Is recipient’s body mass index a

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Progrèsenurologie(2020)30,663—674

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ORIGINAL ARTICLE

Is recipient’s body mass index a

determinant of short term complications in early renal transplantation?

L’IMC du patient receveur inﬂuence-t-il les complications à court terme en transplantation rénale ?

V. Queruel

^a^,∗

, R. Kabore

^b

, A. Guillaume

^a

, K. Moreau

^c

, K. Leffondre

^b

, P. Merville

^c

, J.-M. Ferriere

^a

, W. Hanf

^d

, J.-C. Bernhard

^a

aServiced’UrologieetTransplantationrénale,HôpitalPellegrin,CentreHospitalier UniversitairedeBordeaux,PlaceAmélieRabaLéon,33076Bordeaux,France

bInstitutdesantépublique,d’épidémiologieetdedéveloppement,UniversitédeBordeaux, 146,rueLéoSaignat,33000Bordeaux,France

cServicedeNéphrologieetTransplantationrénale,HôpitalPellegrin,CentreHospitalier UniversitairedeBordeaux,PlaceAmélieRabaLéon,33076Bordeaux,France

dServicedeNephrologie,CentrehospitalierAlpes-Leman,556,routedeFindrol,74130 ContaminesurArve,France

Received25June2019;accepted3July2020 Availableonline18August2020

KEYWORDS BodyMassIndex;

Morbidity;

Renal

transplantation;

Surgical complications

Summary

Objectives.—Obesityprevalencehasincreasedoverthepast20yearsinthegeneralpopula- tionandamongkidneytransplantrecipients.Generalsurgicalbeliefisthatobesityincreases surgicaldifﬁculty.TheaimofthisstudywastoassesstheimpactofBodyMassIndex(BMI)on perioperativecomplications.

Methods.—Allkidneytransplantations performedinadultsinourcentre from2006to2011 were analysed.Data onpatients’ characteristics,surgicalprotocol, intra andpostoperative complicationsandrenalfunctionwerecollected.Patientsweredividedinto4groupsasfol- lows:underweight(BMI<18.5kg/m²),normalweight(18.5kg/m²≤BMI<25kg/m²),overweight (25kg/m²≤BMI<30kg/m²)andobese(BMI≥30kg/m²).WealsostudiedtheimpactofBMIon complicationsusingitasacontinuousvariabletoidentifypotentialthresholdvalues.

∗Correspondingauthor.

E-mailaddress:[email protected](V.Queruel).

https://doi.org/10.1016/j.purol.2020.07.003

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664 V.Querueletal.

Results.—Among694patientsincluded,52%hadnormalBMI,7%,31%and9%wereunderweight, overweight and obese, respectively. In multivariate analysis, overweight was significantly associatedwithlongeroperativetimecomparedtonormal-weightpatients(estimatedmean differenceof10,4min,95%confidenceinterval (CI)[4.0; 16.9])andobesity wasassociated withanincreasedriskofwounddehiscence(oddsratio3.1,95%CI[1.3;7.3]comparedwith normal-weightpatients).ConsideringBMIasacontinuousvariable,theriskofparietaldehis- cencesignificantlyincreasedbeyondaBMIof26kg/m²,intraoperativebloodlossandtherisk ofureteralstenosisbeyond32kg/m²andtheriskofabdominalwallhematomabeyondaBMIof 34kg/m².

Conclusions.—WefoundBMIthresholdsabovewhichintraoperativebloodlossandtheriskof parietaldehiscence,ureteralstenosis,andparietalhematomasigniﬁcantlyincreased.

Levelofevidence.—3.

MOTSCLÉS Indicedemasse corporelle; Morbidité; Transplantation rénale; Complications chirurgicales

Résumé

Objectifs.—Laprévalencedel’obésitén’acesséd’augmenterces20dernières annéesdans la populationgénérale etparmi lespatients receveurs de transplantsrénaux. Dans l’esprit chirurgical,l’obésitéestassociéeàuneaugmentationdesdifﬁcultéschirurgicales.L’objectif decetteétudeétaitd’évaluerl’impactdel’IMCsurlescomplicationspériopératoires.

Méthodes.—Touteslestransplantationsrénalesréaliséeschezl’adultedansnotrecentrede 2006à2011ontétéanalysées.Les donnéesconcernantlescaractéristiquesdespatients,la procédurechirurgicale,lescomplicationsper-etpostopératoiresainsiquelafonctionrénale ontétécollectées.Lespatientsonétérepartis en4groupes:sous-poids(BMI<18,5kg/m²), poids normal (18,5kg/m²≤BMI<25kg/m²), surpoids (25kg/m²≤BMI<30kg/m²) et obésité (BMI≥30kg/m²).Nousavonségalementétudiél’impactdel’IMCsurlescomplicationsentant quevariablecontinueaﬁnd’identiﬁerdepotentiellesvaleursseuils.

Résultats.—Parmi694patientsinclus,52%avaitunIMCnormal,7%,31%et9%étaientres- pectivementensous-poids,surpoidsetobèses.Enanalysemultivariée,lesurpoidsétaitassocié àuneaugmentationdeladuréeopératoirecomparéaupatientsdepoidsnormal(différence moyenneestiméeà10,4min,95%intervalledeconﬁance(IC)[4,0;16,9])etl’obésitéétait associéeàuneaugmentationdurisqued’éventration(oddsratio3,1,95%CI[1,3;7,3]com- paréauxpatientsdepoidsnormal).Enconsidérantl’IMCentantquevariablecontinuelerisque d’éventrationaugmentaitsigniﬁcativementau-delàd’unIMCà26kg/m²,depertessanguines etdesténoseurétéraleau-delàd’unIMCà32kg/m²etd’hématomedeparoiau-delàd’unIMC à34kg/m².

Conclusions.—Nousavonstrouvédes seuilsd’IMCau-delàdesquels lespertessanguines, le risqued’éventration,desténoseurétéraleetd’hématomedeparoiaugmententsigniﬁcative- ment.

Niveaudepreuve.— 3.

Introduction

Obesity is considered as a global epidemic. The World HealthOrganizationreportedinOctober2017thatthenum- ber of obesity cases has globally tripled since 1975. In 2016,itwasestimatedthat39%ofadultswereoverweight (BMI≥25kg/m²)and13% were obese(BMI>30kg/m²)[1].

RegardingtheFrenchpopulation,theprevalenceofobesity amongadultsincreasedfrom8.5%in1997to15%in2012[2].

Obesity has been shown to be associated with a higher risk of chronic kidney disease [3] through

glomerular hyperﬁltration, secondary diabetes, hyperten- sion and inﬂammatory cytokine production triggered by renin-angiotensin-aldosteronesystemactivation.Inameta- analysis of 18 general population cohorts, Wang et al.

estimated that therate of kidney diseasewas40% higher for overweight patients and83% higher for obesepersons comparedwithnormal-weightpatients[4].TheDialysisand transplantation French registry (REIN) reported a steady annualincreaseof2%from2011to2015intheprevalenceof obesepatientsinend-stagerenaldiseaserequiringdialysis [5].

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BMIandrenaltransplantation 665 In thewholepopulation,kidney transplantispreferred

to dialysis asit is has been shown to be associated with abettersurvival[6].Results areevenbetterwhenkidney transplantis performed preemptively[7].However,it has alsobeenshownthatobesepatientshaveabettersurvival ondialysisthannonobesepatients.Somespecificobesesub- group patients such as afro-american with BMI>40kg/m² maynotbenefitfromtransplantation [8,9].Indeed,surgi- calcomplicationsanddelayedgraftfunctionratehavebeen showntobehigherin obesepatients [10],despite several otherstudiesfindingnosurvivaldifferencebetweenobese andnonobesekidneygraftrecipients[9,11].

Obesitymaybetheﬁrstcauseofnon-inclusiononthekid- neytransplantwaitinglist[12],andpatientsonthewaiting listwithanelevatedBMIhavealowerlikelihoodofreceiv- ing atransplant, evenif BMIis not included in allocation rules[13].Yet,thereisstillnoconsensusontheBMIthresh- old above which the risk of complications is signiﬁcantly increased.Inacurrentcontextoforganshortage,abetter understandingoftheBMIimpactonkidneytransplantation morbidityismandatorytohelpclinicaldecision.

The aim of our study was to determine the impact of recipient’s BMI on per and post transplantation complicationsoccurrenceanddeﬁnethresholdvaluesofBMI leadingtoasigniﬁcantriskincrease.

Methods Study design

A retrospective cohort study was conducted including all consecutivekidneytransplantationsperformedattheRenal TransplantUnit of BordeauxUniversity Hospital fromJan- uary 2006 till December 2011. We excluded all patients youngerthan18yearsatthetimeoftransplant,aswellas multipleorganrecipients.

Data collection

Patient records from the Bordeaux University Hospital kidney transplant database were reviewed to retrieve demographic data regarding the pre-, per- and post- transplantationperiods.Allcollecteddatawereanonymized andethicalapprovalwasobtainedfromtheBordeauxUni- versityHospitalethicalcommittee.

BMI and potential confounders

The BMI was calculated as the weight (inkg) divided by the height (in meters) squared, both recorded at the transplantation visit. We investigated both the effect of quantitative BMI (kg/m²) as well as classes of BMI: underweight (BMI<18.5kg/m²), normal weight (18.5kg/m²≤BMI<25kg/m²), overweight (25kg/m²≤BMI<30kg/m²) and obese (BMI≥30kg/m²).

Recipient’s characteristics which were retrieved because they were potential confounders were: age at transplantation, sex, initial kidney disease,diabetes, self-reported smokingstatus,dyslipidaemia,previouspre-transplantation

abdominalsurgery,historyofdialysis,andrankofgrafting.

We also collected graft characteristics including cold ischemia time (inhours), donor age, and donor status (deceasedoralive).

Outcomes

We restricted the study to surgical complications and transplantoutcomesoccurringwithinthethreemonthsfol- lowing transplantation. Intraoperative outcomes included estimated blood loss during surgery (inmL), operative time (inmin) and vascular complications (renal artery and venous thrombosis, vascular injury). Early postoperative outcomes were recorded within the first 30 days following the surgery: delayed graft function (DGF) definedas dialysis required within 7 days of transplantation(yes/no),estimated glomerularfiltration rate (eGFR) at 7 days estimated from the MDRD estimating equa- tion(inmL/1.73mL/min/1.73 m²), length ofhospital stay (in days), sepsis (yes/no), cardiovascular complications (yes/no). Early surgical complications were classified as parietal(hematoma,evisceration,parietalinfection),vas- cularandurinary(urinoma).Allreinterventionsrelatedto transplantationwerealsoreported.Mid-termpostoperative outcomesincluded eGFR and the occurrence of potential surgicalissuesat3months(wounddehiscence,arteryorvein stenosis,ureteralobstructiondueanastomoticstenosis).

Statistical analysis

ToestimatetheassociationbetweencategoriesofBMIand eachoutcome,weusedseparateregressionmodelssystem- aticallyadjustedforrecipientage(inyears),sex, smoking status at surgery, diabetes, pretransplantation abdominal surgery,coldischemiatime(inhours),donorage(inyear), donor status, initial kidney disease (glomerulonephritis, polycystic kidney disease, congenital uropathy, diabetic nephropathy,tubulopathyandinterstitialpathologies,other andundeﬁned),previousdialysis(yes/no),andrankofrenal grafting.Logisticregressionwasusedfor binaryoutcomes andmultiple linear regression for quantitative outcomes.

WhenanassociationwasfoundbetweenoutcomesandBMI categories,theeffectofquantitativeBMIwastheninvesti- gated.

Forthatpurpose,toavoidassumingalinearrelationship withthe outcome and to identify potential thresholds of BMIabovewhichtheriskofcomplicationincreases,weused restrictedcubic spline functions withﬁveknotsplaced at equallyspacedintervals[11].Thelinearityoftheeffectof allquantitativeconfounderswasalsocheckedusingspline functions.

DataanalysiswasperformedusingSAS9.3software(SAS Institute,Cary,NC).

Results

During the study period, 748 patients underwent kidney transplantationinourcentre.Sixhundredandninety-four patients(93%)reachedinclusioncriteriaandwereenrolled.

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666 V.Querueletal.

Table1 DescriptiveresultsoftransplantedpatientscharacteristicsaccordingtoBMI.

BMI Pvalue

Total Underweight Normalweight Overweight Obesity

Effectiven(%) 694 51(7.4) 360(51.9) 218(31.4) 65(9.4) <0.001

Ageatgraft(y) 50.7(12.9) 41.7(13.8) 49.2(13.1) 54.6(11.3) 53.1(11.8) Gendern(%)

Female 230(33.1) 28(54.9) 122(33.9) 56(25.7) 24(36.9) <0.001

Male 464(66.9) 23(45.1) 238(66.11) 162(74.31) 41(63.08)

Currentorformersmokern(%)

No 405(59.1) 30(58.82) 215(60.39) 120(56.34) 40(61.54) 0.78

Yes 280(40.9) 21(41.18) 141(39.61) 93(43.66) 25(38.46)

Diabeticn(%)

No 601(87.6) 51(100) 329(92.16) 176(82.63) 45(69.23) <0.001

Yes 85(12.4) 0(0.0) 28(7.84) 37(17.37) 20(30.77)

Previousdialysisn(%)

No 50(7.3) 4(8) 26(7.3) 19(8.88) 11.61) 0.25

Yes 632(92.7) 46(92) 330(92.7) 195(91.12) 61(98.39)

Previousabdominalsurgeryn(%)

No 231(33.4) 13(26) 110(30.64) 82(37.61) 26(40) 0.14

Yes 461(66.6) 37(74) 249(69.36) 136(62.39) 39(60)

Rankofgraftingn(%)

First 573(82.6) 39(76.47) 281(78.06) 192(88.07) 61(93.85) <0.001

>1 121(17.4) 12(23.53) 79(21.94) 26(11.93) 4(6.15)

Recipient’s characteristics

CharacteristicsofthestudypopulationbyBMIcategoriesare summarizedinTable1.Fifty-onepatientswereunderweight (7%),360hadanormalweight(52%),218wereoverweight (31%) and 65 were obese (9%). Among obese subpopula- tiononly10patientsweresevere(15%)and2weremorbid (3%).Recipients’averageagewas50.7±12.9years.Under- weightpatientswereyounger(41.7±13.8yo).Therewere morementhan women (67%)in allBMI categoriesexcept in underweight patients. Most patients presented one or severalcomorbiditiessuchasdiabetes (12%),dyslipidemia (40%)and41%werecurrentorformersmokers.Thepreva- lenceofdiabeteswassigniﬁcantlyhigherinoverweightand obesepatients.

Graft characteristics

Mostofthegraftscame fromdeceaseddonors(93%)atan averageageof50±15.4years.Averagecoldischemiatime was16.5±7.8hours(Table2).

Association between categories of BMI and perioperative complications risk

Resultsof multivariableanalysis withBMI asacategorical variablearereportedin Table3. Regardingintraoperative complications,theaveragebloodlosswas270mL(±253).It seemedtoincreasewithBMI,withanestimatedmeandiffer- enceof72.5mLbetweenobeseandnormal-weightpatients, butthemeandifferencewasnotstatisticallysigniﬁcant(95%

conﬁdence interval: −9.8; 154.8mL). Operative duration was signiﬁcantly longer by 10.4 (95%CI: 4.0; 16.9) minutes on average for overweight patients compared with

normal-weightpatients.Thedurationforobesewasonaver- agelongerby8.3minutes(95%CI:−1.6;18.1).

Regardingearlypostoperativecomplications,36patients (4.8%)presented anabdominalwallabscessand 30(4.4%) patients had a parietal hematoma. There was no signiﬁ- cant difference between thesubgroups of BMI. Regarding renal function, overweight and obese patients showed a higherincidenceofDGF,38%and39.1%respectivelyascom- paredto 28.8% amongnormal-weightpatients (P=0.002).

Thistendencypersistedafteradjustmentforpotentialcon- founders, although it became only marginally signiﬁcant.

Overweightandobesepatientsalsohadasigniﬁcantlylower eGFRatsevendays(␤=−7.3[−11.5;−3.2]mL/min/1.73m² and␤=−9.2[−13;−1.1]mL/min/1.73m²,P<0.001.

Regardingdelayed postoperativecomplications, wound dehiscence occurred in 80 patients (12%) and more fre- quently in obese patients than in normal-weigth patients (OR3.1,95%CI[1.3—7.3]P=0.05).LengthofHospitalstay and cardio-vascular complications did not seem to differ amongthedifferentBMIsubgroups.Concerningrenalfunc- tionat threemonths post transplantation,results showed alowereGFRinobesepatients(eGFR=47mL/min/1.73m²) as compared to the other groups (63mL/min/1.73m² in underweight; 55mL/min/1.73m² in normal weight and 48mL/min/1.73m²inoverweightpatients;P=0.02).

The sample size did not allow us to performed multivariate analysis for blood transfusion and abdominal wall abscess.

Estimated effect of quantitative BMI

ResultswithBMIasacontinuousvariablearepresented in Figs. 1—3. A BMI threshold was determined as the point beyond which the conﬁdence interval (grey dashed lines)

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BMIandrenaltransplantation 667 Table2 DescriptiveresultsofgraftandkidneydonorsaccordingtoBMIclass.

BMI Pvalue

Underweight Normalweight Overweight Obesity

Donorage(years)

Effective 50 355 212 65 0.77

Mean(SD) 41.0(16.4) 47.7(16.2) 53.6(13.3) 52.0(12.0)

Ischemiccoldtime(hours)

Effective 51 352 208 65 <0.001

Mean(SD) 15.5(7.7) 16.5(7.8) 16.8(8.4) 16.8(6.7)

Donorstatusn(%)

Dead 48(94.12) 328(91.36) 206(95.37) 63(96.92) 0.20

Living 3(5.88) 31(8.64) 10(4.63) 2(3.08)

oftheBMIeffect(whosepointestimateisindicatedbythe redsolidline)doesnotincludethelinemarkingtheabsence ofeffect(greenhorizontalline).

Inourpopulation,bloodlosssigniﬁcantlyincreasedwhen the BMI became higher than 32kg/m², with a mean esti- mateddifferenceof65.3mL(95%CI[5.1;125.4])between a patient with a BMI of 32kg/m² compared to a patient withaBMIof24kg/m² (correspondingtothemedian BMI) (Fig. 1). Operating time signiﬁcantly increased when BMI increased from 22 to 28kg/m², and levelled off beyond 28kg/m²(Fig.1).

The risk of wound dehiscence increased amongrecipi- entswithaBMIhigherthan26kg/m²(OR1.4,95%[1.0;1.8]

comparativelytopatients withaBMIof24kg/m²,Fig.2).

The riskof wallhematomasigniﬁcantlyincreasedonlyfor patients withaBMI above34kg/m² comparedtopatients witha BMI of 24kg/m² (OR=3.6 (95% CI [1.2,10.9]). For ureteralstenosis,thethresholdwasatabout32kg/m²(OR 3.1,95%CI[1.2—8.5]comparativelywithmedianBMI).There wasnosigniﬁcantassociationbetweenBMIandpostopera- tiveinfection(Fig.2).

Concerning renal function(Fig.3), theeGFR at 7 days almost linearly decreased when BMI at transplantation increased.At3months,eGFRalsodecreasedwithBMI,but withaweakereffect.

Discussion

Asexpected,ourstudyconﬁrmsgeneralthinkingthatrecip- ients BMItendstoinﬂuence pertransplantation outcomes andthattheriskofshort-termsurgicalcomplicationsrises withBMI.

InmostpreviousseriesstudyingtheeffectofBMIonrenal transplantoutcomes,patientswerestratiﬁedaccordingto their weight using usual weight categories. Nevertheless, obesepatientscannotbeconsideredasahomogeneoussin- glegroupandBMIneedstobeseenasacontinuousvariable.

The distinctive designof ourwork wastouseBMI asa continuous variable and analyze its relationship with the riskof surgicalcomplicationsthanks tosplinesfunctionof BMI.The influenceofBMIvaries foreach studiedparame- ter.Consequently,significantthresholdsaredifferent,anda fewareevenbelowobesitythresholddefinedasBMIhigher than30kg/m².However,thehighertheBMIthegreaterthe risk of complications adds up. Beyond aBMI of 34kg/m²,

patientshada2.8foldincreasedriskofwounddehiscence asfoundbyHumaretal.inastudyincludingmorethan2000 patients[14].This subgroup alsohada 5.4foldincreased riskofureteralstenosisand3.6foldincreasedriskofwall hematoma.

In several previous studies using BMI as a categorical parameter,obesitywasnotreportedtobeassociatedwith ureteral stenosis [15—17] and wall hematoma [18]. We foundsimilarresultsintheﬁrstpartofouranalysis.Apply- ingacubic spline functiontoestimate BMIeffect,risk of ureteralstenosisandwallhematomawerefoundsigniﬁcan- tlyincreasedforBMIgreater than32kg/m² and34kg/m², respectively.

The high rates of DGF among overweight and obese patientscorroboratesseveralmajorstudies[19—21]. That could be explained by a longer operative time and an increasedglomerular filtrationdue toaninsufficient graft sizeproportionallytorecipient’sbodysurfacearea.Indeed, theratiobetweendonorkidneyweightandrecipientbody weightinfluencescreatinine clearance valuesafter transplantation [22]. Underweight patients were younger and tendedtoreceivegraftsfromyoungerdonorswithashorter cold ischemiatime.These could influence the lowerrate of DFG we found in this subgroup. In our study, rate of DGFamongnormalpatientsishighercomparedtonational average(29%vs21%).Thisfindingmaybeexplainedbythe inclusionofprimarynon-functiongraftsinthisgroup[23].

Hetetetal.showedacorrelationbetweenureteralsteno- sisandDGFwithoutdeterminingifureteralstenosisisthe consequenceortheoriginofDGF[17].

As Furriel et al. [24], no signiﬁcant difference in the lengthofhospitalstayaccordingtoBMIwasdemonstrated inourstudy.However,in aretrospective analysisfocusing onmorbidobeserecipients,thelengthofhospitalstaywas almost30%longer[25].Wehadprobablynotenoughmorbid obesepatients in ourpopulation tobe ableto showsuch results.

As reported by Furriel et al. [24], obesity was associated with an increased risk of parietal complications;

wounddehiscence especially.We didnot observeanysig- niﬁcantcorrelationbetweensurgicalsiteinfectionandBMI, thoughsomeauthors[18,26—28]revealedahigherincidence beyond 30kg/m². This discrepancy may be explained by thelowerpercentageofdiabeticpatientsamongourobese patients group compared withother studies (31% vs 43%) [28].

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668V.Querueletal.

Table3 Analysisofper-andpostoperativemorbidityofkidneytransplantationstratiﬁedonBMI.

Complications BMI P-value

Underweight (n=51)

Normal weight (n=360)

Overweight (n=218)

Obesity (n=65)

No-adjusted Adjusted

Variables

(modalities/units)

n(%) Mean(SD) n(%)

mean(SD)

n(%) mean(SD)

n(%) mean(SD) Peroperativecomplications

Vascular peroperative complication

51 347 207 61

No 614(92.2) 24.4(4.2) 46(90.2) 322(92.8) 188(90.8) 58(95.5)1 0.63^a

Yes 52(7.8) 24.6(4.4) 5(9.8) 25(7.2) 19(9.2) 3(4.9)

OR[IC] 0.7[0.2;

3.3]

1 1.0[0.5;

2.1]

0.50[0.1;

1.9]

0.71

Bloodtransfusion 45 327 198 64

No 608(95.9) 24.5(4.3) 43(95.6) 314(96.0) 189(95.6) 62(96.9) 0.96^a

Yes 26(4.1) 24.5(4.5) 2(4.4) 13(4.0) 9(4.5) 2(3.1)

OR[IC] Noconvergenceofmodel

Bloodloss(ml) 40

238.6 (273.0)

278 254.5 (250.7)

168 287.8 (269.5)

51

328(188.8)

0.16^b

B[IC] −1.2 [−94.8;

97.1]

0.00 14.2

[−38.3;66.7] 72.5[−9.8;

154.8]

0.38

Operativeduration (min)

43

151.6(29.6)

315

154.2(32.1)

187

164.7(37.5) 60

161.3(38.5)

0.001^b B[IC] 1.0[−10.8;

12.8]

0.00 10.4[4.0;

16.9]

8.3[−1.6; 18.1]

0.01 Postoperativecomplications

Hematomaof abdominalwall

49 357 214 64

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BMIandrenaltransplantation669 Table3(Continued)

Underweight (n=51)

Overweight (n=218)

Obesity (n=65)

Variables

(modalities/units)

n(%) Mean(SD) n(%)

mean(SD)

n(%) mean(SD)

No 654(95.6) 24.4(4.2) 47(95.9) 344(96.4) 204(95.3) 59(92.2) 0.45^a

Yes 30(4.4) 25.3(5.4) 2(4.1) 13(3.6) 10(4.7) 5(4.8)

OR[IC] 1.7[0.3;

8.8]

1 1.3[0.5;

3.3]

2.33[0.7;

8.1]

0.58 Peritransplant

hematoma

50 357 214 64

No 601(87.7) 24.5(4.2) 41(82.0) 317(88.8) 186(86.9) 57(89.1) 0.54

Yes 84(12.3) 24.2(4.4) 9(18.0) 40(11.2) 28(13.1) 7(10.9)

OR[IC] 1.8[0.7;

4.5]

1 1.3[0.7;

2.4]

1.2[0.4;

3.0]

0.59

Earlyreoperation 49 359 215 64

No 604(87.9) 24.4(4.2) 44(89.8) 319(88.9) 183(85.1) 58(90.6) 0.48

Yes 83(12.1) 24.7(4.4) 5(10.2) 40(11.1) 32(14.9) 6(9.4)

OR[IC] 1.1[0.3;

3.4]

1 1.6[0.9;

2.9]

0.9[0.3;

2.5]

0.31 Postoperative

infection

50 357 214 64

No 490(71.5) 24.4(4.1) 30(60.0) 269(75.4) 145(67.8) 46(71.9) 0.06

Yes 195(28.5) 24.6(4.5) 20(40.0) 88(24.6) 69(32.2) 18(28.2)

OR[IC] 2.1[1.0;

4.3]

1 1.2[0.8;

1.9]

1.0[0.5;

2.1]

0.23 Cardiovascular

complication

49 358 215 64

No 582(84.8) 24.4(4.2) 42(85.7) 303(84.6) 183(85.1) 54(84.4) 0.99

Yes 104(15.2) 24.6(4.4) 7(14.3) 55(15.4) 32(14.9) 10(15.6)

OR[IC] 1.4[0.5;

3.7]

1 0.88[0.5;

1.5]

1.02[0.4;

2.8]

0.84

Wounddehiscence 48 354 203 63

No 588(88.0) 24.2(4.1) 44(91.7) 323(91.2) 171(84.2) 50(79.4) 0.01

Yes 80(12.0) 25.9(4.2) 4(8.3) 31(8.8) 32(15.8) 13(20.6)

OR[IC] 1.3[0.3;

5.1]

1 1.6[0.9;

2.9]

3.1[1.3;

7.3]

0.05

Ureteralstenosis 48 354 199 62

No 639(96.4) 24.3(4.1) 47(97.9) 340(96.1) 195(98.0) 57(91.9) 0.15^a

Yes 24(3.6) 25.2(5.6) 1(2.1) 14(3.9) 4(2.0) 5(8.1)

OR[IC] 0.6[0.1;

5.6]

1 0.5[0.2;

1.8]

3.0[0.9;

9.6]

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670V.Querueletal.

Table3(Continued)

Underweight (n=51)

Overweight (n=218)

Obesity (n=65)

Variables

(modalities/units)

n(%) Mean(SD) n(%)

mean(SD)

n(%) mean(SD)

n(%) mean(SD) Delayedgraft

function

48 354 213 64

No 461(67.9) 24.2(4.1) 38(79.2) 252(71.2) 132(62.0) 39(60.9) 0.02

Yes 218(32.1) 25.0(4.4) 10(20.8) 102(28.8) 81(38.0) 25(39.1)

OR[IC] 0.2[0.3;

1.7]

1 1.44[0.9;

2.2]

1.4[0.8;

1.7]

Abdominalwall abscess

49 358 215 64

No 653(95.2) 24.4(4.2) 49(100.0) 337(94.6) 204(94.9) 63(98.4) 0.20^a

Yes 33(4.8) 24.6(4.4) 0(0.0) 21(5.9) 11(5.1) 1(1.6)

OR Noconvergenceofmodel

Hospitalstay(days) 48

16.6(10.8)

354 16.1(8.4)

212 17.4(10.7)

64

17.92(9.7)

0.29^b B[IC] 1.1[−2.0;

4.1]

0.00 1.1[−0.5;

2.7]

0.8[−1.7;

3.3]

0.57 Glomerularﬁltration

rateatsevendays (ml/min/1.73m²)

47

55.5(24.0)

347 46.9(25.8)

197 37.5(17.8)

62

35.8(18.4)

<0.001

B[IC] 4.9[−2.6;

12.3]

0.00 −7.3

[−11.5;

−3.2]

−9.2[−15.7;

−2.8]

<0.001

Glomerularﬁltration rateatthree

months(ml/min/1.73 m²)

48

63.0(23.0)

351 55.0(22.3)

203 48.0(20.1)

61

46.6(20.6)

<0.001

B[IC] 4.7[−2.1;

11.6]

0.00 −3.2[−7.0;

0.5]

−7.0[−13.0;

−1.1]

0.02

Analysisadjustedto:ischemiccoldtime,sex,ageoftransplant,tobacco,diabetes,initialkidneydisease,previousabdominalsurgery,previousdialysis,rankofgrafting,donorage, donorstatus,previousdialysis.

aFisher’sexacttest.

b ANOVAtest.

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BMIandrenaltransplantation 671

Figure1. EstimatedeffectofBMIattransplantationonbloodlossandoperativetimecomparedtomedianBMI.Continuousredlinesshow respectivelytheoveralltrendofoccurrenceofbloodloss(leftgraph)andoperativetime(right).Crosses(obs)representthedistribution ofpatientsateach pointofBMI.Westudied themeanvariationofbloodlossatdifferentpointsofBMI(knots)comparedto median BMI(24,12kg/m²).Theriskofbloodlossincreasesintherecipient’spopulationwithaBMIhigherthan32kg/m^2. Theoperativetimeis signiﬁcantlyincreasedforaBMIbetween22and30kg/m².Inthetables,signiﬁcantresultsaregrayedout.

Figure2. Risk(OddRatio)ofwallhematoma(upper left),postoperativeinfection(upperright),parietaldehiscence(lowerleft)and ureteralstenosis(lowerright)accordingtoBMIandcomparedtomedianBMI.Riskofwallhematoma,parietaldehiscenceanduretralstenosis issignificantlyincreasedforaBMIhigherthan34,26and32kg/m²,respectively.Inourpopulation,BMIdidnotinfluencesignificantlypost operativeinfectionrisk.

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672 V.Querueletal.

Figure3. EstimatedeffectofBMIonrenalfunctionat7daysand3monthscomparedtomedianBMI.At7dayspost-transplantation, thereisasignificantinversecorrelationbetweenBMIandGFRtill32kg/m².At3months,onlypatientshavingaBMIlessthan20have asignificantadvantageintermsofGFR.*:significantdifferencecomparedtomedianBMI.BMI:bodymassindex;␤:meanvariation;CI:

confidenceinterval;LowerCL:lowerconfidencelimit;UpperCL:upperconfidencelimit;GFR:GlomerularFiltrationRate;Obs:observation.

Immunosupressivetherapyisconsideredasariskfactor forparietalcomplications.Corticosteroidsincreasetherisk ofwound dehiscenceand lymphocele[29].More recently, introductionofmorepotentantiproliferativedrugsin par- ticularmycophenolatemofetilandsirolimusor everolimus have accentuated the incidence of wound complications.

Several studies highlight deleterious effect of sirolimus [30—32].Giventhelargenumberofdifferentimmunospres- sive combinations used in our population, this parameter couldnotbestudied.

Because of ahigher risk of surgical complications, the obesepopulationisconfrontedwithamuchlowerlikelihood ofreceivingakidneytransplant.Todate,thereisnoconsen- sus ona BMIthreshold notto exceedto beincluded in a kidneytransplantationprogram,resultinginheterogeneous practices.Inourcentre,accordingtoFrenchguidelinespub- lished by HAS (HauteAutorité de Santé), patients witha BMI greater than 50kg/m² were systematically excluded.

Between35and50kg/m²,ﬁnaldecisionwasdebatedduring acommissioncomposedofnephrologistsandtransplantation surgeons[33].

Inthecontextoforganshortage,itisessentialtobetter standardizeclinicalassessmenttoensureequityandfairness ofkidney allocation andbetter graft survival.Part of the wideninggapbetweenobesetransplantedpatientsrate(9%

inourseries)andobesepatientsindialysis(23%inFrance and21.6%inAquitaine)couldbeattributedtounwarranted policiesinwaitlistingduetoarbitraryBMIlimitsandraises ethicalissues.

Holley[34]foundthataBMIgreaterthan35kg/m² was thethirdmostcommonreasonforexcludingtransplantcan- didates (10%) following medical comorbities and patient decline. In a more recent study, Toapanta-Gaibor et al.

reportedthat30%ofexclusionsfromtransplantlistingwere attributedtoobesity[12].

Gill proposed to limit access to renal transplantation to those patients less than 40kg/m². Indeed, his study foundalowerbeneﬁtoftransplantationabovethisthresh- old.Furthermore,inthesubgroupanalysisofAfro-American patients witha BMI≥40kg/m², kidney transplantwas no longer superior to dialysis in terms of survival. Glanton andal.foundthatkidney transplantationindialysisobese patients wasassociated witha 3 to4 folddecreased risk of mortality. This beneﬁt did not apply to patients with BMIgreaterthan41kg/m².Forthissub-population,authors promotedpre-transplantweightlossprocedurestoimprove transplantationoutcomes.

InaFrenchcohort,Lassalle etal observedthatweight losswasassociatedwithanincreasedlikelihoodofreceiving atransplant.

However,suchstrategycouldbedeleterious.Initsstudy, Kuoetal.[35]observedthatweightlosspriortothetrans- plantation was associated with a higher rate of wound complications.Itcanbeexplainedbymalnutritionandbody contour changeswithunfavourable abdominalpanniculus.

Molnar etal.studied theimpactof weightlossonpatient survivalamongdialysispatientswait-listedforkidneytrans- plant.Hefoundaninverseassociationbetweenweightloss andhazardofdeath[36].Othersproposedbariatricsurgery [37]but thisapproachneedsfurtherinvestigationsbefore establishinganyrecommendation.

Insteadof an absolute weight loss, focusingeffortson changes in bodycompositionby dietary recommendations andexerciseprogramstoincreasetheleanmasscouldbea morevaluablestrategy.Initsstudy,Cambos etal.showed that lifestyle intervention programs alone allowed obese patients to reachkidney transplant wait listingin 42% of casesandtobetransplantedin25%.

Moregenerally,these conﬂictingresultsregarding obesity impact on kidney transplantation outcomes and its

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BMIandrenaltransplantation 673 management,highlightthatBMIaloneisprobablyaninsuf-

ﬁcienttool.

Few authors explored additional parameters to assess more accurately the surgical risk of kidney transplantation associated with overweight. Kovesdy et al. showed an increased all-cause mortality associated with higher waist circumference but lower mortality associated with higher BMI in kidney transplant recipient. As waist circumference and waist hip ratio better reﬂect visceral adiposity,theycouldbebetteranthropometricpredictorsof adverseeffectofobesityonsurgicaloutcomesandmortality [38].

We believe also that the deﬁnition of speciﬁc risk thresholds could help to more accurately improve pre- operative patient information and education. This study promotes preventive care for patients with BMI greater thanpreviouslydetailedriskthresholds.Duringsurgery,per- fectureteralvascularizationismandatory.Specialvigilance must be given to hemostasis and parietal reconstruc- tion. Immunosupressive modalities should be adjusted for obese patients considering their co-existing risk factors.

Our study presents some limitations. Itssingle institution and retrospective naturemay limit generalization of ourresults.Indeed,theycouldbeinﬂuencedbylocalprac- tice,potentially differentgeneral clinicalcare. Given the intrinsiclimitationsofsuchastudy,theseresultsshouldbe consideredaspreliminary,urgingforprospectiveandprefer- ablymulticenterstudiestoconﬁrmthem.

Thestudiedcohortincludedalimitedsampleofpatients with extreme BMI (10 patients with BMI>35kg/m² and 2 patients>40kg/m²). This induced very large conﬁdence intervalsfor thesevaluesof BMIandthus only fewstatis- tically signiﬁcantresults.This wouldbethus importantto replicateouranalysesinlargercohorts.

Our work was also restricted to short-term postoperative follow up. Complications occurring after 3 months werenottakenintoaccount.Afterthisdelay,somepatients continue their post transplantation medicalmonitoring in a different institution. We chose to restrict our analysis to the 3-month period to limit possible under reported complications.

Since 2012, European Urological guidelines propose to assess surgical quality according to functional conse- quences and management of postoperative complications usingClavien-Dindoscore[39].Inourretrospectiveseries, patients were included before this recommendation, so detailedcomplications management wasnotavailable for mostpatients.

Althoughpreviousstudiesdemonstratedthatright-sided deceased [40] donor kidneyswere associated with higher incidenceofDGFandpoorrenalfunction,resultswerenot ajustedonthisparameterinourmultivariateanalysis.

Patientsreceivingdeceasedandlivingdonortransplants were not analyzed in different groups though it is well establishedthatpostoperativeoutcomesaredifferent.Con- sideringthelowproportionoflivingdonortransplantations (6.6%)andtheabsenceofsigniﬁcantdifferenceindistribu- tionbetweensubgroups,ithadprobablyalowinﬂuenceon ourresults.

Conclusion

We conﬁrmed that obese patients may have more complications thannon-obese and we identiﬁedpotential thresholdsfor severalcomplications.Thisstudycouldthus helpustosetupbetterindividualstrategiesduringsurgery forpatientsknowntobeatrisk.

Further investigations are required to ﬁndmore accu- ratemorphologicalcriteriassuchaswaistcircumferenceor andwaisthipratiotobetterassessrecipients’riskpriorto transplantationandimproveourpoliciesofcaretoreduce complicationrates.

Disclosure of interest

Theauthorsdeclarethattheyhavenocompetinginterest.

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