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.
Materials and 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 105 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.
Conclusion: 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.
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.
The authors report no funding or conflict of interest.
S.O. participated in the preparation of RNA samples for microRNA testing, real-time PCR validation, and PCR data analysis. A.B. participated in data collection on the patient study cohort. U.N. contributed in the data collection on the patient study cohort and critical review of the manuscript. K.H.M. participated in the statistical analysis of the NanoString microRNA data. J.M.B.-L. participated in the microbiology workup of the patients in the study cohort. S.B. participated in the critical review of the manuscript. R.P. contributed in the expert clinical advise and critical review of the manuscript. M.H. participated in the expert clinical advise and critical review of the manuscript. A.R.S. contributed in the new reagents and participated in research design. T.N. participated in the critical review of themanuscript and participated in research design. A.A.S. participated inresearch design, selecting and preparing biopsies for micro-RNA analysis, data analysis, financial support for Nanostring experiments, and writing of the manuscript.
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Accepted February 12, 2014