Hypomagnesemia and Calcineurin Inhibitors in Kidney Transplant Recipients

Year 2023, , 327 - 331, 31.08.2023

Engin Onan , Saime Paydas , Mustafa Balal , Nebi Cankat Geygel , İbrahim Akkaya , Erhan Tatar

https://doi.org/10.36516/jocass.1317894

Abstract

Aim: Post-transplant hypomagnesemia is a frequently encountered and significant electrolyte disorder and is more common in patients using calcineurin inhibitors (CNIs). This study aimed to evaluate the frequency of hypomagnesemia and accompanying conditions in the outpatient follow-up of renal transplant recipients.
Methods: This cross-sectional study included 236 renal transplant patients. Demographic characteristics of the patients and their biochemical values, including drug levels, were recorded.
Results: Of the patients, 69 (29.2%) were female, and 194 (82.3%) were living donor recipients. The mean age of the entire group was 43.1 years. The frequency of hypomagnesemia was 40% (10/25) in the first 12 months, 26.1% (23/88) between the 12th and 60th months, 26% (32/123) after 60 months, and 27.5% (65/236) in all patients. In patients with higher levels of tacrolimus compared to those with the target level, the frequency of hypomagnesemia increased in those with a posttransplant period of 12-60 months (40.9% vs. 20.8%, p: 0.018) and over 60 months (44% vs. 26%, p: 0.046). In addition, the magnesium (Mg+2) level was lower in patients using tacrolimus compared to those using cyclosporine (CsA) (1.80±0.18 vs 1.91±0.25, p: 0.003). The effect of hypomagnesemia on graft functions was statistically insignificant in all groups.
Conclusion: Hypomagnesemia is a common electrolyte disorder in the early and late periods after transplantation. In our study, hypomagnesemia did not differ according to proton pump inhibitor (PPI) use, gender, fasting blood glucose, and glomerular filtration rate. However, the frequency increased in patients using tacrolimus and those with above-target serum tacrolimus levels.

Keywords

Hypomagnesemia, kidney transplant, calcineurin inhibitor, posttransplant electrolyte disorders

Böbrek Nakli Alıcılarında Hipomagnezemi Ve Kalsinörin İnhibitörleri

Abstract

Giriş: Böbrek nakli sonrası hipomagnezemi sık karşılaşılan ve önemli bir elektrolit bozukluğudur. Kalsinörin inhibitörü kullanan hastalarda daha sık görülür. Bu çalışmada böbrek nakli alıcılarının poliklinik takiplerinde hipomagnezemi sıklığı ve bur duruma eşlik eden süreçlerin değerlendirilmesi amaçlandı.

Gereç ve yöntemler: Bu kesitsel çalışmaya 236 böbrek nakli hastası dahil edildi. Hastaların demografik özellikleri ve ilaç düzeylerini de içeren biyokimyasal değerleri kaydedildi.

Bulgular: Hastaların 69'u (%29,2) kadın, 194'ü (%82,3) canlıdan böbrek nakli alıcısıydı. Tüm grubun ortalama yaşı 43.1’di. Hipomagnezemi sıklığı ilk 12 ayda %40 (10/25), 12-60. aylar arasında %26,1 (23/88), 60 aydan sonra %26 (32/123) ve tüm hastalarda %27,5 (65/236) olarak bulunmuştur. Takrolimus düzeyi hedef düzeyin üzerinde olan posttransplant 12-60 ay olan hastalarda (%40,9'a karşı %20,8, p: 0,018) ve 60 ayın üzerinde olanlarda (%44’e karşı %26, p: 0.046) hipomagnezemi sıklığı artmıştır. Ayrıca takrolimus kullanan hastalarda magnezyum (Mg+2) düzeyi siklosporin (CsA) kullananlara göre daha düşük bulunmuştur. (1,80±0,18- 1,91±0,25, p: 0,003). Hipomagnezeminin greft fonksiyonları üzerindeki etkisi tüm gruplarda istatistiksel olarak anlamlı bulunmamıştır.

Sonuç: Hipomagnezemi böbrek nakli sonrası erken ve geç dönemlerde sık görülen bir elektrolit bozukluğudur. Çalışmamızda hipomagnezemi sıklığı proton pompa inhibitörü (PPI) kullanımına, cinsiyete, açlık kan şekerine ve glomerüler filtrasyon hızına göre farklılık göstermemiştir. Ancak takrolimus kullanan hastalarda ve serum takrolimus düzeyi hedefin üzerinde olan hastalarda sıklık artmıştır.

Keywords

Hipomagnezemi, böbrek nakli, kalsinörin inhibitörü, nakil sonrası elektrolit bozuklukları

References

• 1. Jahnen-Dechent,W, Ketteler, M. Magnesium basics. Clin. Kidney J. 2012; 5: i3–i14. https://doi.org/10.1093/ndtplus/sfr163
• 2. Weisinger JR, Bellorín-Font E. Magnesium and phosphorus. Lancet 1998 ; 352 : 391–6. https://doi.org/10.1016/s0140-6736(97)10535-9
• 3. Garnier AS, Duveau A, Planchais M, et al. Serum Magnesium after kidney transplantation: a systematic review. Nutrients. 2018;10(6):729. https://doi.org/10.3390/nu10060729
• 4. Stefanelli LF, Alessi M, Bertoldi G, et al. Calcineurin-inhibitor-induced hypomagnesemia in kidney transplant patients: a monocentric comparative study between sucrosomial magnesium and magnesium pidolate supplementation. J Clin Med. 2023; 12(3):752. https://doi.org/10.3390/jcm12030752
• 5. Van Laecke S, Van Biesen W. Hypomagnesaemia in kidney transplantation. Transplantation Reviews. 2015; 29(3):154-60. https://doi.org/10.1016/j.trre.2015.05.002
• 6. Ledeganck KJ, De Winter BY, Van den Driessche A, et al. Magnesium loss in cyclosporine-treated patients is related to renal epidermal growth factor downregulation. Nephrology Dialysis Transplantation. 2014; 29(5):1097-102. https://doi.org/10.1093/ndt/gft498
• 7. Margreiter R. European tacrolimus vs. ciclosporin microemulsion renal transplantation study group efficacy and safety of tacrolimus compared with ciclosporin microemulsion in renal transplantation: A randomized multicentre study. Lancet. 2002; 359: 741–6. https://doi.org/10.1016/s0140-6736(02)07875-3
• 8. Stevens RB, Lane JT, Boerner BP, et al. Single-dose rATG induction at renal transplantation: Superior renal function and glucoregulation with less hypomagnesemia: RATGS minimizes glucose dysregulation. Clin. Transplant. 2012; 26:123–32. https://doi.org/10.1111/j.1399-0012.2011.01425.x
• 9. Van de Cauter J, Sennesael J, Haentjens P. Long-term evolution of the mineral metabolism after renal transplantation: A prospective, single-center cohort study. Transplant. Proc. 2011; 43:3470–5. https://doi.org/10.1016/j.transproceed.2011.09.030
• 10. Suh SM, Tashjian AH Jr, Matsuo N, et al. Pathogenesis of hypocalcemia in primary hypomagnesemia: normal end-organ responsiveness to parathyroid hormone, impaired parathyroid gland function. J Clin Invest. 1973; 52(1):153-60. https://doi.org/10.1172/jci107159
• 11. Chien-Te Lee, Hwee-Yeong Ng, Yeong-Hau Lien, et al. Effects of cyclosporine, tacrolimus and rapamycin on renal calcium transport and vitamin D metabolism. Am J Nephrol. 2011; 34(1):87-94. https://doi.org/10.1159/000328874
• 12. Robert Higgins, Karam Ramaiyan, Tanaji Dasgupta, et al. Hyponatraemia and hyperkalemia are more frequent in renal transplant recipients treated with tacrolimus than with cyclosporin. Further evidence for differences between cyclosporin and tacrolimus nephrotoxicities, Nephrology Dialysis Transplantation. 2004; 19(2): 444–50. https://doi.org/10.1093/ndt/gfg515
• 13. Vincenti F, Jensik SC, Filo RS, Miller J, et al. A long-term comparison of tacrolimus (FK506) and cyclosporine in kidney transplantation: evidence for improved allograft survival at five years. Transplantation. 2002; 73: 775–82. https://doi.org/10.1097/00007890-200203150-00021
• 14. Chapman JR. The KDIGO clinical practice guidelines for the care of kidney transplant recipients. Transplantation. 2010; 89:644–5. https://doi.org/10.1097/tp.0b013e3181d62f1b
• 15. Gratreak BDK, Swanson EA, Lazelle RA, et al. Tacrolimus-induced hypomagnesemia and hypercalciuria require FKBP12 suggesting a role for calcineurin. Physiol Rep. 2020; 8(1): e14316. https://doi.org/10.14814/phy2.14316
• 16. Augusto JF, Subra JF, Duveau A, et al. Relation between pretransplant magnesemia and the risk of new-onset diabetes after transplantation within the first year of kidney transplantation. Transplantation. 2014; 97(11): 1155-60. https://doi.org/10.1097/01.tp.0000440950.22133.a1