Allograft, rejection function

The literature on chemokines in transplantation has been extensively reviewed in recent years (7-9). In this chapter, we focus on a limited number of chemo-kine receptors where evidence for a functional role has been verified. From the plethora of chemokine receptors, this has been demonstrated for CXCR1/2 in reperfusion injury and for CCR1, CCR5, and CXCR3 during acute and chronic allograft rejection. 

Extensive preclinical studies have shown that sensitivity to mTOR inhibition may correlate with aberrant activation of the PI3K pathway or loss of functional tuberous sclerosis complex (TSC), as occurred in patients with tuberous sclerosis syndrome [151,152]. Rapamycin (compound 31, Fig. 6), which was the first compound shown to inhibit mTOR kinase activity, is an approved drug for prevention of allograft rejection. Rapamycin is a macrocyclic... 

Adhesion molecules also play a crucial role in allograft rejection. The migration of activated T cells from secondary lymphoid organs to the graft site is regulated by adhesion molecules. Furthermore, these molecules are pivotal in the interaction of T cells with the functional components of tissue allografts that are epithelial in origin. 

Acute ciclosporin-induced nephrotoxicity, causing reduced renal function, develops within the first month, and includes a dose-related rise in serum creatinine concentrations and hyperkalemia. Fatal acute tubular necrosis has also been noted after very high intravenous doses (SEDA-19, 345). Although it is clinically often difficult to differentiate from acute allograft rejection in renal transplant patients, the alteration in renal function promptly resolves on ciclosporin withdrawal or dosage reduction, and initial acute renal insufficiency is not clearly associated with the development of subsequent chronic renal dysfunction (93). Several conditions, such as pre-existing hypovolemia, concomitant diuretic treatment, or renal artery stenosis, are susceptibility factors. 

Murnmonab-CD3 blocks the function of T cells that are involved in acute renal rejection. Hence, it is indicated for the treatment of acute allograft rejection in heart and liver transplant recipients resistant to standard steroid thcrapie.s. 

Alteration of renal function during therapy of allograft rejection by OKT3 is not limited to the transplanted kidney. Indeed, four of sixteen cardiac transplant patients developed a rise in creatinine following therapy of rejection with OKT3. Renal dysfunction resolved spontaneously in all cases [114]. 

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