1. Infections in Kidney
Transplantation
Dr. Sunil Kumar Daksh Prajapati

2. Layout
 Risk factors
 The Timeline of Posttransplant Infections
 Viral infections
 Bacterial infections
 Fungal infections
 Parasitic infections

3. Source
 Various articles
 Handbook of Gabriel M. Danovitch
 Various other standard text books
 2010 KDIGO clinical practice guideline for the
care of kidney transplant recipients

6. Kidney transplant(KT) infection –
Risk factors
 Pretranspaltation
 Comorbid illness (DM, malnutrtion, immunosupression)
 Immunosuppression for chonic conditons
 Unrecognized or undertreated infections
 Colonization by unusual or resistant organism (VRE - stool, MRSA – nares/skin,
Pseudomonas/enterobacteriace – UTI, yeast - skin)
 Preoperative antibiotic exposure
 Duration/frequency of hospitalization
 Perioperative
 Complexity of surgery/requirement of re-exploration
 Prolonged operative time
 Graft injury or prolonged ischemia
 Bleeding/multiple BT
 Infected graft
 Contaminated preservation fluid
 Foreign body

7. Kidney transplant(KT) infection –
Risk factors
 Post-transplantation
 Graft failure/dysfunction- needing immunosuppresion
 Complicated post op management – development or worsening of comorbid
illness
 Infection with immunomodulating viruse
 Prolonged hospitalization, catheters,stents, intubation
 Drains
 Anastomotic breakdown
 Leucopenia, thrombocytopenia, acquired hypogammaglobulinemia
 Prolonged antibiotic therapy
 Selected occupation/endemic infections
 Lack of appropriate hand hygiene by caregivers
 Marijuana abuse

8. Making clinical decision
 Factors that may assist in recognizing the
causative organism
 Timing of infection
 Status of donor and recipient
 State of immunosuppresion

9. The Timeline of Posttransplant
Infections
Nosocomial
Technical Opportunistic, Relapsed, Residual Common infections
HSV, CMV, HBV, HCV,
Transplantation 4 Weeks LISTERIA, PCP, TOXO
6-12 Months Long-term
Donor- Nosocomial
derived infection Period of most intensive
infection immune suppression
Common Variables in Immune Suppression
 Rejection, antirejection therapy, new agents
 Neutropenia, lymphopenia
 Viral coinfection (CMV, HCV, EBV)

10. Changing Timeline of Infection after Transplantation
Fishman J. N Engl J Med 2007;357:2601-2614

11. Conditions predisposing to early
and nosocomial infection
 Intubation (>3 days)
 Catheters (urinary, venous, balloon pumps, dialysis, other mucosal injuries)
 Ascites, peritoneal dialysis
 Constipation, endoscopy, Clostridium difficile colitis
 Broad-spectrum antimicrobial agents
 Deep vein thrombosis, atelectasis, decubitus ulcers
 Metabolic (malnutrition/uremia/hyperglycemia)
 Latent infections (viral and parasitic)
 Colonization (bacterial and fungal)
 Exogenous immune suppression

12. Donor derived infections
Possible infections from the allograft include:
 Tuberculosis
 Known pathogens (screened): HBV, HCV, HIV
 Uncommon pathogens: West Nile virus, Chagas’
disease,
Toxoplasma gondii, rabies, lymphocytic choriomeningitis
virus
 Common “sticky” bacteria (may be nosocomial
colonizers of donor): Pneumococcus, Staphylococcus,
Streptococcus, Pseudomonas, Salmonella, Aspergillus, Candida

13. Donor-derived Infection
 Most are latent
 CMV, TB, T.cruzi
 The majority of these are sub-clinical in healthy patients,
but can be catastrophic when transplanted into an
immunosuppresed patient
 Rarely can be acute
 West Nile, rabies, HIV, hepatitis
 At present, routine evaluations of donors for infectious
diseases relies upon serologic antibody testing, and thus
sensitivity is not 100% for those that may not have had time
to seroconvert

14. Donor-derived
 Transplantation of organs from deceased donors with viral
syndromes is controversial
 Livers with known Chagas or Hep B infection may be used as there
are effective treatments for these infections
 Hep C infected organs are sometimes transplanted into Hep C(+)
donors

15. Fishman J. N Engl J Med 2007;357:2601-2614

16. Recipient-derived Infections
 Infections that can be treated or controlled do not
necessarily preclude transplantation
 Most commonly screened for:
 TB
 Syphilis and other STD
 Viral: CMV, EBV, VZV, HSV, HIV, HBV, HCV
 Other things to think of
 T.cruzi, strongyloides, cryptococcus
 Endemic fungi: histoplasma, coccidioides, paracoccidioides,
aspergillus, blastomycosis

17. Fishman J. N Engl J Med 2007;357:2601-2614

18. Immunizations
 Pt’s should be immunized for
Consider in endemic area
 MMR
•Rabies, (2D)
 HBV •Tick-borne (2D)
 Influenza •Meningoencephalitis, (2D)
 Strep pneumoniae •Japanese B encephalitis-
 Tetanus inactivated (2D)
 Diphtheria •Meningococcus, (2D)
•Pneumococcus, (2D)
 Pertussis
•Salmonella typhi-
 Polio inactivated. (2D)
 VZV – if never infected
 Consideration should be given to boosters for any of the above prior to
transplantation as live vaccines are generally contraindicated post-
transplant, and immunologic memory will become impaired

19. Monitoring Immunosuppression
 There are no specific tests currently available to
determine the overall susceptibility of patients to
infection…
 …but they are being developed
 Currently, the known determinants contributing to the
overall risk of infection are the dose, duration, and
sequence of immunosuppressive therapies

20. Infection
 Types
 Viral
 Bacterial
 Fungal
 Parasitic
27

21. Viral Infection

22. Figure 1. Time of presentation of common viral illnesses post-transplant
Weikert, B. C. et al. Clin J Am Soc Nephrol 2008;3:S76-S86
Copyright ©2008 American Society of Nephrology

23. CMV

24. CMV
• Among all organ transplant KT pt have lowest risk for
CMV disaese
• CMV is still among the most important infectious
complications after transplant
• It is widely distributed in general population ranging from
40-97%
• Once CMV infection is established, then its replication is
highly dynamic with rapid increases in viral load
• Transmitted by Allograft, blood products, Sexual contacts
24

25. CMV and Kidney Transplantation
 It usually develops during the first few months of
Tx. when patient is immunosuppressed.
 In the absence of prophylaxis, CMV reactivation can
occur in over 75% of recipients depending on other
risk factors
 It has also been implicated as a cause of acute and
chronic allograft injury.
 CMV may play a crucial role in chronic graft
vasculopathy resulting CAN, bronchiolitis and
accelerated CAD

26. CMV Infection: Risk Categories in
Solid Organ Transplant Recipients
Donor (D) or Recipient (R)
Risk Category
Seropositivity (+/-)
High D+/R-
Intermediate D+/R+, D-/R+
Low D-/R-
Fishman JA, Emery V, Freeman R, et al. Cytomegalovirus in transplantation –
26 challenging the status quo. Clinical Transplantation. 2007;21:149-158.

27. CMV Pathogenesis
• Viral factors • Host factors
– replication dynamics – CD4+, CD8+ T-cell
– immune evasion
– NK cell, B-cell,
neutropenia
– viral heterogeneity – exogenous
– viral co-infections immunosuppression/
lymphocyte depletion
– D/R immune status
27

28. ANTILYMPHOCYTE OTHER SEPSIS/
ANTIBODIES HERPES VIRUSES REJECTION SURGERY
INFLAMMATION
(CYTOKINES, NF-κB)
LATENT CMV INFECTION
28

29. CMV Infection
Latent CMV infection
Active CMV infection
(viral replication)
Direct Indirect
effects effects
29

30. Direct Effects of CMV Infection
Direct Effects
CMV Viral Syndrome Tissue Invasive
• Fever, malaise, myalgias Disease
• Leukopenia, • Hepatitis
thrombocytopenia, and other • Pneumonitis(most serious)
laboratory abnormalities • Colitis(diagnostic endoscopy)
• Carditis
• Nephritis
• Pancreatitis
• Retinitis
30

31. Indirect Effects of CMV Infection
Indirect Effects
Altered host immune
response
• Graft rejection; graft dysfunction
• Opportunistic infections: Bacterial
fungal superinfection
• Decreased graft and patient survival
• Herpesvirus interactions:
EBV/PTLD
31

32. Diagnosis of CMV
 Pretransplantation screening
 CMV – IgM, IgG
 Disease
 Culture based – Tissue culture
 PCR
 New era for CMV diagnosis by the PP65
antigenemia assay. This test is sensitive and specific.
 Quantitative method is used for monitoring
response

33. Anti-CMV Therapy
 Valganciclovir: a prodrug form of ganciclovir with improved oral
bioavailability(=Ganciclovir)
 Ganciclovir: intravenous or oral
 Foscarnet: is an inhibitor CMV DNA polymerase (UL54)
‒ Useful for ganciclovir resistant CMV
‒ Major limitation is nephrotoxicity
 Cidofovir: inhibits viral DNA polymerase
‒ Useful for ganciclovir resistant CMV
 Maribavir: is an investigational agent that prevents viral encapsidation
and nuclear egress
33

34. Ganciclovir
 Adverse effects:
– Hematologic: neutropenia, anemia, thrombocytopenia(additive with
Azathiopurine)
– Gastrointestinal: nausea, vomiting, diarrhea, abdominal pain, flatulence,
anorexia
– Neurologic: headache, confusion, hallucination, seizures
– Other: pain and phlebitis at injection site (due to high pH), sweating, rash,
itch, increased serum creatinine and blood urea concentrations
 Toxicity:
– Human carcinogen, teratogen, and mutagen
– Inhibits spermatogenesis
– Increased seizure threhold on use with Imipenem
 Pharmacokinetics:
– 90% of plasma ganciclovir is eliminated unchanged in the urine with a half-life
of 2-6 hrs, depending on renal function (elimination takes over 24 hours in
end-stage renal disease)
 5-10 mg/kg/d in two divided dose for 4-6 weeks for treatment
34

35. Valganciclovir
 Dose :
 Oral 900mg BD for mild to moderate CMV disease for 14-21 days
 Pt with severe tissue invasive disease, who fail to achieve a reduction in viral load
after 7 days should receive iv ganciclovir
 Weekly monitoring of viral load
 Adverse effects:
– Similar to ganciclovir
– Myelosuppression is one of the main side effects that may limit prolonged use of
valganciclovir
 Pharmacokinetics:
– Oral bioavailability ~ 60%
• Fatty foods significantly increase the bioavailability
– Eliminated as ganciclovir in the urine, with a half-life of about
4 hours
35

36. CMV Prevention
• Two strategies
• Universal prophylaxis
– Therapy from the time of transplant to all patients
or a subgroup of patients at high risk for CMV disease
• Pre-emptive therapy
– Patients are monitored at regular intervals for early evidence of
CMV replications guided by laboratory monitoring
– Treatment is started when CMV viral load or antigenemia
reaches a certain threshold
– Useful for low/intermediate risk
– In patients with CMV disease, we suggest weekly monitoring of CMV
by NAT or pp65 antigenemia.(2D)
36

37. Pre-emptive Therapy
CMV disease
TEST _ _ _ + + + + + + + _ _
0 4 8 12
weeks
Initiate pre-emptive therapy to prevent
CMV disease
37

38. Prophylaxis vs. Pre-emptive Therapy
Prophylaxis Pre-emptive
Evidence of efficacy +++ ++
Indirect effects/mortality ++ +
Other viruses + for some ?
Ease ++ +/-
Late onset disease ++ -
Resistance Low Very Low
38

39. Effects of Anti-CMV Prophylaxis
on Concomitant Infections
39
Hodson EM, et al. Lancet. 2005;365:2105-2115.

40. Universal prophylaxis
Acyclovir, ganciclovir, valacyclovir, valgancilovir and immune-
globulin.
Acyclovir: Possesses comparatively poor vitro activity against CMV
at clinically achievable levels.
Ganciclovir:
 Use in D+ & R-ve patients immediate after Tx.
Valacyclovir:
 Oral 8 gm per day for 3 months
 Less effective than gancyclovir.
 All prophylaxsis for 3mth or 6 wk after tt with T cell depleting
antibody
 (Dose adjustment necessary for all)

41. Guidelines for CMV prevention in kidney
recipients
Group: Recommendations:
* Kidney * Oral ganciclovir
D+ve/R-ve for 3 months/IV
ganciclovir 1-3 M
*Kidney
R+ve * As above
Start prophylaxis within 10 days post Tx. And continue for 100 days

42. Polyvalent I/V Immunoglobulin
The efficacy of I/V Ig in KT has been
investigated.
Unclear status

43. Late Onset CMV Disease Definition
• CMV disease occurring > 3 months post
transplant
• May be primary infection (D+/R-) or recurrence
(R+)
• Incidence 3%-17%
• In IMPACT study 37% with 3 months of
prophylaxis in D+/R-
43 Limaye, AP, et al. Transplantation. 2004;78(9):1390-1396.

44. CMV Prophylaxis: Late-Onset Disease
100 Valganciclovir
90
364 D+/R- patients
Patients With No CMV Disease (%)
80
70
60 Ganciclovir (oral)
50
40
30
20
10
Prophylaxis period
0
0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200
Time (days)
44 Paya, et al. Am J Transplant. 2004;4:611-620.

45. Herpes Simplex Virus
and Varicella Zoster Virus

46. HSV & HZV
 Seroprevalence for HSV-1 in the adult population is
as high as 60 percent, while VZV rates can be as
high as 90 percent
 Infection in the renal transplant patient is usually
caused by reactivation of latent virus.
 Within 6 weeks
 HSV infection usually presents with oral or genital
lesions, but in some instances can cause
esophagitis,hepatitis, encephalitis or pneumonitis

47. HSV & HZV
 ZV reactivation usually presents as dermatomal zoster,
but can disseminate
 In the absence of prophylaxis, HSV and VZV may be
seen early
 The incidence of HSV in renal transplant recipients is
estimated to be approximately 53% and VZV 4 to 12%
 Due to high seroprevalence in the adult
population, serologies are rarely helpful in the setting of
active infection.

48. HSV & HZV
 Diagnosis
 Direct fluorescence antibody for HSV and VZV from vesicular lesions or
PCR from CSF or visceral tissue samples.
 Treatment
 Disseminated infections involves intravenous acyclovir,
 Less severe infection ; oral acyclovir, valacyclovir, or famciclovir
 Acyclovir resistance - foscarnet, cidofovir, and topical trifluridine
-monitoring of KFT
 VZV immunoglobulin ASAP but no later than 96 hr
 If immunoglobulin is N/A or more than 96 h have passed, a 7-day course of
oral acyclovir begun 7–10 days after varicella exposure. (2D)

49. Epstein Barr Virus

50. Epstein Barr Virus
 EBV remains latent in lymphocytes following
primary infection.
 Can cause replication and clonal expansion of the B
cells that serve as its primary reservoir and other
cell lines as well.
 However, a competent immune system, specifically
T cell response, prevents these cells from
propagating.
 When T cell function is impaired, as is the case in
renal transplant patients, this surveillance system
can fail and post transplant lymphoproliferative
disorder (PTLD) can develop

51. Epstein Barr Virus & PTLD
 Risk of development of PTLD,
 with higher incidence rates observed in patients
receiving cytolytic therapies,
 including antithymocyte globulin and
 OKT3
 Occur more commonly in pediatric kidney recipient
 EBV seropostive donor and recipient both are at
increased risk of PTLD
 PTLD most commonly occurs in the first year post
transplant

52. Serologies for EBV
 Serologies for EBV of both donor and recipient should be
obtained before transplant.
 Allograft recipients who are EBV negative before transplant
and receive an organ from a seropositive donor are at
greatest risk for PTLD;
 Currently there is no single standard strategy to prevent
PTLD.
 In some centers, high-risk individuals are screened regularly
for the presence of EBV viremia and immunosuppression
decreased when viremia is observed.
 Effective prevention of CMV may also prevent EBVinfections
 A recent trial demonstrated that CMV Ig did not prevent the
onset of PTLD in high risk recipients

53. PTLD
 Definitive diagnosis of PTLD requires histopathologic
confirmation, preferably of tissue obtained by excisional biopsy.
 In the case of CNS PTLD, analysis of CSF for EBV PCR and
cytology should be performed.
 Although viremia may be noted at the time of PTLD, its
detection cannot be used to confirm or refute the diagnosis.
 Staging is performed by histologic type
(monoclonal versus polyclonal, T cell versus B cell) and location
(allograft, other organ, metastasis).
 Often the Ann Arbor classification, used for other non-Hodgkin
lymphomas, is utilized

54. Human Herpesvirus-6,
Human Herpesvirus-7,
and Human Herpesvirus-8

55. HHV-6,7,8
 HHV-6 is a cofactor for CMV
 Human Herpes Virus 8 (HHV8) is a gamma
herpes virus that has been associated with
Kaposi's Sarcoma(30 month), primary effusive
lymphoma, and Multicentric Castleman's
Disease (lymphoproliferative disorder)
 Routine screening of HHV 6 & 8 are not
performed

56. Hepatitis B and C

57. Hepatitis B
 All nonimmune patients with chronic renal failure
should be vaccinated with Hepatitis B vaccine and
immunity verified with Hepatitis B surface antibody
screening following completion of the vaccination
series
 HBsAb titer o10 mIU/ml receive booster vaccination to
raise the titer to X100 mIU/ml.
 All HBsAg positive pt should undergo live biopsy,
because it is difficult on clinical ground only to
estimate severity of liver disease in CKD(AST tend to be
spuriously low)

58. HBsAg +ve Biopsy
liver
Decompensated Cirrhosis or Precirrhosis Mild Histology
cirrhosis
Preclude RT
LKT
No replication Replication
RT Antiviral therapy
RT
Antiviral therapy

59. Hepatitis B
 Risk factor for progression of HBV related liver disease
 Alcohol
 Infection- ↑ duration, ↑ HBV DNA, genotype C, coinfection with
hepatitis C & D, HIV, immunosuppresion
 Calcineurin inhib & Azathioprine
 All pt with Hep B should receive antiviral therpy after transplantation
(Only 5% fail to recover)
 Tenofovir or entecavir are preferable to lamivudine
 Adefovir or tenofovir for KTRs with lamivudine resistance (>5 log10
copies/ml rebound of HBV-DNA).
 Dose reduction is needed – Lamivudine, Adefovir, IFN
 During therapy with antivirals, measure HBV DNA and ALT levels
every 3 months to monitor efficacy and to detect drug resistance.
 Screen for hepatocellular carcinoma every 12 m with liver ultrasound
and alpha feto-protein

60. HCV
 Graft dysfunction
 NODAT(40%)

61. Anti HCV +ve
HCV RNA -ve HCV RNA +ve
Liver Bx
Normal LFT
Normal Hepatitis Cirrhosis or precirrhosis
Antiviral Rx Defer transplant or
List for renal transplant consider combined liver-
kidney transplant
HCV RNA -ve HCV RNA +ve
Pt by pt decision

62. HCV
 Cyclosporin inhibit HCV replication, Azathioprine &
Antilymphocye therapy ↑ replication
 For sustained virological response IFN & ribavirin should be
co administered very carefully because of risk of hemolytic
anemia and its metabolites are not cleared by HD
 Dose modification needed - Ribavirin
 Measure ALT monthly for the first 6 m & every 3–6
months,thereafter
 Perform imaging annually to lookfor cirrhosis and
hepatocellular carcinoma.
 Test HCV-infected patients at least every 3–6 months for
proteinuria. (Not Graded)

63. West Nile Virus
 West Nile Virus is a flavivurus that causes a febrile
illness, associated with encephalitis, and can be fatal
 To prevent infection, summer seasonal screening
should be considered for donors before transplant
 Preventive measures regarding mosquito bites
 Treatment not standardized - reduction in
immunosuppression

64. Adenovirus
 Causes
 Hemorrhagic cystitis
 Fever
 Renal dysfunction
 Pneumonia
 Hepatitis
 Definitive diagnosis – renal biopsy (Granulomatous
interstitial nephritis, ground glass intranuclear
inclusion body)
 TT –Ribavirin with or without IVIG

65. Parvovirus B19
 Causes
 Refractory anemia
 Pancytopenia
 Thrombotic microangiopathy
 Fibrosing cholestatic hepatitis
 Encephlitis
 Graft dysfunction
 80% in first three month
 Diagnosis
 Bone marrow – Giant proerythroblast
 Confirm by detection of B19 in serum by PCR
 High dose IVIG x 10 days
 Reduction of immunsuppresion

66. Bacterial infections

67. Bacterial infections
 UTI – Prophylaxsis for 6 m with TMP-SMX
 Even low level of bacteriuria can lead to
septicemia
 2 set of blood culture should be obtained
 Surgical site infection – 2-25%

68. Vancomycin-Resistant Enterococci
in Transplantation
 Common bacterial pathogen after kidney
transplantation
 “Predictor” of morbidity and mortality that reflects
overall “illness” of patient
 VRE may not be detectable from a single stool culture
and 3 samples should be obtained at weekly interval
for 3 weeks before discontinuing search for VRE

69. Clostridium difficile infection
 With in 2 weeks - diarrhea
 Diarrhea occur in 13% of kidney transplant
 Infectious agent 41%
 Medications 34%

70. Bacterial infection contd..
 Nocardia
 Early rejection, ↑imunnosupp, neutropenia, uremia
 1-6 m after acute or subacute chest presentation
 High dose TMP-SMX 15mg/kg for at least 12 month
 TB
 RIF>ETH – neutropenia
 INH increase levels of cyclosporin, tacrolimus. RIF decrease
these level
 Interactions are predictable occurs in 1-3 days of initiating
ATT, dose adjustment needed
 Consider substituting rifabutin for rifampin to minimize
interactions with CNIs and mTORi

71. Bacterial infection contd..
 Legionella
 Urinary antigen test 70-100% specific
 Tt for 21 days
 Rhodococcus
 Months to years after Tx
 D/d with PTB
 Mixed infection

72. Fungal infections

73. Fungal infections
 Incidence of fungal infections in renal transplant recipients is
less than other SOT but mortality high :
 Limited diagnostic tools
 Potential for rapid clinical progression
 Risk factor for colonization with yeast and molds after KT:
 Corticosteroid therapy
 Broad spectrum antibiotic
 Co morbid disease
 Domiciliary exposure
Hand book of renal transplant:( Gabriel)

74. Fungal infections
Clincal scenario where fungal infection is seen
1. Presence of urinary catheter
2. Endotracheal tube
3. Immunomodulating viral inf reactivation
4. Ch. Graft dysfunction
5. During treatment of post transplant malignancies
Hand book of renal transplant:( Gabriel)

75. Extent of problem
 Incidence of major invasive fungal
infection(IFI) among Kidney recipient patient:
2. Candida:76-95%
3. Cryptococcus:0-39%
4. Other fungi:0-39%
5. Aspergillus:0-26%
Hand book of renal transplant:( Gabriel)

76. Candida
 Occurs most commonly  Sources:
during the 1st month  Endogenous: Source of
following transplant colonization
associated with  Exogenous: lack of hand
washing of health workers
Hand book of renal transplant:( Gabriel)

77. Candidal colonization
Esophageal / GI
Pulmonary
tree
Vagina Bowel

78. Disseminated infection: <5%
Kidney candidiasis: 0.5-2.2%

79. PROGNOSTIC FACTORS IN CANDIDEMIA
Associated with death:
-more severe clinical symptoms
-persisting neutropenia
-organ involvement
-↑ age
Beter survival if:
*catheter is removed
*neutropenic patients given antifungals

80. Aspergillosis

81. DEVELOPMENT OF ASPERGILLOSIS
INHALATION COLONIZATION INFECTION Dissemination
1 2 3

82. Renal aspergillosis

83. Invasive aspergillosis : diagnosis
 Radiology: chest X-ray and CT
 Microbiology
 Respiratory secretions: BAL/biopsy
 Direct microscopy
 culture
 Serological surveillance
 ELISA for galactomannan
 PCR

84. Invasive aspergillosis: Treatment
 Conventional amphoterin B: 20-83% response
 ?iv itraconazole: limited data
 Lipid formulations of ampho B
 5 mg/kg/day liposomal ampho B
 Surgical intervention

85. Zygomycosis
 Median 2 months post-transplant
 Most cases occur within 6 months of
transplant
 Rhinocerebral form
 76% diabetes and corticosteroids
 56% mortality

86. Prophylaxis
 AmBisome
 Itraconazole
 Prophylaxsis with systemic antifungal agent is not
recommended after uncomplicated KT, it may be
indicated in those with persistent candiduria.
 Azole Ambisome for a period of risk for infection
 Those with past history fo endemic mucosis,
radiographic e/o healed leison – life long azole

87. Successful management
 Prompt recognition of infection
 Adjustment of level of immunosuppression
 Antifungal therapy and surgery

88. Treatment
 Conventional amphotericin B
 1-1.5 mg/kg/day
 Nephrotoxicity big issue
 18% require haemodialysis
 Liposomal amphotericin B
 Much reduced nephrotoxicity
 Superior efficacy
 Itraconazole: iv formulation: little data
 Voriconazole/caspofungin: little data. (apppears to be
superior to Amb)

89. Future Strategy Against Probable
Invasive Fungal Infection?
C Fluconazole
U le
p tib
L s ce
T su
Empirical U
or R
AmBisome E
positve risk of aspergillosis AmBisome
test
R
E
no
S re
U sp glucan synthesis
o ns inhibitor (IV) or
L e new azole orally
T

90. PNEUMOCYSTIS JIROVECII
PNEUMONIA
 PCP prophylaxis with daily TMP-SMX for 3–6
months after transplantation. and for 6wk after
treatment for acute rejection
 Diagnosed by BAL and/or lung biopsy be treated
with high-dose intravenous TMP-SMX,
corticosteroids, and a reduction in
immunosuppressive medication
 Treat with corticosteroids for KTRs with moderate
to severe PCP (as defined by PaO2 o70mmHg in
room air or an alveolar gradient of 435mmHg)

91. Parasites

92. Malaria
 Usually severe
 Pyrexia, which may lack the typical periodicity or rigors
 Anemia is severe, being typically hemolytic and occasionally
hemophagocytic, often associated with thrombocytopenia
 Acute graft dysfunction may occur as a consequence of the
hemodynamic consequences of falciparum infection*. Whether the
immune response to malarial infection has an impact on
subsequent rejection is unknown
 Antimalarial drugs can be used safely
 Drug-drug interactions must be taken into consideration as those
between quinine & chloroquine with cyclosporine *
*Barsoum RS. Malarial acute renal failure. J Am Soc Nephrol 2000.;11(11):2147-54
Tan HW, Ch’ng SL. Drug interaction between cyclosporine A and quinine in a renal transplant patient with malaria. Singapore Med J 1991; 32: 189-190
Nampoory MR, Nessim J, Gupta RK, Johny KV. Drug interaction of chloroquine with ciclosporin. Nephron 1992; 62: 108-109

93. Schistosomiasis
 Recrudescence of schistosomal glomerulopathy
has been reported in an endemic area in South
America, where mesangioproliferative
glomerulonephritis with schistosomal antigen
deposits developed in a recent kidney transplant
recipient who originally had been infected with
S. mansoni.
 Prophylactically treat patients with such
infection

94. Toxoplasmosis gondii
 Lack of T cell immunity
 Diagnosis by PCR
 Protected when given TMP-SMX for P. carnii

95. Approach to the kidney
transplant pt with fever
 Infection
 Graft rejection
 Drug allergy
 Non infective systemic inflammatory response
 Pancreatitis
 Pulm. Embolism
 Cytokine release syndrome

96. Thank you