UTI IN RENAL TRANSPLANT RECIPIENTS

K L GuptaPGIMER

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 involveLower 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 RecipientsValera

– 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