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Medical Complications of Renal Transplantation Thitisak Kitthaweesin,MD.

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Presentation on theme: "Medical Complications of Renal Transplantation Thitisak Kitthaweesin,MD."— Presentation transcript:

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 7-10 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 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

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 –Ganciclovir1000 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-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 … 20-30% … 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) 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 –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 –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 –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 –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 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 IHD23% in 15 yrs CVA15% in 15 yrs PVD15% 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 –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 –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 High steroid dose CsA / FK506 DM. Nephrotic syndrome Excessive wt.gain High fat diets Use of diuretic, beta-blockers Genetic susceptibility

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

101 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

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%) –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 –10% women with postTx CA –In situ lesion … 70% of case –Incidence … 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 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

112 Thank you & Happy Valentines Day

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