Adjunctive oral corticosteroids reduce renal scarring: The piglet model ofreflux and acute experimental pyelonephritis

Purpose: We investigate the efficacy of antibiotics combined with corticost eroid in diminishing post-pyelonephritic renal scarring compared to standar d antibiotic therapy. Materials and Methods: Bilateral vesicoureteral reflux was surgically creat ed in 36 piglets (72 kidneys). A week later each bladder was inoculated by percutaneous injection with a standardized broth culture of Escherichia col i and molten paraffin. (99m)Technetium dimercapto-succinic acid (DMSA) scin tigraphy was performed 3 days after introduction of urinary infection to de tect the presence of acute pyelonephritis. Acute pyelonephritic lesions see n on DMSA scans were graded according to the percentage of renal zone invol vement 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. prednisolo ne daily. (99m)Technetium-DMSA scintigraphy was repeated 2 months after com pletion of therapy, and the kidneys were harvested for gross and histopatho logical examination. Each kidney was divided into upper, middle and lower z ones for correlation of pathological and imaging findings. Severity of rena l 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-grea ter than 2 cm. Results: Acute pyelonephritis was induced in 136 of 216 renal zones. The si tes of renal scarring corresponded anatomically to sites of acute pyeloneph ritis in all but 5 cases. Overall, the prevalence of post-pyelonephritic sc arring was 56.6% (77 of 136) of renal zones. The severity of scarring in bo th groups correlated with the severity of the initial pyelonephritic lesion . Of the 31 zones that formed grade 3 renal scars the distribution of grade s 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 i n 40% of controls and 51% of steroid treated animals. However, only 9% of c ontrol animals with grade 3 acute pyelonephritis demonstrated complete reso lution, as opposed to 28% of those receiving steroids. Conclusions: The risk of renal scarring is greatest after severe acute pyel onephritis involving greater than 66% of a renal zone. Adjunctive oral pred nisolone appears to be effective in diminishing renal scarring in severely affected kidneys. In kidneys with mild and moderate acute pyelonephritis an tibiotics alone appear to be equally effective in preventing scarring.