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Pirfenidone Effect on the Recovery of Renal Function in Septic Acute Kidney Injury (AKI)

Primary Purpose

Acute Kidney Injury, Sepsis

Status
Unknown status
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Pirfenidone extended release
Placebo equivalent
Sponsored by
Hospital Civil de Guadalajara
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Kidney Injury focused on measuring septic acute kidney injury, pirfenidone

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

. sepsis

  • AKI by serum creatinine, according to the KDIGO guide 2012 Acute Kidney Injury • acute on Chronic kidney disease (baseline creatinine <2 mg / dL)

Exclusion Criteria:

  • Chronic kidney disease stage 3b, 4 or 5 (basal serum creatinine > 2mg/dl) known and / or sharpened.

    • chronic dialysis (peritoneal dialysis or hemodialysis)
    • History of AKI and / or RRT in the last three months
    • Pregnancy AKI by other causes other than sepsis

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Active Comparator

    Active Comparator

    Placebo Comparator

    Arm Label

    Group 1

    Group 2

    Group 3

    Arm Description

    Pirfenidone extended release 600mg per mouth every 12 hours for 7 days.

    Pirfenidone extended release 600mg per mouth in the morning and placebo by night (each treatment every 12 hrs) for 7 days.

    Placebo equivalent per mouth every 12 hrs for 7 days.

    Outcomes

    Primary Outcome Measures

    renal function recovery
    serum creatinine in serum <2mg/dl and urinary output >1,200 ml/day
    renal function recovery
    serum creatinine in serum <2mg/dl and urinary output >1,200ml/day

    Secondary Outcome Measures

    Urinary Volume
    Urinary Volume in milliliters in 24 hours
    need of renal replacement therapy (RRT)
    the patient still need renal replacement (RRT) by the judgment of the nephrologist.
    mortality
    the patient dead
    serum creatinine levels
    serum creatinine levels in mg/dL
    serum urea levels
    serum urea levels in mg/dL
    pirfenidone levels in serum ug/mL
    pirfenidone levels in serum ug/mL
    IL-1
    Interleucin 1 in serum pg/mL
    IL-6
    Interleucin 6 in serum pg/mL
    TNF-α
    tumor necrosis factor in serum pg/dL
    Toll-like receptor 4
    Toll-like receptor 4 in serum pg/dL

    Full Information

    First Posted
    June 17, 2015
    Last Updated
    August 19, 2015
    Sponsor
    Hospital Civil de Guadalajara
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02530359
    Brief Title
    Pirfenidone Effect on the Recovery of Renal Function in Septic Acute Kidney Injury
    Acronym
    AKI
    Official Title
    Pirfenidone Effect on the Recovery of Renal Function in Patients With Septic Acute Kidney Injury
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2015
    Overall Recruitment Status
    Unknown status
    Study Start Date
    October 2015 (undefined)
    Primary Completion Date
    March 2016 (Anticipated)
    Study Completion Date
    July 2016 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Hospital Civil de Guadalajara

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    Patients with Septic AKI will be randomized in three arms, group PFD 1,200 will receive PDF 600mg every 12 hrs per mouth, group PDF 600 will receive PFD 600mg in the morning and placebo equivalent at night and Group Placebo will receive placebo every 12 hrs, all for 7 days, all receive conventional treatment KDIGO guides. We analyze the recovery of renal function as a primary objective.
    Detailed Description
    Septic acute kidney injury (AKI) is the most common cause of AKI in the world, there is no specific treatment for this pathology; the pathophysiology is related to inflammatory pathway and strategies that modulate this are potentially useful. The Pirfenidone (PDF) is an anti-fibrotic and anti-inflammatory treatment, in animal models has shown a beneficial effect on the recovery of renal function immediately after administrated. The investigators propose a triple blind clinical trial,in which septic AKI patients will be randomized in three arms, all receive conventional treatment KDIGO guides, groupPDF 1,200 will receive PDF 600mg every 12 hrs per mouth, group PDF 600 will receive 600mg in the morning and placebo equivalent at night and Group Placebo will receive placebo every 12 hrs, all for 7 days. The Investigators analyze the recovery of renal function as a primary objective, as a secondary objectives clinical variables associated with renal recovery, biochemical variables, inflammatory, molecular variables and measurement of PDF in blood will be analyzed. Patients will be follow-up for 7 days and 28 days after randomization.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Acute Kidney Injury, Sepsis
    Keywords
    septic acute kidney injury, pirfenidone

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigator
    Allocation
    Randomized
    Enrollment
    90 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Group 1
    Arm Type
    Active Comparator
    Arm Description
    Pirfenidone extended release 600mg per mouth every 12 hours for 7 days.
    Arm Title
    Group 2
    Arm Type
    Active Comparator
    Arm Description
    Pirfenidone extended release 600mg per mouth in the morning and placebo by night (each treatment every 12 hrs) for 7 days.
    Arm Title
    Group 3
    Arm Type
    Placebo Comparator
    Arm Description
    Placebo equivalent per mouth every 12 hrs for 7 days.
    Intervention Type
    Drug
    Intervention Name(s)
    Pirfenidone extended release
    Intervention Description
    Pirfenidone extended release 600mg per mouth
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo equivalent
    Other Intervention Name(s)
    Placebo
    Intervention Description
    Placebo equivalent per mouth
    Primary Outcome Measure Information:
    Title
    renal function recovery
    Description
    serum creatinine in serum <2mg/dl and urinary output >1,200 ml/day
    Time Frame
    within the first 7 days
    Title
    renal function recovery
    Description
    serum creatinine in serum <2mg/dl and urinary output >1,200ml/day
    Time Frame
    within the first 28 days
    Secondary Outcome Measure Information:
    Title
    Urinary Volume
    Description
    Urinary Volume in milliliters in 24 hours
    Time Frame
    within the first 7 days
    Title
    need of renal replacement therapy (RRT)
    Description
    the patient still need renal replacement (RRT) by the judgment of the nephrologist.
    Time Frame
    within the first 7 days
    Title
    mortality
    Description
    the patient dead
    Time Frame
    within the first 7 days
    Title
    serum creatinine levels
    Description
    serum creatinine levels in mg/dL
    Time Frame
    within the first 7 days
    Title
    serum urea levels
    Description
    serum urea levels in mg/dL
    Time Frame
    within the first 7 days
    Title
    pirfenidone levels in serum ug/mL
    Description
    pirfenidone levels in serum ug/mL
    Time Frame
    on day 1 and day 7
    Title
    IL-1
    Description
    Interleucin 1 in serum pg/mL
    Time Frame
    on day 1 and day 7
    Title
    IL-6
    Description
    Interleucin 6 in serum pg/mL
    Time Frame
    on day 1 and day 7
    Title
    TNF-α
    Description
    tumor necrosis factor in serum pg/dL
    Time Frame
    on day 1 and day 7
    Title
    Toll-like receptor 4
    Description
    Toll-like receptor 4 in serum pg/dL
    Time Frame
    on day 1 and day 7

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    85 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: . sepsis AKI by serum creatinine, according to the KDIGO guide 2012 Acute Kidney Injury • acute on Chronic kidney disease (baseline creatinine <2 mg / dL) Exclusion Criteria: Chronic kidney disease stage 3b, 4 or 5 (basal serum creatinine > 2mg/dl) known and / or sharpened. chronic dialysis (peritoneal dialysis or hemodialysis) History of AKI and / or RRT in the last three months Pregnancy AKI by other causes other than sepsis
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Jonathan Chavez, Dr
    Phone
    0443313299609
    Email
    jonarchi_10@hotmail.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Guillermo Garcia, Dr
    Phone
    0443336622288
    Email
    ggarcia1952@gmail.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Juan Armenzadriz, Dr
    Organizational Affiliation
    Centro Universitario Ciencias de la Salud
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    20813868
    Citation
    Hsu CY. Where is the epidemic in kidney disease? J Am Soc Nephrol. 2010 Oct;21(10):1607-11. doi: 10.1681/ASN.2010050546. Epub 2010 Sep 2. No abstract available.
    Results Reference
    background
    PubMed Identifier
    23222124
    Citation
    Hsu RK, McCulloch CE, Dudley RA, Lo LJ, Hsu CY. Temporal changes in incidence of dialysis-requiring AKI. J Am Soc Nephrol. 2013 Jan;24(1):37-42. doi: 10.1681/ASN.2012080800. Epub 2012 Dec 6.
    Results Reference
    background
    PubMed Identifier
    19557705
    Citation
    James M, Pannu N. Methodological considerations for observational studies of acute kidney injury using existing data sources. J Nephrol. 2009 May-Jun;22(3):295-305.
    Results Reference
    background
    PubMed Identifier
    16106006
    Citation
    Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C; Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005 Aug 17;294(7):813-8. doi: 10.1001/jama.294.7.813.
    Results Reference
    background
    PubMed Identifier
    8605788
    Citation
    Brivet FG, Kleinknecht DJ, Loirat P, Landais PJ. Acute renal failure in intensive care units--causes, outcome, and prognostic factors of hospital mortality; a prospective, multicenter study. French Study Group on Acute Renal Failure. Crit Care Med. 1996 Feb;24(2):192-8. doi: 10.1097/00003246-199602000-00003.
    Results Reference
    background
    PubMed Identifier
    15458458
    Citation
    Mehta RL, Pascual MT, Soroko S, Savage BR, Himmelfarb J, Ikizler TA, Paganini EP, Chertow GM; Program to Improve Care in Acute Renal Disease. Spectrum of acute renal failure in the intensive care unit: the PICARD experience. Kidney Int. 2004 Oct;66(4):1613-21. doi: 10.1111/j.1523-1755.2004.00927.x.
    Results Reference
    background
    PubMed Identifier
    12205335
    Citation
    Metcalfe W, Simpson M, Khan IH, Prescott GJ, Simpson K, Smith WC, MacLeod AM; Scottish Renal Registry. Acute renal failure requiring renal replacement therapy: incidence and outcome. QJM. 2002 Sep;95(9):579-83. doi: 10.1093/qjmed/95.9.579.
    Results Reference
    background
    PubMed Identifier
    21814177
    Citation
    Grams ME, Rabb H. The distant organ effects of acute kidney injury. Kidney Int. 2012 May;81(10):942-948. doi: 10.1038/ki.2011.241. Epub 2011 Aug 3.
    Results Reference
    background
    PubMed Identifier
    21975865
    Citation
    Singbartl K, Kellum JA. AKI in the ICU: definition, epidemiology, risk stratification, and outcomes. Kidney Int. 2012 May;81(9):819-25. doi: 10.1038/ki.2011.339. Epub 2011 Oct 5.
    Results Reference
    background
    PubMed Identifier
    22547749
    Citation
    Heyman SN, Evans RG, Rosen S, Rosenberger C. Cellular adaptive changes in AKI: mitigating renal hypoxic injury. Nephrol Dial Transplant. 2012 May;27(5):1721-8. doi: 10.1093/ndt/gfs100.
    Results Reference
    background
    PubMed Identifier
    19759527
    Citation
    Heyman SN, Rosenberger C, Rosen S. Experimental ischemia-reperfusion: biases and myths-the proximal vs. distal hypoxic tubular injury debate revisited. Kidney Int. 2010 Jan;77(1):9-16. doi: 10.1038/ki.2009.347.
    Results Reference
    background
    PubMed Identifier
    24136922
    Citation
    Kinsey GR, Sharma R, Okusa MD. Regulatory T cells in AKI. J Am Soc Nephrol. 2013 Nov;24(11):1720-6. doi: 10.1681/ASN.2013050502. Epub 2013 Oct 17.
    Results Reference
    background
    PubMed Identifier
    24480828
    Citation
    Kaushal GP, Shah SV. Challenges and advances in the treatment of AKI. J Am Soc Nephrol. 2014 May;25(5):877-83. doi: 10.1681/ASN.2013070780. Epub 2014 Jan 30.
    Results Reference
    background
    PubMed Identifier
    11979336
    Citation
    Nash K, Hafeez A, Hou S. Hospital-acquired renal insufficiency. Am J Kidney Dis. 2002 May;39(5):930-6. doi: 10.1053/ajkd.2002.32766.
    Results Reference
    background
    PubMed Identifier
    21852670
    Citation
    Mehta RL. Management of acute kidney injury: it's the squeaky wheel that gets the oil! Clin J Am Soc Nephrol. 2011 Sep;6(9):2102-4. doi: 10.2215/CJN.07720811. Epub 2011 Aug 18. No abstract available.
    Results Reference
    background
    PubMed Identifier
    24586237
    Citation
    Yang F, Zhang L, Wu H, Zou H, Du Y. Clinical analysis of cause, treatment and prognosis in acute kidney injury patients. PLoS One. 2014 Feb 21;9(2):e85214. doi: 10.1371/journal.pone.0085214. eCollection 2014.
    Results Reference
    background
    PubMed Identifier
    21694939
    Citation
    Akcay A, Turkmen K, Lee D, Edelstein CL. Update on the diagnosis and management of acute kidney injury. Int J Nephrol Renovasc Dis. 2010;3:129-40. doi: 10.2147/IJNRD.S8641. Epub 2010 Sep 29.
    Results Reference
    background
    PubMed Identifier
    7491052
    Citation
    Brady HR, Singer GG. Acute renal failure. Lancet. 1995 Dec 9;346(8989):1533-40. doi: 10.1016/s0140-6736(95)92057-9. No abstract available.
    Results Reference
    background
    PubMed Identifier
    17038736
    Citation
    Hilton R. Acute renal failure. BMJ. 2006 Oct 14;333(7572):786-90. doi: 10.1136/bmj.38975.657639.AE. No abstract available.
    Results Reference
    background
    PubMed Identifier
    16495376
    Citation
    Waikar SS, Curhan GC, Wald R, McCarthy EP, Chertow GM. Declining mortality in patients with acute renal failure, 1988 to 2002. J Am Soc Nephrol. 2006 Apr;17(4):1143-50. doi: 10.1681/ASN.2005091017. Epub 2006 Feb 22.
    Results Reference
    background
    PubMed Identifier
    9077523
    Citation
    Chiao H, Kohda Y, McLeroy P, Craig L, Housini I, Star RA. Alpha-melanocyte-stimulating hormone protects against renal injury after ischemia in mice and rats. J Clin Invest. 1997 Mar 15;99(6):1165-72. doi: 10.1172/JCI119272.
    Results Reference
    background
    PubMed Identifier
    22913596
    Citation
    Thompson JD, Kornbrust DJ, Foy JW, Solano EC, Schneider DJ, Feinstein E, Molitoris BA, Erlich S. Toxicological and pharmacokinetic properties of chemically modified siRNAs targeting p53 RNA following intravenous administration. Nucleic Acid Ther. 2012 Aug;22(4):255-64. doi: 10.1089/nat.2012.0371.
    Results Reference
    background
    PubMed Identifier
    22306733
    Citation
    Sugimoto H, LeBleu VS, Bosukonda D, Keck P, Taduri G, Bechtel W, Okada H, Carlson W Jr, Bey P, Rusckowski M, Tampe B, Tampe D, Kanasaki K, Zeisberg M, Kalluri R. Activin-like kinase 3 is important for kidney regeneration and reversal of fibrosis. Nat Med. 2012 Feb 5;18(3):396-404. doi: 10.1038/nm.2629.
    Results Reference
    background
    Citation
    24. A study to evaluate the safety and efficacy of AC607 for the treatment of kidney injury in cardiac surgery subjects (ACT-AKI).
    Results Reference
    background
    PubMed Identifier
    21844075
    Citation
    Briguori C, Visconti G, Focaccio A, Airoldi F, Valgimigli M, Sangiorgi GM, Golia B, Ricciardelli B, Condorelli G; REMEDIAL II Investigators. Renal Insufficiency After Contrast Media Administration Trial II (REMEDIAL II): RenalGuard System in high-risk patients for contrast-induced acute kidney injury. Circulation. 2011 Sep 13;124(11):1260-9. doi: 10.1161/CIRCULATIONAHA.111.030759. Epub 2011 Aug 15.
    Results Reference
    background
    PubMed Identifier
    22269279
    Citation
    Pickkers P, Heemskerk S, Schouten J, Laterre PF, Vincent JL, Beishuizen A, Jorens PG, Spapen H, Bulitta M, Peters WH, van der Hoeven JG. Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: a prospective randomized double-blind placebo-controlled trial. Crit Care. 2012 Jan 23;16(1):R14. doi: 10.1186/cc11159.
    Results Reference
    background
    PubMed Identifier
    18272842
    Citation
    Tumlin J, Wali R, Williams W, Murray P, Tolwani AJ, Vinnikova AK, Szerlip HM, Ye J, Paganini EP, Dworkin L, Finkel KW, Kraus MA, Humes HD. Efficacy and safety of renal tubule cell therapy for acute renal failure. J Am Soc Nephrol. 2008 May;19(5):1034-40. doi: 10.1681/ASN.2007080895. Epub 2008 Feb 13.
    Results Reference
    background
    PubMed Identifier
    23106607
    Citation
    Tumlin JA, Chawla L, Tolwani AJ, Mehta R, Dillon J, Finkel KW, DaSilva JR, Astor BC, Yevzlin AS, Humes HD. The effect of the selective cytopheretic device on acute kidney injury outcomes in the intensive care unit: a multicenter pilot study. Semin Dial. 2013 Sep-Oct;26(5):616-23. doi: 10.1111/sdi.12032. Epub 2012 Oct 29.
    Results Reference
    background
    PubMed Identifier
    22442183
    Citation
    Faubel S, Chawla LS, Chertow GM, Goldstein SL, Jaber BL, Liu KD; Acute Kidney Injury Advisory Group of the American Society of Nephrology. Ongoing clinical trials in AKI. Clin J Am Soc Nephrol. 2012 May;7(5):861-73. doi: 10.2215/CJN.12191111. Epub 2012 Mar 22.
    Results Reference
    background
    PubMed Identifier
    9143872
    Citation
    Taniyama M, Ohbayashi S, Narita M, Nakazawa R, Hasegawa S, Azuma N, Teraoka S, Ota K, Yamauchi S, Margolin SB. Pharmacokinetics of an antifibrotic agent, pirfenidone, in haemodialysis patients. Eur J Clin Pharmacol. 1997;52(1):77-8. doi: 10.1007/s002280050252. No abstract available.
    Results Reference
    background
    PubMed Identifier
    12371954
    Citation
    Sutton TA, Fisher CJ, Molitoris BA. Microvascular endothelial injury and dysfunction during ischemic acute renal failure. Kidney Int. 2002 Nov;62(5):1539-49. doi: 10.1046/j.1523-1755.2002.00631.x.
    Results Reference
    background
    PubMed Identifier
    11818695
    Citation
    Okusa MD. The inflammatory cascade in acute ischemic renal failure. Nephron. 2002 Feb;90(2):133-8. doi: 10.1159/000049032.
    Results Reference
    background
    PubMed Identifier
    18802372
    Citation
    Kinsey GR, Li L, Okusa MD. Inflammation in acute kidney injury. Nephron Exp Nephrol. 2008;109(4):e102-7. doi: 10.1159/000142934. Epub 2008 Sep 18.
    Results Reference
    background
    PubMed Identifier
    15232604
    Citation
    Schrier RW, Wang W, Poole B, Mitra A. Acute renal failure: definitions, diagnosis, pathogenesis, and therapy. J Clin Invest. 2004 Jul;114(1):5-14. doi: 10.1172/JCI22353. Erratum In: J Clin Invest. 2004 Aug;114(4):598.
    Results Reference
    background
    PubMed Identifier
    8618585
    Citation
    Thadhani R, Pascual M, Bonventre JV. Acute renal failure. N Engl J Med. 1996 May 30;334(22):1448-60. doi: 10.1056/NEJM199605303342207. No abstract available.
    Results Reference
    background
    PubMed Identifier
    9853246
    Citation
    Star RA. Treatment of acute renal failure. Kidney Int. 1998 Dec;54(6):1817-31. doi: 10.1046/j.1523-1755.1998.00210.x.
    Results Reference
    background
    PubMed Identifier
    7573008
    Citation
    Conger JD. Interventions in clinical acute renal failure: what are the data? Am J Kidney Dis. 1995 Oct;26(4):565-76. doi: 10.1016/0272-6386(95)90590-1.
    Results Reference
    background
    PubMed Identifier
    12411754
    Citation
    Ronco C, Bellomo R. Prevention of acute renal failure in the critically ill. Nephron Clin Pract. 2003 Jan;93(1):C13-20. doi: 10.1159/000066646.
    Results Reference
    background
    PubMed Identifier
    10651214
    Citation
    Kelly KJ, Molitoris BA. Acute renal failure in the new millennium: time to consider combination therapy. Semin Nephrol. 2000 Jan;20(1):4-19.
    Results Reference
    background
    PubMed Identifier
    9648068
    Citation
    Shimizu T, Kuroda T, Hata S, Fukagawa M, Margolin SB, Kurokawa K. Pirfenidone improves renal function and fibrosis in the post-obstructed kidney. Kidney Int. 1998 Jul;54(1):99-109. doi: 10.1046/j.1523-1755.1998.00962.x.
    Results Reference
    background
    PubMed Identifier
    11783601
    Citation
    Hewitson TD, Kelynack KJ, Tait MG, Martic M, Jones CL, Margolin SB, Becker GJ. Pirfenidone reduces in vitro rat renal fibroblast activation and mitogenesis. J Nephrol. 2001 Nov-Dec;14(6):453-60.
    Results Reference
    background
    PubMed Identifier
    15729167
    Citation
    Shihab FS, Bennett WM, Yi H, Andoh TF. Effect of pirfenidone on apoptosis-regulatory genes in chronic cyclosporine nephrotoxicity. Transplantation. 2005 Feb 27;79(4):419-26. doi: 10.1097/01.tp.0000151721.99418.48.
    Results Reference
    background
    PubMed Identifier
    20006961
    Citation
    Takakuta K, Fujimori A, Chikanishi T, Tanokura A, Iwatsuki Y, Yamamoto M, Nakajima H, Okada M, Itoh H. Renoprotective properties of pirfenidone in subtotally nephrectomized rats. Eur J Pharmacol. 2010 Mar 10;629(1-3):118-24. doi: 10.1016/j.ejphar.2009.12.011. Epub 2009 Dec 13.
    Results Reference
    background
    PubMed Identifier
    23002925
    Citation
    Takakura K, Tahara A, Sanagi M, Itoh H, Tomura Y. Antifibrotic effects of pirfenidone in rat proximal tubular epithelial cells. Ren Fail. 2012;34(10):1309-16. doi: 10.3109/0886022X.2012.718955. Epub 2012 Sep 24. Erratum In: Ren Fail: 2012;34(10):1316.
    Results Reference
    background
    PubMed Identifier
    23152296
    Citation
    Chen JF, Ni HF, Pan MM, Liu H, Xu M, Zhang MH, Liu BC. Pirfenidone inhibits macrophage infiltration in 5/6 nephrectomized rats. Am J Physiol Renal Physiol. 2013 Mar 15;304(6):F676-85. doi: 10.1152/ajprenal.00507.2012. Epub 2012 Nov 14.
    Results Reference
    background
    Citation
    46. Hartung J: A note on combining dependent tests of significance. Biometrical J 1999, 41:849-855.
    Results Reference
    background
    PubMed Identifier
    20809935
    Citation
    Macias-Barragan J, Sandoval-Rodriguez A, Navarro-Partida J, Armendariz-Borunda J. The multifaceted role of pirfenidone and its novel targets. Fibrogenesis Tissue Repair. 2010 Sep 1;3:16. doi: 10.1186/1755-1536-3-16.
    Results Reference
    background
    PubMed Identifier
    17906160
    Citation
    Shi S, Wu J, Chen H, Chen H, Wu J, Zeng F. Single- and multiple-dose pharmacokinetics of pirfenidone, an antifibrotic agent, in healthy Chinese volunteers. J Clin Pharmacol. 2007 Oct;47(10):1268-76. doi: 10.1177/0091270007304104.
    Results Reference
    background
    PubMed Identifier
    20050822
    Citation
    Cho ME, Kopp JB. Pirfenidone: an anti-fibrotic therapy for progressive kidney disease. Expert Opin Investig Drugs. 2010 Feb;19(2):275-83. doi: 10.1517/13543780903501539.
    Results Reference
    background
    PubMed Identifier
    15640628
    Citation
    Panacek EA, Marshall JC, Albertson TE, Johnson DH, Johnson S, MacArthur RD, Miller M, Barchuk WT, Fischkoff S, Kaul M, Teoh L, Van Meter L, Daum L, Lemeshow S, Hicklin G, Doig C; Monoclonal Anti-TNF: a Randomized Controlled Sepsis Study Investigators. Efficacy and safety of the monoclonal anti-tumor necrosis factor antibody F(ab')2 fragment afelimomab in patients with severe sepsis and elevated interleukin-6 levels. Crit Care Med. 2004 Nov;32(11):2173-82. doi: 10.1097/01.ccm.0000145229.59014.6c.
    Results Reference
    background
    PubMed Identifier
    9851930
    Citation
    Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, Birdwell D, Alejos E, Silva M, Galanos C, Freudenberg M, Ricciardi-Castagnoli P, Layton B, Beutler B. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science. 1998 Dec 11;282(5396):2085-8. doi: 10.1126/science.282.5396.2085.
    Results Reference
    background
    PubMed Identifier
    10196138
    Citation
    Chow JC, Young DW, Golenbock DT, Christ WJ, Gusovsky F. Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction. J Biol Chem. 1999 Apr 16;274(16):10689-92. doi: 10.1074/jbc.274.16.10689.
    Results Reference
    background
    PubMed Identifier
    15155619
    Citation
    Samuelsson P, Hang L, Wullt B, Irjala H, Svanborg C. Toll-like receptor 4 expression and cytokine responses in the human urinary tract mucosa. Infect Immun. 2004 Jun;72(6):3179-86. doi: 10.1128/IAI.72.6.3179-3186.2004.
    Results Reference
    background
    PubMed Identifier
    16332927
    Citation
    El-Achkar TM, Huang X, Plotkin Z, Sandoval RM, Rhodes GJ, Dagher PC. Sepsis induces changes in the expression and distribution of Toll-like receptor 4 in the rat kidney. Am J Physiol Renal Physiol. 2006 May;290(5):F1034-43. doi: 10.1152/ajprenal.00414.2005. Epub 2005 Dec 6.
    Results Reference
    background
    PubMed Identifier
    14764737
    Citation
    Cunningham PN, Wang Y, Guo R, He G, Quigg RJ. Role of Toll-like receptor 4 in endotoxin-induced acute renal failure. J Immunol. 2004 Feb 15;172(4):2629-35. doi: 10.4049/jimmunol.172.4.2629.
    Results Reference
    background
    PubMed Identifier
    16316333
    Citation
    Patole PS, Schubert S, Hildinger K, Khandoga S, Khandoga A, Segerer S, Henger A, Kretzler M, Werner M, Krombach F, Schlondorff D, Anders HJ. Toll-like receptor-4: renal cells and bone marrow cells signal for neutrophil recruitment during pyelonephritis. Kidney Int. 2005 Dec;68(6):2582-7. doi: 10.1111/j.1523-1755.2005.00729.x.
    Results Reference
    background
    PubMed Identifier
    24378526
    Citation
    Morrell ED, Kellum JA, Hallows KR, Pastor-Soler NM. Epithelial transport during septic acute kidney injury. Nephrol Dial Transplant. 2014 Jul;29(7):1312-9. doi: 10.1093/ndt/gft503. Epub 2013 Dec 29.
    Results Reference
    background
    PubMed Identifier
    18922884
    Citation
    Leelahavanichkul A, Yasuda H, Doi K, Hu X, Zhou H, Yuen PS, Star RA. Methyl-2-acetamidoacrylate, an ethyl pyruvate analog, decreases sepsis-induced acute kidney injury in mice. Am J Physiol Renal Physiol. 2008 Dec;295(6):F1825-35. doi: 10.1152/ajprenal.90442.2008. Epub 2008 Oct 15.
    Results Reference
    background
    PubMed Identifier
    14531793
    Citation
    Miyaji T, Hu X, Yuen PS, Muramatsu Y, Iyer S, Hewitt SM, Star RA. Ethyl pyruvate decreases sepsis-induced acute renal failure and multiple organ damage in aged mice. Kidney Int. 2003 Nov;64(5):1620-31. doi: 10.1046/j.1523-1755.2003.00268.x.
    Results Reference
    background
    PubMed Identifier
    22586448
    Citation
    Chatterjee PK, Yeboah MM, Dowling O, Xue X, Powell SR, Al-Abed Y, Metz CN. Nicotinic acetylcholine receptor agonists attenuate septic acute kidney injury in mice by suppressing inflammation and proteasome activity. PLoS One. 2012;7(5):e35361. doi: 10.1371/journal.pone.0035361. Epub 2012 May 7.
    Results Reference
    background
    PubMed Identifier
    25575158
    Citation
    Morrell ED, Kellum JA, Pastor-Soler NM, Hallows KR. Septic acute kidney injury: molecular mechanisms and the importance of stratification and targeting therapy. Crit Care. 2014 Sep 2;18(5):501. doi: 10.1186/s13054-014-0501-5.
    Results Reference
    background
    PubMed Identifier
    18382186
    Citation
    Hoste EA, Schurgers M. Epidemiology of acute kidney injury: how big is the problem? Crit Care Med. 2008 Apr;36(4 Suppl):S146-51. doi: 10.1097/CCM.0b013e318168c590.
    Results Reference
    background
    PubMed Identifier
    23353941
    Citation
    Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013 Feb;41(2):580-637. doi: 10.1097/CCM.0b013e31827e83af.
    Results Reference
    background
    PubMed Identifier
    19066848
    Citation
    Bagshaw SM, Lapinsky S, Dial S, Arabi Y, Dodek P, Wood G, Ellis P, Guzman J, Marshall J, Parrillo JE, Skrobik Y, Kumar A; Cooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group. Acute kidney injury in septic shock: clinical outcomes and impact of duration of hypotension prior to initiation of antimicrobial therapy. Intensive Care Med. 2009 May;35(5):871-81. doi: 10.1007/s00134-008-1367-2. Epub 2008 Dec 9.
    Results Reference
    background
    PubMed Identifier
    21734090
    Citation
    Plataki M, Kashani K, Cabello-Garza J, Maldonado F, Kashyap R, Kor DJ, Gajic O, Cartin-Ceba R. Predictors of acute kidney injury in septic shock patients: an observational cohort study. Clin J Am Soc Nephrol. 2011 Jul;6(7):1744-51. doi: 10.2215/CJN.05480610.
    Results Reference
    background
    PubMed Identifier
    33520317
    Citation
    Chavez-Iniguez JS, Poo JL, Ibarra-Estrada M, Garcia-Benavides L, Navarro-Blackaller G, Cervantes-Sanchez C, Nungaray-Pacheco E, Medina-Gonzalez R, Armendariz-Borunda J, Garcia-Garcia G. Effect of Prolonged-Release Pirfenidone on Renal Function in Septic Acute Kidney Injury Patients: A Double-Blind Placebo-Controlled Clinical Trial. Int J Nephrol. 2021 Jan 13;2021:8833278. doi: 10.1155/2021/8833278. eCollection 2021.
    Results Reference
    derived

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    Pirfenidone Effect on the Recovery of Renal Function in Septic Acute Kidney Injury

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