Dirk G. Struijk

PERITONEAL DIALYSIS-RELATED INFECTIONS RECOMMENDATIONS: 2010 UPDATE

Department of Medicine and Therapeutics,1 Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong; University of Pittsburgh School of Medicine,2 Pittsburgh, PA, USA; Faculdade de Enfermagem, Nutrição e Fisioterapia,3 Pontifícia Universidade Católica do Rio Grande do Sul, Brazil; Sanjay Gandhi Postgraduate Institute of Medical Sciences,4 Lucknow, India; Department of Nephrology,5 Princess Alexandra Hospital, and School of Medicine, University of Queensland, Brisbane, Australia; Department of Medical Microbiology,6 Leiden University Medical Center, Leiden, The Netherlands; Centre for Kidney Diseases,7 Mount Elizabeth Medical Centre, Singapore; Section of Infectious Disease,8 Department of Internal Medicine, University of Missouri-Columbia School of Medicine, Columbia, MO, USA; Pediatric Nephrology Division,9 University Children’s Hospital, Heidelberg, Germany; Dianet Dialysis Centers,10 Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Growth factors VEGF and TGF-β1 in peritoneal dialysis ☆ ☆☆ ★ ★★

The morphologic alterations in the kidney and the retina that can be present in patients with diabetic microangiopathy are mediated by growth factors. Vascular endothelial growth factor (VEGF) is a mediator of neoangiogenesis in diabetic retinopathy. Transforming growth factor-β (TGF-β) is involved in the extracellular matrix proliferation in diabetic nephropathy. The aim of the present study was to investigate the presence of VEGF and TGF-β1 in peritoneal effluents of patients undergoing continuous ambulatory peritoneal dialysis who are being treated with glucose-containing dialysis solutions in relation to parameters of peritoneal transport. Standard peritoneal permeability analyses with 3.86% glucose dialysate were performed in 16 stable patients undergoing peritoneal dialysis (PD) (median duration of PD 39 months, range 1 to 104 months). The power relationship that is present between dialysate/serum (D/S) ratios of serum proteins that are transported only across the peritoneal membrane and their molecular weights was used to predict the D/S ratios when diffusion would be the only explanation for the measured dialysate concentration. It was assumed that all TGF-β1 in the circulation was bound to α2-macroglobulin. The D/S ratios of VEGF (P < .0005) and TGF-β1 (P < .015) were significantly higher than expected when VEGF and TGF-β1 would have been transported from the circulation only by diffusion. No relationship was present between the effluent concentration attributed to the local production of VEGF (LVEGF) and that of TGF-β1 (LTGF-β1). LVEGF correlated with the mass transfer area coefficient (MTAC) creatinine value (r = 0.69, P < .007), MTAC urate value (r = 0.60, P < .02), and glucose absorption value (r = 0.75, P < .004), all reflections of the peritoneal vascular surface area. A negative correlation was observed between the transcapillary ultrafiltration (926 mL/4 h, 394 to 1262 mL/4 h) and LVEGF (r = –0.52, P < .045). This negative tendency was also observed between the net ultrafiltration (622 mL/4 h, –43 to 938 mL/4 h) and LVEGF (r = –0.48) but did not reach significance. LVEGF and the duration of treatment did not correlate, possibly because of the relatively small number of patients. LTGF-β1 showed no relationship with transport parameters or duration of treatment. In conclusion, we found evidence for the local production of both VEGF and TGF-β1 in the peritoneal membrane of patients undergoing long-term peritoneal dialysis with glucose-based dialysate solutions. The analogy with VEGF in diabetic retinopathy suggests a pathogenetic role of high dialysate glucose concentrations in the development of these alterations in the peritoneal membrane. (J Lab Clin Med 1999;134:124-32)

Clinical practice guidelines for peritoneal access.

Faculdade de Enfermagem, Nutricao e Fisioterapia,1 Pontificia Universidade Catolica do Rio Grande do Sul, Brazil; Department of Nephrology,2 Serdang Hospital, Jalan Puchong, Kajang, Selangor, Malaysia; Sheffield Kidney Institute,3 Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom; Nephrology,4 Princess Alexandra Hospital, Woolloongabba, Brisbane, Queensland, Australia; Renal Services,5 Glasgow Royal Infirmary, Glasgow, Scotland, United Kingdom; Nephrology,6 Sri Ramachandra University, Chennai, India; Dialysis Unit,7 Dianet Dialysis Centers and Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Damage of the Endothelial Glycocalyx in Dialysis Patients

Damage to the endothelial glycocalyx, which helps maintain vascular homeostasis, heightens the sensitivity of the vasculature to atherogenic stimuli. Patients with renal failure have endothelial dysfunction and increased risk for cardiovascular morbidity and mortality, but the state of the endothelial glycocalyx in these patients is unknown. Here, we used Sidestream Darkfield imaging to detect changes in glycocalyx dimension in dialysis patients and healthy controls from in vivo recordings of the sublingual microcirculation. Dialysis patients had increased perfused boundary region and perfused diameters, consistent with deeper penetration of erythrocytes into glycocalyx, indicating a loss of glycocalyx barrier properties. These patients also had higher serum levels of the glycocalyx constituents hyaluronan and syndecan-1 and increased hyaluronidase activity, suggesting the shedding of these components. Loss of residual renal function had no influence on the imaging parameters but did associate with greater shedding of hyaluronan in blood. Furthermore, patients with higher levels of inflammation had more significant damage to the glycocalyx barrier. In conclusion, these data suggest that dialysis patients have an impaired glycocalyx barrier and shed its constituents into blood, likely contributing to the sustained endothelial cell activation observed in ESRD.

ISPD PERITONITIS RECOMMENDATIONS: 2016 UPDATE ON PREVENTION AND TREATMENT

Abstract Peritonitis is a common and serious complication of peritoneal dialysis (PD). Although less than 5% of peritonitis episodes result in death, peritonitis is the direct or major contributing cause of death in around 16% of PD patients (1-6). In addition, severe or prolonged peritonitis leads to structural and functional alterations of the peritoneal membrane, eventually leading to membrane failure. Peritonitis is a major cause of PD technique failure and conversion to long-term hemodialysis (1,5,7,8). Recommendations under the auspices of the International Society for Peritoneal Dialysis (ISPD) were first published in 1983 and revised in 1993, 1996, 2000, 2005, and 2010 (9-14). The present recommendations are organized into 5 sections: 1. Peritonitis rate 2. Prevention of peritonitis 3. Initial presentation and management of peritonitis 4. Subsequent management of peritonitis 5.

The Time Course of Peritoneal Transport Kinetics in Continuous Ambulatory Peritoneal Dialysis Patients Who Develop Sclerosing Peritonitis

The time course of measurements of peritoneal solute transport in four continuous ambulatory peritoneal dialysis (CAPD) patients who developed sclerosing peritonitis is described. Loss of fluid removal capacity was found in all of them. In three, this loss was associated with an increase in peritoneal absorption of glucose from the dialysate and an increase in the transperitoneal transport rates of low-molecular-weight solutes and proteins. In the other patient a decrease in all these parameters was found. This seems to imply that the effective peritoneal surface area was increased in three patients and decreased in one. Peritoneal permeability to macromolecules remained unchanged as judged by the ratio between the clearance of IgG and albumin. Among the possible factors that contribute to the development of sclerosing peritonitis, some are likely to lead to a larger effective peritoneal surface area, like prostacyclin and the formation of new capillaries in poorly vascularized parts of the peritoneum. Others, such as extensive formation of collagen, could lead to a smaller effective surface area. Individual differences in susceptibility to these factors may lead to an increase or decrease in peritoneal solute transport rates. Follow-up measurements of peritoneal solute kinetics are necessary to identify those patients who are at risk.

Peritoneal changes in patients on long-term peritoneal dialysis

Long-term peritoneal dialysis can lead to morphological and functional changes in the peritoneum. Although the range of morphological alterations is known for the peritoneal dialysis population as a whole, these changes will not occur in every patient in the same sequence and to the same extent. Longitudinal studies are therefore required to help identify which patients might develop the changes. Although longitudinal studies using peritoneal biopsies are not possible, analyses of peritoneal effluent biomarkers that represent morphological alterations could provide insight. Longitudinal studies on peritoneal transport have been performed, but follow-up has often been too short and an insufficient number of parameters have been investigated. This Review will firstly describe peritoneal morphology and structure and will then focus on peritoneal effluent biomarkers and their changes over time. Net ultrafiltration will also be discussed together with the transport of small solutes. Data on the peritoneal transport of serum proteins show that serum protein levels do not increase to the same extent as levels of small solutes with long-term peritoneal dialysis. Early alterations in peritoneal transport must be distinguished from alterations that only develop with long-term peritoneal dialysis. Early alterations are related to vasoactive mediators, whereas later alterations are related to neoangiogenesis and fibrosis. Modern peritoneal dialysis should focus on the early detection of long-term membrane alterations by biomarkers—such as cancer antigen 125, interleukin-6 and plasminogen activator inhibitor 1—and the improved assessment of peritoneal transport.

Antifungal Treatment of Candida Peritonitis in Continuous Ambulatory Peritoneal Dialysis Patients

Nine peritonitis episodes caused by Candida sp were diagnosed in eight continuous ambulatory peritoneal dialysis (CAPD) patients. Treatment with intraperitoneal administration of amphotericin B and 5-fluorocytosine while the peritoneal catheter was left in situ was effective in six episodes in five patients. Of the three other patients, two started again with CAPD after peritonitis had been cured, but one patient preferred to stay on hemodialysis. In four episodes, peritoneal white cell counts remained high during treatment despite negative cultures. This was probably the result of irritation of the peritoneal membrane caused by the antifungal treatment, possibly by amphotericin B. Persistently-elevated leukocyte counts during antifungal therapy, with or without signs and symptoms of peritonitis, are not necessarily an indication of treatment failure.

Are phospholipase A2 and nitric oxide involved in the alterations in peritoneal transport during CAPD peritonitis

The alterations in peritoneal permeability characteristics during peritonitis can only partly be explained by the increased concentrations of prostaglandins and cytokines in the dialysate. Fifteen patients undergoing continuous ambulatory peritoneal dialysis (CAPD) with 16 peritonitis episodes were examined in the acute phase of the infection by using standard peritoneal permeability analyses (SPAs). In 9 of these patients, a control SPA could be performed. The contribution of nitric oxide (NO), prostaglandins, and the acute phase reactants C-reactive protein (CRP) and secretory phospholipase A2 (sPLA2) were analyzed. The mass transfer area coefficients (MTACs) of low-molecular-weight solutes increased during peritonitis: urea 26%, creatinine 45%, and urate 45%. The MTAC of CO2, calculated to estimate peritoneal blood flow, was 71 mL/min (34 to 254 mL/min) during peritonitis and 55 mL/min (42 to 63 mL/min) after recovery, P < or = .05. The peritoneal protein clearances were also greater during peritonitis, but this increase was not related to the molecular weight of the protein. Therefore the restriction coefficients to macromolecules were not different. The net ultrafiltration in all peritonitis episodes was lower as compared with the control dwells: -97 mL (-196 to 19 mL) versus 25 mL (-132 to 216 mL), P = .03. The prostaglandin concentrations in dialysate were greater during peritonitis than after recovery. The median increase was 199% for prostaglandin E2 (PGE2), 68% for 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha), and 44% for thromboxane B2 (TxB2). Plasma sPLA2 values were 22.7 microg/L (7.3 to 407.6) during peritonitis and 8.9 microg/L (5.5 to 11.5) after recovery, P < .01. The increased plasma sPLA2 during peritonitis correlated with plasma CRP (r = .6; P = .02). The peritoneal clearances of sPLA2 were greater during peritonitis, but this could be attributed completely to the increased peritoneal transport. Both during peritonitis and after recovery, the sPLA2 clearances did not exceed the predicted values based on transport from the circulation to the dialysate. No evidence was found for local production of nitrite or nitrate. However, the MTAC of cyclic guanosine monophosphate (cGMP) was greater during the experiments performed 48 to 72 hours after the onset of peritonitis, which suggests the synthesis of NO. It can be concluded that peritonitis does not induce detectable local release of sPLA2 and that the inflammation-induced increase in the vascular surface area could not be attributed to NO in the acute phase. The activation of inducible NO synthase may occur after 48 hours.

Peritoneal Albumin and Protein Losses Do Not Predict Outcome in Peritoneal Dialysis Patients

BACKGROUND AND OBJECTIVES Peritoneal clearance of albumin-unlike the transport of small molecules-is defined by both vascular surface area and size-selective permeability. Few studies have supported a positive correlation between peritoneal albumin loss and mortality. The aim of this study was to investigate whether baseline peritoneal loss and clearance of albumin and other proteins is a risk factor of death in peritoneal dialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS All incident peritoneal dialysis patients in our center during the last 15 years were included. Mass-transfer area coefficient of creatinine and peritoneal clearances of albumin, β₂-microglobulin, α₂-macroglobulin, and immunoglobulin G were calculated during a standard peritoneal permeability analysis. The total amount of albumin loss in the dialysate was also calculated. Overall mortality was studied with an intention-to-treat analysis. RESULTS Two hundred fifty-seven patients were included. High baseline albumin clearance was associated with fast transport status, the presence of peripheral arterial disease, and a high comorbidity index, whereas C-reactive protein levels did not differ from the patients with low albumin clearance. Age, high comorbidity score, C-reactive protein levels >10 mg/L, and a low serum albumin were associated with mortality. Peritoneal albumin clearances and albumin loss were not associated with death in crude and adjusted analysis. Similarly, peritoneal clearances of immunoglobulin G, α₂-macroglobulin, and β₂-microglobulin were not determinants of survival. CONCLUSIONS Baseline peritoneal albumin and protein clearances are associated with signs of comorbidity, but this does not have a measurable effect on patient survival.