Examination of Serum miRNAs as Possible Biomarkers for the Diagnosis of Acute Rejection after Kidney Transplantation

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Abstract

Introduction

Because of the lack of non-invasive, specific biomarkers, early detection of acute rejection after kidney transplantation represents a challenge. microRNAs (miRNAs) belong to a class of small, noncoding RNAs and they were found to be involved in pathological processes that occur following kidney transplantation. We analyzed the association of serum expression levels of miR-15b, miR-16, miR-24, miR-103a and miR-107 with acute rejection episodes that occur during the early phase after transplantation. We also investigated the capability of these miRNAs to differentiate between acute rejection episodes and other pathological processes.

Patients and Methods

Prospectively collected serum samples of kidney allograft recipients with stable graft function (n=10), urinary tract infection (UTI) (n=9), borderline rejection (n=9), acute tubular necrosis (ATN) (n=9) or biopsy-proven acute rejection (n=9), who were transplanted between 2015 and 2017 were analyzed. In addition, serum samples of 7 patients with an acute rejection episode were also investigated at different time points after kidney transplantation. miRNA expression levels were determined by real-time quantitative reverse-transcription-polymerase chain reaction (RT-PCR). Spiked-in cel-miR-39 was used as a normalization control. The expression levels were determined relative to the levels before transplantation.

Results and Discussion

As compared to patients with stable graft function, decreased serum levels of miR-15b, miR-16 and miR-24 were observed on post-Tx day 8 in kidney transplant patients with borderline rejection, ATN or acute rejection. miR-15b and miR-24 levels were lower in patients with ATN than in patients with UTI. miR-103a level was also lower in patients with ATN or acute rejection (but not borderline rejection) than in patients with stable function. Although the serum miR-107 level did not significantly differ between patients with acute rejection and stable function, longitudinal analysis of individual patients showed that miR-107 is increased during acute rejection and decreases with the improvement of the kidney function. One patient with ABMR showed extremely decreased levels at all timepoints.

Conclusion

The determination of serum miR-15b, miR-16, miR-24 and miR-103a levels may allow the detection of allograft damage after kidney transplantation; however, these miRNAs do not seem to distinguish acute rejection from other transplant pathologies. In contrast, the quantification of serum miR-107 appears to be useful for monitoring the therapy success in patients with an acute rejection episode.

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