Hypomagnesemia and Its Association With Calcineurin Inhibitors Use in Renal Transplant Recipients

December 12, 2022 updated by: Mohamed Mamdouh Mahmoud Mohamed Elsayed , MD, Alexandria University

Hypomagnesemia and Its Association With Calcineurin Inhibitors Use in Egyptian Renal Transplant Recipients

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

80

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Alexandria, Egypt
        • Faculty of Medicine, Aexandria University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: transplant recipients
They will be recruited from the Renal Transplantation Clinic at Alexandria Main University hospital
Diagnostic test: serum magnesium level, FEMg

Blood (serum) for: Magnesium (Mg).Urea, creatinine. Calcium (ca), phosphorus (ph).Sodium (Na), potassium (k), chloride (CL).Fasting blood glucose, cholesterol, triglycerides. Intact PTH, 25OH vitamin D.uric acid, albumin. CBC.

Trough level of cyclosporine or tacrolimus. ii. Urine for:24 hour urinary: Mg, Ca, Ph, Cl and protein. Spot urine sample to calculate fractional excretion of Mg (FEmg)

. Detailed history taking, Thorough Systemic physical examination.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
decrease in serum magnesium
Time Frame: one month
serum magnesium below normal values
one month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
risk factors of hypomagnesemia
Time Frame: one month
odds ratio of developing hypomagnesemia
one month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alexandria University

Investigators

  • Study Chair: montasser M Zeid, MD, professor
  • Study Chair: Iman E El Gohary, MD, professor
  • Study Chair: shady Fouad Abouelnaga, MD, Fellow
  • Study Chair: Fathyia A Elian, MBBCh, Resident

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 10, 2022

Primary Completion (Actual)

July 30, 2022

Study Completion (Actual)

September 10, 2022

Study Registration Dates

First Submitted

April 25, 2022

First Submitted That Met QC Criteria

April 25, 2022

First Posted (Actual)

April 29, 2022

Study Record Updates

Last Update Posted (Actual)

December 14, 2022

Last Update Submitted That Met QC Criteria

December 12, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • magnesium and renal transplant

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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