To assess the prevalence and risk factors of hypomagnesemia and its association with calcineurin inhibitor use among Egyptian renal transplant recipients.

Magnesium (Mg) is the fourth cation in the body and the second most prevalent intracellular cation. Intracellular magnesium concentrations range from 5 to 20 mmol/L; 1-5% of it is ionized, the remainder is bound to proteins.

Extracellular Mg represents only 1% of total body Mg and is mostly found in serum with concentrations ranging between 0.65 to 1.05 mmol/L and in red blood cells. It is present in three states; ionized Mg (55-70%), protein bound Mg (20-30%), and Mg complexed with anions such as bicarbonate or phosphate (5-15%). Ionized magnesium has the greatest biological activity. Magnesium homeostasis is maintained by the intestine, bones and kidneys. It is absorbed in the gut and stored in bone mineral, and excess magnesium is excreted by the kidneys and faeces. The majority of magnesium is absorbed in the small intestine by a passive paracellular mechanism, which is driven by an electrochemical gradient. A minor regulatory fraction of magnesium is transported via the transcellular transporter called transient receptor potential channel melastatin member (TRPM) 6 and TRPM7-members of the long transient receptor potential channel family.

Only about 24-76% of dietary consumed magnesium is absorbed in the gut and the rest is eliminated in the faeces.

Intestinal absorption is not directly proportional to magnesium intake but is dependent mainly on magnesium status. Hypomagnesemia is frequently observed after kidney transplantation, in part to immunosuppressive regimens including calcineurin inhibitors (CNI). The incidence of hypomagnesemia has been reported to be higher among tacrolimus compared to cyclosporine-(CsA) treated patients.

Many other factors influence Mg levels after kidney transplantation such as post-transplantation volume expansion, metabolic acidosis, insulin resistance, decreased gastro-intestinal absorption due to diarrhea, low Mg intake and medications such as diuretics or proton pump inhibitors.

Hypomagnesemia was reported to develop frequently within the first few weeks following transplantation. Hypomagnesemia may persist for several years after kidney transplantation. As observed in the general population, serum Mg levels were inversely correlated with glomerular filtration rate.Hypomagnesemia was associated with a greater decline in allograft function and an increased risk of development of chronic fibrotic lesions andgraft loss for patients with ciclosporin induced nephropathy.

In subjects treated with cyclosporine, Mg supplementation improved renal function, reduced tubular atrophy and interstitial fibrosis and prevented kidney function decline. Mg supplementation has been shown to exert an effect of preventing renal damage by using several mechanisms, including innate immune pathways. Indeed, Mg supplementation inhibits monocyte and macrophage recruitment by abolishing expression of chemoattractant proteins (osteopontin and monocyte chemo attractant protein-1), fibrogenic molecules and extracellular matrix proteins. Moreover, Mg induces down-regulation of endothelin-1 expression. Hypomagnesemia has been shown to play a role in the pathogenesis of arterial hypertension, endothelial dysfunction, dyslipidemia and inflammation leading to coronary heart disease (CHD). Low intracellular Mg levels lead to significantly impaired endothelial function together with decreased endothelial NO synthase expression.

Inclusion Criteria:

• Duration more than one year after transplantation.
• Serum creatinine less than 2.5 mg/dL.

Exclusion Criteria:

1. Serum creatinine more than 2.5 mg/dL.
2. Patients on diuretics.
3. Patients on magnesium supplementation.
4. Patients with diabetes mellitus.
5. Chronic alcoholism.
6. Patients on proton pump inhibitors.