Lucia Federica Stefanelli

The 2012 KDIGO staging system standardized acute kidney injury (AKI) diagnosis; however, its reliance on serum creatinine and urine output primarily captures established functional impairment and incompletely reflects early biological injury, patient susceptibility, and temporal trajectories. The March 2026 KDIGO Public-Review Draft substantially expands this paradigm by incorporating biomarkers, susceptibility and kidney functional reserve, and temporal phenotyping, although these dimensions remain only partially integrated into a unified longitudinal phenotype architecture. This narrative review introduces a pragmatic, bedside-oriented extension of this emerging framework, integrating function, biology, susceptibility, and trajectory to support anticipatory risk stratification across the AKI–acute kidney disease (AKD) continuum. We developed a modular taxonomy based on an analytical review of stress and damage biomarkers, renal functional reserve (RFR) assessment, including emerging ultrasound-based renal stress testing, and temporal disease mapping. These elements were integrated into a multidimensional phenotyping framework (F–B–R–D) and a structured clinical pathway. Function (F) remains anchored to KDIGO serum creatinine and urine output criteria; Biology (B) captures kidney stress or structural damage using context-appropriate biomarkers; Reserve (R) describes preserved or reduced RFR as a proposed operational descriptor of reserve-related vulnerability; and Duration (D) captures persistence, recovery, and progression toward AKD. AKI risk is conceptualized as a qualitative interaction between susceptibility and exposure load (E), allowing candidate multidimensional phenotypes to be mapped to proposed action bundles for prevention, diagnostic escalation, and structured follow-up. The F–B–R–D taxonomy is intended to complement, rather than replace, KDIGO classification. If prospectively validated, it could support more proactive monitoring, individualized prevention, and longitudinal risk assessment.

Background/Objectives: Rituximab is widely used in primary glomerular diseases, but treatment may fail for several reasons, including primary non-response, incomplete response, relapse, intolerance or anti-rituximab antibodies. We assessed within-patient efficacy and safety after switching to another anti-CD20 antibody, considering the reason for switching. Methods: PubMed and Scopus were searched from inception to 15 May 2026 without language restrictions. Eligible reports included adults with primary glomerular disease treated with a non-rituximab anti-CD20 antibody after rituximab and reporting within-patient outcomes. Risk of bias was assessed with design-specific JBI tools and certainty with GRADE. Heterogeneity precluded meta-analysis, and findings were synthesized narratively. Results: A total of 309 patients were included across 43 studies: 283 had membranous nephropathy (MN), 18 had minimal change disease (MCD), 6 had focal segmental glomerulosclerosis (FSGS), and 2 had IgA nephropathy (IgAN). Obinutuzumab was the principal drug used, and the main reasons for switching were primary non-response, with immunization, relapse, or intolerance occurring less frequently. In MN, among the 262 patients with available response data, 217 achieved complete or partial remission, and relapse was rare. For MCD, 17 of 18 patients with active disease attained remission, and only one relapsed during follow-up. On the other hand, five out of the six FSGS patients responded, but three of them relapsed. The two patients with IgAN achieved either complete or partial remission. Notably, these results may not apply to conventional IgAN, since one biopsy showed contextually MCD and the other was proliferative and crescentic. Infusion-related reactions were the most frequent adverse events and were generally mild, while infections were the main issue during the follow-up. Evidence certainty for all outcomes was very low. Conclusions: Switching to a non-rituximab anti-CD20 antibody may be a feasible rescue strategy, most convincingly after intolerance, rituximab immunization, or relapse. The uncontrolled, very-low-certainty evidence precludes firm recommendations, and controlled studies are warranted.

Background/Objectives: Oxidative stress is a major contributor to the pathogenesis of cardiovascular diseases, including hypertension, ischemic cardiomyopathy, and heart failure. MicroRNAs (miRNAs) have been extensively investigated in various contexts, and some of them have been identified to play a role in cardiovascular disease. This narrative review focuses on miR-103 and miR-155, two miRNAs implicated in the modulation of oxidative stress and cardiovascular remodeling. Methods: The following queries were used in PubMed since inception until May 2026: ((“miR-155” OR “microRNA-155” OR miR155) AND (“oxidative stress” OR ROS OR “reactive oxygen species”) AND (“cardiovascular disease” OR cardiovascular OR cardiac OR heart OR vascular)); ((“miR-103” OR “microRNA-103” OR miR103) AND (“oxidative stress” OR ROS OR “reactive oxygen species”) AND (“cardiovascular disease” OR cardiovascular OR cardiac OR heart OR vascular)). Results: A total of seven citations for miR-103 and 79 citations for miR-155 were identified. Reviews and papers about diseases other than those on cardiac/vascular involvement were excluded. miR-155 emerges as a potential regulator of inflammatory-redox signaling, whereas miR-103 appears more closely linked to cell fate and metabolic pathways. In both cases, available evidence supports a context-dependent role that challenges simplistic classification as pro- or antioxidant miRNAs. Conclusions: Available evidence suggests that both miR-103 and miR-155 are important regulators of oxidative stress-related pathways in cardiovascular disease. Nevertheless, the context-dependent effects observed across different cardiovascular disorders raise concerns regarding the safety of systemic miRNA modulation-based therapeutic strategies. Future studies should clarify the determinants of this context-dependent behavior and identify the specific conditions under which these miRNAs exert protective or harmful effects, which might pave the way for the development of miRNA-based therapeutic strategies targeting oxidative stress and cardiovascular remodeling.

Background: Respiratory syncytial virus (RSV) infection is a cause of respiratory morbidity in high-risk patients, including those with chronic lung disease (CLD) and those undergoing hemodialysis (HD). In HD patients, evidence on the clinical impact of RSV vaccination on respiratory complications remains limited. We aimed to assess the clinical impact of RSV vaccination in HD patients by comparing vaccinated and unvaccinated patients with a focus on CLD. Methods: We retrospectively evaluated 56 adult HD patients: 28 received the RSV vaccine in autumn 2024 and 28 did not. Clinical data were collected from electronic medical records. Outcomes included influenza-like illness (ILI), pneumonia, and respiratory infection requiring hospitalization between September 2024 and September 2025. Results: Patients had a mean age of 74.4 years and a median Charlson Comorbidity Index (CCI) of 10. The RSV-vaccinated group had a greater comorbidity burden than the unvaccinated group (CCI 11 IQR 10–12 vs. 9 IQR 8–11, p = 0.02) and a higher prevalence of CLD (46.4% vs. 25.0%, p = 0.09). During follow-up, 28 patients (50.0%) had at least one ILI episode, 23 (41.1%) developed pneumonia, and 15 (26.8%) were hospitalized for respiratory infection. The incidence of ILI was 46.4% in vaccinated patients and 53.6% in unvaccinated patients (p = 0.28), while the incidence of pneumonia was 39.3% and 42.9%, respectively (p = 0.78). Respiratory infection requiring hospitalization occurred in 14.3% of vaccinated patients and 39.3% of unvaccinated patients (p = 0.035). CLD was significantly associated with pneumonia (p = 0.001) and showed trends toward higher rates of ILI (p = 0.09) and hospitalization for respiratory infection (p = 0.1). Conclusions: In our exploratory study, RSV vaccination in HD patients was associated with fewer hospitalizations for respiratory infection, despite greater comorbidity in vaccinated patients. CLD was associated with a higher incidence of respiratory complications, particularly pneumonia. The retrospective design and small sample size do not allow definitive conclusions; future prospective studies with an adequate sample size are needed to confirm our results.

Background/Objectives: Oxidative stress is a major contributor to the pathogenesis of cardiovascular diseases including hypertension, ischemic cardiomyopathy, heart failure. MicroRNAs (miRNAs) have been extensively investigated in various contexts, and some of them have been identified to play a role in cardiovascular disease. This review focuses on miR-103 and miR-155, two miRNAs implicated in the modulation of oxidative stress and cardiovascular remodeling. Methods: The following queries were used in PubMed since inception until May 2026: (("miR-155" OR "microRNA-155" OR miR155) AND ("oxidative stress" OR ROS OR "reactive oxygen species") AND ("cardiovascular disease" OR cardiovascular OR cardiac OR heart OR vascular)); (("miR-103" OR "microRNA-103" OR miR103) AND ("oxidative stress" OR ROS OR "reactive oxygen species") AND ("cardiovascular disease" OR cardiovascular OR cardiac OR heart OR vascular)). Results: A total of 7 citations for miR-103 and 79 citations for miR-155 were identified. Reviews and papers about diseases other than those on cardiac/vascular involvement were excluded. miR-155 emerges as a potential regulator of inflammatory-redox signaling, whereas miR-103 appears more closely linked to cell fate and metabolic pathways. In both cases, available evidence supports a context-dependent role that challenges simplistic classification as pro- or anti-oxidant miRNAs. Conclusions: Available evidence suggests that both miR-103 and miR-155 are important regulators of oxidative stress-related pathways in cardiovascular disease. Nevertheless, the context-dependent effects observed across different cardiovascular disorders raise concerns regarding the safety of systemic miRNA modulation-based therapeutical strategies. Future studies should clarify the determinants of this context-dependent behavior and identify the specific conditions under which these miRNAs exert protective or harmful effects, which might pave the way for the development of miRNA-based therapeutic strategies targeting oxidative stress and cardiovascular remodeling.

Background/Objectives: Kidney transplantation (KT) in older recipients remains challenging due to age-related conditions such as frailty and comorbidities, as well as immunological changes related to immunosenescence, which expose older KTRs to a higher risk of infection and infection-related complications. The aim of this study was to evaluate clinical and immunological outcomes in older KTRs, analyzing the incidence of cardiovascular, infective, and neoplastic complications, as well as graft and patient survival and the associated risk factors. Methods: This monocentric study includes 157 KTRs aged over 65 years, followed at the Transplant Ambulatory of Padua University Hospital and transplanted between January 2013 and December 2023. Clinical and immunological outcomes were evaluated, including surgical complications, incidence of delayed graft function (DGF), and renal function at 1, 3, and 5 years after KT. Results: Patient survival rates were 96%, 91.5%, and 71.6% at 1, 3, and 5 years after KT, respectively, while graft survival rates were 94%, 87%, and 68%. Major complications were malignancies (40.1%), cardiovascular disease (33.1%), and bacterial infections (22%). In the multivariate analysis, donor age and history of malignancy were identified as independent risk factors for mortality (p = 0.048 and p = 0.056, respectively). Kaplan–Meier survival analysis confirmed donor age as the only significant risk factor for patient survival. Regarding graft survival, multivariate analysis identified hypertension as an independent risk factor for graft failure (p = 0.009), while Kaplan–Meier analysis showed diabetes (p = 0.040) and single-kidney transplantation (p = 0.003) as significant risk factors. Conclusions: KT in older recipients represents a safe and beneficial therapeutic option, offering favorable patient and graft survival outcomes. However, this epidemiological study highlights the need for personalized follow-up strategies and improved prognostic assessment in older KTRs.

Background: Pregnancy following liver and kidney transplantation is rare. The presence of a rare genetic disorder and advanced chronic kidney disease (CKD) further complicates clinical management, for which evidence-based guidelines are limited. Case presentation: A 29-year-old woman with Alagille syndrome underwent combined liver and kidney transplantation in early childhood. She had stage 4 CKD, and her baseline creatinine was around 250 umol/L. Her pregnancy was unplanned and diagnosed at 19+1 weeks of gestation. After the diagnosis of pregnancy, immunosuppressive therapy was promptly adjusted, and potentially teratogenic medications were discontinued. At 21+1 weeks’ gestation, creatinine and urea levels rose despite multidisciplinary management, and she started renal replacement therapy. Despite ongoing multidisciplinary care, the pregnancy was complicated by placental abruption at 24+5 weeks, requiring a preterm cesarean section. A live-born female infant weighing 590 g was delivered. Discussion: The coexistence of CKD, long-term immunosuppression, and high obstetric risk requires early multidisciplinary assessment and individualized management. Currently, standardized protocols for monitoring and treatment are lacking in this rare population, making clinical decision-making particularly challenging, especially regarding CKD progression. Conclusion: Pregnancy in women with combined liver and kidney transplantation and advanced CKD carries a high risk of severe renal and obstetric complications. Preconception counseling and early referral to multidisciplinary teams may help improve management in similar rare clinical scenarios.

Background/Objectives: Asymptomatic hyperuricemia has been associated with increased cardiovascular risk; it is related to factors such as diet, genetic predisposition, and drug-related side effects. Impairment of uric acid control has been associated with the calcineurin inhibitors cyclosporin and tacrolimus, although available studies did not reach the same conclusions. Their widespread use in solid organ transplantation potentially exposes this population to higher cardiovascular risk. This systematic review aimed to assess their role in hyperuricemia risk compared with other immunosuppressive treatments and to clarify potential differences between cyclosporin and tacrolimus. Methods: The search was conducted in MEDLINE and Embase, limited to adult subjects, using the following terms: ((cyclosporin) OR (cyclosporine) OR (tacrolimus) OR (calcineurin inhibitor)) AND ((uric acid) OR (urate) OR (hyperuricemia)) AND ((transplant) OR (transplantation)). We assessed the quality of the studies according to the Critical Appraisal Skills Programme checklist. Results: After screening 639 manuscripts, we selected 36 studies that were relevant to our focus: 28 evaluated kidney transplant patients, while only eight focused on other solid organ transplants. Specifically, 20 studies compared calcineurin inhibitors with other immunosuppressants, while 15 assessed the impact of cyclosporin versus tacrolimus, and one study contributed to both scenarios. The prevalence of hyperuricemia ranged from 30 to 80% among patients receiving calcineurin inhibitors, with a slightly higher prevalence with cyclosporin than with tacrolimus (51–61% vs. 36–42%, respectively). The overall quality of the included studies was generally rated as low to moderate, with only ten studies focusing on uric acid control. Conclusions: Given the heterogeneity and overall quality of the available studies, no definitive conclusions can be drawn. In particular, the comparative effect of cyclosporin and tacrolimus remains uncertain because of conflicting findings across studies. Although calcineurin inhibitors may adversely affect uric acid control in transplant recipients, this association may be influenced by several confounding factors.

Chronic kidney disease [CKD] is associated with profound alterations of both gut microbiota composition and functions, commonly referred to as gut dysbiosis. These changes are driven by several factors such as dietary restrictions, medications, and uremia, which further contribute to patients with CKD to their pro-inflammatory and immunocompromised state. Recent evidence suggests that dysbiosis may also increase susceptibility to infections, which remain a leading cause of morbidity and mortality in CKD patients. In this review, we aimed at examining the features of the altered gut microbiome in patients with CKD, its potential role in promoting infection risk, and current therapeutic strategies targeting the gut microbiota to mitigate CKD-related complications.