Association of Sex with Persistent Albumin Dysfunction After Kidney Transplantation Despite Good Graft Function

Abstract Background and Aims Albumin plays a central role as a carrier molecule for numerous drugs, fatty acids, and other endogenous and exogenous compounds. In chronic kidney disease (CKD), both albumin concentration and functional integrity are markedly impaired. Following kidney transplantation (KTx) and the subsequent restoration of renal function, the improvement of albumin functionality especially with the focus on sex differences has not been studied systematically. Therefore, the aim of the present prospective observational study was to investigate albumin binding and detoxification capacity, as well as non-esterified fatty acids (NEFA) levels, before and after kidney transplantation. Methods In this monocentric, prospective, observational study, albumin binding (BE) and detoxification efficiency (DTE) were assessed before and at eight time points up to 180 days after KTx. Both parameters were measured by electron spin resonance spectroscopy under varying ethanol concentrations. BE reflects albumin’s ability to bind spin-labeled fatty acids, while DTE reflects its conformational adaptability. Both parameters are expressed relative to healthy controls (100%). Results The study included 42 patients (62% male, median age 44 years). Before KTx, albumin function was markedly impaired (median BE 73.9%, IQR 59.9–83.6%; median DTE 62.8%, IQR 48.3–83.1%) and declined pronouncedly further during the first week after KTx (median BE 41.0%, IQR 32.2–51.2%; median DTE 31.1%, IQR 23.6–43.8%; p < 0.01 for both). In most patients, albumin function exceeded baseline levels only two months after KTx, although estimated glomerular filtration rate (eGFR) had often recovered much earlier. Sex, dialysis modality, and residual diuresis prior to KTx appeared to be relevant influencing factors. Conclusion This study provides longitudinal evidence of changes in albumin function following KTx. Recovery of albumin function beyond baseline levels occurs only several weeks after KTx, despite substantially earlier restoration of graft function. This temporal dissociation may be relevant for understanding the pharmacokinetic implications of altered albumin binding, particularly for highly protein-bound immunosuppressive drugs and warrants further investigation in the early post-transplant period. A key finding of this study is the observation of sex-related differences in albumin function, including its interaction with NEFA, after KTx.