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

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: p < 0.0001 vs. p = 0.72 ns, respectively, with a ∆% increase of 12.4% vs. 5.4%, p = 0.04. Both preparations increased blood Mg at T2, p < 0.0001 and p = 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.

Magnesium matters: unveiling hidden risks in kidney transplant patients through total and ionized magnesium profiling

“…Indeed, after analysis of various factors, only the use of CNI correlated statistically significantly with hypomagnesemia. CNI induces hypomagnesemia through urinary Mg 2+ wasting by downregulating the renal expression of the epidermal growth factor (EGF) and the Mg 2+ channel Transient Receptor Potential Pelastatin 6 (TRMP6) in the distal collecting tubule ( 1 , 22 ). The incidence of tacrolimus- or cyclosporine-induced hypomagnesemia has been studied in-depth, and these common side effects are now well known in the medical world ( 20 , 21 , 23 ).…”

“…Studies demonstrated that hypomagnesemia is associated with unfavorable outcomes and mortality ( 21 , 22 ). Favoring iMg 2+ over tMg 2+ could enhance the detection of hypomagnesemia, enabling more accurate identification of patients in need of supplementation.…”

Immunosuppressive Therapy and Nutritional Status of Patients after Kidney Transplantation: A Protocol for a Systematic Review

“…Hypomagnesemia is a common finding in most patients after kTx, particularly during the initial period. The use of calcineurin inhibitors, notably tacrolimus, tends to contribute to its occurrence [58]. What is more, patients who have undergone kTx may experience fluctuations in serum potassium levels, including both low and high values.…”