Renal Transplantation; ComplicationNCT05352880
Hypomagnesemia and Its Association With Calcineurin Inhibitors Use in Renal Transplant Recipients
A study testing serum magnesium level, FEMg in people with Renal Transplantation; Complication, run by Alexandria University at 1 site in Egypt.
Trial summary
To assess the prevalence and risk factors of hypomagnesemia and its association with calcineurin inhibitor use among Egyptian renal transplant recipients. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Renal Transplantation; Complication
- What is being tested?
- serum magnesium level, FEMg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteEgypt
- Study dates
- 10 May 2022to 10 Sep 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Duration more than one year after transplantation.
- Serum creatinine less than 2.5 mg/dL.
Who cannot join
- Serum creatinine more than 2.5 mg/dL.
- Patients on diuretics.
- Patients on magnesium supplementation.
- Patients with diabetes mellitus.
- Chronic alcoholism.
- Patients on proton pump inhibitors.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Renal Transplantation; Complication
- Being tested
- serum magnesium level, FEMg
- Keywords
- hypomagnesemia, renal transplant, calcineurin inhibitors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
serum magnesium level, FEMgDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| transplant recipients | Experimental | They will be recruited from the Renal Transplantation Clinic at Alexandria Main University hospital Receives: Diagnostic Test: serum magnesium level, FEMg |
What is being measured
The primary outcome is the main question the study is designed to answer.
decrease in serum magnesium
serum magnesium below normal values
Measured: one month
Secondary outcomes (1)
risk factors of hypomagnesemia
odds ratio of developing hypomagnesemia
Measured: one month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2022
- Study start10 May 2022
- Primary completion30 Jul 2022
- Study completion10 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Renal Transplantation; ComplicationStudies of the same condition, open and under way.
- More trials run by Alexandria UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexandria University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mohamed Mamdouh Mahmoud Mohamed Elsayed , MD, Alexandria University
- Investigators
- Mohamed Mamdouh Elsayed, MD, Principal investigator, lecturermontasser M Zeid, MD, Study chair, professorIman E El Gohary, MD, Study chair, professorshady Fouad Abouelnaga, MD, Study chair, fellowFathyia A Elian, MBBCh, Study chair, resident
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05352880
- Sponsor's protocol ID
- magnesium and renal transplant
- Status last verified
- Dec 2022
- First submitted
- 25 Apr 2022
- Last updated
- 14 Dec 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Jahnen-Dechent W, Ketteler M. Magnesium basics. Clin Kidney J. 2012 Feb;5(Suppl 1):i3-i14. doi: 10.1093/ndtplus/sfr163.
PubMed 26069819Konrad 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.
PubMed 15001450de 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.
PubMed 26069817Van 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.
PubMed 26001746Nijenhuis 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.
PubMed 14978156Stevens 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.
PubMed 21401720Rodrigues 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.
PubMed 28457398Paravicini 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.
PubMed 19103997Ahmadi 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.
PubMed 19736470Pham 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.
PubMed 17699436
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hypomagnesemia and Its Association With Calcineurin Inhibitors Use in Egyptian Renal Transplant Recipients
- ClinicalTrials.gov ID
- NCT05352880
- Acronym / sponsor ID
- magnesium and renal transplant
- Conditions
- Renal Transplantation; Complication
- Keywords
- hypomagnesemia, renal transplant, calcineurin inhibitors
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Alexandria UniversityUniversity, hospital or other
- Study start
- 10 May 2022 (actual)
- Primary completion
- 30 Jul 2022 (actual)
- Study completion
- 10 Sep 2022 (actual)
- First posted
- 29 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To assess the prevalence and risk factors of hypomagnesemia and its association with calcineurin inhibitor use among Egyptian renal transplant recipients.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| transplant recipients | Experimental | Diagnostic Test: serum magnesium level, FEMgThey will be recruited from the Renal Transplantation Clinic at Alexandria Main University hospital |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Duration more than one year after transplantation.
- Serum creatinine less than 2.5 mg/dL.
Key exclusion criteria (6 listed)
- Serum creatinine more than 2.5 mg/dL.
- Patients on diuretics.
- Patients on magnesium supplementation.
- Patients with diabetes mellitus.
- Chronic alcoholism.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| serum magnesium level, FEMgBlood (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. | Diagnostic test | transplant recipients |
Primary outcome
decrease in serum magnesium
Time frame: one month
serum magnesium below normal values
1 secondary outcome
risk factors of hypomagnesemia
Time frame: one month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2022.
- Background: PubMed 26069819Jahnen-Dechent W, Ketteler M. Magnesium basics. Clin Kidney J. 2012 Feb;5(Suppl 1):i3-i14. doi: 10.1093/ndtplus/sfr163.
- Background: PubMed 15001450Konrad 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.
- Background: PubMed 26069817de 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.
- Background: PubMed 26001746Van 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.
- Background: PubMed 14978156Nijenhuis 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.
- Background: PubMed 21401720Stevens 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.
- Background: PubMed 28457398Rodrigues 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.
- Background: PubMed 19103997Paravicini 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.
- Background: PubMed 19736470Ahmadi 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.
- Background: PubMed 17699436Pham 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mohamed Mamdouh Elsayed, MD principal investigator
lecturer
montasser M Zeid, MD study chair
professor
Iman E El Gohary, MD study chair
professor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing serum magnesium level, FEMg in people with Renal Transplantation; Complication, run by Alexandria University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
decrease in serum magnesium (time frame: one month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05352880, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Dec 2022.