Anniek Vlijm

Biological markers in the peritoneal dialysate effluent: are they useful.

A review is given on biomarkers in peritoneal effluent. It comprises methods to distinguish between diffusion and local production. This is followed by examples of various biomarkers. Their potential use is discussed in 4 situations: inherent fast transporters, longitudinal follow-up of patients, biocompatibility testing of new dialysis solutions, and their potential use in the detection of patients who are likely to develop encapsulating peritoneal sclerosis.

Encapsulating Peritoneal Sclerosis in a Peritoneal Dialysis Patient Using Biocompatible Fluids Only: Is Alport Syndrome a Risk Factor?

A 30-year-old Caucasian male known to have Alport syndrome presented acutely in 2002 with end-stage kidney failure and tertiary hyperparathyroidism. A parathyroidectomy was performed and automated peritoneal dialysis (PD) was initiated. The dialysis prescription consisted of a 7.5% icodextrin-based solution (Extraneal; Baxter Healthcare, IRL-Dublin, Ireland) for the long dwell and 1.1% amino acidbased solution (Nutrineal, Baxter) and lactate/bicarbonate solution (Physioneal, Baxter) for the short dwells. Five episodes of peritonitis occurred during follow-up, caused by either coagulase-negative staphylococci (n = 2) or Staphylococcus aureus (n = 3). All episodes were successfully treated with antibiotics. It appeared difficult to keep the calcium × phosphorus product below target and the patient developed calcifications in his hands and feet. After 6 years of PD a diagnosis was made of encapsulating peritoneal sclerosis (EPS). The diagnosis was based on abdominal complaints, especially bowel obstruction, ultrafiltration failure, a low effluent calcium antigen-125 and a computed tomographic (CT) scan compatible with EPS (1). The CT scan showed peritoneal thickening, calcifications, adhesions, and fluid loculations/septation. The patient was transferred to hemodialysis. After removal of the Tenckhoff catheter he developed massive ascites. Encapsulating peritoneal sclerosis is a severe complication of long-term PD. Long-term exposure to conventional dialysis solutions is an important risk factor for EPS (2). The pathological role of dialysis solutions may be due to the large amounts of glucose and glucose degradation products (GDPs), which enhance the formation of advanced glycosylation end products. More biocompatible solutions are now available. These solutions have a physiological pH and contain low amounts of GDPs (3).To our knowledge no patient has yet been described who developed EPS while being treated with biocompatible fluids exclusively. Alport syndrome is a rare disorder of collagen IV, which is present in basement membranes throughout the body (4). Whether Alport syndrome affects the basement membranes of peritoneal tissue and vessels is unknown. EPS is associated with an increase in interstitial and endothelial collagen IV deposits (5). We hypothesized that Alport syndrome could affect the peritoneum because interstitial collagen IV synthesis in the peritoneum may be disturbed. Our research question was, Does Alport syndrome predispose to the development of EPS in PD patients?

The effects of a dialysis solution with a combination of glycerol/amino acids/dextrose on the peritoneal membrane in chronic renal failure.

♦ Background: Long-term peritoneal dialysis (PD) with conventional glucose based, lactate-buffered PD fluids may lead to morphological and functional alterations of the peritoneal membrane. It was hypothesized that long-term exposure to a different buffer and a mixture of osmotic agents would cause less peritoneal abnormality. ♦ Objectives: To investigate the effects of long-term exposure to a bicarbonate/lactate-buffered dialysis solution with a mixture of osmotic agents: glycerol 1.4%, amino acids 0.5%, and dextrose 1.1% (= 1% glucose) (GLAD) in a rat model with chronic kidney failure. ♦ Methods: All rats underwent a peritoneal catheter implantation and a 70% nephrectomy. Thereafter, the rats were randomly divided into 3 groups: GLAD, 3.86% Dianeal (Baxter, Nivelles, Belgium), and buffer (Physioneal without glucose, Baxter). All rats were infused daily for 16 weeks with the appropriate PD fluid. Afterwards, a peritoneal permeability analysis (SPARa) was performed using 3.86% Physioneal in all groups. After the SPARa, the rats were sacrificed to obtain tissue samples for morphometric determinations. Omental tissue was stained with picro Sirius red for assessment of fibrosis and with CD31 for vessel density. ♦ Results: GLAD and Dianeal showed faster small solute transport compared to the hypotonic buffer. No differences between the groups were present in ultrafiltration. Dianeal had the lowest value for free water transport and the highest protein clearances. Total triglyceride in plasma was not different between GLAD and the buffer. Vessel density after GLAD exposure (20 V/F) was very similar to the value found for the buffer solution (17 V/F); Dianeal caused a significantly higher value (35 V/F, p < 0.01). Also, the amount of fibrosis was higher in the Dianeal-exposed rats (p < 0.01). ♦ Conclusion: Both hypertonic dialysis solutions increased peritoneal solute transport. GLAD exposure was associated with the best preservation of peritoneal morphology. The results of GLAD were very similar to those of the bicarbonate/lactate-buffered solution without osmotic agents. Studies in humans are needed for further assessment of GLAD.

Imaging in encapsulating peritoneal sclerosis

Encapsulating peritoneal sclerosis (EPS) is a rare but very severe complication of long-term peritoneal dialysis (PD). Since the first reports on this disease in the eighties, several imaging techniques have been used for its diagnosis. Because of the rarity of this condition, uniformity in modality and protocols for abdominal imaging for diagnosis has been lacking overtime. Nowadays, computed tomography (CT) is most often used. In this review, we provide an overview of all imaging modalities that have been used overtime to diagnose EPS as a late complication of PD. Imaging features characteristic for EPS and advantages as well as shortcomings of all modalities are discussed. We believe that when EPS is suspected, CT with contrast enhancement should be the modality of first choice in clinical practice.

Experimental Peritoneal Sclerosis Models Should Not Be Based on Chlorhexidine Gluconate Anymore

Background/Aims: Currently available rodent models of peritoneal sclerosis are not based on clinically relevant factors: renal failure in combination with exposure to bioincompatible fluids. Our aim was to develop a chronic peritoneal infusion model of peritoneal sclerosis in rats with renal failure. Methods: Male Wistar rats underwent a catheter implantation and a 70% nephrectomy. They were randomly divided into three peritoneal infusion groups: chlorhexidine gluconate/ethanol (CGE) + Dianeal (Baxter Healthcare, Castlebar, Ireland), CGE + buffer (Physioneal without glucose; Baxter, Nivelles, Belgium) and Dianeal alone. After 8 weeks a peritoneal permeability test was performed and omental tissue was obtained for morphometrics. Results: The CGE + Dianeal group (n = 6) and CGE + buffer (n = 6) group showed high peritoneal clearances of small solutes and proteins, ultrafiltration failure, impaired free water transport, severe fibrosis and high vessel counts, but the groups did not differ significantly. The Dianeal group (n = 6) showed significantly lower clearances of small solutes and proteins, normal ultrafiltration and sodium sieving, and significantly lower fibrosis scores and vessel counts. Conclusions: Abnormalities seen in peritoneal sclerosis can be induced in a peritoneal infusion model in rats with renal failure. However, the addition of a bioincompatible dialysis solution had no contributing role, probably because the effects were overruled by those of CGE.

Are peritoneal calcifications in long-term peritoneal dialysis related to aortic calcifications and disturbances in mineral metabolism?

BACKGROUND Peritoneal calcifications are associated with long-term peritoneal dialysis (PD). Case reports have suggested a relation with disturbances in mineral metabolism such as the presence of severe hyperparathyroidism. Our aim was to investigate whether relationships are present between peritoneal calcifications and aortic calcifications or disturbances in mineral metabolism in long-term PD patients. METHODS We included all long-term PD patients (PD ≥ 4 years) in our centre from 1996 to 2008 who had undergone an abdominal computed tomographic (CT) scan. The scans were reviewed by two experienced radiologists in consensus. The presence or absence of peritoneal calcifications was scored, and a severity scoring system for abdominal aortic calcifications was used: 1 = none, 2 = mild, 3 = moderate, 4 = severe and 5 = very severe. For each patient, laboratory data on plasma calcium corrected for albumin, phosphorus and parathyroid hormone (PTH) levels were retrieved every 6 months up to 5 years prior to the CT scan. Individual mean values over 5 years were calculated. RESULTS We included 31 patients: 12 patients with peritoneal calcifications and 19 patients without. No difference was found in aortic calcification scores (median scores: 3 versus 3). Also, median (range) calcium, 10.7 (9.6-11.5) versus 10.3 (9.4-11.3) mg/dL; phosphorus, 5.2 (3.4-7.0) versus 4.9 (2.9-6.5) mg/dL; and PTH levels, 271 (101-910) versus 263 (40-1197) pg/mL were not different between patients with and without peritoneal calcifications. CONCLUSIONS The presence of peritoneal calcifications in long-term PD patients could not be related to the presence of aortic calcifications or disturbances in mineral metabolism. Perhaps, local peritoneal factors play a role in the formation of peritoneal calcifications.

No need for an "expiry date" in chronic peritoneal dialysis to prevent encapsulating peritoneal sclerosis: comments from around the world.

Following the publication of our editorial [1], we encouraged a number of our colleagues to communicate and express their views on the pathogenesis and future prevention of this serious complication of chronic peritoneal dialysis and their views on our position regarding its management. Their letters give a great insight into current views and future directions in the prevention, detection and management of this serious complication. The two reports from China assert that this is a rare complication among their patients, contrary to reports from Japan. If these Chinese findings are supported by longer and prospective studies, we will have to revise our current views on the pathogenesis of this condition, which will lead to new approaches to its prevention.

Identification of Gene Transcripts Implicated in Peritoneal Membrane Alterations

♦ Background: Permanent stimulation of the peritoneum during peritoneal dialysis (PD) is likely to result in increased expression of genes encoding proteins involved in inflammation and tissue remodeling. Peritoneal fibrosis and neoangiogenesis may develop. ♦ Objective: To assess highly expressed genes potentially in volved in peritoneal alterations during PD treatment using an animal model. ♦ Methods: A PD catheter was implanted in 36 male Wistar rats after 70% nephrectomy. The rats were divided into 3 groups, exposed to dialysis solution for 8 weeks, and sacrificed 2 weeks later. Group B was exposed to a buffer, group D was exposed to a 3.86% glucose-based dialysis solution, and in group D+H, a second hit of intraperitoneal blood on top of the dialysis solution was given to induce the development of peritoneal sclerosis. Before sacrifice, peritoneal function was assessed. Omental tissue was obtained for analysis of gene expression using RT-qPCR. ♦ Results: Fibrosis scores, vessel counts, and peritoneal function parameters were not different between the groups. Genes involved in the transforming growth factor beta signaling pathway, cell proliferation, angiogenesis, and inflammation were more expressed (p < 0.05) in the D+H group. Almost no differences were found between the control groups. We identified 4 genes that were related to peritoneal transport. ♦ Conclusion: Already a mid-term peritoneal exposure, when no microscopical and functional alterations are present, provokes activation of gene pathways of cell proliferation, fibrosis, neoangiogenesis, and inflammation.