Transcript Document 7290358

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 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 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%
Conventional…grade B
Immunosuppression with ALA…grade 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 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
–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/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 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
– Recommendation…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 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
LDL,Lp(a),fibrinogen level…lower in
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 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
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 HPTH…acute severe
hypercalcemia after KT, can cause
acute allograft dysfunction and rarely
calciphylaxis

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

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 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 cysts…rare

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
postKT…1.6 % per month in first 5 mo
 After early period…bone loss continue
at slower rate…1.7 % 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 bisphosphonate…if 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 bone…most often
affected esp. Femoral head
 Usually multifocal may develop at any
time after Tx
 Incidence…15 % 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




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
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 factor…excess 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,ATRA…inhibit 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,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
Polymorphic PTLD
Lymphomatous (monomorphic)
PTLD
Other..myeloma
b-celllymphoma with HD like
Neoplasia
Lymphoma &
lymphoproliferations

Predisposing factors
– Intense immunosuppression
 Non renal allograft recipients > renal
recipients
– EBV infection
 90-95% of PTLD…positive for EBV
 Risk 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

Recommendation
– 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
Thank you
&
Happy Valentine’s Day