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Introduction Preservation of peritoneal function is essential in long-term peritoneal dialysis. Biocompatible dialysis solutions might prevent or postpone the membrane alteration resulting in ultrafiltration failure and consecutive morbidity and mortality. Methods We conducted an observational cohort study in which we made a longitudinal comparison between the course of peritoneal solute and fluid transport during treatment with conventional and biocompatible solutions. Therefore, prospectively collected peritoneal transport data from the yearly standard peritoneal permeability analysis were analyzed in 251 incident patients treated between 1994 and censoring in 2016. Fluid transport included small pore and free water transport. Solute transport was assessed by creatinine mass transfer area coefficient and glucose absorption. Linear mixed models including change point analyses were performed. Interaction with peritonitis was examined. Results One hundred thirty-five patients received conventional and 116 biocompatible solutions. Sixty-seven percent (conventional) and 64% (biocompatible) of these underwent minimally three transport measurements. Initially, biocompatible fluids showed higher small solute transport and lower ultrafiltration than conventional fluids up to 3 years. Thereafter, conventional fluids showed an increase in small solute transport (+2.7 ml/min per year; 95% confidence interval [CI]: 0.9 to 4.5) and a decrease of free water transport (−28.0 ml/min per year; 95% CI: −60.4 to 4.4). These were minor or absent in biocompatible treatment. Peritonitis induced a decrease of transcapillary ultrafiltration after 2 years on dialysis with conventional solutions (−291 ml/min per year; 95% CI: −550 to −32) while this was absent in biocompatible treatment. Conclusion Despite a higher initial solute transport with biocompatible solutions, these have less influence on functional long-term peritoneal alterations than conventional solutions., Graphical abstract

Aim Approximately 40% of dialysis patients are durably treated with peritoneal dialysis (PD) in our teaching hospital. Patients' perspectives were studied by patient-reported outcome measurements (PROMs) to find possible explanations for why the generally-reported decline in the use of PD hardly occurred in our facility. Materials and methods All 75 prevalent adult dialysis patients hemodialysis (HD) duration 27, PD 16 months) were included. All had received predialysis care and education for > 6 month. Cross-sectional sociodemographic and clinical data, SF-36, KDQOL-SF, and predialysis anxiety/depression scores were collected in February 2016. Differences in PROMs between PD and HD patients were analyzed. Results Despite more comorbidity in the PD population, generally-used dialysis parameters were adequate and similar between HD (n = 42) and PD (n = 33) patients as was annual mortality. Many factors associated with a predialysis modality choice for PD were absent. A higher anxiety/depression score was found in pre-HD compared to pre-PD patients. PROMs were returned by 97%. PD patients performed better on a number of PROMs than their HD counterparts. Conclusion This single-center cross-section with a modest number of patients but an almost 100% patient response shows that having 40% of patients on PD is possible with excellent results in terms of patient-reported outcomes. A structured patient education with attention to personal needs of patients, an adequate infrastructure for PD, and a dedicated team with ongoing patient support are key factors. Sharing best practices may help to slow down or even reverse the decline of PD, which is a pity both for patients and society. .

SummaryWhether the risk of both venous and arterial thrombosis is increased in dialysis patients as compared to the general population is unknown. In addition, it is unknown which subgroups are at highest risk. Fur-thermore, it is unknown whether having a history of venous thrombosis or arterial thrombosis prior to dialysis treatment increases mortality risk. A total of 455 dialysis patients were followed for objectively verified symptomatic thrombotic events between January 1997 and June 2009. The incidence rates in dialysis patients as compared to the general population was 5.6-fold (95% CI 3.1–8.9) increased for venous thrombosis, 11.9-fold (95% CI 9.3–14.9) increased for myocardial infarction, and 8.4-fold (95% CI 5.7–11.5) increased for ischaemic stroke. The combination of haemodialysis, lowest tertile of albumin, history of venous thrombosis, and malignancy was associated with subsequent venous thrombosis. Increased age, renal vascular disease, diabetes, high cholesterol levels, history of venous thrombosis, and history of arterial thrombosis were associated with subsequent arterial thrombosis. The all-cause mortality risk was 1.9-fold (95% CI 1.1–3.3) increased for patients with a history of venous thrombosis and 1.9-fold (95% CI 1.4–2.6) increased for patients with a history of arterial thrombosis. A potential limitation of this study was that in some risk categories as-sociations with venous thrombosis did not reach statistical significance due to small numbers. In conclusion, dialysis patients have clearly elev-ated risks of venous thrombosis and arterial thrombosis and occurrence of venous thrombosis or arterial thrombosis prior to the start of dialysis is associated with an increased mortality risk.

Background/Aim: Anemia is associated with increased mortality and morbidity in both early and very late stages of chronic kidney disease (CKD). The aim of this study was to assess whether anemia is a risk factor for mortality or hospitalization in CKD stage 4–5 predialysis patients not yet on dialysis. Methods: Incident predialysis patients were included between 1999 and 2001 and followed until January 2008 or death. Anemia was defined as mean hemoglobin (Hb) ≤11 g/dl in the 3 months before the start of predialysis. Associations were assessed by Cox regression, linear and logistic regression analysis. Results: A total of 472 patients were included (median follow-up time 12 months, 11% died, 79% started dialysis). Mean Hb was 11.2 g/dl (minimum 7.6, maximum 16.9). Forty-eight percent of patients had anemia at the start of predialysis care. The adjusted mortality risk (hazard ratio, 95% confidence interval) for anemic compared to nonanemic patients was 1.92 (1.04, 3.52). Anemia tended to be related to all-cause but not to non-dialysis-related hospitalization risk. Conclusion: At the start of predialysis care, 48% of patients had anemia. Anemia as defined in guideline targets is not associated with an increase in hospitalizations not related to renal replacement therapy, but is likely an important risk factor for mortality in predialysis patients.

Background: Measuring GFR using exogenous markers without a bladder catheter, errors can be easily made due to incomplete urine collection. The aim was to quantify agreement for 125 I-iothalamate GFR measurements with and without a correction for inaccurate urine collection using 131 I-hippuran. Methods: The last available GFR measurement of adult patients was included. GFR was measured in two subsequent clearance periods with 125 I-iothalamate by the standard method with correction for inaccurate urine collections using 131 I-hippuran. The uncorrected and corrected GFR measurements were compared within and between the time periods for each individual patient. To study the agreement between both methods, intra-class correlation coefficients (ICC) were calculated and Bland-Altman plots, with accompanying accuracies and precisions, were used. Cohen's K was calculated to analyze the agreement of both methods for classifying patients according to the stages of chronic kidney disease (CKD). Results: For the 332 stable included patients, the mean GFR of the uncorrected measurements was 77.8 ml/min (34.7) and the mean GFR of the corrected measurements was 81.0 ml/min (34.9). The ICC was 0.80 for the uncorrected measurements with an accuracy of 7.3 ml/min and a precision of 21.7 ml/min. For the corrected GFR measurements the ICC was 0.98, with an accuracy of 2.1 ml/min and a precision of 6.5 ml/min. Comparison between the methods showed an ICC of 0.95, an accuracy of 3.2 and a precision of 11.0. In total, 86% of the patients were classified similarly into CKD stages with both methods, overall Co-hen's K was 0.81. Conclusion: Agreement was better for GFR measurements corrected for inaccurate urine collections. Therefore, GFR measurements with 125 I-iothalamate should be corrected for inaccurate urine collections using 131 I-hippuran. Without such correction the GFR is easily underestimated which may lead to overtreatment.

Chronic peritoneal dialysis (PD) can be complicated by encapsulating peritoneal sclerosis (EPS), a rare but the most severe complication associated with long-term PD. Morbidity and mortality are still high (range from 25% to 55%) especially in the first year after diagnosis. The international Society for Peritoneal Dialysis (ISPD) defined EPS by clinical signs of abdominal pain, bowel obstruction or weight loss in late stages of the disease. Clinical symptoms, radiologic findings and histologic criteria are the three diagnostic pillars.

Background: In evaluations of dialysis therapy, an assessment of health-related quality of life (HRQOL) is often important. The aim of this study was to determine the basic psychometric properties, reliability and validity of the short form of the KDQOLTM i.e. the KDQOL-SFTM, a dialysis-targeted instrument, and to assess its ability to detect changes over time. Methods: In a prospective cohort study (Netherlands Cooperative Study on the Adequacy of Dialysis, NECOSAD), all new adult ESRD patients in 32 different Dutch centers were consecutively enrolled. Demographic, clinical and HRQOL data were obtained 3 and 12 months after the start of chronic dialysis therapy. Results: The reliability of the KDQOL-SFTM was supported by test results that were above the recommended minimal values. Validity of KDQOL-SFTM was confirmed by the hypothesized positive correlations of the overall health rating and renal function, and by the negative correlations between the number of comorbidities and dialysis dose. Moreover, dialysis-targeted dimensions were more sensitive in detecting relevant differences pertaining to kidney diseases than generic dimensions. The KDQOL-SFTM was able to detect clinical changes over time. Conclusions: The psychometric properties of the KDQOL-SFTM were good, and the different dialysis-targeted dimensions were informative with a high reliability and validity. These results support the application of the KDQOL-SFTM in studies evaluating dialysis therapy.

Objective To assess employment status in new end-stage renal disease (ESRD) patients at the start of dialysis and after 1 year, and to determine whether demographic and clinical variables and physical and psychosocial functioning at the start of dialysis are risk factors for loss of employment after 1 year of dialysis. Design Prospective follow-up study in which 38 of 48 Dutch dialysis centers participate. Patients 659 patients who had started on dialysis and who were between 18 and 65 years old were included. Patients were re-examined after 12 months. Main Outcome Measures Demographic data, physical and psychosocial functioning with the Short-Form Health Survey (SF-36), and data on employment status were obtained using questionnaires. Nephrologists provided the clinical data. Results At the start of dialysis, 35% of patients were employed, in contrast to 61% of the general Dutch population. Within 1 year, the proportion of employed patients decreased from 31% to 25% of hemodialysis patients, and from 48% to 40% of peritoneal dialysis patients. In patients who were working at the start of dialysis, independent risk factors for loss of work within 1 year were impaired physical and psychosocial functioning [odds ratio physical: 3.4, 95% confidence interval (%CI), 1.0 – 11.2; odds ratio psychosocial: 4.2, 95% CI, 1.2 – 14.2]. Conclusions As the percentage of employed patients at the start of dialysis is about half the expected percent-age, loss of work is an important issue in both predialysis and dialysis patients. Improvements in physical and psychosocial functioning are potentially preventive of loss of work in patients who are employed when they start dialysis.

Human immunodeficiency virus-associated nephropathy (HIVAN) is a distinct clinico-pathological syndrome that occurs almost exclusively in black patients with an AIDS defining diagnosis. It is characterized by rapidly progressive renal failure with a severe nephrotic syndrome. The renal biopsy typically shows a collapsing glomerular sclerosis and variable tubulo-interstitial nephritis. The pathogenesis most likely involves infection of renal tubular and epithelial cells with HIV. The use of ACE-inhibitors and steroids may slow down the progression to end-stage renal failure. With the introduction of highly active anti-retroviral therapy, HIVAN may now be treated effectively although clinical data are so far limited to case-reports.

ObjectiveThis study reviews relevant publications on the peritoneal vasculature and tries to establish morphological–functional relationships.DesignThe design is a review article.ResultsRecent morphological studies in peritoneal dialysis (PD) patients have shown the presence of diabetiform neoangiogenesis in long-term peritoneal dialysis. The same abnormalities could be induced in rats administered a high glucose dialysis solution daily for 20 weeks. The animals showed functional abnormalities in peritoneal transport similar to those found in long-term PD patients. Evidence was obtained in patients that vascular endothelial growth factor could be involved in glucose-induced peritoneal neoangiogenesis.ConclusionsDiabetiform peritoneal neoangiogenesis is an important pathogenetic factor in ultrafiltration failure in long-term peritoneal dialysis patients.

Kemperman FAW, Weber JA, Gorgels J, van Zanten AP, Krediet RT, Arisz L (University of Amsterdam and Slotervaart Hospital, Amsterdam, The Netherlands). The influence of ketoacids on plasma creatinine assays in diabetic ketoacidosis. J Intern Med 2000; 248: 513–519. Objective. Analysis of the interference of ketoacids on various routine plasma creatinine assays during a clinical episode of diabetic ketoacidosis (DKA). Design. Observational study. Blood samples were drawn before, during and after standard in-hospital treatment. Plasma creatinine was measured with two dissimilar enzymatic assays (creatininase PAP + and creatinine iminohydrolase Serapak), a kinetic alkaline picrate method (Jaffe) and a high-performance liquid chromatography (HPLC) procedure. Acetoacetate and β-hydroxybutyrate were analysed by enzymatic methods. Setting. Department of Medicine, University Hospital. Subjects. Nine patients who experienced 10 episodes of DKA. Main outcome measures. Agreement of the routine plasma creatinine assays with HPLC and analysis of possible interferents. Results. At presentation, the Jaffe assay gave falsely high values of plasma creatinine (median 99 µmol L–1), in contrast to the PAP+ (median 60.5 µmol L–1) and HPLC assays (median 67.5 µmol L–1). This positive error decreased during treatment. This was due to a decrease in acetoacetate, as the positive error by the Jaffe method correlated with the acetoacetate concentration (r = 0.79, P

Objective To assess health-related quality of life (QL) in a group of Dutch predialysis end-stage renal disease (ESRD) patients prior to the initiation of dialysis, and to compare QL between patients with different intended initial dialysis treatments. Design In a prospective cohort study, demographic, clinical, and QL data were obtained from Dutch adult patients who were consecutively enrolled from 27 different centers 0 – 4 weeks prior to the beginning of their chronic dialysis treatment. Patients Of the 301 patients who completed the QL questionnaires (of a possible 337 enrolled patients), 152 intended to start with hemodialysis (pre-HD) and 149 patients with peritoneal dialysis (pre-PD). Main Outcome Measure Perceived QL of pre-HD and pre-PD patients. Quality of life was assessed with two generic health assessment instruments: the SF-36 and the EuroQol. Results After correction for group differences, pre-HD patients scored consistently, but not significantly, lower for all separate dimensions of the SF-36 and the overall health score of the EuroQol compared to pre-PD patients. However, analyzing the dimensions of the SF-36 together, adjusted for case-mix, pre-HD patients scored significantly lower than pre-PD patients. Mean difference was 6.5 points ( p = 0.04). Conclusion Multivariate adjustment for known case-mix differences at the start of dialysis therapy was not sufficient to adjust for all patient selection effects on QL. Consequently, published QL comparisons between HD and PD in nonrandomized cohort studies should be interpreted with caution. Assessment of QL just before start of dialysis therapy and subsequent adjustment for baseline values may be the only valid alternative for randomized studies.

Objective To analyze morphological changes in the peritoneum of peritoneal sclerosis (PS) patients. Emphasis was put on vascular abnormalities, because the continuous exposure to glucose-based dialysis solutions could cause diabetiform changes and because longitudinal transport studies suggested the development of a large peritoneal vascular surface area. Design Peritoneal biopsies from continuous ambulatory peritoneal dialysis (CAPD) patients were investigated in two studies. Diabetic patients were excluded. In study 1, 11 PS biopsies were compared to three control groups varying in duration of CAPD treatment: 0 months ( n = 15), 2 – 25 months ( n = 7), and > 25 months CAPD ( n = 7). The second study was a case-control study, comparing six biopsies from the long-term control group to six PS biopsies, matched for age and duration of CAPD. All biopsies were scored for presence and type of fibrosis [Picro Sirius red, type IV collagen, α-smooth muscle actin (αSMA)] and for neoangiogenesis (factor VIII). Thickening of vascular walls by type IV collagen and vasodilation of capillaries were measured by computer-aided planimetry. Results In study 1 the presence of sclerosing fibrosis, deposition of interstitial type IV collagen, and the number of myofibroblasts (αSMA-positive cells) was greater in the PS biopsies than biopsies from all control groups ( p < 0.002). Moreover, the number of vessels per field was higher in PS biopsies ( p < 0.01). Vascular wall thickening of small arteries ( p < 0.008) and vasodilation of capillaries were found in PS biopsies compared to all control groups ( p < 0.007). The second study revealed differences in the presence of sclerosis but not in the extent of fibrosis between PS biopsies and their controls. The number of vessels per field in PS biopsies was higher compared to controls ( p = 0.04). Also, thickening of the vascular wall was more marked in PS biopsies ( p = 0.03). Vasodilation of capillaries was greater in PS biopsies than in controls ( p = 0.07). Conclusion Fibrosis of the peritoneum may precede peritoneal sclerosis. The deposition of type IV collagen and the presence of myofibroblasts in the interstitial layer could be part of a pathologic process similar to the scarring in diabetic nephropathy. Neoangiogenesis and thickening of the vascular wall by type IV collagen are consistent with glucose-induced microangiopathy. These abnormalities and the vasodilation of the capillaries can explain the high dialysate-to-plasma ratios or mass transfer area coefficients of low molecular weight solutes that can be found in long-term CAPD patients.

Objective The development of an experimental peritoneal dialysis (PD) model in rabbits to investigate peritoneal transport characteristics during a longitudinal follow-up and to assess normal values of these peritoneal transport parameters. Design Peritoneal transport parameters were determined in conscious, unrestrained rabbits by standard peritoneal permeability analysis adjusted for rabbits (SPAR). In this test a 1-hour dwell with 3.86% glucose dialysate is used. Dextran 70 (1 g/L) was added to the dialysate to allow calculation of fluid kinetics. Dialysate samples were taken before, 10, and 40 minutes after instillation and at the end of the dwell. Blood was drawn at the end of the dwell. Experimental Animals Eighteen female New Zealand White rabbits (2565 g) were included for catheter implantation. SPARs were performed in 15 animals; the other 3 were excluded due to complications. Main Outcome The mass transfer area coefficients (MTACs) of the low molecular weight solutes urea (MTACurea) and creatinine (MTACcr) were calculated. The clearances of albumin (Clalb) and IgG (ClIgG), glucose absorption, and fluid transport were computed. Coefficients of intraindividual variation (Vc) were calculated for these parameters. Results The main complications were catheter obstruction and/or dislocation. Five rabbits underwent uncomplicated PD during a 4-week period. Fifteen SPARs in 15 stable rabbits were performed and analyzed to obtain normal values. Means and standard deviations of the transport parameters were as follows: MTACurea 2.24 ± 0.57 mL/min, MTACcr 1.61 ± 0.30 mL/min, Clalb 52.9 ± 17.2 μL/min, ClIgG 44.5 ± 22.9 μL/min. The transcapillary ultrafiltration rate was 0.66 ± 0.13 mL/min and the lymphatic absorption rate 0.47 ± 0.26 mL/min. The parameters of solute transport were upscaled to those in humans using two different methods. MTACs of low molecular weight solutes in rabbits and patients were of the same order of magnitude, but the clearance of albumin was approximately four times higher in rabbits than in patients, and that of IgG eight times. In all rabbits sieving of sodium was observed. The dialysate/plasma (D/P) of sodium decreased to a minimum at 40 min ( p < 0.003 vs the initial value), followed by a rise to 60 min. The minimal value was 0.884 ± 0.002. The coefficients of variation calculated on 7 rabbits that underwent two or more SPARs were similar to those assessed from the patient data. This indicates stability of the model and reproducibility of the SPAR. Conclusion The conscious rabbit model for PD can be used for repeated studies on peritoneal transport.

SummaryRecently we showed the in vivo relevance of chemokines in cases of bacterial peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients. Mesothelial cells, the most numerous cells in the peritoneal cavity, are hypothesized to function as a main source of chemokine production. We investigated the time- and dose-dependent expression patterns of four chemokines by mesothelial cells at the mRNA and protein level in response to stimulation with physiological doses of proinflammatory mediators that are present at the site of bacterial inflammation. Besides the chemokines huGRO-α (attractant for neutrophils), MCP-1 and RANTES (monocyte attractants), the expression and production of IP-10 was analysed. Mesothelial cells were cultured and stimulated with either IL-1β, tumour necrosis factor-alpha (TNF-α) or IFN-γ or combinations of these. The time- and dose-dependent mRNA expression of the chemokines was determined by Northern blot analysis and the protein production by ELISA. It was concluded that mesothelial cells could indeed be triggered by the mentioned stimuli to induce mRNA and protein production (huGRO-α and IP-10) or to augment constitutive protein production (MCP-1). However, RANTES mRNA and protein production could only be induced in some cases and only in small amounts. The chemokine response of mesothelial cells was regulated differentially, depending on the stimulus and the chemokine measured. In distinct cases, combination of the stimuli led to synergy in mRNA expression and protein production. The presented in vitro data support our hypothesis that mesothelial cells in vivo are the main source of relevant chemokines in response to proinflammatory mediators, suggesting an important role for mesothelial cells in host defence.

Background Ultrafiltration failure (UFF) is a complication of peritoneal dialysis (PD) treatment that occurs especially in long-term patients. Etiological factors include a large effective peritoneal surface area [measured as high mass transfer area coefficient (MTAC) of creatinine], a high effective lymphatic absorption rate (ELAR), a large residual volume, or combinations. Objective The prevalence and etiology of UFF were studied and the contribution of transcellular water transport (TCWT) was analyzed. A new definition of UFF and guidelines for the analysis of its etiology were derived from the results. Setting Peritoneal dialysis unit in the Academic Medical Center in Amsterdam. Design Cross-sectional study of standard peritoneal permeability analyses (4-hr dwells, dextran 70 as volume marker) with 1.36% glucose in 68 PD patients. Patients with negative net UF (change in intraperitoneal volume, dlPV < 0 mL) were analyzed further using 3.86% glucose, whenever possible. Results Among 68 patients (duration of PD 0.3 -178 months), 39 had negative net UF with 1.36% glucose. These patients had greater MTAC creatinine and glucose absorption, and higher ELAR (p < 10–4) than the patients with positive UF. dIPV and transcapillary UF rate (TCUFR) were lower (p < 10–5). Twenty of these patients could be studied using 3.86% glucose. dlPV was greater than 400 mL/4 hr in this test in 12 patients, implying that no clinically important UFF was present. Ultrafiltration failure (dIPV < 400 mL) was found in 8 patients, giving a prevalence of 23%. This last group had been treated with PD for a longer period (p = 0.03), had higher ELAR (p = 0.07), but lower residual volume (p = 0.03), and lower TCUFR (p = 0.01). Ultrafiltration failure was associated with a high MTAC creatinine in 3 patients, a high ELAR in 4 patients, and a combination of factors in one. As an additional possible cause, TCWT was studied, using the sodium gradient in the first hour of the dwell, corrected for diffus ion (dNA). Five patients had dNA > 5 mmol/L, indicating normal TCWT. The 3 patients with dNA < 5 mmol/L tended to be treated longer (p = 0.19) and had lower TCUFR (p = 0.04). A smaller difference was found between dlPV 3.86% and 1.36% (p = 0.04) compared to the dNA > 5 mmol/L group, but no differences were present for MTAC creatinine, ELAR, residual volume, or glucose absorption. Conclusions ln addition to known factors, impairment of TCWT can be a cause of UFF. A standardized dwell with 1.36% glucose overestimates UFF. Therefore, 3.86% glucose should be used for identification of patients with UFF, especially because it provides additional information on TCWT. Ultrafiltration failure can be defined as net UF < 400 mL/4 hr with 3.86% glucose during a 4-hour exchange.

Objective To analyze clinical features of peritoneal sclerosis (PS) in a group of peritoneal dialysis (PD) patients, and to compare potential risk factors and peritoneal transport characteristics with a control group matched for duration of PD. Design Study 1: Retrospective study of 16 PD patients with PS. Study 2: Case-control study comparing 10 patients with evident PS to 30 control patients who were matched for duration of PD. Setting Continuous Ambulatory Peritoneal Dialysis unit in the Academic Medical Centre in Amsterdam. Results The incidence of PS was 3.5 per 1000 patient years. PS was diagnosed either during PD (n = 10), in patients on hemodialysis (n = 2), or after successful transplantation (n = 4). Presenting symptoms were bowel obstruction, ascites, blood-stained effluent, and impaired net ultrafiltration. Macroscopic confirmation of the diagnosis was possible in 13 patients. Sclerotic encapsulation was present in 8 of them. Patients with PS were divided into three groups based on clinical symptoms and typical macroscopical findings. In category I the diagnosis PS was obvious (10 patients), in category II the diagnosis was highly suggestive (3 patients), and in category III it was doubtful (3 patients). Treatment was conservative in most patients. Surgical treatment was only possible in four and immunosuppressive therapy was given in 5 patients. Peritoneal sclerosis was the direct cause of death in 1 patient. Five patients died during follow-up due to other causes. At present, 7 patients are well and 3 patients (all from category I) still have recurrent bowel obstruction. Compared to matched controls, no difference existed in peritonitis incidence, or in the percentage of patients with former renal transplantations. The number of patients treated with β-blocking agents and the number of previous abdominal surgeries were not different. The number of catheter-related surgical procedures was higher in the PS patients than in the control group. The mass transfer area coefficient (MTAC) of creatinine was higher in PS patients and net ultrafiltration with 1.36% glucose was lower. The estimated cumulative glucose exposure until the diagnosis of PS was made was larger in PS patients than in their controls. This difference was already present in the first year of PD treatment in 8 of 10 patients. The initial values for the MTAC creatinine were similar in both groups. Conclusions The presenting symptoms of PS were bowel obstruction, ascites, and blood-stained effluent, often in combination with loss of net ultrafiltration. Peritoneal sclerosis is a complication of long-duration PD and could also become manifest after a successful renal transplant. Treatment should be conservative unless complications require surgical intervention. Patients with PS had lower net ultrafiltration and higher transport rates compared to controls who were matched for duration of PD. Although peritonitis incidence was similar, a relation of PS with severe peritonitis may be present in some patients. Glucose exposure is likely to be an important risk factor for PS.

Objective To give a survey of the principles of peritoneal fluid transport in general, followed by an analysis of the effects of icodextrin on the transport of fluid and solutes. Design A review of the literature and of data on the effects of icodextrin in continuous ambulatory peritoneal dialysis (CAPD) patients at the Academic Medical Center, Amsterdam. Results Icodextrin had no effect on the mass transfer area coefficients of low molecular weight solutes. Also no effect was found on the clearances of albumin and larger serum proteins. Due to convective transport, the clearance of β2-microglobulin was greater with icodextrin than with glucose solutions. Icodextrin was especially superior to glucose in the induction of net ultrafiltration during long dwells, during peritonitis, and in patients with ultrafiltration failure caused by a large effective peritoneal surface area. Conclusion Icodextrin has no effect on the permeability characteristics of the peritoneal membrane, but increases convective flow through the small-pore system. As a result, the peritoneal clearance of β2-microglobulin is higher than with glucose-based solutions.lcodextrin is especially indicated for long dwells and in patients with impaired ultrafiltration caused by a large peritoneal surface area, leading to high transport rates of low molecular weight solutes.

Existing prognostic methods were compared in their ability to predict mortality in intensive care unit (ICU) patients on dialysis for acute renal failure (ARF). The clinical goal of this study was to determine whether these models could iden- tify a group of patients where dialysis would provide no benefit because of a near 100% certainty of death even with dialysis treatment. This retrospective cohort study included 238 adult patients who received a first dialysis treatment for ARF in the ICU. This study examined the performance of seven general ICU mortality prediction models and four mortality prediction models developed for patients with ARF. These models were assessed for their ability to discriminate mortality from sur- vival and for their ability to calibrate the observed mortality rate with the expected mortality rate. The observed inhospital mortality was 76% for our patient group. Areas under the receiver operating characteristic curve ranged from 0.50 to 0.78. With the Acute Physiology and Chronic Health Evalua- tion (APACHE) III and the Liano models, the observed mor- tality in the highest quintiles of risk were 97% and 98%. In conclusion, although none of the models examined in this study showed excellent discrimination between those patients who died in hospital and those who did not, some models (APACHE III, Liano) were able to identify a group of patients with a near 100% chance of mortality. This indicates that these models may have some use in supporting the decision not to initiate dialysis in a subgroup of patients. (1 Am Soc Nephrol 8: 111-117, 1997)

Objective To make a comparison of serum levels of immunoglobulin G (lgG) subclasses in adult continuous ambulatory peritoneal dialysis (CAPD) patients with those in age-and sex-matched hemodialysis patients and healthy volunteers, and to analyze the contribution of removal of these proteins in peritoneal effluent to their plasma values. Design A cross-sectional study. Setting A renal unit of a university hospital. Patients Twenty-three CAPD patients, 21 hemodialysis patients, and 21 healthy volunteers. Peritoneal transport studies were done in 8 of the 23 CAPD patients. Methods IgG subclasses were measured in serum by nephelometry. For the peritoneal transport studies an ELISA method on ethylenediamine tetracetic acid plasma was used. The same method was used in seven-to ten-fold concentrated peritoneal dialysate. Results CAPD patients had lower IgG2 and IgG4 1evels than hemodialysis patients and healthy volunteers (p < 0.01). lgG2 values below 1.5 glL were present in 43% of the CAPD patients (p < 0.001 compared to healthy volunteers). Peritonitis incidence was not different between CAPD patients with low or normal IgG2 plasma levels. Peritoneal clearance of IgG3 was lower than that of the other subclasses. Evidence was obtained for a depressed synthesis of IgG2 and IgG4 in CAPD patients. The hypothesis that interleukin-2 may be involved in the low synthesis rate of IgG2 is discussed. Conclusion Low serum IgG2 and IgG4 1evels are present in stable, adult CAPD patients. These were not caused by increased peritonealloss, but by decreased synthesis.

The standard peritoneal permeability analysis: A tool for the assessment of peritoneal permeability characteristics in CAPD patients. Peritoneal transport characteristics in CAPD patients are often assessed by the peritoneal equilibration test (PET), which uses a four hour dwell with glucose 2.27% dialysate. From the test, the dialysate/plasma ratio of creatinine (D/P Cr ), the dialysate/initial dialysate ratio of glucose (D/D 0 ) and net ultrafiltration (NUF, drained minus instilled volume) are calculated. The standard peritoneal permeability analysis (SPA) is a modification and extension of the PET: glucose 1.36% dialysate is used, to which dextran 70 (1 g/liter) is added for the calculation of fluid kinetics. Mass transfer area coefficients (MTAC's) of low molecular weight solutes, clearances of proteins and the change in intraperitoneal volume (ΔIPV) can be assessed. In this study the SPA was analyzed, and a comparison with the PET was made. A total number of 138 SPA's was analyzed in 86 different clinically stable patients. Normal values were calculated for both SPA and PET parameters in the same tests. Median (ranges) of comparable transport parameters from SPA and PET were: MTAC Cr , 10.4 ml/min (5.7 to 19.3); glucose absorption, 61% (35 to 87); ΔIPV, 9.5 ml (-761 to 310); D/P Cr , 0.76 (0.53 to 1.14); D/D 0 , 0.37(0.13 to 0.56); NUF, -75 ml (-675 to 450). The agreement between SPA and PET was analyzed using the method of Bland and Altman. A fairly good agreement was present between NUF and ΔIPV. Systematic errors were found when D/P Cr and MTAC Cr were compared: D/P overestimated MTAC mainly in the low range, whereas in the high range values were underestimated. A similar pattern was seen for the transport parameters of glucose. In 40 patients negative net ultrafiltration was present, and possible reasons for this were assessed. In 9 patients no reason could be identified. It can be concluded that the SPA provides useful and extensive information on peritoneal transport parameters. Compared to the PET, the SPA has better discriminative power for the transport of glucose and creatinine.

The incidence, causes and complications of severe rhabdomyolysis (creatine phosphokinase (CK) > or = 5000 U/l) were studied during a 7-year study period in a large university hospital population. This condition was present in 0.074% of all admitted patients. The mortality in the study group (n = 93) was 32% and the incidence of acute renal failure (ARF) 51%. Ischaemia was the most frequent cause, and drugs, alcohol and/or coma were the second most common cause of severe rhabdomyolysis. Patients with rhabdomyolysis due to ischaemia were older, had ARF more often, and also had the highest mortality. Hyperkalaemia (potassium > or = 5.5 mmol/l) occurred in 13% of the patients, and all of them had or developed an impaired renal function. Hypocalcaemia (calcium < or = 2.00 mmol/l) was found in 41%. The incidence of ARF and electrolyte disturbances was higher in patients with CK levels exceeding 15,000 U/l. Mortality was significantly higher in patients with ARF. Plasma concentrations of potassium and calcium correlated better with the severity of renal failure than with the maximal height of plasma CK.

Background. Low levels of circulating fetuin-A are associated with increased mortality in dialysis patients. This study aimed to examine a potential causative role for fetuin-A on mortality by investigating whether a functional polymorphism in the alpha2-Heremans-Schmid glycoprotein (AHSG) gene associates with mortality, and by estimating the causative effect of fetuin-A levels on mortality using a Mendelian randomization design. Methods. One thousand and forty-three incident dialysis patients were genotyped for the Thr256Ser polymorphism (rs4918) and followed up for 5 years; in 549 patients, serum fetuin-A levels were measured. Results. Carriers of a serine allele displayed lower fetuin-A levels (-0.07 g/L per allele, P < 0.001). A small increased mortality risk was observed for the Thr/Ser and Ser/Ser genotype compared with the Thr/Thr genotype (HR 1.03, 95% CI 0.83-1.28 and HR 1.10, 95% CI 0.78-1.55, respectively). Using the AHSG genotype as an instrumental variable, the causative HR of fetuin-A levels on mortality was estimated as 1.01 per 0.1-g/L increase. Inflammation and diabetes partially modified the association of fetuin-A levels with outcome. Conclusions. The Thr256Ser polymorphism was weakly associated with mortality, and no causative effect of fetuin-A levels on this outcome was observed. Other risk factors, including inflammation and diabetes, might lead to lower fetuin-A levels, and/or modify the effect of low fetuin-A on mortality in end-stage renal disease patients.

Few studies have been published on the magnitude of the surface area of the peritoneum. Wegener mentioned a surface area of 1.72 m 2 in one adult woman [1] and Putiloff a value of 2.07 m 2 in one adult male [2]. More recent autopsy studies reported lower values [3–5]; the average peritoneal surface area in adults ranged from 1.0 m 2 [3] to 1.3 m 2 [5]. Using CT scanning in continuous ambulatory peritoneal dialysis (CAPD) patients a value of 0.55 m 2 has been found [6]. Some studies reported relationships between peritoneal surface area and body weight and/or body surface area, while others did not. The ratio between peritoneal surface area and body weight in adults is about half of that found in newborn infants [3]. A difference between adults and infants is barely present when peritoneal surface area is related to body surface area [3]. The peritoneal/body surface area averaged 0.6–0.8 in adults and 0.5–0.6 in infants. About 60% of the peritoneum consists of visceral peritoneum, 10% of which covers the liver, 30% of mesenterium and omentum, and 10% is parietal peritoneum [3–5]. The latter includes the diaphragmatic peritoneum, which comprises 3–8% of the total peritoneal surface area. Species differences are present, especially with regard to the contribution of diaphragmatic peritoneum, which is larger in humans than in rodents [5]. The contribution of the various parts of the peritoneum to solute transport during peritoneal dialysis may vary. Evisceration was found to cause a marked reduction in the transport of creatinine in rabbits [7] but not in rats [8, 9]. Effective peritoneal dialysis has been described in a neonate with extensive resection of the small intestine [10]. It has been hypothesized that the peritoneum covering the liver might be especially important in solute transport during peritoneal dialysis because of the close proximity with the liver sinusoids, but this could not be confirmed in experimental studies in rats [11, 12]. The diaphragmatic part of the peritoneum is especially involved in the absorption of solutes and fluid from the peritoneal cavity into the lymphatic system [13]. Observations in rats have shown that the peritoneal surface area increases with the age of the animals, with a proportional increase in dialysate/plasma (D/P) ratios of urea and creatinine [14]. The proportion of the peritoneum that is involved in transport during peritoneal dialysis is not known. The abovementioned evisceration experiments suggest that the relative contribution of the parietal peritoneum may be more important than that of the visceral peritoneum. Although similar diffusion rates were found during experiments in rats undergoing peritoneal dialysis using a diffusion chamber, placed at various parts of the peritoneum, it appeared that only 25–30% of the visceral peritoneum was in contact with the dialysis solution [11]. Furthermore, it has been shown in cats that commercial dialysis solutions increase blood flow to the mesentery, omentum, intestinal serosa, and parietal peritoneum without altering total splanchnic blood flow [15]. This study, using microspheres, points to hyperemia of these tissues, thereby increasing the peritoneal capillary surface area. It appears from the above data that the surface area of the peritoneal membrane involved in peritoneal dialysis is not a static property but should be defined in a functional way. The functional surface area of the peritoneal membrane cannot be measured directly, but the functional cross-sectional exchange pore area divided by the effective diffusion path length can be estimated. This parameter takes not only the capillary surface area into account, but also the distance to the dialysate/mesothelial contact. Using kinetic modeling, values of 117–250 m have been reported [16–19]. When the surface area of the peritoneum that is involved in transport is 0.6 m 2 and the unrestricted area over diffusion distance is set at 190 m, it can be calculated that the length from the capillary wall to the peritoneal cavity would be 3 mm in case of unrestricted diffusion in water. As the peritoneum is much thinner, this means that the resistance to diffusion of interstitial tissue must greatly exceed that of water. This will be discussed further in the following section.

The effects of intraperitoneal administration of two different batches of human albumin (batch A and batch B) on peritoneal solute transport and dialysate white cell count were studied in 16 CAPD patients. The studies were done on two separate days during a 4-h dwell, one day without and one day with the intraperitoneal administration of 10 g/l human albumin. Marked differences were found between the two batches. The transport of all measured solutes increased during administration of batch A compared to the control experiments: urea 78% +/- 62%, lactate 51% +/- 38%, creatinine 96% +/- 54%, glucose 67% +/- 55%, inulin 27% +/- 33% IgG 126% +/- 80%, mean +/- SD; P less than 0.02). In the experiments with batch A the white cell count of the test bag was greater than that of the effluent ('night bag') before the test (13 +/- 5 vs 194 +/- 61 mm3/l; P less than 0.02). These effects were also observed when the dialysate was buffered to pH = 7.4 before inflow. Albumin batch B showed no effect on solute transport and white cell count. The effects of solute transport and white cell count are probably caused by the greater concentration of prekallikrein activator in batch A when compared to batch B (30.1 vs 0 U/l). Caution is warranted when human albumin is used for simultaneous measurement of peritoneal fluid and solute kinetics.

To elucidate the importance of possible trapping of macromolecules in peritoneal tissue on the calculation of peritoneal lymphatic drainage, we compared the transport of inulin administered i.v. and i.p. in nine continuous ambulatory peritoneal dialysis (CAPD) patients on two separate days. In the intraperitoneal study inulin (5 g) was added to the dialysate and in the intravenous study inulin (5 g) was given i.v. 3 h before the test. No differences were found in the mass transfer area coefficients (MTC) of urea, creatinine, and glucose between the two tests. The MTC after inulin i.p. was 3.2 ± 0.7 mLlmin (mean ± SD) and after inulin i.v. 1.8 ± 0.5 (p < 10-5). As the difference in transport kinetics between i.v. and i.p. administration is likely to be caused by lymphatic absorption, a mean lymphatic flow of 1.4 mLlmin could be calculated. This value corresponds to the data obtained with macromolecules. Our results therefore favor the hypothesis that no local accumulation of macromolecules in the peritoneal tissues takes place and that their disappearance from the peritoneal cavity represents lymphatic absorption.

A noncharacteristic solute, appearing in gradient elution liquid chromatography (HPLC) profiles of body fluids of dialyzed renal patients, was isolated and identified by preparative HPLC, beta-glucuronidase induced enzymatic peak shift, and mass spectrometry. The compound was shown to be p-acetylaminophenol ('paracetamol')-glucuronide (PG). Serum and peritoneal dialysate PG concentrations were determined in a number of patients. Cuprophan in vivo dialyzer clearances were calculated. Peritoneal membrane mass transfer coefficients (MTC) of PG were calculated and compared with those of molecular mass markers for peritoneal diffusive mass transport studies (urea, creatinine, uric acid, and inulin). By extrapolation of an MTC versus molecular mass calibration line for urea, creatinine, and uric acid it is shown that PG behaves as expected from its molecular mass. We suggest that PG (Mr = 327) is suitable as a molecular mass marker for the molecular mass range between Mr 200 and 500. It may also be used as a marker for diffusive solute transport in hemodialysis treatment. The HPLC gradient elution technique used here appears to be suitable for the simultaneous analysis of the molecular mass markers creatinine, uric acid, and paracetamolglucuronide.

Background: Hemolytic uremic syndrome (HUS) is a disease characterized by nonimmune hemolytic anemia, thrombocytopenia and renal impairment. There are many causes for HUS, but adverse reactions to drugs have been increasingly reported. Even the NSAIDs which have been reported as safe and effective painkillers are described as cause of recurrent HUS. Patient case: We describe a case of a 44-year-old woman who was admitted to our hospital because of thrombocytopenia and anemia after the use of 8 tablets of 400 mg ibuprofen (NSAIDs). The diagnosis HUS was made and she recovered completely after treatment with fresh-frozen plasma and seven plasma exchanges. Conclusion: No cause could be identified except the use of ibuprofen. Recognition of a drug-induced HUS is necessary to avoid reexposure and recurrent HUS.

New peritoneal dialysis (PD) patients have a better survival than new haemodialysis (HD) patients in the first years on dialysis. During long-term treatment, this changes into a survival advantage for HD. The superior initial survival on PD is related to a better preservation of residual renal function of PD patients compared to HD. The importance of residual renal function is probably due to additional properties of native kidneys, such as a better removal of organic acids and low molecular weight proteins than occurs during dialysis. The magnitude of the residual glomerular filtration rate (rGFR) in PD patients is not only associated with better survival, but also with less uraemic symptoms, such as loss of appetite, and also with higher scores on quality of life tests. These relationships are absent for peritoneal clearance. Consequently measures to preserve rGFR are extremely important. Studies on an effect of peritoneal transport status on survival have given variableA large meta-analysis showed that fast transport patients have a 15% increased risk of death, but this is only the case for continous ambulatory peritoneal dialysis (CAPD) with conventional dialysis solutions. This suggests that the development of overhydration may be the link between transport status and mortality. A fast transport status can be inherent or acquired. The inherent form can either be due to an inflammatory state or to a large mesothelial cell mass. In both situations vasoactive mediators may be locally released. A permanent acquired fast transport status, leading to severe ultrafiltration failure develops in about one third of the patients. It is conceivable that the excess mortality in fast transport patients is caused by the types associated with an inflammatory status and with the acquired type of long-term PD. The latter, linked to morphological peritoneal alterations, is mainly caused by exposure to conventional dialysis solutions. An icodextrin based solution is especially indicated to treat ultrafiltration failure. The aim of the ''biocompatible'' solutions is to prevent the peritoneal changes. The results of animal and clinical studies are promising so far. The objective of modern PD is to extent its initial survival advantage to long-term treatment. Recent advances in knowledge of mechanisms and new dialysis solutions are likely to make this possible.

Malnutrition and chronic inflammation are frequently-occurring complications in dialysis patients. These conditions are associated with cardiovascular diseases and predict hospitalisation and mortality. There is assumed to be a pathophysiologic association between malnutrition, inflammation and atherosclerosis in this patient population. Indeed, chronic inflammation can induce an atherogenic and catabolic state, while a low food intake can lead to malnutrition and inflammation, but can also result from it. These complex associations constitute the basis for 'malnutrition, inflammation and atherosclerosis (MIA syndrome)'. Inflammation and malnutrition associated atherosclerosis may explain a large part of the high mortality in dialysis patients. An integrated approach is needed to treat this multifactorial complication. Randomised clinical trials on this subject are lacking as yet.

Ultrafiltration failure (UFF) is a serious complication of peritoneal dialysis (PD). The aim of the study was to analyze changes in water transport and their determinants in UFF patients over the time on PD. Standard peritoneal permeability analyses of 50 stable PD patients with UFF were analyzed. Fluid transport through small pores (SPT), free water transport (FWT) at 60 min, their contributions on total ultrafiltration (SPTC and FWTC), and their determinants were assessed. Patients were divided in Group I (UFF) treated for less than 24 months, Group II treated 24-60 months, and Group III treated for more than 60 months. Group I (UFF) was compared with Group I (non-UFF) matched for the duration of PD treatment and age. Transcapillary ultrafiltration (TCUF), SPT, FWT, and FWTC were significantly lower in Group III when compared to the other UFF groups. In this group also, negative relationship was present between FWT, the ultrafiltration coefficient LpA, and osmotic conductance to glucose on one hand and PD duration on the other. FWT was positively related to osmotic conductance to glucose in all groups. Group I (UFF) showed significantly higher solute transport, effective lymphatic absorption rate, lower TCUF, and lower FWT than Group I (non-UFF). The patterns of UFF in PD patients are dependent on the duration of treatment.

In evaluations of dialysis therapy, an assessment of health-related quality of life (HRQOL) is often important. The aim of this study was to determine the basic psychometric properties, reliability and validity of the short form of the KDQOL i.e. the KDQOL-SF, a dialysis-targeted instrument, and to assess its ability to detect changes over time.In a prospective cohort study (Netherlands Cooperative Study on the Adequacy of Dialysis, NECOSAD), all new adult ESRD patients in 32 different Dutch centers were consecutively enrolled. Demographic, clinical and HRQOL data were obtained 3 and 12 months after the start of chronic dialysis therapy.The reliability of the KDQOL-SF was supported by test results that were above the recommended minimal values. Validity of KDQOL-SF was confirmed by the hypothesized positive correlations of the overall health rating and renal function, and by the negative correlations between the number of comorbidities and dialysis dose. Moreover, dialysis-targeted dimensions were more sensitive in detecting relevant differences pertaining to kidney diseases than generic dimensions. The KDQOL-SF was able to detect clinical changes over time.The psychometric properties of the KDQOL-SF were good, and the different dialysis-targeted dimensions were informative with a high reliability and validity. These results support the application of the KDQOL-SF in studies evaluating dialysis therapy.

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.Review article.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 more-biocompatible PD solutions causes an increase in dialysate CA125.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.

To assess employment status in new end-stage renal disease (ESRD) patients at the start of dialysis and after 1 year, and to determine whether demographic and clinical variables and physical and psychosocial functioning at the start of dialysis are risk factors for loss of employment after 1 year of dialysis.Prospective follow-up study in which 38 of 48 Dutch dialysis centers participate.659 patients who had started on dialysis and who were between 18 and 65 years old were included. Patients were re-examined after 12 months.Demographic data, physical and psychosocial functioning with the Short-Form Health Survey (SF-36), and data on employment status were obtained using questionnaires. Nephrologists provided the clinical data.At the start of dialysis, 35% of patients were employed, in contrast to 61% of the general Dutch population. Within 1 year, the proportion of employed patients decreased from 31% to 25% of hemodialysis patients, and from 48% to 40% of peritoneal dialysis patients. In patients who were working at the start of dialysis, independent risk factors for loss of work within 1 year were impaired physical and psychosocial functioning [odds ratio physical: 3.4, 95% confidence interval (% CI), 1.0-11.2; odds ratio psychosocial: 4.2, 95% CI, 1.2-14.2].As the percentage of employed patients at the start of dialysis is about half the expected percentage, loss of work is an important issue in both predialysis and dialysis patients. Improvements in physical and psychosocial functioning are potentially preventive of loss of work in patients who are employed when they start dialysis.

It is unknown whether a given level of urea clearance by the native kidneys provides better or similar control of uremia than the same level of urea clearance by continuous peritoneal dialysis (PD). More insight into possible differences between renal and peritoneal urea clearances is warranted. Therefore, we investigated the relationship between Kt/V(urea) and protein equivalent of total nitrogen appearance normalized to body weight (nPNA), the relationship between urea clearance and creatinine appearance, and other nutritional parameters in PD patients without residual renal function, and in predialysis end-stage renal disease patients.All patients participated in the Netherlands Cooperative Study on the Adequacy of Dialysis. This is a prospective cohort study of incident dialysis patients, in whom regular assessments of renal function are done. A group of 75 PD patients was identified at the first follow-up assessment in which their urine production was less than 100 mL/day. These patients were considered the anuric group. This group was compared with a control group of 97 predialysis patients studied 0-4 weeks before the start of dialysis treatment.Linear relationships were present between Kt/V(urea) and nPNA, in both the predialysis patients and the anuric PD patients. A significant difference was present between the slopes of the two regression lines (0.40 vs 0.18, p = 0.007). When Kt/V(urea) exceeded 1.3/week, a given level of Kt/V(urea) was associated with a higher nPNA in predialysis than in anuric PD patients. Similar relationships were found between Kt(urea) and PNA. Kt(urea) was also significantly related to urine or dialysate creatinine appearance. A significant difference existed between the slopes of the regression lines in the two groups of patients (p0.001). A weekly Kt(urea) of 70 L was associated with a urine creatinine appearance of 11.0 mmol/day and a dialysate creatinine appearance of 8.4 mmol/day. Nutritional status measured with creatinine appearance and Subjective Global Assessment was better in the predialysis population, despite much lower values for Kt/V(urea) in these patients.The relationship between Kt/V(urea) and nPNA in anuric PD patients is different from that in a predialysis population. It follows from our results that, when Kt/V(urea) is above 1.3/week, a given level of Kt/V(urea) is associated with a higher nPNA in predialysis than in anuric PD patients. This challenges the concept of equivalency between renal and peritoneal Kt/V(urea) with respect to control of uremic morbidity.

To investigate the presence of cancer antigen 125 (CA125) on mesothelial cells in the effluent of peritoneal dialysis (PD) patients and to analyze the effect of duration of PD on the number of mesothelial cells in peritoneal effluent, the number of CA125-positive cells, and dialysate CA125 concentration.A cross-sectional study in which long-dwell peritoneal effluents were investigated for mesothelial cells and CA125.A university hospital population of chronic PD patients.33 stable PD patients who were free of peritonitis during the investigation and during the 4 weeks prior to the study.Examination of cytospin preparations of peritoneal effluent stained with May-Grünwald Giemsa, and also with an immunocytochemical double-staining method consisting of anticalretinin (pan-mesothelial cell marker) and OC125.A close relationship was present between the numbers of mesothelial cells counted with the two staining methods (r= 0.998, p0.001). On average, 92% of mesothelial cells were positive for CA125, ranging between 75% and 100% in 80% of the patients. Correlations were found between the effluent CA125 concentration and the total number of mesothelial cells (r = 0.64, p0.001), and also the number of CA125-positive cells (r = 0.66, p0.001). A negative effect of time was seen on the effluent CA125 concentration, the total number of mesothelial cells, and the number of CA125-positive mesothelial cells. However, no effect of time was present on the percentage CA125-positive cells.On average, 92% of mesothelial cells in peritoneal effluent are positive for CA125. This figure is not dependent on the duration of PD. Long-term PD is associated with low dialysate CA125 concentrations, a low number of mesothelial cells, and a low number of CA125-positive mesothelial cells in effluent. These results support the hypothesis that dialysate CA125 can be used as a marker of mesothelial cell mass in stable PD patients.

The effect of glucose-induced ultrafiltration in peritoneal dialysis is dependent on the presence and function of ultrasmall transendothelial cell water channels. The mercury-sensitive aquaporin-1 was thought to represent these transcellular pores. Amphotericin B (ampho B) has been reported to increase ultrafiltration in both experimental and patient studies. The objective of this study was to investigate the hypothesis that intraperitoneal ampho B increases and mercury chloride inhibits aquaporin-1-mediated water transport in a chronic peritoneal dialysis model in the rabbit.Eighteen female New Zealand White rabbits were included for peritoneal catheter implantation. Peritoneal transport parameters were determined in all rabbits by standard peritoneal permeability analysis (SPAR) with 3.86% glucose-based dialysis solution during a one-hour dwell prior the intervention SPARs, as a control. Ampho B (0.06 mg/kg body weight) was added to the dialysate for 3 (n = 9) or 5 consecutive days (n = 5) before investigation. Four rabbits were investigated after 3-day i.p. 0.6 mg/kg body weight ampho B. In 3 rabbits 0.06 mg/kg body weight liposomal ampho B was administered i.p. during 3 days before intervention SPAR. Fifteen rabbits were investigated during a one-hour dwell with 0.1 mM HgCl2 containing 3.86% glucose-based dialysis solution, while they were anesthetized. Three of these underwent in vivo fixation with glutaraldehyde prior to the HgCl2 SPAR to prevent toxic effects of mercury on peritoneal tissues.Intraperitoneal administration of ampho B did enhance the change in intraperitoneal volume during a one-hour dwell after 3-day i.p. treatment with the low dose (p0.02), but it did not affect peritoneal solute permeability. This was likely mediated by transcellular water channels, but not by aquaporin-1. No beneficial effects on the ultrafiltration were found with prolonged treatment or with the higher dose. Ultrafiltration decreased (8 ml/4 h to 1 ml/4 h, p0.03) after i.p. administration of HgCl2 with and without in vivo fixation, accompanied by a significant decrease in aquaporin-mediated water transport, estimated as the sieving of sodium (p0.001). Marked increases in the clearances of macromolecules were found after i.p. HgCl2 administration due to toxic effects: total protein clearance from 97 to 172 microl/min, p0.005, and albumin clearance from 59 to 158 microl/min, p0.005. These changes were less pronounced after in vivo fixation.Ampho B has likely no clinical relevance in treatment of ultrafiltration failure in PD patients. Aquaporin-mediated water transport could be inhibited and consequently ultrafiltration was reduced by i.p. administration of mercury chloride in our rabbit model.