Background: Gut microbiota plays a critical role in host metabolism, immunity, and intestinal barrier integrity. Both chronic kidney disease (CKD) and kidney transplantation (KTR) are associated with gut dysbiosis, driven by uremic toxins, comorbidities, and immunosuppressive therapy. However, direct comparisons between hemodialysis (HD), KTR, and healthy controls (HC), while accounting for dietary factors, remain limited. Methods: We conducted a cross-sectional study including 48 HD patients, 75 KTR patients, and 13 HC. Stool patient samples were analyzed using 16S rRNA amplicon sequencing targeting the V4-V4 region to assess microbial composition and diversity. Data on clinical status, laboratory parameters, and dietary intake were collected and integrated with microbiome profiling. Results: Firmicutes and Bacteroidota dominated all groups, with Akkermansia enriched in HD and SCFA-producing genera (Faecalibacterium, Roseburia) more abundant in KTR. LEfSe and sPLS-DA analyses identified Akkermansia and Clostridia-related taxa as discriminants of HD, while Acidaminococcus and Megasphaera characterized KTR. HD patients exhibited higher alpha diversity (Faith’s PD and Chao1) than KTR (p < 0.05). Dietary intake differed across groups, but explained only a small proportion of microbial variance. Conclusions: Both HD and KTR patients display persistent gut dysbiosis with distinct microbial signatures. While transplantation partially restores SCFA producers, immunosuppression and diet shape new ecological shifts. These findings underscore the potential of microbiota as a biomarker and therapeutic target in renal replacement therapies.

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.