup of patients who had acute coronary syndromes, the adjusted OR for this composite outcome was 0.46 (95% CI 0.35–0.61). During the 3 years of observation, the relative risks for death and repeat revascularization varied over time. In year 1, there was an initial period of lower risk in the group with drug-eluting stents than in the group with bare-metal stents; this was followed by a shift toward outcome rates favouring bare-metal stents in years 2 and 3. The adjusted relative risk of the composite outcome of death or repeat revascularization associated with drug-eluting stents relative to bare-metal stents was 0.73 early in the first year of follow-up; it then rose gradually over time, to a peak of 2.24 at 3 years.

Interpretation

Drug-eluting stents are safe and effective in the first year following insertion. Thereafter, the possibility of longer term adverse events cannot be ruled out.Drug-eluting stents now comprise at least 85% of stents used in the United States and up to 40% or more of stents elsewhere. The overwhelming worldwide use of drug-eluting stents has, however, been tempered by the cost differential to bare-metal stents, the lack of data on long-term outcomes in large patient populations and, more recently, emerging concerns about safety because of reports of late thrombosis.^1–8The use of stents has been shown to reduce the rates of repeat revascularization and restenosis after angioplasty compared with angioplasty alone.⁹ Despite this, the long-term efficacy of stent use has been limited by the need for repeat revascularization owing to restenosis.¹⁰ Drug-eluting stents were developed to address this problem. Both clinical trials^11–20 and registry data^21–25 have shown reduced rates of restenosis with drug-eluting stents up to 4 years after implantation. This advantage appears to extend to patients with acute coronary syndromes: a recent 2-year follow-up study involving 7217 patients with acute coronary syndromes suggested that rates of death were lower among patients with drug-eluting stents than among those with bare-metal stents.²⁶The possibility of late thrombosis associated with drug-eluting stents is, however, a concern. Rates of late thrombosis have been reported to be 3.6–5.9 events per 1000 patients receiving drug-eluting stents.²⁷ This adverse event has been the subject of a review by the US Food and Drug Administration and has captured the attention of authoritative bodies around the world.Because of concerns about the long-term safety of drug-eluting stents, we compared the rates of death and of death or repeat revascularization over 3 years among patients who received either bare-metal or drug-eluting stents during angioplasty.     

Tuberculous peritonitis in a case receiving continuous ambulatory peritoneal dialysis(CAPD) treatment

Background

Tuberculosis continues to be an important health problem in the world. Besides pulmonary involvement extrapulmonary involvement becomes an affair in developing countries, even in developed countries.

Case presentation

A thirty-six year old male patient was admitted with abdominal pain, diarrhea, nausea, vomiting and fever which had started one week before. The patient had been followed up with predialisis Chronic Renal Failure(CRF) diagnosis for 4 years and receiving continuous ambulatory peritoneal dialysis (CAPD) treatment for 4 months. In peritoneal fluid, 1600/mm3 cells were detected and 70% of them were polymorphonuclear leukocytosis. The patient begun nonspesific antibiotherapy but no benefit was obtained after 12 days and peritoneal fluid bacterial cultures remained negative. Peritoneal smear was positive for Asid-fast basilli (AFB), and antituberculosis therapy was started with isoniazid, rifampicine, ethambutol and pyrazinamide. After 15 days his peritoneal fluid cell count was decreased and his symptoms were relieved. Peritoneal fluid tuberculosis culture was found positive.

Conclusion

Considering this case, we think that in patients with CAPD catheter and peritonitis; when peritoneal fluid leukocytes are high and PMNL are dominant, AFB and tuberculosis culture must be investigated besides bacterial culture routinely.     

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.     

Factors influencing skin autofluorescence of patients with peritoneal dialysis

Skin autofluorescence (SAF) measurement is a simple, noninvasive method to assess tissue advanced glycation end products (AGE). In patients with end-stage renal disease and in those on hemodialysis AGE production is increased. Less is known about those treated with peritoneal dialysis (PD). In this study we tested if SAF is influenced by clinical and treatment characteristics in PD patients.This cross-sectional study included 198 PD patients (of those, 128 were on traditional glucose-based solutions and 70 patients were partially switched to icodextrin-based PD). SAF measurements were done with a specific AGE Reader device. The impact of patients' age, gender, current diabetes, duration of PD, cumulative glucose exposure, body mass index, smoking habits and use of icodextrin on SAF values were tested with multiple regression analysis.Our analysis revealed that patients' age, current diabetes and icodextrin use significantly increase patients' SAF values (p = 0.015, 0.012, 0.005, respectively). AGE exposure of PD patients with diabetes and on icodextrin solution is increased. Further investigation is required whether this finding is due to the icodextrin itself or for a still unspecified clinical characteristic of PD population treated with icodextrin.     

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.