Long-Term Trends in Allograft Survival

Brennan, Daniel C.

doi:10.1053/j.ackd.2005.10.006

Cited by 26 publications

(20 citation statements)

References 30 publications

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“…New treatments are linked to a reduced incidence of acute rejection [13], and -as Takemoto et al showed, also to graft loss [12]. However, because of their lower nephrotoxicity, it may be assumed that newer drugs are more tolerant of non adherence and that higher levels of non adherence are necessary to show long-term effects.…”

Section: Discussionmentioning

confidence: 99%

Clinical consequences of non adherence to immunosuppressive medication in kidney transplant patients

Denhaerynck

Burkhalter

Schäfer-Keller

et al. 2009

Transplant International

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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.

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Section: Discussionmentioning

confidence: 99%

Clinical consequences of non adherence to immunosuppressive medication in kidney transplant patients

Denhaerynck

Burkhalter

Schäfer-Keller

et al. 2009

Transplant International

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“…Currently, based on data published by the Collaborative Transplant Study, the half-life reaches approximately 16 years in Europe, whereas in the United States, it is only 8.8 years. 1,2 The data are a stimulus for seeking the causes of this phenomenon. Traditionally, the side effects of immunosuppressive drugs have been considered to be one of the main reasons for this situation.…”

Section: Introductionmentioning

confidence: 99%

Effects of Immunosuppressive Treatment On Protein Expression in Rat Kidney.

et al. 2014

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Abstract:The structural proteins of renal tubular epithelial cells may become a target for the toxic metabolites of immunosuppressants. These metabolites can modify the properties of the proteins, thereby affecting cell function, which is a possible explanation for the mechanism of immunosuppressive agents' toxicity. In our study, we evaluated the effect of two immunosuppressive strategies on protein expression in the kidneys of Wistar rats. Fragments of the rat kidneys were homogenized after cooling in liquid nitrogen and then dissolved in lysis buffer. The protein concentration in the samples was determined using a protein assay kit, and the proteins were separated by two-dimensional electrophoresis. The obtained gels were then stained with Coomassie Brilliant Blue, and their images were analyzed to evaluate differences in protein expression. Identification of selected proteins was then performed using mass spectrometry. We found that the immunosuppressive drugs used in popular regimens induce a series of changes in protein expression in target organs. The expression of proteins involved in drug, glucose, amino acid, and lipid metabolism was pronounced. However, to a lesser extent, we also observed changes in nuclear, structural, and transport proteins' synthesis. Very slight differences were observed between the group receiving cyclosporine, mycophenolate mofetil, and glucocorticoids (CMG) and the control group. In contrast, compared to the control group, animals receiving tacrolimus, mycophenolate mofetil, and glucocorticoids (TMG) exhibited higher expression of proteins responsible for renal drug metabolism and lower expression levels of cytoplasmic actin and the major urinary protein. In the TMG group, we observed higher expression of proteins responsible for drug metabolism and a decrease in the expression of respiratory chain enzymes (thioredoxin-2) and markers of distal renal tubular damage (heart fatty acid-binding protein) compared to expression in the CMG group. The consequences of the reported changes in protein expression require further study.

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“…Other characteristics associated with greater distance between home and transplant center included living (vs. deceased) donor, male sex, diabetes (vs. hypertension) as primary cause of kidney failure and fewer HLA mismatches. Kasiske et al 2 Adjusted ratios of the medians were estimated from a log-linear regression model. 3 OPTN regions were combined into broader regions that were included in the full model; individual OPTN regions were not included.…”

Section: Geography Of Kidney Transplantationmentioning

confidence: 99%

“…Unfortunately, the rate of late graft failure has declined more slowly (1), and further improvements in patient and graft survival will undoubtedly require careful follow-up and management of transplant recipients long after transplantation (2). The distance patients live from the centers where they undergo transplantation could be a major barrier to optimal follow-up care.…”

Section: Introductionmentioning

confidence: 99%

The Geography of Kidney Transplantation in the United States

Kasiske

Snyder

Skeans

et al. 2008

American Journal of Transplantation

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The distance kidney transplant patients live from the centers where they undergo transplantation could affect long-term care and outcomes, but little is known about this distance and its associations. We used data from the United States Renal Data System to examine distance between home and transplant cen- Hispanics lived closer (14.7 miles) than non-Hispanics (24.3 miles). Even after adjusting for center density, we found substantial regional variability, with median distance of 15.1 miles for patients living in the Northeast and 40.6 miles for those in the Southeast. Distance was also associated with center size, median zip code income, listing on more than one deceased-donor waiting list and other factors, but greater distance (adjusted for these other factors) was not associated with worse patient or graft survival. The substantial variability in geographical access to kidney transplantation could have important implications for long-term care.

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Long-Term Trends in Allograft Survival

Cited by 26 publications

References 30 publications

Clinical consequences of non adherence to immunosuppressive medication in kidney transplant patients

Clinical consequences of non adherence to immunosuppressive medication in kidney transplant patients

Effects of Immunosuppressive Treatment On Protein Expression in Rat Kidney.

The Geography of Kidney Transplantation in the United States

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