1、Diagnosis and Management of VUR after first UTIRon Keren,MD,MPHDivision of General PediatricsCenter for Pediatric Clinical EffectivenessChildrens Hospital of PhiladelphiaCase 2.5 year old old white girl with 3 days of:Fever(Tmax=40C)Poor appetite Fussiness 2 loose stools a day Urine dip shows modera
2、te leukocyte esterase Treatment with PO TMP/SMZ initiated Urine culture(cath specimen)grows 105 E.coli Child defervesces in 2 days and completely well in 3 days.Next steps?Screening for VUR Infants and children 2 months to 2 years with initial UTI should have either a VCUG or RNC performed to detect
3、 the presence and severity of VUR.(Strength of evidence:fair)(AAP,Practice Parameter:The Diagnosis,Treatment,and Evaluation of the Initial UTI in Febrile Infants and Young Children,Pediatrics,103:4;843-852,1999)Screening for VUR Infants and children 2 months to 2 years with initial UTI should have e
4、ither a VCUG or RNC performed to detect the presence and severity of VUR.(Strength of evidence:fair)(AAP,Practice Parameter:The Diagnosis,Treatment,and Evaluation of the Initial UTI in Febrile Infants and Young Children,Pediatrics,103:4;843-852,1999)Age at First UTIConway,P.H.et al.JAMA 2007;298:179
5、-186.Screening for VUR Infants and children 2 months to 2 years with initial UTI should have either a VCUG or RNC performed to detect the presence and severity of VUR.(Strength of evidence:fair)(AAP,Practice Parameter:The Diagnosis,Treatment,and Evaluation of the Initial UTI in Febrile Infants and Y
6、oung Children,Pediatrics,103:4;843-852,1999)No recommendations on how to manage VURManagement of VURScarring at DxNoYesAgeInitialF/UInitialF/U 1Proph AbxIII-V:Surgery Proph AbxIII-V:Surgery1-5Proph AbxB/L grade V:SurgeryIII-V:SurgeryV:SurgeryIII-V:Surgery6-10Proph AbxB/L grade III-IV or U/L V:Surger
7、yIII-IV:SurgeryProph AbxB/L grade III-IV or U/L V:SurgeryIII-IV:Surgery(AUA,Report on The Management of Primary VUR in Children,Journal of Urology,May,1997.)Management of VURScarring at DxNoYesAgeInitialF/UInitialF/U3/5)VURAPNRenal ScarringNormalDMSA Renal ScansRenal Scarring on DMSADilating VUR(Gra
8、des 3-5)Normal DMSAAbnormal DMSANo VUR3664VUR 1-2516VUR 3-5021Normal DMSAAbnormal DMSANo VUR133105VUR 1-2718VUR 3-5126“Top Down”Approach Perform DMSA within 30 days of UTI Normal:reassure parents that kidneys are normal and child unlikely to have dilating VUR skip the VCUG Abnormal:obtain VCUG,consi
9、der antibiotics v.surgery if VUR present,repeat DMSA in 4-6 months to diagnose scars“Top Down”Approach Spares a lot of children a VCUG(48%in Preda study)DMSA less than half the radiation of a VCUG DMSA less invasive than a VCUG DMSA gives information about the health of the kidneys,which can be foll
10、owed over time.No Work-up Defer work-up until 2nd or 3rd UTI Heightened vigilance Educate on early signs and symptoms Emphasize need for rapid diagnosis Treat dysfunctional elimination?Provide urine collection kits and dip sticks Likely that early diagnosis and treatment will prevent most UTI-relate
11、d scarring.Copyright 2007 American Academy of PediatricsDoganis,D.et al.Pediatrics 2007;120:e922-e928DMSA results in the acute phase and day of treatmentRefer to RIVUR study Randomized Intervention for Children with VesicoUreteral Reflux CMH KC Site PI:Dr.Uri AlonStudy Design NIDDK funded(U01 contra
12、ct)Multi-center 15 Clinical Trial Centers across the US Data Coordinating Center at UNC Chapel Hill Randomized Placebo Controlled Trial Initial UTI,presence of grades I-IV VUR Effect of prophylactic TMP/SMZ on:Recurrent UTI Renal scarring Antimicrobial resistanceInclusion Criteria 2 months 6 years a
13、t time of randomization Diagnosed 1st or 2nd F/SUTI within 16 weeks prior to randomization Presence of Grade I-IV VUR on VCUGTime Line Recruitment started July 2007 2 years of recruitment 2 years of follow-up Plan to recruit 600 patientsEndpoints Primary Recurrence of F/SUTI Secondary Time to first
14、recurrence of F/SUTI Renal scars on DMSA scan Stool E.coli resistant to TMP/SMZ Recurrent F/SUTI caused by TMP/SMZ resistant organismsModified Conceptual ModelVURRenalScarringEnd Stage Renal DiseasePre-eclampsiaHypertension Prompt diagnosis and treatment of UTIProphylactic antibiotics prevent recurr
15、ent UTIUTI(s)VUR UTI(s)Congenital VUR and renal dysplasiaDelayed UTI diagnosis and treatmentQuestionsInternational Classification of VURRenal UltrasoundDefluxEndoscopic Correction of VUR Deflux procedure Endoscopic injection of bulking agent(Dextranomer/hyaluronic acid)into submucosal layer of bladd
16、er just beneath or within the ureteric orifice.“Minimally invasive”compared with open surgery Day surgery Requires sedationDeflux:Capozza 1 y.o Grades II-IV VUR persistent for at least 6 months Randomly assigned(2:1)to:Dextranomer/Hyaluronic Acid(n=40)Prophylactic abx(n=21)12 months later 69%v.38%(p
17、=0.03)had bilateral grade I or less VUR.11(25%)needed 2nd injection at month 3,only 2 successfulCapozza,N,Dextranomer/hyaluronic acid copolymer implantation for VUR:a randomized comparison with antibiotic prophylaxis,J Pediatr,2002 Feb;140(2):230-4.Deflux:CapozzaDefluxProph abxp-valueRecurrent UTI6/
18、40(15%)0/21(0%)0.08New renal scars*3/80(4%)1/42(2%)0.6Renal scars healed*11/80(14%)7/42(16%)0.4Parenchymal kidney damage*1/40(3%)3/21(14%)0.11*As determined by renal US,not DMSA.PIC VURPatientsRenal UnitsInterpretationRecurrent febrile UTIs/No VUR on conventional VCUG30/3048/60(all 48 ureteral orifi
19、ces lateral and/or patulous)“Explains”recurrent UTIsNo febrile UTIs/No VUR on conventional VCUG0/150/30(all 30 ureteral orifices normal appearing)Doesnt show VUR in kids with no h/o UTIRecurrent febrile UTIs/VUR on conventional VCUG12/1220/24(all 20 ureteral orifices lateral and/or patulous)Shows VU
20、R in kids with h/o UTI PIC VUR Invasive Requires general anesthesia and instrumentation of bladder Specificity needs confirmation 0/15 does not mean no false positives%children with febrile UTI found to have PIC VUR after negative VCUG fell to 82%in small prospective validation study(Edmonson,Urol,2
21、006)No evidence that treating those found to have PIC VUR prevents recurrent UTI or renal scarring.International Reflux StudyEffectiveness of Interventions for VURAuthor,Journal,YearRR recurrent UTI 2 yearsRR recurrent UTI 5 yearsWheeler,ADC,2003(meta-analysis)1.1(0.6-2.1)0.99(0.8-1.3)Open surgical
22、correction of VUR plus prophylactic antibiotics v.prophylactic antibiotics alone to prevent recurrent UTIsEffectiveness of Interventions for VURAuthor,Journal,YearRR new renal scars(2 years)RR new renal scars(5 years)Wheeler,ADC,2003(meta-analysis)1.1(0.3-3.4)1.1(0.8-1.5)Open surgical correction of
23、VUR plus prophylactic antibiotics v.prophylactic antibiotics alone to prevent renal scarring“It is not clear whether any intervention for children with primary VUR does more good than harm.Well designed and adequately powered placebo controlled randomized trials of antibiotics alone in children with
24、 VUR are now required.”(Wheeler et al,Antibiotics and surgery for VUR:a meta-analysis of RCTs,ADC,2003)RIVUR StudyDefinitionsAppropriately treated UTIAntibiotic therapy continues for a minimum of 7 days AND:1)There is documented sensitivity of the organism to the antibiotic used for treatment OR2)Th
25、ere is a documented test of cure(negative urine culture)1-14 days after initiation of therapy.DefinitionsUTI Pyuria on urinalysis10 WBC/mm3(uncentrifuged specimen)OR5 WBC/hpf(centrifuged specimen),OR1+leukocyte esterase on dipstick Culture proven infection with a single organism 5 x 104 CFU/mL(cathe
26、terized or suprapubic aspiration urine specimen)OR105 CFU/mL(clean voided specimen).DefinitionsFever Documented temperature of at least 100.4 F(38 C),measured anywhere on the body either at home or at doctors officeSymptoms Suprapubic,abdominal,or flank pain or tenderness Urinary urgency,frequency,h
27、esitancy,or dysuria,or foul smelling urine In infants 3),QOL assessment X X X Parent Questionnaire X X X X X Randomization X Study medication dispensation X X X X Study medication Accountability X X X X X Urine tests Urinalysis,Culture*,Microalbumin/Creatinine,Urine for central Repository X X Blood
28、tests CBC with diff;Creatinine,lytes,SGOT,SGPT;Cystatin;Blood for central Repository X X Rectal Swabs X X Telephone Follow-up X XRenal ScarringAuthor,Journal,YearVURNo VURRR(95%CI)Rushton,J Urol,199240%43%0.9(0.4-2)Jakobsson,ADC,199442%19%2.2(1.3-3.8)Hoberman,NEJM,200315%6%2.4(1.1-5.2)Garin,Pediatri
29、cs,20066%6%1.1(0.4-3.1)Renal Scarring Less CommonAuthor,Journal,YearN#(%)F/URushton,J Urol,19923316(48)11 mo(mean)Jakobsson,ADC,19947628(37)2 yearsStokland,J Peds,199615759(38)1 yearHoberman,NEJM,200327526(9)6 moGarin,Pediatrics,20061186(5)1 yearDecreasing rates of renal scarring possibly due to inc
30、reased awareness and earlier Dx and Rx of UTIs in febrile infants?Potential Harms and Costs VCUG and RNC are invasive and cause physical discomfort and psychological distress.VCUG involves exposure to ionizing radiation.Diagnosis of VUR and perceived risk of renal scarring causes anxiety to patient
31、and family.Prophylactic antibiotics contribute to antimicrobial resistance in the patient and the community.Recurrent UTIs with bacteria resistant to Cefotaxime=27%in children receiving prophylactic antibiotics v.3%in children not receiving them(RR=9.9;95%CI 4-24.5).(Lutter et al.,Antibiotic resistance patterns in children hospitalized for UTIs,APAM,2006)Costs of diagnosis and treatment potentially great.
