Compensatory post-diuretic renal sodium reabsorption is not a dominant mechanism of diuretic resistance in acute heart failure
Abstract Aims In healthy volunteers, the kidney deploys compensatory post-diuretic sodium reabsorption (CPDSR) following loop diuretic-induced natriuresis, minimizing sodium excretion and producing a neutral sodium balance. CPDSR is extrapolated to non-euvolemic populations as a diuretic resistance...
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| Veröffentlicht in: | European heart journal 2021-11, Vol.42 (43), p.4468-4477 |
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| creator | Cox, Zachary L Rao, Veena S Ivey-Miranda, Juan B Moreno-Villagomez, Julieta Mahoney, Devin Ponikowski, Piotr Biegus, Jan Turner, Jeffrey M Maulion, Christopher Bellumkonda, Lavanya Asher, Jennifer L Parise, Helen Wilson, Perry F Ellison, David H Wilcox, Christopher S Testani, Jeffrey M |
| description | Abstract
Aims
In healthy volunteers, the kidney deploys compensatory post-diuretic sodium reabsorption (CPDSR) following loop diuretic-induced natriuresis, minimizing sodium excretion and producing a neutral sodium balance. CPDSR is extrapolated to non-euvolemic populations as a diuretic resistance mechanism; however, its importance in acute decompensated heart failure (ADHF) is unknown.
Methods and results
Patients with ADHF in the Mechanisms of Diuretic Resistance cohort receiving intravenous loop diuretics (462 administrations in 285 patients) underwent supervised urine collections entailing an immediate pre-diuretic spot urine sample, then 6-h (diuretic-induced natriuresis period) and 18-h (post-diuretic period) urine collections. The average spot urine sodium concentration immediately prior to diuretic administration [median 15 h (13–17) after last diuretic] was 64 ± 33 mmol/L with only 4% of patients having low ( |
| doi_str_mv | 10.1093/eurheartj/ehab620 |
| format | Article |
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Aims
In healthy volunteers, the kidney deploys compensatory post-diuretic sodium reabsorption (CPDSR) following loop diuretic-induced natriuresis, minimizing sodium excretion and producing a neutral sodium balance. CPDSR is extrapolated to non-euvolemic populations as a diuretic resistance mechanism; however, its importance in acute decompensated heart failure (ADHF) is unknown.
Methods and results
Patients with ADHF in the Mechanisms of Diuretic Resistance cohort receiving intravenous loop diuretics (462 administrations in 285 patients) underwent supervised urine collections entailing an immediate pre-diuretic spot urine sample, then 6-h (diuretic-induced natriuresis period) and 18-h (post-diuretic period) urine collections. The average spot urine sodium concentration immediately prior to diuretic administration [median 15 h (13–17) after last diuretic] was 64 ± 33 mmol/L with only 4% of patients having low (<20 mmol/L) urine sodium consistent with CPDSR. Paradoxically, greater 6-h diuretic-induced natriuresis was associated with larger 18-h post-diuretic spontaneous natriuresis (r = 0.7, P < 0.001). Higher pre-diuretic urine sodium to creatinine ratio (r = 0.37, P < 0.001) was the strongest predictor of post-diuretic spontaneous natriuresis. In a subgroup of patients (n = 43) randomized to protocol-driven intensified diuretic therapies, the mean diuretic-induced natriuresis increased three-fold. In contrast to the substantial decrease in spontaneous natriuresis predicted by CPDSR, no change in post-diuretic spontaneous natriuresis was observed (P = 0.47).
Conclusion
On a population level, CPDSR was not an important driver of diuretic resistance in hypervolemic ADHF. Contrary to CPDSR, a greater diuretic-induced natriuresis predicted a larger post-diuretic spontaneous natriuresis. Basal sodium avidity, rather than diuretic-induced CPDSR, appears to be the predominant determinate of both diuretic-induced and post-diuretic natriuresis in hypervolemic ADHF.
Graphical Abstract</description><identifier>ISSN: 0195-668X</identifier><identifier>EISSN: 1522-9645</identifier><identifier>DOI: 10.1093/eurheartj/ehab620</identifier><identifier>PMID: 34529781</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Clinical Research ; Diuretics - therapeutic use ; Heart Failure - drug therapy ; Humans ; Natriuresis ; Sodium ; Sodium Potassium Chloride Symporter Inhibitors</subject><ispartof>European heart journal, 2021-11, Vol.42 (43), p.4468-4477</ispartof><rights>Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com. 2021</rights><rights>Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c436t-a13c38d266e6bb9805513979667538e7bf1c122e7d20ef0125bc08f6485f18153</citedby><cites>FETCH-LOGICAL-c436t-a13c38d266e6bb9805513979667538e7bf1c122e7d20ef0125bc08f6485f18153</cites><orcidid>0000-0001-6966-8795 ; 0000-0001-9977-7722 ; 0000-0001-7761-4973 ; 0000-0001-9059-1083 ; 0000-0002-9317-9067 ; 0000-0001-8800-7298 ; 0000-0002-4919-0146 ; 0000-0002-2633-2412 ; 0000-0003-2915-265X ; 0000-0002-2510-4266</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,1584,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34529781$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cox, Zachary L</creatorcontrib><creatorcontrib>Rao, Veena S</creatorcontrib><creatorcontrib>Ivey-Miranda, Juan B</creatorcontrib><creatorcontrib>Moreno-Villagomez, Julieta</creatorcontrib><creatorcontrib>Mahoney, Devin</creatorcontrib><creatorcontrib>Ponikowski, Piotr</creatorcontrib><creatorcontrib>Biegus, Jan</creatorcontrib><creatorcontrib>Turner, Jeffrey M</creatorcontrib><creatorcontrib>Maulion, Christopher</creatorcontrib><creatorcontrib>Bellumkonda, Lavanya</creatorcontrib><creatorcontrib>Asher, Jennifer L</creatorcontrib><creatorcontrib>Parise, Helen</creatorcontrib><creatorcontrib>Wilson, Perry F</creatorcontrib><creatorcontrib>Ellison, David H</creatorcontrib><creatorcontrib>Wilcox, Christopher S</creatorcontrib><creatorcontrib>Testani, Jeffrey M</creatorcontrib><title>Compensatory post-diuretic renal sodium reabsorption is not a dominant mechanism of diuretic resistance in acute heart failure</title><title>European heart journal</title><addtitle>Eur Heart J</addtitle><description>Abstract
Aims
In healthy volunteers, the kidney deploys compensatory post-diuretic sodium reabsorption (CPDSR) following loop diuretic-induced natriuresis, minimizing sodium excretion and producing a neutral sodium balance. CPDSR is extrapolated to non-euvolemic populations as a diuretic resistance mechanism; however, its importance in acute decompensated heart failure (ADHF) is unknown.
Methods and results
Patients with ADHF in the Mechanisms of Diuretic Resistance cohort receiving intravenous loop diuretics (462 administrations in 285 patients) underwent supervised urine collections entailing an immediate pre-diuretic spot urine sample, then 6-h (diuretic-induced natriuresis period) and 18-h (post-diuretic period) urine collections. The average spot urine sodium concentration immediately prior to diuretic administration [median 15 h (13–17) after last diuretic] was 64 ± 33 mmol/L with only 4% of patients having low (<20 mmol/L) urine sodium consistent with CPDSR. Paradoxically, greater 6-h diuretic-induced natriuresis was associated with larger 18-h post-diuretic spontaneous natriuresis (r = 0.7, P < 0.001). Higher pre-diuretic urine sodium to creatinine ratio (r = 0.37, P < 0.001) was the strongest predictor of post-diuretic spontaneous natriuresis. In a subgroup of patients (n = 43) randomized to protocol-driven intensified diuretic therapies, the mean diuretic-induced natriuresis increased three-fold. In contrast to the substantial decrease in spontaneous natriuresis predicted by CPDSR, no change in post-diuretic spontaneous natriuresis was observed (P = 0.47).
Conclusion
On a population level, CPDSR was not an important driver of diuretic resistance in hypervolemic ADHF. Contrary to CPDSR, a greater diuretic-induced natriuresis predicted a larger post-diuretic spontaneous natriuresis. Basal sodium avidity, rather than diuretic-induced CPDSR, appears to be the predominant determinate of both diuretic-induced and post-diuretic natriuresis in hypervolemic ADHF.
Graphical Abstract</description><subject>Clinical Research</subject><subject>Diuretics - therapeutic use</subject><subject>Heart Failure - drug therapy</subject><subject>Humans</subject><subject>Natriuresis</subject><subject>Sodium</subject><subject>Sodium Potassium Chloride Symporter Inhibitors</subject><issn>0195-668X</issn><issn>1522-9645</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU2LFDEQhoMo7rj6A7xIjh5sNx-ddHIRZPALFrwoeAvV6WonS3fSJumFvfjbbZ1xWG-eQqWeeqrgJeQ5Z685s_IK13xAyPXmCg_Qa8EekB1XQjRWt-oh2TFuVaO1-XZBnpRywxgzmuvH5EK2StjO8B35uU_zgrFATfmOLqnUZghrxho8zRhhoiVtH_NWQF9SXmpIkYZCY6oU6JDmECFWOqM_QAxlpmmk9wwllArRIw2Rgl8r0j8X0xHCtEFPyaMRpoLPTu8l-fr-3Zf9x-b684dP-7fXjW-lrg1w6aUZhNao-94aphSXtrNad0oa7PqRey4EdoNgODIuVO-ZGXVr1MgNV_KSvDl6l7WfcfAYa4bJLTnMkO9cguD-7cRwcN_TrTPKWibEJnh5EuT0Y8VS3RyKx2mCiGktTqiubZlqudxQfkR9TqVkHM9rOHO_c3Pn3Nwpt23mxf37zhN_g9qAV0cgrct_-H4BZmiq0w</recordid><startdate>20211114</startdate><enddate>20211114</enddate><creator>Cox, Zachary L</creator><creator>Rao, Veena S</creator><creator>Ivey-Miranda, Juan B</creator><creator>Moreno-Villagomez, Julieta</creator><creator>Mahoney, Devin</creator><creator>Ponikowski, Piotr</creator><creator>Biegus, Jan</creator><creator>Turner, Jeffrey M</creator><creator>Maulion, Christopher</creator><creator>Bellumkonda, Lavanya</creator><creator>Asher, Jennifer L</creator><creator>Parise, Helen</creator><creator>Wilson, Perry F</creator><creator>Ellison, David H</creator><creator>Wilcox, Christopher S</creator><creator>Testani, Jeffrey M</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6966-8795</orcidid><orcidid>https://orcid.org/0000-0001-9977-7722</orcidid><orcidid>https://orcid.org/0000-0001-7761-4973</orcidid><orcidid>https://orcid.org/0000-0001-9059-1083</orcidid><orcidid>https://orcid.org/0000-0002-9317-9067</orcidid><orcidid>https://orcid.org/0000-0001-8800-7298</orcidid><orcidid>https://orcid.org/0000-0002-4919-0146</orcidid><orcidid>https://orcid.org/0000-0002-2633-2412</orcidid><orcidid>https://orcid.org/0000-0003-2915-265X</orcidid><orcidid>https://orcid.org/0000-0002-2510-4266</orcidid></search><sort><creationdate>20211114</creationdate><title>Compensatory post-diuretic renal sodium reabsorption is not a dominant mechanism of diuretic resistance in acute heart failure</title><author>Cox, Zachary L ; Rao, Veena S ; Ivey-Miranda, Juan B ; Moreno-Villagomez, Julieta ; Mahoney, Devin ; Ponikowski, Piotr ; Biegus, Jan ; Turner, Jeffrey M ; Maulion, Christopher ; Bellumkonda, Lavanya ; Asher, Jennifer L ; Parise, Helen ; Wilson, Perry F ; Ellison, David H ; Wilcox, Christopher S ; Testani, Jeffrey M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c436t-a13c38d266e6bb9805513979667538e7bf1c122e7d20ef0125bc08f6485f18153</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Clinical Research</topic><topic>Diuretics - therapeutic use</topic><topic>Heart Failure - drug therapy</topic><topic>Humans</topic><topic>Natriuresis</topic><topic>Sodium</topic><topic>Sodium Potassium Chloride Symporter Inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cox, Zachary L</creatorcontrib><creatorcontrib>Rao, Veena S</creatorcontrib><creatorcontrib>Ivey-Miranda, Juan B</creatorcontrib><creatorcontrib>Moreno-Villagomez, Julieta</creatorcontrib><creatorcontrib>Mahoney, Devin</creatorcontrib><creatorcontrib>Ponikowski, Piotr</creatorcontrib><creatorcontrib>Biegus, Jan</creatorcontrib><creatorcontrib>Turner, Jeffrey M</creatorcontrib><creatorcontrib>Maulion, Christopher</creatorcontrib><creatorcontrib>Bellumkonda, Lavanya</creatorcontrib><creatorcontrib>Asher, Jennifer L</creatorcontrib><creatorcontrib>Parise, Helen</creatorcontrib><creatorcontrib>Wilson, Perry F</creatorcontrib><creatorcontrib>Ellison, David H</creatorcontrib><creatorcontrib>Wilcox, Christopher S</creatorcontrib><creatorcontrib>Testani, Jeffrey M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>European heart journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cox, Zachary L</au><au>Rao, Veena S</au><au>Ivey-Miranda, Juan B</au><au>Moreno-Villagomez, Julieta</au><au>Mahoney, Devin</au><au>Ponikowski, Piotr</au><au>Biegus, Jan</au><au>Turner, Jeffrey M</au><au>Maulion, Christopher</au><au>Bellumkonda, Lavanya</au><au>Asher, Jennifer L</au><au>Parise, Helen</au><au>Wilson, Perry F</au><au>Ellison, David H</au><au>Wilcox, Christopher S</au><au>Testani, Jeffrey M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Compensatory post-diuretic renal sodium reabsorption is not a dominant mechanism of diuretic resistance in acute heart failure</atitle><jtitle>European heart journal</jtitle><addtitle>Eur Heart J</addtitle><date>2021-11-14</date><risdate>2021</risdate><volume>42</volume><issue>43</issue><spage>4468</spage><epage>4477</epage><pages>4468-4477</pages><issn>0195-668X</issn><eissn>1522-9645</eissn><abstract>Abstract
Aims
In healthy volunteers, the kidney deploys compensatory post-diuretic sodium reabsorption (CPDSR) following loop diuretic-induced natriuresis, minimizing sodium excretion and producing a neutral sodium balance. CPDSR is extrapolated to non-euvolemic populations as a diuretic resistance mechanism; however, its importance in acute decompensated heart failure (ADHF) is unknown.
Methods and results
Patients with ADHF in the Mechanisms of Diuretic Resistance cohort receiving intravenous loop diuretics (462 administrations in 285 patients) underwent supervised urine collections entailing an immediate pre-diuretic spot urine sample, then 6-h (diuretic-induced natriuresis period) and 18-h (post-diuretic period) urine collections. The average spot urine sodium concentration immediately prior to diuretic administration [median 15 h (13–17) after last diuretic] was 64 ± 33 mmol/L with only 4% of patients having low (<20 mmol/L) urine sodium consistent with CPDSR. Paradoxically, greater 6-h diuretic-induced natriuresis was associated with larger 18-h post-diuretic spontaneous natriuresis (r = 0.7, P < 0.001). Higher pre-diuretic urine sodium to creatinine ratio (r = 0.37, P < 0.001) was the strongest predictor of post-diuretic spontaneous natriuresis. In a subgroup of patients (n = 43) randomized to protocol-driven intensified diuretic therapies, the mean diuretic-induced natriuresis increased three-fold. In contrast to the substantial decrease in spontaneous natriuresis predicted by CPDSR, no change in post-diuretic spontaneous natriuresis was observed (P = 0.47).
Conclusion
On a population level, CPDSR was not an important driver of diuretic resistance in hypervolemic ADHF. Contrary to CPDSR, a greater diuretic-induced natriuresis predicted a larger post-diuretic spontaneous natriuresis. Basal sodium avidity, rather than diuretic-induced CPDSR, appears to be the predominant determinate of both diuretic-induced and post-diuretic natriuresis in hypervolemic ADHF.
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | Clinical Research Diuretics - therapeutic use Heart Failure - drug therapy Humans Natriuresis Sodium Sodium Potassium Chloride Symporter Inhibitors |
| title | Compensatory post-diuretic renal sodium reabsorption is not a dominant mechanism of diuretic resistance in acute heart failure |
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