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Fluid balance, change in serum creatinine and urine output as markers of acute kidney injury post cardiac… Chau, Katrina; Schisler, Travis; Er, Lee; Jaswal, Dharmvir; Cheung, Christopher; Israel, Amanda; Bowering, John; Levin, Adeera Sep 2, 2014

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RESEARCH Open AccessFluid balance, change in serum creatinine andurine output as markers of acute kidney injuryConclusions: Oliguria and positive fluid balance is associated with a trend towards longer LOS as compared to oliguriaChau et al. Canadian Journal of Kidney Health and Disease 2014, 1:19http://www.cjkhd.org/content/1/1/19Columbia, St Paul’s Hospital, 1081 Burrard St, Vancouver, BC V6Z1Y6, CanadaFull list of author information is available at the end of the articlealone. Fluid balance may therefore be a useful marker of AKI, in addition to urine output and serum creatinine.Keywords: Acute kidney injury, Diagnosis, Fluid resuscitation, Cardiac surgery* Correspondence: dr.katrina.chau@gmail.com1Division of Nephrology, Faculty of Medicine, The University of BritishLimitations: Single centre, small sample, LOS as outcomeKatrina Chau1*, Travis Schisler2, Lee Er1, Dharmvir Jaswal1, Christopher Cheung3, Amanda Israel3,John Bowering2 and Adeera Levin1AbstractBackground: Acute kidney injury (AKI) is defined as oliguria or rise in serum creatinine but oliguria alone as adiagnostic criterion may over-diagnose AKI.Objectives: Given the association between fluid overload and AKI, we aimed to determine if positive fluid balancecan complement the known parameters in assessing outcomes of AKI.Design: Prospective observational study.Setting: Teaching hospital in Vancouver, Canada.Patients: 111 consecutive patients undergoing elective cardiac surgery from January to April 2012.Measurements: Outcomes of cardiac surgery intensive care unit (CSICU) and hospital length of stay (LOS) inrelation to fluid balance, urine output and serum creatinine.Methods: All fluid input and output was recorded for 72 hours post-operatively. Positive fluid balance was definedas >6.5 cc/kg. Daily serum creatinine and hourly urine output were recorded and patients were defined as havingAKI according to the AKIN criteria.Results: Of the patients who were oliguric, those with fluid overload trended towards longer LOS than thosewithout fluid overload [CSICU LOS: 62 and 39 hours (unadjusted p-value 0.02, adjusted p-value 0.58); hospital LOS:13 and 9 days (unadjusted p-value: 0.05, adjusted p-value: 0.16)]. Patients with oliguria who were fluid overloadedhad similar LOS to patients with overt AKI (change in serum creatinine≥ 26.5 µmol/L), [CSICU LOS: 62 and 69 hours(adjusted p value: 0.32) and hospital LOS: 13 and 14 days (adjusted p value: 0.19)]. Patients with oliguria regardlessof fluid balance had longer CSICU LOS (adjusted p value: 0.001) and patients who were fluid overloaded in theabsence of AKI had longer hospital LOS (adjusted p value: 0.02)..post cardiac surgery: an observational study© 2014 Chau et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly credited. The Creative Commons Public DomainDedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,unless otherwise stated.mt miononce scstiasChau et al. Canadian Journal of Kidney Health and Disease 2014, 1:19 Page 2 of 11http://www.cjkhd.org/content/1/1/19Résultats: Parmi les patients oliguriques, ceux qui avaient une surcharge liquidienne tendaient davantage versune hospitalisation prolongée que ceux qui n’en avaient pas [durée de soins actifs à l’USICC: 62 et 39 heures(valeur de p non ajustée: 0,02, valeur de p ajustée: 0,58); durée de soins actifs à l’hôpital: 13 et 9 jours (valeur dep non ajustée: 0,05, valeur de p ajustée: 0,16)]. Les patients présentant une oligurie qui présentaient aussi unesurcharge liquidienne requéraient une durée de soins actifs similaire aux patients souffrant d’IRA (modificationde la créatininémie≥ 26,5 µmol/L), [soins actifs USICC: 62 et 69 heures (valeur de p ajustée: 0,32) soins actifs àl’hôpital: 13 et 14 jours (valeur de p ajustée: 0,19)]. Les patients présentant une oligurie, indépendamment de labalance liquidienne, bénéficiaient d’une durée de soins actifs à l’USICC prolongée (valeur p ajustée: 0,001), tandisque les patients en surcharge liquidienne, mais ne souffrant pas d’IRA bénéficiaient davantage de soins actifs àl’hôpital (valeur de p ajustée: 0,02).Limites de l’étude: Un seul centre, un échantillon restreint, les soins actifs considérés comme une issue.Conclusion: Les patients avec oligurie et une balance liquidienne positive ont nécessité des soins actifsprolongés à l’USICC, comparativement aux patients ne présentant qu’une oligurie. La balance liquidienne peutdonc constituer un marqueur d’IRA, en plus de la diurèse et la créatininémie.What was known beforeOliguria as a sole diagnostic criterion may over-diagnoseacute kidney injury.What this addsConsidering oliguria in the context of fluid status may bemore useful than using oliguria as a sole diagnostic criter-ion. This study suggests that oliguria in the context of fluidoverload identifies patients who require a longer length ofstay as compared to patients who have oliguria alone.BackgroundAcute kidney injury (AKI) describes a spectrum of condi-tions ranging from a biochemical abnormality to oligoanu-ric renal failure requiring renal replacement therapy. It isassociated with adverse short and long term outcomes inall populations studied, irrespective of the definition used.[1] include the parameters of both serum creatinine andurine output. Consistency of definitions is important forclinical care and research across jurisdictions.AKI as defined by the Acute Kidney Injury Network(AKIN) [2] is based on measurements of urine output orserum creatinine. According to AKIN, the urine outputcriterion for the diagnosis of AKI is a urine output ≤0.5 cc/kg/hour for greater than 6 hours. Changes in serumcreatinine of as small as 26.5 µmol/L (or 0.3 mg/dl), areconsidered Stage 1 AKI within the AKIN classification.These small changes in serum creatinine have been consist-ently demonstrated to be associated with adverse outcomes,in numerous populations [3,4]. The AKIN classification haslargely been adopted as the KDIGO AKI definition.Although reduced urine output often precedes develop-ment of AKI as defined by a rise in serum creatinine, oli-guria as a sole diagnostic criterion has been questioned byAbrégéContexte: L’insuffisance rénale aiguë (IRA) se définit comcontre, l’oligurie comme unique critère diagnostique peuObjectifs: Étant donné l’association entre l’hyperhydratatliquidienne positive peut complémenter les paramètres cType d’étude: Étude d'observation prospective.Contexte: Hôpital universitaire à Vancouver, Canada.Participants: 111 patients consécutifs qui subissent uneavril 2012.Mesures: On a mis en parallèle les résultats de l’unité dmême que la durée de l’hospitalisation (soins actifs), aveMéthodes: On a mesuré les ingesta et excreta durant leliquidienne positive à >6,5 cc/kg. On a enregistré la créaa déterminé que les patients souffraient d’IRA en nous bNetwork (AKIN).The definitions have varied over time in the published lit-erature as well as in clinical practice. Recently published,standardized definitions from the KDIGO AKI Guidelinee une oligurie ou une élévation de la créatininémie. Parener abusivement au diagnostic d’IRA.et l’IRA, nous cherchons à déterminer si une balancenus dans l’évaluation des résultats de l’IRA.hirurgie cardiaque non urgente, entre janvier etoins intensifs en chirurgie cardiaque (USICC), dela balance liquidienne, la diurèse et la créatininémie.72 heures postopératoires. On a défini une balanceninémie quotidienne et la diurèse aux heures, et onant sur les critères de l’Acute Kidney Injurymany as being too sensitive, and classifies too many peopleas having ‘AKI’ [5]. There is controversy as to whether re-duced urine output alone is associated with adverseChau et al. Canadian Journal of Kidney Health and Disease 2014, 1:19 Page 3 of 11http://www.cjkhd.org/content/1/1/19outcomes. Creatinine as a solitary biomarker for AKI itselfhas a multitude of well known flaws, and fluid overloadmay dilute creatinine concentration, thus potentiallydelaying the diagnosis of AKI.Fluid balance or evidence of fluid overload has cometo the attention of both clinicians and researchers as analternative ‘biomarker’ for AKI. Fluid overload has beenassociated with adverse outcomes in critical care popula-tions, and is often seen in association with AKI. Therehas been an ongoing ‘chicken and egg’ debate [6] regard-ing the role of fluid overload in AKI. It is unclearwhether AKI is a consequence of fluid overload or ratherthat the presence of fluid overload in AKI indicates amore critically unwell patient requiring aggressive fluidresuscitation. Regardless, the association has been con-sistently demonstrated in the literature.The current study sought to describe the individualparameters of fluid balance, urine output and changes inserum creatinine in varying combinations, in a popula-tion of patients undergoing elective cardiac surgery. Wewere interested in describing the constellations of these3 parameters and their association with outcomes in thisspecific population.The hypothesis of the study is that fluid balance is a use-ful parameter for the identification of patients - broadlydiagnosed with AKI – who have worse outcomes.MethodsOne hundred and eleven consecutive patients who wereundergoing elective coronary artery bypass grafting(CABG), valve replacement or combined surgery over a3-month period from January and April 2012 (conveni-ence sample) were prospectively enrolled in this obser-vational study. Patients on dialysis, those undergoing offpump surgical procedures, trans-catheter valve replace-ment surgery and isolated or combined thoracic aortasurgery were excluded.Demographic and clinical baseline characteristics and riskfactors were obtained from medical records and included:age, sex, weight, presence of diabetes, serum creatinine,eGFR (MDRD equation) <60 ml/min/1.73 m [2], exposureto intravenous contrast within two weeks of surgery andmedications. Details of the surgical procedure were cap-tured: duration of surgery (skin to skin), cardiopulmonarybypass (CPB) time and fluid administration totals from per-fusionist records (type and amount of crystalloid and col-loid), urine output, blood loss and blood transfusions.Patients were observed and data tabulated for all fluidinputs and outputs for 72 hours post operatively, irre-spective of location of the patient (critical care area orward). Fluid balance was determined from all recordsupon discharge from the cardiac surgery intensive careunit (CSICU) and expressed as cc/kg. Daily serum cre-atinine and body weight was also recorded.For the purposes of this study we defined AKI as per theAKIN criteria: the definition of AKI based on serum cre-atinine (AKICr)) was an increase from baseline of ≥26.5µmol/L and the definition based on urine output (AKIUO)was urine output ≤ 0.5 cc/kg/hour for greater than 6 hours.We defined positive fluid balance for the purposes of thisstudy as ≥ 6.5 cc/kg based on the rationale that insensiblelosses per day are approximately 500 cc/day. Thus, usingthe mean weight in the population (81 kg), we calculatedthat 6.5 cc/kg would approximate insensible losses (525 cc)over one day – the median CSICU length of stay – so thatamounts over that would constitute a positive fluid balance.Patients were categorized based on the combination of theirstatuses on the change in serum creatinine (≥26.5 µmol/L, de-noted as SCr+/−), urine output (≤0.5 cc/kg/hr for greater than6 hours, denoted as UO+/−) and fluid balance (≥6.5 cc/kg, de-noted as FOL+/−). The combinations under considerationwere: 1) SCr-, UO-, FOL- (no AKI), 2) SCr-, UO-, FOL+, 3)SCr-, UO+, FOL-, 4) SCr-, UO+, FOL+, and 5) SCr +.The main outcomes of interest were duration of CSICU(hours/days) and hospital length of stay (LOS) (days).Statistical analysisContinuous variables are presented as mean with stand-ard deviation if normally distributed or median withinterquartile range. Frequencies and percentages werepresented for categorical variables.The comparisons on the demographics, preoperative andintraoperative measures across groups were conductedusing One-way ANOVA, Kruskal-Wallis test, Chi-square orFisher’s exact tests where appropriate.The relationships between various combinations ofchange in serum creatinine/urine output/fluid balance andoutcomes were examined by fitting two separate models,one for CSICU LOS and one for hospital LOS. Each LOSoutcome was assumed to be log-normally distributed. Wefitted a multiple linear regression model to examine the as-sociation between mean of log(LOS) and groups adjustingfor potential confounding variables. The group variable (ie:combination of SCr/UO/FOL status) was parameterized [7]as in Table 1 for two reasons:1) We wanted to treat the group variable as an ordinalvariable as these group variables reflected severity asseen in Figures 1 and 2. By this parameterization, wecould preserve the ordinal ranks without treating itas a continuous variable by arbitrarily assigning anumerical value to each category.2) We could then compare between any two adjacentcategories and hence obtain the best estimate of theincrement/decrement (depending on whether theestimated parameter value was positive or negative)in the mean outcome between any two adjacentcategories from the data. In other words, this wouldTable 1 Parameterization of the group variable in the multiple linear regression modelsParameterization (corresponding parameter in the model)Group X1 (β1) X2 (β2) X3 (β3) X4 (β4)1) SCr-, UO-, FOL- 0 0 0 02) SCr-, UO-, FOL+ 1 0 0 03) SCr-, UO+, FOL- 1 1 0 04) SCr-, UO+, FOL+ 1 1 1 05) SCr+ 1 1 1 1Each group variable or combination of SCr/UO/FOL status was parameterized as above so that the group variable could be considered as an ordinal variable inthe multiple linear regression model. β1 indicates a comparison between SCr-, UO-, FOL- and SCr-, UO-, FOL+, β2 indicates a comparison between SCr-, UO-, FOL +and SCr-, UO+, FOL- and so forth.SCr+: Meeting the criteria of Change in SCr ≥ 26.5 µmol/L; SCr -: Not meeting the Change in SCr criteria.UO+: Meeting the criteria of Urine Output ≤0.5 cc/kg/hour for greater than 6 hours; UO-: Not meeting the Urine Output criteria.FOL+: Meeting the criteria of Fluid Overload, defined as fluid balance ≥ 6.5 cc/kg; FOL-: Not meeting the Fluid Overload criteria.Figure 1 Length of stay in cardiac surgery intensive care unit (CSICU), by categories of combinations of changes in serum creatinine,urine output and fluid overload. Abbreviations: SCr+: Meeting the criteria of Change in SCr≥ 26.5 µmol/L ; SCr-: Not meeting the Change in SCrcriteria. UO+: Meeting the criteria of Urine Output ≤0.5 cc/kg/hour for greater than 6 hours; UO-: Not meeting the Urine Output criteria. FOL+: Meetingthe criteria of Fluid Overload, defined as fluid balance≥ 6.5 cc/kg; FOL-: Not meeting the Fluid Overload criteria. IQR: Interquartile range. BL: Baseline.Chau et al. Canadian Journal of Kidney Health and Disease 2014, 1:19 Page 4 of 11http://www.cjkhd.org/content/1/1/19Chau et al. Canadian Journal of Kidney Health and Disease 2014, 1:19 Page 5 of 11http://www.cjkhd.org/content/1/1/19allow us to identify the ‘breakpoint(s)’ or ‘threshold(s)’ of the group variables at which significantchanges occur in the outcome. For example, if onlyβ3 (comparing group 3 and 4) was statisticallysignificant, this would imply there were nodifferences in the mean log(LOS) in the first 3groups and that furthermore, there was also nodifference in the mean log(LOS) in the last 2 groups;hence group 4 was the critical breakpoint for anincrease/decrease in the outcome.We adjusted for the covariates age, diabetes status, pre-operative eGFR, duration of surgery, CPB time, bloodtransfusion and vasopressor requirement and percentageof patients with negative fluid balance during the intraop-erative phase (only for CSICU LOS) in the models. Thesecovariates were included based on clinical and statisticalFigure 2 Hospital length of stay by categories of combinations of chaAbbreviations: SCr+: Meeting the criteria of Change in SCr≥ 26.5 µmol/L ; SCr-Urine Output ≤0.5 cc/kg/hour for greater than 6 hours; UO-: Not meeting tdefined as fluid balance≥ 6.5 cc/kg; FOL-: Not meeting the Fluid Overloadjudgment on their relations to both group and outcomevariables which resulted in the best fit to the data.We considered a p-value of <0.05 as statistically sig-nificant. All statistical analysis was performed using SAS,version 9.3 (SAS institute, Cary, NC).The study was approved by the institutional reviewboard (Providence Health Care Research Ethics BoardH11-03485) and conformed to the regulations of the insti-tutional ethics committee on human research. Writtenconsent was not required due to the observational natureof the study, and lack of interventions.ResultsPatient characteristics at baseline and peri-operativelyTable 2 describes the patient characteristics at baseline,preoperative and intraoperative measurements for theoverall study cohort and by groups. Of the 111 patients,nges in serum creatinine, urine output and fluid overload.: Not meeting the Change in SCr criteria. UO+: Meeting the criteria ofhe Urine Output criteria. FOL+: Meeting the criteria of Fluid Overload,criteria. IQR: Interquartile range. BL: Baseline.Table 2 Summary of patients’ characteristics at baseline, preoperative and intraoperative measuresAll (n = 111) SCr-, UO-, FOL- (n = 43) SCr-, UO-, FOL + (n = 32) SCr-, UO+, FOL- (n = 11) SCr-, UO+, FOL + (n = 15) SCr + (n = 10) P-valueDemographicsAge (years) 69 ± 10 69 ± 9 73 ± 8 60 ± 14 68 ± 11 69 ± 11 0.03Male 84 (76%) 36 (84%) 21 (66%) 9 (82%) 11 (73%) 7 (70%) 0.43Diabetes 31 (28%) 10 (23%) 4 (12%) 5 (45%) 6 (40%) 6 (60%) 0.01Preoperative MeasuresWeight (kg) 80 (68, 91) 80 (71, 92) 69 (64, 84) 84 (78, 111) 85 (79, 93) 92 (68, 107) 0.01Height (cm) 170 ± 10 170 ± 10 169 ± 11 172 ± 8 171 ± 10 170 ± 12 0.94Creatinine (μmol/L) 85 (71, 103) 87 (69, 101) 80 (71, 93) 81 (70, 103) 88 (70, 96) 117 (90, 144) 0.01eGFR (mL/min/1.73 m2) 72 ± 17 77 ± 23 73 ± 19 81 ± 23 63 ± 28 52 ± 18 0.01eGFR <60 mL/min/1.73 m2 28 (25%) 8 (19%) 7 (23%) 2 (18%) 4 (27%) 7 (70%) 0.03Recent IV Contrast 57 (51%) 15 (35%) 21 (64%) 5 (45%) 9 (60%) 7 (70%) 0.05Pre-op ACE/ARB 73 (66%) 27 (63%) 20 (62%) 9 (82%) 11 (73%) 6 (60%) 0.72Pre-op Diuretics 31 (28%) 11 (25%) 6 (19%) 3 (27%) 5 (33%) 6 (60%) 0.16Surgery TypeMVR Only/AVR Only 35 (32%) 12 (28%) 13 (41%) 2 (18%) 4 (27%) 4 (40%) 0.17CABG Only 59 (53%) 28 (65%) 13 (41%) 8 (73%) 6 (40%) 4 (40%)CABG +MVR/AVR 17 (15%) 3 (7%) 6 (18%) 1 (9%) 5 (33%) 2 (20%)Intraoperative MeasuresDuration of Surgery (mins) 177 (146, 209) 188 (150, 209) 156 (122, 190) 176 (117, 200) 186 (151, 233) 200 (173, 243) 0.007CPB Time (mins) 92 (72, 108) 92 (77, 105) 75 (62, 96) 84 (46, 100) 103 (88, 148) 103 (95, 140) 0.01Intraoperative pRBC 24 (22%) 6 (12%) 9 (25%) 1 (0%) 7 (40%) 6 (50%) 0.007Intraoperative Crystalloid (cc) 1260 (875, 1727) 1200 (900, 1780) 1350 (900, 1663) 850 (700, 1260) 1050 (845, 1650) 1386 (1000, 1880) 0.43Intraoperative Colloid (cc) 500 (500, 500) 500 (500, 650) 500 (500, 600) 500 (500, 500) 500 (500, 500) 500 (500, 500) 0.54Total Fluid Administered (cc) 1850 (1485, 2380) 1820 (1500, 2380) 1901 (1715, 2398) 1350 (1100, 1960) 1730 (1520, 2404) 2165 (1600, 3412) 0.08Total Urine Output (cc) 250 (160, 400) 325 (175, 500) 250 (187, 470) 220 (150, 350) 260 (125, 400) 125 (70, 225) 0.07Total Fluid Balance (cc) 129 (846, 1700) 1350 (900, 1720) 1147 (875, 1519) 1240 (515, 1825) 1200 (−686, 1650) 1765 (105, 2003) 0.68Negative Fluid Balance atCompletion of Surgery8 (7%) 1 (2%) 0 (0%) 0 (0%) 5 (33%) 2 (20%) <0.001Chauetal.CanadianJournalofKidneyHealthandDisease2014,1:19Page6of11http://www.cjkhd.org/content/1/1/19Table 2 Summary of patients’ characteristics at baseline, preoperative and intraoperative measures (Continued)Postoperative MedicationsVasopressors 85 (77%) 29 (67%) 27 (84%) 6 (54%) 13 (87%) 10 (100%) 0.04Number of Vasopressors 1 (1, 2) 1 (0, 1) 1.5 (1, 2) 1 (0, 2) 2 (1, 2) 2.5 (2, 4) <0.001Vasopressors used were: Adrenaline, noradrenaline, dobutamine, milirinone and vasopressin.SCr+: Meeting the criteria of Change in SCr ≥ 26.5 µmol/L ; SCr -: Not meeting the Change in SCr criteria.UO+: Meeting the criteria of Urine Output ≤0.5 cc/kg/hour for greater than 6 hours; UO-: Not meeting the Urine Output criteria.FOL+: Meeting the criteria of Fluid Overload, defined as fluid balance ≥ 6.5 cc/kg; FOL-: Not meeting the Fluid Overload criteria.Continuous variables are presented in mean ± standard deviation or median with interquartile range. Categorical variables are presented in count with percentage.One-way ANOVA or Kruskal-Wallis test were used to compare among groups for the continuous variables; Chi-Square test or Fisher’s Exact test were used for the categorical variables.eGFR was calculated using the MDRD equation.Chauetal.CanadianJournalofKidneyHealthandDisease2014,1:19Page7of11http://www.cjkhd.org/content/1/1/1976% were male, the mean age was 69 years and 28% werediabetic. The median serum creatinine was 85 μmol/L, cor-responding to an eGFR of 72 ml/min/1.73 m [2], and 25%of patients had a pre-operative eGFR <60 ml/min. Over halfthe cohort received IV contrast within 2 weeks of the sur-gery, and 66% were receiving ACEi/ARB pre-operatively.85% of the patients received a CABG or valve replacementsurgery with the remainder having combined surgery.The median duration of surgery was 177 minutes witha median CPB time of 92 minutes. 22% received intraop-erative blood transfusion, and the median total fluid ad-ministered intraoperatively was 1850 cc. At the end ofsurgery, the median total fluid balance measured waspositive 1269 cc, while 7% of patients had a negative bal-ance at completion. Intraoperative urine output was lessthan 500 cc in all groups.Chau et al. Canadian Journal of Kidney Health and Disease 2014, 1:19 Page 8 of 11http://www.cjkhd.org/content/1/1/19AKI by urine output and serum creatinine criteria andrelationship to fluid balanceUsing the accepted definitions of AKI, the incidence ofAKICr was 9% (n = 10) and AKIUO was 31% (n = 35). Ofthose with AKICr, 9/10 also met urine output criteria.Figure 3 describes the amount of positive fluid balancein patients with SCr-/UO- (no AKI), SCr-/UO + (AKIUO)and SCr + (AKICr). Note that those with AKICr had thelargest proportion of positive fluid balance (>6.5 cc/kg),and those with AKI by either definition had larger pro-portion of positive fluid balance than those who did nothave AKI using either parameter.OutcomesLength of stay in CSICUThe median intensive care unit LOS was 24 (IQR: 21,47) hours.Figure 3 Fluid balance as categorized by AKIN criteria for acutekidney injury. Abbreviations: AKIN: Acute Kidney Injury Networkdiagnostic criteria for AKI [2]. SCr+: Meeting the criteria of Change inSCr≥ 26.5 µmol/L; SCr-: Not meeting the Change in SCr criteria. UO+:Meeting the criteria of Urine Output ≤0.5 cc/kg/hour for greater than6 hours; UO-: Not meeting the Urine Output criteria.Figure 1 depicts the distribution of LOS in CSICU in as-sociation with the five combinations of changes in serumcreatinine, urine output and fluid overload. Note thatthose with no change in serum creatinine and no reducedurine output (irrespective of fluid overload) [ie: 1) SCr-,UO-, FOL- and 2) SCr-, UO-, FOL+)] had the shortestLOS in CSICU (medians of 21–23 hours). Among thosewith oliguria and no change in serum creatinine [ie: 3)SCr-, UO+, FOL- and 4) SCr-, UO+, FOL+], those withfluid overload had longer LOS in CSICU (median =62 hours) compared to those without (median = 39 hours).Those with no change in serum creatinine but with oli-guria and positive fluid balance had similarly long LOS inthe CSICU as those who simply had elevated serum cre-atinine [ie: 5) SCr+] (medians of 62 and 69 hours,respectively).Table 3 provides the parameter estimates from themultiple linear regression models. The unadjusted ana-lyses indicated that there were two comparisons of pa-tient groups in which there was a significant increase inmean LOS in CSICU. Firstly when patients had oliguriaalone (SCr-, UO+, FOL-) compared to patients withfluid overload alone (SCr-, UO-, FOL+) the estimated in-crease in mean log(LOS) was 0.31 [95% C.I.: 0.04, 0.57;p-value = 0.02]. Secondly when comparing patients with oli-guria and fluid overload (SCr-, UO+, FOL+) to those witholiguria alone (SCr-, UO+, FOL-), there was an estimatedincrease in mean log(LOS) of 0.35 [95% C.I.: 0.05, 0.65; p-value = 0.02]. In the adjusted analyses, the only differenceremained was between those with and without oliguria (es-timated increase in mean log(LOS): 0.44 [95% C.I.: 0.18,0.70]; p-value = 0.001).Length of stay in hospitalThe median hospital LOS for the population was 9(IQR: 6, 14) days.Figure 2 depicts the relationship between the LOS in hos-pital with various combinations of change in serum creatin-ine, urine output and fluid overload. Of the patients whowere oliguric with no change in serum creatinine [ie: 3)SCr-, UO+, FOL- and 4) SCr-, UO+, FOL+] those whowere fluid overloaded had longer hospital LOS (median =13 days) as opposed to those who were not fluid overloaded(median = 9 days). Note that patients were who oliguricand fluid overloaded but with no change in serum cre-atinine [ie: 4) SCr-, UO+, FOL+] had similarly longlength hospital LOS as those who simply had elevatedserum creatinine [ie: 5) SCr+] (medians of 13 and14 days, respectively).In the unadjusted analyses (see Table 3), we found twogroup comparisons which were marginally associated withlonger LOS. There was a significant increase in the meanlog(LOS) when comparing oliguric patients with fluidoverload (SCr-, UO+, FOL+) and without fluid overloaddUE00000−00han; UOOL-Chau et al. Canadian Journal of Kidney Health and Disease 2014, 1:19 Page 9 of 11http://www.cjkhd.org/content/1/1/19(SCr-, UO+, FOL-): the estimated increase was 0.39 [95%C.I.: −0.004, 0.79; p-value = 0.05]. There was also somesuggestion of an increase in the mean log(LOS) in patientswith AKICr when compared to oliguric patients with fluidoverload (SCr-, UO+, FOL+): the estimated increase was0.36 [95% C.I.: −0.05, 0.77; p-value = 0.08].In the adjusted analyses (also see Table 3), the onlycritical breakpoint in an increase in mean log(LOS) waswhen we compared patients who had no AKI and werenot fluid overloaded (SCr-, UO-, FOL-) to those whohad no AKI but were fluid overloaded: the estimated in-crease was 0.29 [95% C.I.: 0.04, 0.54; p-value = 0.02].The change in serum creatinine, fluid balance and weightgain in each of the different categories is described in thelower panel of Figures 1 and 2. Those with highest weightgain had more positive fluid balance. Patients who were oli-guric but not fluid overloaded were in mild negative bal-ance (SCr-, UO+, FOL-; median −3.8 cc/kg) as werepatients who did not have AKI (median −6.1 cc/kg). Pa-tients that were oliguric and fluid overloaded (SCr-, UO+,Table 3 Estimates of the group variable parameters resulteOutcome ParameterCSICU Length of Stay β1 (SCr-, UO-, FOL + vs. SCr-, UO-, FOL-)β2 (SCr-, UO+, FOL- vs. SCr-, UO-, FOL+)β3 (SCr-, UO+, FOL + vs. SCr-, UO+, FOL-)β4 (SCr + vs. SCr-, UO+, FOL+)Hospital Length of Stay β1 (SCr-, UO-, FOL + vs. SCr-, UO-, FOL-)β2 (SCr-, UO+, FOL- vs. SCr-, UO-, FOL+)β3 (SCr-, UO+, FOL + vs. SCr-, UO+, FOL-)β4 (SCr + vs. SCr-, UO+, FOL+)SCr+: Meeting the criteria of Change in SCr ≥ 26.5 µmol/L; SCr -: Not meeting the CUO+: Meeting the criteria of Urine Output ≤0.5 cc/kg/hour for greater than 6 hoursFOL+: Meeting the criteria of Fluid Overload, defined as fluid balance ≥ 6.5 cc/kg; FFOL+) had the same degree of fluid overload as those pa-tients that had AKICr with a median positive fluid balanceof 30 cc/kg. Given the average weight of the patients(81 kg), 30 cc/kg equates to approximately 2 litres, after ac-counting for insensible losses.DiscussionThis study describes the outcomes for patients undergoingelective cardiac surgery who develop AKI, using variousdefinition parameters. We used an integrated categorizationof AKI that incorporates both the AKIN criteria and fluidbalance. We wanted to demonstrate the merits of consider-ing each parameter - serum creatinine, urine output andfluid balance - together, as they are associated with the rele-vant outcomes of CSICU and hospital LOS. Our data sug-gests a potential difference in LOS for cardiac surgerypatients with AKI as defined using these different parame-ters in various constellations. In those patients witholiguria, there was an increased duration of CSICU LOS,but those with oliguria and fluid overload had trends to-wards longer LOS in both CSICU and in hospital. Thevalue of ‘contextualizing’ urine output by including a meas-ure of overall fluid balance has not been overtly discussedin any of the recent guideline proposals.Since oliguria as a sole diagnostic criterion for the diag-nosis of AKI has been considered oversensitive, we suggestthat in the context of fluid overload it may in fact portendworse outcomes (defined here as longer LOS). Some pub-lications suggest that the current criterion of ≤0.5 cc/kg/hour for greater than 6 hours may identify patients whoare at no greater risk of mortality or need for dialysis [8,9].This analysis reaffirms that oliguria is still a marker of riskthat should be taken seriously, but needs to be contextual-ized within the clinical situation, and fluid balance mea-surements. This is consistent with other data [10]. Giventhat weight is a sensitive indicator of positive fluid balance,this may allow practical measurements in non critical caresettings to be used.from the multiple linear regression modelsnadjusted model Adjusted modelstimate 95% C.I. p-value Estimate 95% C.I. p-value.09 −0.08, 0.26 0.31 0.12 −0.05, 0.29 0.16.31 0.04, 0.57 0.02 0.44 0.18, 0.70 0.001.35 0.05, 0.65 0.02 0.08 −0.21, 0.37 0.58.16 −0.15, 0.46 0.31 0.14 −0.14, 0.41 0.32.18 −0.06, 0.41 0.14 0.29 0.04, 0.54 0.020.05 −0.40, 0.30 0.78 −0.13 −0.52, 0.25 0.49.39 −0.004, 0.79 0.05 0.30 −0.12, 0.67 0.16.36 −0.05, 0.77 0.08 0.27 −0.14, 0.67 0.19ge in SCr criteria.-: Not meeting the Urine Output criteria.: Not meeting the Fluid Overload criteria.Although AKIUO is imperfect as only a small numberof patients with AKIUO subsequently develop AKICr [11],reduction in urine output below thresholds may serve toalert clinicians as the ‘canary in the coal mine’ [12]. Useof more stringent criteria may lead to delayed recogni-tion of early AKI. While at the current time there arelimited renoprotective strategies, as newer agents be-come available, it will be important to diagnose AKI asearly as possible. A study examining the timing of neph-rology referral and outcomes suggested that delayednephrology consultation is associated with worse prog-nosis [13] in hospitalized patients.Concealed AKI as a result of dilution of creatinine byvolume expansion has been recognized [14-16] as a poten-tial diagnostic pitfall when relying on serum creatininechanges. Fluid overload increases the time to identificationof an increase in creatinine [15] and misses casesaltogether [17]. In this study, patients with oliguria andChau et al. Canadian Journal of Kidney Health and Disease 2014, 1:19 Page 10 of 11http://www.cjkhd.org/content/1/1/19fluid overload did have smaller changes in serum creatin-ine levels. The potentially important (median) rise inserum creatinine of 12 μmol/L (IQR: −1, 17) did not meetthe threshold of 26.5 μmol/L, but within the context ofknown dilution this small increase may be indicative ofrises of serum creatinine within the threshold range. Thedata in our study suggest that oliguria in combination withfluid overload may point towards worse outcomes thanoliguria alone. This may be in part because fluid overloadmasks a true rise in creatinine.The mechanism by which fluid overload may cause in-creased mortality is multifactorial [18]. Intravenous fluidadministered, whether colloid or crystalloid, does not staywithin the vascular space in critically ill patients [19].Interstitial lung oedema leads to requirement for mechan-ical ventilation. Increased cardiac preload secondary tofluid overload may lead to cardiac dysfunction. Specific tothe kidney, elevated renal venous pressure can impair kid-ney perfusion and increase interstitial pressure. In ourstudy, patients with fluid overload even without AKI by ei-ther diagnostic criteria had significantly longer hospitalLOS, suggesting that fluid overload in and of itself may beharmful in addition to perpetuating existing injury. Ofnote, the ‘adverse’ outcomes in our study occurred inthose with approximately 2 litres positive balance in24 hours. This is consistent with findings in the SOAPstudy, where patients had a mean positive daily fluidbalance of 1 to 1.5 litres.Patients in our study with either AKIUO or AKICr hadmore positive fluid balance than those without AKI, againconsistent with other studies [20,21]. Fluid overload is as-sociated with complications [22] of cardiac surgery, failureto recover from AKI [23] and mortality [21,24]. We didnot capture those outcomes in this study.There are limitations to this study. This is a singlecentre study, using a convenience sample of consecutivepatients undergoing elective surgery. The outcomes arelimited to short term (CSICU and hospital LOS), andnot to 30 day mortality or peri-operative complications,as in other studies. However, the purpose of the studywas to describe AKI according to the different criteria,and determine if those definitions had relevance to LOS.It is important to acknowledge that prolonged LOS is animportant outcome from an individual patient andhealth care utilization perspective. We did not capturethe rationale for fluid administration so the issue ofcause and effect are not easy to disentangle from thesedata. This was an observational study and there weredifferences in across the 5 categories of fluid balance,urine output and serum creatinine. However, in the ad-justed models, these were taken into account. As a de-scriptive study, these data serve to catalogue currentpractice in post cardiac surgery patients and allow gen-eration of testable hypotheses.The strengths of this study are the careful tabulationof all input and output from the time of surgery until72 hours post operatively; that patients appeared to re-ceive similar amounts of volume within the operativeperiod, and had similar urine outputs. Thus, all of thedifferences that occurred with fluid administration tookplace after similar intraoperative volume resuscitation,which may permit the development of interventions tobe tested in the postoperative period.There is accumulating literature on the benefits of re-strictive fluid management strategies [25,26] in criticallyill patients. It may be prudent to trial similar strategiesin this highly vulnerable cardiac surgery population. Abalance must be struck between the importance of peri-operative fluid resuscitation and the potential adverse ef-fect of post-operative fluid overload. In this study, of the8 patients in negative balance following surgery, 7 hadAKIUO with fluid overload or AKICr.ConclusionsOur study has an important practical message. Attentionto fluid balance, with and without perturbations inserum creatinine or oliguria, may help to more accur-ately identify those patients with AKI at risk of adverseoutcomes. Our data suggest that oliguric patients withfluid overload may have worse outcomes than those witholiguria alone. The definition and recognition of AKI isevolving. It is important that our approach to fluid man-agement, resuscitation and limitations in fluid accumula-tion similarly evolve.Competing interestsAL is the editor-in-chief of the CJKHD.Authors’ contributionsAL, KC, TS, DJ and JB conceived the research idea and participated in thedesign of the study. CC, AI and TS made significant contributions to dataacquisition. LE, KC, AL performed data analysis and interpretation. KC and TSdrafted the manuscript for the article. AL gave final approval of the versionto be published. All authors read and approved the final manuscript.Author details1Division of Nephrology, Faculty of Medicine, The University of BritishColumbia, St Paul’s Hospital, 1081 Burrard St, Vancouver, BC V6Z1Y6, Canada.2Department of Anesthesiology, Pharmacology and Therapeutics, TheUniversity of British Columbia, St Paul’s Hospital, 1081 Burrard St, Vancouver,BC V6Z1Y6, Canada. 3Faculty of Medicine, The University of British Columbia,St Paul’s Hospital, 1081 Burrard St, Vancouver, BC V6Z1Y6, Canada.Received: 30 April 2014 Accepted: 8 August 2014Published: 19 August 2014References1. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney InjuryWork Group: KDIGO Clinical Practice Guideline for Acute Kidney Injury.Kidney Int 2012, 2(Suppl):1–138.2. 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Crit Care 2013, 17(1):R14.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistribution25. Stewart RM, Park PK, Hunt JP, McIntyre RC Jr, McCarthy J, Zarzabal LA,Michalek JE: Less is more: improved outcomes in surgical patients withconservative fluid administration and central venous cathetermonitoring. J Am Coll Surg 2009, 208(5):725–735.26. Lobo SM, Ronchi LS, Oliveira NE, Brandão PG, Froes A, Cunrath GS,Nishiyama KG, Netinho JG, Lobo FR: Restrictive strategy of intraoperativefluid maintenance during optimization of oxygen delivery decreasesmajor complications after high-risk surgery. Crit Care 2011, 15(5):R226.doi:10.1186/s40697-014-0019-4Cite this article as: Chau et al.: Fluid balance, change in serumcreatinine and urine output as markers of acute kidney injury postcardiac surgery: an observational study. Canadian Journal of Kidney HealthSubmit your manuscript at www.biomedcentral.com/submit


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