Neutrophilic tubulitis as a marker for urinary tract infection in renal allograft biopsies with C4d deposition.
BACKGROUND
Neutrophilic tubulitis accompanied by intratubular neutrophil clusters in the renal allograft is a surrogate marker for urinary tract infection (UTI). Overlapping histologic findings can occur in antibody-mediated rejection, which is characterized by peritubular capillary (PTC) deposition of C4d. This study evaluated the incidence of UTI in biopsies with concurrent neutrophilic tubulitis and PTC C4d staining.


METHODS
Thirty-three allograft biopsies from 27 patients selected for the presence of simultaneous C4d staining and neutrophilic tubulitis were correlated with urine culture (U/C) results.


RESULTS
U/C obtained on the same day as the biopsy confirmed UTI in 13 of 33 (39%) biopsies. Among 20 patients with negative U/C; prior culture results within 10 days of the biopsy were available for nine patients, and 5 of 9 (55%) were positive. Thus, UTI was confirmed in 18 of 33 (54%) biopsies. Biopsy interpretation and clinical management was confounded by changes of concurrent acute cellular rejection and antibody-mediated rejection confirmed by demonstration of donor-specific antibodies. Combined therapy with antibiotics and antirejection medications (ART) was administered to 12 of 18 (67%) patients.


CONCLUSIONS
Neutrophilic tubulitis accompanied by neutrophil clusters in the tubular lumen is a useful marker of UTI, even in the presence of PTC C4d deposition. Therapeutic response to antibiotics is limited by co-existent T-cell or antibody-mediated rejection and underlying chronic allograft nephropathy.
Department of Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. guptag@upmc.edu
Gaurav
G
Gupta
Ron
R
Shapiro
Alin
A
Girnita
Ibrahim
I
Batal
Jerry
J
McCauley
Amit
A
Basu
Henkie
H
Tan
Parmjeet
P
Randhawa
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D015935:Complement C4b / Q000032:analysis*; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000473:pathology*; D007684:Kidney Tubules / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology; D010446:Peptide Fragments / Q000032:analysis*; D011704:Pyelonephritis / Q000175:diagnosis / Q000276:immunology / Q000473:pathology; D014184:Transplantation, Homologous; D014552:Urinary Tract Infections / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology*
D015415:Biomarkers; D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d