De Novo Immunosuppression With Sirolimus and Tacrolimus in Heart Transplant Recipients Compared With Cyclosporine and Mycophenolate Mofetil: A One-Year Follow-Up Analysis

Zucker, Mark; Baran, David A.; Arroyo, Luis H.; Goldstein, Daniel J.; Neacy, C.; Mele, L; Weinberg, Alan; Prendergast, Thomas; Ribner, Hillel S.

doi:10.1016/j.transproceed.2005.03.086

Cited by 20 publications

(24 citation statements)

References 39 publications

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“…The effect of PSI on pleural and pericardial effusions in studies have been conflicting, with no correlation with trough sirolimus levels (23,27) and variable associations with PSI treatment after heart transplantation (10,18 …”

Section: Bacterial Infections Early and Late Bacterial Infections Wermentioning

confidence: 99%

Outcomes Following De Novo CNI-Free Immunosuppression After Heart Transplantation: A Single-Center Experience

Leet¹,

Bergin²,

Richardson³

et al. 2009

American Journal of Transplantation

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Renal impairment at the time of heart transplantation complicates the choice of subsequent immunosuppressive therapy. Calcineurin (CNI)-free regimens utilizing proliferation signal inhibitors (PSI) may mitigate against nephrotoxicity in this group; however, their effectiveness remains unclear.We present our 7-year experience with de novo CNIfree, PSI-based immunosuppression after heart transplantation. Of the 152 patients transplanted between July 1999 and July 2006, de novo immunosuppression regimens were 49 CNI-free, PSI-based, 88 CNI, 15 combination of CNI+PSI.Pretransplant creatinine clearance improved within 6 months in the PSI group (0.69 ± 0.34 mL/s vs. 1.00 ± 0.54 mL/s, p < 0.05) but not the CNI (1.32 ± 0.54 mL/s vs. 1.36 ± 0.53 mL/s, p = ns) or CNI+PSI (1.20 ± 0.24 mL/s vs. 1.20 ± 0.41 mL/s, p = ns) groups. The PSI group had more episodes of early (≤6 months) acute rejection, bacterial or fungal infections and pleural effusions but less CMV infection (p < 0.05 for all comparisons). Early CNI addition occurred in 37% of the PSI group for acute rejection. 33% of the entire cohort changed immunosuppression regimens over 3.6 ± 2.2 years follow-up.De novo CNI-free, PSI-based immunosuppression in patients with significant renal dysfunction allowed significant posttransplantation renal recovery but with increased early acute rejection, bacterial and fungal infections and pleural effusions.

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Section: Bacterial Infections Early and Late Bacterial Infections Wermentioning

confidence: 99%

Outcomes Following De Novo CNI-Free Immunosuppression After Heart Transplantation: A Single-Center Experience

Leet¹,

Bergin²,

Richardson³

et al. 2009

American Journal of Transplantation

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“…No rejections were noted in the CNI arm. The combination of PSIs with CNIs in de novo OHT patients does not improve renal function even when a reduced dose CNI is used [22,32,35,49,50]. There is no change in survival.…”

Section: Results In De Novo and Early Ohtmentioning

confidence: 96%

“…They can worsen proteinuria [32][33][34]. Finally, they are associated with increased risk of mediastinitis and other infections [35]. …”

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confidence: 99%

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Cardiac Troponin I Level in STEMI and Clinical Correlation with Left Ventricular Dysfunction in Indian Population

Sharma¹,

Sharma²

2013

J Cardiovasc Dis Diagn

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Calcium Channel Blockers (CCBs): CNIs cause vasoconstriction as noted above. CCBs, specifically vasodilating dihydropyridines, have been shown to improve renal plasma flow and GFR [9,16]. A small prospective study comparing amlodipine to placebo showed a slower decline in GFR at one year [13]. There was no effect on LV mass and only a modest decrease in proteinuria. Diltiazem did not appear to offer the same protection [14]. RAAS Inhibitors:The use of RAAS inhibitors is beneficial in most patients with CKD; however, this has not been shown in OHT patients. A systematic review of randomized studies in CSA-treated kidney AbstractBackground: The use of calcineurin inhibitors revolutionized transplantation by prolonging patients' survival. However, their utility is limited by the development of significant chronic kidney disease. Methods:We reviewed the English literature looking for recent publications regarding the management of chronic kidney disease in cardiac transplant patients. We chose relevant papers based on design, number of patients and clinical utility.Results: Most publications on the subject involve small populations with few prospective, randomized studies. Early use of tacrolimus appears to be associated with better kidney function after one year compared to cyclosporine. Once chronic kidney disease is established, successful strategies include reduction or elimination of calcineurin inhibitors while relying on mycophenolate mofetil, proliferation signal inhibitors or anti-CD 25 antibodies to prevent rejection. There is no follow up longer than two years with these approaches. Kidney transplantation might offer improved long-term survival compared to dialysis in end-stage disease. Conclusions:Prospective studies with long-term follow-up are needed to decide about the timing and to confirm the utility of replacing calcineurin inhibitors with other agents in cardiac transplant patients with chronic kidney disease. transplant patients show, after a median of 27 months, a reduction in GFR (around 5.8 cc/min) with a reduction of proteinuria (decrease of 470 mg/day) [17]. It is uncertain if the reduction in proteinuria would translate into better outcomes in the long run. In fact, Opelz et al. showed, in a retrospective study of 1,744 OHT patients, that the use of RAAS inhibitors did not improve patient survival after 6 years [18]. The same study looked at 17,209 kidney transplant patients and showed no difference in graft or patient survival [18]. The use of spironolactone in rat models prevented the decline in GFR and the histologic changes seen with CSA [19]. There are no data in patients. Management of Calcineurin Modification of immunosuppressive drugsTransplant centers have tried multiple immunosuppressive strategies in OHT patient with CKD to prevent progression of renal dysfunction. Most of the data come from small studies, limiting the strength of recommendations that can be made. Larger studies come usually from kidney transplantation literature. Tacrolimus:In small studies, Tacrolimus (TAC) do...

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“…3,13 Aggregate rejection, as assessed by ISHLT mean biopsy score, was reduced in the MONO Group at both 6 and 12 months posttransplant, despite less overall immunosuppression. This end point was driven by an excess of grade 1R biopsies of debatable clinical significance in the COMBO Group and a preponderance of 0R biopsies in the MONO Group.…”

Section: Discussionmentioning

confidence: 92%

Randomized Trial of Tacrolimus Monotherapy: Tacrolimus In Combination, Tacrolimus Alone Compared (The TICTAC Trial)

Baran

Zucker

Arroyo

et al. 2007

The Journal of Heart and Lung Transplantation

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De Novo Immunosuppression With Sirolimus and Tacrolimus in Heart Transplant Recipients Compared With Cyclosporine and Mycophenolate Mofetil: A One-Year Follow-Up Analysis

Cited by 20 publications

References 39 publications

Outcomes Following De Novo CNI-Free Immunosuppression After Heart Transplantation: A Single-Center Experience

Outcomes Following De Novo CNI-Free Immunosuppression After Heart Transplantation: A Single-Center Experience

Cardiac Troponin I Level in STEMI and Clinical Correlation with Left Ventricular Dysfunction in Indian Population

Randomized Trial of Tacrolimus Monotherapy: Tacrolimus In Combination, Tacrolimus Alone Compared (The TICTAC Trial)

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