Antibody-mediated rejection (AMR) is a leading cause of kidney graft failure. Complement activation is involved in the AMR process. Our aim is to provide the current understanding of the pathophysiology related to complement-mediated injury in AMR, to present the current evidence regarding complement blockade in AMR management, and to point out emerging therapies and future directions in this area. The complement system plays an important role in the onset and progression of AMR. There is a balance between complement-dependent and -independent mechanisms in the development of rejection lesions. Classic and leptin pathways are involved in this process. C4d positivity is no longer a mandatory feature for AMR diagnosis but remains an independent predictor of negative outcomes. The current evidence regarding AMR treatment is limited. Terminal and proximal complement blockade has gained recognition in clinical practice. Eculizumab and C1 inhibitors are effective in the treatment of AMR as adjuvant therapies to the standard of care. The availability of novel complement inhibitors will lead to more effective and tailored treatment strategies.

Background/Objectives: Candidates with cardiometabolic risk are considered for living kidney donation more frequently because of the global organ shortage. The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines introduced individualized risk assessment based on composite donor profiles rather than categorical exclusion, but the long-term implications of accepting donors with potential risk factors require careful evaluation. This review synthesizes current evidence on outcomes of living kidney donors with obesity, prediabetes, hypertension, and smoking. Methods: A literature search was conducted in PubMed/MEDLINE for studies published between 1 January 2000 and 28 February 2026, including cohort studies, registry analyses, meta-analyses, and clinical guidelines evaluating living kidney donors with obesity, smoking, prediabetes, or hypertension. Priority was given to large cohorts with long-term follow-up. Over 70 publications were included in the final synthesis. Findings were synthesized narratively by risk factors and outcomes. Results: Obesity was associated with an 86% increased end-stage kidney disease (ESKD) risk and 32% increased 20-year mortality. Central adiposity measures outperformed body mass index (BMI) for predicting estimated glomerular filtration rate (eGFR) decline. Post-donation weight gain increased the risk for developing hypertension and diabetes. Smoking conferred a 7.5-fold chronic kidney disease (CKD) risk, with impaired compensatory renal adaptation after donation. Prediabetic donors showed comparable outcomes to normoglycemic donors, with 57.8% reverting to normoglycemia at 10 years. Pre-donation hypertension increased 15-year ESKD risk 3-fold, but absolute risk remained low. At 15 years post-donation, over 50% of the donors developed hypertension. Glucagon-like peptide-1 (GLP-1) receptor agonists reduce diabetes progression by 73–94% in at-risk populations, but prospective studies in donors are lacking. Conclusions: Each risk factor carries quantifiable risks for individualized stratification. These risk factors usually coexist and interact. Refinement of risk prediction models, strategies for metabolic optimization and prospective evaluation of emerging pharmacologic therapies are key priorities.

Fabry disease (FD) is a rare, X-linked, lysosomal storage multisystemic disorder which may lead to kidney failure and require kidney transplantation (KT). Data on long-term kidney allograft outcomes and the evolution of systemic FD under dis-ease-specific therapy after KT remain limited. We retrospectively evaluated six kidney transplant recipients (KTRs) with FD followed in our center for median tine after KT of 7 years (range, 4-13). Five patients (83.3%) were males and five had a classic Fabry phe-notype. At last follow-up patient survival was 100% and five out of six KTR had a func-tional kidney graft. Among KTRs with a functioning graft, the median change is esti-mated glomerular filtration rate from 1-year to last follow-up was +3.3 ml/min/1.73m2 (range, -50.7 to +10.5), while proteinuria remained low. One patient developed late an-tibody-mediated rejection with de novo donor-specific antibodies and graft loss at 8 years post-transplantation. Five KTRs were receiving enzyme replacement therapy at the time of KT. Three patients were subsequently switched to migalastat and two later returned to enzyme replacement therapy. Lyso-Gb3 and cardiac structural parameters showed heterogenous longitudinal trajectories despite generally preserved kidney graft function. No cardiovascular events occurred during follow-up. These findings support KT as an effective renal replacement therapy in FD and highlight the need for contin-uous Fabry-specific therapy and multidisciplinary surveillance after transplantation.