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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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