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      Intraperitoneal heparin reduces peritoneal permeability and increases ultrafiltration in peritoneal dialysis patients

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      Nephrology Dialysis Transplantation
      Oxford University Press (OUP)

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          Abstract

          Patients on long-term treatment with peritoneal dialysis (PD) suffer from increasing peritoneal permeability and loss of ultrafiltration as a result of persistent inflammation, which may be triggered by bioincompatible dialysis fluids. Heparins have anti-inflammatory and anticoagulant properties. We have examined the effect of intraperitoneal (IP) low-molecular weight heparin (tinzaparin) on peritoneal permeability and ultrafiltration in PD patients.

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          Inflammation and thrombosis.

          Systemic inflammation is a potent prothrombotic stimulus. Inflammatory mechanisms upregulate procoagulant factors, downregulate natural anticoagulants and inhibit fibrinolytic activity. In addition to modulating plasma coagulation mechanisms, inflammatory mediators appear to increase platelet reactivity. In vivo, however, natural anticoagulants not only prevent thrombosis, but they also dampen inflammatory activity. Some insights into the evolution and linkages between inflammatory mechanisms and the coagulation/anticoagulation mechanisms have become evident from recent structural studies. This review will summarize the interactions between inflammation and coagulation.
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            What really happens to people on long-term peritoneal dialysis?

            Several risk factors for patients treated with peritoneal dialysis (PD) have now been identified. These include age, comorbid disease, nutritional status, loss of residual renal function (RRF) and high peritoneal solute transport. This is not the same, however, as knowing what actually happens to these patients, particularly in the long-term. The purpose of this review was to give as complete a description as is currently possible of the long-term PD patient. The literature was surveyed for publications that provide longitudinal cohort data of either selected or unselected patient groups. Detailed data from the Stoke PD Study is presented in the context of these studies. Three principle aspects of what really happens to patients were considered: (1) death, both cause and mode of death; (2) technique failure, with reference to peritoneal function and how the cause of technique failure related to patient survival; and (3) evolution of clinically relevant parameters of patients on PD, such as nutrition and peritoneal function. Sudden death and debilitation were the predominant modes of death, with sepsis playing a contributory role. Debilitation was important regardless of co-existent comorbid disease, and time to death was not influenced by the mode of death. Predominant causes for technique failure remain peritonitis and ultrafiltration, the latter becoming more important with time on treatment. Technical failure is associated with poorer survival, particularly when due to multiple peritonitis or failure to cope with treatment. Cox regression demonstrated that whereas low albumin, loss of RRF and high solute transport predicted patient death, only high solute transport predicted technique failure. Longitudinal changes over the first five years of treatment included loss of RRF, increasing solute transport and following an initial improvement in nutritional state, a decline after two years. Patients surviving long-term PD (at least five years, N = 25) were characterized by prolonged RRF, maintained nutrition and lower solute transport in the medium term. Several studies of long-term PD in the literature now complement each other in providing a picture of what really happens to PD patients. The links between loss of solute clearance and poor peritoneal ultrafiltration combining to exacerbate sudden or debilitated death and technique failure are emerging. For PD to be successful as a long-term therapy, strategies that maintain nutrition and preserve peritoneal membrane function must be developed.
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              Accumulation of advanced glycation end products in the peritoneal vasculature of continuous ambulatory peritoneal dialysis patients with low ultra-filtration.

              Ultra-filtration failure is a serious complication of long-term continuous ambulatory peritoneal dialysis (CAPD). This complication is related to histological changes of the peritoneum, i.e. severe interstitial fibrosis and microvascular sclerosis. Although their pathogenesis has not been elucidated yet, advanced glycation end products (AGEs) have been shown to accumulate in the peritoneal tissue of CAPD patients. Peritoneal biopsy specimens from 14 CAPD patients with low ultra-filtration (n = 9) and high ultra-filtration (n = 5) capacity were immunohistochemically investigated using a monoclonal antibody against AGEs (6D12). The severity of peritoneal fibrosis, microvascular sclerosis and intensity of AGE accumulation were semi-quantitatively evaluated. Peritoneal ultra-filtration capacity was evaluated by calculating daily ultrafiltration volume per body weight (UFV/BW) and D/D0 (glucose) of the peritoneal equilibration test. In all patients with low ultra-filtration, AGE accumulated in the peritoneal fibrous tissue and microvascular walls. Remarkably, AGE accumulated more intensely in hyalinized fibrosis of small venular media. Extent of AGE accumulation in peritoneal interstitium and vascular walls correlated with the progression of interstitial fibrosis (rho = 0.727, P = 0.0088) and vascular sclerosis (rho = 0.915, P = 0.001). UFV/BW was inversely correlated to interstitial fibrosis (rho = -0.660, P = 0.0174), microvascular sclerosis (rho = -0.671, P = 0.0155) and microvascular AGE accumulation (rho = -0.678, P = 0.0145). In CAPD patients, AGE formation in the peritoneum correlates with the development of severe interstitial fibrosis and microvascular sclerosis, which is associated clinically with impaired peritoneal ultra-filtration.
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                Author and article information

                Journal
                Nephrology Dialysis Transplantation
                Nephrology Dialysis Transplantation
                Oxford University Press (OUP)
                0931-0509
                1460-2385
                April 21 2004
                May 01 2004
                February 19 2004
                May 01 2004
                : 19
                : 5
                : 1264-1268
                Article
                10.1093/ndt/gfh065
                14993509
                4e327283-b283-4423-8fae-64907b36fa5b
                © 2004
                History

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