title: Interventions for protecting renal function in the perioperative period.
abstract: BACKGROUND
  Various methods have been used to try to protect kidney function in patients undergoing surgery. These most often include pharmacological interventions such as dopamine and its analogues, diuretics, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, N-acetyl cysteine (NAC), atrial natriuretic peptide (ANP), sodium bicarbonate, antioxidants and erythropoietin (EPO).
  
  
  OBJECTIVE
  This review is aimed at determining the effectiveness of various measures advocated to protect patients' kidneys during the perioperative period.We considered the following questions: (1) Are any specific measures known to protect kidney function during the perioperative period? (2) Of measures used to protect the kidneys during the perioperative period, does any one method appear to be more effective than the others? (3) Of measures used to protect the kidneys during the perioperative period,does any one method appear to be safer than the others?
  
  
  METHODS
  In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2012), MEDLINE (Ovid SP) (1966 to August 2012) and EMBASE (Ovid SP) (1988 to August 2012). We originally handsearched six journals (Anesthesia and Analgesia, Anesthesiology, Annals of Surgery, British Journal of Anaesthesia, Journal of Thoracic and Cardiovascular Surgery, and Journal of Vascular Surgery) (1985 to 2004). However, because these journals are properly indexed in MEDLINE, we decided to rely on electronic searches only without handsearching the journals from 2004 onwards.
  
  
  METHODS
  We selected all randomized controlled trials in adults undergoing surgery for which a treatment measure was used for the purpose of providing renal protection during the perioperative period.
  
  
  METHODS
  We selected 72 studies for inclusion in this review. Two review authors extracted data from all selected studies and entered them into RevMan 5.1; then the data were appropriately analysed. We performed subgroup analyses for type of intervention, type of surgical procedure and pre-existing renal dysfunction. We undertook sensitivity analyses for studies with high and moderately good methodological quality.
  
  
  RESULTS
  The updated review included data from 72 studies, comprising a total of 4378 participants. Of these, 2291 received some form of treatment and 2087 acted as controls. The interventions consisted most often of different pharmaceutical agents, such as dopamine and its analogues, diuretics, calcium channel blockers, ACE inhibitors, NAC, ANP, sodium bicarbonate, antioxidants and EPO or selected hydration fluids. Some clinical heterogeneity and varying risk of bias were noted amongst the studies, although we were able to meaningfully interpret the data. Results showed significant heterogeneity and indicated that most interventions provided no benefit.Data on perioperative mortality were reported in 41 studies and data on acute renal injury in 44 studies (all interventions combined). Because of considerable clinical heterogeneity (different clinical scenarios, as well as considerable methodological variability amongst the studies), we did not perform a meta-analysis on the combined data.Subgroup analysis of major interventions and surgical procedures showed no significant influence of interventions on reported mortality and acute renal injury. For the subgroup of participants who had pre-existing renal damage, the risk of mortality from 10 trials (959 participants) was estimated as odds ratio (OR) 0.76, 95% confidence interval (CI) 0.38 to 1.52; the risk of acute renal injury (as reported in the trials) was estimated from 11 trials (979 participants) as OR 0.43, 95% CI 0.23 to 0.80. Subgroup analysis of studies that were rated as having low risk of bias revealed that 19 studies reported mortality numbers (1604 participants); OR was 1.01, 95% CI 0.54 to 1.90. Fifteen studies reported data on acute renal injury (criteria chosen by the individual studies; 1600 participants); OR was 1.03, 95% CI 0.54 to 1.97.
  
  
  CONCLUSIONS
  No reliable evidence from the available literature suggests that interventions during surgery can protect the kidneys from damage. However, the criteria used to diagnose acute renal damage varied in many of the older studies selected for inclusion in this review, many of which suffered from poor methodological quality such as insufficient participant numbers and poor definitions of end points such as acute renal failure and acute renal injury. Recent methods of detecting renal damage such as the use of specific biomarkers and better defined criteria for identifying renal damage (RIFLE (risk, injury, failure, loss of kidney function and end-stage renal failure) or AKI (acute kidney injury)) may have to be explored further to determine any possible benefit derived from interventions used to protect the kidneys during the perioperative period.
authors.affiliation: Department of Anaesthesia & Intensive Care, Dunedin Hospital, Great King Street, Dunedin, New Zealand, Private Bag 192.
authors.forename: Mathew
authors.initials: M
authors.lastname: Zacharias
authors.forename: Mohan
authors.initials: M
authors.lastname: Mugawar
authors.forename: G Peter
authors.initials: GP
authors.lastname: Herbison
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Walker
authors.forename: Karen
authors.initials: K
authors.lastname: Hovhannisyan
authors.forename: Pal
authors.initials: P
authors.lastname: Sivalingam
authors.forename: Niamh P
authors.initials: NP
authors.lastname: Conlon
mesh_terms: D000328:Adult; D003404:Creatinine / Q000652:urine; D006801:Humans; D011183:Postoperative Complications / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D051437:Renal Insufficiency / Q000517:prevention & control*; D013514:Surgical Procedures, Operative / Q000009:adverse effects*; D014556:Urine
chemical_list: D003404:Creatinine
references.citation: Nature. 1986 Dec 4-10;324(6096):473-6
references.pmid: 2946962
references.citation: Surgery. 1975 Sep;78(3):291-303
references.pmid: 1154272
references.citation: Chest. 1994 Sep;106(3):835-41
references.pmid: 7915979
references.citation: Br J Surg. 2007 Apr;94(4):427-33
references.pmid: 17380548
references.citation: Am J Kidney Dis. 1997 Nov;30(5 Suppl 4):S89-95
references.pmid: 9372985
references.citation: Lancet. 2000 Dec 23-30;356(9248):2139-43
references.pmid: 11191541
references.citation: Br J Anaesth. 1996 May;76(5):632-9
references.pmid: 8688261
references.citation: J Cardiothorac Vasc Anesth. 1993 Dec;7(6):711-6
references.pmid: 8305662
references.citation: Eur J Vasc Endovasc Surg. 1995 Jul;10(1):82-90
references.pmid: 7633974
references.citation: J Urol. 2002 Jan;167(1):24-8
references.pmid: 11743267
references.citation: JAMA. 2005 Jul 20;294(3):342-50
references.pmid: 16030279
references.citation: Kidney Int. 2011 May;79(10):1119-30
references.pmid: 21307838
references.citation: Clin Radiol. 2004 May;59(5):381-9
references.pmid: 15081843
references.citation: Nephrol Dial Transplant. 2002 May;17(5):910-5
references.pmid: 11981083
references.citation: Eur J Cardiothorac Surg. 2002 Jul;22(1):118-23
references.pmid: 12103384
references.citation: Anaesth Intensive Care. 1993 Feb;21(1):56-61
references.pmid: 8447608
references.citation: J Clin Anesth. 2006 Sep;18(6):422-6
references.pmid: 16980158
references.citation: Paediatr Anaesth. 1999;9(6):505-14
references.pmid: 10597554
references.citation: Eur J Cardiothorac Surg. 2008 Mar;33(3):370-6
references.pmid: 18243724
references.citation: Ann Thorac Surg. 2000 Mar;69(3):732-8
references.pmid: 10750752
references.citation: Anesth Analg. 2003 Nov;97(5):1222-1229
references.pmid: 14570627
references.citation: Cardiovasc Surg. 1995 Oct;3(5):519-24
references.pmid: 8574537
references.citation: Anesth Analg. 1992 Jul;75(1):18-23
references.pmid: 1616156
references.citation: Ann Thorac Surg. 2003 Mar;75(3):859-64
references.pmid: 12645707
references.citation: Crit Care Med. 1979 Jan;7(1):9-13
references.pmid: 367709
references.citation: Lancet. 2005 May 28-Jun 3;365(9474):1890-2
references.pmid: 15924987
references.citation: Chest. 1995 May;107(5):1260-5
references.pmid: 7750316
references.citation: Crit Care Med. 1996 Jun;24(6):947-52
references.pmid: 8681596
references.citation: Anesth Analg. 1995 Sep;81(3):446-51
references.pmid: 7653802
references.citation: Surg Today. 2006;36(6):508-14
references.pmid: 16715419
references.citation: Scand J Surg. 2004;93(1):52-6
references.pmid: 15116821
references.citation: Clin Kidney J. 2013 Feb;6(1):8-14
references.pmid: 27818745
references.citation: Am J Physiol. 1988 Oct;255(4 Pt 2):F666-73
references.pmid: 2845809
references.citation: Eur J Anaesthesiol. 2002 Jan;19(1):32-9
references.pmid: 11913801
references.citation: J Cardiovasc Pharmacol Ther. 2001 Jan;6(1):31-6
references.pmid: 11452334
references.citation: J Endovasc Ther. 2009 Feb;16(1):1-12
references.pmid: 19281283
references.citation: Cochrane Database Syst Rev. 2005 Jul 20;(3):CD003590
references.pmid: 16034904
references.citation: Surgery. 1983 Jul;94(1):41-51
references.pmid: 6857511
references.citation: Cardiovasc Surg. 2001 Dec;9(6):608-14
references.pmid: 11604346
references.citation: Anesthesiology. 1990 Jan;72(1):23-7
references.pmid: 2404429
references.citation: Nephrology (Carlton). 2006 Aug;11(4):306-12
references.pmid: 16889570
references.citation: Ren Fail. 1994;16(3):383-90
references.pmid: 8059021
references.citation: Med Sci Monit. 2002 May;8(5):PI45-50
references.pmid: 12011785
references.citation: Can J Anaesth. 1999 Jul;46(7):626-34
references.pmid: 10442956
references.citation: JAMA. 2005 Jan 5;293(1):90-5
references.pmid: 15632341
references.citation: Chest. 2001 May;119(5):1476-9
references.pmid: 11348956
references.citation: J Cardiothorac Anesth. 1990 Aug;4(4):469-73
references.pmid: 2132343
references.citation: J Vasc Surg. 1993 Nov;18(5):858-66
references.pmid: 8230574
references.citation: Anaesthesia. 2001 Oct;56(10):953-60
references.pmid: 11576097
references.citation: Anesth Analg. 1999 Nov;89(5):1124-30
references.pmid: 10553822
references.citation: J Cardiothorac Vasc Anesth. 2003 Feb;17(1):17-21
references.pmid: 12635055
references.citation: J Am Coll Cardiol. 2009 Sep 15;54(12):1058-64
references.pmid: 19744614
references.citation: Ann Vasc Surg. 1995 Sep;9(5):488-92
references.pmid: 8541200
references.citation: Masui. 1995 Mar 3;44(3):357-61
references.pmid: 7745788
references.citation: Natl Med J India. 1996 Mar-Apr;9(2):66-9
references.pmid: 8857040
references.citation: Ann Intensive Care. 2011 Mar 21;1(1):3
references.pmid: 21906325
references.citation: Circulation. 1998 Apr 14;97(14):1411-20
references.pmid: 9577953
references.citation: J Cardiothorac Vasc Anesth. 1992 Jun;6(3):299-303
references.pmid: 1610995
references.citation: Ann Intern Med. 1994 May 1;120(9):744-7
references.pmid: 8147547
references.citation: Br J Surg. 1994 Mar;81(3):437-9
references.pmid: 8173923
references.citation: Eur J Cardiothorac Surg. 2007 Feb;31(2):290-7
references.pmid: 17174559
references.citation: Br J Surg. 1986 Aug;73(8):634-6
references.pmid: 3527321
references.citation: Anesth Analg. 1997 May;84(5):950-7
references.pmid: 9141914
references.citation: Ann Thorac Surg. 2004 Mar;77(3):789-93
references.pmid: 14992872
references.citation: Br J Anaesth. 2001 Feb;86(2):169-75
references.pmid: 11573655
references.citation: Anesteziol Reanimatol. 2005 Jul-Aug;(4):18-22
references.pmid: 16206579
references.citation: Br J Anaesth. 2004 Dec;93(6):793-8
references.pmid: 15377582
references.citation: Science. 1986 Mar 28;231(4745):1572-3
references.pmid: 3006248
references.citation: Nature. 1987 Apr 16-22;326(6114):697-8
references.pmid: 2951600
references.citation: Anesthesiology. 2006 Jan;104(1):65-72
references.pmid: 16394692
references.citation: Masui. 1997 Apr;46(4):464-70
references.pmid: 9128016
references.citation: Circulation. 2005 Jun 21;111(24):3230-5
references.pmid: 15967861
references.citation: Anesth Analg. 1998 Jan;86(1):3-8
references.pmid: 9428842
references.citation: Ann Thorac Surg. 1995 Jul;60(1):160-4
references.pmid: 7598580
references.citation: Chest. 2002 Apr;121(4):1190-4
references.pmid: 11948052
references.citation: Surg Gynecol Obstet. 1987 Dec;165(6):519-22
references.pmid: 3120329
references.citation: J Cardiothorac Vasc Anesth. 2003 Aug;17(4):491-4
references.pmid: 12968238
references.citation: J Am Coll Surg. 2002 Oct;195(4):476-83
references.pmid: 12375752
references.citation: Anaesthesia. 1999 Feb;54(2):121-7
references.pmid: 10215706
references.citation: Int Angiol. 2001 Dec;20(4):282-7
references.pmid: 11782693
references.citation: Circulation. 2007 Sep 11;116(11 Suppl):I134-8
references.pmid: 17846293
references.citation: Ann Thorac Surg. 2002 Jan;73(1):153-5
references.pmid: 11834004
references.citation: Surgery. 1988 Jan;103(1):39-44
references.pmid: 3122349
references.citation: Br J Anaesth. 2006 Nov;97(5):611-6
references.pmid: 16914459
references.citation: Br J Anaesth. 1997 Dec;79(6):719-25
references.pmid: 9496202
references.citation: Cochrane Database Syst Rev. 2008 Oct 08;(4):CD003590
references.pmid: 18843647
references.citation: Artif Organs. 2006 Aug;30(8):615-21
references.pmid: 16911315
references.citation: J Clin Invest. 1986 Jun;77(6):1993-2000
references.pmid: 3011863
references.citation: N Engl J Med. 2000 Jul 20;343(3):180-4
references.pmid: 10900277
references.citation: Can J Anaesth. 1992 Nov;39(9):932-7
references.pmid: 1451221
references.citation: J Cardiothorac Vasc Anesth. 2002 Jun;16(3):294-9
references.pmid: 12073199
references.citation: J Am Coll Surg. 1994 Dec;179(6):714-20
references.pmid: 7952483
references.citation: J Cardiovasc Surg (Torino). 2002 Feb;43(1):25-30
references.pmid: 11803323
references.citation: J R Coll Surg Edinb. 1991 Oct;36(5):303-5
references.pmid: 1757907
references.citation: Surg Endosc. 2002 Sep;16(9):1297-301
references.pmid: 12000983
references.citation: Eur J Anaesthesiol. 2008 Dec;25(12):986-94
references.pmid: 18492315
references.citation: Crit Care. 2007;11(2):R31
references.pmid: 17331245
references.citation: Br J Surg. 2008 Jan;95(1):50-6
references.pmid: 18027383
references.citation: Cell Mol Life Sci. 2003 Jan;60(1):6-20
references.pmid: 12613655
references.citation: Anesth Analg. 2006 Oct;103(4):833-40
references.pmid: 17000789
references.citation: Am J Physiol. 1984 Aug;247(2 Pt 2):F365-9
references.pmid: 6431829
references.citation: J Am Coll Cardiol. 2011 Aug 23;58(9):897-903
references.pmid: 21851876
references.citation: Am J Nephrol. 2009;30(3):253-60
references.pmid: 19494484
references.citation: Crit Care Med. 1991 Jan;19(1):36-42
references.pmid: 1702696
references.citation: Eur J Anaesthesiol. 2010 Nov;27(11):973-7
references.pmid: 20299984
references.citation: Hepatogastroenterology. 2000 Nov-Dec;47(36):1691-4
references.pmid: 11149033
references.citation: Am J Nephrol. 1986;6(6):427-34
references.pmid: 3105319
references.citation: Br J Surg. 1996 Sep;83(9):1230-3
references.pmid: 8983613
references.citation: Ann Thorac Surg. 1992 Sep;54(3):449-57; discussion 457-9
references.pmid: 1510511
references.citation: Eur J Clin Pharmacol. 1993;45(3):217-20
references.pmid: 8276044
references.citation: J Clin Invest. 1964 Jun;43:1116-24
references.pmid: 14171789
references.citation: Ann Thorac Surg. 1999 Aug;68(2):493-8
references.pmid: 10475418
references.citation: Neth J Surg. 1990 Aug;42(4):113-7
references.pmid: 2216006
references.citation: Ann Thorac Surg. 1995 Oct;60(4):1076-80
references.pmid: 7574952
references.citation: Ann Thorac Surg. 2004 Feb;77(2):569-73
references.pmid: 14759439
references.citation: Nephron. 1996;74(4):668-73
references.pmid: 8956299
references.citation: Anesth Analg. 2006 Jun;102(6):1638-45
references.pmid: 16717300
references.citation: J Endovasc Ther. 2003 Apr;10(2):195-202
references.pmid: 12877599
references.citation: Ann Thorac Surg. 1996 Dec;62(6):1659-67; discussion 1667-8
references.pmid: 8957369
references.citation: Kidney Int Suppl. 1998 May;66:S75-80
references.pmid: 9573579
references.citation: Eur J Cardiothorac Surg. 1999 May;15(5):717-21; discussion 721-2
references.pmid: 10386423
references.citation: J Cardiovasc Surg (Torino). 2002 Aug;43(4):483-8
references.pmid: 12124559
references.citation: Perfusion. 2002 Nov;17(6):401-6
references.pmid: 12470028
references.citation: Int J Surg. 2008 Jun;6(3):197-204
references.pmid: 18424200
references.citation: Am J Physiol. 1997 Feb;272(2 Pt 2):F257-9
references.pmid: 9124404
references.citation: Crit Care Med. 2000 Dec;28(12):3935-6
references.pmid: 11153640
references.citation: Vasc Health Risk Manag. 2009;5(2):489-94
references.pmid: 19554089
references.citation: Anaesthesist. 1992 Jan;41(1):39-46
references.pmid: 1536439
references.citation: Anesth Analg. 2006 Jul;103(1):191-9, table of contents
references.pmid: 16790652
references.citation: J Cardiothorac Vasc Anesth. 2007 Dec;21(6):847-50
references.pmid: 18068064
references.citation: Crit Care Med. 2009 Jun;37(6):2079-90
references.pmid: 19384211
references.citation: Am Heart J. 2008 Jun;155(6):1143-9
references.pmid: 18513531
references.citation: Circulation. 1995 Oct 15;92(8):2236-44
references.pmid: 7554207
references.citation: Ren Fail. 2001 Mar;23(2):217-30
references.pmid: 11417953
references.citation: J Thorac Cardiovasc Surg. 2004 Dec;128(6):860-5
references.pmid: 15573070
references.citation: Ann Thorac Surg. 2009 Feb;87(2):489-95
references.pmid: 19161766
references.citation: Urology. 2009 May;73(5):1056-60
references.pmid: 19394503
references.citation: Spine (Phila Pa 1976). 1996 Mar 15;21(6):724-7
references.pmid: 8882695
references.citation: Chest. 2003 Nov;124(5):1852-62
references.pmid: 14605060
references.citation: Crit Care Med. 2002 Jan;30(1):107-12
references.pmid: 11902251
references.citation: Crit Care Med. 2009 Jan;37(1):39-47
references.pmid: 19112278
references.citation: J Am Soc Nephrol. 2000 Jan;11(1):97-104
references.pmid: 10616845
references.citation: JAMA. 2003 Feb 5;289(5):553-8
references.pmid: 12578487
references.citation: Head Neck. 1993 May-Jun;15(3):208-15
references.pmid: 8491584
references.citation: Crit Care Med. 2008 May;36(5):1427-35
references.pmid: 18434903
references.citation: Anadolu Kardiyol Derg. 2009 Dec;9(6):499-504
references.pmid: 19965324
references.citation: Anaesthesiol Reanim. 1997;22(4):102-7
references.pmid: 9376042
references.citation: Anesth Analg. 1996 Aug;83(2):262-8
references.pmid: 8694303
references.citation: Eur J Anaesthesiol. 2008 Apr;25(4):319-25
references.pmid: 18182121
references.citation: Ann Thorac Cardiovasc Surg. 2008 Oct;14(5):294-302
references.pmid: 18989245
references.citation: Crit Care Med. 2007 May;35(5):1324-31
references.pmid: 17414730
references.citation: J Cardiovasc Pharmacol. 1991;18 Suppl 6:S38-43
references.pmid: 1725916
references.citation: Perfusion. 1998 May;13(3):181-6
references.pmid: 9638715
references.citation: Ann Chir Gynaecol. 1976;65(4):258-66
references.pmid: 970902
references.citation: Arch Surg. 1985 Aug;120(8):911-5
references.pmid: 3893389
references.citation: Br J Anaesth. 2005 Apr;94(4):459-67
references.pmid: 15653704
references.citation: Gen Thorac Cardiovasc Surg. 2012 Jan;60(1):21-30
references.pmid: 22237735
references.citation: Br J Surg. 1991 Apr;78(4):467-9
references.pmid: 2032107
references.citation: Ann Thorac Surg. 2006 Feb;81(2):573-6
references.pmid: 16427854
references.citation: Anesteziol Reanimatol. 1996 Jan-Feb;(1):55-8
references.pmid: 8686945
references.citation: Kyobu Geka. 1995 Mar;48(3):198-201
references.pmid: 7534838
references.citation: J Cardiothorac Vasc Anesth. 2000 Jun;14(3):264-268
references.pmid: 10890478
references.citation: Ann Thorac Surg. 2000 Oct;70(4):1319-26
references.pmid: 11081892
references.citation: J Card Surg. 2004 Mar-Apr;19(2):128-33
references.pmid: 15016048
references.citation: Nephrology (Carlton). 2012 Mar;17(3):215-24
references.pmid: 22117606
references.citation: Eur J Anaesthesiol. 1997 Mar;14(2):184-9
references.pmid: 9088818
references.citation: Heart Surg Forum. 2000;3(4):313-8
references.pmid: 11178293
references.citation: Can J Anaesth. 2003 Mar;50(3):285-92
references.pmid: 12620953
references.citation: Curr Med Res Opin. 2005 Aug;21(8):1161-4
references.pmid: 16083524
references.citation: Crit Care Med. 2008 Mar;36(3):745-51
references.pmid: 18431264
references.citation: Intensive Care Med. 2007 Mar;33(3):409-13
references.pmid: 17165018
references.citation: Br J Surg. 2001 Oct;88(10):1363-5
references.pmid: 11578293
references.citation: Masui. 2001 Feb;50(2):122-6
references.pmid: 11244764
references.citation: Chest. 2005 Oct;128(4):2677-87
references.pmid: 16236942
references.citation: Eur J Cardiothorac Surg. 2002 Jul;22(1):106-11
references.pmid: 12103382
references.citation: Zentralbl Chir. 1993;118(7):390-4
references.pmid: 8372519
references.citation: Am J Physiol. 1986 Jun;250(6 Pt 2):F963-6
references.pmid: 2940876
references.citation: N Engl J Med. 1998 Jul 30;339(5):321-8
references.pmid: 9682046
references.citation: Obes Surg. 2001 Feb;11(1):40-5
references.pmid: 11361167
references.citation: Obes Surg. 2010 Jun;20(6):698-701
references.pmid: 20198451
references.citation: J Thorac Cardiovasc Surg. 2007 Mar;133(3):704-9
references.pmid: 17320568