Mycophenolate and Sirolimus as Calcineurin Inhibitor-Free Immunosuppression Improves Renal Function Better Than Calcineurin Inhibitor-Reduction in Late Cardiac Transplant Recipients With Chronic Renal Failure

Groetzner, J; Kaczmarek, Ingo; Schulz, Uwe; Stegemann, Emilia; Kaiser, Kristina; Wittwer, Thorsten; Schirmer, Johannes; Voß, Meinolf; Strauch, Justus; Wahlers, Thorsten; Sohn, Hae-Young; Wagner, Florian; Tenderich, Gero; Stempfle, Hans‐Ulrich; Mueller-Ehmsen, J.; Schmid, Çhristof; Vogeser, Michael; Koch, Karrl Christian; Reichenspurner, Hermann; Daebritz, Sabine; Meiser, Bruno; Reichart, Bruno; VENINAHTx-Investigators,

doi:10.1097/tp.0b013e3181963371

Cited by 76 publications

(66 citation statements)

References 26 publications

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“…At one year, GFR improved only in the CNI withdrawal group (baseline to 12 months change of 36 to 55 ml/ min versus 41 to 40 ml/min in the CNI dose reduction group). Six patients on low dose CNI (versus none off CNI) progressed to dialysis [36]. Lower baseline GFR did not predict poorer response as in other studies.…”

mentioning

confidence: 47%

“…More recently, VENINAHTx, a randomized study enrolled 63 late OHT patients with CKD (GFR between 15 and 60 mL/min) [36]. CNI was stopped in 30 patients and was replaced with SRL.…”

Section: Discontinuation Of Cnismentioning

confidence: 99%

“…The VENINAHTx study, discussed above, is a prospective randomized study that showed improved renal function only in patients completely withdrawn from CNI therapy [36].…”

Section: Reduction Of Cnis Dosementioning

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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mentioning

confidence: 47%

“…More recently, VENINAHTx, a randomized study enrolled 63 late OHT patients with CKD (GFR between 15 and 60 mL/min) [36]. CNI was stopped in 30 patients and was replaced with SRL.…”

Section: Discontinuation Of Cnismentioning

confidence: 99%

See 1 more Smart Citation

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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“…On the other hand, CNI-free immunosuppression after cardiac transplantation using MMF and the mTORi, sirolimus, showed a good clinical course in the absence of acute rejection in a patient with impaired renal function. 9 In Japan, the mTORi, everolimus, is already approved for use after HTx. However, as mTORi have several side effects, such as impairment of wound healing, hypercholesterolemia, inhibition of sperm production and so on, we did not chose everolimus as the first choice after pediatric HTx.…”

Section: Discussionmentioning

confidence: 99%

First Pediatric Heart Transplantation From a Pediatric Donor Heart in Japan

Ueno

Fukushima

Sakaguchi

et al. 2012

Circ J

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“…Different trials have shown that sirolimus conversion can preserve 15,35 or reverse 36,37,38,39 renal function in other organ transplanted patients receiving CNIbased immunosuppression. These studies found sirolimus as a useful alternative immunosuppressant, allowing CNI withdrawal in transplant recipients with renal impairment.…”

Section: Sirolimus Conversion In Organ Transplantmentioning

confidence: 99%

Conversion of Calcineurin Inhibitors With Mammalian Target of Rapamycin Inhibitors After Kidney Transplant

Nikoueinejad

Soleimani²,

Mirshafiey³

et al. 2012

Exp Clin Transplant

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One way to overcome chronic allograft nephropathy induced by calcineurin inhibitors in immunosuppression protocols for organ transplants is to replace such inhibitors with mammalian target of rapamycin inhibitors, which are not clinically nephrotoxic because they have better renal function. If patients tolerate replacement, there could be a clear preference for mammalian target of rapamycin inhibitors as a maintenance immunosuppressant after renal transplant. This replacement could be sufficient if it were used for a certain time after calcineurin inhibitors. This review considers the conversion effects of calcineurin inhibitors with mammalian target of rapamycin inhibitors from the view point of kidney function during different periods after a kidney transplant.

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Mycophenolate and Sirolimus as Calcineurin Inhibitor-Free Immunosuppression Improves Renal Function Better Than Calcineurin Inhibitor-Reduction in Late Cardiac Transplant Recipients With Chronic Renal Failure

Abstract: Conversion toward a CNI-free immunosuppression (Mycophenolate, sirolimus) is superior to CNI-reduced immunosuppression in improving renal failure in late HTx-recipients. However, this benefit is relativized by the increased incidence and severity of sirolimus/MMF-associated side effects.

Cited by 76 publications

References 26 publications

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

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

First Pediatric Heart Transplantation From a Pediatric Donor Heart in Japan

Conversion of Calcineurin Inhibitors With Mammalian Target of Rapamycin Inhibitors After Kidney Transplant

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