Low serum magnesium levels in the first 1 to 12 months of kidney transplantation may portend better long-term graft and patient survival, according to a new study.
“We believe that hypomagnesemia could serve as a biomarker of better tubular function early on and be a good predictor of long-term patient and allograft outcomes,” investigators Ofer Isakov, MD, PhD, of Tel Aviv Souraski Medical Center, Tel Aviv University, Israel, and colleagues concluded.
Dr Isakov and colleagues conducted a retrospective analysis of 726 kidney transplant recipients (KTRs) treated at Brigham and Women’s Hospital in Boston, Massachusetts from 2000 to 2013. For every 0.1 mg/dL increment in serum magnesium, the risk for graft loss or death, all-cause mortality, and death with a functioning graft significantly increased 11%, 14%, and 12% respectively, the investigators reported in Kidney and Blood Pressure Research.
In subgroup analyses, patients older than 60 years, women, and those with delayed graft function had significantly increased risks.
In a multivariate model, the risk for all-cause mortality significantly increased 57% in patients with a median magnesium level of 1.7 mg/dL or more compared with lower levels.
Post-transplant hypomagnesemia is commonly observed among patients prescribed calcineurin inhibitors (CNIs), according the investigators. CNI therapy was started after transplantation, using mostly tacrolimus, aiming for trough levels of 8-10 ng/mL in the first 3 months, and 5-8 ng/mL thereafter. The study findings remained significant even after adjustment for CNI trough levels, baseline graft function, and delayed graft function.
The associations between CNI use and graft and patient survival disappeared after adjustment for magnesium levels, suggesting that the CNI effect on outcomes is partly related to hypomagnesemia, the investigators noted. CNIs reduce the abundance of key divalent cation transport proteins along the distal convoluted tubule, they explained, causing renal magnesium wasting. It is possible that the mechanism of tacrolimus-induced nephrotoxicity differs from that of cyclosporine, “possibly weaker and not mediated via hypomagnesemia.”
“Hypomagnesemia as well as hypophosphatemia early post-transplant may indicate a better tubular graft function,” Dr Isakov’s team wrote. “Beyond that, phosphate depletion can further enhance Mg loss by reducing Mg ion reabsorption in the distal convoluted tubule.”
Isakov O, Patibandla BK, Christopher KB, Chandraker A, Hod T. Impact of post-transplantation hypomagnesemia on long-term graft and patient survival after transplantation. Kidney Blood Press Res. Published online February 23, 2022. doi:10.1159/000522233