In recent decades, improvements in immunosuppressive medication have considerably increased the shortterm life expectancy of transplanted kidneys by reducing the incidence of acute rejections, primarily in the first year post-transplant. However, over the same period, long-term patient survival curves have been relatively flat [1,2]. Extending the perspectives of kidney transplant recipients is therefore a profound challenge and an important research priority [3][4][5].A major limiter of long-term survival is the gradual deterioration of kidney graft function [3][4][5][6], resulting from a range of function-impairing problems known collectively as chronic kidney dysfunction. Among the possible cause of chronic kidney dysfunction are behavioural aspects of the medication regimen, such as non adherence to the immunosuppressive prescription [5,7,8]. Next to the observation that non adherence has been linked to increased serum creatinine levels, a marker of decreased kidney function [9], the microscopic morphology of transplanted kidney tissue in non adherent patients shows a greater number of histological lesions than in those who adhere closely [10]. As surveys have shown that at least 28% of kidney transplant patients are non adherent to their regimens, non adherence may be a significant contributor to long-term kidney dysfunction [11].One common disadvantage of existing studies exploring the associations between non adherence and clinical outcomes is that they were based predominantly on the older azathioprine-and cyclosporine-based regimens, which are no longer considered state-of-the-art. How far their conclusions can be applied to regimens using subsequent generations of medications, such as tacrolimus, mycophenolate mofetil or sirolimus is an issue that has previously only been investigated in a retrospective study of SummaryLittle is known of the long-term clinical effects of non adherence on transplanted kidneys, especially regarding newer immunosuppressive regimens. In a study of 356 adult Swiss kidney transplant patients, non adherence was measured at inclusion by means of self-reporting, electronic monitoring, collateral reporting and blood assay. Long-term clinical outcomes regarding graft loss and creatinine levels were collected prospectively over a period of 5 years. A Cox proportional hazards model and mixed regression analysis were used, respectively, to examine the effects of non adherence on kidney survival and kidney function. The majority of patients (62%) were on immunosuppressive regimens that included mycophenolate mofetil, tacrolimus or sirolimus. No associations were found between non adherence and kidney graft survival or graft function. Notwithstanding weaknesses of this study, this negative result suggests that high adherence may protect patients against detrimental clinical outcomes, and/or that immunosuppressive regimens containing newer drugs allow wider non adherence margins than those based on previous generation medications such as cyclosporine, azathioprine and corticosteroids.
Kidney transplantation from emotionally related living donors represents a valuable option, allowing more patients with end-stage renal disease to avoid chronic dialysis. Recipient and graft outcomes were superior to cadaver kidney transplantation. Motivated and emotionally related donors should be allowed to donate one of their kidneys provided that they are carefully selected and thoroughly informed.
In the near future several new immunosuppressive substances will be available: Cyclosporin G, IMM125 (both are new derivates of Cyclosporin A), FK506, Rapamycin, Leflunomid, Mycophenolic acid (RS-61443), Bredinin (Mizorinin), Brequinar, Deoxyspergualin and several new monoclonal antibodies (anti-CD4, anti-II-2-Receptor, anti-CD8, anti-CD45, anti-ICAM1 and others). Side-effects of immunosuppressants are classified in 1) relative drug-specific or 2) unspecific effects of over-immunosuppression (infections and malignancies). Nephrotoxicity of Cyclosporin A and guidelines for its prevention are covered in more detail. The authors fear, that the proliferation of new immunosuppressive drugs will make it more difficult, to carefully evaluate their side-effects.
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