Beneficial effects of conversion from cyclosporine to azathioprine on fibrinolysis in renal transplant recipients

Dorpel, Marinus A. van den; Levi, Marcel; IJzermans, Jan N. M.; Cate, J. W. Ten; Weimar, Willem

doi:10.1016/s0041-1345(98)01649-2

Cited by 8 publications

(13 citation statements)

References 20 publications

(18 reference statements)

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“…The beneficial effects of CsA on graft survival have been mostly attributable to the reduction in acute rejection that occurs early after kidney transplantation (4–6). On the other hand, hypertension (7–9), dyslipidemias (9–12), glucose intolerance (13), and hypercoagulability (14, 15) probably all contribute to the high incidence of cardiovascular disease in the late post‐transplant period, and each of these risk factors is adversely affected by CsA. In addition, chronic CsA nephrotoxicity may contribute to long‐term graft dysfunction and possibly even graft failure from chronic allograft nephropathy (16–19).…”

Section: Discussionmentioning

confidence: 99%

Defining the Risk of Elective Cyclosporine Withdrawal in Stable Kidney Transplant Recipients

Anjum

Andany

McClean

et al. 2002

American Journal of Transplantation

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Although it is known that elective cyclosporine (CsA) withdrawal increases the risk for acute rejection, few studies have been large enough to identify risk factors for acute rejection after CsA withdrawal. We examined risk factors for acute rejection in 464 kidney transplant recipients who underwent elective CsA withdrawal. The incidence of acute rejection within 6 months of CsA withdrawal was 20/141 (14.2%) in the period January 1986 to May 1989, but only 14/323 (4.5%) since May 1989 (p = 0.0002). Among those transplanted since May 1989, the incidence was 5/20 (25%) for those with both 2 HLA‐B and 2 HLA‐DR mismatches, compared with only 9/298 (3.0%) for those with fewer mismatches (p < 0.0001). In Cox proportional hazards analysis, risk factors for acute rejection within 6 months, or at any time after elective CsA withdrawal, were date of transplant January 1986 to May 1989 (compared with more recently May 1989 to March 1999), younger age, obesity, as well as B and DR mismatches. Recipient race (83% were white), acute rejection during the first year before withdrawal (31%), mycophenolate mofetil (17%), and other variables failed to predict postwithdrawal acute rejection. We concluded that avoiding CsA withdrawal in the relatively small number of recipients with both 2 HLA‐B and 2 HLA‐DR mismatches could further reduce our already low incidence of acute rejection following elective CsA withdrawal.

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Section: Discussionmentioning

confidence: 99%

Defining the Risk of Elective Cyclosporine Withdrawal in Stable Kidney Transplant Recipients

Anjum

Andany

McClean

et al. 2002

American Journal of Transplantation

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“…In a small, prospective, controlled study of renal transplantation patients initially receiving steroids and CsA or AZA, a substantial increase in the activity of the fibrinolytic system was observed in patients who were randomized to convert from CsA to AZA at 6 months post transplantation. This increase in fibrinolytic activity at 12 weeks after conversion to AZA was accompanied by a significant decrease in the plasma concentrations and activity of PAI‐1 (p = 0.016 and 0.009, respectively) (119).…”

Section: Coronary Artery Diseasementioning

confidence: 99%

Cardiovascular Toxicities of Immunosuppressive Agents

Miller

2002

American Journal of Transplantation

401

257

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Cardiovascular disease is one of the major causes of morbidity and mortality following solid organ transplantation. Many of the current immunosuppressive drugs are associated with an increase of one or more risk factors for the development of atherosclerosis. This review compares the mechanism by which individual immunosuppressive agents may impact on these risk factors and the differential contribution of cyclosporine, tacrolimus, mycophenolate, azathioprine, and Rapamycin to these individual risk factors. Attention to the potential cardiovascular toxicities of individual immunosuppressive agents may help design strategies for maintenance of immunosuppression tailored to individual patients.

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“…Hampering impact of CsA on endothelial function was partly eliminated by administration of L-arginine, what proves CsA impact on bioavailability of NO. Also van den Dorpel et al [24] proved that PAI-1 levels was higher in patients after transplantation, treated with cyclosporine, than in patients from the control group and in patients after transplantation, to whom that drug was not administered. Cyclosporine was replaced with azathioprine in patients with stable transplant function [6] and decrease in PAI-1 activity was found within approx.…”

Section: Original Articlesmentioning

confidence: 99%

“…Action of the assessed markers of endothelial function also depends of application of immunosuppressive therapy. Cyclosporine provokes extension of euglobulin lysis time, decrease in t-PA activity and increase in activity and concentration of PAI-1 antigen [6,17,23,24]. It is suggested that a mechanism of toxic influence of CsA and tacrolimus (Tac), a calcineurin inhibitor, is related to hampering of activity of nitric oxide synthase, which is calcium/calmodulin-dependent enzyme.…”

Section: Original Articlesmentioning

confidence: 99%

Assessment of plasminogen activator inhibitor-1 and von Willebrand factor as a marers of endothelial function in patients with end-stage kidney disease after allotransplantation during a one-year follow-up

Doroszewski

Włodarczyk²,

Stróżecki³

et al. 2007

Polish Archives of Internal Medicine

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Objectives. The aim of our study was to determine the endothelial function in patients with chronic kidney disease (CKD), stage V (end-stage renal disease-ESRD), before and during a one-year observation after kidney allotransplantation. Patients and methods. We studied 40 patients with stabile graft function after their first kidney transplantation, including 21 females (mean age 41 ±12.5 yrs) and 19 males (mean age 43.6 ±13.3 yrs), treated already with hemodialysis because of ESRD. Results. After transplantation we observed significant decrease in serum creatinine concentrations (Cr) (7.32 ±2.07 mg/dl to 1.50 ±0.45 mg/dl at 6 months and 1.61 ±0.58 mg/dl after 12 months after transplantation). During 12 months we found changes only in plasminogen activator inhibitor-1 (PAI-1) levels. Von Willebrandt factor (vWF) levels remained unaltered during follow-up and total homocysteine (tHcy) concentration decreased, but this change was not statistically significant. There was no correlation between vWF and PAI-1 concentrations and other clinical and laboratory findings. Conclusions. In our study we did not find any improvement of endothelial function during the first year after kidney allotransplantation. The mean Cr concentration at the end of study was 1.6 mg/dl, which indicates the chronic kidney graft insufficiency. We conclude that despite kidney allotransplantation endothelial function is impaired like in CKD, but with more advanced abnormalities in the cardiovascular system.

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Beneficial effects of conversion from cyclosporine to azathioprine on fibrinolysis in renal transplant recipients

Cited by 8 publications

References 20 publications

Defining the Risk of Elective Cyclosporine Withdrawal in Stable Kidney Transplant Recipients

Defining the Risk of Elective Cyclosporine Withdrawal in Stable Kidney Transplant Recipients

Cardiovascular Toxicities of Immunosuppressive Agents

Assessment of plasminogen activator inhibitor-1 and von Willebrand factor as a marers of endothelial function in patients with end-stage kidney disease after allotransplantation during a one-year follow-up

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