Purification of human complement factor D from the peritoneal fluid of patients on chronic ambulatory peritoneal dialysis

We describe a simple procedure for the purification of human factor D from the peritoneal fluid (PF) of patients with end stage renal failure (ESRF) on chronic ambulatory peritoneal dialysis (CAPD). The main advantages of this method are: (1) a relative enrichment of factor D in PF versus plasma (factor D/total protein enriched 3.8-fold); thus, added to the elevated concentration of factor D in ESRF, the enrichment compared to normal human serum is approximately 50 fold. (2) This biological source of factor D is almost unlimited, since around 10 liters of PF are removed per day from each patient. The purification is performed in three simple steps-Bio Rex 70, Heparin Sepharose CL 6B and Mono S FPLC- and milligrams of highly purified factor D are obtained. Peritoneal fluid might be a valuable source for the purification of other low MW proteins which accumulate in renal failure.     

Hyperglycemia and the outcome of pediatric cardiac surgery patients requiring peritoneal dialysis

OBJECTIVE: To study the nature of the association between glycemia and ICU mortality in pediatric cardiac surgery patients treated with peritoneal dialysis (PD). MATERIALS AND METHODS: Retrospective observational study in the ICU of a tertiary hospital involving forty pediatric cardiac surgery patients treated with PD. We selected patients requiring PD, extracted glucose measurements and nutritional intake data during ICU stay and calculated mean and maximum blood glucose values i) during ICU stay; ii) during dependence on PD; and iii) during independence from PD. We statistically assessed the relationship between glycemia-related variables and ICU mortality. MEASUREMENTS AND RESULTS: Twenty-two patients treated with PD died (mortality 55%). In the PD cohort, 9725 blood glucose measurements were performed (every 3.3 hours on average). The mean glycemia during dependence on PD was significantly higher in non-survivors than survivors (p<0.0001), but not during independence from PD (p=0.49). The area under the receiver operator characteristic curve for the mean glycemia during dependence on PD was significantly greater than that obtained during independence from PD. Even after adjustment for severity of illness using multivariate logistic analysis, the mean glycemia and calorie intake during PD were significant and independent predictors of ICU mortality. CONCLUSIONS: A higher mean blood glucose concentration during PD, but not during PD-free periods was associated with greater ICU mortality. Mean glycemia and calorie intake during PD were significant and independent predictors of ICU mortality.     

Mortality in peritoneal dialysis patients

The incidence of end-stage renal disease is growing. Mortality remains high, despite improvements in care. Much of this can be explained by the presence of cardiovascular disease and other co-morbid conditions that are present at the start of dialysis. However, the dialysis treatment itself may exacerbate these conditions, and dialysis related factors such as adequacy, cytokine production, and dialysis-related infections are important factors in survival. Early studies reported similar or better survival on peritoneal dialysis (compared with hemodialysis), although more recent studies have questioned this finding. This review summarizes the information on mortality in peritoneal dialysis patients.     

MicroRNAs in peritoneal dialysis effluent are promising biomarkers for peritoneal fibrosis in peritoneal dialysis patients

Peritoneal fibrosis is a common complication of long-term peritoneal dialysis, and contributes to encapsulating peritoneal sclerosis and eventually peritoneal ultrafiltration failure, which restricts the wide application of peritoneal dialysis. Therefore, the prevention and treatment of peritoneal fibrosis is important to maintain peritoneal membrane integrity and prolong peritoneal dialysis treatment. Unfortunately, neither specific biomarkers nor effective therapies are available for peritoneal fibrosis in the clinic up to now. Emerging evidence suggests that extracellular microRNAs in body fluids are promising biomarkers for the diagnosis of diseases. microRNAs were reported to be involved in multiple fibrotic diseases and the serum levels of specific microRNAs were correlated with the degree of fibrosis. Moreover, extracellular microRNAs were found in peritoneal fluids and ascites. Based on these findings, here we present our hypothesis that extracellular microRNAs associated with peritoneal epithelial-to-mesenchymal transition and fibrosis could potentially be detected in peritoneal dialysis effluent, and serve as novel biomarkers for early assessment and diagnosis of peritoneal fibrosis.     

Characterization of eosinophils in a continuous ambulatory peritoneal dialysis patient with eosinophilic peritonitis

A continuous ambulatory peritoneal dialysis patient developed eosinophilic peritonitis and was followed for 7 months. After 1 month, the peritonitis resolved, with a concomitant drop in percentage of hypodense eosinophils (Eos) recovered from peritoneal dialysate (PD) as well as a drop in fluid major basic protein levels. Blood eosinophil differential percentages were low, but the percentage of hypodense Eos in the blood tended to be relatively increased. Stool samples showed no evidence of parasitic infection, and epicutaneous skin tests were negative. Leukotriene C4 levels remained relatively constant as did white blood cell counts. Flow cytometric analysis of lymphocytes and granulocytes from PD and blood revealed high levels of CD23-positive lymphocytes.     

Cytokines and growth factors involved in peritoneal fibrosis of peritoneal dialysis patients

Peritoneal fibrosis is initiated by exposure of peritoneal tissues to numerous harmful agents encountered during peritoneal dialysis. These agents interact with cells within the peritoneum to induce growth factors and cytokines that are important in the initiation, progression and maintenance of fibrosis. Some of the mediators implicated in the pathogenesis of peritoneal fibrosis include transforming growth factor (TGF) beta, connective tissue growth factor (CTGF), fibroblast growth factors (FGF), and platelet derived growth factor (PDGF).     

Morphologic characteristics of macroscopic peritoneal finding in patients with peritoneal dialysis

Peritoneal dialysis (PD) has been an attractive treatment for end-stage kidney disease. Long-term exposure to the PD solution creates functional and morphological alterations, and these alterations diminish the efficacy of PD. It is important to establish an evaluation of the changes in PD patients and strategies for the prevention of PD damage and encapsulating peritoneal sclerosis (EPS). We determined the relationship between clinical findings and macroscopic morphological findings by laparoscopy in patients receiving PD. Macroscopic intraperitoneal findings were recorded at the PD catheter removal in 23 PD patients. We examined macroscopic morphological findings such as fibrin deposition, peritoneal turbidity, vasculopathy, adhesion and calcification in both parietal and visceral peritoneum of upper and lower peritoneal cavities, and assessed the score semi-quantitatively. We then evaluated the relationship between the morphological score and clinical findings, especially observational parts and findings in EPS patients. The total macroscopic score increased with PD duration. Peritoneal turbidity, fibrin deposition, and calcification were observed in the whole peritoneal cavity. Scores of fibrin deposition, turbidity, and calcification increased with PD duration. Vasculopathy in the parietal peritoneum was more serious compared with that in the visceral peritoneum, but there was no difference in the vasculopathy between the upper and lower areas. A characteristic of the macroscopic findings in EPS patients was peritoneal calcification in this study. It appears that macroscopic findings using laparoscopy is significant in evaluating the degree of the peritoneum damage and predicting EPS development.     

Sympathetic skin response in peritoneal dialysis patients

To determine if there is any difference in nerve conduction studies or sympathetic skin response (SSR) between patients on peritoneal dialysis and those on regular hemodialysis, we did a cross-sectional observational study. The study group consisted of 24 patients on peritoneal dialysis (PD) (12 men, aged 45 +/- 17 years) and 20 patients on hemodialysis (HD) (11 men, aged 50 +/- 22 years). All of these patients were in stable clinical condition, they were receiving adequate dialysis, and none of them had systemic diseases. Motor and sensory nerve conduction studies of the common and medial peroneal nerve and SSR were performed in all patients. There were no differences in motor and sensory nerve conduction velocities between PD and HD patients. All PD patients had detectable SSR. However, six patients on HD (30%) failed to show SSR (p < 0.05). Mean SSR amplitude was higher in PD patients than in HD patients (1233 +/- 843 vs. 605 +/- 771 microv, p < 0.05). There were no differences in mean SSR latency between PD and HD patients. PD modality (continuous ambulatory PD vs. automated PD) or the presence of residual renal function did not influence nerve conduction studies or SSR. In conclusion, using standard nerve conduction studies, no differences could be found between HD and PD. However, a higher proportion of patients on HD showed an impaired SSR, suggesting that subclinical neuropathy may be more common in HD than PD patients.     

Fibronectin and complement secretion by monocytes and peritoneal macrophages in vitro from patients undergoing continuous ambulatory peritoneal dialysis

We investigated the role of the opsonic glycoprotein fibronectin in the host defense of the peritoneum in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Fibronectin concentration in peritoneal dialysate from high infection rate CAPD patients (greater than 1.50 episodes peritonitis per year) was significantly less than from low infection rate CAPD patients (less than 0.55 episodes peritonitis per year). In vitro secretion of fibronectin by cultured peritoneal macrophages from patients with high infection rate was less than from low infection rate patients (P less than 0.05) and controls (P less than 0.01). In vitro secretion of the second component of complement, however, was similar in both high and low infection rate patients. Plasma fibronectin concentration and in vitro fibronectin secretion by cultured peripheral blood monocytes was not different between high infection rate patients and low infection rate patients, but was less than normals. Decreased fibronectin secretion by peritoneal macrophages is associated with a higher incidence of peritonitis among CAPD patients.     

Clinical outcomes and mortality in elderly peritoneal dialysis patients

OBJECTIVES:

To evaluate the clinical outcomes and identify the predictors of mortality in elderly patients undergoing peritoneal dialysis.

METHODS:

We conducted a retrospective study including all incident peritoneal dialysis cases in patients ≥65 years of age treated from 2001 to 2014. Demographic and clinical data on the initiation of peritoneal dialysis and the clinical events during the study period were collected. Infectious complications were recorded. Overall and technique survival rates were analyzed.

RESULTS:

Fifty-eight patients who began peritoneal dialysis during the study period were considered for analysis, and 50 of these patients were included in the final analysis. Peritoneal dialysis exchanges were performed by another person for 65% of the patients, whereas 79.9% of patients preferred to perform the peritoneal dialysis themselves. Peritonitis and catheter exit site/tunnel infection incidences were 20.4±16.3 and 24.6±17.4 patient-months, respectively. During the follow-up period, 40 patients were withdrawn from peritoneal dialysis. Causes of death included peritonitis and/or sepsis (50%) and cardiovascular events (30%). The mean patient survival time was 38.9±4.3 months, and the survival rates were 78.8%, 66.8%, 50.9% and 19.5% at 1, 2, 3 and 4 years after peritoneal dialysis initiation, respectively. Advanced age, the presence of additional diseases, increased episodes of peritonitis, the use of continuous ambulatory peritoneal dialysis, and low albumin levels and daily urine volumes (<100 ml) at the initiation of peritoneal dialysis were predictors of mortality. The mean technique survival duration was 61.7±5.2 months. The technique survival rates were 97.9%, 90.6%, 81.5% and 71% at 1, 2, 3 and 4 years, respectively. None of the factors analyzed were predictors of technique survival.

CONCLUSIONS:

Mortality was higher in elderly patients. Factors affecting mortality in elderly patients included advanced age, the presence of comorbid diseases, increased episodes of peritonitis, use of continuous ambulatory peritoneal dialysis, and low albumin levels and daily urine volumes (<100 ml) at the initiation of peritoneal dialysis.     

匹多莫德对腹膜透析腹膜炎患者的疗效

目的:观察口服匹多莫德对腹膜透析相关性腹膜炎的疗效.方法:选取2014年5月至2016年5月在华润武钢总医院肾内科住院的130名腹膜透析相关性腹膜炎患者,随机分为治疗组与对照组,对照组给予头孢唑啉联合头孢他啶,治疗组在对照组基础上加用匹多莫德片.比较两组一般情况、初治及2周后有效率、换液次数及微炎症、血脂与免疫学指标.结果:治疗组与对照组在年龄、性别、透析龄、原发病、体重、改良定量主观整体评分(Modified Quantitative Subjective Global Assessment,MQSGA)、血尿素氮(blood urea nitrogen,BUN)、血肌酐(serum creatinine,Scr)、内生肌酐清除率(endogenous creatinine clearance rate,Ccr)等方面差异无统计学意义;对照组与治疗组之间菌谱差异无统计学意义;治疗组与对照组初治有效率分别为77.7％ vs.80.0％,差异无统计学意义(x2=0.18,P=0.66);2周后的有效率分别为93.3％ vs.82.2％,差异有统计学意义(x2=4.56,P=0.03);治疗组与对照组至透出液清亮的换液次数分别为4.60±1.90 vs.5.30±2.60,差异无统计学意义(t=1.75,P=0.08);治疗组与对照组至发热消失的换液次数分别为7.00±3.30 vs.7.70±2.50,差异无统计学意义(t=1.36,P=0.17);治疗组与对照组至腹痛消失的换液次数分别为7.75±2.5 vs.11.38±2.70,差异有统计学意义(t=7.95,P＜0.001),治疗组至腹痛消失的次数显著少于对照组;治疗组与对照组至白细胞计数＜50/μL的换液次数分别为8.60±3.60 vs.13.75±4.70,差异有统计学意义(t=7.10,P＜0.001),治疗组白细胞计数＜50/μL的次数显著少于对照组;治疗后治疗组和对照组较治疗前超敏C反应蛋白(high-sensitivity C-reactive protein,hs-CRP)、高迁移率族蛋白1 (high mobility group box-1 protein,HMGB1)显著降低,治疗组hs-CRP、HMGB-1显著低于对照组,在血脂指标中,治疗组与对照组在治疗前和治疗后2周指标均无显著差异,免疫学指标中治疗组在治疗后免疫球蛋白G与免疫球蛋白A显著上升.结论:匹多莫德能够改善腹膜透析相关性腹膜炎抗生素治疗的有效率,缩短患者的临床症状和体征消失时间,同时改善患者的微炎症状态、免疫学功能.     

Pentraxin 3 as a new biomarker of peritoneal injury in peritoneal dialysis patients

It is well known that bioincompatible peritoneal dialysate plays a central role in the development of peritoneal fibrosis. Peritoneal inflammation continues even after the cessation of peritoneal dialysate stimulation. It is important to establish the definition of persistent inflammation in the peritoneal cavity at the cessation of peritoneal dialysis (PD). The objective of the present study was to determine whether pentraxin 3 (PTX3) in peritoneal effluent (PE) may be a new biomarker in PD patients. Serum, PE, and peritoneal specimens were obtained from 50 patients with end-stage kidney disease at Juntendo University Hospital. Samples of 19 patients were obtained at the initiation of PD and those of 31 patients at the cessation of PD. PTX3, high-sensitivity CRP, and MMP-2 and IL-6 were analyzed. An immunohistological examination using an anti-PTX3 antibody was performed. Expressions of PTX3 were observed in endothelial cells, fibroblasts, and mesothelial cells in the peritoneum. The PTX3 level in PE at the cessation of PD was significantly higher than that at the initiation of PD. Effluent PTX3 levels in patients with a history of peritonitis or a PD duration of more than 8 years were significantly higher than those in patients without peritonitis or patients with a PD duration of <8 years. The PTX3 level was significantly correlated with MMP-2 and IL-6 levels in PE, as well as the thickness of the submesothelial compact zone and the vasculopathy. It appears that PTX3 may be a new biomarker of peritoneal inflammation and progressive fibrosis.