Acute kidney injury (AKI) is a frequent and serious complication among hospitalized patients, particularly in critical care settings, where its incidence can exceed 50%. AKI is associated with increased mortality, prolonged hospitalization, dialysis dependence, and higher health care costs. Although the KDIGO (Kidney Disease: Improving Global Outcomes) guidelines emphasize supportive care, hemodynamic optimization, and avoidance of nephrotoxins, their implementation remains inconsistent, partly due to the lack of timely risk stratification. Recent advances in artificial intelligence have enhanced early prediction and detection of AKI, offering new opportunities to improve patient outcomes and intensive care unit (ICU) efficiency. The U-Care Renal Platform (UCRP; U-Care Medical S.r.l), a Conformité Européenne (CE)-marked artificial intelligence-powered medical device, integrates directly with the ICU electronic health record to continuously analyze patient data and predict the risk of moderate or severe AKI within 24 hours, providing actionable, guideline-based recommendations. While the predictive performance of UCRP has been validated previously, its real-world impact on clinical and operational outcomes in the ICU remains underexplored. This single-center uncontrolled before-and-after implementation study aims to evaluate the association between UCRP implementation and selected ICU clinical and operational outcomes in routine practice at SCIAS Hospital, Barcelona. This study was conducted as a retrospective service evaluation of a workflow-embedded clinical decision support system between March 2023 and March 2025. It included 202 postsurgical adult ICU patients. Outcomes of interest were assessed by comparing preimplementation and postimplementation periods. Months during which the UCRP was inactive were excluded from the analysis (total excluded duration: 10 months; 5 in the preimplementation period and 5 in the postimplementation period). The outcomes included the incidence of moderate-to-severe AKI (KDIGO stages 2 and 3), the use of nephrotoxic medications, the frequency of hypotensive episodes among patients with AKI, and the ICU length of stay. During the postimplementation period, lower rates of moderate-to-severe AKI (9/99, 9.1% vs 12/103, 11.7%), nephrotoxic drug administration, and hypotensive episodes among patients with AKI were observed compared with the preimplementation period. Integration of the UCRP into ICU workflows was associated with differences in selected AKI-related process and intermediate clinical outcomes in this single-center uncontrolled before-and-after implementation study. However, given the study design, causal relationships cannot be established, and the findings should be interpreted as preliminary signals requiring confirmation in larger, controlled, and multicenter studies, including patient-centered outcomes.
Acute kidney injury (AKI) is a common but often underrecognized complication in ischemic stroke patients undergoing mechanical thrombectomy, particularly among those with pre-existing renal impairment. This study evaluated the incidence, risk factors, and clinical impact of AKI in this high-risk population. This retrospective, two-center study involved 310 patients who underwent MT for ischemic stroke and presented with impaired renal function at baseline (eGFR < 60 mL/min/1.73 m2). AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria and categorized as post-contrast AKI (PC-AKI), which occurred within 48 h following contrast administration, and late-onset AKI (L-AKI), which developed later during hospitalization. We analyzed the clinical and laboratory factors that might predispose patients to the development of AKI and compared the clinical profiles of those with PC-AKI and L-AKI. Acute kidney injury occurred in 91 patients, including 49 with PC-AKI and 42 with L-AKI. Patients who developed AKI were more likely to have pre-existing chronic kidney disease, prior NSAIDs use, and higher serum glucose and potassium levels at admission. Additionally, AKI was associated with longer hospitalization, increased in-hospital and 3-month mortality, and less favorable clinical outcomes overall. The independent predictors of AKI included NIHSS > 15 (OR: 3.441), WBC count (OR: 1.128), female sex (OR: 0.311), and the comorbidity burden (OR: 2.414). Acute kidney injury represents a frequent and clinically relevant complication following MT in patients with pre-existing renal impairment. Early recognition and the implementation of preventive strategies are essential, particularly in patients with established risk factors for AKI.
Proliferative lupus nephritis (LN) is triggered by deposition of autoantibodies in glomeruli and paralleled by a T cell-rich kidney infiltrate. Although these T cells have been attributed to the propagation of tissue injury, it is unclear how they are activated and whether T cell autoreactivity drives local inflammation. Kidney-infiltrating T cells are also observed in urine, where they have high resemblance to interstitial T cells. Therefore, urinary T cells are a proxy for investigating tissue pathogenesis. Here, we analyzed urinary T cells to elucidate whether a kidney-specific T cell autoimmune reaction contributes to tubulointerstitial inflammation in LN. Using single-cell RNA sequencing, we compared transcriptomes and clonotypes of T cells from the blood and urine of patients with active LN and showed that urinary T cells were mostly activated CD8 effector memory cells recruited from a circulating CX3CR1+ subset. Several urinary CD8 T cell clones were expanded. However, upon in vitro testing of their T cell receptors, we did not observe autoreactivity against autologous tubular epithelial cells. Instead, ~20% of expanded clonotypes were Epstein-Barr virus-specific or cytomegalovirus-specific, but respective viral antigens were undetectable in kidney biopsies or urine. Conversely, kidney-infiltrating T cells had access to interleukin-15 and interferon-β (IFN-β), and stimulation with these cytokines was sufficient to trigger degranulation and production of tumor necrosis factor, IFN-γ, and granzyme K. Together, these results show that CD8+CX3CR1+ T cells are recruited into the kidney in LN, where they are activated by cytokines, enabling them to contribute to local inflammation.
Implementing evidence-informed healthcare services is typically approached as a structured, time-limited project, focused largely on what to do. Less well understood is how implementation actually unfolds in practice: the ways in which those involved navigate change and generate solutions in diverse community settings. Without understanding how implementation happens in unique contexts, implementation failure may remain poorly understood. The aim was to understand what it means for kidney care team providers, information technology staff, and patients to engage in implementing an evolving virtual kidney care service in a large, sparsely populated rural and remote region. We interviewed eight kidney care service providers, two information technology specialists, and 17 patients in northern British Columbia, Canada, for their experiences in implementing, delivering, and receiving virtual kidney care and how their practices changed with COVID-19. Through an inductive, reflexive process of analysis and hermeneutic interpretation, we identified patterns in how virtual kidney care was implemented. The analysis showed six hermeneutic principles of implementation at work in the everyday practices of the kidney care and information technology teams: acknowledging central concerns, creating new common understandings, collectively acting, surfacing tensions, being responsive to context, and engaging in ongoing dialogue. Rather than discrete, technical, and time-limited, we found implementation to be an ongoing, evolving, relational, generative, and iterative process that is inextricably connected to its context, and that never fully ends. Attending to the how revealed dimensions of implementation practice that are seldom visible in conventional implementation research. A hermeneutic sensibility, marked by openness, humility, and dialogue, with a commitment to understanding, responsiveness, and relationship-building, is key to implementation, especially in the ever-changing contexts of rural and remote areas. The findings point to the value of a hermeneutic approach in implementing, sustaining, and researching innovations in dynamic healthcare systems and rural settings.
Albuminuric chronic kidney disease (CKD) remains a high cardiorenal-risk state despite renin-angiotensin system blockade and sodium-glucose cotransporter 2 inhibitor (SGLT2i) therapy. Endothelin receptor antagonists (ERAs) reduce albuminuria, but clinical use is limited by fluid retention, edema, hemodilution, and concern for heart-failure decompensation. This review examines the testable hypothesis that SGLT2i background therapy may mitigate ERA-associated fluid retention and improve ERA usability in albuminuric CKD without compromising antiproteinuric efficacy. We conducted a narrative review prioritizing human studies and practice-relevant data on selective endothelin A receptor antagonism in albuminuric CKD, emphasizing quantitative efficacy signals, fluid retention, heart-failure risk, SGLT2i combination therapy, molecular mechanisms, and therapeutic sequencing and monitoring. Available evidence supports a biologically coherent but not yet clinically established strategy. SONAR showed that atrasentan reduced kidney events in a responder-enriched population but retained a numerically higher heart-failure hospitalization signal. ZENITH-CKD showed that zibotentan added to dapagliflozin reduced urinary albumin-to-creatinine ratio at 12 weeks, with dose-sensitive fluid-retention events that were more favorable with lower-dose zibotentan. However, evidence remains short-term, agent-specific, and centered mainly on zibotentan plus dapagliflozin. Mechanistically, ERA-associated fluid retention probably reflects interacting tubular, neurohormonal, vascular-permeability, and hemodilution pathways, whereas SGLT2i mitigation may involve natriuresis, plasma-volume contraction, hemoconcentration, tubuloglomerular effects, and non-diuretic cardiovascular mechanisms. Combined ERA/SGLT2i therapy should be viewed as a mechanistically plausible and clinically testable positioning strategy, not an established treatment paradigm. Broader adoption requires confirmation of durable kidney benefit, cardiovascular safety, real-world feasibility, and reproducible tolerability across eGFR strata and congestion-prone CKD phenotypes.
To assess selenium (Se) and zinc (Zn) Status, mechanisms, analytical methods and biomarker potential in acute kidney injury (AKI). The search was conducted in PubMed, Embase, Web of Science, and Scopus databases, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) up to February 2026. Only primary experimental, clinical and analytical studies that reported quantitative data for Se or Zn in AKI were included. Design-specific tools were used for methodological quality and risk of bias assessment. Low plasma Se (<70 µg/L; <0.89 µmol/L) and Zn (<60 µg/dL; <9.2 µmol/L) was associated with increased incidence, severity, and mortality of AKI in clinical cohorts (n = 453-11,238); however, these relationships may be confounded by inflammation, acute-phase redistribution, and disease severity. Although preclinical evidence points to a role for glutathione peroxidase 4 (GPX4)-regulated ferroptosis, and for the zinc importer/zinc exporter (ZIP/ZnT)-nuclear factor kappa B (NF-κB)-NOD-, leucine-rich repeat- and pyrin domain-containing protein 3 (NLRP3) signalling, these have not yet been validated in humans. Selenoprotein P (SELENOP), glutathione peroxidase 3 (GPX3) and urinary Zn(II) and metallothionein (MT) constitute a proposed panel for clinical implementation, which needs to be analytically validated, discriminated and calibrated, externally validated, incrementally valued and clinically utility evaluated in prospective multicentre studies.
Early diagnosis of acute kidney injury (AKI) remains a major clinical challenge due to the delayed and insensitive nature of conventional markers such as serum creatinine. Urinary protein biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (CysC), provide earlier and complementary information on kidney injury, but their clinical translation is limited by the lack of rapid, quantitative, and multiplexed point-of-care (POC) diagnostic tests. Here, we report a multiplexed plasmonic-fluor-based lateral flow assay (p-LFA) that enables sensitive, quantitative, and simultaneous detection of NGAL and CysC. By harnessing ultrabright plasmonic-fluor nanolabels and ratiometric fluorescence analysis, the p-LFA achieves picogram-per-milliliter analytical sensitivity comparable to that of the enzyme-linked immunosorbent assay (ELISA). In addition, the simplified assay format enables sample-to-answer times as short as 10 min, while maintaining sensitivity sufficient for accurate AKI detection. Clinical validation using pediatric urine samples demonstrates a strong correlation with ELISA measurements for both biomarkers. Combined analysis of NGAL and CysC significantly improves AKI diagnostic performance, yielding an area under the receiver operating characteristic curve of 0.973 with a clinical sensitivity of 90.9% and specificity of 91.2% in the studied cohort. Furthermore, a low-cost, portable fluorescence reader enables quantitative performance equivalent to benchtop imaging while dramatically reducing instrument cost and complexity. Collectively, this work establishes a scalable and adaptable p-LFA platform that bridges laboratory-grade immunoassays and practical POC diagnostics, offering a promising solution for early AKI detection and multiplexed biomarker analysis in decentralized healthcare settings.
Iatrogenic ureteral injuries represent a significant problem in urology and occur predominantly during surgical procedures in the pelvis and abdominal cavity performed for gynecological, urological, and other conditions, leading to serious complications, including impaired renal function and reduced quality of life. With the increasing use of minimally invasive procedures, the incidence of iatrogenic ureteral injuries is rising. A critical challenge is the difficulty of intraoperative diagnosis, which results in delayed detection of injuries and more severe consequences. To investigate the etiology, clinical characteristics, and treatment efficiency of iatrogenic ureteral injuries. A retrospective and prospective study of 141 patients with diagnosed iatrogenic ureteral injuries was carried out at the Urology Research Center of the National Hospital of the Ministry of Health of the Kyrgyz Republic from 2010 to 2024. Diagnosis was based on analysis of clinical manifestations (pain, fever, vaginal urine leakage) and instrumental methods (ultrasound, contrast-enhanced CT, pyelography). Injuries were classified according to the AAST (American Association for the Surgery of Trauma) scale. Treatment efficiency was assessed using clinical and radiological outcomes during 1 year after surgery. Statistical analysis was performed using SPSS 24.0. Women predominated (87.2%); the median age was 38 years. The main causes of injury in women were surgeries for gynecological diseases (72.3%), whereas in men injuries were mainly related to urological interventions (88.9%). In 92.2% of cases, injuries were located in the distal ureter. AAST grade II injuries predominated (53.2%). Intraoperatively, injury was identified in only 7.1% of cases; most cases (82.3%) were diagnosed postoperatively. Ureterovaginal fistulas occurred in 23.4% of women. Reconstructive surgery (predominantly ureteroneocystostomy, 68.1%) was required in 69.5% of patients. Nephrectomy was performed in 12 patients (8.5%), mainly as a consequence of very late diagnosis. Complete clinical efficiency of reconstruction was achieved in 87.2% of patients, with preservation of renal function in the long term. The analysis confirms that the majority of iatrogenic ureteral injuries occur during gynecological surgery and are localized to the distal ureter. In men, injuries related to endourological interventions predominate, including procedures using the Ho:YAG laser. The main factor associated with worse outcomes was delayed diagnosis, which led to an increased number of repeat procedures and a higher rate of complications, particularly fistulas and strictures. The predominance of AAST grade II-III injuries resulted in the need for reconstructive interventions in most patients, most commonly ureteroneocystostomy and Boari flap reconstruction. Despite the severity of complications, reconstructive surgery demonstrates high effectiveness. The identified tactical principles include early detection, active use of instrumental diagnostics, drainage in cases of delayed diagnosis, and an individualized choice of reconstructive technique. The study showed that iatrogenic ureteral injuries in Kyrgyzstan most often occur after obstetric and gynecological surgical procedures and involve the distal ureter. Unfavorable outcomes are mainly associated with chronic kidney disease, prior radiotherapy, and late detection. In the absence of these factors, reconstructive procedures, including ureteroneocystostomy, allow preservation of renal function in the long term. Improving intraoperative diagnosis and standardizing management approaches remain key priorities to increase treatment efficiency.
Observational studies have linked inflammatory cytokines to cardiometabolic disorders; however, whether these associations reflect causal effects across interconnected organ systems remains unclear. This Mendelian randomization (MR) study investigates causality between 91 inflammatory cytokines and multiorgan dysfunction across cardiovascular, kidney, and metabolic systems in the cardiovascular-kidney-metabolic (CKM) syndrome era. Genetic instruments associated with 91 inflammatory cytokines were obtained from the Olink Target Inflammation panel across 11 European-ancestry cohorts. The inverse variance weighting (IVW) method was considered as the main analysis, complemented by sensitivity analyses including MR-Egger and weighted median methods. Genetically predicted levels of inflammatory cytokines showed widespread causal associations across CKM-related traits. Specifically, 31 cytokines were associated with cardiovascular outcomes, 26 with kidney traits, 10 with obesity-related traits, and 21 with diabetes-related traits, yielding a total of 60 cytokines with at least one significant association. Notably, FGF5 and IL6 emerged as paradoxical regulators, exerting opposing effects across different organ systems, while MCSF was consistently identified as a pan-vascular risk amplifier for cardiovascular diseases. This comprehensive MR analysis reveals substantial causal heterogeneity in inflammatory cytokine effects across cardiovascular, kidney, and metabolic systems. These findings highlight the clinical importance of tissue- and context-specific inflammatory modulation, supporting the development of precision therapeutic strategies for CKM syndrome. Estudos observacionais têm relacionado citocinas inflamatórias a distúrbios cardiometabólicos; no entanto, ainda não está claro se essas associações refletem efeitos causais em sistemas orgânicos interconectados. Este estudo de randomização mendeliana (RM) investiga a causalidade entre 91 citocinas inflamatórias e disfunção multiorgânica nos sistemas cardiovascular, renal e metabólico na era da síndrome cardiovascular-renal-metabólica (CKM). Foram obtidos instrumentos genéticos associados a 91 citocinas inflamatórias do painel Olink Target Inflammation em 11 grupos de ascendência europeia.A método da foi considerado a principal análise, complementadas por análises de sensibilidade, incluindo os métodos MR-Egger e da mediana ponderada. Os níveis de citocinas inflamatórias previstos geneticamente mostraram amplas associações causais em diversas características relacionadas à matriz extracelular (CKM). Especificamente, 31 citocinas foram associadas a desfechos cardiovasculares, 26 a características renais, 10 a características relacionadas à obesidade e 21 a características relacionadas ao diabetes, totalizando 60 citocinas com pelo menos uma associação significativa. Notavelmente, FGF5 e IL6 emergiram como reguladores paradoxais, exercendo efeitos opostos em diferentes sistemas orgânicos, enquanto o MCSF foi consistentemente identificado como um amplificador de risco pan-vascular para doenças cardiovasculares. Esta análise abrangente de RM revela uma heterogeneidade causal substancial nos efeitos das citocinas inflamatórias nos sistemas cardiovascular, renal e metabólico. Esses achados destacam a importância clínica da modulação inflamatória específica para cada tecido e contexto, apoiando o desenvolvimento de estratégias terapêuticas de precisão para a síndrome de CKM.
Foreign bodies in the upper urinary tract are relatively rare. Publications on this topic primarily consist of clinical case reports describing the removal of foreign bodies discovered after surgical interventions. However, in modern combat trauma care, the relevance of this issue has increased. In cases of penetrating abdominal or lumbar injuries involving the kidney, the penetrating projectile may remain in the renal parenchyma and subsequently migrate or initially lodge in the pelvicalyceal system. In the vast majority of cases, patients present with multiple (18.6%) or combined (71.2%) injuries, making minimally invasive surgical approaches the preferred method for foreign body removal. Modern technologies allow for the use of percutaneous and/or transurethral techniques in such situations. In this context, we present a clinical case of endoscopic removal of a fragment from the pelvicalyceal system of the right kidney.
Clinical outcomes of critically ill COVID-19 patients admitted to intensive care units (ICUs) remain heterogeneous, and factors influencing mortality require further characterization. This retrospective study evaluated clinical outcomes among 1,344 adult patients with confirmed COVID-19 admitted to ICUs across four governmental hospitals in Kuwait between June 2020 and December 2022. Survival outcomes were assessed using Kaplan-Meier survival analysis and compared by demographic and clinical characteristics. Cox proportional hazards regression was applied to identify factors associated with mortality, while comorbidities and treatment patterns were evaluated in relation to patient outcomes. Survival probability declined from 98% at 5 days to 50% at one year. Kaplan-Meier analysis showed significant differences in survival according to age and diabetes status. Non-survivors were older (66 vs. 55 years, p < 0.001), had a higher prevalence of diabetes (60.9%) and hypertension (70.4%), and experienced longer hospital stays. Hypoxia was strongly associated with mortality (p < 0.001). In Cox regression analysis, adjusted for pandemic admission wave to account for evolving ICU management, increasing age (HR = 1.04 per year, 95% CI 1.03-1.04), fever (HR = 1.18, 95% CI 1.01-1.39), and chronic kidney disease (HR = 1.40, 95% CI 1.11-1.76) were associated with higher mortality. In contrast, anti-inflammatory drug use was associated with reduced risk (HR = 0.52, 95% CI 0.43-0.63) as was anticoagulant (HR = 0.80, 95% CI 0.66-0.97). Antifungal use was associated with increased mortality risk (HR = 1.68, 95% CI: 1.30-2.16); however, associations involving medications likely reflect underlying disease severity and treatment indication rather than direct causal effects. Sensitivity analysis using a split follow-up at day 30 demonstrated that antifungal-associated risk was concentrated during the late follow-up period (HR = 2.10, days 31-365), consistent with late-onset secondary fungal infections among patients with prolonged critical illness.
Pediatric acute kidney injury (AKI) is increasingly recognized as a condition with long-term chronic consequences, rather than a transient, self-limiting event, carrying an elevated risk of both cardiovascular and renal sequelae. Conventional clinic-based blood pressure measurements may fail to detect subclinical hemodynamic abnormalities, potentially underestimating this burden. This systematic review and meta-analysis aimed to evaluate the pooled prevalence of masked hypertension and abnormal nocturnal blood pressure dipping patterns-assessed specifically by 24-hour ambulatory blood pressure monitoring (ABPM)-in pediatric AKI survivors. A systematic search of PubMed/MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science was conducted from database inception to March 2, 2026, without language restrictions. We targeted observational studies tracking children or adolescents with a prior history of AKI who underwent long-term ABPM follow-up. Screening, data extraction, and quality appraisal using the Joanna Briggs Institute Critical Appraisal Checklist were performed independently by two reviewers. Data were synthesized from six studies capturing a total of 150 pediatric AKI survivors. The pooled prevalence of masked hypertension across five cohorts was 12% (95% CI: 4%-23%), and the pooled prevalence of a non-dipping blood pressure profile across five cohorts was 37% (95% CI: 26%-49%). Sensitivity analyses demonstrated the stability of these estimates. The high prevalence of subclinical blood pressure abnormalities suggests that office-based measurements alone may be insufficient for risk detection. Incorporating ABPM into the post-AKI follow-up of selected pediatric populations may enhance cardiovascular risk stratification and warrants consideration in future clinical guidelines.
Background Large-scale clinical studies have shown that finerenone reduces the risk of cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease (CKD). Similarly, sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce the risk of cardiovascular death and heart failure in patients with type 2 diabetes at high cardiovascular risk, with contributing factors reported to include improvements in anemia and changes in plasma volume markers, such as serum albumin (ALB) levels. The impact of finerenone on anemia and plasma volume markers has not been reported. Therefore, we hypothesized that finerenone administration might improve these factors and examined the effects of its administration on these factors. Materials and methods This retrospective observational study included 20 patients with type 2 diabetes and CKD at our hospital who initiated finerenone and had no additional medications added during the 12 months before and after administration. Changes in clinical test data, including hemoglobin (Hb), hematocrit (Ht), and serum ALB levels, were evaluated using trend-shift analysis with a mixed-effects model. Repeated measurements before and after finerenone administration were collected, and the rate of change during each period was approximated with a linear trend line. A shift in the slope of the trend line was considered an intervention effect of finerenone. Analyses were performed for all 20 participants and were stratified by concomitant SGLT2i use and baseline anemia status. Results Overall, finerenone administration significantly increased Hb and Ht levels; however, the increase was significant only in the eight patients also taking SGLT2is and not in the 12 patients who were not. Among the five patients with anemia, Hb and Ht levels increased significantly, but no significant change was observed in the three anemic patients not receiving SGLT2is. Additionally, six patients receiving SGLT2is without anemia also showed significant increases in Hb and Ht levels. These findings suggest that the combination of finerenone and SGLT2is may improve anemia. Furthermore, serum ALB levels were significantly increased with combination therapy. Conclusions Our study suggests that finerenone may improve anemia and increase ALB levels when used in combination with SGLT2is. Since the cardiovascular death and heart failure risk reduction effects of SGLT2is have already been reported, it suggests that finerenone may act additionally to the effects of SGLT2is. We believe that adding finerenone to SGLT2is could potentially provide further cardiovascular and renal risk reduction effects.
Natural killer (NK) cells are increasingly recognized as central effectors in kidney allograft injury, extending beyond their traditional role in innate immunity. This narrative review summarizes current evidence linking NK cells to microvascular inflammation, with a focus on both antibody-dependent and antibody-independent rejection. In antibody-mediated rejection, NK cells may be activated through Fc gamma receptor IIIa (CD16a) engagement with endothelium-bound donor-specific antibodies, leading to antibody-dependent cellular cytotoxicity and proinflammatory cytokine release. In parallel, emerging data highlight donor-specific antibody-independent pathways of NK cell activation, most prominently "missing-self" recognition, driven by donor-recipient killer immunoglobulin-like receptor-HLA incompatibility. Direct proof of concept for an effector role of NK cells in rejection comes from a series of experimental models. High-dimensional transcriptomic and spatial profiling of clinical transplant biopsies consistently demonstrate NK cell enrichment in antibody-mediated rejection and microvascular inflammation, with expression signatures correlating with graft injury severity and outcomes. Moreover, functional genetic polymorphisms in NK cell receptors, including Fc gamma receptor IIIa and the activating receptor NK group 2 member C, might modulate NK cell responsiveness and as a consequence susceptibility to microvascular injury. Therapeutically, emerging strategies such as CD38-targeting monoclonal antibodies, mammalian target of rapamycin inhibition, and, still in experimental phase, interleukin-15 blockade suggest potential to modulate NK cell activity and counteract rejection. Collectively, these findings position NK cells as central effector cells integrating innate and adaptive alloimmune responses and highlight them as promising therapeutic targets in kidney transplantation.
Background Bladder and kidney cancer burden rises globally, with environmental toxicants driving their progression. Methods We integrated global epidemiological analysis, single-cell transcriptomics, cell-cell communication analysis, epithelial subclustering, pseudotime inference, toxicological target prediction, survival modeling, cross-cohort validation, single-cell virtual knockout, spatial transcriptomic deconvolution, molecular docking/dynamics, CETSA, and in vitro assays to define a shared molecular interface linking triphenyl phosphate (TPP) to bladder and kidney cancer. Results Both malignancies exhibited age- and SDI-associated burden patterns. Single-cell profiling identified conserved epithelial, stromal, and immune ecosystems, with tumor epithelial cells occupying central positions in intercellular communication networks. Epithelial subclustering revealed a reproducible EMT-high subcluster 4 in both cancers, which localized to a terminal-like pseudotime state and was associated with poor survival. Predicted TPP targets intersected with subcluster 4 signatures and converged on extracellular matrix organization, adhesion, and leukocyte transendothelial migration pathways. Integrative survival modeling and multi-cohort validation identified MMP9 as a robust prognostic candidate associated with tumor progression. Importantly, single-cell virtual knockout of MMP9 revealed convergent remodeling of proliferative, inflammatory, hypoxia-related, and stress-response programs across bladder and renal cancer epithelial cells, highlighting conserved regulatory circuitry. Spatial transcriptomics further localized MMP9 to macrophage- and fibroblast-enriched niches in both tumor types. Structural modeling and CETSA supported an interaction between TPP and MMP9. Experimentally, TPP upregulated MMP9 at both mRNA and protein levels in T24 and 786-O cells; higher concentrations reduced viability, whereas lower concentrations enhanced migration and clonogenic growth. Conclusions TPP promotes the malignant phenotypes of bladder and kidney cancer via MMP9, which is validated by virtual knockout and in vitro experiments.
High-output stoma (HOS) is a clinically relevant complication after stoma formation and may increase postoperative morbidity and healthcare utilization. This study aimed to evaluate clinical, biochemical, and perioperative factors associated with early HOS and to examine its relationship with postoperative outcomes and 30-day readmission. This retrospective single-center cohort study included 159 adult patients who underwent ileostomy or colostomy formation between January 2015 and January 2025. Data were extracted from electronic medical records, operative reports, and postoperative nursing documentation. Early HOS was defined as stoma output exceeding 1500 mL/day during the early inpatient postoperative period. Univariable and multivariable logistic regression analyses were performed to evaluate factors associated with HOS. Hierarchical modeling assessed the incremental contribution of predefined variable domains, and exploratory mediation analysis examined the relationship between HOS, dehydration, and readmission. Early HOS developed in 46 patients (28.9%). In multivariable analysis, ileostomy formation (OR = 4.12, p = 0.002), longer operative time (OR = 1.01 per minute, p = 0.01), lower albumin level (OR = 0.55, p = 0.02), lower sodium level (OR = 0.90, p = 0.02), and diuretic use (OR = 2.58, p = 0.03) were independently associated with early HOS. Model discrimination increased across hierarchical blocks, with AUC values ranging from 0.66 to 0.86. Patients with HOS had higher rates of dehydration, acute kidney injury, prolonged hospital stay, and 30-day readmission. HOS remained independently associated with readmission (OR = 2.87, p = 0.009), and exploratory mediation analysis suggested partial mediation through dehydration. Early HOS was common after stoma formation and was associated with baseline biochemical vulnerability, perioperative factors, and adverse postoperative outcomes. Given the retrospective design and heterogeneity between ileostomy and colostomy, these findings should be interpreted as exploratory and require confirmation in prospective, multicenter, stoma type-specific studies.
Patients with end-stage kidney disease (ESKD) have a high rate of hospitalizations related to fluid overload and infections. Artificial intelligence (AI)-driven models may improve patient care by predicting the risk of hospitalization. The authors conducted a retrospective, observational matched cohort study of adult patients with ESKD who were receiving value-based hemodialysis at integrated kidney care clinics across the United States in 2023. Two AI-powered machine learning models calculated risk scores (range: 0-1) and the models identified patients with a risk score of 0.64 or above who were at risk for hospitalization within 7 days in relation to infections or fluid status abnormalities. To prevent avoidable hospitalizations, case reviews and interventions were conducted for the patients identified by the models. The AI models generated scores for all patients, but only high-risk scores triggered case review and possible intervention. The authors linked electronic medical records and Medicare claims data and conducted multivariate logistic regression analyses to examine the impact of AI-driven interventions on the odds of all-cause hospitalization in patients with ESKD. A total of 10,294 patients representing 83,928 risk scores were included in the analysis. AI-driven intervention was associated with an 8% reduction in the odds of hospitalization within 7 days (odds ratio=0.92; P=0.025). These interventions were most effective for high-risk patients with scores between 0.64 and 0.85, but had no statistically significant effect for patients with scores above 0.85. Factors that were independently associated with higher rates of hospital admission included a higher risk score (>0.75), chronic high-risk scores, older age, and a higher number of hospital admissions in the year prior. AI-driven interventions were associated with a reduction in the odds of hospitalization among patients with ESKD receiving managed kidney care. These findings underscore AI's potential to assist health care providers with targeted risk interventions for patients with ESKD.
Roxadustat is an oral hypoxia-inducible factor prolyl-hydroxylase inhibitor. Recent studies have shown no inferiority of roxadustat compared to erythropoietin in chronic kidney disease and in post-transplant patients. We evaluated roxadustat versus erythropoiesis-stimulating agents (ESAs) in very early posttransplant patients. We performed a retrospective analysis of the clinical course and laboratory changes in posttransplant patients treated with roxadustat (16 patients) or a high-dose erythropoiesis-stimulating agent (ESA) (16 patients) for anemia between March and September 2025. We compared haemoglobin, creatinine, lipid levels, and iron status. The therapy was started after the kidney transplant, respectively, after a median of 3.5 and two days. Every patient was followed up at two weeks, one month, two months, and three months. Patients treated with roxadustat showed a significantly greater and faster increase in Hb levels at 2 weeks (p = 0.047) than the ESA group. After 2 weeks, we observed a significant difference in the need for blood transfusions between the groups (p = 0.029; 18.8% in the roxadustat group vs. 62.5% in the ESA group). No significant differences were observed in iron or inflammation status during the study. The roxadustat group achieved a significantly better lipid profile after one month (p < 0.05 for cholesterol and LDL). During the follow-up, no adverse events related to roxadustat were reported. Administration of oral roxadustat in very early post-transplant patients is effective and safe, rapidly improving anemia and reducing the need for transfusions.
An association between delayed graft function (DGF) and BK polyomavirus (BKPyV) DNAemia is not well defined. We investigated this with 1) a retrospective review of a single-center cohort analysis, and 2) a systematic review & meta-analysis of published data. Kidney transplant recipients at a single-center between 01/01/2007-30/06/2018 were analyzed. Comparative analyses were done with logistic regression models based upon clinical risk factors. Following a systematic review of published studies, meta-analysis was performed using the DerSimonian-Laird random effects model. In our single-center analysis, we analyzed 1,770 kidney transplant recipients with median follow up 5.3 years (interquartile range 2.7-8.7 years). BKPyVDNAemia was associated with; male sex (8.3% versus 5.3% respectively, p=0.017), ABO-incompatible transplantation (10.3% versus 4.6% respectively, p=0.004) and DGF (9.0% versus 6.3% respectively, p=0.048). In a multivariate analysis, only recipient male sex and ABO-incompatible transplantation was associated with BKPyVDNAemia. In a systematic review of published literature, we identified 11 studies and performed a meta-analysis of empirical data including our Birmingham cohort data. No significant association was observed between DGF rates and BKPyVDNAemia (OR 1.00, 95% CI 0.67-1.50). We did not identify any association between DGF rates and subsequent BKPyVDNAemia.
To evaluate changes in the anteroposterior renal pelvis diameter (APD) from the first to the third trimester in healthy primigravid women. A prospective observational study was conducted from March 2021 to July 2022, involving 30 healthy pregnant women aged 18-40 years. Inclusion criteria were: primigravida, singleton pregnancy, absence of significant medical conditions, and no history of urinary tract infections. Renal ultrasound examinations was performed in the first (10-12 weeks), second (22-24 weeks) and third (34-36 weeks) trimesters. Statistical analysis was performed using nonparametric methods (Statistica 10, StatSoft). In 10 women, APD was not detectable throughout the pregnancy. In the right kidneys, the APD increased from the first to the second trimester in 40% of women, while in the left kidneys? in increased in 33.3%. From the first to the third trimester, an increase in APD was observed in 30% of women in the right kidneys and in 53.3% in the left kidneys. Significant differences in the APD were noted only in the left kidneys between the first and second trimesters (p=0.005) and the first and third trimesters (p=0.003). In the right kidneys, the changes approached significance (p=0.072 and p=0.075, respectively). Differences between the second and third trimesters were not statistically significant. The study results demonstrated that dilation of the renal pelvis in pregnant women can vary: some women exhibit no dilation, while others shou an increase or decrease. Notably, an increase in APD was more frequently observed in the left kidneys, which contradicts the common belief of a predominance of right-sided hydronephrosis. It is important to note that changes in the APD do not always correlate with clinical symptoms, making it difficult to distinguish between physiological and pathological dilation. These findings highlight the need for further research to refine diagnostic criteria and understand the factors influencing the progression of maternal hydronephrosis. Dilation of the renal collecting system in healthy primigravid women may be absent, increase, or decrease during pregnancy. The most significant changes in the collecting system of the kidneys occur from the first to the second trimester, particularly in the left kidneys. These findings underscore the necessity for further studies to differentiate between physiological and pathological dilation of the upper urinary tract and to clarify their clinical significance.