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      Elevation of Platelet and Monocyte Activity Markers of Atherosclerosis in Haemodialysis Patients Compared to Peritoneal Dialysis Patients

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          Abstract

          Purpose

          The predominant cause of mortality in dialysis patients are cardiovascular events. Platelet and monocyte activity markers play an important role in cardiovascular mortality and were assessed and related to dialysis quality criteria in haemodialysis (HD) and peritoneal dialysis (PD) patients.

          Methods

          For this prospective comparative study, HD patients ( n = 41) and PD patients ( n = 10) were included. In whole blood samples, surface expression of CD62P and CD40L on platelets, tissue factor binding on monocytes, and platelet-monocyte aggregates were measured by flow cytometry. Plasma levels of MCP-1, IL-6, TNF α, and soluble CD40L were analysed by enzyme-linked immunosorbent assay.

          Results

          Haemodialysis patients showed a significantly higher CD62P expression on platelets ( p = 0.017), significantly higher amount of platelet-monocyte aggregates ( p < 0.0001), and significantly more tissue factor binding on monocytes ( p < 0.0001) compared to PD patients. In PD patients, a significant correlation between Kt/V and platelet CD40L expression ( r = 0.867; 0.001) and between Kt/V and platelet CD62P expression ( r = 0.686; p = 0.028) was observed, while there was no significant correlation between Kt/V and tissue factor binding on monocytes and platelet-monocyte aggregates, respectively.

          Conclusion

          Platelet and monocyte activity markers are higher in HD patients in comparison with those in PD patients, possibly suggesting a higher risk of cardiovascular morbidity and mortality.

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          Most cited references36

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          Rosuvastatin and cardiovascular events in patients undergoing hemodialysis.

          Bengt C Fellström, Alan Jardine, Roland E Schmieder … (2009)
          Statins reduce the incidence of cardiovascular events in patients at high cardiovascular risk. However, a benefit of statins in such patients who are undergoing hemodialysis has not been proved. We conducted an international, multicenter, randomized, double-blind, prospective trial involving 2776 patients, 50 to 80 years of age, who were undergoing maintenance hemodialysis. We randomly assigned patients to receive rosuvastatin, 10 mg daily, or placebo. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Secondary end points included death from all causes and individual cardiac and vascular events. After 3 months, the mean reduction in low-density lipoprotein (LDL) cholesterol levels was 43% in patients receiving rosuvastatin, from a mean baseline level of 100 mg per deciliter (2.6 mmol per liter). During a median follow-up period of 3.8 years, 396 patients in the rosuvastatin group and 408 patients in the placebo group reached the primary end point (9.2 and 9.5 events per 100 patient-years, respectively; hazard ratio for the combined end point in the rosuvastatin group vs. the placebo group, 0.96; 95% confidence interval [CI], 0.84 to 1.11; P=0.59). Rosuvastatin had no effect on individual components of the primary end point. There was also no significant effect on all-cause mortality (13.5 vs. 14.0 events per 100 patient-years; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.51). In patients undergoing hemodialysis, the initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. (ClinicalTrials.gov number, NCT00240331.) 2009 Massachusetts Medical Society
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            Effects of increased peritoneal clearances on mortality rates in peritoneal dialysis: ADEMEX, a prospective, randomized, controlled trial.

            Ramón Paniagua, Dante Amato, Edward F Vonesh … (2002)
            Small-solute clearance targets for peritoneal dialysis (PD) have been based on the tacit assumption that peritoneal and renal clearances are equivalent and therefore additive. Although several studies have established that patient survival is directly correlated with renal clearances, there have been no randomized, controlled, interventional trials examining the effects of increases in peritoneal small-solute clearances on patient survival. A prospective, randomized, controlled, clinical trial was performed to study the effects of increased peritoneal small-solute clearances on clinical outcomes among patients with end-stage renal disease who were being treated with PD. A total of 965 subjects were randomly assigned to the intervention or control group (in a 1:1 ratio). Subjects in the control group continued to receive their preexisting PD prescriptions, which consisted of four daily exchanges with 2 L of standard PD solution. The subjects in the intervention group were treated with a modified prescription, to achieve a peritoneal creatinine clearance (pCrCl) of 60 L/wk per 1.73 m(2). The primary endpoint was death. The minimal follow-up period was 2 yr. The study groups were similar with respect to demographic characteristics, causes of renal disease, prevalence of coexisting conditions, residual renal function, peritoneal clearances before intervention, hematocrit values, and multiple indicators of nutritional status. In the control group, peritoneal creatinine clearance (pCrCl) and peritoneal urea clearance (Kt/V) values remained constant for the duration of the study. In the intervention group, pCrCl and peritoneal Kt/V values predictably increased and remained separated from the values for the control group for the entire duration of the study (P < 0.01). Patient survival was similar for the control and intervention groups in an intent-to-treat analysis, with a relative risk of death (intervention/control) of 1.00 [95% confidence interval (CI), 0.80 to 1.24]. Overall, the control group exhibited a 1-yr survival of 85.5% (CI, 82.2 to 88.7%) and a 2-yr survival of 68.3% (CI, 64.2 to 72.9%). Similarly, the intervention group exhibited a 1-yr survival of 83.9% (CI, 80.6 to 87.2%) and a 2-yr survival of 69.3% (CI, 65.1 to 73.6%). An as-treated analysis revealed similar results (overall relative risk = 0.93; CI, 0.71 to 1.22; P = 0.6121). Mortality rates for the two groups remained similar even after adjustment for factors known to be associated with survival for patients undergoing PD (e.g., age, diabetes mellitus, serum albumin levels, normalized protein equivalent of total nitrogen appearance, and anuria). This study provides evidence that increases in peritoneal small-solute clearances within the range studied have a neutral effect on patient survival, even when the groups are stratified according to a variety of factors (age, diabetes mellitus, serum albumin levels, normalized protein equivalent of total nitrogen appearance, and anuria) known to affect survival. No clear survival advantage was obtained with increases in peritoneal small-solute clearances within the range achieved in this study.
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              Platelet dysfunction in renal failure.

              Paola Boccardo, Giuseppe Remuzzi, Miriam Galbusera (2004)
              Patients with end-stage renal disease suffer from complex hemostatic disorders. Uremic patients show a bleeding diathesis that is mainly due to abnormalities of primary hemostasis; in particular, platelet dysfunction and impaired platelet-vessel wall interaction. However, despite decreased platelet function, these patients have a high prevalence of cardiovascular and thrombotic complications. Platelet dysfunction in uremic patients is partially due to uremic toxins present in circulating blood. Dialysis improves platelet abnormalities and reduces, but does not eliminate, the risk of hemorrhage. Hemodialysis can even contribute to the bleeding through the continuous platelet activation induced by the interaction between blood and artificial surfaces. Thrombocytopenia, glomerular thrombosis, and thrombi in small arteries and glomerular capillaries are common pathological features in many renal diseases. Platelets are also involved directly in the pathogenesis of glomerular diseases through a variety of mechanisms, including release of active molecules, by enhancing immune complex deposition, and by altering glomerular permeability.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Mediators Inflamm
                Journal ID (iso-abbrev): Mediators Inflamm
                Journal ID (publisher-id): MI
                Title: Mediators of Inflammation
                Publisher: Hindawi
                ISSN (Print): 0962-9351
                ISSN (Electronic): 1466-1861
                Publication date (Print): 2017
                Publication date (Electronic): 9 July 2017
                Volume: 2017
                Electronic Location Identifier: 8506072
                Affiliations
                11st Medical Department, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany
                25th Medical Department, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany
                3Herzzentrum Weinheim, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany
                Author notes
                *Anna-Isabelle Kälsch: Anna-isabelle.kaelsch@ 123456umm.de

                Academic Editor: Giuseppe Valacchi

                Author information
                http://orcid.org/0000-0002-3206-934X
                http://orcid.org/0000-0003-4285-244X
                http://orcid.org/0000-0002-4751-4709
                Article
                DOI: 10.1155/2017/8506072
                PMC ID: 5523345
                SO-VID: 01ae265f-0a0e-4e47-8f50-2d835ea7d271
                Copyright © Copyright © 2017 Ksenija Stach et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 24 January 2017
                Date revision received : 29 May 2017
                Date accepted : 11 June 2017
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Immunology
                Data availability:
                ScienceOpen disciplines: Immunology

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