Hypomagnesaemia in Renal Transplant Recipients: A Review of Mechanistic Complexity, Diagnostic Gaps, and Emerging Therapeutic Strategies

Hypomagnesaemia, a common complication ranging from 20% to over 90%, depending on the diagnostic criteria and population studied, significantly contributes to adverse outcomes, including new-onset diabetes after transplantation, cardiovascular complications, neurological dysfunction and increased infection risk. A total serum magnesium below 0.70 mmol/L is commonly used to define deficiency. In kidney transplant recipients, calcineurin inhibitors downregulate TRPM6 in the distal nephron, leading to early and persistent hypomagnesaemia with links to adverse metabolic and cardiovascular outcomes. Arrhythmia risk rises steeply at total magnesium of <0.50 mmol/L, while neuromuscular irritability and neuropsychiatric symptoms may appear at levels below 0.70 mmol/L. Severe manifestations, such as seizures or tetany, usually occur at ≤0.50 mmol/L and coma at <0.30 mmol/L. Normal ionised magnesium is typically ~0.48–0.65 mmol/L; transplant-specific intervention thresholds remain unvalidated. This narrative review addresses critical diagnostic gaps and explores emerging therapeutic strategies. It highlights three areas: the diagnostic accuracy of ionised magnesium over total magnesium, the critical role of pharmacogenomics in individualising immunosuppression to mitigate tacrolimus-induced hypomagnesaemia and the promising link between gut microbiome modulation and magnesium homeostasis. The implications of these insights are profound: enabling more precise diagnosis and personalised management, reducing the incidence and severity of hypomagnesaemia-related complications, and ultimately supporting more precise diagnosis and personalised management; prospective validation in transplant cohorts is required before outcome claims can be made. This review exposes current diagnostic and therapeutic limitations, advocating for more precise and personalised strategies to address this critical electrolyte imbalance. Identifying hypomagnesaemia as a mechanistically complex and clinically undertreated complication, this review proposes a thematic roadmap that serves as a scientific and clinical framework for advancing personalised electrolyte care in renal transplantation. It is emphasised that while these approaches appear promising, most remain under-evaluated or hypothesis-generating. Addressing hypomagnesaemia through validated thresholds, new research is required to test novel diagnostics and personalised strategies to improve patient and graft outcomes.