bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intermittent Intravenous Piperacillin Pharmacokinetics in Automated Peritoneal Dialysis Patients
Authors: Manley Harold J. , Bailie George R. , Frye Reginald , McGoldrick M. Donald 
Published: February 2020

Background Use of intermittent antibiotic dosing is increasing in the treatment of peritoneal dialysis (PD)-related peritonitis. We studied the pharmacokinetics of intravenous (IV) piperacillin in automated PD patients. Patients and Methods Eight patients (3 males, 5 females) were recruited and received a single IV dose of piperacillin (35 mg/kg actual body weight). Blood and dialysate samples were collected at the beginning, middle, and end of dwells 1 – 3 (on cycler), and end of dwells 4 – 5 (off cycler) for a 24-hour period. Baseline and 24-hour urine samples (nonanuric patients, n = 7) were collected. Pharmacokinetic parameters were calculated assuming a one-compartment model. Glomerular filtration rate (GFR) and piperacillin clearance (CL) values were normalized to 1.73 m2. Results The patients were 49.5 ± 10.1 years of age (mean ± SD) and had been receiving PD for a median of 3 months (range 2 – 66 months). Dwell times were 2.25 ± 0.06 hours on cycler and 7.26 ± 0.14 hours off cycler. Piperacillin half-life was not statistically different on or off the cycler (on cycler 1.99 ± 0.39 hr, off cycler 4.39 ± 5.4 hr; p = 0.12) and remained insignificant, even accounting for an outlier (on cycler 2.01 ± 0.41 hr, off cycler 2.54 ± 1.48 hr; p = 0.19). Piperacillin total CL (CLT) was 31.29 ± 6.02 mL/minute. Renal CL (CLR) and PD CL (CLPD) accounted for 8.8% and 16.8% of CLT; CLR correlated well with GFR (CLR = 0.86 GFR + 0.1; p < 0.000 03). Mean piperacillin serum and dialysate end-of-dwell concentrations were above minimum inhibitory concentration of susceptible organisms (8 μg/mL) for the three cycler exchanges only. Serum and dialysate concentrations predicted using a one-compartment model suggest that IV piperacillin 4000 mg would provide adequate concentrations for susceptible organisms over a 12-hour period. Conclusion The current IV piperacillin dosing recommendations of 4000 mg every 12 hours for PD-related peritonitis are appropriate for patients on automated PD. Intermittent intraperitoneal piperacillin is not recommended.
Human Peritoneal Mesothelial Cells Produce Nitric Oxide: Induction by Cytokines
Authors: Chen Jinn-Yang , Chiu Jen-Hwey , Chen Hui-Ling , Chen Tzen-Wen , Yang Wu-Chang , Yang An-Hang 
Published: February 2020

Objective To investigate the induction of nitric oxide synthase type II (iNOS) in human peritoneal mesothelial cells (HPMC) using cytokines and bacterial lipopolysaccharide (LPS). Design Confluent monolayers of HPMC were exposed to cytokines [tumor necrosis factor alpha (TNFα), interleukin-1 beta (IL-1β), interferon gamma (IFNγ)] or LPS, individually or in various double and triple combinations, for 24 – 72 hours. Concentrations of nitrate and nitrite in the media were quantified using the Griess reaction and used as indirect indices of nitric oxide (NO) production. The expression of iNOS was assessed using reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot. Results Neither single cytokines nor LPS was able to induce iNOS mRNA or NO production. Both double combinations of TNFα+ IFNγ and IL-1β + IFNγ were able to induce iNOS mRNA expression, but only TNFα + IFNγ induced significant NO production. The triple combination of TNFα + IFNγ + IL-1β induced even more NO production than TNFα + IFNγ. There was no constitutive NO synthase type III (eNOS) expression in HPMC. Conclusions Certain combinations of cytokines could stimulate cultured HPMC to produce NO, and HPMC might be a source of intraperitoneal NO production during peritonitis.
Uremic Anorexia: A Consequence of Persistently High Brain Serotonin Levels? The Tryptophan/Serotonin Disorder Hypothesis
Authors: Aguilera Abelardo , Selgas Rafael , Codoceo Rosa , Bajo Auxiliadora 
Published: February 2020

Anorexia is a frequent part of uremic syndrome, contributing to malnutrition in dialysis patients. Many factors have been suggested as responsible for uremic anorexia. In this paper we formulate a new hypothesis to explain the appetite disorders in dialysis patients: “the tryptophan/serotonin disorder hypothesis.” We review current knowledge of normal hunger–satiety cycle control and the disorders described in uremic patients. There are four phases in food intake regulation: ( 1 ) the gastric phase, during which food induces satiety through gastric distention and satiety peptide release; ( 2 ) the post absorptive phase, during which circulating compounds, including glucose and amino acids, cause satiety by hepatic receptors via the vagus nerve; ( 3 ) the hepatic phase, during which adenosine triphosphate (ATP) concentration is the main stimulus inducing hunger or satiety, with cytokines inhibiting ATP production; and ( 4 ) the central phase, during which appetite is regulated through peripheral (circulating plasma substances and neurotransmitters) and brain stimuli. Brain serotonin is the final target for peripheral mechanisms controlling appetite. High brain serotonin levels and a lower serotonin/ dopamine ratio cause anorexia. Plasma and brain amino acid concentrations are recognized factors involved in neurotransmitter synthesis and appetite control. Tryptophan is the substrate of serotonin synthesis. High plasma levels of anorectics such as tryptophan (plasma and brain), cholecystokinin, tumor necrosis factor alpha, interleukin-1, and leptin, and deficiencies of nitric oxide and neuropeptide Y have been described in uremia; all increase intracerebral serotonin. We suggest that brain serotonin hyperproduction due to a uremic-dependent excess of tryptophan may be the final common pathway involved in the genesis of uremic anorexia. Various methods of ameliorating anorexia by decreasing the central effects of serotonin are proposed.
Effect of High Glucose on Peritoneal Mesothelial Cell Biology
Authors: Ha Hunjoo , Lee Hi Bahl 
Published: February 2020

Objective This study reviews evidence that implicates high glucose (HG) in the pathogenesis of peritoneal fibrosis and proposes mechanisms potentially involved in the HG-induced peritoneal fibrosis that is observed in long-term peritoneal dialysis (PD) patients. Design Selected Western literature is reviewed, examining the effect of HG on rat or human peritoneal mesothelial cell (HPMC) biology with particular reference to extracellular matrix (ECM) gene expression and protein synthesis. Results HG up-regulated the expression of monocyte chemotactic peptide–1 (MCP-1), transforming growth factor beta 1 (TGFβ1), and fibronectin messenger RNAs (mRNAs) and proteins. These HG-induced up-regulations were effectively blocked by the inhibition of protein kinase C (PKC). In addition, cytosolic reactive oxygen species (ROS) rapidly increased in HPMC cultured under HG, and treatment with antioxidant effectively inhibited HG-induced fibronectin protein synthesis by HPMC. Conclusion Continuous exposure of the peritoneal membrane to HG may induce changes in HPMC biology, leading to excessive deposition of ECM and peritoneal injury. HG-induced activation of diacylglycerol PKC (DAG–PKC) plays a major role in up-regulation of MCP-1, TGFβ1, and fibronectin synthesis by HPMC cultured under HG. In addition, ROS, recently recognized as signalling molecules, are rapidly generated in HPMC as a result of increased glucose metabolism and may prove to be an important mediator of HG-induced peritoneal injury.
Urea is the Best Molecule to Target Adequacy of Peritoneal Dialysis
Authors: Gotch Frank A. 
Published: February 2020

For hemodialysis, a large base of data shows the validity of modelling the dialysis dose and reliably estimating protein intake from equilibrated Kt/V urea (eKt/VU), the total dialyzer urea clearance provided during each treatment divided by the urea distribution volume. An eKt/VU of 1.05 thrice weekly is judged adequate, but is still under study. In continuous ambulatory peritoneal dialysis (CAPD), two dosage criteria are widely recognized: continuous (“standard”) Kt/VU (stdKt/VU = 2.0 weekly), and total creatinine (Cr) clearance normalized to body surface area (KCrT = 70 L/week/1.73 m2). The CANUSA study concluded that a stdKt/VU of 2.1 and a KCrT of 70 L/week/1.73 m2 gave equivalent clinical outcomes. The Dialysis Outcomes Quality Initiative (DOQI) recommends values of 2.0 and 60 L/ week/1.73 m2 respectively. An analysis of these two parameters for males and females over a wide range of body surface areas (BSAs) was done and the analysis showed: ( 1 ) The U and Cr dose criteria are incommensurable—that is, they can virtually never be achieved simultaneously in anephric patients. ( 2 ) The Cr criterion varies widely with the sex of the patient and with the BSA-dependent variation in stdKt/VU over a range of 2.1 to 3.0. ( 3 ) The U criterion always produces a KCrT < 60 L/week/1.73 m2 in females and 60 – 70 L/ week/1.73 m2 in males. With respect to U and Cr, the CANUSA results were concluded to be valid in patients with substantial residual renal function, but probably not applicable to anephric patients where the doses are clearly incommensurable.
Patients on Chronic Peritoneal Dialysis for Ten Years or More in North America
Authors: Maitra Sanjay , Burkart John , Fine Adrian , Prichard Sarah , Bernardini Judy , Jindal Kailash K. , Oreopoulos Dimitrios G. 
Published: February 2020

Thirty-six patients on peritoneal dialysis (PD) for more than ten years in six North American centers were analyzed retrospectively. In the six centers, the percentage of patients surviving for more than ten years varied between 0.8% and 7.3%. The study group included 27 females and 9 males aged 38.6 ± 14.2 years [mean ± standard deviation (SD)] at the start of treatment. Of the 36 patients, 28 were Caucasian. The most common cause of end-stage renal disease (ESRD), present in 12 patients, was chronic glomerulonephritis. Only 4 patients had diabetes. At the beginning of the study, 19 patients had hypertension (the most common comorbid condition); 11 had no comorbid conditions at the start. Creatinine clearance at the start was 4.12 ± 3.5 mL per minute, and the mean duration to anuria was 51 ± 25 months. Mean initial body weight was 55 ± 9 kg, and mean body surface area was 1.5 ± 0.2 m2. Serum albumin levels showed an increase from 33.8 ± 3.6 g/L at the start of the study to 38.2 ± 3.9 g/L at the end. Hospitalization rate was low at 0.5 ± 0.3 admissions per patient–year, and duration of hospitalization was 4.8 ± 3.7 days per patient–year. Peritonitis was the most common cause of hospitalization. The mean peritonitis rate was 1 episode every 52 ± 48 patient–months. There were 36 catheter changes in 18 patients; 16 patients had a single PD catheter throughout the period of study. Autonomous hyperparathyroidism was the most common long-term complication. At the end of the study period, 11 patients were still on PD, 9 had died, 5 had been transferred to hemodialysis (HD), 1 was alive with a functioning allograft, and 1 was lost to follow-up. We conclude that patients who survive longer than ten years on PD are most likely to be young Caucasian females, small in body size, who are non diabetic, with few comorbid conditions. These long-term survivors have few hospitalizations, and their peritonitis rate is low. In this group of patients, severe autonomous hyperparathyroidism is the most common long-term complication.
Biocompatibility of New Peritoneal Dialysis Solutions: Clinical Experience
Authors: Garcia–Lopez Elvia , Lindholm Bengt , Tranæus Anders 
Published: February 2020

The successful development of peritoneal dialysis (PD) during the last two decades has been made possible by using well-established glucose-based solutions with lactate as buffer. On the other hand, awareness has been increasing about the potentially negative effects of the high concentrations of glucose and lactate, and the low pH of conventional PD solutions. This awareness has prompted an intensive effort to search for and test alternative solutions. As a result, three new, more biocompatible solutions— containing either less glucose or less lactate—are available. Amino acid–based solution uses amino acids instead of glucose as the osmotic agent; it is indicated for treatment of malnutrition. The higher pH and absence of glucose in this solution may prevent alterations of the peritoneal membrane caused by acidity and high glucose concentrations. Bicarbonate/lactate–buffered solution contains a physiologic concentration of bicarbonate and a reduced concentration of lactate; it also has a physiologic pH and markedly reduced levels of glucose degradation products (GDPs). Icodextrin-based solution contains icodextrin as the osmotic agent; it is indicated for long dwells, delivering sustained ultrafiltration for more than 16 hours. This iso-osmolar glucose-free solution may reduce peritoneal membrane alterations caused by glucose or the hyperosmolality (or both) of conventional solutions. Clinical experience of the new solutions is now extensive, and their efficacy and safety are well documented. It therefore seems appropriate to state that we have entered a new era of PD therapy. Each of the new solutions may be less damaging to the peritoneal membrane than conventional solution. In addition, they permit better management of malnutrition and fluid status, and may thus help to improve PD patient survival. Although the effects of each of these new solutions have been well described, clinical documentation of the combined use of these new biocompatible PD solutions is still insufficient. However, the results of studies are expected, during the coming years, to support the combined use of the new solutions as the preferred standard practice for PD.
Effects of Peritoneal Dialysis with an Overnight Icodextrin Dwell on Parameters of Glucose and LIPID Metabolism
Authors: Bredie Sebastian J.H. , Bosch Frank H. , Demacker Pierre N.M. , Stalenhoef Anton F.H. , Van Leusen Robert 
Published: February 2020

Objective To examine whether a reduced daily glucose load by overnight application of the less-absorbed glucose polymer icodextrin would have favorable effects on lipid profiles of continuous ambulatory peritoneal dialysis (CAPD) patients. Study Design Randomized crossover study with two subsequent periods of 6 weeks. Setting Home PD unit of a secondary-care hospital. Patients Twenty-one nondiabetic CAPD patients (15 male, 6 female; mean age 50.3 ± 11.8 years). Intervention Participants were randomly assigned to receive an overnight dwell with either standard glucose solution or with a 7.5% icodextrin-containing solution. Main Outcome Measures Relation between reduction in the total amount of intraperitoneal infused glucose and parameters of glucose (plasma glucose, insulin, and HbA1C) and lipid metabolism [free fatty acids, plasma lip-ids, lipoproteins, and low density lipoprotein (LDL) sub-fraction profile]. Results After the icodextrin dwells, a reduction of plasma total cholesterol (from 5.43 ± 0.85 to 4.86 ± 0.70 mmol/L, p < 0.001) and LDL cholesterol (from 3.38 ± 0.87 to 2.93 ± 0.73 mmol/L, p = 0.001) was observed. Also, high density lipoprotein (HDL) cholesterol (from 0.95 ± 0.27 to 0.90 ± 0.24 mmol/L, p = 0.029) was reduced, but the plasma total cholesterol-to-HDL ratio remained similar. Plasma free fatty acids and triglyceride levels tended to decrease (from 0.16 ± 0.10 to 0.13 ± 0.08 mmol/L, p = 0.06, and from 2.14 ± 1.96 to 1.92 ± 1.03 mmol/L, respectively). Evaluation of LDL subfraction profiles after ultra-centrifugation showed a more buoyant LDL subfraction profile with fewer dense LDL particles in 6 patients and no changes in 14 patients after icodextrin. The effects on lipids were not accompanied by a decrease in fasting plasma glucose (from 5.76 ± 1.29 to 5.86 ± 0.80 mmol/L) or insulin levels (from 19.5 ± 14.4 to 20.3 ± 13.0 mU/L). Conclusion These results suggest a beneficial effect on lipid profiles of CAPD patients with the use of an overnight dwell with icodextrin.
Association of Hypertriglyceridemia and Insulin Resistance in UREMIC Patients Undergoing CAPD
Authors: Cheng Shu Chien , Chu Tzong Shinn , Huang Kuan Yu , Chen Yung Ming , Chang Wei Kuang , Tsai Tun Jun , Wu Kwan Dun 
Published: February 2020

Objective Hyperlipidemia is frequently encountered in uremic patients and may be worsened by continuous ambulatory peritoneal dialysis (CAPD) treatment. The lipid abnormalities in these patients may be multifactorial. Insulin resistance (or its compensatory hyperinsulinemia) is commonly observed in uremic patients, but its association with hyperlipidemia in these patients has not been studied. Patients and Methods Lipid profiles of 35 nondiabetic nonobese patients undergoing CAPD for more than 1 year (mean 52.3 months) were studied. Current laboratory data and parameters related to peritoneal dialysis (PD) within the previous 3 months were recorded. After overnight fasting and interruption of PD, an oral 75-g glucose tolerance test (OGTT) was examined. Results After CAPD treatment for more than 12 months, these patients had higher serum triglyceride (TG) ( p = 0.001) and total cholesterol ( p = 0.0058) levels than their values before commencing CAPD. Twelve of 14 patients with serum TG higher than 200 mg/dL (high-TG) were diagnosed de novo, in contrast with only 1 patient diagnosed of de novo hypercholesterolemia (total cholesterol > 240 mg/dL). There was no difference in age, gender, body mass index (BMI), duration of PD treatment, serum albumin, hematocrit, intact serum parathyroid hormone (iPTH), peritoneal glucose load, solute transport, or weekly Kt/V urea between normal-TG and high-TG patients. After adjusting for age, gender, BMI, weekly Kt/V urea, and iPTH, the high-TG patients had higher levels of area under the curve for glucose (AUCGlu), area under the curve for insulin (AUCIns), and AUCIns/AUCGlu ratios (F = 10.63, 10.14, and 8.65; p = 0.0029, 0.0035, and 0.0065, respectively), indicating that the high-TG patients were more insulin resistant. There were 24 patients with normal glucose tolerance (NGT), and 11 patients with impaired glucose tolerance (IGT). The IGT group had higher serum TG (F = 10.43, p = 0.003) and total cholesterol (F = 8.05, p = 0.009) than the NGT group, after adjusting for BMI, duration of CAPD treatment, peritoneal glucose load, solute transport, serum albumin, and lipid levels before PD treatment. The TG levels after CAPD treatment were positively correlated with AUCGlu, AUCIns, and AUCIns/AUCGlu ratio ( r = 0.48, 0.53, and 0.49; p = 0.0037, 0.001, and 0.0028, respectively). Conclusions These results indicate that insulin resistance is an important factor in the development of hypertriglyceridemia in CAPD patients.
Experience with a Large Dose (500 MG) of Intravenous Iron Dextran and Iron Saccharate in Peritoneal Dialysis Patients
Authors: Prakash Sunil , Walele Aziz , Dimkovic Nada , Bargman Joanne , Vas Stephen , Oreopoulos Dimitrios 
Published: February 2020

Objective To compare efficacy in anemia correction and side effects of large doses of intravenous (IV) iron dextran and iron saccharate preparations in peritoneal dialysis (PD) patients. Setting Tertiary-care teaching hospital of University of Toronto. Design Retrospective analysis of 379 PD patients who attended PD clinics in past 5 years. Of these 379 patients, 62 were selected to receive IV iron based on ferrokinetic markers of iron deficiency, noncompliance to or ineffectiveness of oral iron, or increased erythropoietin (EPO) requirement. Intervention Sixty-one patients received two IV iron injections of 500 mg each, 1 week apart, 33 patients received iron dextran, 23 received iron saccharate, and 5 received both iron dextran and iron saccharate. One patient developed anaphylaxis to a test dose of iron dextran and was excluded from further therapy. Blood samples were collected before and 3 and 6 months after iron infusions. Results At 3 months, the group's average hemoglobin rose from 98.3 ± 18.3 g/L to 110.6 ± 16.4 g/L ( p < 0.0001). Ferritin rose from 104.9 ± 115.4 μg/L to 391.5 ± 294.1 μg / L ( p < 0.0001), and iron saturation from 0.17 ± 0.07 to 0.26 ± 0.19 ( p < 0.0001). Erythropoietin requirements fell from 7278.7 IU/week to 5900 IU/week ( p < 0.01). Five of the 34 patients who received iron dextran developed minor side effects and 1 patient had anaphylaxis to the test dose. Of the 23 patients who received iron saccharate, 1 had an anaphylactic reaction and 2 had transient chest pain, which subsided without therapy. Overall, there were more side effects with iron dextran (7.4% of injections) compared to the iron saccharate group (4.3% of injections), but this difference was statistically insignificant. Although statistically insignificant, there was an increase in the number of peritonitis episodes during the 6 months after IV iron infusion, especially with iron dextran, compared to the peritonitis episodes during the 6 months before iron infusions. Conclusion Our study indicates that IV iron in PD patients is effective in restoring iron stores and in decreasing EPO requirements. One anaphylactic reaction occurred in each group. Our data suggest that as much caution be exercised with iron saccharate as with iron dextran. The slight trend toward increased peritonitis rates after iron infusions needs to be investigated in a larger group of patients.
Dialysate Cancer Antigen 125 Concentration as Marker of Peritoneal Membrane Status in Patients Treated with Chronic Peritoneal Dialysis
Authors: Krediet Raymond T. 
Published: February 2020

Objective This study reviews publications on the history of cancer antigen 125 (CA125), the background of its use as a marker of mesothelial cell mass, determination in peritoneal effluent, and its practical use in both the follow-up of peritoneal dialysis (PD) patients and as a marker of in vivo biocompatibility of dialysis solutions. Design Review article. Results CA125 is a high molecular weight glycoprotein. Previous studies in ascites suggested its release by mesothelial cells. In vitro studies with cultured mesothelial cells showed constitutive production, the majority of which was dependent on mesothelial cell mass. Serum CA125 is normal in PD patients, but its concentration in peritoneal dialysate suggests local release, probably from mesothelial cells. Effluent CA125 can be considered a marker of mesothelial cell mass in stable PD patients, but large amounts are found during peritonitis, due probably to necrosis of mesothelial cells. The majority of studies found no relationship between dialysate CA125 and peritoneal transport parameters. Some cross-sectional studies reported a relationship with duration of PD, but others were unable to confirm this, due probably to the large interindividual variability. Longitudinal follow-up has shown a decrease in dialysate CA125, indicating loss of mesothelial cell mass. Application of theoretically morebiocompatible PD solutions causes an increase in dialysate CA125. Conclusions Dialysate CA125 is a mesothelial cell mass marker. The concentration of CA125 should be determined after a standardized dwell. A single low value is not informative. A decrease with time on PD suggests loss of mesothelial cell mass. Dialysate CA125 is a marker of in vivo biocompatibility of (new) dialysis solutions. More research is necessary on the best methodology for measuring low concentrations and establishing normal values and a significant change.