Detection of early renal transplant rejection by minimally-invasive monitoring of impedance variability

Abstract

Background Allograft rejection that occurs after renal transplants is identified by surveillance biopsies or by abnormal laboratory and/or hemodynamic data. The latter are insensitive markers of rejection that may not appear until significant histologic damage has already occurred. Therefore, a sensitive and specific non-invasive method of detecting early rejection of transplanted solid organs is needed. Method A single canine renal allograft was implanted followed by bilateral nephrectomy. Bipolar pacing electrodes were implanted at each end of the transplanted kidney. A second set of electrodes was implanted in the liver, which served as a non-rejecting normal organ. Electrodes were connected to an implantable sensor placed in the subcutaneous tissue. Electrical tissue impedance levels were telemetrically downloaded daily. The clinical status of the transplanted organ was monitored by following the blood urea nitrogen and serum creatinine levels, urine output, and clinical appearance. After tissue impedance levels had stabilized, all immunosuppressants were abruptly discontinued. Clinical signs of rejection were then observed after a few days. Results Rejection was accompanied by changes in electrical impedance of the implanted organ. These changes, when observed, occurred 1–5 days before clinical signs of rejection appeared. Conclusion Analyses of these data suggest that development of a minimally-invasive high-confidence sensor of early rejection of solid organ transplants is feasible.