Pedi gu review uti and vur


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Pedi gu review uti and vur

  1. 1. UTI and VUR Pediatric GU Review UCSD Pediatric Urology George Chiang MD Sara Marietti MD Outlined from The Kelalis-King-Belman Textbook of Clinical Pediatric Urology 2007 (not for reproduction, distribution, or sale without consent)
  2. 2. UTI <ul><li>Second most common bacterial infection in children </li></ul><ul><li>In the first year of life, uncircumcised boys more susceptible to bacteriuria than girls (2.5:1) </li></ul><ul><li>After year one, females are more susceptible than males (20:1) </li></ul><ul><li>Infants with symptomatic infections have a 26% chance of recurrence, usually within the next 3 mo </li></ul>
  3. 3. UTI <ul><li>Risk of UTI in susceptible children persists as they get older, and increases risk of bacteriuria of pregnancy </li></ul><ul><li>Study showed that 68% of those with bacteriuria of childhood had bacteriuria of pregnancy, compared to 26% of controls with no childhood bacteriuria </li></ul><ul><li>Gillenwater, NEJM. 1979 </li></ul>
  4. 4. Etiology <ul><li>E. coli is most common organism (85%) </li></ul><ul><li>E. coli, Klebsiella, Proteus, Psuedomonas, and enterococci represent 95% of all infections </li></ul><ul><li>High frequency of proteus in older uncircumcised boys </li></ul><ul><li>Higher likelihood of staphylococcal infection in adolescent girls </li></ul><ul><li>Greater frequency of E.coli uti in neonatal boys than girls </li></ul><ul><li>Winberg, Acta Ped Scand, 1974. </li></ul>
  5. 5. Virulence Factors <ul><li>Endotoxin – lipopolysaccharide present in bacterium’s cell wall, initiates acute inflammatory response, this response may cause scarring </li></ul><ul><li>K-capsular antigen – increase the bacterium’s resistance to phagocytosis by polymorphonuclear leukocytes </li></ul>
  6. 6. Virulence Factors <ul><li>Hemolysin – digests cells surrounding the site of bacterial adherence, thus aiding in invasion </li></ul><ul><li>Cell surface adhesions molecules (fimbria) – appendages on E.coli that help to adhere to human epithelial cells </li></ul>
  7. 7. P-Fimbriae <ul><li>Bind to specific carbohydrate moiety on the uroepithelial cell surface </li></ul><ul><li>Allow bacteria to ascend up the urinary tract </li></ul><ul><li>Important factor in non-reflux pyelo </li></ul><ul><li>Protective adhesins such as Tamm-Horsfall, can competitively bind to fimbriae thus prohibiting binding to the uroepithelium </li></ul>
  8. 8. Risk Factors for UTI <ul><li>Perineal colonization by intestinal flora is source of most infections </li></ul><ul><li>Females – colonization of the introitus </li></ul><ul><li>Males – colonization of the preputial epithelium </li></ul><ul><li>This colonization may explain why infant boys (uncircumcised) have higher rates of uti than infant girls despite longer urethras </li></ul><ul><li>Risk of pyelo 10x greater in boys not circumcised at birth compared to circumcised boys </li></ul><ul><li>Wiswell. J of Pediatrics. 1988 </li></ul>
  9. 9. Risk Factors for UTI <ul><li>Most explain the higher prevalence of female to male UTI’s (past the age of 12 mo) by the short length of the urethra </li></ul><ul><li>No evidence to suggest improper wiping or bubble baths lead to increased infections </li></ul>
  10. 10. Risk Factors for UTI <ul><li>Dysfunctional voiding is associated with increased risk of infections, management of the dysfuctional voiding can decrease UTI incidence </li></ul><ul><li>One study found 50% of girls with UTI between age 3-5 were dysfunctional voiders </li></ul><ul><li>Fecal elimination is a factor also, must treat constipation </li></ul><ul><li>Hellstrom. Arch Dis Children. 1991. </li></ul>
  11. 11. Risk Factors for UTI <ul><li>Presence of VUR increases chance that organism will access the renal perenchyma </li></ul><ul><li>Reflux allows those organisms that do not have specific virulence factors to gain access to the upper tract </li></ul><ul><li>Thus, LESS virulent organisms are more often isolated in reflux pyelonephritis </li></ul><ul><li>However, the majority of cases of acute pyelo in kids are not associated with reflux </li></ul>
  12. 12. Renal Scarring <ul><li>Renal scarring in a/w VUR occurs only with infection, not sterile urine </li></ul><ul><li>Studies found that scarring occurred with reflux of sterile urine only when obstruction was present (PUV, Hinman’s Syndrome) </li></ul><ul><li>The intermittent high pressure of voiding is not enough to cause scarring </li></ul><ul><li>Ransley. Br J Radiol. 1988 </li></ul>
  13. 13. Renal Scarring <ul><li>Related to number of pyelonephritic episodes </li></ul><ul><li>Severity of scarring is associated with severity of VUR </li></ul><ul><li>Bacteria attach to uroepithelium and start inflammatory response </li></ul><ul><li>Granulocytes aggregate within capillaries and occlude vessels leading to ischemia </li></ul><ul><li>Reperfusion of the ischemic tissue leads to generation of oxygen radicals which are toxic to bacteria and renal tissue </li></ul>
  14. 14. Congenital Reflux Nephropathy <ul><li>Severe reflux may be a/w significant renal dysplasia from abnormal induction of metanephric blastema by ureteral bud </li></ul><ul><li>More often a/w small kidneys or global loss of perenchyma vs focal defects from pyelo scars </li></ul><ul><li>Most have severe VUR (III or higher), detected prenatally, and are male </li></ul><ul><li>DMSA scans done prior to infection show functional abnormalities in 20-60% </li></ul>
  15. 15. Consequences of Scar <ul><li>Hypertension </li></ul><ul><li>More common in severe bilateral scarring </li></ul><ul><li>With longer follow up, percentage of kids with hypertension increases </li></ul><ul><li>One study found 38% with 34 years of follow-up </li></ul><ul><li>Jacobson. Br Med Journal. 1989. </li></ul>
  16. 16. Renal Insufficiency <ul><li>5-10% of kids on dialysis, from reflux nephropathy </li></ul><ul><li>Studies show that kids who stay infection free with their VUR usually do not have progressive renal damage </li></ul><ul><li>Most severe damage from infection usually occurs early in life </li></ul>
  17. 17. Diagnosis of UTI <ul><li>Pyuria on UA not 100% reliable </li></ul><ul><li>LE 88-95% sensitive for detection of pyuria </li></ul><ul><li>Nitrite 30-45% sensitive, 98% specific </li></ul><ul><li>Combined 78-92% sensitive, 60-98% specific </li></ul><ul><li>Should diagnose by urine culture </li></ul>
  18. 18. Diagnosis of UTI <ul><li>>100,000 colonies in voided specimen </li></ul><ul><li>>10,000 colonies in catheterized or suprapubic aspirate </li></ul><ul><li>Bagged specimen helpful if negative </li></ul>
  19. 19. Evaluation of Children with UTI <ul><li>Varies widely </li></ul><ul><li>High recurrence rate within one year of first infection (30% in girls, 15% in boys) </li></ul><ul><li>About 1/3 of those with UTI’s will have reflux </li></ul><ul><li>Significant renal scarring can occur after 1 documented episode of pyelonephritis </li></ul><ul><li>Who do you evaluate? All kids less than 5 with culture documented UTI, all girls with recurrent or febrile infections (Gil Rushton, .M.D.) </li></ul>
  20. 20. Bottom Up Approach <ul><li>Goal is to identify all reflux </li></ul><ul><li>Cystogram (VCUG or radionuclide) </li></ul><ul><li>Ultrasound to evaluate the upper tract </li></ul><ul><li>Based on caveat that all kids with reflux need treatment </li></ul>
  21. 21. Bottom Up Approach <ul><li>VCUG very helpful to evaluate male urethra, and better anatomic detail </li></ul><ul><li>Radionuclide cystogram has less radiation exposure, but VCUG starting to minimize exposure </li></ul><ul><li>Both require catheterization </li></ul><ul><li>Indirect radionuclide cystogram has been introduced, but it misses up to 2/3 of refluxing ureters </li></ul>
  22. 22. Bottom Up Approach <ul><li>Some recommend waiting 4-6 weeks after infection resolves, so that mild transient reflux from inflammation is not picked up </li></ul><ul><li>Others believe that this is very rare </li></ul><ul><li>Others believe that any reflux is meaningful, especially during infection and recommend imaging after sx resolve and ucx is sterile </li></ul><ul><li>No role for routine cystoscopy </li></ul>
  23. 23. Bottom Up Approach <ul><li>Upper tract imaging timing and modality also varies from place to place </li></ul><ul><li>Some recommend US to evaluate for hydro or renal structural abnormalities </li></ul><ul><li>However, yield after first UTI is low </li></ul><ul><li>Less than 1% have obstruction requiring intervention </li></ul><ul><li>Hoberman. NEJM. 2003. </li></ul>
  24. 24. Bottom Up Approach <ul><li>Ultrasound is not great at detecting scarring </li></ul><ul><li>DMSA scan is best to detect scar and acute pyelonephritis </li></ul><ul><li>Clinical parameters have low sensitivity in detecting pyelonephritis (CRP, ESR, WBC count and fever) </li></ul><ul><li>DMSA is test of choice to demonstrate pyelonephritis </li></ul>
  25. 25. Top Down Approach <ul><li>Focus is on renal status, than on presence of VUR </li></ul><ul><li>Goal is to identify clinically significant VUR, those patients at risk for renal scarring </li></ul><ul><li>Begins with the DMSA scan </li></ul><ul><li>VCUG only for those with abnormal DMSA or recurrent UTI’s </li></ul><ul><li>Attempt to avoid treating “clinically insignificant” reflux and decrease number of VCUG’s </li></ul>
  26. 26. Treatment of UTI <ul><li>Cystitis – optimal duration is controversial, 3-5 day po antibiotic, if < 5 should continue prophylactic antibiotic until radiologic eval completed </li></ul><ul><li>Pyelonephritis – Treat quickly, delays cause increase scar, non-toxic and >2mo can be treated as outpt (oral 3 rd generation cephalosporin) </li></ul>
  27. 27. Treatment of UTI <ul><li>Pyelonephritis – toxic or less than 2 mo need immediate IV treatment </li></ul><ul><li>Start with amp/gent until culture back </li></ul><ul><li>Can start with 3 rd generation cephalosporin, but missing gram pos coverage such as enterococcus </li></ul><ul><li>Cipro now FDA approved for complicated UTI’s in kids </li></ul><ul><li>14 day course total, can change to po when afebrile for 48 hours </li></ul>
  28. 28. Asymptomatic Bacteriuria <ul><li>Studies have shown that ABU does not produce new scarring in the absence of reflux </li></ul><ul><li>Treatment of ABU may produce more virulent strains </li></ul><ul><li>Should be treated in children that have reflux </li></ul><ul><li>Linshaw. Kid Intern. 1996. </li></ul>
  29. 29. Renal Abscess <ul><li>In the past, usually from hematogenous route, staph </li></ul><ul><li>Urine cultures often negative </li></ul><ul><li>Now, if present more often from ascending infections of gram- bacteria </li></ul><ul><li>No great studies in treatment of abscess in children, but recommend starting with IV abx and if fail, percutaneous drainage </li></ul><ul><li>Surgical treatment is last option </li></ul>
  30. 30. Xanthogranulomatous Pyelonephritis <ul><li>Destruction of perenchyma and accumulation of lipid-laden macrphages called xanthoma cells </li></ul><ul><li>Case reports in children </li></ul><ul><li>Non specific symptoms, fever, FTT, lethargy, palpable mass occasionally </li></ul><ul><li>Proteus is MC organism </li></ul>
  31. 31. XGP <ul><li>Focal and diffuse forms, focal MC in children </li></ul><ul><li>Can mimic malignancy on imaging, making diagnosis difficult </li></ul><ul><li>Nephrectomy for diffuse, may attempt partial for focal </li></ul>
  32. 32. Non-Surgical Management of Reflux <ul><li>Based on belief that VUR will often resolve over time and morbidity can be reduced by keeping the urine sterile </li></ul><ul><li>Low dose septra, nitrofurantoin, trimethoprim alone, or in very young amoxicillin </li></ul><ul><li>Some recommend UA and UCX every 6 mo, some only with symptoms </li></ul><ul><li>Follow up cystogram every 18 mo </li></ul><ul><li>Some recommend baseline DMSA scan on higher risk patients </li></ul>
  33. 33. Non-Surgical Management <ul><li>Resolution affected by grade of reflux, age at presentation, laterality, and presence of dysfunctional voiding </li></ul><ul><li>Lower grades more likely to resolve within 5 years </li></ul><ul><li>More likely to resolve if child is less than 1 year </li></ul>
  34. 34. Non-Surgical Management <ul><li>DES found in 43% of children with primary VUR </li></ul><ul><li>These children are more likely to require surgery and surgery is more likely to fail </li></ul><ul><li>Timed frequent voids are important, vibrating wrist watch reminder, treat constipation </li></ul>
  35. 35. Non-Surgical Managment <ul><li>Prospective studies have shown no change in renal growth or new scarring in kids with surgical vs non-surgical treatment if urine is kept sterile </li></ul><ul><li>Elder. J Urol. 1997. </li></ul>
  36. 36. Non-Surgical Management <ul><li>Some advocate ending prophylaxis in children 6-8 with I-III reflux who have not had UTI’s, normal voiders, and do not have severe scarring </li></ul><ul><li>???? </li></ul>
  37. 37. Non-Surgical Management <ul><li>Females with h/o recurrent childhood UTI’s need to be watched closely during pregnancy </li></ul><ul><li>Need close surveillance urine cultures regardless of whether VUR was surgically corrected </li></ul><ul><li>Untreated asymptomatic bacteriuria during pregnancy increases risk of low birth weight baby and preterm delivery </li></ul><ul><li>Women with severe scarring or impaired renal function have increases htn, pre-eclampsia and increased fetal loss </li></ul>
  38. 38. Non-Surgical Management <ul><li>Lacking prospective proof that prophylactic antibiotics actually reduce UTI and/or renal scarring </li></ul><ul><li>Studies are pending </li></ul>
  39. 39. Surgical Treatment <ul><li>Indications for surgical intervention are tailored to the individual </li></ul><ul><li>Breakthrough UTI’s and poor compliance/tolerance </li></ul><ul><li>UTI’s with progressive renal damage, persistent reflux, renal growth retardation, older females with persistent reflux </li></ul>
  40. 40. Surgical Treatment <ul><li>95-98% success for grades I-IV </li></ul><ul><li>80-85% for grade V </li></ul><ul><li>? Need for post-operative VCUG? </li></ul><ul><li>Renal ultrasound in 4-6 weeks post-operatively </li></ul><ul><li>Antibiotics generally continued post-operatively but duration is individualized </li></ul>
  41. 41. Surgical Management <ul><li>1% obstruction, if severe place PCN and wait, possible resolution, may need re-op </li></ul><ul><li>New contralateral reflux – 1-18%, low grade, usually resolves </li></ul><ul><li>Persistent reflux – consider failed procedure vs ureterovesical fistula </li></ul>
  42. 42. Tapered Reimplants <ul><li>Imbricate if not extremely large </li></ul><ul><li>Starr or Kalicinski – Kalicinski may be more bulky </li></ul><ul><li>Advantage to plication is preservation of blood supply and decreased chance of leak </li></ul><ul><li>Excisional tapering – needed for extremely large ureters </li></ul>
  43. 43. Tapered Reimplant <ul><li>Taper over 10 Fr tube, 2-layer closure </li></ul><ul><li>Must leave stent in place to decrease extravasation and for renal protection during period of ureteral edema </li></ul><ul><li>Higher risk of urinary leakage </li></ul>
  44. 44. Surgical Treatment Endoscopic <ul><li>Of all substances used, Deflux (cross-linked dextranomer microspheres) is only FDA approved </li></ul><ul><li>Debate: specific indications for use </li></ul><ul><li>Some use same as indications for open surgery, some inject after 18 mo if reflux not resolved </li></ul>
  45. 45. Deflux <ul><li>Success rates between 68-91% </li></ul><ul><li>Meta-analysis: 78% grade I-II, 72% grade III, 63% grade IV, 51% grade V </li></ul><ul><li>Elder. J Urol. 2005. </li></ul><ul><li>Success likely depends upon grade of reflux, injection technique, and surgeon experience </li></ul><ul><li>Deflux can be repeated or followed by open reimplant </li></ul>
  46. 46. Endoscopic Therapy for Vesicoureteral Reflux: A Meta-Analysis Elder, J. of Urol. 2006 <ul><li>Meta-analysis of 63 articles </li></ul><ul><li>Included deflux, collagen, chondrocytes, blood, and other injectables </li></ul><ul><li>5,5027 patients identified </li></ul><ul><li>After 1 tx resolution by grade was: I/II-78.5%, III-72%, IV-63%, V-51% </li></ul>
  47. 47. Meta-Analysis <ul><li>If first injection was unsuccessful, 68% of second injection was successful, 34% for third injection </li></ul><ul><li>Lower success for duplications – 50% overall </li></ul><ul><li>Neuropathic bladder overall success rate was 62% </li></ul><ul><li>Following failed open reimplant, success of deflux was 65% </li></ul>
  48. 48. Long-Term Follow Up of Children Treated with Deflux for VUR Lackgren, J. of Urol. 2001. <ul><li>221 patients identified </li></ul><ul><li>Followed for 2-7 years </li></ul><ul><li>On 3-month follow up had 68% success rate </li></ul><ul><li>49 patients had repeat VCUG 2-5 years post-op </li></ul><ul><li>96% remained reflux free </li></ul>
  49. 49. Deflux <ul><li>Don’t know true durability </li></ul><ul><li>Those who initially were cured, may recur at a later date </li></ul><ul><li>How do we follow these pt??? </li></ul>