Delayed recovery of kidney function in a multiple myeloma patient treated with high cut-off hemodialysis: A case report

(1)

Case report/Kazuistyka

Delayed recovery of kidney function in a multiple myeloma patient treated with high cut-off

hemodialysis: A case report

Katarzyna Kakareko *, Alicja Rydzewska-Rosolowska, Tomasz Hryszko, Beata Naumnik

IDepartmentofNephrologyandTransplantationwithDialysisUnit,MedicalUniversityofBialystok,Poland

Introduction

Castnephropathyisthemostcommoncauseofrenalinjury in patients withmultiple myeloma (MM) – it accounts for 41%ofcases[1]andisresponsiblefor upto70%ofdialysis dependent acute kidney injury in MM [2]. Previously only about 20% of patients became independent of dialysis [3].

Novel therapeutic agents – bortezomib and high cut-off hemodialysis(HCO)greatlyimprovedrenaloutcome.Recov- ery of renal function is crucial for patients' survival. Cast nephropathyisaresultofexcessiveproductionoffreelight chains(FLC)byplasmacells.Thereisaprovedrelationship betweenserumFLCreductionandkidneyfunctionrecovery

inpatientsdiagnosedwithcastnephropathy[4].Removalof serumFLCcanbedonebyplasmaexchangeorhemodialysis using high cut-off dialyzer. While effectiveness of plasmapheresis is disputable, results from studies with HCO are very encouraging and suggest that HCO improves clinical outcome. Wewouldliketopresentacaseofapatientwho haddelayedrenalrecovery–3monthsaftertreatmentwith HCO.

Case report

A 68-year-old femalewas admitted tothe I Department of Nephrology and Transplantation with Dialysis Unit due to acta haematologica polonica 46 (2015)61–64

article info

Articlehistory:

Received:30.07.2014 Accepted:29.12.2014 Availableonline:07.01.2015

Keywords:

Castnephropathy

Multiplemyeloma

Highcut-offhemodialysis

Kidneyinjury

abstract

Wepresentacaseofa68-year-oldwomanwithdialysisdependentacutekidneyinjury secondaryto multiple myeloma.The treatmentconsisted ofplasmaexchange, 10 ses- sionsofhigh-cut-offhemodialysisandinductionchemotherapy.Freelightchainconcen- tration(FLC)wasreducedfrom1900mg/lto584mg/l(a70%reduction).Recoveryofkid- ney function was observed 3 months afterhospital admission anddiscontinuation of dialysiswaspossible.Thecaseisquiteunusualbecauseofthedelayinrenalrecovery.

*Correspondingauthor at:I DepartmentofNephrologyandTransplantationwithDialysisUnit,MedicalUniversity ofBialystok,Ul.

Zurawia14,15-540Bialystok,Poland.Tel.:+48857409458;fax:+48857434586.

E-mailaddress:kponikwicka@gmail.com(K.Kakareko).

ContentslistsavailableatScienceDirect

Acta Haematologica Polonica

journalhomepage:www.elsevier.com/locate/achaem

http://dx.doi.org/10.1016/j.achaem.2014.12.003

(2)

oliguria and acute kidney injury (AKI). Medical history revealed bone pain lasting for about 6 months (mostly in the back)and acomputed tomography performed 2weeks previously showed soft tissue masses: 45mm51mm locatedattheleftsecondrib(Fig.1),17mm36mmatthe leftseventhrib,20mm31mmattherightseventhriband costallesionsinthethoracicvertebras–Th2,Th5,Th6,Th8- 12. Two days before hospital admission a ﬁne needle aspirationbiopsyofthetumorlocatedinthesecondribwas performed.

Onadmissionlaboratorytestsrevealed:serumcreatinine 6.17mg/dl, urea 115mg/dl, white blood cells 7.9510⁹l ¹, platelets 15710⁹l ¹, hemoglobin 9.6g/dl, calcium 10.92mg/dl and serum total protein 63.8g/l. Renal ultraso- nographyshowed kidneysof normal sizeand echogenicity withnoevidenceofobstruction.Serumproteinelectrophor- esiswasremarkableforaparaproteininthegammaregion.

Lambda light chains were detected by immunofixation in both serum and urine. The results from tumor biopsy identified MM cells. During hospitalization a bonemarrow biopsywasperformedandconfirmedadiagnosisofmultiple myeloma (40%plasma cell infiltration). Serum lambdaFLC concentration was 1900mg/l. Patient received 5 plasma exchanges within the first week. During each session one plasmavolumewas replaced.Consulting hematologistpre- scribed dexamethasone and cyclophosphamide as initial chemotherapy. After plasmaexchanges serum lambdaFLC concentration was even higher compared to the baseline value (3370mg/l), serum creatinine rose (10.03mg/dl) and daily urine output decreased (to 300ml per day). Initially, standard hemodialysis was started (4 sessions), and after- wards patient received 10 session of HCO (Theralite^TM, Gambro HCO 2100 dialyzer, Lund, Sweden), each of 8h duration. Serum lambda FLC decreased to 584mg/l but neither urineoutput nor renalfunction improved. Patient was dialysis dependent, 4-h sessions with standard high flux membranes trice a week were performed. She was transferred to Hematology Department for further treatment.Thereshewasstartedonbortezomib,melphalanand

predisone (VMP). After 3 months an increase in urine outputwasobservedanddialysiswasdiscontinued.Creati- nine level stabilized at 1.34mg/dl (estimated glomerular ﬁltration rate was 41ml/min/1.73m²) and shestays inde- pendentofdialysistodate.

Discussion

Renal insufﬁciencyiscommon inMM. Acutekidneyinjury complicatingMMshouldbequicklyreversedbecausesurvi- val of patients depends on renal function recovery. The main aimof treatmentisa quickreduction ofthe amount of monoclonal light chains. It can be achieved by a simultaneous decrease in the production of FLC using chemotherapyand loweringlevelsof circulatingserumFLC using extracorporeal methods like plasma exchange or hemodialysiswithHCOdialyzer.

Our patient did not have any dialysis indications at admissiontothe hospital.That iswhywedecided tostart plasma exchanges even though their utility in MM is questionable. The usual regimen of plasmapheresis is 5–7 exchangeswithin7–10days.Adecreaseofminimum50%of serum FLC is probably required for recovery of kidney function[4].Inourcasewedidnotobserveapositiveeffect – FLC levels even increased after procedure.A randomized trial with97 patientsdid not show anybenefit of plasma exchangeinacuterenalfailureassociatedwithMM.Plasma- pheresiswithchemotherapywascomparedtoconventional chemotherapy alone. Theauthors found no differences in probability of death, dialysis dependence or glomerular filtrationratelowerthan30ml/minper1.73m²at6months [5]. Howeverthe mainlimitationof thisstudy–thelackof renal pathology confirmation– isprobablythe reason why the results are in contrary to a more recent trial, which showed effectiveness of plasmapheresis when plasma exchangewasusedincombinationwithbortezomib[6].

Currently, high cut-off dialysis is the most efﬁcient method of removing FLC [7]. High cut-off dialyzer has a membrane with large pores, with a permeability for substanceswithmolecularweightsupto45kD. Itisthere- fore very effective at removing kappa and lambda light chainswhich have molecularweightsof 22.5kDand 45kD respectively. HCO dialysis schedule should be extended to 8hdailytomaximizeFLCremovalduringonesession.This enablesthe removal ofnot onlyintravascularFLC but also FLCdistributedinextravascularcompartments[8,9].

Thehighcut-offdialyzerwasnotavailableatourDialysis Unit as we started dialysis in our patient, therefore we conductedherﬁrstsessionswithastandarddialyzer.How- ever,somereportsevensuggestusingstandarddialyzersfor inductiondialysistherapy,consideringthehighcostofHCO dialyzersandthenecessitytoshortenﬁrstdialysissessions duetotheriskofdisequilibriumsyndrome[10].

At the end of 10 sessions withHCO dialyzer the reduction inserumlambdaFLCswas70%whichisinagreement with previous reports[2]. Despite the signiﬁcant reduction inserumFLClevels wedidnotobserveanimprovementin renal functionand standarddialysis sessions werestarted.

In previous studies median time in which dialysis was Fig.1–Computedtomographyofthechest.Softtissue

masses:45T51mmlocatedattheleftsecondrib(arrow)

acta haematologica polonica46(2015)61–64

62

(3)

discontinuedwas15–27daysandmaximumtimetodialysis independence was 64–120 days [2, 11]. During this time patientswere stilltreated withHCO dialyzers.Our patient recoveredrenalfunction afterover90days, 2monthsafter discontinuation of HCO dialysis sessions. Even though accordingtodefinition3monthsare neededtodistinguish acute kidneyinjury from chronic kidney disease, our case showsthatevenafterthattimeachanceremainsforrenal functionimprovement.Basnayakeetal.documented4cases of dialysis dependent AKI due to myeloma kidney, where biopsywasperformedbeforeandafter6weeksoftreatment with chemotherapy and HCO dialysis [12]. Despite early significant reduction in FLC levels all 4 patient remained dialysisdependentat6weeks,although3ofthemrecovered renalfunctionat 51, 67 and105 days.Their 6-weekbiopsy showedareductioninthenumberoftubuleswithcastsbut anincreaseinindexofchronicdamage.Inonepatientthere wasareductioninthedegreeofinterstitialinfiltrate.Inthis study even patients with significant chronic damage still achievedlaterenalrecovery[12].

Bortezomibwithhighdosedexamethasoneisconsidered thetreatmentof choicefor patientswithrenalimpairment due to MM [13]. In our patient initial chemotherapy with high dose dexamethasone and cyclophosphamide was started at the beginning of the dialysis. Bortezomib based chemotherapy regimen has been postponed due to infec- tious complications. Reported median time to response in patientstreatedwithbortezomibis38days[14].Duringthat timeserumFLClevels canbecontrolledbyHCO dialysisto prevent irreversible damage to the kidneys. The ﬁndings frompreviousstudiesrecommendinitiationofHCOdialysis combinedwithchemotherapyasearlyaspossible[15].

Thefirstlimitationinmanagementofourcaseislackof renalbiopsytoconfirmcastnephropathydiagnosis.Patient hadacutekidneyinjury,serum FLClevels above1500mg/l, withlow urinaryalbumin excretion (30mg/dlinurine dip- stick). Although only kidney biopsy confirms a definitive diagnosistheaforementionedclinicalsymptomsgiveusthe right to diagnose cast nephropathy with high probability.

Secondlimitationisapostponement inchemotherapy(due infectiouscomplicationsand lackof availabilityof bortezo- mibinthenephrologydepartment).

Wethereforereportacaseofpatientsuccessfullytreated with HCO dialysis. Effect of treatment was observed 3 months after hospital admission. In our opinion this delayedeffectisworthmentioningconsideringaverygood renal response. After 3 months of continuous dialysis therapy and 2 months after the discontinuation of HCO dialysis such a result was unexpected but fortunately for thepatientnotimpossible.

Authors' contributions/Wkład autorów

Accordingtoorder.

Conﬂict of interest/Konﬂikt interesu

Nonedeclared.

Financial support/Finansowanie

Nonedeclared.

Ethics/Etyka

The work described in this articlehas been carried out in accordance with The Code of Ethics of the World Medical Association (Declarationof Helsinki)for experiments invol- ving humans; EU Directive 2010/63/EU for animal experiments;UniformRequirementsformanuscriptssubmittedto Biomedicaljournals.

references/pi smiennictwo

[1] MontsenyJJ,KleinknechtD,MeyrierA,etal.Long-term outcomeaccordingtorenalhistologicallesionsin118 patientswithmonoclonalgammopathies.NephrolDial Transplant1998;13:1438–1445.

[2] HutchisonCA,BradwellAR,CookM,etal.Treatmentof acuterenalfailuresecondarytomultiplemyelomawith chemotherapyandextendedhighcut-offhemodialysis.

ClinJAmSocNephrol2009;4:745–754.

[3] KnudsenLM,HjorthM,HippeE.Renalfailureinmultiple myeloma:reversibilityandimpactontheprognosis.Nordic MyelomaStudyGroup.EurJHaematol2000;65:175–181.

[4] LeungN,GertzMA,ZeldenrustSR,etal.Improvementof castnephropathywithplasmaexchangedependsonthe diagnosisandonreductionofserumfreelightchains.

KidneyInt2008;73:1282–1288.

[5] ClarkWF,StewartAK,RockGA,etal.Plasmaexchange whenmyelomapresentsasacuterenalfailure:a randomized,controlledtrial.AnnInternMed2005;

143:777–784.

[6] BurnetteBL,LeungN,RajkumarSV.Renalimprovementin myelomawithbortezomibplusplasmaexchange.NEnglJ Med2011;364:2365–2366.

[7] KanayamaK,OhashiA,HasegawaM,etal.Comparisonof freelightchainremovalbyfourbloodpuriﬁcationmethods.

TherApherDial2011;15:394–399.

[8] CsertiC,HaspelR,StowellC,DzikW.Light-chainremoval byplasmapheresisinmyeloma-associatedrenalfailure.

Transfusion2007;47:511–514.

[9] HutchisonCA,CockwellP,ReidS,etal.Efﬁcientremovalof immunoglobulinfreelightchainsbyhemodialysisfor multiplemyeloma:invitroandinvivostudies.JAmSoc Nephrol2007;18:886–895.

[10] GongD,JiD,ZhangK,etal.Endotoxemiaafterhighcutoff hemodialysisfortreatmentofpatientwithmultiple myelomacanbepreventedbyusingultrapuredialysate:a casereport.HemodialInt2013;17:618–623.

[11] HeyneN,DeneckeB,GuthoffM,etal.Extracorporeallight chainelimination:highcut-off(HCO)hemodialysis paralleltochemotherapyallowsforahighproportionof renalrecoveryinmultiplemyelomapatientswith dialysis-dependentacutekidneyinjury.AnnHematol 2012;91:729–735.

[12] BasnayakeK,CheungCK,SheaffM,etal.Differential progressionofrenalscarringanddeterminantsoflaterenal recoveryinsustaineddialysisdependentacutekidney injurysecondarytomyelomakidney.JClinPathol2010;

63:884–887.

acta haematologica polonica46(2015) 61–64

63

(4)

[13] DimopoulosMA,TerposE,Chanan-KhanA,etal.Renal impairmentinpatientswithmultiplemyeloma:a consensusstatementonbehalfoftheInternational MyelomaWorkingGroup.JClinOncol2010;28:4976–4984.

[14] LudwigH,AdamZ,HajekR,etal.Lightchain-induced acuterenalfailurecanbereversedbybortezomib- doxorubicin-dexamethasoneinmultiplemyeloma:

resultsofaphaseIIstudy.JClinOncol2010;28:

4635–4641.

[15] KhalafallahAA,LoiSW,LoveS,etal.Earlyapplicationof highcut-offhaemodialysisforde-novomyeloma nephropathyisassociatedwithlong-termdialysis- independencyandrenalrecovery.MediterrJHematolInfect Dis2013;5:e2013007.

acta haematologica polonica46(2015)61–64