Introduction: Metabolic acidosis is common after kidney transplantation and is associated with adverse outcomes. However, its vascular and functional correlates in kidney transplant recipients remain insufficiently characterized. Methods: We conducted a cross-sectional study of adult kidney transplant recipients attending routine outpatient visits at a tertiary transplant center. Metabolic acidosis was defined as serum bicarbonate < 22 mmol/L. Arterial stiffness was assessed by carotid–femoral pulse wave velocity (PWV), and physical frailty was evaluated using the Fried frailty phenotype. Multivariable regression models were used to identify determinants of metabolic acidosis and to examine its association with arterial stiffness and frailty severity. Results: Among 239 patients (median age 46 years), 154 (64%) had metabolic acidosis. Lower estimated glomerular filtration rate and higher systemic inflammation were independently associated with metabolic acidosis. Metabolic acidosis was independently associated with higher arterial stiffness, with a 1.41 m/s higher PWV after adjustment for age, sex, blood pressure, kidney function, and diabetes mellitus (p < 0.001). Although metabolic acidosis was associated with greater frailty severity in minimally adjusted models, this association was attenuated and no longer statistically significant after further adjustment for kidney function, diabetes, and inflammation. In stable kidney transplant recipients, metabolic acidosis is independently associated with increased arterial stiffness but not with frailty after accounting for key clinical confounders. Conclusions: These findings highlight metabolic acidosis as a marker of vascular vulnerability and a potential therapeutic target after kidney transplantation.

Background/Objectives: Kidney transplantation remains the gold standard treatment of end-stage kidney disease; however, its recipients exhibit mixed clinical trajectories, with variable renal function and proteinuria evolution over time. Currently used methods to screen these changes are associated with possible adverse effects and limitations. Methods: In this single-center cohort study, 174 adult kidney transplant recipients were enrolled between January 2024 and January 2025 and followed for 12 months. Patients underwent serum and urinary metabolomic profiling using nuclear magnetic resonance (NMR) spectroscopy. Furthermore, clinical and biological data were collected, allowing for assessment of changes in renal function and proteinuria, with patient stratification based on outcome trends. Results: Serum metabolomic profiles were linked to renal outcomes. For ΔeGFR, valine differed between patients with positive and negative trajectories, while GlycA, GlycB and Glyc/SPC were associated with ΔeGFR in adjusted models. For Δproteinuria, GlycA, VLDL particles and triglycerides showed correlations, while glucose differed between patients with improving and worsening proteinuria. In adjusted models, isoleucine, alanine, GlycA and Glyc/SPC were associated with Δproteinuria. Urinary metabolomic profiles showed fewer associations. Dimethylamine and urinary creatinine were associated with ΔeGFR in adjusted models, while acetic acid differed between proteinuria groups. No urinary metabolite was associated with Δproteinuria after adjustment. Conclusions: Overall, metabolomic changes were connected with renal outcomes in kidney transplant patients, with distinct but partially overlapping patterns for ΔGFR and Δproteinuria. Serum findings were more consistent, while urinary associations were more limited. Further longitudinal and externally validated studies are required to confirm these observations and explore the potential of this metabolomic approach in the search for novel biomarkers.

Metabolic acidosis is common after kidney transplantation and has been linked to adverse renal outcomes. However, its relationship with histological injury in kidney allografts remains poorly characterized. We aimed to explore the association between metabolic acidosis and histopathological features in kidney allograft biopsies. This single-center, cross-sectional observational study included 63 adult kidney transplant recipients who underwent clinically indicated allograft biopsies. Metabolic acidosis was defined as a serum bicarbonate level < 22 mmol/L at the time of biopsy. Histological lesions were assessed according to the Banff classification. Lesion severity was evaluated using descriptive statistics, nonparametric comparisons, ordinal logistic regression, and multivariable logistic regression models adjusted for renal function, proteinuria, and time from transplantation. Sensitivity analyses additionally adjusted for hemoglobin and donor-related variables. Patients with metabolic acidosis exhibited numerically higher severity scores for both acute inflammatory lesions and chronic histological changes, including total inflammation and interstitial fibrosis/tubular atrophy (IFTA). Across ordinal analyses and multivariable regression models, consistent directional trends toward a greater histological injury burden were observed among acidotic patients; however, none of these associations reached statistical significance, and confidence intervals were wide. Sensitivity analyses yielded directionally consistent effect estimates. In this biopsy-based analysis, metabolic acidosis showed consistent directional trends toward a higher burden of inflammatory and chronic histological lesions, although these findings did not reach statistical significance.