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MedicalComplications ofRenalTransplantationThitisak Kitthaweesin,MD.

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Main topicsInfectious complications

Cardiovascular complications

Lipid abnormalities after KTPost transplant DM

Parathyroid and mineral metabolism

Post transplant erythrocytosisMalignancies associated with Tx

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Infectious complicationsGeneral principles of transplant

infectious disease

Diagnosis of infection

Management of infection in transplant

recipient

Infection of particular importance intransplant recipient

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General principles

Microorganism causing infection in

transplant recipient

True pathogens

Influenza,typhoid,cholera,bubonic plague

Sometime pathogens

S.aureus,normal gut flora

NonpathogensAspergillus fumigatus,cryptococcus

neoformans HHV-8

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General principles

Risk of infection in transplant recipientis determined by 3 factors

Epidemiologic exposure

The net state of immunosuppression

The preventative antimicrobial strategies

Timetable for posttransplant infections

The first rule of transplant infectiousdisease is that infection is far betterprevented than treated

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Epidemiologic exposure

Exposures within the community M.tuberculosis

Geographically restricted systemic mycoses

Blastomyces , Histoplasma capsulatum, Coccioidesimmitis

Strongyloides stercoralis Community-acquired respiratory dis.

Influenza, Parainfluenza,RSV,Adenovirus

Infections acquired through ingestion of contaminatedfood/waterListeria, Salmonella sp.

Community-acquired opportunistic infection

Crypto.neoformans,Aspergillus,Nocardia,PCP.

Viral infections

VZV,HIV,HBV,HCV.

Exposures within the hospital

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Epidemiologic exposure

Exposures within the communityExposures within the hospital

Environmental exposures

Aspergillus species

Legionella species

P.aeruginosa and other gram negative bacilli

Person to person spread

Azole-resistant Canidida spp.

MRSA.

VRE.

C.difficile

Highly resistant gram negative bacilli

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The net state of

immunosuppression

Dose,duration,and temporal sequence of

immunosuppressive drugs

Host defense defects caused by underlying

diseasesPresence of neutropenia,defect in

mucocutaneous barrier or indwelling of FB.

Metabolic derangements PCM,uremia,hyperglycemia

Infection with immunomodulating viruses:

CMV,EBV,HBV,HCV,HIV

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Timetable for posttransplant infection

Infection in the first month

Infection conveyed with a contaminated

allograft

Infection caused by residual infection in

the recipients

>95% of the infections are the surgical

wound,urinary,pulmonary,vascularaccess,drain related

Key factors:nature of operation andtechnical skill

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Timetable for posttransplant infection

Infection in 1-6 months posttransplant

The immunomodulating viruses

Particular CMV

but also EBV,HHV,HBV,HCV,HIV

opportunistic infection due to

P.carinii

Aspergillus sp. L.monocytogenes

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Timetable for posttransplant infection

Infection more than 6 months posttransplant

The >80% of patients with good result (goodallograft function,baseline immunosuppression)

Community-acquired resp.viruses

Urinary tract infection

The 5-15% with chronic or progressive infection

HBV,HCV,EBV..chronic hepatitis, progression to end

stage liver disease and HCC.

The 10% with poor results (poor allograftfunction,excessive immunosuppression,chronic viral

infection)

PCP,Cryptococcus,Listeria monocytogenes,Aspergillus

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Usual sequence of infection posttransplant

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Diagnosis of infectionRadiological diagnosis

CT.chest and brain for early diagnosis andtreatment

Pathological diagnosis Need for biopsy

Microbiological diagnosis Isolation and identification of microbial species

from appropriately obtained specimens Immunologic methods

Microbial antigen detection

Microbial DNA detection by PCR technique

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Principle of

Antimicrobial Therapy

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Strategies for antimicrobial

therapy

There are three different modes of use

Therapeutic mode

Curative treatment for establishedinfection

Prophylactic mode Prescribed to entire patients before an

event to prevent a form of infection that isimportant to justify ie. intervention

Preemptive mode Prescribed to subgroup of patients that

high risk for clinical significant disease

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Strategies for antimicrobial

therapy

Prophylactic strategies

Low-dose TMP/SMX

Effective againstPneumocystis,Nocardia,Listeria,urosepsisand perhap,Toxoplasma

Perioperative surgical prophylaxis

Protects against wound infection

Oral gancyclovir,valacyclovir Effective against CMV disease

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Strategies for antimicrobialtherapy

Preemptive strategies Appropriate antibacterial or antifungal therapy in

ass.with surgical manipulation of an infectedsitesprotect against syst.disseminated

Fluconazole therapy of candiduria ..protect againstobstructing fungal balls and ascending infection

Intravenous followed by oral ganciclovir in CMVseropositive patient treated with ALGprotect

against symptomatic CMV disease Monitoring bloood for CMV by antigenemia or

PCR,with preemptive ganciclovir therapy once athreshold level of viral reachedprotect againstsymptomatic CMV disease

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Infection of particular

importance in transplant

recipients

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CytomegalovirusCMV ..evidence of replication 50-75%

in transplant recipients

CMV infection Seroconversion with the appearance of

anti-CMV IgMAb

Detection of CMV Ag in infectious cells

Isolation of the virus by C/S of throat,buffy

coat or urine

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CMV disease Requires clinical signs &symptoms ie.

severe leukopenia or organ involvement

(hepatitis,pneumonitis,colitis,

pancreatitis,menigoencephalitis andrarely myocarditis)

Rare feature is progressive

chorioretinitis

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The manifestation of CMV in

transplant recipients

Direct man ifestat ions

Mononucleosis

Leukopenia/thrombocytopenia

Tissue invasive dz.

Ind irect manifestat ion

Depression of host disease

Allergy injury & rejection Increase the risk of PTLD 7-10 fold

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Risk of clinical CMV disease

is determined by 2 factor

Serological status of donor and

recipientNature of the immunosuppressive

therapy

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Role of CMV infection in transplantrecipient

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Prophylactic therapyGancicovir= propylactic therapy of choice

IV

Oral

IV followed by oral

Ant iv i ral therapy

Significant decrease CMV disease and infection

Both antiviral agent asso.with a decrease in

disease Only ganciclovir decrease the risk of infection

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CMV-positive donor

CMV-negative recipient

(D+/R-) 70-90% will develop primary CMV infection

50-80% will have CMV disease

30% will develop pneumonitis

Absence of propylactic Rx..mortality rate 15%

Conventionalgrade B

Immunosuppression with ALAgrade A

Ganciclovir 1000 mg TID orally

5 mg/kg BID IV.

IV. Dose daily x 3 wks. switch to oral 2-12 wks.With ALA IV. 1 month followed by oral 2 months

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CMV-negative donorCMV-positive recipient(D-/R+)

Reactivation of latent CMV infection

CMV infection/disease 20%Pneumonitis is rare

Antiviral propylaxis recommended for pt.

who receive immunosuppression withALA (grade A) or conventional imm.supp.

(grade C)

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CMV-positive donorCMV-positive recipient(D+/R+)

Risk for reactivation of latent virus and

superinfection with new strain

Worst graft and pt.survival at 3 yrs.Post Tx

Antiviral prophylaxis in imm.supp. with

ALA (grade A) or conventional Rx(grade C)

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CMV-negative donorCMV-negative recipient(D-/R-)

Low prevalence of disease

No antiviral prophylaxis therapy wasrecommended

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TreatmentVaried with severity of dz.Mononucleosis-like syndrome

Resolve without antiviral drug

Stop OKT3, AZA & stop if Wbc

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EBVPossible clinical consequens of EBVreplication

Mononucleosis syndrome

Meningoencephalitis

Oral hairy leukoplakia

Malignanciessmooth m.tumor,T-celllymphoma,PTLD

Active replication 20-30% of pt.+conventional Rx>80% of pt.+ALA

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EBVCritical effectits role in pathogenesis of

PTLD usually B cell (benign polyclonal tomalignant monoclonal lymphoma)

Facto rs that inc rease r isks of PTLD

High viral load

Primary EBV infection

High dose immunosuppressionALA,High dose CsA&Tacrolimus, Pulse

steroids or in combination Type of organ Tx

CMV infection

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EBVEBV infect ion

Latent form (great majority)

Not susceptible to antiviral Rx

Replicative form

Susceptible to antiviral Rx

Antiviral therapy alone unlikely to be

effective

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Other viral infectionsVZV.

Primary infect ionwith VZV in Tx pt can

be severe candidatesscreened forAB+Rx with zoster Ig

React ivat ion dzrelatively benign

typical zoster involve few dermatome in

20-30% pt. , antiviral Rx not alwaysneeded

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HSV

Occur in 50% of pt.

Lesions usuallyulcerative > vesicular

Recurs more often & acyclovir oftenbeneficial

Dual infection with HSV + CMV can beRX with ganciclovir alone

HIV

Tx of organ from HIV-infectiondonortransmit virus 100%

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HHV-6

Found in blood 30-50% of pt.

Often asso.with CMV viremia

Clinical effectsmononucleosis , allograft

dysfunction,prolonged hospital length of

stay,inv.pneumonia,encephalitis Combined infection with HHV-6 & CMVmore

severe

Ganciclovir susceptible HHV-8

Putative agent of Kaposis sarcoma

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Bacterial infection UTI

Common after renal Tx

Prevalent within the first post Tx year

Most case inv. Gram negative organisms Risk factor

Indwelling,trauma to kidney and ureter duringSx

Anatomic abnormalities of native or TXkidneys

Neurogenic bladder

Rejection and immunosuppression

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Pathogenssimilar to general

population

E.coli , Enterococci , P.aeruginosa ,

C.urealyticum

UTI in first few months after Txfrequently asso. with pyelonephritis or

sepsis ,may be asso. with allograft

dysfunction and may predispose to

develop acute rejection

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Recommendat ion

low-dose TMP/SMX minimum 4 month

(most centers prophylasis for 1 year)

provides prophylaxis againstP.carinii,Nocardia asteroides and

L.monocytogenes

Pt.with Hx allergy to TMP/SMXoralquinolones

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Opportunistic bacterialinfections

Three important opportunistic bacterial

infection in first year post Tx L.monocytogenes

N.asteroides

M.tuberculosis

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Fungal infection Dissem inated infect ion

Primary infection/reactivation

Dimorrphic fungi

(histoplasmosis,blastomycosis,coccidioidomycosis)cause asymptomatic or limited infection in normalhost

Inv asive infect ion Candida sp.,P.carnii,Aspergillus sp.

C.neoformans, Mucor sp.

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Candida

Mucocutaneous overgrowth can beprevented by Rx of high risk pt. withnystation oral wash

Candiduria should be treated with

fluconazole or low-dose IV. Ampho.Bwith/without flucytosine

Dissemination dzAmpho-B orfluconazole

Life-threatening infectionAmpho-Bprobably more effective

Liposomal Ampho-Blessnephrotoxic,similar efficacy

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Cardiovascularcomplication ofTransplantation

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Cardiovascular complicationof Transplantation

Cardiovascular dzis very common

Incidence new IHD events11.1% (among

pt without Hx IHD) during 46+ 36 mo. F/U

Celebro vascular Dz

6.0% (among ptwithout prior Hx)

CVD 5 fold > pt. similar age &gender

Cumulative incidence

IHD 23% in 15 yrs

CVA 15% in 15 yrs

PVD 15% in 15 yrs

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Pretransp lan t CVD Pre Tx CVD is an important risk factor for

post Tx CVD IHD often asymptomatic in ESRD patients

Asymptomatic CAD pt who underwentrevascularization had sig. fewer IHDevent after Tx

High risk pt would benefit from screening&Rx asymptomatic IHD as part of preTxevaluation

Recommendat ionhigh risk pt shouldundergo a cardiac stress test(Dobutamine stress echo/Radionucludestress test)

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HT after renal TxMajor risk factor for graft survival

Occur in 60-80% of pt.

Prevalence was low in

pt.who received LRKT

bilateral nephrectomy

stable Scr < 2 mg/dL

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Pathogenesis

Acute allograft rejection

Chronic allograft rejection

Cadaveric allografts esp. from a donorwith FHx of HT

High renin state from diseased native

kidney Immunosuppressive therapy such as

Cyclosporine,Tacrolimus andcorticosteroid

Increase BW

Hypercalcemia

New onset essential HT

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#Suggestive evidences:

transplant kidney may have

prohypertensive or antihypertensive

properties

#Experimental models of genetic HT

the inherited tendency to HT residesprimary in the kidney

#Study of 85 pts:

BP+antiHT requirement

occur more frequently in recipient fromnormotensive family received a kidney

from donor with HT family

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Role of corticosteroid

Usually nota major risk factor forchronic HT in Tx recipients

because of rapid dose reduction

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Role of cyc lospor ine

Vasoconstr ict iveeffect HT

volume dependent > renin dependent

Increased systemic and renal vascular resist.

(primary affecting afferent arterio le)

Increase vascular resistance.inadequate

relaxation>active vasoconstriction

Release of vasoconstrictorendothel in

Endothelial injury leading to generation ofNO.

Sympathetic activationadditional factor

Mild hypo Mg,affected intracellular Ca-binding

proteinincrease vascular tone

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RASFunctional significant stenosis occur in

12% of recipients with HT

Correctable form of HT

Renal arter iog raphyprocedure of

choice for Dx RAS in solitary Tx kidney

Renal allograft Bx prior to angiography

to R/O chronic rejection or other renalparenchymal dz

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TreatmentPatient with CsA

Reduced CsA dose

If permanent HTstart CCB,diuretic

Preventionfish oil 4 gm/day

Patient without CsA

Start anti-HTCCB ,ACEI,beta blocker

+diuretic Resistant HTpatient should undergo

renal arteriography to exclude RAS

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Lipid abnormalitiesafter renal Tx

Prevalence 16-78% of recipients

Reported change in serum lipid:elevation in

both cholesterol and triglycerideElevated LDL and apo-B level are common

Low HDL reported in some studies

Hypercholesterolemia occurs within 6 monthsHypertriglyceridemia.. peak incidence at 12 mo

and correlated with excessive BW, elevatedScr

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Lipid abnormalities afterrenal Tx

Post Tx lipoprotein abnormalities may

contribute to the development of CVD

and PVDExpected correlation between high

lipid level and cardiovascular mortality

Increased serum triglycerideimplicated as predictor of chronicrenal allograft failure

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Contributing factors

High steroid dose

CsA / FK506

DM.

Nephrotic

syndrome

Excessive wt.gain

High fat diets

Use of diuretic,

beta-blockers

Genetic

susceptibility

P th i

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PathogenesisMultifactorial

Correlate with corticosteroid dose

& cyclosporineSteroid withdrawal association

17% decreased in total chol. Level

Pt. With CsA ...chol 30-36 mg/dl >pt. with AZA + pred.

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CorticosteroidPeripheral insulin resistanceHyperinsulinemia

Hepatic VLDL synthesis

ACTH releaseAdministration of ACTH 3 weeks TC,LDL,TG & HDL

ACTH may act by upregulate LDLreceptor activity

Steroid may be not benefit to lipidmetabolism in pt with CsA

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Cyclosporine

Dose-dependent

Correlation between Blood CsA level

and degree of hypercholesterol

CsA pt. have higher TG + Lp(a) >

AZA + prednisolone

CsA induced hypoMg ..contribute tohypercholesterol

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TacrolimusSimilar to but less pronounced than CsALDL,Lp(a),fibrinogen levellower in

FK506may be asso.with lower serum TCsubstitution of tacrolimus for CsA may

improved lipid profile

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Treatment

Dietary modification

Weight reduction in obesed pt.

Corticosteroid dose reduction

Drug therapy

unclear role

shoud not be describe early when GCs

dose are relative high

drug-induced complications

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HMG-CoA reductase inhibitor

More likely to induce rhabdomyolysis in

pt with CsA

CsA decreased hepatic met. of drug

Low dose regimen may allow to be used

Pravastatin..less muscle toxic,FDA

approved

Fluvastatin..may also have less adverse

effects

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Low-dose therapy with statin

considered in

stable pat ient 8 mon ths after Tx

total chol > 240 mg/dL

LDL chol > 160 mg/dL

patient with other CV risk factors may

be Rx if LDL 130-160 mg/dL

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Benefits of HMG CoA

reductase inhibitor

Lower risk of rejection Katznelson et al.Transplantation,1996

Lower incidence of chronic rejection

Improved graft survival Kobashigawa et al.N Engl J Med,1995

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Post-transplant DM

Incidence

PTDM varied from 2-46%

variation in criterias

Etiology and Pathogenesis

onset of PTDM is related to

immunosuppressive Rx

occur mostly in first year

exogenous glucocorticoid in predisposed

individuals

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Glucocorticoid ..impair both hepatic &extrahepatic action of insulin

post receptor insulin resistance

impaired phase1,2 and glucagon mediatedinsulin secretion

Cyclosporine..interfere with glucosemetabolism

accum in panc islet cell..insulin secretion

FK506..glucose intolerance more often unclear mechanism..dampen insulin

secretion (Filler et al.NDT2000 )

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Risk factors for PTDM

Obesity

black

age > 40 yearsfirst-degree relative with DM

HLA A28,A30,BW42

CDKTSteroid / FK506

C f

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Clinical features

Incidencenot related to renal dz,number of rejection or graft function

peak onsetduring the first year

(2-3moths)majorityasymptomatic,hyperglycemia

on blood test

40-50 % require insulin therapy

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Prevention/Management

Patient education

dietary

management exercise

insulin

oral hypoglycemic

agents

Screen for and treat

microalbuminuria

and hyperglycemia

regular

ophthalmologic and

podiatry exam

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Go to.. Medicalcomplication of Renaltransplantation Part II

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Parathyroid andMineral metabolism

after Renal Transplant

Successful KT

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Successful KT

Normalize urinaryP,beta-2 microglobulin

excretionNormalize renal calcitriol production

Reverse many abnormalities

lower P to normal

lower PTH level

lower plasma AP

mobilization of soft tissue calcification

improvement in Al-bone dz

prevention of progression of amyloidosteodystrophy

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Primary abnormalities that

can persist after KT

HyperPTH

Aluminum and beta2-microglobulinaccumulation

Adynamic bone disease

OsteopeniaOsteonecrosis

HPTH and

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HPTH and

Hypercalcemia

1 in 3 of pt have persistent PTHhypersecretion

development of hyperCa related toduration of dialysis and parathyroidgland size, secondary to hyperplasia ofgland > hypersecretion of cells

other factors resorption of soft tissue Ca-P deposits

HPTH d H l i

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HPTH and Hypercalcemia

other factors resorption of soft tissue Ca-P deposits

normalization of calcitriol production

PTH effect on bone

direct enhance GI.calcium absorption

increased plasma albumin

total plasma Ca via binding

no effect on ionized Ca concentration

HPTH d H l i

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HPTH and Hypercalcemia

Plasma Ca begin to rise in first 10days after Tx and can be delayed for 6

months or more

patients with preexisting severesecondary HPTHacute severe

hypercalcemia after KT, can cause

acute allograft dysfunction and rarelycalciphylaxis

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Treatment

Persistent HPTHgenerally

asymptomatic

Hypercalcemiausually resolves

spontaneous over 6 months to as long

as 2-3 years

Conservative Rx with oral P

supplement until plasma PTH lowenough to normalize Ca/P balance

P th id t

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Parathyroidectomy

Severe symptomatic hyperCa

usually in early period

Persistent hyperCa

4-10 % after 1 year

Elective parathyroidectomy

if plasma Ca > 12.5 mg/dL more than 1

year esp. if asso.with radiologicevidences of increased bone resorption

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Aluminum toxicity

KT quickly reverses factors leading to

Aluminum accumulation

more effective than desferoxaminetherapy in lower serum and bone Al

level

H h h t i

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Hypophosphatemia

Persistent hypo P 20-35 %Induced by P wasting in urine due to

HPTH and PTH independent pathway

Treatment phosphate supplement

exceptin patients with persistent HPTH

phosphate can exacerbate HPTH bycomplex with Ca and lowering GI calcium

absorption

Dialysis related

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Dialysis-related

Amyloidosis

Primarily induced by beta2-

microglobulin deposits

Articular symptoms asso.with disorderrapidly improve after KT

new cystic lesions unusual

resolution of existing cystsrare

Post transplant Bone

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Post-transplant Bone

disease

Osteopenia

Osteonecrosis

Contributing factors persisting uremia-induced abnormal

calcium homeostasis

acquired defects in mineral metabolisminduced by immunosuppressive Rx

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OsteopeniaHigher risk for pathologic FxPrevalence of atraumatic Fx in KT may

be as high as 22 %

Primary site: High cancellous bonevertebrae and ribs

Bone loss occurs early and rapidly

postKT1.6 % per month in first 5 moAfter early periodbone loss continue

at slower rate1.7 % per year

Pathogenesis

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Pathogenesis

postTx bone loss inv.both HPTH and effectof imm supp drugs

GCs-induced suppression of bone

formation

most important factorsteroids

direct toxic to osteoblast

increase osteoclast activity Promote Ca loss by decrease

GI absorption,gonadal hormone,

IGF-1production and sensitivity to PTH

M it

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Monitor

BMD.of hip&spine prior to Tx and 3 mofollowing KT using DEXA

Rapid bone loss and/or low initial BMD

should be considered to RxNo information regarding the effects of

Rx to prevent bone loss in KT patients

Treatment

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Treatment

Lowest dose of prednisolonecompatible with graft survival

Calcium supplementation 1000 mg/day

Vit.D analog can improve Caabsorption

Calcitonin or bisphosphonateif bone

loss is severe and/or rapid esp. duringfirst 6 months after Tx

O t i

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Osteonecrosis

Non-infectious death of marrow cell

and asso.trabeculae,osteocytes

Weight bearing long bonemost often

affected esp. Femoral head

Usually multifocal may develop at any

time after Tx

Incidence15 % within 3 years

O t i

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Osteonecrosis

Direct asociated with

glucocorticoid exposure

cyclosporine

number of tx

HPTH

low bone mass

fracture

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Pathogenesis

GCs

increase intramarrow pressure

increase adipocyte hyperplasia

fat embolism

microfracture

compromised vascular supply

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Diagnosis

Painpredominant symptom

Higher risk of Fx

Arthritis.secondary to joint deformationChange in density of necrotic bone

10-14 days

Radiolucent band

6-8 weeks

MRImost sensitive

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Treatment

No effective medical Rx

reduction of steroid dose has little effect

once osteonecrosis developedSurgical Rx

vascularized bone grafts and core

decompression

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Bone Pain

Occur only in patients received CsA

often temporally related to higher level

Mechanism intraosseous vasoconstriction and HT

Treatment

CCB..nifedipine SR 30-60 mg,Hscompletely relieve symptom

Erythrocytosis

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Erythrocytosis

following KT

PostTx erythrocytosis (PTE)

Hct > 51% on two or moreconsecutive determination

(Gasten et al.1994)

affect 10-15 % of KT patientsmost often within the first 2 years

Etiology and pathogenesis

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Etiology and pathogenesis

Early case reported ..PTE caused byrenal ischemia from RAS

Risk facto rs

smoking

DM.

Rejection-free course

not RAS

EPO factorexcess EPO release from

native kidney

Etiology and pathogenesis

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Etiology and pathogenesis

Non -EPO facto rs

enhance sensitivity to EPO

directly promote erythrocytosis

IGF-1,IGF-BP,GH..enhance.erythrocytosis

Ang iotensin II

ACEI,ATRAinhibit erythrocytosis

activation of AIIreceptor

may enhance EPO production in the graft or

increased Rbc precursor sensitivity to EPO

Treatment

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Treatment

ACE inhib i tor

low dose..enalapril 2.5mg twice a day

lower Hct to normal or near normal level

effect begin within 6 weeks

complete effect in 3-6 months

some pts..asso.ACEI lower Hct and

plasma EPO level(initially normal or elevated EPO level)

Treatment

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eat e t

AT1receptor antagonists

Losartan 50 mg/day

decrease Hct 53 to 48% in 8 wks

Theophyl l ine

8 weeks course,decrease Hct from 58 to

46%,as much as 10-15%

Act as adenosine antagonist facilitaterelease and BM.response to EPO

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RecommendationACEI and ATRA

Losartan 50 mg/day may be increased

to 100 mg/day, if no response within 4weeks or BP remain elevated

If no adequate lowering of Hct afteranother 4 weeks,enalapril 10-20

mg/day or another ACEI continue Rxfor PTE indefinitely

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Malignanciesassociated with

Transplantation

Malignancies associated

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gwith Transplantation

Cincinnati Transplant TumorRegistry(CTTR)

Average age 41 years,average time ofappearance 5 years after Tx

Most striking malignancies CA.skin&lip,PTLD,Kaposis sarcoma,Renal CA

CA.uterine cervix,anogenital CA,HepatobiliaryCA and Sarcoma

No increase in the incidences of commontumor in general population CA.lung,breast,prostate,colon

CA Skin & Lips

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CA. Skin & LipsSkin cancermost common,38%

Incidence increased with length of F/U

Appeared on sun-exposed area

(light skin,blue eyes,blond hair)

Pt age >40 yrslesion occurred on

the head

Younger ptslesion mainly on dorsum

of hand,forearm,chest

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CA. Skin & Lips

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Contr ibut ing factors

Immunosuppressed state

Exposure to sunlight

Disagreement about papilloma virus

HLA:A11-protect /B27,DR7-high risk!

No relation to any immunosupp agents

Treatment

Surgical excision

Retinoids,topicalRx solar keratosis,risk of CA

Retinoids,systemicincidence in small group

Lymphoma &

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Lymphoma &lymphoproliferations

PTLD:Post-Transplant Lymphoproliferative Disorder

Benign hyperplasia.. to ..malignant lymphoma

86%B cell in origin

Classification of PTLDMicroscopic features Pathologic category

Hyperplasia Infectious mononucleosis

Plasma cell hyperplasiaNeoplasia Polymorphic PTLD

Lymphomatous (monomorphic)PTLDOther..myelomab-celllymphoma with HD like

Lymphoma &

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lymphoproliferations Predispos ing factors

Intense immunosuppression

Non renal allograft recipients > renal

recipients

EBV infection

90-95% of PTLDpositive for EBV

Risk factorSeropositive at time of Tx

Lymphoma &

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lymphoproliferationsClinical man ifestat ion

Asymptomatic

Mononucleosis-like Fever,night sweat,URI,weight loss,diarrhea,

abdominal pain,lymphadenopathy,tonsillitis

Intestinal perforation,GI bleeding,obstruction

Lung lesions,renal mass

Imitating allograft rejection

Lymphoma &f

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lymphoproliferationsTreatment

Localized diseaseexcision,radiation

Extensive diseasestop all imm

supp,minimal prednisoloneAcyclovir,ganciclovir,IFN-alpha

ChemoRx,anti-B cell monoclonalAb,

anti-EBV cytotoxic T cell,anti CD22immunotoxin,etc.

Lymphoma &l h lif ti

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lymphoproliferationsPrevent ion

Avoidance of over immunosuppression..

dose, multiple agents,prolonged,repeated

course of ALA Preemptive antiviral Rx during ALA

Recurrence

< 5% of cases

Retransplant should be delayed more than

1 year after complete remission

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Kaposis SarcomaHHV-8 (KS asso.herpesvirus)was

isolated

Mainly in renal allograft recipientsAverage age 43 yrs (4.5-67 yrs)

Male:Female3:1

Average time 21 months after TxMajority of ptsHIV-negative

Kaposis Sarcoma

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p

Non-visceral(60%)

Skin,conjunctiva,oropharynx

Visceral(40%)

GI.,lung,lymph nodes

98% of pt non-visceral had skin lesions 38% remiss ionafter reduction or cessation

of immunosuppressive drugs

Non-visceral

remission> visceral dz.Mortal i ty

57% of visceral dz (72% from KS per se)

23% of non-visceral KS (infection,rejection)

Renal carcinoma

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24% was discovered incidentally

Related to the underlying kidney dz

Most cancer developed in owndiseased kidney

10% in renal allograftAverage time 75 months after Tx

Predisposing causes

Analgesic nephropathyMostly transitional cell CA

Acquired cystic dzIncreased 30-40 folds over general pop.

Other cancers

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CA cervix

10% women with postTx CA

In situ lesion70% of case

Incidence 14-16 fold

Regular PV & Cx smear

Anogeni tal CA Female > male

Invasive dz in younger

Hepatob i l iary CA

73%hepatoma

Preceding Hx of HBV infection

Increased number of hepatoma related tochronic hepatitis C

Preexisting malignancy

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g g y

Overall recurrence rate 22%,27% with Rx

before and after Tx

Recommendat ion

No wait ing period fo r Tx in low -r isk

tumorIncidental renal CA,CIS,BCC,low grade CA

bladder

Tx delayed > 2 yrs in high r isk o f

recurrenceMalignant melanoma,CA.breast,CA.colon

Tx delayed 2 yrs w ith mos t othertumors

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Thank you&

Happy Valentines Day