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UTI IN RENAL TRANSPLANT

RECIPIENTS

K L Gupta
PGIMER
CHANDIGARH-INDIA
INTRODUCTION
• Incidence of post renal transplantation UTI :
– Varies considerably : 10-98%
» Actas Urol Esp. 1999 Feb;23(2):95-104
– Fallen over the past 30 years
» Clin Transplant,2006 Jul-Aug;20(2):95-104

• Current clinical practice : Prophylactic antibiotics for


the 1st 6 mths after transplantation
– Change in the timing of onset of post-transplantation UTI
• 72% of UTIs : After the 1st 6 months (13.3% in 1st mth)
» Transplant Proc. 2007 May;39(4):1016-7
INTRODUCTION
– Most common type of bacterial infection in renal allografts
recipients in the post-transplantation period. Fungi and
viruses are less common cause of UTIs
– Bacteria account for : 44-47% of the infectious
complications in early post-tx period
» Clin Transplant, 2006 Jul-Aug; 20(4):401-9
– Can involve
Lower and upper urinary tract or Allograft or native kidneys
‗ UTI : >6 months after transplantation : Ass. With
– S.Cr >2mg/dl
– A daily steroid dose>20mg
– Polydrug immunosuppression
– Chronic viral illness
» Clin Infect Dis 2001;33:S53-S57
Late urinary tract infections
• Late urinary tract infection after renal transplantation in the
United States
» Am J Kidney Dis. 2004 Aug;44(2):353-62
– Retrospective cohort study : 28,942 Medicare primary
renal transplant recipients in the USRDS
– Cumulative incidence of UTI :
• First 6 months after renal transplantation : 17%
• At 3 years :
– 60%: Females
– 47%: Males
– Late UTI : Significantly associated with an increased risk of
subsequent death in Cox regression analysis
Risk Factors
Major risk factors include:
• Indwelling bladder catheters
• Handling and trauma to the kidney and ureter during
surgery
• Anatomic abnormalities of the native or transplanted
kidneys:
• Vesicoureteral reflux, stones, stents
• Neurogenic bladder especially in diabetic patients
• Possibly rejection and immunosuppression
UTI: ETIOLOGY

Kidney Int. 2010 Oct;78(8):719-21


UTI: EPIDEMIOLOGY

Pediatr Nephrol. 2009 Jun;24(6):1129-36


Epidemiology of UTI in TX Recipients
Valera

– Prospective evaluation of all the UTIs in 161


kidney Tx recipients for 2 years
– All patients received prophylaxis with sulfadoxine-
pyrimethamine
– Excluded asymptomatic bacteriuria
– 41 patients (25%) suffered at least one UTI
episode
– Incidence rate of 97 UTI episodes per 100 patient-
years
Epidemiology of UTI in TX Recipients

– Most common clinical features:


• Uncomplicated acute bacterial cystitis: 77%
• Acute pyelonephritis: 23%
– Bacterial infections: Most frequent etiologies
• Gram-negative bacilli:90%
• Gram-positive cocci: 7%)
– Fungal:3%
– BK virus:2%
– At the end of the study period:
• Graft Survival: 90.7%
• Transplant recipients survival: 97.5%
UTI Pathogens Differ in Renal
Transplant Patients
– Comparision of data from all urine cultures from
investigator’s institution's renal transplant
recipients with the findings of UTI specimens from
the general population
– 225 renal transplant patients
• 52: At least one episode of significant bacteriuria
• 157: Episodes of significant bacteriuria

» J A Charnow, June 27,2010; ERA-EDTA 2010 Congress


UTI Pathogens
– Etiology:
• Coliforms:76% of episodes
• Pseudomonas: 12%
• Enterococci: 6.4%
• Group B streptococci:1.9%
– Non-coliform bacteria caused 24% of UTIs transplant
recipients compared with only 11% in the general
population
– Coliform bacteria in the transplant population:
Significantly more resistant to amoxicillin (69% vs. 50.5%),
coamoxiclav (17% VS. 7%), and trimethoprim (43% vs.
27%)
UTI: SYMPTOMS
• Lower urinary tract symptoms (cystitis)
– Frequency
– Urgency
– Dysuria
– Hematuria
– Suprapubic pain
• Upper urinary tract symptoms (pyelonephritis)
– Rigors and/or pyrexia
– Hematuria
– Loin pain in native kidney
– Pain over graft
UTI: DIAGNOSIS
• Must be Thorough and Timely
• In pts with Pyelonephritis: Important to exclude
coexisting CMV infection
• Graft rejection and UTI:
– Allograft biopsy: Only tool that can differentiate
• Early post-transplantation UTI
– Sample of the transplant organ storage perfusate for
culture (if available)
UTI: DIAGNOSIS -Imaging

– Plain X-ray and/or CT of kidney, ureter and bladder


• Stones in transplanted or native kidneys
– CT of kidneys with intravenous contrast
• Complex cysts of transplanted or native kidneys
– CT–PET
• Localized infection of polycystic kidneys
– Micturating cystogram
• Suspected reflux
UTI DIAGNOSIS- Interventions

– Cystoscopy (flexible or rigid), with or without


retrograde ureteropyelogram
• Careful inspection of urethra and/or bladder with or without
retrograde studies of native and/or transplanted systems
– Urodynamics (pressure and flow cystometry with or
without video urodynamics)
• Bladder dysfunction and/or outflow obstruction
– Measurement of urine free-flow rate (uroflowmetry)
in all men with urinary tract infection
• Bladder dysfunction and/or outflow obstruction
UTIDIAGNOSIS – Nuclear Studies
• Investigations for suspected post-
transplantation UTI and their indications
– Static renogram (DMSA scan)
• Renal scarring
– Dynamic renogram (MAG3 scan)
• Transplant ureteric obstruction
– Percutaneous transplant nephrostomy
• Transplant ureteric obstruction and/or pyonephrosis
UTIDIAGNOSIS
– Urine Routine and Cultures for bacteria and
atypical organisms.
– Measurement of cytomegalovirus load
• Cytomegalovirus infection
– Urine and blood polymerase chain reaction and/or
urine cytology for decoy cells
• BK virus infection
– Chest X-ray, purified protein derivative test,
polymerase chain reaction of early morning urine
• Suspected tuberculosis
UTI: PEDIATRIC POPULATION
UTI: PEDIATRIC POPULATION
UTI: PEDIATRIC POPULATION
UTI: PEDIATRIC POPULATION
UTI: MANAGEMENT
• Empirical antibiotics (both Gram -ve and Gram
+ve bacteria) → Targeted therapy
• Lower UTI without signs of sepsis: Outpatient
• Eradication of organisms: Confirmed by a
follow-up culture
• Remove ureteric stent if present and send for
culture
• Polycystic kidneys: Lipophilic antibiotics
UTI: ASYMPTOMATIC
UTI: ASYMPTOMATIC
UTI: MANAGEMENT
• Treatment Duration:
– 10-14 days:
• Early UTI (<6 mths)
• Lower UTI associated with systemic features
• Pyelonephritis
– Upto 6 wks
• Recurrent UTI
• Relapsing UTI
UTI: MANAGEMENT
• Surgical principles
– Ensuring adequate urinary tract drainage, no
obstruction
– Prevention and treatment of reflux of infected urine
to transplanted and native kidneys
– Differentiate between obstruction and reflux
– Detection and treatment of urinary tract calculi
– Treatment of infected cysts of native kidneys by
drainage or nephrectomy
– Timely removal of urinary catheters and ureteric
stents
UTI: MANAGEMENT
UTI: MANAGEMENT
UTI: MANAGEMENT
UTI: PREVENTION
UTI: PREVENTION
Post-tx Fungal UTI
• Fungal UTIs are uncommon in Tx Recipients.
• May be asymptomatic but sometimes cause severe
morbidty.
• Can be caused by Candida, Aspergillus, Mucor and
other rarer fungi.
• Candida Spp are the most common organisms
causing fungal UTI.
‗ Candida albicans accounts for 74%
‗ Glabrata 8%
‗ Parapsolosis7%
‗ Tropicalis 3%
Management of candiduria
• Asymptomatic candiduria rarely requires therapy
• Reducing risk factors such as removal of bladder
catheters or urologic stents and discontinuation of
antibiotics
• Symptomatic candiduria should always be treated.
• Treatment should be tailored according to….
– Identified Candida species
– Whether localized or disseminated infection is present
Post-tx Viral UTIs
• Viruses are an uncommon cause of UTIs in an
immunocompetent host; but they may present with
serious complications in Transplant recipients.
• BK virus, adenovirus, and cytomegalovirus are
predominant pathogens.
• Early diagnosis and treatment may prevent significant
morbidity.
• The diagnosis of viral lower UTI is based on molecular
techniques, and real-time PCR allows quantification of
viral load.
• Cidofovir is becoming a drug of choice in viral UTIs
PGIMER EXPERIENCE
• 2006-2007: 1270 patients
– 231 infectious episodes in 196 patients
– UTI: Most common infection within the first month
following transplantation
– Predominant infection among all infections:
• Bacterial infection: 59.3%
– UTI: Most common: 80% Overall, 13%: UTI
– Isolated graft tuberculosis:
• 3 pts ;4.8% of all tuberculosis pts
– BKV Nephropathy:
• 11 pts
UTI: RELATION TO GRAFT OUTCOME
UTI: RELATION TO GRAFT OUTCOME
UTI: RELATION TO GRAFT OUTCOME
• Transplant pyelonephritis:
– Independent risk factor for poorer long term graft
outcome Am J Transplant. 2007 Apr;7(4):899-907
• Recent study:
– Retrospective analysis of 189 pts with min. f/u 36 mths
– S. Cr, CrCl and 24-h proteinuria: No significant diff. b/w
pts with or without graft pyelonephritis
» Nephrol Dial Transplant. 2010 Aug 30

• Repeated ‘non-pyelonephritis’ UTI in the adult


transplant population
– Cumulative adverse effect on grafts: Not clear
UTI: FUTURE
UTI: FUTURE
UTI: FUTURE
THANK YOU

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