Effects of Immunosuppressive Agents on Magnesium Metabolism Early after Allogeneic Hematopoietic Stem Cell Transplantation

Aisa, Yoshinobu; Mori, Takehiko; Nakazato, Tomonori; Shioiri, Takayuki; Yamazaki, Rie; Ikeda, Yasuo; Okamoto, Shinichiro

doi:10.1097/01.tp.0000174340.40585.d4

Cited by 36 publications

(22 citation statements)

References 26 publications

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“…To our knowledge, we are the first to culture primary human lung cells derived from HSCT patients with BOS, and by using these cells we were able to demonstrate that CsA and FK506 at clinically relevant immunosuppressive concentrations have a significant pro-proliferative effect on primary human lung myofibroblasts. The concentrations at which this effect was observed lay between 0.001 mg?L [33]. Our in vitro data showing a pro-proliferative effect of calcineurin inhibitors in primary human lung cells are in line with data obtained in other cell types [22,23], and correspond to the observed pro-fibrotic effect in vivo [34].…”

Section: Bronchiolitis | Ke Hostettler Et Alsupporting

confidence: 76%

Calcineurin inhibitors in bronchiolitis obliterans syndrome following stem cell transplantation

Hostettler¹,

Gerull²,

Lardinois³

et al. 2013

European Respiratory Journal

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Bronchiolitis obliterans is a complication after allogeneic haematopoietic stem cell transplantation (HSCT). Management of bronchiolitis obliterans comprises intensive immunosuppression, but treatment response is poor. We investigated the effect of cyclosporine A (CsA), tacrolimus (FK506), methylprednisolone (mPRED), mycophenolate mofetil (MMF) and everolimus on the proliferation of primary lung myofibroblasts from HSCT patients with bronchiolitis obliterans syndrome (BOS).Cells were isolated from surgical lung biopsies of eight HSCT patients with BOS. Proliferation was assessed by [ 3 H]-thymidine incorporation. Biopsies revealed constrictive bronchiolitis obliterans in three patients and lymphocytic bronchiolitis in five patients. CsA and FK506 significantly induced proliferation of myofibroblasts. mPRED and MMF caused a significant inhibition of proliferation, whereas everolimus had no effect. Costimulation with FK506, mPRED and MMF significantly inhibited proliferation. Serial pulmonary function tests over 12 months after lung biopsy and under triple therapy demonstrated that patients with lymphocytic bronchiolitis had a significant improvement in forced expiratory volume in 1 s (FEV1), whereas FEV1 of patients with bronchiolitis obliterans was unchanged.Our data demonstrate a pro-proliferative effect of calcineurin inhibitors on primary human lung myofibroblasts obtained from patients with BOS after HSCT. In contrast, based on the observed antiproliferative capacity of MMF in vitro, MMF-based calcineurin inhibitor-free treatment strategies should be further evaluated in patients with bronchiolitis obliterans after HSCT. @ERSpublications Calcineurin inhibitor-free regimens need further evaluation in bronchiolitis obliterans after stem cell transplantation

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Section: Bronchiolitis | Ke Hostettler Et Alsupporting

confidence: 76%

Calcineurin inhibitors in bronchiolitis obliterans syndrome following stem cell transplantation

Hostettler¹,

Gerull²,

Lardinois³

et al. 2013

European Respiratory Journal

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“…Several reports also indicate that the development of PRES does not require supratherapeutic CNI levels [11,20,28]. The neurotoxicity of CNI therapy has been associated with hypomagnesemia due to a drug-related renal loss [50,51]. We observed hypomagnesemia in 4 out of 7 patients, but hypomagnesemia is not a prerequisite [8], and continuous substitution of magnesium to normal levels seems not to prevent the development of PRES [20].…”

Section: Discussionmentioning

confidence: 83%

Clinical Management of Posterior Reversible Encephalopathy Syndrome after Allogeneic Hematopoietic Stem Cell Transplantation: A Case Series and Review of the Literature

et al. 2015

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Background: Posterior reversible encephalopathy syndrome (PRES) is a rare but serious complication after allogeneic hematopoietic stem cell transplantation (alloHSCT). Among others, calcineurin inhibitors (CNI) for prophylaxis of graft-versus-host disease (GvHD) may promote the development of PRES, but the pathomechanism is still controversial. Discontinuation of CNI facilitates remission of symptoms but might contribute to the unfavorable prognosis of PRES due to an elevated incidence of GvHD. Methods: This is a case series of 7 patients with PRES from a retrospective analysis of 146 consecutive patients who received alloHSCT for hematologic malignancies. Results: At the onset of PRES, all patients presented a systemic infection, while no influence was seen for underlying disease, conditioning regimen, donor type, or GvHD. Discontinuation of CNI and control of the blood pressure reversed neurological symptoms in 6 patients, while 1 patient died from septic multiorgan failure. After bridging with prednisolone and/or mycophenolic acid, replacement of CNI by the mammalian target of rapamycin (mTOR) inhibitor everolimus effectively prevented severe GvHD without recurrence of PRES. Conclusions: A systemic infection/inflammation may be an important cause of PRES. Prophylaxis of GvHD by the mTOR inhibitor everolimus in case of PRES after alloHSCT demonstrated promising results but needs to be validated in larger cohorts.

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“…The use of immunosuppressive regimens including cyclosporine (CsA) and tacrolimus are associated with hypomagnesemia due to the suppressed reabsorption of Mg from renal tubules through the reduction of TRPM6 expression [69,70] . This has raised the hypothesis that renal Mg wasting might be a contributory factor for CsA and tacrolimus toxicity.…”

Section: Mg In Renal Transplantationmentioning

confidence: 99%

Magnesium in Chronic Kidney Disease: Challenges and Opportunities

Kanbay¹,

Goldsmith

Uyar

et al. 2010

Blood Purif

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Cardiovascular disease is the leading cause of mortality and morbidity in patients with chronic kidney disease, which is partly explained by the fact that 40–70% of patients receiving dialysis have significant coronary artery disease. Recent clinical studies have shown that lower serum magnesium (Mg) levels are associated with vascular calcification and cardiovascular mortality among patients with end-stage renal disease (ESRD). On the other hand, hypermagnesemia inhibits parathyroid hormone secretion, which is considered an important independent risk factor for vascular calcification, left ventricular hypertrophy and mortality in ESRD patients. Finally, increasing evidence points towards a link between Mg and cardiovascular disease, even in subjects without chronic kidney disease. The purpose of this review was to critically review the current literature examining the effects of plasma Mg levels on cardiovascular disease and parathyroid hormone homeostasis in ESRD, and renal transplant patients.

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Effects of Immunosuppressive Agents on Magnesium Metabolism Early after Allogeneic Hematopoietic Stem Cell Transplantation

Cited by 36 publications

References 26 publications

Calcineurin inhibitors in bronchiolitis obliterans syndrome following stem cell transplantation

Calcineurin inhibitors in bronchiolitis obliterans syndrome following stem cell transplantation

Clinical Management of Posterior Reversible Encephalopathy Syndrome after Allogeneic Hematopoietic Stem Cell Transplantation: A Case Series and Review of the Literature

Magnesium in Chronic Kidney Disease: Challenges and Opportunities

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