Increased Urine Aquaporin-2 Relative to Plasma Arginine Vasopressin Is a Novel Marker of Response to Tolvaptan in Patients With Decompensated Heart Failure
Background:Preserved function of the renal collecting duct may be essential for response to the vasopressin V2receptor antagonist, tolvaptan (TLV), but the predictors of response to TLV are unknown.Methods and Results:Sixty consecutive patients with stage D decompensated heart failure (HF) who had r...
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| Veröffentlicht in: | Circulation Journal 2014/08/25, Vol.78(9), pp.2240-2249 |
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| creator | Imamura, Teruhiko Kinugawa, Koichiro Fujino, Takeo Inaba, Toshiro Maki, Hisataka Hatano, Masaru Yao, Atsushi Komuro, Issei |
| description | Background:Preserved function of the renal collecting duct may be essential for response to the vasopressin V2receptor antagonist, tolvaptan (TLV), but the predictors of response to TLV are unknown.Methods and Results:Sixty consecutive patients with stage D decompensated heart failure (HF) who had received TLV on a de novo basis were retrospectively enrolled (TLV(+) group). Among them, 41 patients were responders defined according to urine volume (UV) increase after TLV initiation. In the UV-defined responders, plasma arginine vasopressin (P-AVP) had a close correlation with urine aquaporin-2 (U-AQP2; 5.42±3.54 ng/ml; r=0.843, P |
| doi_str_mv | 10.1253/circj.CJ-14-0244 |
| format | Article |
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Among them, 41 patients were responders defined according to urine volume (UV) increase after TLV initiation. In the UV-defined responders, plasma arginine vasopressin (P-AVP) had a close correlation with urine aquaporin-2 (U-AQP2; 5.42±3.54 ng/ml; r=0.843, P<0.001). In contrast, 19 were UV-defined non-responders, and they had extremely low U-AQP2 (0.76±0.59 ng/ml, P<0.001 vs. responders) regardless of P-AVP level. On receiver operating characteristic analysis, U-AQP2/P-AVP ≥0.5×103clearly separated the UV-defined responders from the non-responders. We then identified AQP-defined responders as having U-AQP2/P-AVP ≥0.5×103. Sixty propensity score-matched HF patients without TLV treatment were examined, and exactly the same number of patients as that of the AQP-defined responders (n=41) was selected. These patients had a poorer survival without TLV than the TLV-treated responders during a 2-year observation period (73.8% vs. 94.8%, P=0.034).Conclusions:U-AQP2/P-AVP is a novel predictor of response to TLV in patients with decompensated HF. AQP-defined responders may have a better prognosis on TLV treatment. (Circ J 2014; 78: 2240–2249)</description><identifier>ISSN: 1346-9843</identifier><identifier>EISSN: 1347-4820</identifier><identifier>DOI: 10.1253/circj.CJ-14-0244</identifier><identifier>PMID: 24954239</identifier><language>eng</language><publisher>Japan: The Japanese Circulation Society</publisher><subject>Adult ; Aged ; Antidiuretic Hormone Receptor Antagonists - administration & dosage ; Aquaporin 2 - urine ; Arginine Vasopressin - blood ; Benzazepines - administration & dosage ; Biomarkers - blood ; Biomarkers - urine ; Chronic kidney disease ; Congestive heart failure ; Diabetes insipidus ; Disease-Free Survival ; Diuretics ; Female ; Heart Failure - blood ; Heart Failure - drug therapy ; Heart Failure - metabolism ; Heart Failure - urine ; Humans ; Male ; Middle Aged ; Survival Rate ; Tolvaptan</subject><ispartof>Circulation Journal, 2014/08/25, Vol.78(9), pp.2240-2249</ispartof><rights>2014 THE JAPANESE CIRCULATION SOCIETY</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c494t-a9d6393b4e8136e725c9488d98097098aa5c45103b529c058c21c4bf50138fc53</citedby><cites>FETCH-LOGICAL-c494t-a9d6393b4e8136e725c9488d98097098aa5c45103b529c058c21c4bf50138fc53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,4010,27900,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24954239$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Imamura, Teruhiko</creatorcontrib><creatorcontrib>Kinugawa, Koichiro</creatorcontrib><creatorcontrib>Fujino, Takeo</creatorcontrib><creatorcontrib>Inaba, Toshiro</creatorcontrib><creatorcontrib>Maki, Hisataka</creatorcontrib><creatorcontrib>Hatano, Masaru</creatorcontrib><creatorcontrib>Yao, Atsushi</creatorcontrib><creatorcontrib>Komuro, Issei</creatorcontrib><title>Increased Urine Aquaporin-2 Relative to Plasma Arginine Vasopressin Is a Novel Marker of Response to Tolvaptan in Patients With Decompensated Heart Failure</title><title>Circulation Journal</title><addtitle>Circ J</addtitle><description>Background:Preserved function of the renal collecting duct may be essential for response to the vasopressin V2receptor antagonist, tolvaptan (TLV), but the predictors of response to TLV are unknown.Methods and Results:Sixty consecutive patients with stage D decompensated heart failure (HF) who had received TLV on a de novo basis were retrospectively enrolled (TLV(+) group). Among them, 41 patients were responders defined according to urine volume (UV) increase after TLV initiation. In the UV-defined responders, plasma arginine vasopressin (P-AVP) had a close correlation with urine aquaporin-2 (U-AQP2; 5.42±3.54 ng/ml; r=0.843, P<0.001). In contrast, 19 were UV-defined non-responders, and they had extremely low U-AQP2 (0.76±0.59 ng/ml, P<0.001 vs. responders) regardless of P-AVP level. On receiver operating characteristic analysis, U-AQP2/P-AVP ≥0.5×103clearly separated the UV-defined responders from the non-responders. We then identified AQP-defined responders as having U-AQP2/P-AVP ≥0.5×103. Sixty propensity score-matched HF patients without TLV treatment were examined, and exactly the same number of patients as that of the AQP-defined responders (n=41) was selected. These patients had a poorer survival without TLV than the TLV-treated responders during a 2-year observation period (73.8% vs. 94.8%, P=0.034).Conclusions:U-AQP2/P-AVP is a novel predictor of response to TLV in patients with decompensated HF. AQP-defined responders may have a better prognosis on TLV treatment. (Circ J 2014; 78: 2240–2249)</description><subject>Adult</subject><subject>Aged</subject><subject>Antidiuretic Hormone Receptor Antagonists - administration & dosage</subject><subject>Aquaporin 2 - urine</subject><subject>Arginine Vasopressin - blood</subject><subject>Benzazepines - administration & dosage</subject><subject>Biomarkers - blood</subject><subject>Biomarkers - urine</subject><subject>Chronic kidney disease</subject><subject>Congestive heart failure</subject><subject>Diabetes insipidus</subject><subject>Disease-Free Survival</subject><subject>Diuretics</subject><subject>Female</subject><subject>Heart Failure - blood</subject><subject>Heart Failure - drug therapy</subject><subject>Heart Failure - metabolism</subject><subject>Heart Failure - urine</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Survival Rate</subject><subject>Tolvaptan</subject><issn>1346-9843</issn><issn>1347-4820</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkU1vEzEQhlcIREvhzgn5yGWLP7P2MQoNTVWgQi0crYkz2zps7K3tjcRv4c-y-aC9jOfwvI9GfqvqPaPnjCvxyfnk1uezq5rJmnIpX1SnTMimlprTl_t9UhstxUn1Juc1pdxQZV5XJ1waJbkwp9XfRXAJIeOK3CUfkEwfB-jjuNac_MAOit8iKZHcdJA3QKbp3ocd9xNy7BPm7ANZZALkW9xiR75C-o2JxHYM5z6GvA_fxm4LfYFARvpmdGIomfzy5YF8Rhc3PYYMZbzhEiEVMgffDQnfVq9a6DK-O75n1d384nZ2WV9__7KYTa9rJ40sNZjVRBixlKiZmGDDlTNS65XR1DTUaADlpGJULBU3jirtOHNy2SrKhG6dEmfVx4O3T_FxwFzsxmeHXQcB45AtU2rCddMYPqL0gLoUc07Y2j75DaQ_llG7q8TuK7GzK8uk3VUyRj4c7cNyg6unwP8ORmB-ANa5wD0-AeNPeNfh0dhoa3bj2fwMPECyGMQ_P6Sirw</recordid><startdate>2014</startdate><enddate>2014</enddate><creator>Imamura, Teruhiko</creator><creator>Kinugawa, Koichiro</creator><creator>Fujino, Takeo</creator><creator>Inaba, Toshiro</creator><creator>Maki, Hisataka</creator><creator>Hatano, Masaru</creator><creator>Yao, Atsushi</creator><creator>Komuro, Issei</creator><general>The Japanese Circulation Society</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></search><sort><creationdate>2014</creationdate><title>Increased Urine Aquaporin-2 Relative to Plasma Arginine Vasopressin Is a Novel Marker of Response to Tolvaptan in Patients With Decompensated Heart Failure</title><author>Imamura, Teruhiko ; Kinugawa, Koichiro ; Fujino, Takeo ; Inaba, Toshiro ; Maki, Hisataka ; Hatano, Masaru ; Yao, Atsushi ; Komuro, Issei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c494t-a9d6393b4e8136e725c9488d98097098aa5c45103b529c058c21c4bf50138fc53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antidiuretic Hormone Receptor Antagonists - administration & dosage</topic><topic>Aquaporin 2 - urine</topic><topic>Arginine Vasopressin - blood</topic><topic>Benzazepines - administration & dosage</topic><topic>Biomarkers - blood</topic><topic>Biomarkers - urine</topic><topic>Chronic kidney disease</topic><topic>Congestive heart failure</topic><topic>Diabetes insipidus</topic><topic>Disease-Free Survival</topic><topic>Diuretics</topic><topic>Female</topic><topic>Heart Failure - blood</topic><topic>Heart Failure - drug therapy</topic><topic>Heart Failure - metabolism</topic><topic>Heart Failure - urine</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Survival Rate</topic><topic>Tolvaptan</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Imamura, Teruhiko</creatorcontrib><creatorcontrib>Kinugawa, Koichiro</creatorcontrib><creatorcontrib>Fujino, Takeo</creatorcontrib><creatorcontrib>Inaba, Toshiro</creatorcontrib><creatorcontrib>Maki, Hisataka</creatorcontrib><creatorcontrib>Hatano, Masaru</creatorcontrib><creatorcontrib>Yao, Atsushi</creatorcontrib><creatorcontrib>Komuro, Issei</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><jtitle>Circulation Journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Imamura, Teruhiko</au><au>Kinugawa, Koichiro</au><au>Fujino, Takeo</au><au>Inaba, Toshiro</au><au>Maki, Hisataka</au><au>Hatano, Masaru</au><au>Yao, Atsushi</au><au>Komuro, Issei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased Urine Aquaporin-2 Relative to Plasma Arginine Vasopressin Is a Novel Marker of Response to Tolvaptan in Patients With Decompensated Heart Failure</atitle><jtitle>Circulation Journal</jtitle><addtitle>Circ J</addtitle><date>2014</date><risdate>2014</risdate><volume>78</volume><issue>9</issue><spage>2240</spage><epage>2249</epage><pages>2240-2249</pages><issn>1346-9843</issn><eissn>1347-4820</eissn><abstract>Background:Preserved function of the renal collecting duct may be essential for response to the vasopressin V2receptor antagonist, tolvaptan (TLV), but the predictors of response to TLV are unknown.Methods and Results:Sixty consecutive patients with stage D decompensated heart failure (HF) who had received TLV on a de novo basis were retrospectively enrolled (TLV(+) group). Among them, 41 patients were responders defined according to urine volume (UV) increase after TLV initiation. In the UV-defined responders, plasma arginine vasopressin (P-AVP) had a close correlation with urine aquaporin-2 (U-AQP2; 5.42±3.54 ng/ml; r=0.843, P<0.001). In contrast, 19 were UV-defined non-responders, and they had extremely low U-AQP2 (0.76±0.59 ng/ml, P<0.001 vs. responders) regardless of P-AVP level. On receiver operating characteristic analysis, U-AQP2/P-AVP ≥0.5×103clearly separated the UV-defined responders from the non-responders. We then identified AQP-defined responders as having U-AQP2/P-AVP ≥0.5×103. Sixty propensity score-matched HF patients without TLV treatment were examined, and exactly the same number of patients as that of the AQP-defined responders (n=41) was selected. These patients had a poorer survival without TLV than the TLV-treated responders during a 2-year observation period (73.8% vs. 94.8%, P=0.034).Conclusions:U-AQP2/P-AVP is a novel predictor of response to TLV in patients with decompensated HF. AQP-defined responders may have a better prognosis on TLV treatment. (Circ J 2014; 78: 2240–2249)</abstract><cop>Japan</cop><pub>The Japanese Circulation Society</pub><pmid>24954239</pmid><doi>10.1253/circj.CJ-14-0244</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Antidiuretic Hormone Receptor Antagonists - administration & dosage Aquaporin 2 - urine Arginine Vasopressin - blood Benzazepines - administration & dosage Biomarkers - blood Biomarkers - urine Chronic kidney disease Congestive heart failure Diabetes insipidus Disease-Free Survival Diuretics Female Heart Failure - blood Heart Failure - drug therapy Heart Failure - metabolism Heart Failure - urine Humans Male Middle Aged Survival Rate Tolvaptan |
| title | Increased Urine Aquaporin-2 Relative to Plasma Arginine Vasopressin Is a Novel Marker of Response to Tolvaptan in Patients With Decompensated Heart Failure |
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