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

NCT ID: NCT05352880

Last Updated: 2022-12-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-05-10

Study Completion Date

2022-09-10

Brief Summary

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

Detailed Description

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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.

Conditions

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Renal Transplantation; Complication

Keywords

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hypomagnesemia renal transplant calcineurin inhibitors

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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transplant recipients

They will be recruited from the Renal Transplantation Clinic at Alexandria Main University hospital

Group Type EXPERIMENTAL

serum magnesium level, FEMg

Intervention Type DIAGNOSTIC_TEST

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.

Interventions

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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.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Alexandria University

OTHER

Sponsor Role lead

Responsible Party

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Mohamed Mamdouh Mahmoud Mohamed Elsayed , MD

Lecturer

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Mohamed Mamdouh Elsayed, MD

Role: PRINCIPAL_INVESTIGATOR

lecturer

montasser M Zeid, MD

Role: STUDY_CHAIR

professor

Iman E El Gohary, MD

Role: STUDY_CHAIR

professor

shady Fouad Abouelnaga, MD

Role: STUDY_CHAIR

fellow

Fathyia A Elian, MBBCh

Role: STUDY_CHAIR

resident

Locations

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Faculty of Medicine, Aexandria University

Alexandria, , Egypt

Site Status

Countries

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Egypt

References

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Jahnen-Dechent W, Ketteler M. Magnesium basics. Clin Kidney J. 2012 Feb;5(Suppl 1):i3-i14. doi: 10.1093/ndtplus/sfr163.

Reference Type BACKGROUND
PMID: 26069819 (View on PubMed)

Konrad M, Schlingmann KP, Gudermann T. Insights into the molecular nature of magnesium homeostasis. Am J Physiol Renal Physiol. 2004 Apr;286(4):F599-605. doi: 10.1152/ajprenal.00312.2003.

Reference Type BACKGROUND
PMID: 15001450 (View on PubMed)

de Baaij JH, Hoenderop JG, Bindels RJ. Regulation of magnesium balance: lessons learned from human genetic disease. Clin Kidney J. 2012 Feb;5(Suppl 1):i15-i24. doi: 10.1093/ndtplus/sfr164.

Reference Type BACKGROUND
PMID: 26069817 (View on PubMed)

Van Laecke S, Van Biesen W. Hypomagnesaemia in kidney transplantation. Transplant Rev (Orlando). 2015 Jul;29(3):154-60. doi: 10.1016/j.trre.2015.05.002. Epub 2015 May 7.

Reference Type BACKGROUND
PMID: 26001746 (View on PubMed)

Nijenhuis T, Hoenderop JG, Bindels RJ. Downregulation of Ca(2+) and Mg(2+) transport proteins in the kidney explains tacrolimus (FK506)-induced hypercalciuria and hypomagnesemia. J Am Soc Nephrol. 2004 Mar;15(3):549-57. doi: 10.1097/01.asn.0000113318.56023.b6.

Reference Type BACKGROUND
PMID: 14978156 (View on PubMed)

Stevens RB, Lane JT, Boerner BP, Miles CD, Rigley TH, Sandoz JP, Nielsen KJ, Skorupa JY, Skorupa AJ, Kaplan B, Wrenshall LE. Single-dose rATG induction at renal transplantation: superior renal function and glucoregulation with less hypomagnesemia. Clin Transplant. 2012 Jan-Feb;26(1):123-32. doi: 10.1111/j.1399-0012.2011.01425.x. Epub 2011 Mar 14.

Reference Type BACKGROUND
PMID: 21401720 (View on PubMed)

Rodrigues N, Santana A, Guerra J, Neves M, Nascimento C, Goncalves J, da Costa AG. Serum Magnesium and Related Factors in Long-Term Renal Transplant Recipients: An Observational Study. Transplant Proc. 2017 May;49(4):799-802. doi: 10.1016/j.transproceed.2017.01.070.

Reference Type BACKGROUND
PMID: 28457398 (View on PubMed)

Paravicini TM, Yogi A, Mazur A, Touyz RM. Dysregulation of vascular TRPM7 and annexin-1 is associated with endothelial dysfunction in inherited hypomagnesemia. Hypertension. 2009 Feb;53(2):423-9. doi: 10.1161/HYPERTENSIONAHA.108.124651. Epub 2008 Dec 22.

Reference Type BACKGROUND
PMID: 19103997 (View on PubMed)

Ahmadi F, Naseri R, Lessan-Pezeshki M. Relation of magnesium level to cyclosporine and metabolic complications in renal transplant recipients. Saudi J Kidney Dis Transpl. 2009 Sep;20(5):766-9.

Reference Type BACKGROUND
PMID: 19736470 (View on PubMed)

Pham PC, Pham PM, Pham SV, Miller JM, Pham PT. Hypomagnesemia in patients with type 2 diabetes. Clin J Am Soc Nephrol. 2007 Mar;2(2):366-73. doi: 10.2215/CJN.02960906. Epub 2007 Jan 3.

Reference Type BACKGROUND
PMID: 17699436 (View on PubMed)

Other Identifiers

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magnesium and renal transplant

Identifier Type: -

Identifier Source: org_study_id