Adjunctive oral corticosteroids reduce renal scarring: the piglet model of reflux and acute experimental pyelonephritis.
OBJECTIVE
We investigate the efficacy of antibiotics combined with corticosteroid in diminishing post-pyelonephritic renal scarring compared to standard antibiotic therapy.


METHODS
Bilateral vesicoureteral reflux was surgically created in 36 piglets (72 kidneys). A week later each bladder was inoculated by percutaneous injection with a standardized broth culture of Escherichia coli and molten paraffin. 99mTechnetium dimercapto-succinic acid (DMSA) scintigraphy was performed 3 days after introduction of urinary infection to detect the presence of acute pyelonephritis. Acute pyelonephritic lesions seen on DMSA scans were graded according to the percentage of renal zone involvement as grade 1--less than 33%, grade 2--33 to 66% and grade 3--greater than 66% involved. When pyelonephritis was present, piglets were randomized to receive either standard antibiotics or antibiotics and 2 mg./kg. prednisolone daily. 99mTechnetium-DMSA scintigraphy was repeated 2 months after completion of therapy, and the kidneys were harvested for gross and histopathological examination. Each kidney was divided into upper, middle and lower zones for correlation of pathological and imaging findings. Severity of renal scarring was then assessed using histopathological confirmation of gross anatomical findings as grade 1--less than 1, grade 2-1 to 2 and grade 3-greater than 2 cm.


RESULTS
Acute pyelonephritis was induced in 136 of 216 renal zones. The sites of renal scarring corresponded anatomically to sites of acute pyelonephritis in all but 5 cases. Overall, the prevalence of post-pyelonephritic scarring was 56.6% (77 of 136) of renal zones. The severity of scarring in both groups correlated with the severity of the initial pyelonephritic lesion. Of the 31 zones that formed grade 3 renal scars the distribution of grades 1, 2 and 3 acute pyelonephritis on the initial DMSA scan was 3, 26 and 71%, respectively. Grade 3 acute pyelonephritis was more likely to result in severe (grade 3) renal scars in the control compared to the steroid treated group (59 versus 31%). Overall, acute pyelonephritis completely resolved in 40% of controls and 51% of steroid treated animals. However, only 9% of control animals with grade 3 acute pyelonephritis demonstrated complete resolution, as opposed to 28% of those receiving steroids.


CONCLUSIONS
The risk of renal scarring is greatest after severe acute pyelonephritis involving greater than 66% of a renal zone. Adjunctive oral prednisolone appears to be effective in diminishing renal scarring in severely affected kidneys. In kidneys with mild and moderate acute pyelonephritis antibiotics alone appear to be equally effective in preventing scarring.
Pohl
H G
HG
Department of Urology, Children's National Medical Center, Washington, DC 20010, USA.
Rushton
H G
HG
Park
J S
JS
Chandra
R
R
Majd
M
M
D000208:Acute Disease; D000818:Animals; D000892:Anti-Infective Agents, Urinary / Q000627:therapeutic use*; D002921:Cicatrix / Q000209:etiology* / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D005938:Glucocorticoids / Q000627:therapeutic use*; D008297:Male; D011239:Prednisolone / Q000627:therapeutic use*; D011704:Pyelonephritis / Q000150:complications* / Q000382:microbiology*; D011897:Random Allocation; D012720:Severity of Illness Index; D013420:Sulfamethoxazole / Q000627:therapeutic use*; D013552:Swine; D014295:Trimethoprim / Q000627:therapeutic use*; D014552:Urinary Tract Infections / Q000150:complications* / Q000517:prevention & control*; D014718:Vesico-Ureteral Reflux / Q000150:complications* / Q000382:microbiology*
D000892:Anti-Infective Agents, Urinary; D005938:Glucocorticoids; D011239:Prednisolone; D014295:Trimethoprim; D013420:Sulfamethoxazole