Peritoneal Dialysis Fluid Research Articles

Peritoneal Dialysis in Extremely Low Birth Weight Baby using Chronic PD Catheter

Acute kidney injury (AKI) and fluid overload are serious and common complication in premature babies and may increase morbidity and mortality. Renal replacement therapy should be considered for babies who fail medical interventions. Peritoneal dialysis (PD) is considered a safe and practical option for premature infants by producing efficient gentle removal of solutes and excessive water. There are few reports of PD done in extremely low birth weight (ELBW) infants. Acute PD catheters commonly used in children are reported to have more complications thus seldom used in premature babies. Several authors report using regular intravenous or central venous catheters to dialyze premature babies. We describe an ELBW (700g, twin A) infant born at 24 weeks gestation, who was dialyzed on the 34th day (910g) via pediatric size chronic PD catheter. Filling and drainage of PD fluid were performed manually. We encountered few complications and they were easily controlled. The dialysis resulted in normalization of serum creatinine and correction of fluid and electrolyte imbalance within 10 days. The infant continued to grow and eventually was discharged in good condition, with normal renal function at an adjusted age of 40 weeks (term).

High glucose concentration-induced expression of pentraxin-3 in a rat model of continuous peritoneal dialysis.

Continuous exposure to peritoneal dialysis fluids (PDFs) is associated with pathological responses such as persistent micro-inflammation, which leads to ultrafiltration failure. Pentraxin-3 (PTX3), a multifunctional soluble pattern recognition receptor, is produced at sites of inflammation by a wide range of cell types. This study investigates the in vivo expression of PTX3 in the peritoneal membrane of a rat continuous peritoneal dialysis (PD) model, as well as the effect of high glucose on the in vitro expression of PTX3. The expression of PTX3 was analyzed using RT-PCR, real-time PCR, immunohistochemistry and western blotting in a PD rat model receiving saline or conventional PDF containing 3.86% glucose for 8 weeks. The effects of high glucose on the expression of PTX3 were examined in cultured rat peritoneal mesothelial cells (RPMCs), mouse macrophage-like cells, and mouse fibroblasts. In a rat model of PD, eight-week instillation of the conventional PDF produced increased submesothelial thickening, followed by substantially enhanced PTX3 protein levels in the submesothelial layer of peritoneal membrane. PTX3 was detected in peritoneal mesothelial cells, macrophages and fibroblasts in the thickened submesothelial area. Glucose was found to induce PTX3 protein expression in RPMCs as well as macrophage-like cells and fibroblasts. Continuous exposure to conventional PDF induces PTX3 expression in the peritoneal membrane of rats. High glucose may be involved in the mechanism of PDF-induced local micro-inflammation in the peritoneum.

Mycobacterial Peritonitis in CAPD Patients in Limpopo: A 6-Year Cumulative Report from a Single Center in South Africa

South Africa has one of the highest incidences of tuberculosis (TB) worldwide due to the ongoing human immunodeficiency virus (HIV) epidemic. There are, however, no reports on peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients due to Mycobacterium tuberculosis in South Africa. The aim of this study is to discuss our experience of tuberculous peritonitis in CAPD patients from a rural endemic area of South Africa. This is a retrospective descriptive study of CAPD patients diagnosed with mycobacterium peritonitis infection from January 2008 to August 2014 at the Limpopo Kidney and Dialysis Centre (LKDC) in South Africa. The diagnosis of peritonitis was based on the International Society for Peritoneal Dialysis (ISPD) 2010 recommendations. Peritoneal fluid samples were collected in BACTEC Myco/F Lytic Culture Vials (Becton, Dickinson and Company, Dublin, Ireland). Tenckhoff catheter tips were sent for acid-fast bacilli (AFB) smear and TB culture. Mycobacterium infection was considered in patients with clinical features of peritonitis if 1) AFB smear or TB culture was positive or 2) if the patient was smear- or culture-negative but had suggestive radiological features of TB in the lungs or abdomen or 3) if the patient improved clinically following treatment with anti-tuberculous drugs. Of 170 patients on CAPD for the period reviewed, 12 (7.1%) were diagnosed and treated for mycobacterial peritonitis. There was an equal number of males and females, and all the patients were Black Africans with a mean age of 35.4 years (17-51 years). Eight of the 12 patients (66.7%) had had previous episodes of non-tuberculous peritonitis. Four patients (33.3%) had elevated white blood cell count (WCC) while 9 had higher polymorph count in the PD fluid than lymphocyte count. Mycobacterial organism was confirmed in 9/12 (75%), while the diagnosis was made on clinical and radiological features in the remaining 3 patients. Seven patients (58.3%) died, 10 patients were permanently transferred to hemodialysis (HD), 1 patient returned to PD after a short stay on HD, 1 patient died after 2 years on HD due to lack of further access to dialysis, and in 1 patient, the catheter could not be removed before death. This case series corroborates findings from other previous series that mycobacterial infection in PD patients carries a high mortality and can often pose a diagnostic challenge to attending clinicians. Clinicians should have a high index of suspicion for mycobacterial peritonitis in CAPD patients with features of peritonitis who do not respond promptly to conventional anti-microbial agents. We feel that the recommendation about catheter removal during mycobacterial peritonitis should be revisited, as it had no impact on our patients' outcome.

The dipeptide alanyl-glutamine ameliorates peritoneal fibrosis and attenuates IL-17 dependent pathways during peritoneal dialysis

Peritoneal dialysis (PD) can result in chronic inflammation and progressive peritoneal membrane damage. Alanyl-Glutamine (Ala-Gln), a dipeptide with immunomodulatory effects, improved resistance of mesothelial cells to PD fluids. Recently, interleukin-17 (IL-17) was found to be associated with PD-induced peritoneal damage. Here we studied the capacity of intraperitoneal Ala-Gln administration to protect against peritoneal damage by modulating IL-17 expression in uremic rat and mouse PD exposure models. Supplementation of PD fluid with Ala-Gln resulted in reduced peritoneal thickness, αSMA expression and angiogenesis. Addition of Ala-Gln also attenuated the IL-17 pathway expression induced by PD, reflected by substantial reduction or normalization of peritoneal levels of IL-17, transforming growth factor β, IL-6, and the transcription factor retinoic acid receptor-related orphan receptor gamma T. Moreover, increased levels of IL-17 were associated with PD-induced peritoneal thickening. Conversely, Ala-Gln treatment prevented peritoneal extracellular matrix deposition, an effect seen with IL-17 blockade. Thus, intraperitoneal administration of Ala-Gln, a stable dipeptide commonly used in parenteral nutrition, ameliorates PD-induced peritoneal damage in animal models, in part by modulating IL-17 expression. Hence, Ala-Gln supplementation of dialysate may be a potential strategy to ameliorate peritoneal deterioration during PD.

Evaluation of continuous ambulatory peritoneal dialysis fluid C-reactive protein in patients with peritonitis.

Severe peritonitis causing death is one of the most devastating complications of peritoneal dialysis (PD). Since the predictive value of C-reactive protein (CRP) in PD fluid has not been assessed, the objective of the present study is to evaluate its predictive value and clinical correlation in patients on PD with peritonitis. One hundred and twenty patients on continuous ambulatory PD (CAPD) were enrolled and their serum and fluid CRP (Fl. CRP) were evaluated at the start of CAPD. All patients who developed peritonitis were further evaluated for serum and fluid CRP. The patients were categorized into four groups, namely: normal patients (control group), patients with peritonitis, patients with peritonitis leading to catheter removal, and death due to peritonitis. Sixty-five patients developed peritonitis of whom, catheter removal was performed in eight patients. Five patients died due to peritonitis-related complications. Fl. CRP showed a significant difference among the three groups, unlike S. CRP. Estimation of CRP in the peritoneal fluid may be a useful marker to monitor the onset of peritonitis.

Therapeutic mechanisms of adjunct peritoneal resuscitation for the early hepatic injury in rats after hemorrhagic shock

Objective To investigate the therapeutic effect of adjunct peritoneal resuscitation (APR) on the early hepatic injury in rats with hemorrhagic shock in order to explore its possible mechanisms. Methods Ninety-six male Wistar rats were assigned randomly (random number) into control group, shock group, APR1 group and APR2 group. Each group was further divided into 3 subgroups (n=8 in each) as per the animals sacrificed separately at 1 h, 2 h, and 6 h after resuscitation. The rat model of hemorrhagic shock was made by exsanguination under amytal anesthesia and heparinization. The rats in shock group received shed blood plus twice amount of normal saline as conventional intravenous resuscitation (CIR). Besides CIR, at the beginning of resuscitation, those rats in APR1 and APR2 groups were administered intra-peritoneally with 100 mL/kg of Ringer's solution or 2.5% glucose-based peritoneal dialysis solution, respectively. The shock rats in the four groups were sacrificed separately at above mentioned intervals after resuscitation. Liver enzymes and wet/dry weight ratio (W/D) of liver tissue were measured, and pathological changes of liver tissue were observed under optic microscope. The expressions of NF-κB and hot shock protein-70 (HSP70) mRNA in the liver tissue of rats were detected with RT-PCR. All data were statistically analyzed using SPSS 16.0 software. Results Compared with the shock group and APR1 group, the expressions of HSP70 mRNA in the liver tissue of rats at all given intervals after resuscitation in APR2 group increased significantly (P <0.05) , but the W/D ratios of liver tissue at 2 h, 6 h, the degree of pathological changes of liver tissue in 6 h, serum levels of ALT and AST at all given intervals and the expressions of NF-κB mRNA at all given intervals decreased significantly (P <0.05). Conclusions APR with 2.5% glucose-based peritoneal dialysis solution can significantly mitigate the early hepatic injury secondary to hemorrhagic shock, and the mechanisms may be associated with enhancement the expressions of HSP70 mRNA and inhibition the expressions of NF-κB mRNA. Key words: Adjunct peritoneal resuscitation; Hemorrhagic shock; Nulear factor kappa B; Heat- shock protein 70; Hepatic lesion; Peritoneal dialysis fluid; Liver function; Wet/dry weight ratio (W/D) of liver tissue

Attenuation of methylglyoxal-induced peritoneal fibrosis: immunomodulation by interleukin-10

Peritoneal fibrosis (PF), a serious pathophysiology of peritoneal dialysis (PD), is implicated in various types of chronic inflammation. In the present study, we examined the benefits of interleukin (IL)-10, which exerts anti-inflammatory effects, in an experimental rat model of methylglyoxal (MGO)-induced PF. We injected an adeno-associated virus (AAV) vector encoding rat IL-10 or enhanced green fluorescent protein (GFP) into male Sprague-Dawley rats at 6 weeks of age. Four weeks later, the rats received continuous peritoneal injections of conventional PD fluid (PDF) with MGO for 3 weeks. Then, the peritoneal histology and the expression levels of fibrogenic mediators and proinflammatory cytokines were analyzed. The rats demonstrating persistent IL-10 expression showed significantly reduced fibrous peritoneal thickening compared with those with GFP expression. The infiltration of macrophages, the expression of tumor necrosis factor-α, IL-1β, IL-6, transforming growth factor-β1, Snail, and matrix metalloproteinase 2 genes as well as the proliferation of mesenchymal-like mesothelial cells augmented by MGO were all significantly suppressed by IL-10 expression. IL-10 also abrogated the extent of MGO-induced bowel adhesions mimicking a cocoon-like mass. Our findings provide valuable insight into the potential benefit of immunomodulation with IL-10 as one potentially effective therapeutic strategy for preventing the onset of peritoneal injury resulting in PF.

Increased storage and secretion of phosphatidylcholines by senescent human peritoneal mesothelial cells.

Human peritoneal mesothelial cells (HPMC) secrete phosphatidylcholines (PC) which form a lipid bilayer lining the peritoneum. They prevent frictions and adhesions and act as a barrier to the transport of water-soluble solutes while permitting water flux. PC may play an essential role in peritoneal integrity and function, the role of PD induced HPMC senescence on PC homeostasis, however, is unknown. HPMC cell lines were isolated from four non-uremic patients. Expression of the three PC synthesis genes (rt-PCR), and cellular storage and secretion of PC (ESI-mass-spectrometry) were analyzed in young and senescent HPMC (>Hayflick-limit). Senescent cells displayed significantly altered morphology; flow cytometry demonstrated extensive staining for senescence-associated beta galactosidase. Nine different PC were detected in HPMC with palmitoyl-myristoyl phosphatidylcholine (PMPC) being most abundant. In senescent HPMC mRNA expression of the three key PC synthesis genes was 1.5-, 2.4- and 6-fold increased as compared to young HPMC, with the latter, phosphatidylcholine cytidylyltransferase, being rate limiting. Intracellular storage of the nine PC was 75-450% higher in senescent vs. young HPMC, PC secretion rates were 100-300% higher. Intracellular PC concentrations were not correlated with the PC secretion rates. Electron microscopy demonstrated lamellar bodies, the primary storage site of PC, in senescent but not in young cells. Senescent HPMC store and secrete substantially more PC than young cells. Our findings indicate a novel protective mechanism, which should counteract peritoneal damage induced by chronic exposure to PD fluids.

Effects of a Statewide Protocol for the Management of Peritoneal Dialysis-Related Peritonitis on Microbial Profiles and Antimicrobial Susceptibilities: A Retrospective Five-Year Review.

♦ Peritonitis is a major complication of peritoneal dialysis (PD) and is associated with significant morbidity and mortality. Early empirical antibiotic therapy is recommended, with the choice of agents guided by local resistance patterns. As routine use of specific antimicrobial agents can drive resistance, regular assessment of causative organisms and their susceptibility to empirical therapy is essential. ♦ We conducted a retrospective review of all PD peritonitis cases and positive PD fluid cultures obtained over a 5-year period in Western Australia following the introduction of a statewide protocol for the initial management of PD peritonitis with intraperitoneal vancomycin and gentamicin. ♦ The incidence of PD peritonitis decreased from 1 in 16 patient months (0.75/year at risk) to 1 in 29 patient months (0.41/year at risk) over the 5 years. There were 1,319 culture-positive samples and 1,069 unique isolates identified. Gram-positive bacteria accounted for 69.9% of positive cultures, with vancomycin resistance averaging 2% over the study period. Gram-negative bacteria accounted for 25.4% of positive cultures, with gentamicin resistance identified in an average of 8% of organisms. No increase in antimicrobial resistance to vancomycin or gentamicin occurred over the 5 years and there was no change in the proportion of gram-positive (69.9%), gram-negative (25.4%) or fungal (4.4%) organisms causing PD peritonitis. ♦ Over time, the peritonitis rates have dramatically improved although the profile of causative organisms remains similar. Empirical treatment of PD peritonitis with intraperitoneal vancomycin and gentamicin remains efficacious, with high levels of susceptibility and no evidence that the introduction of this statewide empirical PD peritonitis treatment protocol is driving resistance to these agents.

Hydrogen Sulfide Alleviates Peritoneal Fibrosis via Attenuating Inflammation and TGF-β1 Synthesis

Background/Aims: Peritoneal fibrosis is one of the long-term complications in peritoneal dialysis (PD) patients. Recent evidences have suggested that hydrogen sulfide (H₂S) is beneficial in treating various fibrotic diseases, including pulmonary fibrosis, cirrhosis, kidney fibrosis and cardiac hypertrophy. However, no information is known about the effect of H₂S on peritoneal fibrosis. In the present study, we investigated the effect of H₂S on peritoneal fibrosis and explored its potential mechanisms. Methods: We developed a model of peritoneal fibrosis by intraperitoneally injecting 4.25%-glucose PD fluids and lipopolysaccharide to Sprague-Dawley rats. The rats received daily intraperitoneal injections of NaHS (56 μg/kg), an H₂S donor. After 28 days, the peritoneal equilibration test (PET) was used to assess peritoneal function. At the end of dialysis, the rats were killed and parietal peritoneum was harvested for microscopic examination and immunohistochemistry. Results: On the 28th day, the parietal peritoneum of the PD rats markedly thickened as a result of increased depositions of type III collagen and fibronectin. Moreover, the number of ED-1-positive cells and the expressions of monocyte chemoattractant protein-1, transforming growth factor-β1 (TGF-β1), α-smooth muscle actin and CD31 were significantly increased in the fibrotic peritoneum. Administration of NaHS markedly decreased the biomarkers of inflammation, fibrosis and angiogenesis in the peritoneum. NaHS also improved peritoneal function assessed by PET. Conclusion: Exogenous H₂S ameliorates the pathologic process of peritonitis via attenuating inflammatory events and TGF-β1 synthesis. These results suggest that H₂S may be a potential therapy against peritoneal fibrosis during chronic PD. In the future, compounds releasing H₂S at controlled rate will be assessed as potential candidates to treat peritoneal fibrosis.

Vertical Tunnel-based Low-site Peritoneal Dialysis Catheter Implantation Decreases the Incidence of Catheter Malfunction

Peritoneal dialysis (PD) is often complicated by catheter dysfunction. We designed a PD catheter implantation technique to reduce catheter dysfunction. Between June 2008 and 2012, 89 patients with end-stage renal disease were enrolled into a prospective study and randomly assigned to receive traditional catheter implantation by open surgery (n = 41) or vertical tunnel-based low-site PD catheter implantation (n = 48). Both procedures used Baxter straight double-cuffed Tenckhoff catheters. The novel implantation technique involves a low-site (7 cm above the midpoint of the pubic symphysis), individually tailored intra-abdominal segment, and increased vertical subcutaneous tunnel. Patients were followed for 1-year after procedure. The vertical tunnel-based low-site method implanted catheters were 3.7 ± 0.9 cm long, with an 11.3 ± 0.9 cm intra-abdominal segment. The incidence of postoperative bleeding, PD fluid leakage, outer cuff extrusion, inflow or outflow pain, peritonitis, tunnel inflammation, or exit-site infection did not differ significantly between the two surgical techniques; however, the incidence of catheter displacement and noncatheter displacement malfunctions after the novel technique (4.2%) was significantly lower than that in traditional open surgery (19.5%, P < 0.05). In conclusions, vertical tunnel-based low-site PD catheter implantation can significantly reduce the occurrence of PD catheter malfunction, particularly catheter displacement.

Quantification of reactive carbonyl compounds in icodextrin-based peritoneal dialysis fluids by combined UHPLC-DAD and -MS/MS detection

During heat sterilization of peritoneal dialysis (PD) fluids, the glucose component is partially degraded. The formed glucose degradation products impair biocompatibility and limit the long-term application of PD fluids. As an alternative to glucose, icodextrin, a polyglucose, is used as osmotic agent in PD fluids. After targeted screening for reactive carbonyl compounds, NMR- and MS-analyses very recently revealed 4-deoxyglucosone (4-DG), 3-deoxyglucosone (3-DG), 3-deoxygalactosone (3-DGal), 3,4-dideoxypentosone (3,4-DDPS), and 5-hydroxymethylfurfural (5-HMF) as main polyglucose degradation products (pGDPs) in icodextrin-based PD fluids. Now, the present study established and validated a UHPLC method with DAD as well as a UHPLC-MS/MS method for the first-time quantification of those five major pGDPs in commercial icodextrin PD fluids after derivatization with o-phenylenediamine. Thus, 4-DG was identified to be the main degradation product (in concentrations up to 20μM). In contrast to the values measured in glucose-based products, the concentration of 3-DGal (≤16μM) was higher than the concentration of 3-DG (≤7μM) indicating different reaction pathways starting from polyglucose compared to glucose. The compounds 3,4-DDPS and 5-HMF were present in minor quantities (≤0.3μM each).

Peritoneal dialysis exit-site leak complicated by peritoneal dialysis-related peritonitis due to Actinomyces neuii

Introduction: Actinomyces neuii is a rare cause of peritoneal dialysis-related peritonitis. Case presentation: A 66-year-old male had end-stage renal disease on peritoneal dialysis treatment for 30 months. He developed exit-site leak with infection. Diphtheroids were isolated and considered initially as skin commensals. Dialysis treatment was suspended and on reinstitution he developed peritoneal dialysis-related peritonitis. The organism isolated from the peritoneal dialysis fluid was A. neuii. Conclusion: This case was treated successfully with peritoneal dialysis catheter removal and oral amoxicillin.

Effect of bevacizumab, a vascular endothelial growth factor inhibitor, on a rat model of peritoneal sclerosis.

Peritoneal fibrosis is almost uniform feature encountered in peritoneal dialysis patients. The transition of epithelial cells to mesenchymal phenotype, neovascularization, and consequently development of peritoneal fibrosis occur due to the involvement of peritoneal membrane by various insults such as uremia itself, peritonitis attacks, and exposure to bio-incompatible peritoneal dialysis fluids. Bevacizumab is a monoclonal antihuman antibody developed against vascular endothelial growth factor and can reduce fibrosis by preventing neovascularization. There has been no study so far that demonstrates the effect of bevacizumab on peritoneal fibrosis in a rat model. A total of 41 female Wistar albino rats were divided into six groups. The control group (C) received 0.9 % isotonic saline (2 ml/day) intraperitoneally (i.p) for 21 days. Chlorhexidine group (CH) received 15 % ethyl alcohol and 0.1 % chlorhexidine gluconate (CG) in saline (2 ml/day) i.p for 21 days. The resting group (R) received CG 2 ml/day i.p for 21 days. The bevacizumab-1 group (B1) received CG 2 ml/day i.p for 21 days and bevacizumab 2.5 mg/kg i.p as a single dose on day 21. The bevacizumab-2 group (B2) received CG 2 ml/day for 21 days and bevacizumab 2.5 mg/kg i.p on day 0 and day 21. The bevacizumab-3 group (B3) received bevacizumab 2.5 mg/kg i.p on day 0 and day 21. Peritoneal samples were taken from the left anterior abdominal wall. The thickness, vascularization, and fibrosis scores in the peritoneal samples were assessed using a light microscope. On histopathological evaluations, peritoneum thicknesses, vascularization scores, and fibrosis significantly decreased in bevacizumab groups B1 and B2. Histopathologically, bevacizumab was proven to attenuate fibrotic process in experimental peritoneal sclerosis model.

The effects of Panax notoginseng saponins on the cytokines and peritoneal function in rats with peritoneal fibrosis

Background: Due to the long-term and chronic exposure to the peritoneal dialysis fluid, patients could develop peritoneal fibrosis and ultrafiltration failure which compromises treatment efficacy and outcome, and fibrosis is the major cause of peritoneal dialysis (PD) withdraw among patients. Methods: Twenty-one male WISTAR rats were randomly assigned to three groups, namely saline group, standard peritoneal dialysis fluid (PDF) group, and panax notoginseng saponins (PNS) group. Peritoneal fibrosis was induced by daily injection of PDF for 4 weeks. After execution, multiple histological techniques including HE and Masson's trichrome staining and transmission electron microscopy (TEM) were applied to observe the pathological changes and concentrations of multiple cytokines may involve in the process of fibrosis were determined by enzyme-linked immune sorbent assay (ELISA). Biochemistry parameters were determined by automated chemistry analyzer. Results: PNS can significantly inhibit the expression of transforming growth factor beta (TGF-β1), connective tissue growth factor (CTGF), and monocyte chemoattractant protein (MCP-1) in the peritoneum of rats. Furthermore, pathological damages, including extracellular matrix deposition, vascularization, and fibroblast, were ameliorated in PNS group when being compared with standard PDF group. Peritoneal functions were improved by regular PNS treatment with significantly elevated ultrafiltration. Conclusion: PNS is capable of improving peritoneal function in subjects with PDF exposure and can possibly applied in patients with PD after further verification.

Update on Peritoneal Dialysis: Core Curriculum 2016

Update on Peritoneal Dialysis: Core Curriculum 2016

Injury-induced inflammation and inadequate HSP expression in mesothelial cells upon repeat exposure to dual-chamber bag peritoneal dialysis fluids.

Peritoneal dialysis fluids (PDFs) may induce inadequate heat-shock protein (HSP) expression and injury-related inflammation in exposed mesothelial cells. The aim of this study was to relate cellular injury to these cellular responses in mesothelial cells following repeated exposure to 3 commercial PDFs with different biocompatibility profiles. Primary cultures of human peritoneal mesothelial cells (HPMC) were exposed to a 1:2 mixture of cell culture medium and CAPD2 (single-chamber bag PDF; Fresenius, Bad Homburg, Germany), Physioneal (dual-chamber bag PDF; Baxter, Deerfield, IL, USA) or Balance (dual-chamber bag PDF, Fresenius) for up to 10 days exposure time (4 dwells). Supernatant was analyzed for LDH, IL-6, and IL-8, cells for HSP-72 expression, and protein content. PDF exposure resulted in a biphasic pattern of cell damage switching from an earlier phase with increased injury by single-chamber PDF to a delayed phase with increased susceptibility to dual-chamber PDF. Sterile inflammation was related to LDH release over time and could be reproduced by exposure to necrotic cellular material. PDF exposure resulted in low HSP-72 expression in all tested PDFs. Exposure to single-chamber as well as to dual-chamber bag PDFs induce increased vulnerability of mesothelial cells to repeated exposure of the same solution. These effects were delayed with dual-chamber PDFs. Injury-induced inflammation and impaired HSP expression upon PDF exposure might initiate a vicious cycle with progredient mesothelial cell damage upon repeated PDF exposure. Certainly, interventional studies and translation of these results into the in vivo system is needed.

The influence of different peritoneal dialysis fluids on the in vitro activity of ampicillin, daptomycin, and linezolid against Enterococcus faecalis.

Intraperitoneal administration of antibiotics is recommended for the treatment of peritoneal dialysis-related peritonitis. However, little data are available on a possible interference between peritoneal dialysis fluids and the activity of antimicrobial agents. Thus, the present in vitro study set out to investigate the influence of different peritoneal dialysis fluids on the antimicrobial activity of ampicillin, linezolid, and daptomycin against Enterococcus faecalis. Time-kill curves in four different peritoneal dialysis fluids were performed over 24h with four different concentrations (1 × MIC, 4 × MIC, 8 × MIC, 30 × MIC) of each antibiotic evaluated. Cation-adjusted Mueller-Hinton broth was used as the comparator solution. All four peritoneal dialysis fluids evaluated had a bacteriostatic effect on the growth of Enterococcus faecalis. Compared to the cation-adjusted Mueller-Hinton broth comparator solution, the antimicrobial activity of all antibiotics tested was reduced. For ampicillin and linezolid, no activity was found in any peritoneal dialysis fluid, regardless of the concentration. Daptomycin demonstrated dose-dependent activity in all peritoneal dialysis fluids. Bactericidal activity was observed at the highest concentrations evaluated in Dianeal® PDG4 and Extraneal®, but not in concentrations lower than 30 × MIC and not in Nutrineal® PD4 and Physioneal® 40. The antimicrobial activity of ampicillin and linezolid is limited in peritoneal dialysis fluids in vitro. Daptomycin is highly effective in peritoneal dialysis fluids and might, thus, serve as an important treatment option in peritoneal dialysis-related peritonitis. Further studies are needed to evaluate the clinical impact of the present findings.

Risk factors for loss of residual renal function in children treated with chronic peritoneal dialysis

In dialyzed patients, preservation of residual renal function is associated with better survival, lower morbidity, and greater quality of life. To analyze the evolution of residual diuresis over time, we prospectively monitored urine output in 401 pediatric patients in the global IPPN registry who commenced peritoneal dialysis (PD) with significant residual renal function. Associations of patient characteristics and time-variant covariates with daily urine output and the risk of developing oligoanuria (under 100 ml/m2/day) were analyzed by mixed linear modeling and Cox regression analysis including time-varying covariates. With an average loss of daily urine volume of 130 ml/m2 per year, median time to oligoanuria was 48 months. Residual diuresis significantly subsided more rapidly in children with glomerulopathies, lower diuresis at start of PD, high ultrafiltration volume, and icodextrin use. Administration of diuretics significantly reduced oligoanuria risk, whereas the prescription of renin–angiotensin system antagonists significantly increased the risk oligoanuria. Urine output on PD was significantly associated in a negative manner with glomerulopathies (−584 ml/m2) and marginally with the use of icodextrin (−179 ml/m2) but positively associated with the use of biocompatible PD fluid (+111 ml/m2). Children in both Asia and North America had consistently lower urine output compared with those in Europe perhaps due to regional variances in therapy. Thus, in children undergoing PD, residual renal function depends strongly on the cause of underlying kidney disease and may be modifiable by diuretic therapy, peritoneal ultrafiltration, and choice of PD fluid.

Glucose-based dialysis fluids inhibit innate defense against Staphylococcus aureus.

Staphylococcus aureus peritonitis is a serious complication of Chronic Peritoneal Dialysis (CPD) and associated with a higher risk for severe and recurrent infections compared with other bacteria. We have previously shown that complement-mediated effectors essential for optimal opsonophagocytosis of S. aureus are inhibited by high glucose concentrations. Since most commonly used peritoneal dialysis (PD) fluids are glucose-based, we hypothesized that glucose-based PD fluids likely inhibit complement host defenses against S. aureus. Commercially available PD fluids were tested: glucose-based (Dianeal), Dianeal supplemented with amino acids, icodextrin-based (Extraneal) and amino acid-based (Nutrineal). Control PD fluid was generated to simulate Dianeal excluding the glucose. Three commercially available glucose concentrations were tested: Dianeal 1.5% (15 gm/1000 ml), Dianeal 2.5% (25 gm/1000 ml) and Dianeal 4.25% (42.5 gm/1000 ml). Complement effectors against S. aureus were analyzed including opsonization with C3-fragments, anaphylatoxin generation, and phagocytosis efficiency. We also evaluated clinical strains, including MRSA strains, and specific complement activation pathways. Glucose-based PD fluids inhibited complement opsonization of S. aureus (≥7-fold reduction) and inhibited S. aureus-induced generation of anaphylatoxins C3a and C5a (>10-fold reduction) compared to non-glucose based PD fluids. Dianeal 1.5%, 2.5% and 4.25%, all similarly inhibited C3-mediated opsonization. Glucose-based PD fluids showed a ≥4-fold reduction in opsonization of clinical strains of S.aureus, including MRSA strains. Decreased opsonization of S.aureus in the glucose-based PD fluid compared with non-glucose based fluids correlated with decreased phagocytosis by neutrophils. Complement-mediated opsonophagocytosis of S. aureus and anaphylatoxin generation were severely inhibited in glucose-based PD fluids compared with non-glucose-based PD fluids. By inhibiting complement host defenses, glucose-based PD fluids may increase the risk of and severity of S. aureus peritonitis for CPD patients using these fluids.