Predictors of long-term renal function after conversion to proliferation signal inhibitors in long-term heart transplant recipients

González‐Vílchez, Francisco; Prada, José Antonio Vázquez de; Castrillo, Cristina; Canteli, A.; Llano, Miguel; Martín‐Durán, Rafael

doi:10.1016/j.healun.2010.11.005

Cited by 18 publications

(15 citation statements)

References 21 publications

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“…Whereas decrements in renal function caused by CNI nephrotoxicity may in part be reversible with conversion to sirolimus, the same improvement would not be expected when renal impairment is caused by diabetes-related mechanisms. In a retrospective study of 49 consecutive long-term cardiac transplant patients who were switched to sirolimus or everolimus, renal function declined following 1 year postconversion (33). Multivariate analysis of that data determined that the presence of diabetes was identified as the main factor in the decline in renal function.…”

Section: Discussionmentioning

confidence: 99%

Sirolimus Conversion After Heart Transplant: Risk Factors for Acute Rejection and Predictors of Renal Function Response

Zuckermann

Eisen

Tai

et al. 2014

American Journal of Transplantation

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ClinicalTrials.gov identifier number: NCT00369382.In a randomized, comparative study of cardiac transplant patients with mild-to-moderate renal insufficiency, conversion from calcineurin inhibitors (CNIs) to sirolimus improved renal function at 1 year versus continuing CNIs, with an attendant risk of biopsy-confirmed acute rejection (BCAR). Post hoc analyses were conducted to identify predictors of BCAR and GFR improvement associated with conversion. Patients with proteinuria >500 mg/day were excluded. Univariate and multivariate regression analyses tested 13 parameters for BCAR and six for GFR improvement. In 57 sirolimus-treated patients, mean daily mycophenolate mofetil (MMF) dose was lower in those with versus without BCAR (1000 vs. 1420 mg; p ¼ 0.014). Receiver operating characteristic analysis identified MMF dose 1000 mg/day as the optimal cutoff to predict BCAR. Multivariate analysis confirmed low MMF dose (odds ratio: 9.94; p ¼ 0.007) and non-white race (odds ratio: 15.3; p ¼ 0.06) were independently associated with BCAR. GFR improvement was evaluated in intent-totreat patients (n ¼ 116). Significant interaction was detected between treatment effect and preexisting diabetes status (univariate p ¼ 0.077; multivariate p ¼ 0.022), indicating greater beneficial effect of sirolimus in those without preexisting diabetes. These findings suggest that sirolimus is more effective in improving GFR in patients without preexisting diabetes, and adequate MMF doses are needed for sirolimus conversion.

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Section: Discussionmentioning

confidence: 99%

Sirolimus Conversion After Heart Transplant: Risk Factors for Acute Rejection and Predictors of Renal Function Response

Zuckermann

Eisen

Tai

et al. 2014

American Journal of Transplantation

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“…The presence of baseline proteinuria is cause for concern as is the presence of diabetes and might negate any benefit of PSI use [34,37,46,47,54]. The use of ACE inhibitors and angiotensin receptor blockers might mitigate the adverse effect of PSI induced proteinuria on worsening renal function but this is not based on large number of patients [34,37,57]. The above highlight the need for more studies regarding this evolving issue.…”

Section: Discussionmentioning

confidence: 99%

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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“…SIR has been shown to reduce the incidence of acute rejection among renal-transplant recipients and to prevent CAV in animals [87] . Because of its potent anti-proliferative effects [88] , SIR has also provided beneficial effects on regression of left-ventricular mass [89][90][91] .…”

Section: Mtor and Mtor Inhibitorsmentioning

confidence: 99%

Effects of Immunosuppressive agents on neutrophils inflammatory response in humans: An inflammatory perspective on coronary allograft vasculopathy

White

2016

Inflamm Cell Signal

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Cardiac transplantation (CTx) has improved survival in patients with advanced heart failure. Unfortunately, the conditional survival remains less than 15 years. The primary cause of mortality at 5 years following a CTx is the development of accelerated coronary atherosclerosis named coronary allograft vasculopathy (CAV). The neutrophils likely play an important role in this diffuse inflammatory process. Nevertheless, the contribution of the neutrophils on the pathogenesis of CAV is poorly understood. Regardless of their essential contribution for the prevention of graft rejection, immunosuppressive drugs (IDs) may have detrimental effects via some pro-inflammatory activities. This review presents the role of neutrophils on vascular inflammation and on the biologic effects of diverse immunosuppressive agents including mTOR inhibitors in the context of the pathophysiology of CAV. We investigated the impact of different IDs on the inflammatory responses of isolated human neutrophils harvested from healthy controls and herein, we reported on some novel characteristics of everolimus (EVE) on isolated neutrophils in comparison with other immunosuppressive agents. These biologic effects may contribute to their beneficial effects on the allograft vasculature and consequently on the prevention of CAV.

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Predictors of long-term renal function after conversion to proliferation signal inhibitors in long-term heart transplant recipients

Cited by 18 publications

References 21 publications

Sirolimus Conversion After Heart Transplant: Risk Factors for Acute Rejection and Predictors of Renal Function Response

Sirolimus Conversion After Heart Transplant: Risk Factors for Acute Rejection and Predictors of Renal Function Response

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

Effects of Immunosuppressive agents on neutrophils inflammatory response in humans: An inflammatory perspective on coronary allograft vasculopathy

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