Acute kidney injury after liver resection: A systematic review, meta-analysis and metaregression of factors affecting it

doi:10.21203/rs.3.rs-962952/v1

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Acute kidney injury after liver resection: A systematic review, meta-analysis and metaregression of factors affecting it

https://doi.org/10.21203/rs.3.rs-962952/v1

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Aim

This systematic review and meta-analysis aimed to study the incidence of acute kidney injury after liver resection and to analyze various factors affecting it by metaregression analysis.

Methods

The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (2020) and MOOSE guidelines. The meta-analysis was done using Review Manager 5.4 and the JASP Team (2020). JASP (Version 0.14.1)(University of Amsterdam). Weighted percentage incidence with 95% confidence intervals were used. Univariate metaregression was done by DerSimonian-Laird methods. Factors with a p-value less than 0.05 in the univariate metaregression model were entered in the multivariate metaregression model. Heterogeneity was assessed using the Higgins I² test. The random-effects model was used in meta-analysis.

Results

Total 14 studies including 15510 patients were included in the final analysis. 1247 patients developed Acute Kidney Injury. Weighted Acute kidney injury percentage after liver resection was 15% with a 95% confidence interval of 11%-19%. On univariate metaregression analysis major hepatectomy (p=0.001), Underlying cirrhosis of liver (p=0.031), AKIN definition used (0.017), male sex (p<0.001), open surgery (p=0.032), underlying diabetes (0.026). On multivariate metaregression analysis major hepatectomy (p=0.003), underlying cirrhosis (p<0.001), male sex (p<0.001), AKIN classification used for defining acute kidney injury (p < 0.001, independently predicted heterogeneity and hence acute kidney injury.

Conclusion

Liver resection is associated with a high incidence of acute kidney injury. Major hepatectomy, male sex, underlying cirrhosis were independently predicting acute kidney injury.

Surgery

Acute kidney injury

liver resection

hepatectomy

meta-analysis

metaregression Abbreviations: Acute Kidney Injury Network classification (AKIN)

Risk

Injury

Failure

Loss and End stage renal disease (RIFLE)

Kidney Disease Improving Global Outcomes criteria (KDIGO)

Liver resections or partial hepatectomies are sometimes the only chance of cure in various benign and malignant conditions. Liver resections are still associated with high postoperative complications and mortality. [1,2,3]. The post-operative acute kidney is very common after liver resections. Different literature mentioned different incidences of acute kidney injury in various cohorts.[4].

Acute kidney injury incidence in overall noncardiac surgeries is around 1%, but it is very high after liver resections. However, the different article describes the different incidence of acute kidney injury after liver resection with incidence from 0.9% to around 20%. [5]. Incidence of postoperative acute kidney injury also depends upon various patient, tumor, and liver-related factors.

One of the reasons for heterogeneity in the literature is the variation in the definition of acute kidney injury used in the literature. Some used Acute Kidney Injury Network classification (AKIN), some used Risk, Injury, Failure, Loss and End-stage renal disease (RIFLE criteria) or some studies used Kidney Disease Improving Global Outcomes criteria (KDIGO) which combines RIFLE and AKIN criteria. [6,7,8].

Aim:

This systematic review and meta-analysis aimed to study the prevalence of acute kidney injury after liver resection and to analyze various factors affecting it by metaregression analysis.

The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (2020) and MOOSE guidelines. [9,10]. We conducted a literature search as described by Gossen et al. PubMed, Cochrane Library, Embase, google scholar, web of science with mesh terms “Acute kidney injury” AND “liver resection” OR “hepatectomy”. [11] Two independent authors extracted the data. In case of disagreements, decisions are reached on basis of discussions. We defined major hepatectomy as >= 3 liver segments. We defined chronic renal failure as preoperative eGFR < 90 ml/min/1.73m2 .

Statistical Analysis:

The meta-analysis was done using Review Manager 5.4 and the JASP Team (2020). JASP (Version 0.14.1)(University of Amsterdam). Weighted percentage incidence with 95% confidence intervals were used. Univariate metaregression was done by DerSimonian-Laird methods. Factors with a p-value less than 0.05 in the univariate metaregression model were entered in the multivariate metaregression model. Heterogeneity was assessed using the Higgins I² test [12], with values of 25%, 50%, and 75% indicating low, moderate, and high degrees of heterogeneity, respectively, and assessed p-value for the significance of heterogeneity and tau² and H² value. The random-effects model was used in meta-analysis.

Assessment of Bias:

Cohort studies were assessed for bias using the Newcastle-Ottawa Scale to assess for the risk of bias Publication bias was assessed using a funnel plot. [13,14]. Funnel plot asymmetry was evaluated by Egger’s test.

Inclusion and Exclusion criteria for studies:

Inclusion criteria:

• Studies with full texts

• Studies that evaluated acute kidney injury after liver resection

• English language studies

Exclusion criteria:

• · Studies which were not fulfilling the above criteria.

• · Duplicate studies.

Data extraction, study characteristics, and quality assessment:

‘PUBMED’, ‘SCOPUS’, and ‘EMBASE’ databases were searched using keywords and the search strategy described above. 31700 studies were found using earlier mentioned MESH terms after duplicates were removed 30573 studies were screened, 30556 studies were excluded after applying exclusion criteria. Out of 17 studies remaining full texts of 3 studies could not be retrieved and excluded. 14 studies including 15510 patients who underwent liver resections were included in the final analysis. [Figure 1]. The risk of bias summary is mentioned in Figure 2. Study characteristics are mentioned in table 1. All studies were either retrospective cohort, prospective cohort, or propensity score-matched study. In propensity score-matched analysis unmatched total data were analyzed for postoperative morbidity.

Acute Kidney Injury:

Total 14 studies including 15510 patients were included in the final analysis. [15-28]. 1247 patients developed Acute Kidney Injury. Weighted Acute kidney injury percentage after liver resection was 15% with a 95% confidence interval of 11%-19% as shown in the forest plot. [Figure 3]. 5 studies used AKIN criteria, 6 used KDIGO, and 1 used RFILE criteria, for two studies detailed of Acute kidney injury definitions were not available. [Table 1]. However, the heterogeneity of the analysis was high with I2 98.83 % ( p<0.01). Publication bias was also significant with a p-value <0.01, as shown in the funnel plot. [figure 4]

Meta-regression analysis: [Supplement Table 1]

On univariate metaregression analysis major hepatectomy (p=0.001), Underlying cirrhosis of liver (p=0.031), AKIN definition used (0.017), male sex (p<0.001), open surgery (p=0.032), underlying diabetes (0.026). On multivariate metaregression analysis major hepatectomy (p=0.003), underlying cirrhosis (p<0.001), male sex (p<0.001), AKIN classification used for defining acute kidney injury (p < 0.001, independently predicted heterogeneity and hence acute kidney injury. Residual heterogeneity after multivariate metaregression analysis was nonsignificant (p=0.065) and publication bias with eagers’ test was also nonsignificant. (p= 0.292). Multivariate metaregression forest plot and funnel plot for publication bias is shown in supplement figure 1.

Acute kidney injury post liver resection is a serious problem and is always associated with higher postoperative mortality. [1, 2, 3]. Many individual cohort studies are available to know the incidence of acute kidney injury after liver resection. However, there was a wide difference in incidence rates, one of the reasons for it may be variation in techniques, patient population, type of surgeries, and because of that, we decided to perform systematic review and metaanalysis with metaregression analysis to look for reasons of heterogeneity and factors responsible for heterogeneity and in the process with acute kidney injury, and also to find the pooled prevalence of acute kidney injury post-liver resections.

The weighted pooled prevalence of acute kidney injury after liver resection was 15% ( 95% confidence interval 11-19%), however as expected heterogeneity was significant and high with I2 of 98.83%, suggesting a difference in Acute kidney injury according to the various study population. After multivariate metaregression analysis major hepatectomy, underlying cirrhosis, male sex and AKIN classification used were independently associated with heterogeneity and hence acute kidney injury and difference acute kidney injury rates across various centers.

The fact that Acute Kidney Injury Network or AKIN definition of acute kidney injury independently predicted heterogeneity across various studies shows that acute kidney injury incidence was different across the studies differed somewhat due to definitions used and it shows the need for a standard definition of postoperative acute kidney injury as some decrease in urine output is expected after major abdominal surgery due to increased fluid shifts and third space loss in post-operative periods.

Amount of intraoperative fluids, intraoperative hypotension, blood loss were not associated with heterogeneity in the acute kidney injury incidences in our metanalysis which may suggest the perioperative practices are standardized across the centers. Preoperative diabetes was associated with heterogeneity in univariate analysis but failed to predict heterogeneity independently in multivariate metaregression analysis. Preoperative hypertension and pre-existing chronic renal failure were not associated with heterogeneity across the centers.

There are some limitations in our analysis, as most of the studies were retrospective, so, we could not entirely rule out the selection and reporting bias as shown in the summary of bias. The strength of this analysis was that to our knowledge this is the first metanalysis with metaregression analysis studying various factors associated with heterogeneity across the studies and hence acute kidney injury.

Liver resection is associated with a high incidence of acute kidney injury. Major hepatectomy, male sex, underlying cirrhosis were independently predicting acute kidney injury. Acute kidney injury incidence also varied according to the acute kidney injury definition used.

Gilg S, Sandstro¨m P, Rizell M et al (2018) The impact of post hepatectomy liver failure on mortality: a population-based study. Scand J Gastroenterol 25:1–5
Ray S, Mehta NN, Golhar A et al (2018) Post hepatectomy liver failure–A comprehensive review of current concepts and controversies.Ann Med Surg 34:4–10.
Kauffmann R, Fong Y (2014) Post-hepatectomy liver failure. Hepatobiliary Surg Nutr 3(5):238.
Saner F. Kidney failure following liver resection. Transplant Proc. 2008 May;40(4):1221-4. doi: 10.1016/j.transproceed.2008.03.068.
Peres LA, Bredt LC, Cipriani RF. Acute renal injury after partial hepatectomy. World J Hepatol. 2016 Jul 28;8(21):891-901. doi: 10.4254/wjh.v8.i21.891.
Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A; Acute Kidney Injury Network. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11(2):R31. doi: 10.1186/cc5713.
Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P; Acute Dialysis Quality Initiative workgroup. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004 Aug;8(4):R204-12. doi: 10.1186/cc2872.
KDIGO Board Members. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl. 2012;2:1-138.
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021 Mar 29;372:n71. doi: 10.1136/bmj.n71.
Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000 Apr 19;283(15):2008-12. doi: 10.1001/jama.283.15.2008.
Goossen K, Tenckhoff S, Probst P, Grummich K, Mihaljevic AL, Büchler MW, Diener MK. Optimal literature search for systematic reviews in surgery. Langenbecks Arch Surg. 2018 Feb;403(1):119-129. doi: 10.1007/s00423-017-1646-x.
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003 Sep 6;327(7414):557-60. doi: 10.1136/bmj.327.7414.557.
Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. Edited by Higgins JPT, Green S. [http://www. cochrane-handbook.org]
Wells G, Shea B, O’Connell D, Peterson J, Welch V, Losos M, Tugwell P: The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2013.http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
Bressan AK, James MT, Dixon E, Bathe OF, Sutherland FR, Ball CG. Acute kidney injury following resection of hepatocellular carcinoma: prognostic value of the acute kidney injury network criteria. Can J Surg. 2018 Oct 1;61(5):E11-E16. doi: 10.1503/cjs.002518.
Cho E, Kim SC, Kim MG, Jo SK, Cho WY, Kim HK. The incidence and risk factors of acute kidney injury after hepatobiliary surgery: a prospective observational study. BMC Nephrol. 2014 Oct 23;15:169. doi: 10.1186/1471-2369-15-169.
Garnier J, Faucher M, Marchese U, Meillat H, Mokart D, Ewald J, Delpero JR, Turrini O. Severe acute kidney injury following major liver resection without portal clamping: incidence, risk factors, and impact on short-term outcomes. HPB (Oxford). 2018 Sep;20(9):865-871. doi: 10.1016/j.hpb.2018.03.011.
Dedinská I, Mikolajčík P, Skálová P, Mokáň M, Laca Ľ. Acute kidney injury after liver resection in elderly patients. BMC Nephrol. 2019 Jul 18;20(1):272. doi: 10.1186/s12882-019-1449-0.
Kim M, Kiran RP, Li G. Acute kidney injury after hepatectomy can be reasonably predicted after surgery. J Hepatobiliary Pancreat Sci. 2019 Apr;26(4):144-153. doi: 10.1002/jhbp.615.
Lim C, Audureau E, Salloum C, Levesque E, Lahat E, Merle JC, Compagnon P, Dhonneur G, Feray C, Azoulay D. Acute kidney injury following hepatectomy for hepatocellular carcinoma: incidence, risk factors and prognostic value. HPB (Oxford). 2016 Jun;18(6):540-8. doi: 10.1016/j.hpb.2016.04.004.
Moon YJ, Jun IG, Kim KH, Kim SO, Song JG, Hwang GS. Comparison of acute kidney injury between open and laparoscopic liver resection: Propensity score analysis. PLoS One. 2017 Oct 13;12(10):e0186336. doi: 10.1371/journal.pone.0186336.
Slankamenac K, Breitenstein S, Held U, Beck-Schimmer B, Puhan MA, Clavien PA. Development and validation of a prediction score for postoperative acute renal failure following liver resection. Ann Surg. 2009 Nov;250(5):720-8. doi: 10.1097/SLA.0b013e3181bdd840.
Tomozawa A, Ishikawa S, Shiota N, Cholvisudhi P, Makita K. Perioperative risk factors for acute kidney injury after liver resection surgery: an historical cohort study. Can J Anaesth. 2015 Jul;62(7):753-61. doi: 10.1007/s12630-015-0397-9.
Tsai MS, Lin CL, Chang SN, Lee PH, Kao CH. Diabetes mellitus and increased postoperative risk of acute renal failure after hepatectomy for hepatocellular carcinoma: a nationwide population-based study. Ann Surg Oncol. 2014 Nov;21(12):3810-6. doi: 10.1245/s10434-014-3777-4.

Milan Z, Gomes AR. Perioperative risk factors for acute kidney injury following liver resection surgery. Edorium J Anesth 2019;5:100017A05ZM2019.
Bredt LC, Peres LAB. Risk factors for acute kidney injury after partial hepatectomy. World J Hepatol. 2017 Jun 28;9(18):815-822. doi: 10.4254/wjh.v9.i18.815.
Mizunoya K, Yagi Y, Kamachi H, Kamiyama T, Morimoto Y, Taketomi A. Diagnostic timing dependent characteristics of acute kidney injury following hepatectomy: a retrospective historical cohort analysis. HPB (Oxford). 2021 May 18:S1365-182X(21)00142-8. doi: 10.1016/j.hpb.2021.05.003.
Kim SK, Choi SS, Sim JH, Baik J, Hwang S, Lee SG, Kim YK. Effect of Hydroxyethyl Starch on Acute Kidney Injury After Living Donor Hepatectomy. Transplant Proc. 2016 Jan-Feb;48(1):102-6. doi: 10.1016/j.transproceed.2015.12.016.

Table 1. Patients’ characteristics.

study	Type of Study	AKI (n)	AKI (%)	Total Patients(n)	Major Hepatectomy	intraoperative hypotension	Cirrhosis	Operative time (minutes)	Blood loss (ml)	Akin Classification	Sex (male) (n)	Open Surgery(n)	Diabetes	Age (mean)	Intra operative fluid (ml)	Hypertension	Kidigo Criteria	Chronic Renal Failure	RIFILE Criteria
Alexsander2018 [15]	Retrospective cohort	43	53	80	20		64		250	Yes	61	67	20	62		28	No	44	No
cho 2014 [16]	Retrospective cohort	52	40	131	100	34	7	300	350	Yes	82	131	32	56	1985	44	No	0	No
Garneir 2017 [17]	Retrospective cohort	24	21.6	111	106	46	2	340	500	No	55	109	13	66	3000		No	11	No
Dedinska 2019 [18]	Retrospective cohort	26	3	785	107					No				58.7			Yes		No
kim2019 [19]	Retrospective cohort	432	16.04	2692	918		257	250		No	1358	2692	444	60		1193	Yes	1154	No
lim2016 [20]	Retrospective cohort	67	14.6	457	241		206	208		No	379	329	75	60.5			Yes	70	No
moon2017 [21]	Propensity score matched	77	6.56	1173	790			271		No	951	926	75	55.7	2263	80	Yes	866	No
Slenkamenac2009 [22]	Prospective cohort	86	15.11	569	326		40	294.2	551	No	311	573	59	57.2			No	73	Yes
Tomozawa2015 [23]	Retrospective cohort	78	12.14	642	230		93	300	1310	Yes	473	642	130	67	4400	310	No	124	No
tsai2014 [24]	Retrospective cohort	62	10.46	5924	1140		1957			No	4273		2962	63		577	No	80	No
Milan 2019 [25]	Retrospective cohort	17	15.45	109	46			233		No	55	92	26	61			Yes		No
Bredt 2017 [26]	Retrospective cohort	80	17.93	446	128	26	23			Yes	223	343	44	54.6		70	No		No
Kazuyuki 2021 [27]	Retrospective cohort	135	18	750	285		111	330	300	No		540	194		2550	385	Yes	569	No
kim2016 [28]	Propensity score matched	68	4.14	1641	1641		0			Yes	1109	1641	0	27.5		0	No	0	No

Supplementfigure1a.png
Metaregression forest plot and funnel plot.
Supplementfigure1b.png
Metaregression forest plot and funnel plot.
Table2.docx
Supplement table 1

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published 31 Dec, 2021

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Acute kidney injury after liver resection: A systematic review, meta-analysis and metaregression of factors affecting it

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