1. Medical Complications of Renal Transplantation
Thitisak Kitthaweesin,MD.

2. Main topics Infectious complications Cardiovascular complications
Lipid abnormalities after KT
Post transplant DM
Parathyroid and mineral metabolism
Post transplant erythrocytosis
Malignancies associated with Tx

3. Infectious complications
General principles of transplant infectious disease
Diagnosis of infection
Management of infection in transplant recipient
Infection of particular importance in transplant recipient

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. Usual sequence of infection posttransplant

13. 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

14. Principle of Antimicrobial Therapy

15. 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

16. 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

17. 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

18. Infection of particular importance in transplant recipients

19. 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

20. 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

21. 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 fold

22. Risk of clinical CMV disease is determined by 2 factor
Serological status of donor and recipient
Nature of the immunosuppressive therapy

23. Role of CMV infection in transplant recipient

24. Prophylactic therapy Gancicovir = propylactic therapy of choiceIV
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

25. 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

26. CMV-positive recipient (D-/R+)
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)

27. 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)

28. CMV-negative donor CMV-negative recipient (D-/R-)
Low prevalence of disease
No antiviral prophylaxis therapy was recommended

29. 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.

30. EBV Possible clinical consequens of EBV replication
Mononucleosis syndrome
Meningoencephalitis
Oral hairy leukoplakia
Malignancies…smooth m.tumor,T-cell lymphoma,PTLD
Active replication … % …of pt.+conventional Rx >80% …of pt.+ALA

31. 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

32. EBV EBV infection Latent form (great majority) Replicative form
Not susceptible to antiviral Rx
Replicative form
Susceptible to antiviral Rx
Antiviral therapy alone unlikely to be effective

33. 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

34. HSV HIV 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%

35. HHV-6 HHV-8 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

36. 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

37. 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

38. 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

39. Opportunistic bacterial infections
Three important opportunistic bacterial infection in first year post Tx
L.monocytogenes
N.asteroides
M.tuberculosis

40. Fungal infection Disseminated infection Invasive 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.

41. 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

42. Cardiovascular complication of Transplantation

43. Cardiovascular complication of Transplantation
Cardiovascular dz is very common Incidence new IHD events…11.1% (among pt without Hx IHD) during 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

44. 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)

45. 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

46. 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

47. #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

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

49. 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

50. 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

51. Treatment Patient with CsA Patient without 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

52. 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

53. 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

54. Contributing factors Excessive wt.gain High steroid dose
High fat diets
Use of diuretic, beta-blockers
Genetic susceptibility
High steroid dose
CsA / FK506
DM.
Nephrotic syndrome

55. Pathogenesis Multifactorial
Correlate with corticosteroid dose & cyclosporine
Steroid withdrawal association 17% decreased in total chol. Level
Pt. With CsA ...chol mg/dl > pt. with AZA + pred.

56. 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

57. 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

58. 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

59. 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

60. 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

61. 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 mg/dL

62. 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

63. Post-transplant DM Incidence Etiology and Pathogenesis
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

64. 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 )

65. Risk factors for PTDM Obesity black age > 40 years
first-degree relative with DM
HLA A28,A30,BW42
CDKT
Steroid / FK506

66. 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

67. Prevention/Management
Patient education
dietary management
exercise
insulin
oral hypoglycemic agents
Screen for and treat microalbuminuria and hyperglycemia
regular ophthalmologic and podiatry exam

68. Go to.. Medical complication of Renal transplantation Part II

69. Parathyroid and Mineral metabolism after Renal Transplant

70. 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

71. Primary abnormalities that can persist after KT
HyperPTH
Aluminum and beta2-microglobulin accumulation
Adynamic bone disease
Osteopenia
Osteonecrosis

72. 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

73. 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

74. 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

75. 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

76. Parathyroidectomy Severe symptomatic hyperCa Persistent 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

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

78. 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

79. Dialysis-related Amyloidosis
Primarily induced by beta2-microglobulin deposits
Articular symptoms asso.with disorder rapidly improve after KT
new cystic lesions …unusual
resolution of existing cysts…rare

80. Post-transplant Bone disease
Osteopenia
Osteonecrosis
Contributing factors
persisting uremia-induced abnormal calcium homeostasis
acquired defects in mineral metabolism induced by immunosuppressive Rx

81. 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

82. 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

83. 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

84. 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

85. 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

86. Osteonecrosis Direct asociated with… glucocorticoid exposure
cyclosporine
number of tx
HPTH
low bone mass
fracture

87. Pathogenesis GCs increase intramarrow pressure
increase adipocyte hyperplasia
fat embolism
microfracture
compromised vascular supply

88. 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

89. Treatment No effective medical Rx Surgical Rx
reduction of steroid dose has little effect once osteonecrosis developed
Surgical Rx
vascularized bone grafts and core decompression

90. Bone Pain Occur only in patients received CsA
often temporally related to higher level
Mechanism
intraosseous vasoconstriction and HT
Treatment
CCB..nifedipine SR mg,Hs …completely relieve symptom

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

92. 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

93. 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

94. 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)

95. Treatment AT1receptor antagonists Theophylline 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

96. 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 mg/day or another ACEI continue Rx for PTE indefinitely

97. Malignancies associated with Transplantation

98. 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

99. 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

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

101. CA. Skin & Lips Contributing factors Treatment 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

102. Lymphoma & lymphoproliferations
PTLD:Post-Transplant Lymphoproliferative Disorder
Benign hyperplasia.. to ..malignant lymphoma
86%…B cell in origin
Classification of PTLD

103. 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

104. 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

105. 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.

106. 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

107. Kaposi’s Sarcoma HHV-8 (KS asso.herpesvirus)was isolated
Mainly in renal allograft recipients
Average age 43 yrs ( yrs)
Male:Female…3:1
Average time 21 months after Tx
Majority of pts…HIV-negative

108. Kaposi’s Sarcoma Non-visceral (60%) Visceral (40%)
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)

109. 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 folds over general pop.

110. Other cancers CA cervix Anogenital CA Hepatobiliary CA
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

111. 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

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