Cardiac Disease in Chronic Kidney Disease: Current Understandings and Opportunities for Change

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Abstract

Cardiovascular disease (CVD) is prevalent in patients with kidney disease: in populations prior to dialysis, on dialysis and after transplantation. Publications over the last decade have focused on this, and more recently, patients with cardiac disease are now recognized as being at increased risk in the presence of even mild kidney dysfunction. The presence of both traditional and non-traditional risk factors contributes to this overwhelming burden of cardiovascular disease in patients with chronic kidney disease (CKD). Recent studies have focused on the impact of anemia and disorders of mineral metabolism on CVD outcomes, in the context of inflammation and evidence of cytokine activation. Cross-sectional and prospective observational studies have led to improved understanding, and generated novel hypotheses. To date, no clinical trial has determined the positive impact of interventions targeted at these novel risk factors. This overview describes the current state of knowledge and emphasizes the interplay between CVD and CKD as two aspects of a set of pathophysiological processes, which impact on patient outcomes.

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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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The impact of renal insufficiency on clinical outcomes in patients undergoing percutaneous coronary interventions.

Carolyn Best, Angela H. Ting, Charanjit Rihal … (2002)

We sought to determine the effect of varying degrees of renal insufficiency on death and cardiac events during and after a percutaneous coronary intervention (PCI). Patients with end-stage renal disease have a high mortality from coronary artery disease. Little is known about the impact of mild and moderate renal insufficiency on clinical outcomes after PCI. Cardiac mortality and all-cause mortality were determined for 5,327 patients undergoing PCI from January 1, 1994, to August 31, 1999, at the Mayo Clinic, based on the estimated creatinine clearance or whether the patient was on dialysis. In-hospital mortality was significantly associated with renal insufficiency (p = 0.001). Even after successful PCI, one-year mortality was 1.5% when the creatinine clearance was > or =70 ml/min (n = 2,558), 3.6% when it was 50 to 69 ml/min (n = 1,458), 7.8% when it was 30 to 49 ml/min (n = 828) and 18.3% when it was < 30 ml/min (n = 141). The 18.3% mortality rate for the group with < 30 ml/min creatinine clearance was similar to the 19.9% mortality rate in patients on dialysis (n = 46). The mortality risk was largely independent of all other factors. Renal insufficiency is a strong predictor of death and subsequent cardiac events in a dose-dependent fashion during and after PCI. Patients with renal insufficiency have more baseline cardiovascular risk factors, but renal insufficiency is associated with an increased risk of death and other adverse cardiovascular events, independent of all other measured variables.

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The prognostic implications of renal insufficiency in asymptomatic and symptomatic patients with left ventricular systolic dysfunction.

Daniel L Dries, Derek Exner, Michael Domanski … (2000)

The present analysis examines the prognostic implications of moderate renal insufficiency in patients with asymptomatic and symptomatic left ventricular systolic dysfunction. Chronic elevations in intracardiac filling pressures may lead to progressive ventricular dilation and heart failure progression. The ability to maintain fluid balance and prevent increased intracardiac filling pressures is critically dependent on the adequacy of renal function. This is a retrospective analysis of the Studies of Left Ventricular Dysfunction (SOLVD) Trials, in which moderate renal insufficiency is defined as a baseline creatinine clearance <60 ml/min, as estimated from the Cockroft-Gault equation. In the SOLVD Prevention Trial, multivariate analyses demonstrated moderate renal insufficiency to be associated with an increased risk for all-cause mortality (Relative Risk [RR] 1.41; p = 0.001), largely explained by an increased risk for pump-failure death (RR 1.68; p = 0.007) and the combined end point death or hospitalization for heart failure (RR 1.33; p = 0.001). Likewise, in the Treatment Trial, multivariate analyses demonstrated moderate renal insufficiency to be associated with an increased risk for all-cause mortality (RR 1.41; p = 0.001), also largely explained by an increased risk for pump-failure death (RR 1.49; p = 0.007) and the combined end point death or hospitalization for heart failure (RR 1.45; p = 0.001). Even moderate degrees of renal insufficiency are independently associated with an increased risk for all-cause mortality in patients with heart failure, largely explained by an increased risk of heart failure progression. These data suggest that, rather than simply being a marker of the severity of underlying disease, the adequacy of renal function may be a primary determinant of compensation in patients with heart failure, and therapy capable of improving renal function may delay disease progression.

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Journal

Journal ID (publisher-id): BPU

Journal ID (nlm-ta): Blood Purif

Journal ID (doi): 10.1159/issn.0253-5068

Title: Blood Purification

Publisher: S. Karger AG

ISBN: 978-3-8055-7683-3

ISBN: 978-3-318-01049-7

ISSN (Print): 0253-5068

ISSN (Electronic): 1421-9735

Publication date Subscription-year: 2004

Publication date (Print): July 2004

Publication date (Electronic): 20 January 2004

Volume: 22

Issue: 1

Pages: 21-27

Affiliations

St Paul’s Hospital, University of British Columbia, Vancouver, Canada

Article

Publisher ID: 74920 Other ID: Blood Purif 2004;22:21–27

DOI: 10.1159/000074920

PubMed ID: 14732808

SO-VID: 143230cd-7a02-4a2a-87af-b6f8f420ae70

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Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

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Cardiac Disease in Chronic Kidney Disease: Current Understandings and Opportunities for Change

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Karger: Nephrology

Most cited references 11

Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study.

The impact of renal insufficiency on clinical outcomes in patients undergoing percutaneous coronary interventions.

The prognostic implications of renal insufficiency in asymptomatic and symptomatic patients with left ventricular systolic dysfunction.

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