b15efd4f7cc6e6d6d4671d98a306889e toxics-13-00417-v2.pdf 101a5c0242ac0426f311dbc4362b1c0c0e85cb68 toxics-13-00417-v2.pdf 9f8b1c7e4a8244d491fe849926c0979afa824b398e11272ec0d231d29eb0a67e toxics-13-00417-v2.pdf Title: Does Metamizole Cause Less Acute Kidney Injury than Non-Steroidal Anti-Inflammatory Drugs When Combined with Diuretics and Antihypertensives? Subject: The concurrent use of (a) diuretics, (b) renin–angiotensin–aldosterone system inhibitors (RAASIs), and (c) non-steroidal anti-inflammatory drugs (NSAIDs) or metamizole, known as the triple whammy (TW) combination, increases the risk of acute kidney injury (AKI). This study compared TWs including metamizole versus NSAIDs regarding hospitalisation for AKI, need for renal replacement therapy (RRT), and all-cause mortality during hospitalisation. Serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) changes in the first year after TW initiation were also assessed. A nested case–control study was conducted within a cohort of adults receiving TW therapy (2009–2018). Logistic regression models analysed the associations between TW type and outcomes. Among 65,077 individuals (mean age 79.7 years; 26.3% male), TW including an NSAID was associated with a lower risk of AKI-related hospitalisation [adjusted odds ratio (aOR) 0.81, 95%CI 0.74–0.87] and all-cause mortality (aOR 0.64, 95%CI 0.49–0.82) compared to TW including metamizole. No significant differences were found in other variables. These findings suggest that TW including an NSAID may reduce the risk of AKI-related hospitalisation and mortality compared to TW including metamizole, although kidney function parameters remained unaffected. Further research is needed to confirm these results. Keywords: acute kidney injury; antihypertensives; diuretics; metamizole; non-steroidal anti-inflammatory agents; safety; triple whammy Author: Dulce Maria Calvo, Luis Carlos Saiz, Leire Leache, Maria C. Celaya, Marta Gutiérrez-Valencia, Alvaro Alonso and Juan Erviti Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Thu May 22 14:32:17 2025 CEST ModDate: Thu May 22 14:36:04 2025 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 13 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 235321 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- GARYOS+URWPalladioL-Roma Type 1 Custom yes yes yes 10 0 JQBVJU+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 OUZRAE+URWPalladioL-Ital Type 1 Custom yes yes yes 21 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 56 0 EILUJF+CMSY10 Type 1 Builtin yes yes yes 61 0 QDCWHF+EURM10 Type 1 Builtin yes yes yes 69 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-06-12 02:07:51 CEST RepresentationInformation: toxics-13-00417-v2.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-06-11 13:43:44 CEST Size: 235321 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 196 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Study Design and Source of Data Destination: subsection.2.1 Item: Title: Study Cohort and Follow-Up Destination: subsection.2.2 Item: Title: Exposure to TW and Comparison Destination: subsection.2.3 Item: Title: Variables Destination: subsection.2.4 Item: Title: Data Analysis Destination: subsection.2.5 Item: Title: Results Destination: section.3 Children: Item: Title: Outcomes in Primary and Secondary Variables Destination: subsection.3.1 Item: Title: Sensitivity Analysis of the Primary Outcome Destination: subsection.3.2 Item: Title: Subgroup Analysis of the Primary Outcome Destination: subsection.3.3 Item: Title: Discussion Destination: section.4 Children: Item: Title: Evidence from Other Published Studies Destination: subsection.4.1 Item: Title: Strengths Destination: subsection.4.2 Item: Title: Limitations Destination: subsection.4.3 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: Does Metamizole Cause Less Acute Kidney Injury than Non-Steroidal Anti-Inflammatory Drugs When Combined with Diuretics and Antihypertensives? Author: Dulce Maria Calvo, Luis Carlos Saiz, Leire Leache, Maria C. Celaya, Marta Gutiérrez-Valencia, Alvaro Alonso and Juan Erviti Subject: The concurrent use of (a) diuretics, (b) renin angiotensin aldosterone system inhibitors (RAASIs), and (c) non-steroidal anti-inflammatory drugs (NSAIDs) or metamizole, known as the triple whammy (TW) combination, increases the risk of acute kidney injury (AKI). This study compared TWs including metamizole versus NSAIDs regarding hospitalisation for AKI, need for renal replacement therapy (RRT), and all-cause mortality during hospitalisation. Serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) changes in the first year after TW initiation were also assessed. A nested case control study was conducted within a cohort of adults receiving TW therapy (2009 2018). Logistic regression models analysed the associations between TW type and outcomes. Among 65,077 individuals (mean age 79.7 years; 26.3% male), TW including an NSAID was associated with a lower risk of AKI-related hospitalisation [adjusted odds ratio (aOR) 0.81, 95%CI 0.74 0.87] and all-cause mortality (aOR 0.64, 95%CI 0.49 0.82) compared to TW including metamizole. No significant differences were found in other variables. These findings suggest that TW including an NSAID may reduce the risk of AKI-related hospitalisation and mortality compared to TW including metamizole, although kidney function parameters remained unaffected. Further research is needed to confirm these results. Keywords: acute kidney injury; antihypertensives; diuretics; metamizole; non-steroidal anti-inflammatory agents; safety; triple whammy Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Thu May 22 14:32:17 CEST 2025 ModDate: Thu May 22 14:36:04 CEST 2025 ID: 0x5fea2f06fe51efe855a533e0a1c635a6, 0x5fea2f06fe51efe855a533e0a1c635a6 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: JQBVJU+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 233 FontDescriptor: FontName: JQBVJU+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: OUZRAE+URWPalladioL-Ital FontSubset: true FirstChar: 45 LastChar: 121 FontDescriptor: FontName: OUZRAE+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: QDCWHF+EURM10 FontSubset: true FirstChar: 11 LastChar: 12 FontDescriptor: FontName: QDCWHF+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true ToUnicode: true Font: BaseFont: WBVKDJ+URWPalladioL-BoldItal FontSubset: true FirstChar: 112 LastChar: 112 FontDescriptor: FontName: WBVKDJ+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: GARYOS+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 243 FontDescriptor: FontName: GARYOS+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: EILUJF+CMSY10 FontSubset: true FirstChar: 0 LastChar: 21 FontDescriptor: FontName: EILUJF+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true ToUnicode: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 34, 177, 152, 186 Annotation: Subtype: Link Rect: 34, 167, 82, 174 Annotation: Subtype: Link Rect: 36, 75, 152, 84 Annotation: Subtype: Link Rect: 34, 63, 89, 72 Annotation: Subtype: Link Rect: 34, 773, 117, 809 Annotation: Subtype: Link Rect: 515, 773, 560, 809 Annotation: Subtype: Link Rect: 134, 643, 145, 656 Annotation: Subtype: Link Rect: 242, 643, 253, 656 Annotation: Subtype: Link Rect: 333, 643, 344, 656 Annotation: Subtype: Link Rect: 163, 629, 174, 643 Annotation: Subtype: Link Rect: 250, 629, 261, 643 Annotation: Subtype: Link Rect: 245, 121, 252, 130 ActionDest: 90 Annotation: Subtype: Link Rect: 287, 107, 294, 116 ActionDest: 93 Annotation: Subtype: Link Rect: 297, 107, 304, 116 ActionDest: 93 Annotation: Subtype: Link Rect: 549, 93, 556, 102 ActionDest: 93 Annotation: Subtype: Link Rect: 415, 27, 560, 37 Annotation: Subtype: Link Rect: 34, 356, 87, 375 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 416, 759, 423, 767 ActionDest: 93 Annotation: Subtype: Link Rect: 478, 703, 484, 712 ActionDest: 93 Annotation: Subtype: Link Rect: 304, 647, 311, 656 ActionDest: 93 Annotation: Subtype: Link Rect: 516, 452, 528, 461 ActionDest: 93 Annotation: Subtype: Link Rect: 265, 341, 277, 350 ActionDest: 93 Annotation: Subtype: Link Rect: 277, 341, 289, 350 ActionDest: 93 Annotation: Subtype: Link Rect: 225, 114, 232, 123 ActionDest: 93 Annotation: Subtype: Link Rect: 232, 114, 244, 123 ActionDest: 93 Annotation: Subtype: Link Rect: 495, 98, 560, 110 Annotation: Subtype: Link Rect: 165, 84, 207, 96 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 297, 758, 304, 767 ActionDest: 93 Annotation: Subtype: Link Rect: 305, 759, 317, 767 ActionDest: 93 Annotation: Subtype: Link Rect: 287, 744, 294, 754 ActionDest: 93 Annotation: Subtype: Link Rect: 544, 634, 556, 643 ActionDest: 93 Annotation: Subtype: Link Rect: 340, 274, 352, 283 ActionDest: 93 Annotation: Subtype: Link Rect: 222, 162, 234, 171 ActionDest: 93 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 363, 332, 375, 341 ActionDest: 93 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 468, 420, 475, 432 ActionDest: 53 Page: Sequence: 6 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 213, 466, 220, 478 ActionDest: 74 Annotation: Subtype: Link Rect: 394, 121, 401, 133 ActionDest: 77 Annotation: Subtype: Link Rect: 513, 107, 519, 119 ActionDest: 77 Page: Sequence: 8 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 284, 370, 296, 379 ActionDest: 93 Annotation: Subtype: Link Rect: 453, 314, 460, 323 ActionDest: 93 Annotation: Subtype: Link Rect: 460, 314, 472, 323 ActionDest: 93 Annotation: Subtype: Link Rect: 475, 314, 487, 323 ActionDest: 93 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 285, 730, 292, 740 ActionDest: 93 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 207, 452, 219, 461 ActionDest: 93 Annotation: Subtype: Link Rect: 536, 242, 560, 253 Annotation: Subtype: Link Rect: 165, 229, 383, 240 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 478, 91, 515, 102 Annotation: Subtype: Link Rect: 521, 91, 557, 102 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 243, 731, 280, 742 Annotation: Subtype: Link Rect: 286, 731, 322, 742 Annotation: Subtype: Link Rect: 168, 692, 206, 703 Annotation: Subtype: Link Rect: 212, 692, 248, 703 Annotation: Subtype: Link Rect: 59, 655, 96, 665 Annotation: Subtype: Link Rect: 102, 655, 138, 665 Annotation: Subtype: Link Rect: 388, 616, 426, 627 Annotation: Subtype: Link Rect: 432, 616, 468, 627 Annotation: Subtype: Link Rect: 481, 603, 560, 614 Annotation: Subtype: Link Rect: 56, 590, 111, 601 Annotation: Subtype: Link Rect: 201, 577, 315, 588 Annotation: Subtype: Link Rect: 302, 565, 560, 576 Annotation: Subtype: Link Rect: 232, 526, 560, 537 Annotation: Subtype: Link Rect: 56, 513, 289, 524 Annotation: Subtype: Link Rect: 258, 475, 560, 486 Annotation: Subtype: Link Rect: 56, 462, 136, 473 Annotation: Subtype: Link Rect: 272, 411, 309, 422 Annotation: Subtype: Link Rect: 315, 411, 351, 422 Annotation: Subtype: Link Rect: 254, 373, 291, 384 Annotation: Subtype: Link Rect: 297, 373, 333, 384 Annotation: Subtype: Link Rect: 86, 347, 348, 358 Annotation: Subtype: Link Rect: 286, 309, 324, 320 Annotation: Subtype: Link Rect: 397, 284, 435, 295 Annotation: Subtype: Link Rect: 441, 284, 477, 295 Annotation: Subtype: Link Rect: 59, 233, 96, 244 Annotation: Subtype: Link Rect: 102, 233, 138, 244 Annotation: Subtype: Link Rect: 59, 195, 96, 205 Annotation: Subtype: Link Rect: 102, 195, 138, 205 Annotation: Subtype: Link Rect: 409, 156, 446, 167 Annotation: Subtype: Link Rect: 453, 156, 489, 167 Annotation: Subtype: Link Rect: 308, 130, 345, 141 Annotation: Subtype: Link Rect: 352, 130, 388, 141 Checksum: 8ee6ce54 Type: CRC32 Checksum: b15efd4f7cc6e6d6d4671d98a306889e Type: MD5 Checksum: 101a5c0242ac0426f311dbc4362b1c0c0e85cb68 Type: SHA-1 Checksum: 9f8b1c7e4a8244d491fe849926c0979afa824b398e11272ec0d231d29eb0a67e Type: SHA-256