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

In kidney transplant (KT) patients, magnesium (Mg²⁺) deficiency is widespread. It is often encountered early after KT, may persist longer, and is frequently promoted by calcineurin inhibitors (CNIs) and tubular leakage. Studies demonstrated an association between post-KT hypomagnesemia and allograft dysfunction. The concentration of the active form, the ionized Mg²⁺ (iMg²⁺), is not measured clinically, and total Mg²⁺ (tMg²⁺) and iMg²⁺ correlations are conflicting. We assess the cross-sectional prevalence of hypomagnesemia in KT patients. The correlation of demographic and anthropometric parameters was also studied.

A prospective, single-center analysis of KT patients was conducted at the University Hospital of Bern, Switzerland (March 2023-August 2023). Blood samples were collected at least twice for the majority of patients. tMg²⁺ has been quantified from a plasma sample at the Clinical Chemistry Department of the University Hospital of Bern. The PRIME^® ES analyzer (Nova Biomedical, USA) provided results for iMg²⁺. The following co-variables were considered: age, comorbidities, kidney disease, KT history, estimated glomerular filtration rate (eGFR), and treatment (including Mg²⁺ supplementation and immunosuppression).

A total of 208 measurements in 104 patients were performed [once in 9/104 patients (8.7%), twice in 86/104 (82.7%), and three times in 9/104 (8.7%)]. Compared to that in healthy volunteers (51 measurements in 51 participants), mean iMg²⁺ was significantly lower in KT patients {KT: 0.46 mmol/L [interquartile range (IQR): 0.40-0.50], volunteers: 0.57 mmol/L (IQR 0.54-0.61), p < 0.01}. Overall, iMg²⁺ and tMg²⁺ showed strong category agreement (r² = 0.93, p < 0.01). In linear regression, low iMg²⁺ correlated with CNI exposure. For 110/208 measurements (52.9%), a reduced iMg²⁺ (cutoff: 0.42 mmol/L) was shown. In 58/208 (27.9%), both values were reduced, and 52/208 (25%) had isolated reduced iMg²⁺. In principal component analysis, patients with isolated low iMg²⁺ clustered with patients with low iMg²⁺ and tMg²⁺.

iMg²⁺ and tMg²⁺ were strongly correlated. A substantial proportion of patients show isolated low iMg²⁺. Currently, it is unclear if these patients suffer from Mg²⁺ deficiency.