Introduction

Monitoring of kidney allograft condition is important. We had exhibited non-invasive diagnostic modality of post-kidney transplant complications using urine exosomal and microvesicule (EMV) mRNA of some combinations of markers for kidney injury, inflammatory molecules and so on. And we also successfully developed formulas to diagnose biopsy-proven complications, in part TCMR in ATC2015. This time we focused on the specific immune modulator annexin A1 (ANXA1) and examined the relationship with some post-transplant complications.

Material & Methods

Using a recently developed urinary exosome and microvesicle (EMV) mRNA assay, early kidney injury biomarkers were screened by analyzing 299 urine samples obtained from 155 patients who received kidney transplantation. The obtained mRNA data were analyzed based on the diagnosis of post-transplant complications and Banff codes of kidney biopsy.

Results

Compared to the patients with stable recovery, ANXA1 expression level in urinary EMV significantly increased when T-cell mediated rejection (TCMR, 10.2-fold), antibody-mediated rejection (ABMR, 14.4-fold), interstitial fibrosis and tubular atrophy (IFTA, 22.0-fold) and other post-transplant complications such as Immunoglobulin A (IgA) nephropathy and calcineurin inhibitor (CNI) toxicity (8.7-fold) were observed. The expression level of ANXA1 increased at least 6.5 days before transplant rejection, 56 days before IFTA and 64 days before any other complications, and it remained high after the complications disappeared. ROC curve analysis indicated that urinary ANXA1 level was able to predict and diagnose post-transplant complications with high specificity and sensitivity: transplant rejection (AUC = 0.857 to 0.946), IFTA (AUC = 0.777 to 0.995) and other post-transplant complications (AUC = 0.698 to 0.797). Furthermore, urinary ANXA1 level was linearly correlated with Banff scores ci (interstitial fibrosis,r = -0.236, p < 0.05), ct (tubular atrophy, r = -0.329, p < 0.0005) and ti (total interstitial inflammation, r = -0.255, p < 0.01) of the matched kidney biopsies.

Conclusions

Although further validation should be required, these data strongly suggest that urinary EMV ANXA1 mRNA could be a promising predictive marker of interstitial fibrosis and tubular atrophy and useful for non-invasive post-transplant graft monitoring.

CITATION INFORMATION: Harada H, Murakami T, Yamamoto C, Hotta K, Fukuzawa N, Mitsuhashi M. Urinary Exosomal Annexin A1 Is a Predictive Biomarker of Post Kidney Transplant Complications. Am J Transplant. 2016;16 (suppl 3).

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