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      Long-term outcome of chronic dialysis in children

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          Abstract

          As the prevalence of children on renal replacement therapy (RRT) increases world wide and such therapy comprises at least 2% of any national dialysis or transplant programme, it is essential that paediatric nephrologists are able to advise families on the possible outcome for their child on dialysis. Most children start dialysis with the expectation that successful renal transplantation is an achievable goal and will provide the best survival and quality of life. However, some will require long-term dialysis or may return intermittently to dialysis during the course of their chronic kidney disease (CKD). This article reviews the available outcome data for children on chronic dialysis as well as extrapolating data from the larger adult dialysis experience to inform our paediatric practice. The multiple factors that may influence outcome, and, particularly, those that can potentially be modified, are discussed.

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          Clinical epidemiology of cardiovascular disease in chronic renal disease.

          RN Foley, PS Parfrey, MJ Sarnak (1998)
          Article 0 comments Cited 640 times – based on 0 reviews     Review now
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            The elephant in uremia: oxidant stress as a unifying concept of cardiovascular disease in uremia.

            Jonathan Himmelfarb, Peter Stenvinkel, T Alp Ikizler … (2002)
            Cardiovascular disease is the leading cause of mortality in uremic patients. In large cross-sectional studies of dialysis patients, traditional cardiovascular risk factors such as hypertension and hypercholesterolemia have been found to have low predictive power, while markers of inflammation and malnutrition are highly correlated with cardiovascular mortality. However, the pathophysiology of the disease process that links uremia, inflammation, and malnutrition with increased cardiovascular complications is not well understood. We hereby propose the hypothesis that increased oxidative stress and its sequalae is a major contributor to increased atherosclerosis and cardiovascular morbidity and mortality found in uremia. This hypothesis is based on studies that conclusively demonstrate an increased oxidative burden in uremic patients, before and particularly after renal replacement therapies, as evidenced by higher concentrations of multiple biomarkers of oxidative stress. This hypothesis also provides a framework to explain the link that activated phagocytes provide between oxidative stress and inflammation (from infectious and non-infections causes) and the synergistic role that malnutrition (as reflected by low concentrations of albumin and/or antioxidants) contributes to the increased burden of cardiovascular disease in uremia. We further propose that retained uremic solutes such as beta-2 microglobulin, advanced glycosylated end products (AGE), cysteine, and homocysteine, which are substrates for oxidative injury, further contribute to the pro-atherogenic milieu of uremia. Dialytic therapy, which acts to reduce the concentration of oxidized substrates, improves the redox balance. However, processes related to dialytic therapy, such as the prolonged use of catheters for vascular access and the use of bioincompatible dialysis membranes, can contribute to a pro-inflammatory and pro-oxidative state and thus to a pro-atherogenic state. Anti-oxidative therapeutic strategies for patients with uremia are in their very early stages; nonetheless, early studies demonstrate the potential for significant efficacy in reducing cardiovascular complications.
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              Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study.

              Markus Ketteler, Philipp Bongartz, Ralf Westenfeld … (2003)
              Vascular calcification is the most prominent underlying pathological finding in patients with uraemia, and is a predictor of mortality in this population. Fetuin-A (alpha2-Heremans Schmid glycoprotein; AHSG) is an important circulating inhibitor of calcification in vivo, and is downregulated during the acute-phase response. We aimed to investigate the hypothesis that AHSG deficiency is directly related to uraemic vascular calcification. We did a cross-sectional study in 312 stable patients on haemodialysis to analyse the inter-relation of AHSG and C-reactive protein (CRP) and their predictive effect on all-cause and cardiovascular mortality, over a period of 32 months. Subsequently, we tested the capacity of serum to inhibit CaxPO4 precipitation in patients on long-term dialysis (n=17) with apparent soft-tissue calcifications, and in those on short-term dialysis (n=8) without evidence of calcifications and cardiovascular disease. AHSG concentrations in serum were significantly lower in patients on haemodialysis (mean 0.66 g/L [SD 0.28]) than in healthy controls (0.72 [0.19]). Low concentrations of the glycoprotein were associated with raised amounts of CRP and with enhanced cardiovascular (p=0.031) and all-cause mortality (p=0.0013). Sera from patients on long-term dialysis with low AHSG concentrations showed impaired ex-vivo capacity to inhibit CaxPO4 precipitation (mean IC50: 9.0 microL serum [SD 3.1] vs 7.5 [0.8] in short-term patients and 6.4 [2.6] in controls). Reconstitution of sera with purified AHSG returned this impairment to normal. Interpretation AHSG deficiency is associated with inflammation and links vascular calcification to mortality in patients on dialysis. Activated acute-phase response and AHSG deficiency might account for accelerated atherosclerosis in uraemia.
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                Author and article information

                Contributors
                : +44-207-8138309 , +44-207-8298841 , LederS@gosh.nhs.uk
                Journal
                Journal ID (nlm-ta): Pediatr Nephrol
                Title: Pediatric Nephrology (Berlin, Germany)
                Publisher: Springer-Verlag (Berlin/Heidelberg )
                ISSN (Print): 0931-041X
                ISSN (Electronic): 1432-198X
                Publication date (Electronic): 23 January 2008
                Publication date (Print): March 2009
                Volume: 24
                Issue: 3
                Pages: 463-474
                Affiliations
                Department of Nephrourology, Great Ormond Street Hospital for Children NHS Trust London, Great Ormond Street, London, WC1 N3JH UK
                Article
                Publisher ID: 700
                DOI: 10.1007/s00467-007-0700-2
                PMC ID: 2755764
                PubMed ID: 18214549
                SO-VID: c804bb8b-70f0-4dfd-b544-58356c63e4e4
                Copyright © © IPNA 2007
                History
                Date received : 13 July 2007
                Date revision received : 2 October 2007
                Date accepted : 23 October 2007
                Categories
                Subject: Educational Feature
                Custom metadata
                issue-copyright-statement © IPNA 2009

                ScienceOpen disciplines: Nephrology
                Keywords: dialysis,vascular access,long-term outcome,children,cardiovascular mortality
                Data availability:
                ScienceOpen disciplines: Nephrology
                Keywords: dialysis, vascular access, long-term outcome, children, cardiovascular mortality

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