Urinary Exosomes as a Source of Kidney Dysfunction Biomarker in Renal Transplantation

End-stage renal disease (ESRD) requires for its treatment permanent dialysis or kidney transplantation (KT). KT is the best clinical treatment, however, the early function of the allograft varies depending on multiple factors associated with cold ischemia time (CIT) and the allograft rejection process. It is known that serum creatinine is an insensitive and late marker for predicting graft recovery after KT, mainly in patients with delayed graft function (DGF). Neutrophil gelatinase-associated lipocalin (NGAL) is produced in the distal nephron and it is one of the most promising novel biomarkers for acute kidney injury (AM) and chronic kidney disease (CKD). NGAL has been proposed to be a predictor of organ recovery from DGF after KT from donors after cardiac death. Because nonrenal diseases can also induce NGAL, more information is necessary to validate the sensitivity and specificity of urine and plasma NGAL in clinical samples. The exosomes are vesicles released into the urine from the kidney epithelium and they have been proposed as better source to explore as biomarker of renal dysfunction. The molecular composition of the urinary exosomes could be representative of the physiological or physiopathologic condition of the urinary system. We propose that determination of NGAL in urinary exosomes is a better predictor of kidney dysfunction after KT than other urinary fractions. We analyzed 15 kidney allograft recipients, with a mean age of 36 years (range, 16-60 years) and 75% were male: 11 living donors (LD) and 4 deceased donors (DD). The average length of CIT was 14 hours in DD and less than 1 hour in LD. Three patient developed DGF. Using Western blot analysis, NGAL was detectable in the cellular and exosomal fraction of the urine. The exosomes expressed higher levels of NGAL than the cellular fraction. The expression of NGAL was observed from the first day after transplantation. In the cellular fraction of the urine, no significant differences of NGAL were observed between the patients. However, the median of NGAL expression in the exosomes fraction was significantly higher in DD patient, from the first day after KT (P<.05). Moreover, we noticed that NGAL expression in exosomes remained elevated in the patients with DGF compared with non-DGF patients (P<.05). Considering the highest abundance of NGAL in the urinary exosomes and its correlation with DGF patients, we suggest the exosomal fraction as a more sensitive substrate to evaluate early biomarkers of DGF after KT.