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      Measures of Loop Diuretic Efficiency and Prognosis in Chronic Kidney Disease

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          Abstract

          Background: The evolution and prognostic impact of loop diuretic efficiency according to chronic kidney disease (CKD) severity is unclear. Methods: This retrospective cohort study includes 783 CKD patients on oral loop diuretic therapy with a 24-h urine collection available. Acute kidney injury and history of renal replacement therapy were exclusion criteria. Patients were stratified according to Kidney Disease Improving Global Outcomes (KDIGO) glomerular filtration rate class. Loop diuretic efficiency was calculated as urine output, natriuresis, and chloruresis, each adjusted for loop diuretic dose, and compared among strata. Risk for onset of dialysis and all-cause mortality was evaluated. Results: Loop diuretic efficiency metrics decreased from KDIGO class IIIB to IV in furosemide users and from KDIGO class IV to V with all loop diuretics ( p value <0.05 for all comparisons). The correlation between loop diuretic efficiency and creatinine clearance was moderate at best (Spearman’s ρ 0.298–0.436; p value <0.001 for all correlations). During median follow-up of 45 months, 457 patients died (58%) and 63 received kidney transplantation (8%), while dialysis was started before in 328 (42%). All loop diuretic efficiency metrics were significantly and independently associated with both the risk for dialysis and all-cause mortality. In KDIGO class IV/V patients, low loop diuretic efficiency (i.e., urine output adjusted for loop diuretic dose ≤1,000 mL) shortened median time to dialysis with 24 months and median time to all-cause mortality with 23 months. Conclusion: Low loop diuretic efficiency is independently associated with a shorter time to dialysis initiation and a higher risk for all-cause mortality in CKD.

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          Most cited references 25

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          A new equation to estimate glomerular filtration rate.

          Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values. To develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates. Research studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006. 8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16,032 participants in NHANES. GFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age. In the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%). The sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR. The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use. National Institute of Diabetes and Digestive and Kidney Diseases.
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            Diuretic response in acute heart failure: clinical characteristics and prognostic significance.

            Diminished diuretic response is common in patients with acute heart failure, although a clinically useful definition is lacking. Our aim was to investigate a practical, workable metric for diuretic response, examine associated patient characteristics and relationships with outcome. We examined diuretic response (defined as Δ weight kg/40 mg furosemide) in 1745 hospitalized acute heart failure patients from the PROTECT trial. Day 4 response was used to allow maximum differentiation in responsiveness and tailoring of diuretic doses to clinical response, following sensitivity analyses. We investigated predictors of diuretic response and relationships with outcome. The median diuretic response was -0.38 (-0.80 to -0.13) kg/40 mg furosemide. Poor diuretic response was independently associated with low systolic blood pressure, high blood urea nitrogen, diabetes, and atherosclerotic disease (all P < 0.05). Worse diuretic response independently predicted 180-day mortality (HR: 1.42; 95% CI: 1.11-1.81, P = 0.005), 60-day death or renal or cardiovascular rehospitalization (HR: 1.34; 95% CI: 1.14-1.59, P < 0.001) and 60-day HF rehospitalization (HR: 1.57; 95% CI: 1.24-2.01, P < 0.001) in multivariable models. The proposed metric-weight loss indexed to diuretic dose-better captures a dose-response relationship. Model diagnostics showed diuretic response provided essentially the same or slightly better prognostic information compared with its individual components (weight loss and diuretic dose) in this population, while providing a less biased, more easily interpreted signal. Worse diuretic response was associated with more advanced heart failure, renal impairment, diabetes, atherosclerotic disease and in-hospital worsening heart failure, and predicts mortality and heart failure rehospitalization in this post hoc, hypothesis-generating study. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.
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              Diuretic Treatment in Heart Failure

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                Author and article information

                Journal
                CRM
                Cardiorenal Med
                10.1159/issn.1664-5502
                Cardiorenal Medicine
                S. Karger AG
                1664-3828
                1664-5502
                2020
                December 2020
                29 October 2020
                : 10
                : 6
                : 402-414
                Affiliations
                aDepartment of Nephrology, Dialysis and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
                bBiomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium
                cDepartment of Cardiology, Jessa Hospital, Hasselt, Belgium
                dDepartment of Cardiovascular Medicine, Yale Medical Center, New Haven, Connecticut, USA
                eHeart and Vascular Institute, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA
                fNephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
                Author notes
                *Frederik H. Verbrugge, Department of Nephrology, University Hospital Leuven, Herestraat 49, BE–3000 Leuven (Belgium), frederik.verbrugge@zol.be
                Article
                509741 Cardiorenal Med 2020;10:402–414
                10.1159/000509741
                33120398
                © 2020 S. Karger AG, Basel

                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.

                Page count
                Figures: 4, Tables: 2, Pages: 13
                Categories
                Research Article

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