**3. Computed tomography**

and specific detection of early AR exists, with core needle biopsy still being the "gold-stand‐ ard" in rejection diagnostics. However, biopsy as an invasive procedure is cumbersome to the patient, carries the risk of graft injury, and cannot be applied in patients taking anticoagulant drugs. Additionally, the sampling site is small and one might miss AR, i.e., when rejection is focal or patchy. Thus, in diagnostics, non-invasive image-based methods visualizing the whole

Allograft rejection is the result of interactions between the recipient`s innate and adaptive immune system and the graft antigens serving as a target. Cytotoxic T lymphocytes (CTLs) are central effectors within AR whereas B cells and parts of the congenital immunosystem such as the complement system, monocytes/macrophages, neutrophilic granulocytes, and dendritic cells, have their share, too [4;10]. By recognition of their donor antigen CTLs are activated, undergo clonal expansion and differentiation into effector cells. Subsequently, they migrate into the transplant initiating its destruction [4;10;11]. Before CTLs reach the graft parenchyma, they have to pass the vascular endothelium. This extravasation is mediated by chemoattractant cytokines/chemokines. Chemokines induce the expression of vascular adhesion molecules al‐ lowing leukocytes to roll, adhere, and transmigrate into the parenchyma [12]. CTLs destroy their targets through the release of perforin and granzyme or by initiation of the Fas/FasL pathway inducing cell death by triggering the inherent caspase-mediated apoptotic response or caspase-independent cell death [13]. These two cell death-inducing strategies account for almost all contact-dependent target kills. However, activated CTLs can release additional cy‐ tokines, such as tumor-necrosis factor and interferon causing apoptosis or necrosis upon se‐ cretion [11,13]. Moreover, inflammatory edema and micro thrombi / hemorrhage caused by damaged endothelium add ischemia-dependent hypoxic damage to the graft [11]. All of these single, simplified processes sum up and promote allograft dysfunction. However, if they are characterized at least in part, they can be addressed by different imaging technologies dis‐

Standard care in detection of AR includes (Doppler-) ultrasound examination. Typical ultra‐ sound findings in cases of AR are rejection-related graft enlargement (swelling, more globular shape), reduction of corticomedullary differentiation, increased echogenicity, prominent me‐ dullary pyramids, or irregularities in the graft perfusion (reversed plateau of diastolic flow), but its specificity and sensitivity for AR is limited, even when echo enhancers are applied [14;15]. Elevated resistance indices can occur in the presence of acute as well as chronic rejec‐ tion. However, values lower than 0.8 are expected and usually values above 0.8 indicate in‐ creased intrarenal pressure as it occurs for example in acute tubular necrosis (ATN) or AR and is linked to a poor longterm renal allograft function [16-18]. Notably, sensitivity and reliability of this method mainly depend on the investigators experience. A comprehensive overview of "What ultrasound can do and cannot do" in diagnostics of renal transplant pathologies was published by Cosgrove and Chan [16]. Using contrast agent or targeted ultrasound in the

graft would be superior.

90 Current Issues and Future Direction in Kidney Transplantation

cussed in the following.

**2. Ultrasound**

Computed tomography (CT) is commonly available, technology and techniques as well as the applied contrast media constantly improve. CT contrast agents allow accurate evaluation of parenchymal, perirenal, renal sinus, pyeloureteral and vascular diseases in renal transplanta‐ tion in great detail and at lower costs than by magnetic resonance (MR) imaging. Information gathered by CT indicating AR are loss of corticomedullary differentiation, decreased graft enhancement, and delayed or absent contrast excretion [19]. However, this information is rather unspecific and the contrast media used still are nephrotoxic. Thus, at present CT has no role in diagnostics of renal AR.
