Background: Serum creatinine and proteinuria remain the most frequently used test for monitoring allograft function. However, they are non-specific and insensitive markers. Metabolomics is an emerging field, dealing with the high-throughput identification and quantification of small molecules metabolites. We aimed to systematically review all available data regarding kidney transplantation and metabolomics.Methods: This is a systematic review evaluating metabolomic usage in kidney transplant patients. A comprehensive search was assembled in the time span extending from inception until March 2024 across MEDLINE (PubMed), Embase and Cochrane. In addition to the databases above, eligible citation were sought through the screening of ClinicalTrials.gov and Google Scholar. Two authors assessed potential citations for eligibility and quality and extracted all data.Results: A total of 57 articles were identified for inclusion (totaling 3821 patients), containing different methodologies and outcomes related to metabolic profiling. We aimed to offer support for finding new biomarkers that could aid in the evaluation of the kidney transplant patient, covering pathophysiological mechanisms and exploring avenues for personalized care.Conclussion: Our systematic review underlines the possible role of metabolomics in monitoring kidney transplant patients. By integrating data from numerous studies, we have detected possible new biomarkers that might transform the method we screen kidney transplant recipients.

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.

Primary glomerulonephritis encompasses a diverse group of kidney diseases with variable clinical trajectories and outcomes. Accurate prognostic stratification is critical for guiding individualized management and improving long-term renal survival. This narrative review synthesizes current evidence on the prognostic value of histological grading systems, circulating and urinary biomarkers, and integrative risk prediction models across major primary glomerulonephritis subtypes, including IgA nephropathy, membranous nephropathy, and focal segmental glomerulosclerosis. Emphasis is placed on the utility of established classification systems (e.g., Oxford, MEST-C, chronicity scores), emerging tissue and fluid biomarkers (e.g., PLA2R antibodies, complement components, cytokine profiles), and the validation of multivariable prognostic tools and nomograms. We highlight areas of convergence between histopathologic lesions and molecular markers, as well as the evolving role of machine learning in predictive modeling. Ultimately, combining morphological, biochemical, and algorithmic tools holds promise for precision risk assessment and treatment tailoring in primary glomerulonephritis.

Background: Metabolic acidosis is common after kidney transplantation and has been linked to adverse graft outcomes, but its potential contribution to functional decline has not been prospectively evaluated. We investigated whether persistent metabolic acidosis is associated with longitudinal frailty trajectories in kidney transplant recipients. Methods: In this prospective single-center cohort study, 239 adult kidney transplant recipients were followed for 24 months. Serum bicarbonate was measured at baseline, 6, 12, and 24 months, and acidosis persistence was defined by the number of visits with bicarbonate < 22 mmol/L (none, transient, recurrent, or persistent). Frailty was assessed using the Fried phenotype at baseline, 12 months, and 24 months. Longitudinal frailty trajectories were analyzed using mixed-effects ordinal logistic regression. Results: Frailty prevalence at 24 months increased progressively with greater acidosis persistence, from 7.4% in patients without acidosis to 27.4% among those with persistent acidosis (p for trend = 0.004). In mixed-effects models, increasing acidosis persistence was associated with higher odds of worse frailty category (unadjusted proportional OR [pOR] per category 1.91, 95% CI 1.42–2.56). This association remained significant after adjustment for demographic, transplant-related, and clinical variables (pOR 1.52, 95% CI 1.12–2.06) and after additional adjustment for time-varying kidney function (pOR 1.42, 95% CI 1.04–1.95). Persistent acidosis was also associated with higher frailty scores in linear mixed models (β 0.31 per category increase, p < 0.001). Conclusion: Persistent metabolic acidosis was associated with worsening frailty trajectories after kidney transplantation, suggesting that persistent low bicarbonate may represent a clinically relevant marker of functional decline, although causality cannot be established.

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.