Tacrolimus trough monitoring guided by mass spectrometry without accounting for assay differences is associated with acute kidney injury in lung transplant recipients

Abstract

Purpose Tacrolimus is a nephrotoxic immunosuppressant historically monitored via enzyme-based immunoassay (IA). After 2011, the 2 largest laboratory companies in the United States implemented tacrolimus quantification by liquid chromatography–mass spectrometry (LC-MS); this method excludes metabolites, potentially resulting in lower quantified drug concentrations. We sought to determine if tacrolimus therapeutic drug monitoring via LC-MS, as performed using trough targets originally derived from IA values, influences clinical outcomes. Methods In a single-center retrospective cohort study of lung transplant recipients, risks of acute kidney injury, acute renal failure, and new-onset diabetes after transplantation, as well as chronic lung allograft dysfunction–free survival, were compared in 82 subjects monitored by LC-MS and 102 subjects monitored by IA using Cox proportional hazard models adjusted for age, sex, baseline renal function, and race. Results LC-MS–based monitoring was associated with a greater risk of acute kidney injury (adjusted hazard ratio, 1.65; 95% confidence interval, 1.02–2.67). No statistically significant differences in risks of acute renal failure and new-onset diabetes after transplantation were observed. Conclusion Although LC-MS provides a more accurate representation of the blood concentration of the parent compound tacrolimus exclusive of metabolite, established cut points for tacrolimus dosing may need to be adjusted to account for the increased risk of renal injury.

Calcium pyrophosphate deposition (CPPD) in a liver transplant patient: are hypomagnesemia, tacrolimus or both guilty? A case-based literature review

“…Moreover, elevated blood concentration of anticalcineurins is associated to kidney failure [23,24] and thus can lead to overdosage and toxicity of colchicine. Considered with the low level of evidence of colchicine effectiveness in acute and chronic CPPD [25,26], colchicine should be used with caution in solid organ transplant patients receiving tacrolimus and anti-calcineurin drugs.…”

The effect of tacrolimus-induced toxicity on metabolic profiling in target tissues of mice

“…Hence, it is essential to examine Tac-mediated toxicity. In prior investigations, Tac toxicity was examined by analyzing metabolic changes in target tissues like the serum, urine, heart, lung, and kidney [9][10][11][12]. Nevertheless, a systematic evaluation of Tac-driven toxicity in several biological systems is urgently needed.…”