Medical Medical Complications of Complications of

Renal Renal TransplantationTransplantation

Thitisak Kitthaweesin,MD.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 exposureEpidemiologic 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 exposureEpidemiologic 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 The net state of immunosuppressionimmunosuppression

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 Timetable for posttransplant infectioninfection

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 Timetable for posttransplant infectioninfection

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 Timetable for posttransplant infectioninfection

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 Strategies for antimicrobial therapyantimicrobial therapy

There are three different modes of useTherapeutic 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 Strategies for antimicrobial therapyantimicrobial 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 Strategies for antimicrobial therapyantimicrobial 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 reached…protect 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 diseaseis 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 donorCMV-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% Conventional…grade B Immunosuppression with ALA…grade A

– Ganciclovir 1000 mg TID orally5 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 involvement– 2-3 wks. Ganciclovir, +/- hyperimmune globulin

Usual dose 5 mg/kg Q 12 hr.

EBV Possible clinical consequens of EBV

replication– Mononucleosis syndrome – Meningoencephalitis– Oral hairy leukoplakia– Malignancies…smooth m.tumor,T-cell

lymphoma,PTLD Active replication …

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

EBV Critical effect…its role in pathogenesis of

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

Factors that increase risks of PTLD – High viral load – Primary EBV infection – High dose immunosuppression…ALA,

High dose CsA&Tacrolimus, Pulse steroids or in combination

– Type of organ Tx – CMV infection

EBV

EBV infection – Latent form (great majority)

Not susceptible to antiviral Rx

– Replicative form Susceptible to antiviral Rx

– Antiviral therapy alone unlikely to be effective

Other viral infections VZV.

– Primary infection with VZV in Tx pt can be severe candidates…screened for AB+Rx with zoster Ig

– Reactivation dz…relatively 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 donor…

transmit virus 100%

HHV-6– Found in blood 30-50% of pt.– Often asso.with CMV viremia– Clinical effects…mononucleosis , allograft

dysfunction,prolonged hospital length of stay,inv.pneumonia,encephalitis

– Combined infection with HHV-6 & CMV…more severe

– Ganciclovir susceptible

HHV-8– Putative agent of Kaposi’s 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

– Pathogens…similar 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

–RecommendationRecommendation…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/SMX…oral 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 dz…Ampho-B or fluconazole

– Life-threatening infection…Ampho-B probably more effective

– Liposomal Ampho-B…less nephrotoxic,similar efficacy

Cardiovascular complication of Transplantation

Cardiovascular complication of Transplantation

– Cardiovascular dz is very common Incidence new IHD events…11.1% (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 yrsCVA 15% in 15 yrsPVD 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

– RecommendationRecommendation…high 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 activation…additional factor– Mild hypo Mg,affected intracellular Ca-binding

protein…increase vascular tone

RAS Functional significant stenosis occur in

12% of recipients with HT Correctable form of HT Renal arteriography…procedure 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 HT…start CCB,diuretic– Prevention…fish oil 4 gm/day

Patient without CsA– Start anti-HT…CCB ,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 factorsContributing factors

High steroid dose CsA / FK506 DM. Nephrotic

syndrome

Excessive wt.gain High fat diets Use of diuretic,

beta-blockers Genetic

susceptibility

PathogenesisPathogenesis

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 LDL,Lp(a),fibrinogen level…lower in FK

506 may be asso.with lower serum TC substitution of tacrolimus for CsA may i

mproved lipid profile

TreatmentTreatment

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 risk of rejection– Katznelson et al.Transplantation,1996

Lower 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

Incidence…not related to renal dz,number of rejection or graft function

peak onset…during the first year(2-3moths)

majority…asymptomatic,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 HypercalcemiaHPTH 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 albumintotal plasma Ca via bindingno 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 HPTH…acute severe hypercalcemia after KT, can cause acute allograft dysfunction and rarely calciphylaxis

Treatment Treatment

Persistent HPTH…generally asymptomatic

Hypercalcemia…usually 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

ParathyroidectomyParathyroidectomy

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 radiologic evidences of increased bone resorption

Aluminum toxicityAluminum toxicity KT quickly reverses factors leading to

Aluminum accumulation more effective than desferoxamine

therapy in lower serum and bone Al level

Hypophosphatemia 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 Dialysis-related AmyloidosisAmyloidosis

Primarily induced by beta2-microglobulin deposits

Articular symptoms asso.with disorder rapidly improve after KT

new cystic lesions …unusual resolution of existing cysts…rare

Post-transplant Bone Post-transplant Bone diseasedisease

Osteopenia Osteonecrosis Contributing factors

– persisting uremia-induced abnormal calcium homeostasis

– acquired defects in mineral metabolism induced by immunosuppressive Rx

OsteopeniaOsteopenia

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

postKT…1.6 % per month in first 5 mo After early period…bone loss continue

at slower rate…1.7 % per year

PathogenesisPathogenesis 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

MonitorMonitor

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

TreatmentTreatment

Lowest dose of prednisolone compatible with graft survival

Calcium supplementation 1000 mg/day Vit.D analog can improve Ca

absorption Calcitonin or bisphosphonate…if bone

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

OsteonecrosisOsteonecrosis

Non-infectious death of marrow cell and asso.trabeculae,osteocytes

Weight bearing long bone…most often affected esp. Femoral head

Usually multifocal may develop at any time after Tx

Incidence…15 % within 3 years

OsteonecrosisOsteonecrosis

Direct asociated with…

– glucocorticoid exposure

– cyclosporine

– number of tx

– HPTH

– low bone mass

– fracture

PathogenesisPathogenesis

GCs

– increase intramarrow pressure

– increase adipocyte hyperplasia

– fat embolism

– microfracture

– compromised vascular supply

DiagnosisDiagnosis Pain…predominant symptom Higher risk of Fx Arthritis….secondary to joint deformation Change in density of necrotic bone

– 10-14 days Radiolucent band

– 6-8 weeks MRI…most sensitive

TreatmentTreatment

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 pathogenesisEtiology and pathogenesis

Early case reported ..PTE caused by renal ischemia from RAS

Risk factors– smoking– DM.– Rejection-free course– not RAS

EPO factor…excess EPO release from native kidney

Etiology and pathogenesisEtiology and pathogenesis Non-EPO factors

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

Angiotensin II– ACEI,ATRA…inhibit erythrocytosis– activation of AIIreceptor

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

TreatmentTreatment

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 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

RecommendationRecommendation 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,Kaposi’s 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

Skin cancer…most common,38% Incidence increased with length of F/U Appeared on sun-exposed area

(light skin,blue eyes,blond hair) Pt age >40 yrs…lesion occurred on

the head Younger pts…lesion mainly on dorsum

of hand,forearm,chest

CA. Skin & Lips General population…BCC > SCC Renal Tx…SCC > 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

– Retinoids,systemic incidence in small group

Lymphoma & lymphoproliferations

PTLD:Post-Transplant Lymphoproliferative Disorder

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

Microscopic features Pathologic category

Hyperplasia Infectious mononucleosis Plasma cell hyperplasia

Neoplasia 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 infection90-95% of PTLD…positive for EBVRisk factor…Seropositive 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 disease…excision,radiation– Extensive disease…stop 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

Kaposi’s Sarcoma HHV-8 (KS asso.herpesvirus)was

isolated Mainly in renal allograft recipients Average age 43 yrs (4.5-67 yrs) Male:Female…3:1 Average time 21 months after Tx Majority of pts…HIV-negative

Kaposi’s 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-visceral…remission> 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

– Acquired cystic dz Increased 30-40 folds over general pop.

Other cancers CA cervix

– 10% women with postTx CA– In situ lesion…70% 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 RecommendationRecommendation

– No waiting period for Tx in low-risk tumor

Incidental 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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