Report from the 2018 consensus conference on immunomodulating agents in thoracic transplantation: Access, formulations, generics, therapeutic drug monitoring, and special populations

Cochrane, A.; Lyster, Haifa; Lindenfeld, JoAnn; Doligalski, Christina T.; Baran, David A.; Yost, C.; Shullo, M.; Schweiger, Martin; Weill, David; Stuckey, Linda J.; Ivulich, S.; Scheel, Janet; Peters, Lisa; Colvin, Monica; Dawson, Kyle L.; Girgis, Reda E.; Weeks, Phillip; Tse, T.; Russell, Stuart; Flattery, Maureen; Jennings, Doug; Kittleson, M.; Miller, Tara; Khuu, T.; Claridge, Tamara; Uber, Patricia A.; Ford, Katrina; Ensor, Christopher R.; Simpson, Kathleen; Dipchand, Anne I.; Page, Robert L.

doi:10.1016/j.healun.2020.06.024

Cited by 15 publications

(15 citation statements)

References 119 publications

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“…The MMF-LD group maintained a lower median [IQR] MMF dose compared with the MMF-HD group over the study follow-up (2 [0] MMF-LD vs. 3 [1] g MMF-HD, p < 0.01). Both groups had significant MMF dose reductions by the end of the study (Figure 2A), with only 33.6% in the MMF-HD and 42.6% in the MMF-LD remaining on their starting dose (Figure S3).…”

Section: Mmf Dose Adjustments and Concomitant Medicationsmentioning

confidence: 99%

“…Heart transplantation (HT) is the gold‐standard therapy for selected patients with advanced heart failure (HF). Mycophenolate mofetil (MMF) is the anti‐metabolite of choice among HT recipients, with superior survival and improved rejection profile when compared to prior generation immunosuppressants 1 . However, its tolerability is limited by toxicities, including neutropenia from bone marrow suppression and gastrointestinal (GI) intolerance, affecting 20%–60% of patients 2,3 .…”

Section: Introductionmentioning

confidence: 99%

“…Mycophenolate mofetil (MMF) is the anti-metabolite of choice among HT recipients, with superior survival and improved rejection profile when compared to prior generation immunosuppressants. 1 However, its tolerability is limited by toxicities, including neutropenia from bone marrow suppression and gastrointestinal (GI) intolerance, affecting 20%-60% of patients. 2,3 These adverse events are dose-dependent and can be relieved by dose splitting, reduction, or discontinuation of MMF, which in turn exposes patients to heightened risks of rejection.…”

Section: Introductionmentioning

confidence: 99%

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Temporal shifts in safety and efficacy profile of mycophenolate mofetil 2 g versus 3 g daily early after heart transplantation

et al. 2022

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Study Objective: Mycophenolate mofetil (MMF) is the gold-standard immunosuppressive agent in heart transplantation (HT), but dose-dependent toxicities (e.g., neutropenia) are frequent. Gut bacteria βd-glucuronidases (GUS) modulate MMF bioavailability, and changes in the intestinal flora may influence the pharmacokinetics of MMF. The objective of this study was to evaluate the safety and efficacy of MMF 1.5 g every 12 h (q12) [high-dose, HD] versus 1 g q12 [low-dose, LD] and explore the association between neutropenia and GUS. Measurements:We compared the incidence of acute cellular rejection (ACR) and neutropenia during the first 6 months post-HT. The association between neutropenia and GUS was investigated in an exploratory analysis on a subset of patients with prospectively collected stool data. Stool samples were analyzed using 16S rRNA sequencing.Main Results: A total of 168 patients (120 MMF-HD, 48 MMF-LD; mean age 55.7 years, 79% male) were studied. Neutropenia occurred in 38.6% of patients at a median of 106 days. Freedom from neutropenia was lower in MMF-HD compared with MMF-LD (57% vs. 73%, p = 0.03). ACR (≥1R/1B) occurred in 37.5% of patients at a median of 20 [10-96] days, while high-grade ACR (≥2R/3A) occurred in 11.3% at a median of 14 [9-89] days. Freedom from ACR was similar between groups. MMF-LD was associated with more high-grade ACR (hazard ratio [HR] 3.47, 95% confidence interval[CI] 1.09-11.08, p = 0.03) during the first month, but less neutropenia (HR 0.54, 95% CI 0.29-1.00, p = 0.05) between 1 and 6 months. GUS-producing bacteria were more abundant in neutropenic patients.Conclusions: MMF-LD was associated with higher rates of early high-grade ACR and lower rates of later neutropenia. Further studies are warranted to test whether temporal MMF dose adjustments and gut microbial composition could improve clinical outcomes post-HT.

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Section: Mmf Dose Adjustments and Concomitant Medicationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Temporal shifts in safety and efficacy profile of mycophenolate mofetil 2 g versus 3 g daily early after heart transplantation

et al. 2022

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“…While no studies appear to have been published on RF and long‐term mortality after HT in the LVAD population, it is acceptable to infer from studies just on HT: a preserved RF is associated with better survival rates after HT, while higher mortality rates are associated with the progression of renal disease 110 . In the light of these findings, preserving RF is particularly important in patients with LVADs awaiting HT, especially considering the risk of AKI during the HT procedure, and the nephrotoxic immunosuppressants required afterwards 111 …”

Section: Predictors Of Mortality In the Lvad Population With A Specia...mentioning

confidence: 99%

“…110 In the light of these findings, preserving RF is particularly important in patients with LVADs awaiting HT, especially considering the risk of AKI during the HT procedure, and the nephrotoxic immunosuppressants required afterwards. 111…”

Section: Predictors Of Mortalit Y In the Lvad Population With A Speci...mentioning

confidence: 99%

Heart, kidney and left ventricular assist device: a complex trio

Gambaro

Lombardi

Gottin

et al. 2021

Eur J Clin Investigation

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Background: Heart failure (HF) is a complex syndrome affecting the whole body, kidneys included. The left ventricular assist device (LVAD) is a valid option for patients with very severe HF. Focusing on renal function, LVAD implantation could theoretically reverse the detrimental effects of HF syndrome on kidneys. However, implanting an LVAD is a high-risk surgical procedure, and LVAD patients have higher risk of bleeding, device thrombosis, strokes, renal impairment, multi-organ failure and infections. Furthermore, an LVAD has its own particular effects on the renal system. Methods: In this review, we provide a comprehensive overview of the complex interaction between LVAD and the kidneys from the pathophysiological and clinical perspectives. An analysis of the different effects of pulsatile-flow and continuousflow LVAD is provided. Results: Despite their limitations, creatinine-based estimated glomerular filtration rate (eGFR) formulas help to stratify patients by their post-LVAD placement prognosis. Poor basal renal function, the onset of acute kidney injury or the need for renal replacement therapy after LVAD implantation negatively influences a patient's prognosis. LVAD can also prompt an improvement in renal function, however, with some counterintuitive effects on a patient's prognosis. Conclusion: It is still hard to say whether different trends in eGFR depend on different renal conditions before LVAD placement, on a patient's better overall status or on a particular patient management strategy before and/or after the device's implantation. Steps should be taken to solve this question because finding the best candidates for LVAD implantation is of paramount importance to ensure the best outcomes.

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Leitsymptom Dyspnoe, Leistungsschwäche

2022

Facharztprüfung Kardiologie

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Report from the 2018 consensus conference on immunomodulating agents in thoracic transplantation: Access, formulations, generics, therapeutic drug monitoring, and special populations

Cited by 15 publications

References 119 publications

Temporal shifts in safety and efficacy profile of mycophenolate mofetil 2 g versus 3 g daily early after heart transplantation

Temporal shifts in safety and efficacy profile of mycophenolate mofetil 2 g versus 3 g daily early after heart transplantation

Heart, kidney and left ventricular assist device: a complex trio

Leitsymptom Dyspnoe, Leistungsschwäche

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