UTI and VUR Practical points and management Kjell Tullus Consultant Paediatric Nephrologist

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1 UTI and VUR Practical points and management Kjell Tullus Consultant Paediatric Nephrologist

2 Discussion points Diagnosis VUR Radiological investigations

3 1. Contamination Problems 2. Bacterial numbers 3. Febrile UTI vs. ABU in a child with a febrile viral disease

4 Voiding with prepuce flushing

5 Voiding and flushing vagina

6 Contamination rate Comparison of clean-voided urine and suprapubic bladder puncture in 120 infants and children 25% contamination rate in the cleanvoided specimens Aronson AS et al Acta Paediatr 1973;62:396

7 Contamination rates 7584 urine cultures in children <24 month Bag specimens 62.8% Catheter specimens 9.1% Al Orifi et al J Pediatr 2000;137:221

8 AAP Bag urine samples have too many false positive cultures SPA or catherisation needs to be done

9 General view Culture numbers >10 5 bacteria/ml in single culture Or any growth if suprapubic bladder puncture

10 Bacterial numbers Present cut off levels defined by Ed Kass in the 1950-ties in women with cystitis He knew that he had some false negative diagnosis but wanted from scientific purposes to only include true infections

11 Proportion of lower than 10 5 Swedish study in 366 infants with proven symptomatic UTI 73 (20%) had less than 10 5 bacteria on culture from suprapubic aspiration Hansson S, et al J Pediatr 199;132:180

12 Finnish study 477 infants 322 had bacteria on SPA Only 81% of those had more than 10 5 bacteria on a the clean voided specimen done at the same time. Of the missed children 18 showed 10 4 and bacteria on the clean voided specimen Koskimies O. J Pediatr 1995;126:157

13 AAP Lower recommended cut off to 5 x 10 4 bacteria/ml

14 Persistence of infantile ABU - boys

15 Summary A reliable urine culture is difficult to get SPA or bladder catherisation should be preferred in infants A fixed bacterial number defining a UTI does not exist

16 Discussion points Diagnosis VUR Radiological investigations

17 Occurrence of VUR Only a few per cent of all children were thought to have VUR Recent studies have put that notion question.

18 Occurrence of VUR in 347 children Certain UTI Possible UTI Improbable UTI Venhola et al Acta Pædiatrica 99, 12, pages , 2010

19 Occurrence of VUR in 1185 children Hannula et al Ped Nephrol 2010;25:1463

20 Natural history of VUR

21 VUR grading

22 MCUG Isotope Indirect Direct Ultrasound Imaging With contrast Doppler wave measurement

23 MCUG

24 Summary VUR might be seen in normal infants and toddlers VUR is growing away The need to know about VUR is thus not very important in most children BUT There are clearly a small group where the VUR is clinically important

25 Prognosis of acute pyelonephritis Renal scarring on urography 10-15% Uptake defect on DMSA 40%

26 DMSA uptake defect

27 Reflux and renal scarring Reflux grade No. of children Scarring % % % > % Total % Jodal et al

28 Occurrence of the different types Boys Girls Primary (congenital) Acquired 3 37 Wennerström et al J Pediatr 2000;136:30-4

29 Renal scarring Chronic renal failure Hypertension Complications of pregnancy

30 How common is CRF as a consequence of acute pyelonephritis? Very conflicting data from different countries Swedish experience of all children with UTI during 10 years in Gothenburg 232 boys and 989 girls

31 GFR in Gothenburg material Wennerström et al Arch Pediatr Adolesc Med 2000;154:339-45

32 Renal scarring Chronic renal failure Hypertension Complications of pregnancy

33 Hypertension 15 year follow-up of original cohort of 100 children with reflux nephropathy Seven out of the 55 patients that were possible to evaluate had hypertension Goonasekera et al the Lancet 1996;347:640-3

34 Hypertension - Sweden

35 Renal scarring Chronic renal failure Hypertension Complications of pregnancy

36 Pregnancy complications No significant difference in the incidence of pre-eclampsia, operative delivery, prematurity or birth weight in the Gothenburg material Martinell et al BMJ 1990;300:840-4

37 Conclusion Renal scarring in a country with an aggressive policy of treating febrile UTI does not seem to have a high morbidity

38 How to prevent VUR from causing acute pyelonephritis and scarring? If we can do something meaningful with the VUR it might be useful to detect it - otherwise not! Surgery Reimplantation Sting e.g deflux Antibiotic prophylaxis

39 Surgical treatment vs medical treatment Olbing et al J Urol 1992;148:1653-6

40 Medical vs surgical 5-year follow-up Smellie J et al the Lancet 2001;357:

41 Sting or Deflux Does reduce VUR at least for some time Only one comparative study

42 Prophylactic medications Surprisingly few and bad studies until recently

43 Combined estimates of the effect of antimicrobial prophylaxis on prevention of pyelonephritis in children 2 to 24 months of age without VUR, from random-effects modeling. Pediatrics 2011;128:e749-e by American Academy of Pediatrics

44 Combined estimates of the effect of antimicrobial prophylaxis on prevention of pyelonephritis in children 2 to 24 months of age with grade I VUR, from random-effects modeling. Pediatrics 2011;128:e749-e by American Academy of Pediatrics

45 Combined estimates of the effect of antimicrobial prophylaxis on prevention of pyelonephritis in children 2 to 24 months of age with grade II VUR, from random-effects modeling. Pediatrics 2011;128:e749-e by American Academy of Pediatrics

46 Combined estimates of the effect of antimicrobial prophylaxis on prevention of pyelonephritis in children 2 to 24 months of age with grade III VUR, from random-effects modeling. Pediatrics 2011;128:e749-e by American Academy of Pediatrics

47 Combined estimates of the effect of antimicrobial prophylaxis on prevention of pyelonephritis in children 2 to 24 months of age with grade IV VUR, from random-effects modeling. Pediatrics 2011;128:e749-e by American Academy of Pediatrics

48 Estimate of the effect of antimicrobial prophylaxis on prevention of pyelonephritis in children 2 to 24 months of age with grade V VUR, from random-effects modeling. Pediatrics 2011;128:e749-e by American Academy of Pediatrics

49 Combined estimates of the effect of antimicrobial prophylaxis on prevention of pyelonephritis in children with VUR, from random-effects modeling. Pediatrics 2011;128:e749-e by American Academy of Pediatrics

50 Prophylactic medication Swedish study 203 children, 75 boys and 128 girls Grade III and IV VUR Age 1-2 years Treated with Prophylaxis (trimethoprim) n=69 Sting (deflux) n=66 Surveillance n=68 2 year follow-up

51 Outcome of reflux at 2 years Swedish study Still grade III or IV 60% prophylaxis group 30% deflux group 55% surveillance group VUR disappeared 15% prophylaxis group 40% deflux group 20% surveillance group

52 UTI recurrence at 2 years Swedish study Girls 18% prophylaxis group 22% deflux group 55% surveillance group Boys 8% prophylaxis group 17% deflux group 4% surveillance group Significant difference for girls but not for boys

53 New renal scarring at 2 years Swedish study Girls 0 prophylaxis group 4 deflux group 7 surveillance group Boys 0 prophylaxis group 1 reflux group 1 surveillance group Significant difference for girls but not for boys

54 N Engl J Med 2014 Enrollment, Randomization, and Follow-up of Children in the Trial. RIVUR Trial

55 Time to First Recurrent Febrile or Symptomatic UTI. Febrile or symptomatic UTI

56 N Engl J Med Effect of Antimicrobial Prophylaxis on the Risk of Febrile or Symptomatic UTI. Risk for recurrent UTI in subgroups

57 Clinical Outcomes According to Study Group. Clinical outcome - scarring

58 Resolved 50.9% Improved 23.4% Unchanged 18.5% Worse 7.2% VUR at 2 years

59 Side effects from Prophylactic antibiotics Increased number of non-e.coli pathogens Increased resistance to amoxiclav, cotrimoxazole, cefuroxime, cefriaxone, gentamicin and nitrofurantoin Bitsori et al Ped Nephrol 2014;29:1053

60 Summary VUR does predispose to acute pyelonephritis which could cause renal scarring Surgery does not prevent new renal scarring Prophylactic antibiotics might do that in certain groups of children?

61 AAP and NICE Prophylactic antibiotics should not be used routinely but in selected circumstances

62 Discussion point Diagnosis Treatment Radiological investigations

63 What do we want to know? Major malformations US Kidney scars DMSA VUR - MCUG

64 AAP US in all infants after first UTI They recognise that the yield of actionable findings is low,1-2%

65 AAP Timing of US within two days in those who had a complicated course or did not getter better quickly Later in the majority that got better quickly. Too early US can give a lot of false positive reversible findings

66 AAP DMSA in none! DMSA is useful research tool but does rarely affect acute clinical management

67 AAP MCUG should not be performed routinely after first febrile UTI but in selected cases

68 Summary More emphasise is needed to make a correct diagnosis Fewer children need prophylactic antibiotics and for shorter times Fewer children need imaging

Why is the management of UTI so controversial? Kjell Tullus Consultant Paediatric Nephrologist

Why is the management of UTI so controversial? Kjell Tullus Consultant Paediatric Nephrologist Diagnosing a UTI More difficult then most people realise Contaminating culture Bacterial numbers Confusion