important determinants of renal function after partial nephrectomy

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ORIGINAL ARTICLE

No ischemia technique, parenchymal preservation and age are the most

important determinants of renal function after partial nephrectomy

Zéro ischémie, la préservation parenchymateuse et l’âge sont les facteurs prédictifs de la fonction rénale après néphrectomie partielle

L. Mutelica

^a^,∗

, P. Mouracadé

^b^,^c

, O. Kara

^c

, J. Dagenais

^c

, M.J. Maurice

^c

, J.H. Kaouk

^c

aServiced’urologie,NouvelHopitalCivil,1,placedel’Hopital,67000Strasbourg,France

bCliniqueRHENA,10,rueFrancois-Epailly,France

cDepartmentofUrology,GlickmanUrologicalandKidneyInstitute,ClevelandClinic, Cleveland,OH,USA

Received14February2019;accepted28November2019 Availableonline14December2019

KEYWORDS Partialnephrectomy;

Renalfunction;

On-clamp;

Robotics

Summary

Objective.—TheaimofthepresentstudywastocomparetheoutcomesofOff-ClamptoOn -Clampapproachduringrobot-assistedpartialnephrectomy(RAPN).

Materielandmethods.—Retrospectivestudyof940patientswhounderwentaRAPNbetween 2007and2015forcT1atumors usingOn-ClamporOff-Clamp approaches.Patientwithsoli- tarykidneyormultifocalwereexcluded.Overall,103patientsunderwentOff-Clampapproach and37patientsOn-Clampapproach.Wematchedthepatientsintermsoftumorsize,Charlson comorbidityindexandR.E.N.A.L.score.Atall,309patientsfromtheOn-Clampwerematchedto theOff-Clampgroup.Wecomparedtheclinic-pathologicalcharacteristics,perioperativemor- bidityandlatefunctionaloutcomesbetweenthe2propensityscorematchedgroups.Limitation includedretrospectiveanalysis.

∗Correspondingauthor.

E-mailaddress:mtlilian@yahoo.fr(L.Mutelica).

https://doi.org/10.1016/j.purol.2019.11.012

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Results.—After matching,therewere nodifference inclinic-pathologicalcharacteristicsin termsofgender,age,race,bodymassindex,Charlsoncomorbidity index,American Society ofAnesthesiologistsscore,baselineestimatedglomerularﬁltrationrate(e-GFR),tumorsize, R.E.N.A.L.scorecomplexity,hilar(H)locationbetweenthe2groups.Regardingperioperative outcomes;whileoperativetime(P=0,4),estimatedbloodloss(P=0,28),ClaviengradeIII-IV complications(P=0,8)surgicalreoperation(P=1),30-dayreadmission(P=1),positivesurgical margin(5,5% vs. 5,8%, P=0,9)were comparablebetween the 2groups, therewere signiﬁ- cantdifferenceinexcisionalvolumeloss(median,7,08vs.3,51cm³,P<0,01),e-GFRdecline (median,−9,7vs.−2,2ml/min/1,73m²,P<0,01),percentofe-GFRpreservation(median,87%

vs.97%,P<0,01),andCKDupstaging(36,5%vs.23,3%,P=0,01),Off-Clampapproach(P=0,01), andage(P=0,02)werepredictorsofrenalfunctionpreservation,whereasexcisionalvolume loss(OR=1,035,CI95%(1,015—1,06),P<0,01)predictedupstaging.

Conclusion.—RAPNforselectedrenalmassusingOff-Clampapproachofferedrenalfunctional advantageoverOn-Clamp,withoutaddingmorbidities.Whilenoischemiatechniquewasassoci- atedwithlessexcisionalvolumeloss,Off-Clampapproach,andagewereindependentpredictors ofrenalfunctionpreservation.Clinicalsigniﬁcanceoftheseﬁndingsinvariousclinicalsettings willrequirefurtherinvestigation.

MOTSCLÉS Néphrectomie partielle; Fonctionrénale; Clampage; Robotique

Résumé

Objectif.—L’objectifdel’étudeétaitdecomparerlesrésultatsdel’approche«sansclampage» lorsdelanéphrectomiepartielleassistéeparrobot.

Matérieletméthodes.—Étude rétrospective sur 940 patients ayantsubi une néphrectomie partielleassistéeaurobotentre2007et2015pourdestumeurs cT1utilisentdesapproches sansclampage (SC)ouavecclampage(AC).Lespatients présententdestumeurs rénalessur reinuniqueoumultifocalesontétéexclus.Autotal,103patientsonteuuneapprocheSCet 837patientsonteuuneapprocheAC.Nousavonscomparélespatientsentermesdetaillede latumeur,d’indicedecomorbiditédeCharlsonetduscoreR.E.N.A.L.Entout,309patientsdu groupeAContétéappariésaugroupeSCselonlescoredepropension.Nousavonscomparéles caractéristiquesclinico-pathologiques,lamorbiditéperopératoireetlesrésultatsfonctionnels entreles2groupesappariés.Leslimitationscomprenaientuneanalyserétrospective.

Résultats.—Aprèsappariement,iln’yavaitaucunedifférencedanslescaractéristiquesclinico- pathologiques en termesde sexe, âge, race, indice de masse corporelle, indice de Charl- son,scoredel’AmericanSocietyofAnesthesiologists,tauxdeﬁltrationglomérulaire estimé (e-DFG, taille de la tumeur, Complexité du score R.E.N.A.L, position hilaire (h) entre les 2groupes.Encequiconcernelesrésultatsperopératoires;letempsopératoire(p=0,4),les pertesdesangestimées(p=0,28),lescomplicationsdegradeIII-IVselonscoreClavien(p=0,08), lesreinterventionschirurgicales (p=1),les réadmissionsaprès 30jours(p=1), etlesmarges chirurgicales positives(5,5 %vs 5,8 %, p=0,9) étaientcomparables entre les2 groupes.Il yavaitunedifférence signiﬁcativequantauvolumede laperteparenchymateuse décision- nelle(médiane, 7,08parrapportà3,51cm³,p<0,01),une diminutiondu e-DFG(médiane,

−9,7vs−2,2ml/min/1,73m²,p<0,01),dupourcentagedepréservationdue-GFR(médiane, 87%contre97%,p<0,01)etdel’accentuationdelanéphropathiechronique(36,5%contre 23,3%,p=0,01)enfaveurdugroupeSC.L’approchesansclampage(p=0,01)etl’age(p=0,02) ontétélesfacteursdelapreservationdelafonctionrénalealorsquelaperteparenchymateuse excisionnelle(OR=1,035,IC95%(1,015—1,06),p<0,01)étaitprédictivedel’accentuationde lanéphropathiechronique.

Conclusion.—Lanéphrectectomiepartiellerobotassistéepourlestumeurssélectionnéesen utilisent l’approche SCoffre un avantage fonctionnel rénal par rapportau clampage, sans ajouterdemorbidité.Latechniquesansclampageétaitassociéeàunepertemoisimportante duparenchymeexcisé.Laperteparenchymateuseexcisionnelle,l’approcheSCetl’âgeétaient des facteursprédictifs indépendants de la préservation dela fonctionrénale. La signiﬁca- tion cliniquede ces résultatsdansdivers contextes cliniques nécessiterades investigations supplémentaires.

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Introduction

Preoperativeglomerularﬁltrationrate,solitarykidney,age, gender,tumor size,ischemiatime[1],wereconsideredas predictorsofglomerularﬁltrationrateafterpartialnephrec- tomy(PN).Anumberofrecentstudieshavefoundthatthe qualityandquantityofremnantrenalparenchymaafterPN assumeanimportantroleinpredictingfuturerenalfunction.

Although preoperative evaluation and timely consulta- tionwithanephrologist,helpsoptimizerenalfunctionafter PN, ischemia time and parenchymal preservation are the single modiﬁable surgical risk factors for decreased renal function.Efforts tolimit ischemic timeandthe extentof healthytissueexcisionshouldbepursuedwhendoingPN.

Minimization orreducing On-Clamp timeduringPN has ledtoalternativetechnicalmodiﬁcations[1,2].Theconcept ofOff-ClampPNwhichaimstoavoidtheischemicinjuryon thehealthyparenchymaoftheoperated kidneyshasbeen describedintheliteratureforopen[3—5],laparoscopic,and robotassisted[2,6—8]partialnephrectomy.

Ideally,wewouldliketoevaluatetheperioperativemor- bidityandfunctional outcomeofOff-Clampincomparison toOn-Clamp,inordertoassesstheburden ofPN andthe extentofrenalfunctionpreservationinthissetting.Several studiestriedtocomparethe2differenttechniquesbutmost of thesestudieslack robust conclusion-nodifferentiation betweenopenandlaparoscopicsurgery[3].Lackofinforma- tionabouttumorsize[6],tumorcomplexity[5],excisional volumeloss, parenchymal preservation or late postopera- tiverenalfunction[9].Signiﬁcantdifferencesintumorsize betweenthegroups[9]makingthecomparisoninappropri- ate.

Theaimofthepresentstudywastocompare,perioper- ative morbidityand functionaloutcomesof Off-Clamp,to On-Clampapproach,duringrobot-assistedpartialnephrectomy(RAPN)inamatchedgroups.

Materiel and methods Study population

Weretrospectivelyreviewedourinstitutionalreviewboard- approved PN database. Data consisted of consecutive records of patients who underwent robot assisted partial nephrectomyby8 senior surgeonsin thesamecenter between 2007 and 2015 for cT1a tumors using On-Clamp or Off-Clampapproaches. Patients withsolitarykidney or multifocaltumorswereexcluded.Overall940patientswere includedinthisstudy.Ofthiscohort,103patientsunderwent Off-Clampapproachand837patientsunderwentOn-Clamp approach.

In order to reduce differences between groups due to selection bias andconfounding, we performed a matched analysisusing the propensity scoremethod witha greedy matchingalgorithm.Atall,309patientsfromtheOn-Clamp werematchedtothe103patientsfromOff-Clampgroup.

Surgical technique

All RAPN procedures were performed with the da Vinci Surgical System (Intuitive Surgical, Inc., Sunnyvale, CA,

USA).Therenalarterywasroutinelylocalizedanddissected and left unclamped in the off-clamp group and clamped in the on-clamp group. Warm Ischemia time (WIT) was deﬁnedasthetimefromtheclamping tillunclamping.No coldischmiawasused.Tumorexcisionwasperformedwith parenchymal margin resection.After tumor resection, an inner parenchymal layer sutured reconstruction was performed,followedbycapsularsuturesforapproximationof therenaldefect.

Data collection

Patient demographics (age, gender, race, body mass index [BMI], Charlson comorbidity index [CCI], Ameri- can Society of Anesthesiologists score [ASA], baseline estimated glomerular ﬁltration rate [e-GFR], baseline CKDstage), and clinical tumor characteristics (R.E.N.A.L.

nephrometry score: consists of [R]adius [tumor size as maximal diameter], [E]xophytic/endophytic properties of the tumour, [N]earness of tumor deepest portion to the collecting system or sinus, [A]nterior [a]/posterior [p] descriptor and the [L]ocation relative to the polar line, radiological maximum tumor diameter, hilar (h) location, laterality, malignancy, American Joint Can- cer Committee staging and tumor grade) were col- lected.

Propensity score matching

We matched the 2 groups in terms of preoperative factors:Tumorsize,Charlsoncomorbidityindex,andR.E.N.A.L score,factorsconsideredtoberelatedtothedecisioncon- cerning the surgical approach (On-Clamp vs. Off-Clamp).

The nearest neighbor matching was used, meaning that Off-Clamp patients were matched to On-Clamp patients who have the most similar estimated propensity score.

To ensure good matches, a caliper (maximum allowable difference between two patients) of 0.1 was deﬁned.

BecausethesamplesizesofOn-ClampandOff-Clampgroups vary greatly, 1 to 3 matching was performed in which a single Off-Clamp patient was matched to 3 On-Clamp patients [10]. Matching was done with replacement, in which a patient in the On-Clamp group had been reused tobematchedtomorethanonepatientintheOff-Clamp group,thisreducestheoverallimbalancebetweenthetwo groups.

Primary endpoints

Our primary outcomes were decline in e-GFR [ e- GFR],e-GFR preservation, andCKD upstaging. The e-GFR was calculated according to MDRD formula. Decline in e-GFR was defined as the difference between postoperative e-GFR (measured at 6 months) and baseline e- GFR. e-GFR preservation was defined as postoperative e-GFR divided by baseline e-GFR, expressed as a percentage. The CKD was defined according to the Kidney Disease Outcome Quality Initiative-Chronic Kidney Dis- ease with stages 1, 2, 3, 4 and 5 corresponding to an e- GFR >90, 60-89, 30-59, 15-29 and <15 respectively [11].

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Table1 Baselinecharacteristicsforpatientsinthestudygroup.

Variable On-clamp Off-clamp P

N(%) 837(100%) 103(100%)

Gendern(%) 0,5

Male 490(58,5) 57(55,3%)

Female 347(41,5) 46(44,7)

Age(year) 0,1

Median[IQR] 59[51—67] 63[53—69]

Racen(%) 0,2

White 734(87,7) 86(83,5)

Other 103(12,3) 17(16,5)

BMI(kg/m²)n(%) 0,9

[<25] 153(18,3) 21(20,4)

[25—29,9] 304(36,3) 35(34,0)

[30—34,9] 210(25,1) 25(24,3)

[>35] 170(20,3) 22(21,4)

CCindexn(%) <0,01

CCindex<=1 585(69,9) 56(54,4)

CCindex>1 252(30,1) 47(45,6)

ASAscoren(%) 0,2

ASA<=2 287(34,3) 28(27,2)

ASA>2 550(65,7) 75(72,8)

Baselinee-GFRml/min 0,3

Median[IQR] 82[69—99] 83[64—94]

Tumorsize(cm) <0,01

Median[IQR] 2,5[2,0—3,1] 2,0[1,4—2,5]

Siden(%) 0,1

Left 414(49,4) 59(57,3)

Right 423(50,6) 44(42,7)

R.E.N.A.L.score <0,01

<7 327(39,1) 78(75,7)

>=7 510(60,9) 25(24,3)

Location:Hilar(h)n(%) 0,3

Yes 111(13,3) 10(9,7)

No 726(86,7) 93(90,3)

CCindex:CharlsonComorbiditiesIndex;ASAscore:AmericanSocietyofanesthesiologistsscore;BMI:Bodymassindex;e-GFR:estimated glomerularfiltrationratedefinitebytheModificationofDietinRenalDisease(MDRD);R.E.N.A.L.nephrometryscoreconsistofradius (R)(tumorsizeasmaximaldiameter),exophytic/endophytic(E)propertiesofthetumor,nearness(N)oftumordeepestportiontothe collectorsystemorsinus,anterior(A)/posterior(a/p)descriptorandthelocation(L)relativetothepolarline.

Secondary endpoints

Secondary outcomes included, operative time, estimated blood loss [EBL], transfusion rate, postoperative Clavien complications, surgical reoperation, 30-day readmission, surgicalmarginstatusandexcisionalvolumeloss.Theexci- sionalvolume loss wascalculated aspreviously described [12]. The volume of healthy rim of renal parenchyma removedatthe timeof RAPNwasestimatedby deducting thecalculatedtumorvolume,fromthePNspecimenvolume.

Thetumorvolumewasmeasuredusingtheellipsoidformula:

(0.523x’y’z’),wherex’,y’andz’wherethe threedimen- sionsofthetumormeasuredonpathologyassessment.The volumeofPNspecimenwasalsomeasuredusingtheellip- soidformula (0.523xyz) [12],where x,yand z wherethe threedimensions ofthe specimenmeasured onpathology assessment.

Statistical analysis

Continuous variable were described as median and interquartile range. Categorical variables were described as frequency and percentage. The nonparametric Mann—Whitney U-test and the ␹² test were used for comparing the continuous and categorical variables betweentheOn-ClampandOff-Clampgroups.Linearmul- tipleregressionwasusedtoidentifyindependentpredictors of e-GFR decline. Variable inclusion in the multivariable model was decided using stepwise regression. Logistic regression wasusedtoidentify independentpredictors of CKDupstaging.VariableswithP<0.2onUnivariateanalysis wereintroducedinthelogisticmultivariatemodel.Statisti- calsigniﬁcancewassetatp<0.05.Analysiswasperformed using SPSS v22 software. (IBM SPSS Statistics, Armonk, NY: IBMCorp.,USA).The Rsoftwareandplug-inthat link

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Table2 Baselinecharacteristicsforpatientsinthematchedgroup.

N(%) 309(100%) 103(100%)

Gendern(%) 0,8

Male 174(58,0) 57(55,3)

Female 135(42,0) 46(44,7)

Age(year) 0,2

Median[IQR] 60[52—67] 63[53—69]

Racen(%) 0,6

White 264(85,4) 86(83,5)

Other 45(14,6) 17(16,5)

BMI(kg/m²)n(%) 0,9

[<25] 58(18,8) 21(20,4)

[25—29,9] 115(37,2) 35(34,0)

[30—34,9] 72(23,3) 25(24,3)

[>35] 64(20,7) 22(21,4)

CCindexn(%) 0,2

CCindex<= 193(62,5) 56(54,4)

CCindex>1 116(37,5) 47(45,6)

ASAscoren(%) 0,3

ASA<=2 99(32,0) 28(27,2)

ASA>2 210(68,0) 75(72,8)

Baselinee-GFRml/min 0,2

Median[IQR] 84[69—98] 83[64—94]

CCindex:CharlsonComorbiditiesIndex;ASAscore:AmericanSocietyofanesthesiologistsscore;BMI:Bodymassindex;e-GFR:estimated glomerularfiltrationratedefinitebytheModificationofDietinRenalDisease(MDRD).Continuousvariablewasdescribedasmedianand interquartilerange.Categoricalvariablesweredescribedasnumberandfrequency.Mann—WhitneyU-testwasusedforcontinuousand chi-squaredtestwasusedforcategoricalvariablesAlltestused5%asasignificantthreshold.

with the corresponding version of SPSS and propensity scorematching packagewereinstalled.Apropensityscore modulewasaddedintheSPSSinterface.

Results

Patient demographics and tumor characteristics between thetwogroupswerecomparedbeforematching.The Off- Clampgrouphadhighercomorbidityburden(CCI>1,45.6%

vs.30.1%,P<0.01),lowertumorsize(median2.0vs.2.5cm, P<0.01) and lower tumor complexity (R.E.N.A.L score, P<0.01).Therewerenodifferenceingender(p=0.5),age (P=0.1),race (P=0.2), BMIsubclasses(P=0.9),ASA score (P=0.2)andbaselinee-GFR(P=0.3),(Table1).

Aftermatchingwefoundthattherewerenodifference ingender(P=0.80,age(P=0.2),race(P=0.6),BMIsubclass (P=0.9),CCI index(P=0.2),ASA score (P=0.3) andbaselinee-GFR(P=0.2)betweenthetwomatchedgroups.The baselinepatientcharacteristicsforOn-ClampandOff-Clamp groupsaftermatchingshowsintheTable2.

Also,thecharacteristicsoftheOff-ClampandOn-Clamp tumorswerecomparedaftermatching.Therewerenodif- ference in tumor size (median, 2.0 vs. 2.0cm, p=0.3), laterality(P=0.1),R.E.N.A.Lscore(P=0.1),hilar(h)location(P=0.5)andpTstage(P=0.8)betweenthe2matched groups(Table3).

The outcome measures regarding secondary endpoints werecomparedforOff-ClampandOn-Clampgroups.Nodif- ferencefound in operative time(median172 vs. 170min, P=0.4), EBL (median 100 vs. 120ml, P=0.3), transfu- sionrate(5.2% vs.10.7%,P=0.051),overallpostoperative complications (17.7% vs. 22.3%, P=0.3), Clavien grade (III-IV)complications(5.5%vs.4.8%,P=0.8),surgicalreoperation(1.6%vs.1.9%,p=1),30-dayreadmissionrate(4.5%

vs.3.9%,P=1),andpositivesurgicalmargins(5.5%vs.5.8%, P=0.9)betweenthematchedgroupsrespectively.Theexci- sionalvolumeloss(median,9.08vs.4.51cm³,P<0.01)was signiﬁcantlydifferentinfavorofOff-Clampgroup.Regard- ing primary endpoints, e-GFR decline (median, −9.7 vs.

−2.2ml/min/1.73m²,P<0.01),percentofe-GFRpreserva- tion(median,87vs.97percent,P<0.01),andCKDupstaging (36.5% vs. 23.3%, P=0.01) were signiﬁcantly different in favorofOff-Clampgroup(Table4).

Usingthelinearregression model,thethreepredictive variables for preserving kidney function were identiﬁed.

Ischemiatype(P=0.01), excisional volume loss(P=0.01), and age (P=0.02),) were signiﬁcant predictors of e-GFR preservation(Table5).

The singlepredictor factor of upstaging wasexcisional volume loss (OR 1.035, CI 95% [1.015—1.06] P<0.01).

Ischemia type (P=0.12), tumor size (P=0.16) and age (P=0.3)werenot.Thelogisticregressionmodelpredicting CKDupstagingshowsintheTable6.

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Table3 Tumor’scharacteristicsforpatientsinthematchedgroups.

N(%) 309(100%) 103(100%)

Tumorsize(cm) 0,3

Median[IQR] 2,0[1,5—2,5] 2,0[1,4—2,5]

Siden(%) 0,1

Left 149(48,2) 59(57,3)

Right 160(51,8) 44(42,7)

R.E.N.A.L.score 0,3

<7 216(69,9) 78(75,7)

>=7 93(30,1) 25(24,3)

Location:Hilar(h)n(%) 0,5

Yes 37(12) 10(9,7)

No 272(88) 93(90,3)

Tumorhistologyn(%) 0,03

Clearcell 159(51,5) 34(33,0)

Papilary 59(19,1) 27(26,2)

Chromophobe 11(3,6) 4(3,9)

Othermalignant 18(5,8) 8(7,8)

Benign 62(20,1) 30(29,1)

pTstagen(%) 0,8

pT1a 230(74,4) 69(67)

pT3a 17(5,5) 4(3,9)

Graden(%) 0,9

Low(I—II) 141(45,6) 38(36,9)

High(III—IV) 78(25,3) 23(22,3)

NC^a 90(29,1) 42(40,8)

R.E.N.A.L.nephrometryscoreconsistofradius(R)(tumorsizeasmaximaldiameter),exophytic/endophytic(E)propertiesofthetumor, nearness(N) oftumordeepest portiontothecollectorsystemorsinus,anterior(A)/posterior (a/p)descriptorand thelocation(L) relativetothepolarline.Continuousvariablewasdescribedasmedianandinterquartilerange.Categoricalvariablesweredescribed asnumberandfrequency.Mann—WhitneyU-testwasusedforcontinuousandChi²testwasusedforcategoricalvariablesAlltestused 5%asasigniﬁcantthreshold.

aNC:NotConcerned(benigntumors,chromophobetumors,unclassiﬁed).

Discussion

The potential renal functional benefit of Off-Clamp com- pared with renal arterial clamping remains difficult to assess,especiallyinretrospectivecomparisons.Omittingto takeintoconsiderationconfoundingfactorsandexplanatory variables(preoperative glomerular filtration rate, solitary kidney,multipletumors,age,gender,tumorsize,R.E.N.A.L score,thequantityofremnantrenalparenchyma)maycon- tributetomisstherealconclusion.Inordertoreduceany difference between groups we excluded solitary kidney, and multiple tumor resection from our study population.

Patientswithsolitarykidney have alower baselinee-GFR [13]andmultipletumorexcisionmayhavehigherpostoper- ativecomplicationrate[14].Thepropensityscoreanalysis was developed to minimize the differences in patients’

covariates,whichcouldbecomeconfoundingfactorsinthe examinationoftreatmenteffectsinobservationalstudies.

The propensity score is deﬁned as the patient’s prob- ability for treatment selection, which is dependent on observedbaselinecovariates.Weidentifyallpreoperative factors that were related to the selection of On-Clamp or Off-Clamp. While age, race, BMI, ASA, laterality were not affecting the surgeon decision to select On-Clamp or

OffClampapproach,wematchedontumorsize,R.E.N.A.L scoreandCharlsoncomorbidityindex,factorsconsideredas related tothe selection of On-Clamp or Off-Clamp:large tumor sizein one groupmay resultinless functional kid- neypresentfollowingsurgerybyrequiringanincrementally largerresectionvolumeofadjacentnormalkidneytoensure complete excision.Inaddition,studies usingtheanatomic classiﬁcationnephrometrysystemhaveshownastrongcor- relationamonghighersurgicalcomplexityofrenaltumors, longerWIT,andpoorerfunctionaloutcomes[15],[16—18].

Regardingperioperativeoutcomes,ourﬁndingswereconsis- tentwithothersseriescomparingOff-clamptoOn-clampPN inselectingcases[19].Therewerenodifferencesbetween groups in terms of operative time,EBL, andcomplication rate, withOff-ClampPNshowing atrend towarda higher transfusionrates(P=0.051).

Parenchymalvolumelossisbelievedtooccurmainlyfrom excisionalvolumeloss,especiallyinsmallrenaltumors(loss ofhealthyparenchymainthemargin)[13].Ourﬁndingssup- portthoseofotherauthorswhoalsoreporteddataattesting tosigniﬁcantlylessparenchymallossduringOff-Clampcom- pared withOn-Clamp PN [20,21].We believe that in Off- Clamp approach, there is a tendency to limit parenchy- malresectioninordertoreducebleeding(minimalmargin

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Table4 Outcomesvariablesinthematchedgroups.

Variable On-Clamp Off-Clamp p

N(%) 309(100%) 103(100%)

Operationtime(min) 0,4

Median[IQR] 172[126—208] 170[118—200]

Warmischemiatime(min)

Median[IQR] 19[14—23] NC

EBL(ml) 0,28

Median[IQR] 100[50—200)] 120[50—300]

Marginstatusn(%) 0,9

Positive 17(5,5) 6(5,8)

Negative 292(94,5) 97(94,2)

Excisionalvolume(cm³) 7,08[3,59—12,9] 3,5[1—5,5,6] <0,01

Surgeonassessmentofvolumepreservation(%)

Median[IQR] 95[86—95] 95[89—95] 0,9

Postoperativerenalscan(relativefunction%) Median[IQR]

Right 48,3[41—57] 48,7[44—55,3] 0,9

Transfusionn(%) 16(5,2) 11(10,7) 0,051

G3—5postoperativecomplicationsn(%) 17(5,5) 5(4,8) 0,8

Overallpostoperativecomplicationsn(%) 55(17,7) 23(22,3) 0,3

SurgicalReoperationn(%) 5(1,6) 2(1,9) 1

30-dayReadmissionn(%) 14(4,5) 4(3,9) 1

Postoperativee-GFR(ml/min) 0,6

Median[IQR] 73[58—87] 74[57—90]

Deltae-GFR(ml/min)

Median[IQR] −9,7[—19—0,05] −2,2[—12—0,0] <0,01

e-GFRpreservation

Median[IQR] 87[76—100] 97[83—100] <0,01

CKDupstaging 113(36,5%) 24(23,3%) 0,01

EBL:EstimatedBloodloss;Deltae-GFR:postoperativee-GFR-baselinee-GFR;e-GFR:estimatedglomerularfiltrationratedefiniteby theModificationofDietinRenalDisease(MDRD).E-GFRpreservationwasdefinedaspostoperativee-GFRdividedbybaselinee-GFR.

TheCKD wasdeﬁnedaccordingtotheKidneyDiseaseOutcomeQuality Initiative-ChronicKidneyDiseasewithstages 1,2,3,4and 5 correspondingtoane-GFR>=90,60—89,30—59,15—30and<15ml/minrespectively.

Table5 Multiplelinearregressionpredictingthee-GFRpreservationrate.

e-GFRpreservation

Variables Coefﬁcient(SE) P

Age(per1year) −0,154(0,065) 0,02

Baselinee-GFR(per 1ml/min/1,73M2)

−0,05(0,032) 0,09

Ischemiatype(Zero=0,Warm=1) −4,2(1,7) 0,011

Excisionalvolumeloss(per1cm³) −0,14(0,06) 0,015 Fratio=29

P<0,01

AdjustedRsquared=22%

Multicollinearitytested:correlation matrix-Tolerance-Varianceinﬂation factor

Thedependentvariable(e-GFRpreservationrate)isacontinuousvariable.Alinearregressionmodelwasusedtopredictthisvariable.

TheoverallF-testdetermineswhethertherelationshipisstatisticallysigniﬁcant.Inthismodel,thepoftheoverallF-testwas<0,05.

We concludethat the R-squared valueis signiﬁcantlydifferent from zero.R-squared provides anestimate ofthe strengthofthe relationshipbetweenthemodelandtheresponsevariable.

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Table6 showsthelogisticregressionmodelpredictingCKDupstaging.

CKDupstaging

Variables OR(95%CI) P

Age(years) 1,01[0,99—1,030] 0,3

Tumorsize(cm) 1,22[0,92—1,61] 0,16

Ischemiatype(Zero=0,Warm=1) 0,652[0,4—1,2] 0,12

Excisionalvolumeloss(per1cm3) 1,035[1,15] <0,01

OR:Oddratio;CIConﬁdenceinterval.

resection),though less volumeexcisiondidnot affectthe positivesurgicalmargininourseries.Thisﬁndingisconsis- tentwiththeliterature[2,22].

Regarding renal function preservation, the relative importance of ischemia type is still debatable. In a multi-institutional study of 886 robot-assisted PN cases, Kaczmareketal.[6]performedananalysisinvolvingpropen- sity score matching between 49 patients who underwent Off-Clamp and 283 who underwent On-Clamp PN. The Off-Clamp group had signiﬁcantly higher renal function preservationatlastfollow-upcomparedwithOn-Clamp(e- GFR2%vs.—6%,P=0.008).

This study had several limitations. One of these limitations was the absence of information on parenchymal volumepreservation.Aretrospectivecomparisonofsuper- selective clamping PN and On-Clamp PN by Desai et al.

[22]showedthatsuperselectiveclampingPNwasassociated withalowerdecrease ine-GFR (P=0.03).Porpiglia etal.

[7] evaluate postoperative renal function after On-Clamp (WIT<25min) and Off-ClampPN.Postoperative functional parametersat 3 monthsafter surgery weresimilarin the twogroups.

Inourstudy,theOff-Clampgrouphadabetterrenalfunc- tionpreservationincomparisontoOn-Clampgroup,though themedianischemiatimeintheOn-Clampgroup wasless than20min(acceptablethresholdforWIT).Thisadvantage one-GFR preservation was not only relatedto Off-Clamp approach.Indeed,thetrendtoresectlessparenchymadur- ingOff-Clamppartialnephrectomyexplainspartoftherenal functionpreservation inOff-Clampgroupasshown bythe multivariateanalysis.

Our multivariate analysis showed that ischemia type, volume loss, and age were predictors of renal function preservation. These results validated that parenchymal preservation, and no ischemia technique are the most importantdeterminantsofrenalfunctionafterPN.

Ourstudy validatesprevious publications reportingthe feasibilityofRAPNOff-Clampapproachinselectedpatients with acceptable morbidity in comparison to On-Clamp approach. Identifyingthe relativebeneﬁts and risksasso- ciatedwithOff-Clampcanhelpwithappropriateselection ofpatientsforthisapproach.

Weacknowledgesomelimitationsinourstudy;mostare inherent problems of retrospective studies, even though datawerecollectedprospectivelybychartreview,onthe basisofapredeterminedregistrationgrid.Propensityscore (PS)analyseshavethelimitationthatremainingunmeasured

confoundingmaystillbepresent.Inaddition,matchingusing thePSdonotovercomeinitialselectionbias.

Conclusion

RAPN for selected renal mass using Off-Clamp approach offered renal functional advantage over On-Clamp, with- out adding morbidities. While no ischemiatechnique was associatedwithlessexcisionalvolumelossthenOn-Clamp;

excisionalvolumeloss,Off-Clampapproach,andagewere independentpredictorsofrenalfunctionpreservation.Clin- icalsigniﬁcanceoftheseﬁndingsinvariousclinicalsettings willrequirefurtherinvestigation.

Disclosure of interest

Theauthorsdeclarethattheyhavenocompetinginterest.

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