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PubMed2000

Newer peritoneal dialysis solutions.

Currently available peritoneal dialysis (PD) solutions provide for adequate removal of metabolic waste and manage fluid and electrolyte imbalances. They are, however, bioincompatible and do lead to peritoneal membrane changes with long-term use. Glucose is now strongly implicated in this. Newer solutions (icodextrin, bicarbonate, those with reduced glucose degradation products, amino acids) provide for greater biocompatibility and also address the question of fluid removal and retention. The future of PD solutions lies in combinations and additives.

Dialysis Solutions↗

PubMed2001

Vascular endothelial growth factor in peritoneal dialysis: a longitudinal follow-up.

In a previous study, vascular endothelial growth factor (VEGF) was found to be locally produced in the peritoneal tissue of patients undergoing peritoneal dialysis (PD) who were being treated with glucose-containing PD solutions. Locally produced VEGF (LVEGF) was positively related to the mass transfer area coefficient (MTAC) of creatinine and to glucose absorption, both of which are representative of the peritoneal vascular surface area. It was therefore hypothesized that VEGF is involved in the peritoneal neoangiogenesis found in long-term PD. The aim of the present study was to investigate the time course of peritoneal VEGF levels in PD patients treated with glucose-based PD solutions during longitudinal follow-up. We also studied the effect of the switch to glucose-free PD treatment on VEGF production. Forty standard peritoneal permeability analyses (SPAs) with 3.86% glucose-containing dialysis solution were investigated. The SPAs were performed in 10 PD patients with a median number of three SPAs per patient during a follow-up of 23 months. Duration of PD treatment at the last SPA was 74 months. All patients were initially treated with glucose-containing dialysis solutions. Four patients switched after 114 months of glucose-based PD to glucose-free PD and were followed for 7 months. A PD regimen of icodextrin, glycerol, and amino acid-based dialysis solutions was applied in these patients. Four SPAs were performed per patient in this period. To predict the VEGF dialysate-to-serum ratio (D/S), when diffusion would be the only explanation for the VEGF dialysate concentration, we calculated the power relationship between D/S ratios of serum proteins that are only transported across the peritoneum and the molecular weights of those proteins. The measured VEGF D/S ratio was higher than expected (P <.001) in each observation, pointing to local production of VEGF. LVEGF increased with duration of glucose PD, 11.7 ng/L to 23.45 ng/L (P <.03). LVEGF decreased in all 4 patients undergoing glucose-free PD, from 57.35 ng/L to 23.10 ng/L. A correlation (r = 0.83, P <.001) was found be-tween the differences in MTAC creatinine between the first and last SPA during glucose-based PD and the difference in LVEGF between these observations. A similar correlation was present between the difference in glucose absorption and the difference in LVEGF (r = 0.85, P <.001). This supports a pathogenetic role of high glucose dialysate concentrations in the development of changes in the peritoneum that are found in long-term PD. Treatment with non-glucose-based PD solutions may inhibit further development of these alterations.

Amino Acids↗

PubMed2003

Survival of functionally anuric patients on automated peritoneal dialysis: the European APD Outcome Study.

The European APD Outcome Study (EAPOS) is a 2-yr, prospective, multicenter study of the feasibility and clinical outcomes of automated peritoneal dialysis (APD) in anuric patients. A total of 177 patients were enrolled with a median age of 54 yr (range, 21 to 91 yr). Previous median total time on dialysis was 38 mo (range, 1.6 to 259 mo), and 36% of patients had previously been on hemodialysis for >90 d. Diabetes and cardiovascular disease were present in 17% and 46% of patients, respectively. The APD prescription was adjusted at physician discretion to aim for creatinine clearance (Ccrea) >/=60 L/wk per 1.73 m(2) and ultrafiltration (UF) >/=750 ml/24 h during the first 6 mo. Baseline solute transport status (D/P) was determined by peritoneal equilibration test. At 1 yr, 78% and 74% achieved Ccrea and UF targets, respectively; median drained dialysate volume was 16.2 L/24 h with 50% of patients using icodextrin. Baseline D/P was not related to UF achieved at 1 yr. At 2 yr, patient survival was 78% and technique survival was 62%. Baseline predictors of poor survival were age (>65 yr; P = 0.006), nutritional status (Subjective Global Assessment grade C; P = 0.009), diabetic status (P = 0.008), and UF (<750 ml/24 h; P = 0.047). Time-averaged analyses showed that age, Subjective Global Assessment grade C and diabetic status predicted patient survival with UF the next most significant variable (risk ratio, 0.5/L per d; P = 0.097). Baseline Ccrea, time-averaged Ccrea, and baseline D/P had no effect on patient or technique survival. This study shows that anuric patients can successfully use APD. Baseline UF, not Ccrea or membrane permeability, is associated with patient survival.

Adult↗

PubMed2005

Renal replacement therapy and acute renal failure.

PURPOSE OF REVIEW: Acute renal failure (ARF) is a syndrome that occurs when there is a sudden decline in the glomerular filtration rate. The purpose of this review is to examine new developments and clinical applications of renal replacement therapies including hemodialysis, continuous renal replacement therapy, the bioartificial kidney, and peritoneal dialysis in the management of this complicated syndrome. RECENT FINDINGS: New developments in hemodialysis include in-line hematocrit monitoring and improved biocompatible dialyzer membranes. While recent studies indicate that increased delivery of dialysis improves the outcome of patients with ARF, the optimal regimen of intermittent dialysis or continuous renal replacement therapy remains to be determined. The bioartificial kidney, combining hemofiltration with a device containing human tubular cells, is currently in clinical trials and represents another alternative in the management of ARF. In peritoneal dialysis, new solutions using icodextrin may improve fluid removal and blood pressure. SUMMARY: The optimal choice of renal replacement therapy depends on many factors. Use of new options in renal replacement therapy and early initiation of dialysis may help to improve survival and outcome of patients with ARF.

Acute Kidney Injury↗

PubMed2006

Effect of PD solutions on patient outcome.

With the recognition of the bio-incompatibility of conventional glucose based peritoneal dialysate (PDF), many new PDF has been developed and commercially available. All of them contain much less low glucose degradation product (GDP) solutions. Additional features are neutral or physiological pH, or glucose replaced by amino acid or glucose polymer icodextrin. These fluid has been shown to be more biocompatible in in-vitro and animal studies. There are short term randomized studies showing some benefit in certain clinical criteria, like increase in CA 125 in effluent PDF, better preservation of residual renal function, nutritional status, fluid and cardiovascular status, but beneficial effect on patient survival and long term peritoneal function has not been demonstrated apart from a non-randomized cohort study. To show such benefit on patient outcome, long term prospective randomized study is needed.

Dialysis Solutions↗

PubMed2006

Dry body weight: water and sodium removal targets in PD.

BACKGROUND/AIMS: Cardiovascular mortality is high in peritoneal dialysis patients. This may be due to the presence of hypertension and fluid overload. Dietary intake of water and sodium are likely to be important, especially in anuric patients. METHODS: A review of the literature on assessment of fluid status, and on peritoneal removal of water and sodium. RESULTS: MF-BIA added to clinical judgement is helpful for the assessment of fluid status. Natriuretic hormones in patients without heart failure are promising, but their value in clinical practice has not been established yet. Peritoneal ultrafiltration and sodium removal in anuric peritoneal dialysis patients are associated with survival. APD patients have lower sodium removal than CAPD, icodextrin increases it. The value of routine use of low sodium dialysis solutions has not been established. Definite targets on fluid and sodium removal have not been established, but the maintenance of euvalemia, while reducing the exposure to 3.86% glucose solutions at the same time, is largely facilitated by dietary salt and water restrictions. CONCLUSION: MF-BIA is a useful addition to clinical judgement of hydration status. The use of high dose loop diuretics facilitates water and salt removal in the presence of residual renal function. A dietary salt restriction of 4 g/day in anuric patients improves hypertension and is likely to reduce fluid intake.

Body Water↗

PubMed2006

Is there a competition between urine volume and peritoneal ultrafiltration in peritoneal dialysis patients?

Many peritoneal dialysis patients are overhydrated. Overhydration may lead to hypertension and left ventricular hypertrophy, and may be related to inflammation and malnutrition. The presence of overhydration is not always detected by clinical examination. Especially patients with peritoneal ultrafiltration failure and/or negligible residual renal function are prone to overhydration. Treatment consists of a combination of sodium and fluid restriction, in combination with increased peritoneal ultrafiltration and loop diuretics in patients with residual diuresis. Peritoneal ultrafiltration can be enhanced by the use of hypertonic glucose solutions or icodextrin. In some, but not all, studies, residual renal function or diuresis declined with an increase in peritoneal ultrafiltration. At least in a subset of patients, underhydration might have played a role in this phenomenon. We propose to treat overhydration using both clinical criteria and objective techniques such as vena cava echography or bioimpedance measurements.

Body Water↗

PubMed2005

A short review of experimental peritoneal sclerosis: from mice to men.

Peritoneal sclerosis has been induced in rodents in vivo by exposing the membrane to a variety of experimental interventions: asbestos, 0.1% chlorexidine, iron dextran, glucose degradation products, AGE deposits derived from uremia per se, sodium hypochlorite, lypopolysaccharide, low pH, pure water, silica or zymosan. With a few exceptions (pure water, chlorhexidine and low pH), the other substances mentioned operate setting out different degrees of oxidative stress. This short review describes several experimental interventions in rodents, aimed at acute exfoliation or long-term, sustained injury of the mesothelial monolayer performed by means of intraperitoneal injections of different oxidant agents. Acute exfoliation induced by deoxycholate resulted in a depopulated monolayer coincident with immediate alteration of the peritoneal permeability, evidenced by increased urea D/P ratio, higher glucose absorption rate, elevated albumin losses in the effluent and significant reduction of the ultrafiltration rate. In the long term (30 days), these manifestations of membrane failure persisted and coincided with substantial peritoneal sclerosis. Peritoneal sclerosis was also induced by IP injections of 0.125% trypsin and 6.6 mM/L solution of formaldehyde. Using the doughnut rat model of mesothelial regeneration, exposure to 4.25% glucose or 7.5% icodextrin solutions severely hampered repopulation of the monolayer, which was replaced by a thick sheet of fibrous tissue. It is concluded that peritoneal sclerosis derives mostly from sustained oxidative injury to the peritoneal membrane. Loss of the mesothelial monolayer is the first step in the chain of events leading to this complication.

Animals↗

PubMedDate not supplied

Intraperitoneal chemotherapy: a prolonged infusion of 5-fluorouracil using a novel carrier solution.

A novel carrier solution, icodextrin 20 (7.5%) has allowed exploration of prolonged intraperitoneal (IP) infusion of the cytotoxic drug, 5-fluorouracil. Eighteen patients with intraperitoneal carcinomatosis were entered into a feasibility and pharmacokinetic study of prolonged regional (IP) chemotherapy.. Specialist nurses trained the patients to self-administer their own treatment via a permanent i.p. catheter. A twin bag delivery system was used to perform one exchange daily. It proved possible to deliver continuous (5 days per week) i.p. 5-fluorouracil at doses of 200 mg/m2 and 300 mg/m2 for up to 12 weeks. The toxicities seen were infective peritonitis, nausea and vomiting, lethargy and anorexia. This was a nurse-led study and the home-based therapy holds promise for patients with malignant peritoneal disease.

Adult↗

PubMedDate not supplied

New drugs of 2003.

OBJECTIVES: To provide information regarding the most important properties of the new therapeutic agents marketed in 2003. DATA SOURCES: Product labeling supplemented selectively with published studies and drug information reference sources. STUDY SELECTION: By the author. DATA EXTRACTION: By the author. DATA SYNTHESIS: The 28 new therapeutic agents marketed in the United States during 2003 are reviewed in this article: adalimumab, agalsidase beta, alefacept, alfuzosin hydrochloride, aprepitant, atazanavir sulfate, atomoxetine hydrochloride, bortezomib, daptomycin, efalizumab, eletriptan hydrobromide, emtricitabine, enfuvirtide, eplerenone, gefitinib, icodextrin, laronidase, memantine hydrochloride, mequinol/tretinoin, miglustat, nitazoxanide, omalizumab, palonosetron hydrochloride, pegvisomant, rosuvastatin calcium, tadalafil, tositumomab and iodine I 131 tositumomab, and vardenafil hydrochloride. Indications and information on dosage and administration for these agents are reviewed, as are the most important pharmacokinetic properties, adverse events, drug interactions, and other precautions. Practical considerations for the use of the new agents are also discussed. When possible, the properties of the new drugs are compared with those of older drugs marketed for the same indications. CONCLUSION: A number of the new therapeutic agents marketed in 2003 have important advantages over older medications. An understanding of the properties of these agents is important for the pharmacist to effectively counsel patients about their use and to serve as a valuable source of information for other health professionals regarding these drugs.

Drug Approval↗

PubMed1998

[Alternative dialysis solutions in continuous ambulatory peritoneal dialysis].

Not satisfactory enough long-term results of applying glucose in CAPD solutions as an osmotic agent were the reason of research on the alternative osmotic substances. The paper presents review of actually used solutions containing amino acids (Nutrineal) or polymer glucose (Icodextrin). The influence of these agents on metabolism of carbohydrate, lipids and nutrition of the organism as well as function and structure of peritoneum is reviewed and discussed.

Glucose↗

PubMed1999

Taking peritoneal dialysis beyond the year 2000.

Over the past 25 years, peritoneal dialysis (PD) has steadily improved so that now its outcomes, in the form of patient survival, are equivalent to, and at times better than, those for hemodialysis. We now have a better understanding of the pathophysiology of peritoneal membrane function and damage and the importance of appropriate prescription to meet agreed-upon targets of solute and fluid removal. In the next millennium, greater emphasis will be put on prescription setting and subsequent monitoring. This will entail an increase in automated PD, especially for lifestyle reasons as well as for patients with a hyperpermeable peritoneal membrane. To improve outcomes, dialysis should be started earlier than is currently the case. It is easy to do this with PD, where an incremental approach is made easier by the introduction of icodextrin for long-dwell PD. In the future, solutions will be tailored to be more biocompatible and to provide improved nutrition and better cardiovascular outcomes. Finally, economic considerations favor PD, which is cheaper than in-centre hemodialysis. Thus, for many, PD has become a first-choice therapy, and with further improvements this trend will continue.

Cost-Benefit Analysis↗

PubMed2001

Sclerosing encapsulating peritonitis: a case series from a single U.K. center during a 10-year period.

Sclerosing encapsulating peritonitis (SEP) is a serious complication of peritoneal dialysis (PD). Previous reports place the prevalence of SEP at 0.54%-7.3%. We estimated the prevalence of SEP in our unit to be 1.4% over the period 1989-1999. We here present the 6 identified cases. All of the patients presented with small-bowel obstruction; hemorrhagic ascites was identified in 3 cases. All 6 patients experienced ultrafiltration inadequacy, and 5 were treated with glucose polymer (icodextrin; duration of treatment: 1 month-2.5 years). Peritoneal dialysis was stopped at the time of diagnosis in 2 cases. In the other 4 cases, PD had been withdrawn some time prior to the SEP being diagnosed (2 weeks-5 years). Five of the patients have died; the 6th currently uses hemodialysis.

Adult↗

PubMed2001

Adequacy targets can be met in anuric patients by automated peritoneal dialysis: baseline data from EAPOS.

OBJECTIVE: Conventional continuous ambulatory peritoneal dialysis (CAPD) in patients without residual renal function and with high solute transport is associated with worse clinical outcomes. Automated peritoneal dialysis (APD) has the potential to improve both solute clearance and ultrafiltration in these circumstances, but its efficacy as a treatment modality is unknown. The European Automated Peritoneal Dialysis Outcomes Study (EAPOS) is a 2-year, prospective, European multicenter study designed to determine APD feasibility and clinical outcomes in anuric patients. The present article describes the baseline data for patients recruited into the study. DESIGN: All PD patients treated in the participating centers were screened for inclusion criteria [urinary output < 100 mL/24 h, or residual renal function (RRF) < 1 mL/min, or both]. After enrollment, changes were made to the dialysis prescription to achieve a weekly creatinine clearance above 60 L per 1.73 m2 and an ultrafiltration rate above 750 mL in 24 hours. SETTING: The study is being conducted in 26 dialysis centers in 13 European countries. BASELINE DATA COLLECTION: The information collected includes patient demographics, dialysis prescription, achieved weekly creatinine clearance, and 24-hour ultrafiltration (UF). RESULTS: The study enrolled 177 anuric patients. Median dialysis duration before enrollment was 22.5 months (range: 0-285 months). Mean solute transport measured as the dialysate-to-plasma ratio of creatinine (D/P(Cr)) was 0.74 +/- 0.12. Patients received APD for a median of 9.0 hours overnight (range: 7-12 hours) using a median of 11.0 L of fluid (range: 6-28.75 L). Median daytime volume was 4.0 L (range: 0.0-9.0 L). Tidal dialysis was used in 26 patients, and icodextrin in 86 patients. At baseline, before treatment optimization, the weekly mean total creatinine clearance was 65.2 +/- 14.4 L/1.73 m2, with 105 patients (60%) achieving the target of more than 60 L/1.73 m2. At baseline, 81% of patients with high transport, 69% with high-average transport, and 40% with low-average transport met the target. At baseline, 70% of patients with a body surface area (BSA) below 1.7 m2, 60% with a BSA of 1.7-2.0 m2, and 56% with a BSA above 2.0 m2 achieved 60 L/1.73 m2 weekly. Median UF was 1090 mL/24 h, and 75% of patients achieved the UF target of more than 750 mL/24 h. CONCLUSION: This baseline analysis of anuric patients recruited into the EAPOS study demonstrates that a high proportion of anuric patients on APD can achieve dialysis and ultrafiltration targets using a variety of regimes. This 2-year follow-up study aims to optimize APD prescription to reach predefined clearance and ultrafiltration targets, and to observe the resulting clinical outcomes.

Adult↗

PubMedDate not supplied

Influence of dialysate on gastric emptying time in peritoneal dialysis patients.

OBJECTIVE: Peritoneal dialysis (PD) patients frequently suffer from dyspeptic complaints such as nausea, vomiting, abdominal distension, early satiety, and anorexia. Gastroparesis might be, at least partially, a source of dyspeptic complaints in PD patients. The aim of the present study was to determine the influence of the presence and composition of dialysate on gastric emptying in PD patients. DESIGN: Prospective study. SETTING: Renal Division, Department of Internal Medicine, Ghent University Hospital, Belgium. PATIENTS: Sixty-one PD patients using different dialysate solutions, and 27 healthy volunteers. MAIN OUTCOME MEASURE: Gastric emptying of solids was assessed by the 13C-octanoic acid breath test. RESULTS: Gastric emptying was impaired in PD patients, regardless of the composition of dialysate and even if tested with an empty peritoneal cavity. Gastric emptying was significantly slower when glucose-containing dialysate was compared to an empty peritoneal cavity, or when glucose-containing dialysate was compared to icodextrin dialysate. No difference in gastric emptying could be demonstrated between glucose-containing dialysate and dialysate containing a mixture of glycerol and amino acids as osmotic agent. CONCLUSIONS: These findings suggest that the delay in gastric emptying demonstrated in the presence of peritoneal dialysate is not the consequence of a mere volume or pressure effect, but of the absorption of substrate substances with caloric and/or metabolic activity, such as glucose or glycerol and amino acids.

Adult↗

PubMedDate not supplied

Rapid diagnosis of peritonitis in peritoneal dialysis patients.

BACKGROUND: Peritonitis is the major complication of peritoneal dialysis (PD) and has acute morbidity and resources implications. Episodes of peritonitis are associated with higher risk of peritoneal membrane failure. Rapid diagnosis of peritonitis would allow early antibiotic commencement with potential benefits of reduced need for in-patient care and dialysis modality change. This study examined the utility of a rapid peritonitis diagnosis method (Periscreen). METHODS: This was a prospective study in a single unit and included all PD patients presenting with symptoms or signs of peritonitis over 12 months. In each clinical circumstance in which the diagnosis or exclusion of peritonitis was required and in follow-up peritonitis cases, PD fluid was sent for standard laboratory analysis but also tested using the Periscreen strip. The relationship between this rapid diagnostic strip and standard laboratory methods for determination of PD fluid neutrophil count was determined. RESULTS: This study found the Periscreen strip easy to use and interpret. All 17 episodes of peritonitis (defined by ISPD criteria) were detected and results of the strip correlated closely with the laboratory cell count. In this study sensitivity of the Periscreen was 100% and specificity was 98%, positive predictive value was 95.6% and negative predictive value was 100%. Results were equally good in glucose containing fluids and icodextrin. CONCLUSIONS: Periscreen is a sensitive, specific rapid tool for the presumptive diagnosis of peritonitis in PD patients used at the "point of care". Results correlated with the laboratory white cell count, a test that takes longer to perform. Widespread use in PD would aid in the early recognition and treatment of peritonitis.

Adult↗

PubMed2003

Incremental dialysis with automated peritoneal dialysis.

Since December 2000, we have proposed incremental dialysis to our patients with a glomerular filtration rate (GFR) of 8-9 mL/min/1.73 m2. The incremental dialysis uses automated peritoneal dialysis (APD) 3-4 days per week ["low frequency APD" (LF-APD)], with or without a full abdomen during the period between the nighttime sessions. From December 1, 2000, to September 30, 2001, LF-APD was selected by 5 patients (2 men, 3 women). Of the 5 patients, 4 worked (age: 53 +/- 12 years; range: 40-69 years), and 1 (age: 78 years) needed assistance from a partner who was available only on certain days of the week. Only 1 patient had diabetic nephropathy. The LF-APD was performed by 4 patients on alternate days ("standard LF-APD"), and by 1 patient 3 times per week (owing to limited availability of the partner). At the beginning of treatment, mean nightly LF-APD was 8.9 +/- 0.9 hours with a volume of 13.4 +/- 3.1 L. In 3 patients, icodextrin was used for the dwell between subsequent APD sessions (1-1.5 L). The other 2 patients kept an empty abdomen (owing to body image). Residual renal function (RRF) was measured every 3 months; adequacy and peritoneal equilibration test (PET), every 6 months. Total nightly APD volume was modified based on the results of the PET. At December 31, 2002, 3 patients with follow-ups of 25, 22, and 15 months were still on LF-APD because their GFR had remained unchanged. In another patient, the frequency of the APD sessions was increased after 5 months to 5 times per week from 3.5 times per week following a clinical assessment of underdialysis; however, that patient had had no significant change in GFR. Following a rapid decline in the diabetic patient's GFR (to 3.6 mL/min/1.73 m2 from 7.9 mL/min/1.73 m2 in 18 months) and refusal by that patient to increase the number of days of APD, the diabetic patient was transferred to hemodialysis. No episodes of peritonitis occurred in a total LF-APD follow-up of 84 patient-months. Compliance, assessed using the HomeChoice Pro system and comparing prescribed and recorded sessions, was total (no missed treatments). In conclusion, LF-APD can be a valid form of incremental dialysis and can help patients to choose PD as their first renal replacement therapy.

Adult↗

PubMed2004

Strategies for managing diabetic patients on peritoneal dialysis.

Failure of the pancreatic beta cells to produce insulin or development of defective molecular signaling of insulin to the peripheral tissue cells (insulin resistance) induces persistent hyperglycemia and accumulation of fatty acids in the blood of patients with diabetes. Over time, those changes lead to microvascular and macrovascular damage in various target organs. In patients on peritoneal dialysis (PD), complications may accelerate with treatment using conventional glucose-containing solutions. Strategies for proper glycemic control in diabetic PD patients are therefore essential to prevent complications and to maintain a good quality of life. Dietary restrictions and weight control remain the foundation of the management approach for glycemic control. Further therapeutic actions include the stepwise addition of oral hypoglycemic agents and insulin, based on individual assessment of PD patients. Other strategies of immediate importance in reducing hyperglycemia are to use PD exchanges with new non glucose PD solutions (such as those with icodextrin or amino acids) in combination with fewer daily exchanges of low-glucose solutions. Combined, these approaches will sufficiently control hyperglycemia in diabetic PD patients. Research is in progress to develop therapeutic agents aimed at correcting various molecular defects of insulin signaling or at reducing protein kinase C activation induced by oxidative stresses in various tissue cells. Clinical experience with the use of such agents in diabetic PD patients is limited at present.

Administration, Oral↗