Plasma Citrate Levels Are Inversely Associated with Estimated Muscle Mass and Strength in Liver Transplant Recipients

Reduced muscle mass and strength are highly prevalent in liver transplant recipients (LTRs). Citrate, a key intermediate of the tricarboxylic acid cycle, may adversely relate to muscle health through disturbances in mitochondrial energy metabolism and metabolic flexibility. We aimed to investigate the association of plasma citrate levels with estimated muscle mass, strength, and physical performance in LTRs. We included stable LTRs from the TransplantLines Biobank and Cohort Study at least 1 year after transplantation. Muscle mass, strength, and physical performance were assessed using the 24 h urinary creatinine excretion rate divided by height squared (creatinine excretion rate index, CERI), handgrip strength, sit-to-stand (STS) and Timed Up and Go (TUG) tests. Associations of plasma citrate with muscle-related parameters were examined using Spearman correlation and linear regression analyses. A total of 501 LTRs were included (median age 59 [49-67] years; 58.7% men) at a median of 14.0 (7.4-22.5) years post-transplantation. Spearman correlation analyses showed that plasma citrate levels were inversely correlated with CERI (ρ= -0.226, p < 0.001) and handgrip strength (ρ= -0.211, p < 0.001). Additionally, plasma citrate levels were positively correlated with STS time (ρ = 0.170, p = 0.019) and TUG time (ρ = 0.203, p = 0.006). In linear regression analyses, higher plasma citrate levels were associated with lower CERI and lower handgrip strength and with longer STS and TUG time. In multivariable linear regression analyses, plasma citrate remained independently associated with CERI (fully adjusted standardized β= -0.14, p = 0.001) and handgrip strength (fully adjusted standardized β= -0.11, p = 0.010), whereas associations with physical performance measures were no longer significant after adjustment. CERI mediated 45.8% of the association between citrate and handgrip strength. In conclusion, higher plasma citrate levels are independently associated with lower estimated muscle mass and strength in LTRs. Circulating citrate may serve as a potential biomarker of post-transplant muscle impairment risk.