{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:20:00Z","timestamp":1787138400261,"version":"build-2736575974"},"update-to":[{"DOI":"10.12688\/f1000research.109987.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T00:00:00Z","timestamp":1658793600000}}],"reference-count":21,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T00:00:00Z","timestamp":1658793600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regional Department of Health of the Government of Navarre, Spain"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Background:<\/ns4:bold>\n                    \u201cTriple whammy\u201d (TW) refers to the simultaneous use of diuretics, renin-angiotensin-aldosterone system inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs). To date, the risk of developing acute kidney injury (AKI) associated to this combination has not been deeply investigated. The objectives are to analyze the incidence of AKI associated to the exposure to \u201ctriple whammy\u201d including all NSAIDs versus non-exposure to this combination. Secondarily, the risk of hospitalization, severe adverse events, requirement of renal replacement therapy and mortality will be assessed. Also, the incidence of AKI associated to the exposure to \u201ctriple whammy\u201d versus non-exposure will be analyzed, including only metamizole as NSAID.\u00a0\u00a0\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods:<\/ns4:bold>\n                    A systematic literature search of intervention studies and analytical observational studies will be conducted in the Cochrane Library, Medline and EMBASE, among others. AKI 12 months after the last prescription of the triple combination will be the main outcome. Relative frequencies, risk of bias and certainty of evidence will be analyzed. Additionally, sensitivity and subgroup analyses will be performed.\u00a0\u00a0\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results:<\/ns4:bold>\n                    Once this systematic review has been completed, the results are expected to provide an estimate of the risk associated with this triple combination and the renal variables, in addition to new guidance on the renal treatment of patients potentially receiving triple therapy.\u00a0\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusions:<\/ns4:bold>\n                    This is intended to be the first systematic review of observational studies to analyse TW combination and AKI's risk based on well-validated epidemiological databases exploring drug safety issues.\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.109987.2","type":"journal-article","created":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T06:00:08Z","timestamp":1658815208000},"page":"496","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Acute Kidney Injury associated with \"Triple whammy\" combination: a protocol for a systematic review."],"prefix":"10.12688","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1811-9099","authenticated-orcid":false,"given":"Dulce Maria","family":"Calvo Barbado","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9143-5709","authenticated-orcid":false,"given":"Luis Carlos","family":"Saiz Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2272-7086","authenticated-orcid":false,"given":"Leire","family":"Leache Alegr\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Concepci\u00f3n","family":"Celaya Lecea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3229-6614","authenticated-orcid":false,"given":"Marta","family":"Guti\u00e9rrez-Valencia.","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2022,7,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"184-185","DOI":"10.5694\/j.1326-5377.2000.tb125548.x","article-title":"Diuretics, ACE inhibitors and NSAIDs--the triple whammy.","volume":"172","author":"M Thomas","year":"2000","journal-title":"Med. 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Regarding your comments, maybe it is something that we will need to clarify in our protocol. We refer &quot;Events (primary and secondary outcomes) within 12 months after the last prescription of the triple combination will be considered&quot;, due to AKI is not to be measured &quot;at&quot; 12 months but &quot;in&quot; the 12 months following the end of exposure to TW. &nbsp;We sought to extend the AKIs not only to the time patients are exposed, but also to the following 12 months (beyond 12 months we interpret the AKI as not being due to previous exposure). Maybe we need to clarify more in our protocol to be understand better for readers. Regarding your second comments, we agree that it will be a lot of work, but thinking that it is a safety problem, observational studies can be a proper way to do it.  Again we are thankful for your comments and will take in mind. Dulce Maria Calvo","URL":"https:\/\/f1000research.com\/articles\/11-496\/v2#referee-comment-8561","order":1,"name":"referee-comment-8561","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.136059.r156948, Cesar Loza Mu\u00f1arriz, Nephrology Unit, National Hospital Cayetano Heredia, Lima, Peru, 31 Jan 2023, version 2, indexed","URL":"https:\/\/f1000research.com\/articles\/11-496\/v2#referee-response-156948","order":2,"name":"referee-response-156948","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Dulce Maria Calvo Barbado<\/b>; \n<i>Posted: 03 Feb 2023<\/i>; Dear Reviewer: Thank you for your suggestion. This systematic review (SR) has included studies such as clinical trials and analytical observational studies assessing the risk of AKI or morbidity and mortality associated with the &quot;triple whammy&quot; combination. We can inform you that we have already finished the SR. A total of 934 references were initially identified through the database search.&nbsp; Finally, three analytical observational studies were selected. We use the ROBINS-I tool to assess the risk of bias in included studies, and for our three studies, although the confounding factor was used to adjust measures in these studies, the domain of bias due to confounding was rated as having a moderate risk of bias. These three studies have been judged as having a low risk of bias. When both unadjusted and adjusted effect estimates were reported, adjusted effects were preferred. &nbsp; &nbsp;","URL":"https:\/\/f1000research.com\/articles\/11-496\/v2#referee-comment-9302","order":3,"name":"referee-comment-9302","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This study received funds from the 2019 call for research grants of the Regional Department of Health of the Government of Navarre, Spain (Project n. 24\/2019). The Government of Navarre had no role in the design, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}