Elsevier

Medical Hypotheses

Volume 75, Issue 6, December 2010, Pages 666-668
Medical Hypotheses

Differential diagnosis of acute rejection and chronic cyclosporine nephropathy after rat renal transplantation by detection of endothelial microparticles (EMP)

https://doi.org/10.1016/j.mehy.2010.08.014Get rights and content

Summary

Endothelial microparticles (EMP) are small vesicles smaller than 1.0 μm, released from endothelial cells (EC) during their activation and (or) apoptosis. The assay of the level of elevated EMP is a new approach to evaluate the dysfunction of endothelial cell. EMP can be classified into several types according to their membrane molecular, and the levels of various types of EMP may be different. As the most cost-effective immunodepressant, cyclosporine A (CsA) has been used widely in organ transplantation. But its dose is hard to control, under-medication may cause the acute rejection (AR) and overdose may cause chronic cyclosporine nephropathy (CCN). The cyclosporine A (CsA) caused CCN and the AR caused renal injury after renal transplantation are both vascular diseases related with endothelial dysfunction, and up to now, there is still no effective method to distinguish the two kinds of diseases. Owing to distinct pathogenesis of the two kinds of vascular diseases, the level of each type of EMP originated from vascular endothelial cells may be different. We hypothesize that maybe we can distinguish them by detecting the different levels of some types of EMP which is also related with vascular disease, and we propose to prove our hypothesis through animal experiment. If our hypothesis is proved, it will be more helpful for clinicians to adjust the dose of CsA promptly according to the differential diagnosis of the two kinds of diseases.

Section snippets

Background

Renal transplantation is an effective therapeutic tool to cure terminal stage nephropathy, but acute rejection (AR) is a major complication after renal transplantation, almost 35% of renal transplant patients have occurred AR. For the past few years, because of the application of new immunodepressants, its incidence rate has declined a lot, but 8% of renal transplant patients had still occurred AR [1]. As the most cost-effective immunodepressant, cyclosporine A (CsA) has significantly enhanced

The introduction of EMP and our hypothesis

According to the definition of International Society on Thrombosis and Haemostasis (ISTH), microparticles (MP) are small vesicles without nuclear, released from various cells during their activation and (or) apoptosis, their diameter is between 0.1 and 1.0 μm [3], and meanwhile, MP are called microvesicles (MV) (Fig. 1). Endothelial microparticles (EMP) are one kind of microparticles from endothelial cells (EC).

Simak et al. [5] reported that each EC can release about 80 microparticles during

The methods to build models and testing of the hypothesis

In our hypothesis, Male Lewis–Brown–Norway (LBN) and Lewis (LEW) rats (250–300 g) are to be used in animal models.

The rat model of renal transplantation is to be performed as published before [14], [15]. In short, the left kidney including ureter, renal artery, a piece of aorta and renal vein is to be transferred into the recipient. For acute rejection kidneys of LBN-rats (n = 10) are to be transplanted into uninephrectomized LEW-rats (n = 10) without any immunosuppression. Donor kidneys of LEW-rats

Consequences of the hypothesis and discussion

As vascular diseases, the percentages of CD144+/105+ EMP, CD144+/CD36+ EMP in total CD144+ EMP may be different in the two kinds of animal models above. In rat acute rejection (AR) models, because their pathogenesis are related with immunologic rejection and it may activate endothelial cell, the percentages of CD144+/CD62E+ EMP and CD144+/105+ EMP in total CD144+ EMP may be elevated. Simultaneously, the impaired endothelial cells are mostly located at renal allograft and their vessels are small

Conflict of interest statement

None declared.

Acknowledgement

This work was supported by Tianjin Municipal Science and Technology Commission, China (No. 08JCYBJ06800) and Scientific Research Fund of Chinese People’s Armed Police Force (No. WY200912).

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