PEDIATRIC UROLOGY

Early treatment of acute pyelonephritis in children fails to reduce renal scarring: data from the Italian Renal Infection Study Trials
Hewitt IK, Zucchetta P, Rigon L, Maschio F, Molinari PP, Tomasi L, Toffolo A, Pavanello L, Crivellaro C, Bellato S, Montini G
Nephrology, Dialysis, and Transplant Unit, Pediatric Department, Azienda Ospedaliera di Padova, Padova, Italy
Pediatrics. 2008; 122: 486-90

• Objectives: The American Academy of Pediatrics recommendation for febrile infants and young children suspected of having a urinary tract infection is early antibiotic treatment, given parenterally if necessary. In support of this recommendation, data suggesting that delay in treatment of acute pyelonephritis increases the risk of kidney damage are cited. Because the risk was not well defined, we investigated renal scarring associated with delayed versus early treatment of acute pyelonephritis in children.
• Methods: The research findings are derived from 2 multicenter, prospective, randomized, controlled studies, Italian Renal Infection Study 1 and 2, whose primary outcomes dealt with initial antibiotic treatment and subsequent prophylaxis, respectively. From the 2 studies, we selected the 287 children with confirmed pyelonephritis on acute technetium-99m-dimercaptosuccinic acid scans who underwent repeat scanning to detect scarring 12 months later. The children were 1 month to < 7 years of age when they presented with their first recognized episode of acute pyelonephritis in northeast Italy.
• Results: Progressive delay in antibiotic treatment of acute pyelonephritis from < 1 to >/= 5 days after the onset of fever was not associated with any significant increase in the risk of scarring on technetium-99m-dimercaptosuccinic acid scans obtained 1 year later. The risk of scarring remained relatively constant at 30.7 +/- 7%. Clinical and laboratory indices of inflammation were comparable in all groups, as was the incidence of vesicoureteric reflux.
• Conclusions: Early treatment of acute pyelonephritis in infants and young children had no significant effect on the incidence of subsequent renal scarring. Furthermore, there was no significant difference in the rate of scarring after acute pyelonephritis when infants and young children were compared with older children.
  
  
• Editorial Comment
  Because of the long-term effects of pyelonephritis in children, including hypertension, proteinuria, and chronic renal failure, these authors studied whether early treatment of acute pyelonephritis diminishes renal scars in 287 children in a multicenter open-label parallel-group trial in Italian children, presenting with their first documented episode of acute pyelonephritis.
  Initially the children were randomized to receive in one group either co-amoxiclav, or parenterally administered ceftriaxone. The second group was randomized to treat with antibiotic prophylaxis versus no treatment in a follow up study. Children were one month to seven years of age and acute pyelonephritis was the diagnosis when WBC > 25 cells/microliter in the urine, and a growth of a single organism of > 100,000 colonies in two consecutive tests as well as two or more of the following criteria: fever > 38°C, increased erythrocyte sedimentation rate or C-reactive protein level or neutrophil levels above normal for the age. Children are only included in the study with acute positive technetium DMSA scans performed within ten days of beginning antibiotic treatment and follow up scans 12 months later, and ultrasounds were also done.
  There was no significant difference in the incidence of scarring with progressive delay and the initiation of antibiotic therapy from 1 to > 5 days after the onset of the fever. This was true for the subgroup of patients under two years of age. The scarring changes were found to be independent of early resolution of fever.
  This article is discouraging in some respects since it has been long-held that prompt aggressive antibiotic treatment will diminish renal scarring in the setting of acute pyelonephritis. It would encourage the use of prophylactic antibiotics to prevent pyelonephritis except recent studies have cast a long shadow on the efficacy of prophylactic antibiotics to do this. Data also shows that the overall risk of scarring was independent of age between one month and seven years in this large study population. This would also suggest that early stoppage of prophylactic antibiotics and follow up in vesicoureteral refluxing patients may not be a wise choice also.
  This is very good data in spite of the results confusing clinicians with older studies, it sheds light on the fact that this topic is one to be watched carefully in the future to guide further management.

Dr. Brent W. Snow
Division of Urology
University of Utah Health Sci Ctr
Salt Lake City, Utah, USA
E-mail: brent.snow@hsc.utah.edu