bluuebunny/crossref_metadata_2025 huggingface dataset:
Degradation in Peritoneal Dialysis Fluids May be Avoided by Using Low pH and High Glucose Concentration
Authors: Kjellstrand Per , Martinson Evi , Wieslander Anders , Kjellstrand Karin , Jeppsson Elin , Svensson Eva , Järkelid Lena , Linden Torbjörn , Olsson Lars-Fride
Published: February 2020

Objective

When glucose is present in a medical fluid, the heat applied during sterilization leads to degradation. The glucose degradation products (GDPs) give rise to bioincompatible reactions in peritoneal dialysis patients. The extent of the degradation depends on a number of factors, such as heating time, temperature, pH, glucose concentration, and catalyzing substances. In the present work, we investigated the influence of pH and concentration in order to determine how to decrease the amounts of GDPs produced.

Design

Glucose solutions (1% - 60% glucose; pH 1 - 8) were heat sterilized at 121°C. Ultraviolet (UV) absorption, aldehydes, pH, and inhibition of cell growth (ICG) were used as measures of degradation.

Results

Glucose degradation was minimum at an initial pH (prior to sterilization) of around 3.5 and at a high concentration of glucose. There was considerable development of acid degradation products during the sterilization process when the initial pH was high. Two different patterns of development of UV-absorbing degradation products were seen: one below pH 3.5, dominated by the formation of 5-hydroxy-methyl-2-furaldehyde (5-HMF); and one above, dominated by degradation products absorbing at 228 nm. 3-Deoxyglucosone (3-DG) concentration and the portion of 228 nm UV absorbance not caused by 5-HMF were found to relate to the in vitro bioincompatibility measured as ICG; there was no relation between 5-HMF or absorbance at 284 nm and bioincompatibility.

Conclusion

In order to minimize the development of bioincompatible GDPs in peritoneal dialysis fluids during heat sterilization, pH should be kept around 3.2 and the concentration of glucose should be high. 5-HMF and 284 nm UV absorbance are not reliable as quality measures. 3-DG and the portion of UV absorbance at 228 nm caused by degradation products other than 5-HMF seem to be reliable indicators of bioincompatibility.
Nutritional Markers during Peritoneal Dialysis: Data from the 1998 Peritoneal Dialysis Core Indicators Study
Authors: Flanigan Michael J. , Frankenfield Diane L. , Prowant Barbara F. , Bailie George R. , Frederick Pamela R. , Rocco Michael V.
Published: February 2020

Objective

This analysis explores the nutritional status of adult U.S. peritoneal dialysis (PD) patients.

Design

The Peritoneal Dialysis Core Indicators Study is a prospective cross-sectional prevalence survey describing the care provided to a random sample of adult U.S. PD patients.

Methods and Population

Prevalence data were collected from a national random sample of 1381 adult PD patients participating in the United States End Stage Renal Disease (ESRD) program.

Results

The median age of these patients was 55 years, 61% were Caucasian; the leading cause of ESRD was diabetes mellitus. Age, sex, size, peritoneal permeability, dialysis adequacy, and nutritional indices did not differ between patients on continuous ambulatory PD and patients on automated PD. The dialysis prescriptions employed achieved mean weekly Kt/V urea (wKt/V) and creatinine clearance (wCCr) values of 2.22 ± 0.57 and 67.8 ± 22.5 L/1.73 m2/week, respectively. The PD patients were large, with a mean body weight of 77 ± 21 kg and body mass index (BMI) of 27 ± 8.6 kg/m2. The mean serum albumin of these patients was 3.5 ± 0.51 g/dL, and 43% of values fell below the National Kidney Foundation Dialysis Outcomes Quality Initiative's desired range. The PD patients had a normalized protein equivalent of nitrogen appearance (nPNA) of 1.0 ± 0.57 g/kg/day, a normalized creatinine appearance rate (nCAR) of 17 ± 7.3 mg/kg/day, and an estimated lean body mass (%LBM) of 62% ± 18% of body weight. Serum albumin correlated positively with patient size, nCAR, and nPNA, but negatively with age, the presence of diabetes mellitus, female gender, erythropoietin dose, the creatinine dialysate-to-plasma ratio results of peritoneal equilibration testing, and the dialysis portion of the wCCr. The duration of ESRD experience correlated negatively with both serum albumin and patient size, although these relationships were complex.

Conclusion

Peritoneal dialysis patients generally have marginal serum albumin levels, a finding incongruent with alternative measures of nutritional status, such as weight, BMI, and creatinine generation. Serum albumin is reduced in patients with high peritoneal permeability ( i.e., rapid transporters) and, because these patients generally have higher than average wCCr values, serum albumin is inversely correlated with the dialysis component of the wCCr. The presumptive nutritional indicators (BMI, %LBM, nPNA, and serum albumin) provide disparate estimates, varying from 10% to 50% for the prevalence of nutritionally stressed PD patients.
Erectile Dysfunction in Chronic Peritoneal Dialysis Patients: Incidence and Treatment with Sildenafil
Authors: Juergensen Peter H. , Botev Ross , Wuerth Diane , Finkelstein Susan H. , Smith J. Douglas , Finkelstein Fredric O.
Published: February 2020

Objectives

Sexual and erectile dysfunction (ED) have been reported to occur frequently in male patients with end-stage renal disease maintained on dialysis. Numerous etiologies for this ED have been suggested. Although a variety of therapies for the ED of the dialysis patient have been suggested, most clinicians indicate that patients report a poor response to therapy. Recently, sildenafil has been reported to be beneficial in treating patients with ED of both organic and psychogenic causes. The present study was designed to document the incidence of ED in male patients maintained on chronic peritoneal dialysis (CPD) and to determine the efficacy of prescribing sildenafil therapy to treat their ED.

Methods

All male patients in our CPD unit were notified by letter of the availability of sildenafil as a treatment modality for ED. A sexuality/erectile dysfunction assessment was conducted in all male patients by their primary nephrologist. Patients who reported ED and who had no medical contraindication to sildenafil were offered this therapy. Those patients who were interested in this treatment were interviewed by a social worker, and patients were asked to complete the International Index of Erectile Function questionnaire. Sildenafil was prescribed at a starting dose of 25 mg and increased to a maximum of 100 mg during a 12-week study trial. Patients were re-evaluated 6 and 12 weeks after the start of therapy.

Results

There were 68 male patients maintained on CPD at the time of the study. Mean age of all patients was 60.8 ± 15.3 years and mean duration on PD was 32.6 ± 25.6 months. Thirty-three patients had diabetes, 66 hypertension, 35 peripheral vascular disease, and 32 coronary artery disease. Thirty-two of 68 male patients in the CPD unit were assessed to have ED. Only 17 of the 32 patients expressed interest in pursuing sildenafil therapy. Two of these patients were excluded because they were receiving nitrate therapy. Of the 15 patients who agreed to take sildenafil, only 6 completed the 12-week study. Two of these patients responded to sildenafil.

Conclusion

Erectile dysfunction is common in male patients maintained on CPD. Only about half of patients with ED in the present study were willing to consider sildenafil therapy to treat the ED and, of those who agreed to treatment, only a minority completed the 12-week trial; 2 of these 6 patients reported a satisfactory response.
Diverticular Disease and Treatment with Gastric Acid Inhibitors do not Predispose to Peritonitis of Enteric Origin in Peritoneal Dialysis Patients
Authors: Del Peso Gloria , Bajo María Auxiliadora , Gadola Liliana , Millán Isabel , Codoceo Rosa , Celadilla Olga , Castro María José , Aguilera Abelardo , Gil Fernando , Selgas Rafael
Published: February 2020

Objective

Enteric peritonitis (EP) is an infrequent complication of peritoneal dialysis (PD), with severe consequences for peritoneal membrane viability and patient outcome. Factors such as diverticular disease and gastric acid inhibitors have been implicated in its appearance. We investigated several risk factors, including those mentioned below, that can influence the development of EP.

Design

Retrospective cross-sectional study.

Setting

Tertiary-care public university hospital.

Patients

Fifty-seven PD patients treated in our PD unit during August 1998.

Main Outcome Measures

A barium enema was performed on 50 of the 57 patients (the remaining 7 patients refused it) in order to exclude the presence of diverticulosis. All episodes of peritonitis occurring in those patients, including EP, were registered. Enteric peritonitis was defined as that caused by gram-positive, gram-negative, or fungus micro-organisms that colonized the intestinal tract, excluding episodes secondary to genitourinary tract or peritoneal catheter exit-site infections.

Results

Twenty-four patients showed diverticular disease in the barium enema, but only 5 of them (21%) had any EP episode. Five of the 26 patients with no diverticula (19%) had EP. Fifty-five episodes of peritonitis were reported in 21 patients; 15 episodes of EP (27.3% of all) developed in 11 patients. Seven of the 11 patients (64%) required peritoneal catheter removal and 3 of them (27%) finally were transferred to hemodialysis due to consequences of the EP episode. Logistic regression analysis did not find any of the independent variables analyzed (age, sex, time on PD, type of PD, peritoneal transport parameters, presence of polycystic kidney disease, constipation or diverticulosis, or treatment with gastric acid inhibitors, or phosphate-binding agents) to be risk factors for developing EP.

Conclusions

Neither diverticulosis nor treatment with gastric acid inhibitors seem to be risk factors for developing peritonitis of enteric origin in PD patients. This type of peritonitis has to be promptly identified and treated in order to diminish the high frequency of peritoneal catheter removal and PD dropout due to such episodes.
Glucose Degradation Products in Peritoneal Dialysis Fluids May Have Both Local and Systemic Effects: A Study of Residual Fluid and Mesothelial Cells
Authors: Linden Torbjörn , Musi Barbara , Järkelid Lena , Forsbäck Gunita , Kjellstrand Per , Deppisch Reinhold , Wieslander Anders
Published: February 2020

Objective

When peritoneal dialysis (PD) fluids are heat sterilized, glucose is degraded to carbonyl compounds. These compounds are known to interfere with many cellular functions and to promote the formation of advanced glycation end-products. However, little is known about what actually happens with glucose degradation products (GDPs) after infusion into the peritoneal cavity. The aim of the present study was to investigate possible targets for GDPs in the peritoneal cavity.

Design

In vitro reactions between residual fluid and GDPs were studied by incubating unused PD fluid with overnight dialysate. Confluent monolayer cultures of human mesothelial cells were used as a model to study the reactions of GDPs with the cells lining the peritoneal cavity.

Methods

Samples were analyzed, using high pressure liquid chromatography, for the presence of formaldehyde, acetaldehyde, 5-hydroxymethyl-2-furaldehyde (5-HMF), methylglyoxal, and 3-deoxyglucosone (3-DG). Cytotoxicity was determined as inhibition of proliferation of cultured fibroblasts.

Results

None of the analyzed GDPs reacted with overnight dialysate. Formaldehyde and methylglyoxal, in contrast to 3-DG and 5-HMF, reacted with the cultured mesothelial cells.

Conclusions

Low molecular weight carbonyls such as formaldehyde and methylglyoxal most probably react with the mesothelial cells lining the peritoneal cavity, and could be responsible for the disappearance of these cells during long-term treatment. 3-Deoxyglucosone showed remarkably low reactivity and was most probably transported within the patient.
Glucose Degradation Products in Peritoneal Dialysis Fluids: How they can be Avoided
Authors: Wieslander Anders , Linden Torbjörn , Kjellstrand Per
Published: February 2020

♦ Objectives

A patient on peritoneal dialysis (PD) uses 3 – 7 tons of PD fluid every year. The result is considerable stress on the peritoneal tissue. Aspects of PD fluids that have been considered responsible for bioincompatibility are low pH, high osmolality, high glucose and lactate concentrations, and the presence of glucose degradation products (GDPs). However, the relative importance of each factor in PD fluid has so far not been investigated. Discovering their relative importance was the aim of the present study.

♦ Methods

Two main methods for investigating biocompatibility were used in this study: cytotoxicity measured as in vitro inhibition of cell growth, and in vitro AGE formation measured as albumin-linked fluorescence.

♦ Results

The two most important factors for determining in vitro bioincompatibility of PD fluids were the presence of GDPs, which caused both severe cytotoxicity and strong AGE promotion, and low pH, which induced severe cytotoxicity.

♦ Conclusions

The biocompatibility of PD fluids can be monitored through fairly simple in vitro methods such as cell proliferation and AGE formation. Bioincompatibility of PD fluids is caused mainly by the presence of GDPs and low pH. These findings correlate well with known clinical bioincompatibility.
Peritoneal Dialysis Fill Volume: Can the Patient Tell the Difference?
Authors: Harris Kevin P.G. , Keogh Anne M. , Alderson Lynne
Published: February 2020

♦ Objective

Patients on continuous ambulatory peritoneal dialysis (CAPD) must receive an increased dialysis dose as they lose residual renal function so that total clearances are optimized. The dialysis dose may be increased by increasing the exchange volume. Patients on CAPD are often reluctant to use a greater exchange volume, fearing increased pain and discomfort and an altered body image. To assess patient perception of various fill volumes, we studied 12 stable patients currently treated with 2-L exchanges who had no surgical contraindication to larger fill volumes.

♦ Method

After an overnight dwell, patients received a 2-L, 2.5-L, or 3-L exchange of Baxter PD4 (Baxter Healthcare SA, Castlebar, Ireland) for 3 hours in a randomized crossover design. Patients and staff were both blinded to the fill volume. At the beginning and end of the exchange, intraperitoneal hydrostatic pressure (IPP) in the supine position was measured, and the patient's perception of the exchange was evaluated using the validated McGill Pain Questionnaire (MPQ).

♦ Results

Initial IPP increased with increasing fill volume (12.5 ± 3.7 cmH2O vs 16.1 ± 4.2 cmH2O vs 18.7 ± 3.6 cmH2O for 2, 2.5 L, and 3L, respectively). For all fill volumes, IPP had fallen by the end of the 3-hour dwell, at which time it was similar to that after an overnight 2-L exchange. The pain rating index by was generally low for all exchange volumes and did not correlate with IPP. Minor degrees of discomfort were reported by 4, 2, and 1 patients with 3-L, 2.5-L, and 2-L exchanges respectively.

♦ Conclusion

Our study suggests that, despite an increased IPP, larger exchange volumes are generally well tolerated by patients, with only a minority of patients feeling mild discomfort.
Implantation of Presternal Catheter Using Moncrief Technique: Aiming for Fewer Catheter-Related Complications
Authors: Kubota Minoru , Kanazawa Megumi , Takahashi Yasuhiro , Io Hiroaki , Ishiguro Nozomi , Tomino Yasuhiko
Published: February 2020

♦ Objectives

To reduce catheter-related complications, we developed a new technique of catheter implantation, combining a presternal catheter with the Moncrief technique.

♦ Methods

The presternal catheter, consisting of 2 catheters joined by a titanium extender, was surgically implanted. Its end was left embedded in the presternal wall. A few weeks after implantation, the embedded subcutaneous catheter was exteriorized, exiting in the 4th intercostal space, and peritoneal dialysis (PD) was commenced.

♦ Results

Using the new technique, 9 catheters were implanted (3 in women and 6 in men). Exteriorization was performed 30.6 ± 14.3 days after implantation of the catheter. Total observation period was 70 patient–months. Average hospitalization was 4.4 ± 1.3 days for catheter implantation, and 2.6 ± 2.6 days for exteriorization. Peritoneal dialysis commenced on the day of exteriorization with an exchange volume of 1.8 ± 0.3 L, using 4 exchanges daily. During the observation period, none of the patients experienced a catheter infection or dialysate leak. One non infectious complication was observed (a catheter wrapped in omentum).

♦ Conclusions

Our approach of combining a presternal catheter and the Moncrief technique had some advantages not only in regard to catheter infection and dialysate leakage, but also in regard to quality of life and hospitalization for the patient.
Hyporesponsiveness to Anemia Therapy—What are we Doing Wrong?
Authors: Macdougall Iain C.
Published: February 2020

Most patients receiving anemia therapy respond well, with a significant rise in hemoglobin concentration. However, approximately 5% – 10% of patients fail to show a satisfactory response despite high doses of erythropoietin. The definition of hyporesponsiveness to anemia therapy is somewhat arbitrary, but it is generally regarded as a failure to achieve a hemoglobin concentration of 10 – 11 g/dL despite a dose of erythropoietin in excess of 200 U/kg weekly.

The condition has many causes, the most important ones being iron deficiency, infection or inflammation, and underdialysis. Investigating a patient's poor response to erythropoietin should begin with a check for compliance, followed by screening for iron deficiency. If doubt exists about the presence of iron deficiency, then a trial of intravenous iron may be given.

A reticulocyte count may be helpful. A significantly elevated count suggests the presence of blood loss or hemolysis. The level of C-reactive protein (CRP) may be useful as an indicator of underlying inflammation, and underdialysis may be corrected by increasing the dialysis prescription. If other, minor causes of hyporesponsiveness to erythropoietin have been excluded, then a bone marrow biopsy should be performed. Some patients may require higher doses of erythropoietin, and it is not unreasonable to increase the dose to 10,000 U thrice weekly.

Some causes of hyporesponsiveness to erythropoietin, such as iron deficiency and underdialysis, are easily corrected; but others, such as primary bone marrow disorders and hemoglobinopathies, are not possible to overcome.
Oral versus Intravenous Iron Supplementation in Peritoneal Dialysis Patients
Authors: Johnson David W. , Herzig Karen A. , Gissane Ruth , Campbell Scott B. , Hawley Carmel M. , Isbel Nicole M.
Published: February 2020

The vast majority of erythropoietin (EPO)–treated peritoneal dialysis (PD) patients require iron supplementation. Most authors and clinical practice guidelines recommend primary oral iron supplementation in PD patients because it is more practical and less expensive. However, numerous studies have clearly demonstrated that oral iron therapy is unable to maintain EPO-treated PD patients in positive iron balance. Once patients become iron-deficient, intravenous iron administration has been found to more effectively augment iron stores and hematologic response than does oral therapy.

We recently performed a prospective, cross-over trial in 28 iron-replete PD patients and showed that twice-monthly outpatient iron polymaltose infusions (200 mg) were a practical and safe alternative to oral iron. That treatment produced significant increases in hemoglobin concentration and body iron stores. The additional expense of intravenous iron therapy was completely offset by reductions in EPO dosage.

Careful monitoring of iron stores is important in patients receiving intravenous iron supplementation in view of epidemiologic links with infection and cardiovascular disease. Nevertheless, a growing body of evidence suggests that, as has been found for hemodialysis patients, intravenous iron therapy is superior to oral iron supplementation in EPO-treated PD patients.
Aggressive Therapy of Congestive Heart Failure and Associated Chronic Renal Failure with Medications and Correction of Anemia Stops or Slows the Progression of Both Diseases
Authors: Silverberg Donald S. , Wexler Dov , Blum Miriam , Sheps David , Schwartz Doron , Yachnin Tatyana , Baruch Ron , Tchebiner Joseph , Zubkov Alexander , Shaked Meital , Steinbruch Shoshana , Keren Gad , Iaina Adrian
Published: February 2020

The prevalence of congestive heart failure (CHF) is increasing rapidly in the community. We and others have shown that the prevalence and severity of both anemia and chronic renal failure (CRF) increase steadily with increasing severity of CHF. We have also shown that CHF patients may be resistant to standard drug therapy for CHF as long as the associated anemia is not corrected, and that correction of the anemia with subcutaneous erythropoietin and intravenous iron sucrose (Venofer: Vifor International, St. Gallen, Switzerland) may improve both the CHF and CRF and markedly reduce hospitalizations without causing side effects. We report here our experience with correcting anemia in this manner in 126 cases of anemic-resistant CHF patients. As in our previous studies, correction of the anemia improved both CHF and CRF, and reduced hospitalizations. Our studies suggest that correction of even mild anemia in CHF may be an important addition to the treatment of patients with the combination of CHF and CRF.
Morphologic Aspects of Chronic Peritoneal Dialysis in a Rat Model
Authors: Wieczorowska–Tobis Katarzyna , Brelinska Renata , Breborowicz Andrzej , Oreopoulos Dimitrios G.
Published: February 2020

Objective

We previously put forward an experimental model for evaluating peritoneal function in chronically dialyzed rats. In the present paper, we show the morphologic alterations detected by electron microscopy in the peritonea of chronically dialyzed rats.

Materials and Methods

The study was done in male Wistar rats. Animals were divided into two groups: control (non dialyzed) rats and dialyzed rats [intraperitoneally exposed to Dianeal 3.86% (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.) for 1 month]. At the end of the study, the rats were humanely killed by bleeding, and samples of the visceral peritoneum covering the liver were taken from 3 rats in each group. The samples were examined by transmission electron microscopy (TEM).

Results

In control rats, the peritoneum was composed of flattened mesothelial cells covering the thin layer of the submesothelial connective tissue (ST), containing few fibroblasts. In dialyzed animals, a dramatic expansion of the ST was found. We saw compartmentalization of the ST, with changed morphology of the fibroblasts, altered organization of collagen fibers, and changes in the cells infiltrating the ST. Apart from the fibroblasts, mast cells were relatively numerous.

Conclusions

Our work underlines the capabilities of morphology studies in an animal model for assessing peritoneal dialysis fluid biocompatibility.
Adequacy Targets of Peritoneal Dialysis in the Asian Population
Authors: Li Philip K.T. , Szeto Cheuk-Chun
Published: February 2020

End-stage renal disease affects a large number of patients in Asia. The percentage of patients utilizing PD varies significantly in Asian countries. Continuous ambulatory peritoneal dialysis (CAPD) accounts for about 80% of the dialysis population in Hong Kong.

In this review, we address several questions related to adequacy targets in Asians: Are Asians different? Is dialysis adequacy important for Asians? What is the magnitude of the benefit and the optimal dose of dialysis prescription? Is the adequacy target realistic?

The current international recommendations, including the Dialysis Outcomes Quality Initiative guidelines, are compared with some of our own data for Asian patients. Our published data on dialysis adequacy, nutrition, residual renal function, and peritoneal membrane transport showed that those factors have a significant impact on the morbidity and mortality of PD patients in Hong Kong.

Our results show that solute clearance as measured by Kt/V has a significant impact on the outcome of Asian CAPD patients. Although Chinese PD patients have excellent medium-term patient and technique survival despite an apparently lower Kt/V as compared with the CANUSA standard, that favorable outcome should not prevent nephrologists from providing adequate dialysis to Asian patients. From our own data and analysis, we propose a target Kt/V of 1.9 in Asian CAPD populations. Small-volume dialysis (6 L daily) may be an acceptable compromise in some Asian populations with a smaller body size, especially with residual renal function, given the financial constraints in some developing countries.

Dialysis adequacy means more than a Kt/V value; other clinical parameters are equally if not more important. Thus we should also aim at achieving adequate fluid removal and volume homeostasis, blood pressure control, good nutrition, normal acid–base balance, normal mineral metabolism, minimal anemia, and normal lipid metabolism.
Methodological Issues in Assessing the Incidence of Peritoneal Dialysis-Associated Peritonitis in Children
Authors: Schaefer Franz , Kandert Marianne , Feneberg Reinhard
Published: February 2020

♦ Objectives

To evaluate the distribution of peritonitis incidence and assess the usefulness of patient-specific peritonitis rates in children.

♦ Design

49 children on automated peritoneal dialysis (PD) followed during a 2-year observation period.

♦ Setting

Single-center, academic children's hospital.

♦ Patients

49 children aged 2 months to 18 years; 24 prevalent, 25 incident during the observation period. Cumulative observation time was 639 patient-months.

♦ Main Outcome Measures

Cohort-specific peritonitis incidence, median patient-specific peritonitis incidence, mean peritonitis incidence by gamma-Poisson (negative binomial) modeling, peritonitis-free survival by Kaplan–Meier life-table analysis.

♦ Results

68 new peritonitis episodes and 21 relapses occurred in 27 patients. The distribution of patient-specific peritonitis incidence was bimodal, with a large group experiencing no or very few episodes, and another cluster around 1 episode per 6 – 9 months. Overall cohort-specific peritonitis incidence was 1.28, median subject-specific incidence 0.99, and mean incidence according to negative binomial modeling 1.04 (95% confidence interval 1.02 – 1.06) episodes per patient-year. Median peritonitis-free survival time was 6.9 months. In those patients who developed peritonitis, subject-specific peritonitis incidence was inversely correlated with patient age ( r = –0.42, p < 0.05) and duration of chronic PD at last observation ( r = –0.42, p < 0.05).

♦ Conclusions

Since the distribution of peritonitis in children is non-Gaussian, the average risk of peritonitis is more accurately expressed by the median of the individual subject-specific peritonitis rates or by the mean incidence estimate obtained by the negative binomial distribution model. The assignment of a personal peritonitis risk to each patient permits risk factor analysis by routine statistical methods, even in smaller populations.
By Reducing Production of Vascular Endothelial Growth Factor Octreotide Improves the Peritoneal Vascular Alterations Induced by Hypertonic Peritoneal Dialysis Solution
Authors: Günal Ali Ihsan , Celiker Hüseyin , Akpolat Nusret , Üstündag Bilal , Duman Soner , Akcicek Fehmi
Published: February 2020

Objective

Chronic peritoneal dialysis (PD) may eventually result in vascular alterations of varying degree, which lead to progressive reduction in dialytic efficacy. Although the pathogenesis has not been elucidated yet, vascular endothelial growth factor (VEGF) has been proposed to play a central role in the process leading to vascular alterations.

Design

Rats were allocated to three groups: no treatment, intraperitoneal introduction of hypertonic PD solution alone, and intraperitoneal introduction of hypertonic PD solution plus octreotide. After 4 weeks, a 1-hour peritoneal equilibration test (PET) was performed. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D1/D0 glucose), ultrafiltration volume (UF), and levels of dialysate protein and VEGF were determined. Peritoneal membrane histology was evaluated by light microscopy.

Results

Compared with the control group, rats treated with hypertonic PD solution showed dramatically deranged peritoneal function tests (UF: 5.8 ± 0.9 mL vs 1.3 ± 0.6 mL; D/P urea: 0.49 ± 0.1 vs 0.74 ± 0.04; D1/D0 glucose: 0.55 ± 0.05 vs 0.34 ± 0.06) and morphology (thickness: 4.6 ± 0.4 μ vs 62 ± 12 μ; neovascularisation: 0.1 ± 0.3 vessels per field vs 2.2 ± 0.3 vessels per field). Similarly, a higher level of VEGF was found in the rats treated with hypertonic PD solution. In rats treated with hypertonic solution plus octreotide, peritoneal thickness was not completely reduced (25 ± 5 μ), but peritoneal functions were protected (UF: 4.0 ± 0.5 mL; D/P urea: 0.58 ± 0.02; D1/D0 glucose: 0.51 ± 0.02). Moreover, VEGF level and neoangiogenesis were significantly less in the octreotide group than in the group treated with hypertonic dextrose alone.

Conclusion

Our data document that, by increasing the production of VEGF, a high glucose concentration can cause vascular alterations within the peritoneal membrane. Octreotide can protect against the vascular alterations and preserve peritoneal function by inhibiting overexpression of VEGF and regulating the inflammatory response in the peritoneum.
Challenging the Current Treatment Paradigm for Methicillin-Resistant Staphylococcus Epidermidis Peritonitis in Peritoneal Dialysis Patients
Authors: Ariano Robert E. , Franczuk Christine , Fine Adrian , Harding Godfrey K.M. , Zelenitsky Sheryl A.
Published: February 2020

Objectives

To analyze clinical outcomes of Staphylococcus epidermidis peritoneal dialysis peritonitis before and after an interventional switch from a vancomycin/tobramycin to a cefazolin/tobramycin regimen for empiric treatment. To examine risk factors associated with clinical failure.

Design

A retrospective study.

Setting

A peritoneal dialysis program within a university-affiliated tertiary-care hospital.

Patients

93 episodes of S. epidermidis peritonitis over a 6-year period.

Interventions

Clinical responses were compared between treatments using chi-square or Fisher's exact test. Univariate and multivariate analyses were used to identify significant risk factors for clinical failure.

Measurements and Main Results

There was no difference in the overall response rates observed with vancomycin (40/49; 81.6%) and cefazolin (23/29; 79.3%) regimens for episodes of S. epidermidis peritonitis. Furthermore, the presence of methicillin resistance in 63 of 93 cases (67.7%) had no influence on clinical outcome, with response rates of 83.9% (26/31) and 82.4% (14/17) for empiric vancomycin and cefazolin regimens, respectively. Tobramycin therapy of less than 2 days was an independent risk factor for clinical failure in multivariate logistic regression analysis (odds ratio 4.44, 95% confidence interval 1.28 – 15.48; p = 0.02).

Conclusions

Empiric treatment with intraperitoneal cefazolin was as effective as vancomycin for S. epidermidis peritonitis despite a high prevalence of methicillin resistance. Tobramycin therapy of less than 2 days was strongly associated with treatment failure.
Comparison of a 2.5% and a 4.25% Dextrose Peritoneal Equilibration Test
Authors: Pride Eric T. , Gustafson Joan , Graham Angie , Spainhour Linda , Mauck Vicki , Brown Paige , Burkart John M.
Published: February 2020

Background

Ultrafiltration (UF) failure develops over time in some patients on peritoneal dialysis. The workup of UF failure can be difficult and the 4.25% peritoneal equilibration test (PET) has been suggested to be more useful than the 2.5% PET for the workup of UF failure. It is unknown how a 4.25% PET compares to a 2.5% PET in individual patients.

Objectives

To assess the differences in drain volumes and sodium sieving using a 4.25% PET compared to a 2.5% PET, and to determine whether peritoneal transport rates, in terms of dialysate-to-plasma (D/P) ratios, are comparable between the two.

Design

Pilot study with each patient serving as his or her own control.

Setting

Outpatient dialysis facility of Wake Forest University Baptist Medical Center.

Patients

47 patients, all of whom had a 2.5% PET and a 4.25% PET performed within 1 week of each other.

Outcome Measures

Dialysate-to-plasma ratios of urea and creatinine, dialysate total protein, and dialysate glucose compared to time zero (D/D0) at 0, 2, and 4 hours. Four-hour drain volumes and sodium sieving at 2 hours were also measured.

Results

There was reproducibility between the 2.5% and 4.25% PET for D/P ratios of urea and creatinine and for dialysate total protein. There were expected differences in drain volume, sodium sieving, and D/D0 glucose between the two methods.

Conclusions

The use of a 4.25% PET may be more useful for the workup of UF failure because of the accentuation of drain volume and sodium sieving, while remaining useful for prescription management.
Metallothionein and Dendritic Cells in Skin of End-Stage Renal Disease Patients not on Dialysis, or on Hemodialysis or Peritoneal Dialysis
Authors: Alscher Dominik M. , Bruckner Andreas , Fritz Peter , Kimmel Martin , Stoeltzing Hartmut , Kuhlmann Ulrich , Mettang Thomas
Published: February 2020

♦ Objective

Renal failure leads to a variety of defects in immune function. The skin, as a major player in the immune system network, also exhibits multiple derangements. The pathogenesis of these defects and derangements are poorly understood; therefore, we studied immune competent cells, dermal dendrocytes (DC), and a special proinflammatory protein, metallothionein (MT), in the skin of these patients.

♦ Design

22 patients with end-stage renal disease (ESRD) but not on dialysis, 18 patients on hemodialysis (HD), 14 patients on peritoneal dialysis (PD), and 35 healthy controls were included in the study. Immunohistochemical staining of skin biopsies for DC and MT was performed with the following antibodies: for DC, antibody against factor XIIIa; and for MT, Dako-MT, E9 (Dako, Carpinteria, California, USA). Measurements were made by counting stained DC per square millimeter, and by optical density (OD) for MT (mean ± SEM).

♦ Results

Metallothionein was increased in the skin of HD (OD 0.42 ± 0.05, p < 0.01) and PD patients (OD 0.33 ± 0.04, p < 0.05) compared to controls (OD 0.23 ± 0.02) and ESRD patients not on dialysis (OD 0.22 ± 0.05). In contrast, numbers of DC were reduced in patients on PD compared to controls (59 ± 13 vs 96 ± 59 DC/mm2, p < 0.01) and increased in patients with ESRD prior to dialysis (141 ± 13 DC/mm2, p < 0.05). Patients on HD were in-between (105 ± 20 DC/mm2), with a significant difference versus patients on PD ( p < 0.05).

♦ Conclusions

Our data show that the mode of dialysis influences the number of antigen-presenting cells in the dermis. However, in both dialysis modes, a proinflammatory immune status of the skin (MT) was present and, therefore, other regulatory elements for dermal dendrocytes apart from proinflammation exist.
Clinical outcomes and Quality of Life in Elderly Patients on Peritoneal Dialysis versus Hemodialysis
Authors:   for the North Thames Dialysis Study (NTDS) Group, Harris Susan A.C. , Lamping Donna L. , Brown Edwina A. , Constantinovici Niculae
Published: February 2020

♦ Objective

To compare clinical outcomes and quality of life (QOL) in elderly patients on peritoneal dialysis (PD) and hemodialysis (HD) in the North Thames Dialysis Study.

♦ Design

A 12-month prospective cohort study.

♦ Setting

Four hospital-based renal units in London, UK.

♦ Patients

174 patients that were 70 years or older at the start of dialysis, separated into two cohorts: 78 new patients (36 PD, 42 HD) that were recruited after 90 days of chronic dialysis; and 96 stock patients (42 PD, 54 HD) that were already on dialysis during the recruitment period.

♦ Main Outcome Measures

12-month survival and hospitalization rate, and QOL assessed at baseline and at 6 and 12 months by the SF-36 and the Symptoms/Problems scale of the Kidney Disease Quality of Life Questionnaire (KDQOL).

♦ Results

Peritoneal dialysis and HD patients were similar for sociodemographic and clinical characteristics. Annual mortality and hospitalization rates in PD versus HD patients were 26.1 versus 26.4 deaths/100 person–years and 1.9 versus 2.0 admissions/person–year, respectively. Adjusted relative risks showed no effect of modality on clinical outcomes. Multiple linear regression analyses of QOL at baseline showed similar SF-36 scores between PD and HD patients, but higher KDQOL scores in PD patients (3.5 points higher, 95% confidence interval 0.3 – 6.6). There was, however, no effect of dialysis modality on QOL at 6 or 12 months.

♦ Conclusions

Clinical outcomes and QOL are similar in elderly people on PD and HD. Peritoneal dialysis is a viable option for more than a carefully selected minority of elderly people requiring dialysis.
Apolipoprotein(a) Phenotype and Lipoprotein(a) Level Predict Peritoneal Dialysis Patient Mortality
Authors: Iliescu Eduard A. , Marcovina Santica M. , Morton Alexander R. , Lam Miu , Koschinsky Marlys L.
Published: February 2020

♦ Objective

To examine the associations between lipoprotein(a) [Lp(a)] level, apolipoprotein(a) [apo(a)] phenotype, and patient mortality in peritoneal dialysis (PD) patients.

♦ Design

Observational prospective study of prevalent PD patients.

♦ Setting

Tertiary-care health sciences center.

♦ Patients

54 prevalent PD patients were followed prospectively for 24 months.

♦ Main Outcome Measures

The exposures were Lp(a) level and apo(a) phenotype, designated by the apo(a) isoform size (number of kringle 4 repeats). Outcome was death from any cause.

♦ Results

There were 24 deaths in 77.9 patient–years’ follow-up. The independent predictors of death in the multivariate survival analysis were age [relative risk (RR) = 1.03, p = 0.23], diabetes (RR = 3.00, p = 0.03), diastolic blood pressure ≤ 70 mmHg (RR = 2.94, p = 0.03), serum albumin (RR = 0.87, p < 0.01), and Lp(a) level (RR = 1.004, p < 0.01). There was strong inverse correlation of Lp(a) with apo(a) isoform size ( r = –0.62, p < 0.01). With Lp(a) removed from the model, apo(a) isoform size was a significant predictor of death (RR = 0.91, p = 0.0497).

♦ Conclusions

Lipoprotein(a) level and apo(a) phenotype are associated with PD patient mortality. Measurement of Lp(a) level and apo(a) phenotype may be useful in clinical practice to identify patients at high risk for cardiovascular disease. Large prospective studies are needed to determine if a reversal of the increase in Lp(a) level associated with renal disease and dialysis is feasible and beneficial in reducing the risk of cardiovascular disease and mortality.
The Effects of Heparin Administration in an Animal Model of Chronic Peritoneal Dialysate Exposure
Authors: De Vriese An S. , Mortier Siska , Cornelissen Maria , Palmans Els , Vanacker Nele J. , Leyssens Anne , Faict Dirk , De Ridder Leo , Lameire Norbert H.
Published: February 2020

Diverse modes of heparin administration have been used in animal models of chronic peritoneal dialysate exposure to maintain catheter patency and prevent fibrinous adhesions. Heparin has biological actions independent of its well-known anticoagulant activity, including the ability to modulate extracellular matrix synthesis, cellular proliferation, angiogenesis, and inflammation. These actions may interfere with peritoneal membrane homeostasis. The present study evaluated the influence of the mode of heparin administration on technique survival and infection rate in a rat model of chronic dialysate exposure. Further, the incorporation of heparin in the peritoneal membrane was examined.

A 3.86% glucose dialysate was injected twice daily into Wistar rats with a heparin-coated catheter (group A1), or with a standard catheter with heparin injections during the entire exposure time (group A2) or only during 1 week (group A3). Sham manipulations were performed in a fourth group and a fifth group was left untreated. Technique survival was 80% in group A1, 60% in group A2, and 40% in group A3. The rate of infection was highest in group A1 and lowest in group A2. Intraperitoneally administered heparin accumulated in the peritoneal membrane, whereas dextran, with a molecular weight similar to that of heparin, was not incorporated in the peritoneum.

In conclusion, intraperitoneal heparin reduced the incidence of infection in an animal model of chronic dialysate exposure. The best technique survival was, however, obtained using a heparin-coated catheter. Heparin is incorporated in the peritoneal membrane, where it may exert diverse biological actions and thus bias study results. The use of a heparin-coated catheter in combination with antibiotics may be the optimal approach to obtaining peritoneal access in animal models of chronic dialysate exposure.
Increased Leukocyte Rolling in Newly Formed Mesenteric Vessels in the Rat during Peritoneal Dialysis
Authors: Zareie Mohammad , Van Lambalgen Anton A. , De Vriese An S. , Van Gelderop Edwin , Lameire Norbert , Ter Wee Piet M. , Beelen Robert H.J. , van den Born Jacob , Tangelder Geert-Jan
Published: February 2020

Objective

Long-term peritoneal dialysis (PD) is associated with the development of functional and structural alterations of the peritoneal membrane. The present study reports the effects of chronic exposure to PD fluid on mesenteric leukocyte–endothelium interactions, using intravital video microscopy.

Methods

Rats ( n = 7) received 10 mL lactate-buffered 3.86% glucose-containing PD fluid daily during a 5-week period via a subcutaneously implanted mini access port that was connected via a catheter to the peritoneal cavity. In a first control group ( n = 8), catheters were implanted but no fluid was instilled; a second control group ( n = 8) remained untreated. The number of rolling and adherent leukocytes as well as blood flow and other fluid dynamic variables were analyzed in mesenteric postcapillary (diameter 10 – 25 μ) and collecting (diameter 26 – 40 μ) venules. Neovascularization was semiquantitatively assessed after inspection of video images and by light and electron microscopy. Using FITC-labeled albumin, microvascular leakage was examined.

Results

Rats exposed to PD fluid showed a more than twofold increase in the number of rolling leukocytes ( p < 0.01); the number of adherent leukocytes was not changed. Furthermore, exposure to PD fluid induced severe neovascularization in rat mesentery. No microvascular leakage was observed in the various groups. The observed differences could not be explained by differences in systemic or local hemodynamic parameters or peripheral leukocyte counts, but is most likely associated with new vessel formation.

Conclusions

Exposure of rat peritoneal membrane to conventional PD fluid for 5 weeks affected local leukocyte–endothelium interactions. In addition, severe angiogenesis was induced, whereas microvascular permeability remained unaltered.
Spatial Distribution of Dialysate in Patients and its Implications to Intradialysate Diffusion
Authors: Hills Brian A. , Birch Seamus , Burke John R. , LaMont Anthony C.
Published: February 2020

Objective

To visualize and quantify the spatial distribution of dialysate in patients on continuous ambulatory peritoneal dialysis (CAPD) and, hence, estimate diffusion times for fluid “pockets” wherever intradialysate concentration gradients may not be dissipated by convective currents.

Design

Contrast medium was added to the dialysate of three supine CAPD patients before an exchange prior to computed tomographic (CT) scanning. Spatial information in the CT scanner was then downloaded to other computers and processed to produce impressive three-dimensional models of dialysate distribution using “wire frame technology.”

Results

Models differed between patients but all demonstrated pooling of dialysate in the paracolic gutters, subphrenic space, and, especially, in the pelvic cavity. Some pockets of fluid were almost isolated. Quantitatively, the models can account for over 80% of the volume of the exchange (2.5 L), displaying an effective area of contact of 913 – 1450 cm2 between parietal peritoneum and dialysate. This amounts to only 11% – 21% of the anatomic area, again emphasizing the uneven distribution of dialysate. Ignoring very thin (< 0.1 mm) films of dialysate, the bulk (80%) had mean thicknesses ranging from 1.6 to 1.9 cm. Transcendental equations for bulk diffusion were then applied to these findings to determine a theoretical time for urea of about 2 – 3 hours to half-saturation, or 5 – 7 hours to 80% saturation, in the absence of convective currents.

Conclusions

The distribution of dialysate within the peritoneal cavity is very uneven, resulting in long diffusion times in fluid pockets wherever convective currents may be minimal. Hence, intradialysate diffusion should not be ignored when modeling peritoneal dialysis.
The Association of Peritoneal Transport Properties with 24-Hour Blood Pressure Levels in Capd Patients
Authors: Tonbul Zeki , Altintepe Lutfullah , Sözlü Çetin , Yeksan Mehdi , Yildiz Alaattin , Türk Süleyman
Published: February 2020

← Objectives

We aimed to investigate the effects of peritoneal transport characteristics on blood pressure (BP) parameters, measured by 24-hour ambulatory blood pressure monitoring (ABPM), and on the development of left ventricular hypertrophy (LVH) in continuous ambulatory peritoneal dialysis (CAPD) patients.

← Design

Cross-sectional and prospective design.

← Setting

Tertiary-care center.

← Patients

25 CAPD patients (11 male, 14 female; mean age 47 ± 14 years) were included. Mean time on CAPD was 22.9 ± 18 months and all patients had been dialyzed for more than 6 months. The patients were divided into high, high-average, low-average, and low transport groups according to peritoneal equilibration test results.

← Main Outcome Measures

Daytime and nighttime systolic and diastolic BP and left ventricular mass index among the different peritoneal transport groups; changes in BP parameters before and after increase in ultrafiltration.

← Results

On 24-hour ABPM records, 13 patients (52%) were found to be hypertensive. Both mean systolic and diastolic BP were significantly increased in high-transporter groups compared to low transporters in both daytime and nighttime BP parameters. Left ventricular mass index was higher in high transporters compared to low transporters, without reaching statistical significance: 160 ± 23 vs 119 ± 41 g/m2, p > 0.05. Following increase in ultrafiltration, mean systolic (145 ± 13 vs 128 ± 5 mmHg, p < 0.001) and diastolic (96 ± 10 vs 81 ± 3 mm Hg, p < 0.001) BP decreased, and BP levels returned to normotensive levels in 6 (46%) of the 13 hypertensive patients, requiring discontinuation of antihypertensive drugs.

← Conclusion

Improvement in volume status resulted in a decrease in both daytime and nighttime BP. Differences in peritoneal transport properties were associated with the development of hypertension and LVH.