Screening of vesicoureteral reflux in pediatric patients with kidney transplantation showing non-specific interstitial fibrosis and tubular atrophy with interstitial Tamm-Horsfall protein deposits in protocol allograft biopsy.

Interstitial fibrosis and tubular atrophy (IF/TA) in kidney allografts are induced by multiple factors, and although much effort has been devoted on the classification of IF/TA, clarification of the causes of non-specific IF/TA is equally important for appropriate therapy. Tamm-Horsfall protein (THP) in renal tissue can be a useful marker for the histological expression of urine backflow and suspected vesicoureteral reflux (VUR). Here, we examined the presence of VUR in pediatric recipients with interstitial THP deposits in kidney allografts to clarify the cause of non-specific IF/TA. Ten pediatric patients showing interstitial THP deposits with non-specific IF/TA were enrolled and voiding cystourethrography was performed. Major histological findings of these patients were interstitial mononuclear cell infiltration and fibrosis associated with interstitial THP deposits. The semiquantitative grading scores of IF/TA were as follows: (i) mild IF/TA (n = 3); (ii) moderate IF/TA (n = 3); and (iii) severe IF/TA (n = 4). In the severe grade, diffuse interstitial mononuclear cell infiltrates were prominent with the appearance of thyroidization classically observed in chronic pyelonephritis. Eight of ten patients (80%) had VUR into the graft. Although symptomatic pyelonephritis was not observed in any of the patients, asymptomatic bacteriuria was detected in 40.0% of the patients. There was no significant correlation between VUR grade and IF/TA histological score. The patients without VUR also showed mild or severe IF/TA. Therefore, VUR and urinary flow stasis accompanied by asymptomatic urinary tract infection appear to be the causes of interstitial mononuclear cell infiltration and fibrosis associated with interstitial THP deposits in kidney allografts.