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The authors have presented a widespread cross-sec- tional analysis of the prevalence of renal scarring after DMSA documented pyelonephritis. They found that overall renal scarring varied geographically, and that children and refluxing renal units were at increased risk for cortical scarring after acute pye- lonephritis. The statistical methods and conclusions based on the results are valid. Given the methodol- ogy of meta-analyses in general, flaws and biases are inevitable. The authors acknowledge this fact and attempt to limit such bias but cannot eliminate it completely. The data reflect and reinforce some of the prevailing wisdom and teaching but refute prior data suggesting that renal cortical scarring occurs equally in kidneys with a refluxing and a nonreflux- ing ureter. Even after excluding influential and out- lying data the conclusion that a cortical scar is ac- quired is still based on the assumption that DMSA assessment can accurately differentiate an acquired renal scar from congenital renal dysplasia. Perform- ing an initial and followup DMSA scan at least 3 months later helps with this determination but can- not eliminate this type of publication bias com- pletely and conclusively. What this type of report does well is reestablish the importance of VUR in the development of child- hood pyelonephritis. It refocuses the debate sur- rounding VUR on, as stated by the authors, a de- tailed risk analysis of children presenting with acute pyelonephritis, which should include not only the presence of VUR, but also important factors such as bladder and bowel function/habits, treatment delay, genetic susceptibility, bacterial virulence factors and parent/physician education. This approach is likely the best way to limit childhood renal scarring. Daniel Herz Department of Urology Children’s Hospital at Dartmouth Dartmouth-Hitchcock Medical Center Lebanon, New Hampshire REPLY BY AUTHORS Both reviewers comment that a particular weakness of our methodology is the inability to discriminate between congenital and acquired renal cortical de- fects, which are characterized by disruption of the normal contour of the kidney and volume loss on DMSA renal scans. They note that in the absence of a baseline DMSA renal scan demonstrating normal renal contour post-pyelonephritic renal cortical de- fects cannot be reliably called scars with which we agree. However, this meta-analysis included articles only when baseline DMSA renal scans were ob- tained near the time of infection and confirmed the presence of lesions consistent with acute inflamma- tion of the renal parenchyma, characterized by pho- topenia with preservation of the renal contour. These acute inflammatory renal cortical lesions can be differentiated from congenital abnormalities or renal scars by experienced clinicians. Thus we have, to the ability provided by the available literature, restricted our analysis to cases conforming to the most robust definitions available for acute inflam- mation and acquired renal cortical scars. INCIDENCE OF POST-PYELONEPHRITIC RENAL SCARRING 298

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INCIDENCE OF POST-PYELONEPHRITIC RENAL SCARRING298

The authors have presented a widespread cross-sec-tional analysis of the prevalence of renal scarringafter DMSA documented pyelonephritis. They foundthat overall renal scarring varied geographically,and that children and refluxing renal units were atincreased risk for cortical scarring after acute pye-lonephritis. The statistical methods and conclusionsbased on the results are valid. Given the methodol-ogy of meta-analyses in general, flaws and biases areinevitable. The authors acknowledge this fact andattempt to limit such bias but cannot eliminate itcompletely. The data reflect and reinforce some ofthe prevailing wisdom and teaching but refute priordata suggesting that renal cortical scarring occursequally in kidneys with a refluxing and a nonreflux-ing ureter. Even after excluding influential and out-lying data the conclusion that a cortical scar is ac-quired is still based on the assumption that DMSAassessment can accurately differentiate an acquired

REPLY BY AUTHORS

only when baseline DMSA renal scans were ob-

ing an initial and followup DMSA scan at least 3months later helps with this determination but can-not eliminate this type of publication bias com-pletely and conclusively.

What this type of report does well is reestablishthe importance of VUR in the development of child-hood pyelonephritis. It refocuses the debate sur-rounding VUR on, as stated by the authors, a de-tailed risk analysis of children presenting with acutepyelonephritis, which should include not only thepresence of VUR, but also important factors such asbladder and bowel function/habits, treatment delay,genetic susceptibility, bacterial virulence factorsand parent/physician education. This approach islikely the best way to limit childhood renal scarring.

Daniel Herz

Department of UrologyChildren’s Hospital at Dartmouth

Dartmouth-Hitchcock Medical Center

renal scar from congenital renal dysplasia. Perform- Lebanon, New Hampshire

Both reviewers comment that a particular weaknessof our methodology is the inability to discriminatebetween congenital and acquired renal cortical de-fects, which are characterized by disruption of thenormal contour of the kidney and volume loss onDMSA renal scans. They note that in the absence ofa baseline DMSA renal scan demonstrating normalrenal contour post-pyelonephritic renal cortical de-fects cannot be reliably called scars with which weagree. However, this meta-analysis included articles

tained near the time of infection and confirmed thepresence of lesions consistent with acute inflamma-tion of the renal parenchyma, characterized by pho-topenia with preservation of the renal contour.These acute inflammatory renal cortical lesions canbe differentiated from congenital abnormalities orrenal scars by experienced clinicians. Thus we have,to the ability provided by the available literature,restricted our analysis to cases conforming to themost robust definitions available for acute inflam-

mation and acquired renal cortical scars.