title: Acute pyelonephritis in renal allografts: a new role for microRNAs?
abstract: BACKGROUND
  Acute pyelonephritis (APN) versus acute rejection (AR) is a frequently encountered diagnostic and therapeutic dilemma in kidney transplants. Variable culture results, overlapping histologic features, and persistent graft dysfunction despite antibiotics are frequently encountered. Therefore, we explored the utility of intragraft microRNA profiles to distinguish between allograft APN and AR.
  
  
  METHODS
  Between 2003 and 2011, we identified 49 patients with biopsy features of APN, within the first 2 years posttransplant. MicroRNA profiling was performed on 20 biopsies (normal kidney, n=4; unequivocal AR, n=5; features of APN, n=11).
  
  
  RESULTS
  Only 32% (16/49) of the patients had concomitant positive urine cultures at biopsy, and in 8 of 16 patients, colony count was less than 10 CFU/mL. In 14 of 49 patients, positive urine culture did not coincide with the biopsy, and in 19 of 49 patients, urine cultures were negative. On microRNA profiling, good clustering was seen among the normal kidneys and among AR biopsies. Among the 11 biopsies with features of APN, 4 biopsies showed good clustering with a pattern distinct from AR; (these patients recovered graft function with antibiotics); 7 of 11 biopsies showed heterogeneity in microRNA profiles and variable outcomes with antibiotic treatment. We identified a panel of 25 microRNAs showing statistical difference in expression between AR and APN. MiR-99b, miR-23b let-7b-5p, miR-30a, and miR-145 were validated using qPCR.
  
  
  CONCLUSIONS
  Allograft pyelonephritis can be a diagnostic and therapeutic challenge. A gestalt approach is required. In addition to histology and cultures, differential intragraft microRNA expression may prove helpful to distinguish APN from AR in renal allograft biopsies.
authors: 1 Department of Pathology, Ohio State University Wexner Medical Center, Columbus, Ohio. 2 Ohio State University Wexner Medical Center, Columbus, Ohio. 3 Department of Internal Medicine, Nephrology, Department of Pathology, Ohio State University Wexner Medical Center, Columbus, Ohio. 4 NanoString Technologies, Seattle, Washington. 5 Comprehensive Transplant Center, Department of Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio. 6 Address correspondence to: Anjali A. Satoskar, M,D., Department of Pathology,Division of Renal and Transplant Pathology, M015 Starling Loving, 320 W 10th Ave., Ohio State University Wexner Medical Center, Columbus, OH.
authors: Steve
authors: S
authors: Oghumu
authors: Anna
authors: A
authors: Bracewell
authors: Uday
authors: U
authors: Nori
authors: Kirsteen H
authors: KH
authors: Maclean
authors: Joan-Miquel
authors: JM
authors: Balada-Lasat
authors: Sergey
authors: S
authors: Brodsky
authors: Ronald
authors: R
authors: Pelletier
authors: Mitchell
authors: M
authors: Henry
authors: Abhay R
authors: AR
authors: Satoskar
authors: Tibor
authors: T
authors: Nadasdy
authors: Anjali A
authors: AA
authors: Satoskar
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D064591:Allografts; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001706:Biopsy; D015331:Cohort Studies; D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006084:Graft Rejection / Q000175:diagnosis* / Q000453:epidemiology*; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D011704:Pyelonephritis / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology*; D012189:Retrospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D035683:MicroRNAs