Medical Complications of Renal Transplantation

Thitisak Kitthaweesin,MD.

Main topics
Infectious

complications Cardiovascular complications Lipid abnormalities after KT Post transplant DM Parathyroid and mineral metabolism Post transplant erythrocytosis Malignancies associated with Tx

Infectious complications
General

principles of transplant infectious disease Diagnosis of infection Management of infection in transplant recipient Infection of particular importance in transplant recipient

General principles
Microorganism

causing infection in transplant recipient

True pathogens
Influenza,typhoid,cholera,bubonic

plague

Sometime pathogens
S.aureus,normal

gut flora

Nonpathogens
Aspergillus

fumigatus,cryptococcus neoformans HHV-8

General principles
Risk

of infection in transplant recipient is determined by 3 factors

Epidemiologic exposure The net state of immunosuppression The preventative antimicrobial strategies

Timetable

for posttransplant infections The first rule of transplant infectious disease is that infection is far better prevented than treated

Epidemiologic exposure
Exposures

within the community

M.tuberculosis Geographically restricted systemic mycoses

Blastomyces , Histoplasma capsulatum, Coccioides immitis

Strongyloides stercoralis Community-acquired respiratory dis.

Influenza, Parainfluenza,RSV,Adenovirus

Infections acquired through ingestion of contaminated food/water Listeria, Salmonella sp. Community-acquired opportunistic infection
Crypto.neoformans,Aspergillus,Nocardia,PCP.

Viral infections
VZV,HIV,HBV,HCV.

Exposures

within the hospital

Epidemiologic exposure
Exposures

within the community Exposures 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

The net state of immunosuppression

Dose,duration,and temporal sequence of immunosuppressive drugs Host defense defects caused by underlying diseases Presence of neutropenia,defect in mucocutaneous barrier or indwelling of FB. Metabolic derangements

PCM,uremia,hyperglycemia

Infection with immunomodulating viruses:

CMV,EBV,HBV,HCV,HIV

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,vascular access,drain related Key factors:nature of operation and technical skill

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

Timetable for posttransplant infection

Infection more than 6 months posttransplant

The >80% of patients with good result (good
allograft 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 allograft

function,excessive immunosuppression,chronic viral infection) PCP,Cryptococcus,Listeria monocytogenes,Aspergillus

Usual sequence of infection posttransplant

Diagnosis of infection

Radiological diagnosis
CT.chest and brain for early diagnosis and treatment

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

Principle of Antimicrobial Therapy

Strategies for antimicrobial therapy

There are three different modes of use Therapeutic mode

Curative treatment for established infection
Prophylactic

mode

Prescribed to entire patients before an event to prevent a form of infection that is important to justify ie. intervention
Preemptive

mode

Prescribed to subgroup of patients that high risk for clinical significant disease

Strategies for antimicrobial therapy

Prophylactic

strategies

Low-dose TMP/SMX
Effective against Pneumocystis,Nocardia,Listeria,urosepsis and perhap,Toxoplasma

Perioperative surgical prophylaxis

Protects against wound infection

Oral gancyclovir,valacyclovir
Effective against CMV disease

Strategies for antimicrobial therapy

Preemptive strategies Appropriate antibacterial or antifungal therapy in ass.with surgical manipulation of an infected sites protect against syst.disseminated Fluconazole therapy of candiduria .. protect against
obstructing fungal balls and ascending infection

Intravenous followed by oral ganciclovir in CMV seropositive patient treated with ALG protect
against symptomatic CMV disease

Monitoring bloood for CMV by antigenemia or PCR,with preemptive ganciclovir therapy once a threshold level of viral reachedprotect against
symptomatic CMV disease

Infection of particular importance in transplant recipients

Cytomegalovirus
CMV

..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

 CMV

disease

Requires clinical signs &symptoms ie. severe leukopenia or organ involvement (hepatitis,pneumonitis,colitis, pancreatitis,menigoencephalitis and rarely myocarditis) Rare feature is progressive chorioretinitis

The manifestation of CMV in transplant recipients

Direct manifestations
Mononucleosis Leukopenia/thrombocytopenia Tissue invasive dz.

Indirect manifestation
Depression of host disease Allergy injury & rejection Increase the risk of PTLD 7-10 fold

Risk of clinical CMV disease is determined by 2 factor

Serological

status of donor and

recipient Nature of the immunosuppressive therapy

Role of CMV infection in transplant recipient

Prophylactic therapy

Gancicovir = propylactic therapy of choice

IV Oral IV followed by oral

Antiviral therapy
Significant decrease CMV disease and infection Both antiviral agent asso.with a decrease in disease Only ganciclovir decrease the risk of infection

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

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

Reactivation

of latent CMV infection CMV infection/disease 20% Pneumonitis is rare Antiviral propylaxis recommended for pt. who receive immunosuppression with ALA (grade A) or conventional imm.supp. (grade C)

CMV-positive donor CMV-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)

CMV-negative donor CMV-negative recipient

(D-/R-)
Low

prevalence of disease No antiviral prophylaxis therapy was recommended

Treatment
Varied

with severity of dz. Mononucleosis-like syndrome

Resolve without antiviral drug Stop OKT3, AZA & stop if Wbc<4000
Organ Usual

involvement
dose 5 mg/kg Q 12 hr.

2-3 wks. Ganciclovir, +/- hyperimmune globulin

EBV
Possible

clinical consequens of EBV replication

Mononucleosis syndrome Meningoencephalitis Oral hairy leukoplakia Malignanciessmooth m.tumor,T-cell lymphoma,PTLD

Active

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

EBV
Critical

effectits role in pathogenesis of that increase risks of PTLD

PTLD usually B cell (benign polyclonal to malignant monoclonal lymphoma)

Factors

High viral load Primary EBV infection High dose immunosuppressionALA, High dose CsA&Tacrolimus, Pulse steroids or in combination Type of organ Tx CMV infection

EBV
EBV

infection
susceptible to antiviral Rx to antiviral Rx

Latent form (great majority)

Not

Replicative form
Susceptible

Antiviral therapy alone unlikely to be effective

Other viral infections

VZV.

Primary infection with VZV in Tx pt can be severe candidatesscreened for AB+Rx with zoster Ig Reactivation dzrelatively benign typical zoster involve few dermatome in 20-30% pt. , antiviral Rx not always needed

 HSV

Occur in 50% of pt. Lesions usually ulcerative > vesicular Recurs more often & acyclovir often beneficial Dual infection with HSV + CMV can be RX with ganciclovir alone
HIV

Tx of organ from HIV-infection donortransmit virus 100%

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

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 during

Sx Anatomic abnormalities of native or TX kidneys Neurogenic bladder Rejection and immunosuppression

 Pathogenssimilar to general population

E.coli

, Enterococci , P.aeruginosa , C.urealyticum

UTI in first few months after Tx frequently asso. with pyelonephritis or sepsis ,may be asso. with allograft dysfunction and may predispose to develop acute rejection

 Recommendation
low-dose

TMP/SMX minimum 4 month (most centers prophylasis for 1 year) provides prophylaxis against P.carinii,Nocardia asteroides and L.monocytogenes

Pt.with Hx allergy to TMP/SMXoral quinolones

Opportunistic bacterial infections

Three

important opportunistic bacterial infection in first year post Tx

L.monocytogenes N.asteroides M.tuberculosis

Fungal infection

Disseminated infection
Primary infection/reactivation Dimorrphic fungi (histoplasmosis,blastomycosis,coccidioidomycosis) cause asymptomatic or limited infection in normal host

Invasive infection
Candida sp.,P.carnii,Aspergillus sp. C.neoformans, Mucor sp.

 Candida

Mucocutaneous overgrowth can be prevented by Rx of high risk pt. with nystation oral wash Candiduria should be treated with fluconazole or low-dose IV. Ampho.B with/without flucytosine Dissemination dzAmpho-B or fluconazole Life-threatening infectionAmpho-B probably more effective Liposomal Ampho-Bless nephrotoxic,similar efficacy

Cardiovascular complication of Transplantation

Cardiovascular complication of Transplantation

Cardiovascular dz is very common Incidence new IHD events11.1% (among pt without Hx IHD) during 46+ 36 mo. F/U Celebrovascular Dz 6.0% (among pt without 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

Pretransplant

CVD

Pre Tx CVD is an important risk factor for post Tx CVD IHD often asymptomatic in ESRD patients Asymptomatic CAD pt who underwent revascularization had sig. fewer IHD event after Tx High risk pt would benefit from screening &Rx asymptomatic IHD as part of preTx evaluation Recommendationhigh risk pt should undergo a cardiac stress test (Dobutamine stress echo/Radionuclude stress test)

HT after renal Tx
Major

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

Pathogenesis
Acute allograft rejection Chronic allograft rejection Cadaveric allografts esp. from a donor with FHx of HT High renin state from diseased native kidney Immunosuppressive therapy such as Cyclosporine,Tacrolimus and corticosteroid Increase BW Hypercalcemia New onset essential HT

#Suggestive evidences: transplant kidney may have prohypertensive or antihypertensive properties #Experimental models of genetic HT the inherited tendency to HT resides primary in the kidney #Study of 85 pts: BP+antiHT requirement occur more frequently in recipient from normotensive family received a kidney from donor with HT family

Role

of corticosteroid

Usually not a major risk factor for chronic HT in Tx recipients because of rapid dose reduction

 Role

of cyclosporine

Vasoconstrictive effect HT volume dependent > renin dependent Increased systemic and renal vascular resist. (primary affecting afferent arteriole) Increase vascular resistance.inadequate relaxation>active vasoconstriction Release of vasoconstrictor endothelin Endothelial injury leading to generation of NO. Sympathetic activationadditional factor Mild hypo Mg,affected intracellular Ca-binding proteinincrease vascular tone

RAS
Functional

significant stenosis occur in 12% of recipients with HT Correctable form of HT Renal arteriographyprocedure of choice for Dx RAS in solitary Tx kidney Renal allograft Bx prior to angiography to R/O chronic rejection or other renal parenchymal dz

Treatment
Patient

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 HT patient should undergo renal arteriography to exclude RAS

Lipid abnormalities after renal Tx

Prevalence 16-78% of recipients Reported change in serum lipid:elevation in both cholesterol and triglyceride Elevated LDL and apo-B level are common Low HDL reported in some studies Hypercholesterolemia occurs within 6 months Hypertriglyceridemia.. peak incidence at 12 mo and correlated with excessive BW, elevated Scr

Lipid abnormalities after renal Tx

Post

Tx lipoprotein abnormalities may contribute to the development of CVD and PVD Expected correlation between high lipid level and cardiovascular mortality Increased serum triglyceride implicated as predictor of chronic renal allograft failure

Contributing factors
High steroid dose CsA / FK506 DM. Nephrotic syndrome

Excessive wt.gain High fat diets Use of diuretic, beta-blockers Genetic susceptibility

Pathogenesis
Multifactorial

Correlate

with corticosteroid dose & cyclosporine Steroid withdrawal association 17% decreased in total chol. Level Pt. With CsA ...chol 30-36 mg/dl > pt. with AZA + pred.

Corticosteroid
Peripheral

insulin resistance Hyperinsulinemia Hepatic VLDL synthesis ACTH release

Administration of ACTH 3 weeks TC,LDL,TG & HDL ACTH may act by upregulate LDL receptor activity Steroid may be not benefit to lipid metabolism in pt with CsA

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 to hypercholesterol

Tacrolimus
Similar

to but less pronounced than CsA

levellower in

LDL,Lp(a),fibrinogen

FK506 may be asso.with lower serum TC

substitution

of tacrolimus for CsA may improved lipid profile

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

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

Low-dose

therapy with statin

considered in
stable patient 8 months 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

Benefits of HMG CoA reductase inhibitor

Lower Lower

risk of rejection

Katznelson et al.Transplantation,1996

incidence of chronic rejection Improved graft survival

Kobashigawa et al.N Engl J Med,1995

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

 Glucocorticoid

..impair both hepatic & extrahepatic action of insulin

post receptor insulin resistance impaired phase1,2 and glucagon mediated insulin secretion

Cyclosporine..interfere

with glucose

metabolism
accum in panc islet cell..insulin secretion
FK506..glucose

intolerance more often

unclear mechanism..dampen insulin secretion ( Filler et al.NDT2000 )

Risk factors for PTDM

Obesity black age

> 40 years first-degree relative with DM HLA A28,A30,BW42 CDKT Steroid / FK506

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

Prevention/Management
Patient education dietary management exercise insulin oral hypoglycemic agents

Screen for and treat microalbuminuria and hyperglycemia regular ophthalmologic and podiatry exam

Go to.. Medical complication of Renal transplantation Part II

Parathyroid and Mineral metabolism after Renal Transplant

Successful KT
Normalize

urinaryP,beta-2 microglobulin

excretion Normalize 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 amyloid osteodystrophy

Primary abnormalities that can persist after KT

HyperPTH Aluminum

and beta2-microglobulin accumulation Adynamic bone disease Osteopenia Osteonecrosis

HPTH and Hypercalcemia

1

in 3 of pt have persistent PTH hypersecretion development of hyperCa related to duration of dialysis and parathyroid gland size, secondary to hyperplasia of gland > hypersecretion of cells other factors
resorption of soft tissue Ca-P deposits

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 and Hypercalcemia

Plasma

Ca begin to rise in first 10 days after Tx and can be delayed for 6 months or more patients with preexisting severe secondary HPTHacute severe hypercalcemia after KT, can cause acute allograft dysfunction and rarely calciphylaxis

Treatment
HPTHgenerally asymptomatic Hypercalcemiausually resolves spontaneous over 6 months to as long as 2-3 years Conservative Rx with oral P supplement until plasma PTH low enough to normalize Ca/P balance
Persistent

Parathyroidectomy
Severe

symptomatic hyperCa hyperCa

usually in early period

Persistent

4-10 % after 1 year

Elective

parathyroidectomy

if plasma Ca > 12.5 mg/dL more than 1 year esp. if asso.with radiologic evidences of increased bone resorption

Aluminum toxicity
KT

quickly reverses factors leading to Aluminum accumulation more effective than desferoxamine therapy in lower serum and bone Al level

Hypophosphatemia
Persistent

hypo P 20-35 % Induced by P wasting in urine due to HPTH and PTH independent pathway Treatment
phosphate supplement except in patients with persistent HPTH phosphate can exacerbate HPTH by complex with Ca and lowering GI calcium absorption

Dialysis-related Amyloidosis
Primarily

induced by beta2microglobulin deposits Articular symptoms asso.with disorder rapidly improve after KT new cystic lesions unusual resolution of existing cystsrare

Post-transplant Bone disease

Osteopenia
Osteonecrosis Contributing

factors

persisting uremia-induced abnormal calcium homeostasis acquired defects in mineral metabolism induced by immunosuppressive Rx

Osteopenia
Higher

risk for pathologic Fx Prevalence of atraumatic Fx in KT may be as high as 22 % Primary site: High cancellous bone vertebrae and ribs Bone loss occurs early and rapidly postKT1.6 % per month in first 5 mo After early periodbone loss continue at slower rate1.7 % per year

Pathogenesis
postTx

bone loss inv.both HPTH and effect of imm supp drugs GCs-induced suppression of bone formation most important factor steroids
direct toxic to osteoblast increase osteoclast activity Promote Ca loss by decrease GI absorption,gonadal hormone, IGF-1production and sensitivity to PTH

Monitor
BMD.of

hip&spine prior to Tx and 3 mo following KT using DEXA Rapid bone loss and/or low initial BMD should be considered to Rx No information regarding the effects of Rx to prevent bone loss in KT patients

Treatment
Lowest

dose of prednisolone compatible with graft survival Calcium supplementation 1000 mg/day Vit.D analog can improve Ca absorption Calcitonin or bisphosphonateif bone loss is severe and/or rapid esp. during first 6 months after Tx

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

Osteonecrosis
Direct

asociated with glucocorticoid exposure cyclosporine number of tx HPTH low bone mass fracture

Pathogenesis
GCs

increase intramarrow pressure increase adipocyte hyperplasia fat embolism microfracture compromised vascular supply

Diagnosis
Painpredominant symptom Higher risk of Fx Arthritis.secondary to joint deformation Change in density of necrotic bone

10-14 days

Radiolucent band
6-8 weeks

MRImost sensitive

Treatment
No

effective medical Rx

reduction of steroid dose has little effect once osteonecrosis developed

Surgical

Rx

vascularized bone grafts and core decompression

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,Hs completely relieve symptom

Erythrocytosis following KT
PostTx

erythrocytosis (PTE) Hct > 51% on two or more consecutive determination (Gasten et al.1994) affect 10-15 % of KT patients most often within the first 2 years

Etiology and pathogenesis

Early

case reported ..PTE caused by renal ischemia from RAS Risk factors
smoking DM. Rejection-free course not RAS
EPO

factorexcess EPO release from native kidney

Etiology and pathogenesis

Non-EPO

factors

enhance sensitivity to EPO directly promote erythrocytosis IGF-1,IGF-BP,GH..enhance.erythrocytosis

Angiotensin

II

ACEI,ATRAinhibit erythrocytosis activation of AIIreceptor

may

enhance EPO production in the graft or increased Rbc precursor sensitivity to EPO

Treatment
ACE

inhibitor

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
AT1receptor

antagonists

Losartan 50 mg/day decrease Hct 53 to 48% in 8 wks

Theophylline

8 weeks course,decrease Hct from 58 to 46%,as much as 10-15% Act as adenosine antagonist facilitate release and BM.response to EPO

Recommendation
ACEI

and ATRA Losartan 50 mg/day may be increased to 100 mg/day, if no response within 4 weeks or BP remain elevated If no adequate lowering of Hct after another 4 weeks,enalapril 10-20 mg/day or another ACEI continue Rx for PTE indefinitely

Malignancies associated with Transplantation

Malignancies associated with Transplantation

Cincinnati Transplant Tumor Registry(CTTR) Average age 41 years,average time of appearance 5 years after Tx Most striking malignancies

CA.skin&lip,PTLD,Kaposis sarcoma,Renal CA CA.uterine cervix,anogenital CA,Hepatobiliary CA and Sarcoma

No increase in the incidences of common tumor in general population

CA.lung,breast,prostate,colon

CA. Skin & Lips

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
Skin

CA. Skin & Lips

General populationBCC > SCC Renal TxSCC > BCC SCC

old age in general population 30 years younger in Tx pts.

Aggressive SCC
Heavy sun exposed area Older individual Multiple lesions Located on the hand Histo:thick tumor involve subcutaneous tissues

CA. Skin & Lips

Contributing

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,topical

Rx

solar keratosis,risk of CA in small group

Retinoids,systemic
incidence

Lymphoma & lymphoproliferations

PTLD:Post-Transplant Lymphoproliferative Disorder

Benign hyperplasia.. to ..malignant lymphoma 86%B cell in origin Classification of PTLD

Microscopic features Hyperplasia Neoplasia Pathologic category Infectious mononucleosis Plasma cell hyperplasia Polymorphic PTLD Lymphomatous (monomorphic) PTLD Other..myeloma b-celllymphoma with HD like

Lymphoma & lymphoproliferations

Predisposing factors Intense immunosuppression Non renal allograft recipients > renal recipients EBV infection 90-95% of PTLDpositive for EBV Risk factorSeropositive at time of Tx

Lymphoma & lymphoproliferations

Clinical

manifestation

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 & lymphoproliferations

Treatment

Localized diseaseexcision,radiation Extensive diseasestop all imm supp,minimal prednisolone Acyclovir,ganciclovir,IFN-alpha ChemoRx,anti-B cell monoclonalAb, anti-EBV cytotoxic T cell,anti CD22 immunotoxin,etc.

Lymphoma & lymphoproliferations

Prevention

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

Kaposis Sarcoma
HHV-8

(KS asso.herpesvirus)was isolated Mainly in renal allograft recipients Average age 43 yrs (4.5-67 yrs) Male:Female3:1 Average time 21 months after Tx Majority of ptsHIV-negative

Kaposis Sarcoma

Non-visceral (60%)
Skin,conjunctiva,oropharynx

Visceral (40%)
GI.,lung,lymph nodes

98% of pt non-visceral had skin lesions 38% remission after reduction or cessation of immunosuppressive drugs Non-visceralremission> visceral dz. Mortality

57% of visceral dz (72% from KS per se) 23% of non-visceral KS (infection,rejection)

Renal carcinoma
24%

was discovered incidentally Related to the underlying kidney dz Most cancer developed in own diseased kidney 10% in renal allograft Average time 75 months after Tx Predisposing causes
Analgesic nephropathy
Mostly

transitional cell CA 30-40 folds over general pop.

Acquired cystic dz
Increased

Other cancers

CA cervix
10% women with postTx CA In situ lesion70% of case Incidence 14-16 fold Regular PV & Cx smear

Anogenital CA
Female > male Invasive dz in younger

Hepatobiliary CA
73%hepatoma Preceding Hx of HBV infection Increased number of hepatoma related to chronic hepatitis C

Preexisting malignancy

Overall recurrence rate 22%,27% with Rx before and after Tx No waiting period for Tx in low-risk tumor
Incidental

Recommendation

renal CA,CIS,BCC,low grade CA

bladder

Tx delayed > 2 yrs in high risk of recurrence

Malignant

melanoma,CA.breast,CA.colon

Tx delayed 2 yrs with most other tumors

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