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肾移植患者中钙调神经磷酸酶抑制剂诱导的低镁血症:蔗糖镁与门冬氨酸镁补充的单中心比较研究

Calcineurin-Inhibitor-Induced Hypomagnesemia in Kidney Transplant Patients: A Monocentric Comparative Study between Sucrosomial Magnesium and Magnesium Pidolate Supplementation.

作者信息

Stefanelli Lucia Federica, Alessi Marianna, Bertoldi Giovanni, Rossato Valentina, Di Vico Valentina, Nalesso Federico, Calò Lorenzo A

机构信息

Nephrology, Dialysis and Transplantation Unit, Department of Medicine, University of Padova, 35128 Padova, Italy.

出版信息

J Clin Med. 2023 Jan 17;12(3):752. doi: 10.3390/jcm12030752.

Abstract

Magnesium (Mg) contributes to DNA stability, protein synthesis and cardiac excitability, while Mg deficiency leads to increased cardiovascular mortality, diabetes, hyperparathyroidism and risk of fractures. In kidney transplant patients, calcineurin inhibitors (CNIs) downregulating Mg channel TRPM6 in the distal collecting tubule induce early hypomagnesemia (HypoMg), which is associated with a faster decline in allograft function. A new formulation, sucrosomial Mg (SucrMg), for oral supplements encapsulates Mg oxide in a phospholipid membrane covered by a sucrester matrix, enhancing gastric and intestinal Mg absorption. This study has evaluated Mg bioavailability, effectiveness and tolerance of SucrMg compared to the conventional preparation of Mg pidolate (PidMg). The association of blood Mg with risk of post-transplant dysglycemia and hyperparathyroidism has also been investigated. Forty hypomagnesemic adult single, double or combined kidney-pancreas or kidney-liver transplant recipients within 2 years from transplantation were recruited. In total, 16 patients received PidMg and 27 received SucrMg. Blood Mg was measured at baseline (T0), after 15 days (T1) and after 6 months (T2) of treatment. PTH, fasting glucose and calcium were measured at baseline and after 6 months of treatment. The tolerance was evaluated at the ambulatory visits. SucrMg compared to PidMg was more efficient at increasing Mg bioavailability at T1: < 0.0001 vs. = 0.72 ns, respectively, with a ∆% increase of 12.4% vs. 5.4%, = 0.04. Both preparations increased blood Mg at T2, < 0.0001 and = 0.002, respectively. SucrMg was better tolerated. No difference was observed for fasting plasma glucose, PTH and calcium. On one hand, our study is the first among transplant patients to evaluate the efficacy of SucrMg in the correction of HypoMg, which might justify the limited number of patients enrolled and the short observation time; on the other hand, our results could serve as a useful working hypothesis for further studies with a larger number of transplant patients and an extended study duration to confirm the benefits observed with SucrMg.

摘要

镁(Mg)有助于DNA稳定性、蛋白质合成和心脏兴奋性,而镁缺乏会导致心血管疾病死亡率增加、糖尿病、甲状旁腺功能亢进和骨折风险。在肾移植患者中,钙调神经磷酸酶抑制剂(CNIs)下调远端集合管中的镁通道TRPM6会诱发早期低镁血症(HypoMg),这与移植肾功能更快下降有关。一种用于口服补充剂的新制剂——蔗糖镁(SucrMg),将氧化镁包裹在由蔗糖酯基质覆盖的磷脂膜中,可增强胃肠道对镁的吸收。本研究评估了SucrMg与传统的pidolate镁制剂(PidMg)相比的镁生物利用度、有效性和耐受性。还研究了血镁与移植后血糖异常和甲状旁腺功能亢进风险的关系。招募了40名移植后2年内出现低镁血症的成年单肾、双肾或肾胰联合或肝肾联合移植受者。总共16名患者接受了PidMg,27名患者接受了SucrMg。在治疗的基线期(T0)、15天后(T1)和6个月后(T2)测量血镁。在基线期和治疗6个月后测量甲状旁腺激素(PTH)、空腹血糖和钙。在门诊就诊时评估耐受性。与PidMg相比,SucrMg在T1时提高镁生物利用度方面更有效:分别为<0.0001和=0.72无显著性差异,增加百分比分别为12.4%和5.4%,P = 0.04。两种制剂在T2时均提高了血镁水平,分别为<0.0001和P = 0.002。SucrMg的耐受性更好。空腹血糖、PTH和钙方面未观察到差异。一方面,我们的研究是移植患者中首个评估SucrMg纠正低镁血症疗效的研究,这可能解释了入组患者数量有限和观察时间较短的原因;另一方面,我们的结果可为进一步研究提供有用的工作假设,即纳入更多移植患者并延长研究时间,以证实SucrMg所观察到的益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a9d/9917957/d09cc22eb6ac/jcm-12-00752-g001.jpg

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