搜索结果：Kidney research and clinical practice

My Kidneys & Me (MK&M) is a digital health intervention (DHI) codeveloped to provide specialist health and lifestyle education aimed at enhancing self-management among individuals with chronic kidney disease. The MK&M DHI was shown to improve self-management behaviors in a multicenter randomized controlled trial (SMILE-K), but strategies to support effective integration into routine clinical practice are not known. This study aimed to explore patient perspectives about real-world implementation and sustainability of the MK&M DHI. For this substudy, participants from the SMILE-K trial were invited to take part in a semistructured qualitative interview to explore their perspectives on the implementation and sustainability of the MK&M DHI in routine clinical practice. Barriers and facilitators that could potentially influence the uptake and usage of the program in real-world settings, outside of a clinical trial, were also explored. Topics included accessibility, usability, integration into routine care, and types of support required to sustain engagement over time. Data were analyzed using reflexive thematic analysis. A total of 42 interviews were conducted with 35 individuals (mean age 62.5, SD 9.9, range 38-84 years; 23/35, 66% male; 33/35, 94% White British; estimated glomerular filtration rate: mean 33.5, SD 12.4 mL/min/1.73 m2). Five themes were identified, encompassing a range of critical factors that should be addressed to ensure the successful implementation of MK&M into routine kidney care and its alignment with real-world clinical needs. These include ensuring that information is timely, relevant, and tailored to individual needs. Participants highlighted the importance of promotion through multimodal strategies and approaches, leveraging diverse communication channels to maximize reach and engagement. Equitable access was identified as a priority, with potential barriers, such as digital literacy and digital poverty, requiring attention. Building trust, through reassurance and endorsement from trusted health care professionals, was seen as essential to strengthen confidence in MK&M. Finally, participants stressed the need for continued engagement and sustainability, ensuring that MK&M is successfully integrated into care pathways and supported over time to maintain its impact. The study findings highlight that timely, well-targeted communication using diverse strategies will be critical for the successful uptake of MK&M among people living with chronic kidney disease. The identification of perceived factors that will influence implementation of the program provides actionable insights to guide the development of tailored implementation strategies to ensure that MK&M is relevant, acceptable, and feasible in real-world practice. These findings provide a foundation for designing approaches that are not only patient-centered and inclusive but also adaptable to diverse clinical contexts. By addressing these factors proactively, implementation efforts can promote equitable access, foster sustained engagement, and support the long-term integration of DHIs, such as MK&M, into routine kidney care.

This umbrella review aimed to synthesize and critically appraise high-level evidence on the effectiveness of digital health interventions across the chronic kidney disease (CKD) continuum, encompassing predialysis, dialysis, and kidney transplant populations, with a focus on patient-centered, behavioral, clinical, and psychosocial outcomes. A systematic search of English peer-reviewed literature up to December 18, 2025, identified 16 eligible systematic reviews and meta-analyses. Methodological quality and risk of bias were assessed using AMSTAR-2 and ROBIS, respectively, and data were independently extracted by independent reviewers in accordance with PRIOR guidelines. Across the included reviews, digital health interventions-such as mobile health applications, telehealth platforms, telemonitoring systems, wearable devices, and web-based self-management tools-demonstrated consistent benefits for proximal outcomes. These included improvements in medication and dialysis adherence, dietary and fluid management, self-efficacy, psychological well-being, and health-related quality of life. Notably, multicomponent interventions with reminders, interactive education, gamification, and personalized feedback were especially effective in promoting engagement and sustained behavior change. Nonetheless, effects on distal clinical outcomes-such as kidney function (estimated glomerular filtration rate), biochemical parameters, hospitalization rates, and long-term morbidity-were heterogeneous and often inconclusive, reflecting variability in study designs, populations, and follow-up durations. Overall, the quality of evidence ranged from low to moderate, with substantial heterogeneity across intervention types, outcome measures, and reporting standards, highlighting the need for standardized frameworks and core outcome sets in future research. Digital health interventions appear effective in enhancing CKD self-management and improving patient-centered outcomes. However, more rigorous and standardized research is required to establish their long-term clinical impact.

Living donor kidney transplantation (LDKT) offers superior outcomes for most patients with end-stage kidney disease (ESKD), yet its uptake across Europe remains highly variable. This proceedings article summarizes key themes from a pan-European symposium held in November 2025 in Prague, organized by the European Kidney Transplant Association (EKITA) in collaboration with the DESCaRTES Working Group. Discussions highlighted substantial heterogeneity in LDKT activity across Europe, driven by differences in healthcare capacity, legal frameworks, donor evaluation practices, and access to kidney exchange programmes. Marked inequities persist between regions, particularly in the Balkans and Western Balkans, for women those who are socioeconomically disadvantaged, ethnic minority populations, paediatric and elderly patients and individuals with obesity. The symposium identified wide variation in donor selection criteria, risk assessment, informed consent practices, and long-term donor follow-up, despite existing international guidelines. Emerging strategies to address these challenges include harmonisation of donor evaluation and consent, expansion of paired and cross-border kidney exchange programmes, increased use of unspecified kidney donation, and adoption of innovative surgical and immunological approaches to safely broaden donor eligibility. Advances in outcome measurement, including validated surrogate endpoints, machine learning methods, and integrated, harmonised transplant registries, were discussed as critical tools to improve quality, transparency, and research efficiency. Collectively, the proceedings underscore the need for coordinated clinical, policy, and data-driven solutions to reduce inequities and unlock the full potential of LDKT across Europe, with implications for international transplant practice.

Despite strong evidence supporting cardiovascular and kidney benefits of sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) in patients with type 2 diabetes, prescribing rates remain suboptimal. The aim of this study was to assess clinicians' knowledge and comfort prescribing SGLT2i and GLP-1 RA in clinical practice and factors influencing prescribing of these agents. This multi-methods study used questionnaires to assess self-reported knowledge and comfort prescribing SGLT2i and GLP-1 RA, and semi-structured interviews based on the Consolidated Framework for Implementation Research (CFIR) to assess factors affecting prescribing decisions among 21 clinicians (12 primary care physicians, 4 pharmacists, 5 nurse practitioners) at a large community-based health system in Virginia. Questionnaire results were analyzed using descriptive statistics, and interviews used a two-phase analytic approach combining inductive and deductive coding. Clinicians self-reported high knowledge (7.9/10) and comfort (8.1 and 8.4/10) prescribing SGLT2i and GLP-1 RA but identified multiple implementation barriers. The most significant barriers were insurance coverage and out-of-pocket costs, with prior authorization requirements delaying therapy initiation. Medicare beneficiaries faced particularly challenging access due to coverage gaps and ineligibility for manufacturer assistance programs. Organizational factors, including high workload, limited appointment time, and the absence of automated patient identification systems, hindered consistent prescribing. Medication burden, side effects, and aversion to injectable medications emerged as patient-related barriers. Facilitators included strong clinical evidence supporting these agents, organizational culture supportive of innovation, and access to pharmacist support. Despite high self-reported knowledge and comfort prescribing SGLT2i and GLP-1 RA, clinicians identified barriers to their use in clinical practice at the patient, clinician, organizational, and medication access levels. Future work should identify the best implementation strategies to address these barriers.

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.

Obesity, diabetes, and cardiovascular disease often co-exist in people with chronic kidney disease, placing them at high risk for adverse health outcomes. Availability of highly effective medications that span cardiovascular-kidney-metabolic (CKM) conditions, but limited uptake in real world settings, calls for a new transformative practice paradigm. We sought to identify key gaps, barriers, and facilitators to implementing a standardized CKM-focused comprehensive medication management (CMM) intervention, including needs/solutions among various care team members involved in CKM care in diverse health systems across the United States. This was a qualitative study guided by the Consolidated Framework for Implementation Research (CFIR) deployed in five health care systems across the United States. Clinical pharmacists, pharmacist administrators, primary care and specialty (nephrology, cardiology, endocrinology) physicians, and advanced practice professionals were interviewed using open-ended questions that were informed by results from three mainly quantitative online surveys. A total of 26 interviews were conducted with 42 participants. Practitioners and administrators reported many similar challenges to successfully implement CMM for people with CKM including lack of standardized CMM practice and workflow across the health system, electronic medical record integrated tools to identify and track patients with CKM, automatic pharmacist referrals, broad clinical practice agreements, and holistic CKM performance metrics, as well as pharmacist time constraints and limited reimbursement. Participants also highlighted CMM-CKM practice facilitators including recognition across most health care professionals that CKM should be a system priority, requiring strong supportive professional relationships among physician and/or administrator champions, and tools, knowledge, and resources that could be shared with others. Successful implementation of a transformative, holistic CMM-CKM interprofessional team-practice will require a tailored implementation strategy for each health system including consolidated tools such as a CMM-CKM Change Package, integrated with coaching, field experts, and peer-to-peer learning.

The regimen of rituximab we not determined based on evidence from pharmacokinetics. However, rituximab exhibited significant pharmacokinetic variability among different clinical populations, which might be a key factor influencing individual exposure and response to this monoclonal antibody. This systematic review aimed to analyze the traditional and population pharmacokinetics of rituximab and to investigate covariates influencing its pharmacokinetics. A systematic search was conducted in three English databases (Medline, Embase, Cochrane Central Register of Controlled Trials) and two Chinese database (China National Knowledge Infrastructure and Wanfang Data). Traditional and population pharmacokinetics of rituximab conducted in humans were included. Study designs, population characteristics, pharmacokinetic parameters, and covariates were extracted. The ClinPK's checklist was used to assess the reporting quality of the included studies. The PROSPERO registered ID was CRD420251085784. The systematic research yield 25 traditional pharmacokinetics studies and 26 population pharmacokinetics studies. The included studies mainly investigated the pharmacokinetics of rituximab in patients with non-Hodgkin's lymphoma, rheumatoid arthritis, kidney disease and anti-neutrophil cytoplasmic antibody-associated vasculitis. Significant variability in pharmacokinetic parameters existed among different clinical populations as well as among different subjects encountering similar clinical conditions. Most (23, 88.5%) population pharmacokinetics studies used a two-compartment model to describe rituximab pharmacokinetics. However, the elimination kinetics were inconsistent including the first-order elimination, time-varying elimination and target-mediated drug disposition. Body size descriptors such as body surface area, body mass index and body weight were the most frequently observed significant covariates, which appeared in 17 studies. Other significant covariates included gender, basal CD19+/20+ count, tumor stage, baseline total metabolic tumor volume, anti-drug antibodies, disease progression, urinary protein to creatinine ratios and the number of rituximab treatment courses. In addition, the pharmacokinetic parameters of rituximab biosimilars were proved to be non-inferior to that of the originators. Compared with intravenous administration, subcutaneous administration with a specific dose of 1600 mg or 1400 mg could achieve non-inferior Ctrough in chronic lymphocytic leukemia and diffuse large B-cell lymphoma respectively. This systematic review presented a comprehensive overview of rituximab's pharmacokinetics across various clinical populations. It highlighted the complexity and variability of rituximab's pharmacokinetics. Future research should place emphasis on the model informed precision dosing of rituximab based on pharmacokinetics and various influencing factors in clinical practice.

Alport syndrome (AS) is a hereditary kidney disorder characterized by progressive hematuria, proteinuria, and kidney failure, frequently accompanied by hearing loss and ocular abnormalities. Although blockade of the renin-angiotensin system (RAS) is established as the first-line therapy, additional pharmacological interventions have been explored. To formulate evidence-based recommendations tailored to the Korean healthcare setting, the Genetic Kidney Disease Study Group of the Korean Society of Nephrology conducted a systematic review evaluating four therapeutic strategies: RAS blockade, cyclosporine, mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter 2 inhibitors (SGLT2i). The quality of evidence and strength of recommendations were assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. The review confirmed that early initiation of RAS blockade delays progression to kidney failure and improves long-term survival, with the greatest benefit when initiated at the stage of microscopic hematuria or microalbuminuria. In contrast, evidence supporting cyclosporine , MRAs, and SGLT2i remains limited, primarily derived from small observational studies with short follow-up and heterogeneous populations. Although cyclosporine and MRAs have demonstrated short-term reductions in proteinuria, neither has shown sustained renoprotective effects, and cyclosporine is associated with a substantial risk of nephrotoxicity. Evidence regarding SGLT2i is inconsistent, with insufficient data on long-term efficacy in AS. Accordingly, these guidelines strongly recommend early RAS blockade as the cornerstone of AS, while no recommendations are made for routine use of cyclosporine, MRAs, or SGLT2i. Well-designed clinical trials are needed to expand therapeutic options and improve long-term outcomes in AS.

Unrecognized contraindications pose risks for adverse drug reactions, hospitalizations or death. Clinical decision support systems (CDSS) aim to mitigate medication-related harm, particularly originating from contraindications. However, many CDSS provide limited benefit, as they focus largely on singular risk situations such as drug-drug interactions and often generate alerts of limited clinical relevance. Comprehensive integration of contraindications into CDSS may support more clinically meaningful alerts. The aim of this work was the development and analysis of machine-readable contraindication lists, including drug-clinical condition, drug-kidney function and drug-drug (group) contraindications, for integration into CDSS and real-world data analysis. We extracted and operationalized contraindications, based on Summaries of Product Characteristics (SmPCs), of the 688 most prescribed drugs in Germany, leveraging common medical coding systems. Moreover, we analyzed extracted contraindications based on operationalizability, overall frequency and frequencies within different contraindication categories. In total, we extracted 4676 contraindications, of which 2129 (45.5%) were deemed operationalizable. Of these 2129 contraindications, 1652 (77.6%) were attributed to drug-clinical condition, 83 (3.9%) to drug-kidney, 140 (6.6%) to drug-drug group and 254 (11.9%) to drug-drug. The most frequently mentioned contraindicated risk situations were 'severe liver insufficiency' (n = 74, 3.5%), 'pregnancy' (n = 66, 3.1%), 'MAO-inhibitors' (n = 44, 2.1%), and 'shock' (n = 44, 2.1%). Our results show, that drug-clinical condition contraindications are listed far more frequently in SmPCs than other contraindication categories. Focusing on clinical condition-related contraindications within CDSS could improve the detection of clinically relevant contraindications in routine data and enhance medication safety. The clinical applicability is currently being evaluated in the INTERPOLAR study.

Kidney allograft rejection exhibits highly complex features due to the intricate immune mechanisms involved. The early and accurate diagnosis of rejection remains challenging, particularly when differentiating between/among subtypes. Herein, the authors present "RenalTransPredNet," an interpretable model that integrates whole-slide images with routine clinicopathological variables to diagnose kidney allograft rejection. This study included kidney allograft biopsies performed at the Headquarters and Lingnan Hospital of the Third Affiliated Hospital of Sun Yat-sen University between January 2015 and August 2024. After screening, 1086 digital whole-slide images from 362 biopsies and their corresponding clinicopathological information were analyzed, comprising 209 other lesions and 153 rejections. By integrating multiple instance learning-based pathological image analysis with random forest-based clinicopathological information analysis, RenalTransPredNet was used to efficiently construct models for kidney allograft rejection-related multiclass and binary classification tasks. RenalTransPredNet achieved a higher area under the curve (AUC) value than both the pathological imaging and clinicopathological information models in detecting and subtyping kidney allograft rejection, yielding an AUC of 0.886 using data from the internal testing set. For the prediction of treatment response to rejection, RenalTransPredNet yielded an AUC of 0.743. In the task predicting graft loss after rejection, RenalTransPredNet demonstrated predictive capabilities for graft loss at 1, 2, 3, and 5 years post-rejection, with AUCs of 0.876, 0.942, 0.904, and 0.978, respectively. These findings support the potential of RenalTransPredNet in improving the diagnostic accuracy of pathologists in detecting and subtyping kidney allograft rejection and in contributing to prognostic assessments.

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end-stage kidney disease worldwide. Activation of the renin-angiotensin system (RAS) plays a central role in the pathogenesis of DKD by promoting intraglomerular hypertension, albuminuria, inflammation, oxidative stress, and progressive fibrosis. Angiotensin II-mediated efferent arteriolar constriction increases glomerular capillary pressure, while non-hemodynamic effects, including upregulation of transforming growth factor-β, NADPH oxidase-dependent reactive oxygen species generation, and podocyte apoptosis, contribute to structural kidney injury. Large, randomized trials have consistently demonstrated that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers reduce albuminuria, slow the glomerular filtration rate decline, and delay kidney failure across different stages of DKD. Evidence also supports cardiovascular benefits, including reduced heart failure events, in patients with DKD. A reduction in albuminuria is closely correlated with long-term kidney outcomes, underscoring its role as a mechanistic and therapeutic marker. Concerns regarding safety in advanced chronic kidney disease have been addressed by recent evidence indicating that routine discontinuation of RAS blockade does not improve kidney function and may increase cardiorenal risk. Although newer agents have expanded the therapeutic options, RAS inhibition remains the foundational therapy for DKD. This review summarizes the mechanistic basis, clinical evidence, safety considerations, and contemporary perspectives of RAS blockade in DKD.

Acute kidney injury (AKI) is a complex and multifactorial syndrome associated with significant morbidity, mortality, and progression to chronic kidney disease. While conventional diagnostic and therapeutic strategies have centered on serum creatinine and supportive care including kidney replacement therapy (KRT), recent advances have expanded our understanding of AKI pathophysiology and treatment. This review outlines current insights into the cellular and molecular mechanisms underlying AKI, including ischemia-reperfusion injury, oxidative stress, endothelial dysfunction, and regulated necrosis. Building upon these mechanisms, emerging pharmacologic interventions, such as anti-inflammatory agents, antioxidants, growth factors, and hemodynamic modulators, show promise in preclinical and early-phase clinical studies. Regenerative therapies using mesenchymal stromal cells and extracellular vesicles represent novel cell-based strategies, while biomarker-guided precision medicine offers a paradigm shift in AKI diagnosis, risk stratification, and treatment selection. Moreover, innovations in KRT, including prolonged intermittent therapies, cytokine adsorption, and bioengineered membranes, aim to enhance solute clearance and hemodynamic stability. The integration of artificial intelligence, machine learning, and clinical decision support systems into AKI care pathways provides new opportunities for early detection and personalized intervention. Lastly, multiomics approaches are redefining AKI subphenotypes and uncovering novel therapeutic targets through comprehensive molecular profiling. Continued research and precision-based clinical trials are essential to realize the full therapeutic potential of these innovations in AKI management.

Mental disorders are highly prevalent among patients with chronic kidney disease (CKD); however, the causal effects of kidney dysfunction on specific brain volume traits and mental disorders remain underexplored. In this Mendelian randomization (MR) study, genetic instruments for kidney function and CKD, derived from genome-wide association studies (GWAS) in Chronic Kidney Disease Genetics and the UK Biobank (n = 1,201,909), were utilized for two-sample MR analysis in the discovery phase. Summary-level data from these GWAS provided exposure-outcome associations to calculate causal estimates using the inverse variance weighted method. Validation analysis was conducted using one-sample MR with individual-level data from the UK Biobank. Two-sample MR identified causal associations (odds ratios [ORs] as point estimates) between estimated glomerular filtration rate (exposures) and amygdala traits (outcomes), with ORs ranging from 0.559 to 0.723 (p < 0.05). Two-sample MR between CKD (exposures) and amygdala volume traits (outcomes) reported ORs ranging from 1.042 to 1.059 (p < 0.05). These associations also linked kidney dysfunction to an increased risk of depression, using two-sample MR across 507 brain volume and 242 mental disorder GWAS datasets. Leave-one-out analyses and pleiotropy tests, including MR Egger, supported the robustness of these findings. Validation analysis confirmed reproducibility using one-sample MR. Our results demonstrate that kidney dysfunction causally alters amygdala volume, increasing susceptibility to mental disorders such as depression. These findings highlight the kidney-brain axis and underscore the importance of integrating mental health screening and interventions into the clinical management of patients with CKD.

Diabetic kidney disease (DKD) is a major contributor to chronic kidney disease (CKD) and end-stage kidney disease worldwide, and is strongly associated with increased cardiovascular morbidity and mortality. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, initially developed for glycemic control, are now established as key therapies for DKD patients. Large, randomized clinical trials, including CREDENCE, DAPA-CKD, and EMPA-KIDNEY, have consistently shown that SGLT2 inhibitors reduce the risk of kidney disease progression, cardiovascular events, and hospitalization for heart failure in patients with and without diabetes. These benefits extend beyond lowering glucose and are attributed to multiple complementary mechanisms, including restoration of tubuloglomerular feedback, reduction of intraglomerular pressure, natriuresis, and pleiotropic effects, such as improved metabolic efficiency, attenuation of inflammation and fibrosis, and enhanced renal oxygenation. The management of DKD is increasingly shifting toward a combination-based strategy targeting diverse pathogenic pathways. Emerging data suggest that combining SGLT2 inhibitors with other cardiorenal protective agents, such as renin-angiotensin system inhibitors, non-steroidal mineralocorticoid receptor antagonists, and glucagon-like peptide 1 receptor agonists, may provide additional benefits. Recent guidelines emphasize the use of SGLT2 inhibitors primarily for cardiorenal protection independent of glycemic control. Despite these advances, important gaps remain in underrepresented populations, including the elderly, non-albuminuric DKD, advanced CKD, kidney transplant recipients, and patients with type 1 diabetes. This review provides an overview of the key mechanisms and clinical evidence supporting the use of SGLT2 inhibitors in DKD, along with emerging insights into combination strategies and their clinical implications.

Dietary management of hyperkalaemia in chronic kidney disease has traditionally focused on potassium restriction. However, contemporary renal nutrition practice increasingly requires dietitians to balance biochemical safety with nutritional adequacy, dietary quality, treatment burden, and patient wellbeing. Limited empirical evidence has examined how renal dietitians reason through these competing priorities in routine practice. To explore how renal dietitians approach dietary hyperkalaemia management in chronic kidney disease and to examine the professional reasoning underpinning dietary decision-making. This qualitative study integrated free-text responses from an international online survey of renal dietitians with semi-structured interviews. Survey free-text responses provided breadth across practice settings, while interviews enabled more detailed exploration of clinical reasoning. Data from 203 survey respondents and eight interview participants were analysed consequently using reflexive thematic analysis to examine how dietitians prioritised, sequenced, and adapted dietary interventions. Dietitians described dietary hyperkalaemia management as a staged but flexible process of professional reasoning. Four interrelated themes were identified: consideration of non-dietary contributors before dietary restriction; prioritisation of potassium additives and highly processed foods; preservation of nutritional adequacy as a central boundary condition; and selective restriction of potassium-rich whole foods only when clinically indicated. Dietary restriction was not described as an automatic response to elevated serum potassium, but as one possible component of a broader reasoning process shaped by biochemical trends, nutritional status, clinical urgency, patient preferences, and psychosocial context. These findings informed development of the Prioritisation and Reasoning in the Management of Elevated Potassium in Chronic Kidney Disease model, known as PRIME-K. Renal dietitians reported using flexible professional judgement to manage hyperkalaemia while minimising unnecessary dietary burden and protecting nutritional adequacy. The PRIME-K model offers a practice-informed representation of professional reasoning in dietary hyperkalaemia management and may support dietetic education, reflective practice, and the development of more context-sensitive approaches to dietary care in chronic kidney disease.

Sarcopenia affects approximately 30%-40% of patients with end-stage kidney disease (ESKD) undergoing maintenance hemodialysis (HD), a prevalence substantially higher than that observed in community-dwelling older adults. Muscle wasting in this population is driven by chronic inflammation, amino acid losses during dialysis, and anabolic resistance, which blunt muscle protein synthesis despite nutritional intake or exercise. Leucine, a branched-chain amino acid that activates mechanistic target of rapamycin complex 1 signaling, plays a key role in muscle anabolism but is often depleted in patients undergoing HD. This pilot study evaluated the feasibility and preliminary effects of combining leucine supplementation with exercise on muscle-related outcomes in ESKD patients. In this single-center randomized pilot trial, 24 patients undergoing maintenance HD were assigned to either exercise alone or exercise plus leucine supplementation for 12 weeks. The intervention group received 6 g/day of leucine in beverage and capsule form. The primary outcome was the change in handgrip strength. Secondary outcomes included physical performance measures (gait speed, five-times sit-to-stand, and Short Physical Performance Battery), skeletal muscle mass indices, body composition, and biochemical markers. Exploratory analyses included responder analysis and metabolomic correlation analysis in an independent cohort. Baseline characteristics were generally comparable between groups. The intervention group showed higher responder rates for handgrip strength and gait speed compared with the exercise-only group, while modest increases in skeletal muscle index were observed only in the intervention group. Several biochemical markers, including total protein, blood urea nitrogen, creatinine, and red blood cell count, showed directional increases in the intervention group. Independent metabolomic profiling demonstrated lower circulating leucine levels and disrupted amino acid correlations in HD patients compared with healthy controls. Adjunct leucine supplementation combined with exercise showed preliminary improvements in muscle function and selected biochemical markers in patients with ESKD undergoing HD. These findings support the potential role of leucine-based nutritional strategies in mitigating sarcopenia in this population, although larger and longer-term trials are required to confirm efficacy.

Intravenous methylprednisolone (MP) pulse therapy remains the standard first-line treatment for acute T-cell-mediated rejection following kidney transplantation. However, the dose and duration of this therapy were established empirically more than three decades ago rather than by contemporary rigorous dose-finding trials. The most common treatment regimens consist of 250-500 mg MP daily for three to five days, but substantial between-center variability persists. This narrative review explores the historical development of steroid pulse dosing, the available comparative clinical data, and the biological rationale underlying current practice. The commonly used dose range of 250-500 mg daily for three to five days rests largely on historical convention rather than on contemporary dose-finding evidence. A series of small prospective and randomized studies failed to demonstrate superior efficacy of more intensive regimens when compared with doses broadly resembling current practice. Mechanistically, glucocorticoids act through genomic and rapid non-genomic pathways, supporting a hypothesis-generating dose-window concept rather than a simple linear dose-response model. Contemporary data further indicate that clinical response does not reliably predict histologic resolution and that MP pulse rejection treatment carries significant toxicity. Overall, steroid pulse therapy remains biologically plausible and clinically entrenched; however, the optimal dose and duration have yet to be established under current tacrolimus- and mycophenolate-based immunosuppression. More precise response monitoring will also be required to develop more effective and less toxic treatment regimens.

Lithium remains a first-line treatment for bipolar disorder, but practice varies regarding dosing frequency. Although once-daily and twice-daily regimens are similarly effective, they produce serum lithium profiles that differ over the day, and whether greater fluctuations with once-daily dosing are attenuated in the brain is unclear. The aim of this study was to evaluate whether brain lithium profiles differed across the day with once-daily versus twice-daily dosing regimens. In this repeated-measures, cross-sectional imaging study, euthymic individuals (aged 18-50 years) with bipolar disorder type I or II receiving stable lithium carbonate treatment were recruited at four psychiatric outpatient departments in Dresden, Germany. In the week before assessment, participants received lithium at 2000 h (full once-daily dose or evening dose of the twice-daily regimen) and 0800 (twice-daily regimen only; withheld until after the 0800 h sampling on assessment day). The core assessment was a 1-day protocol in which participants underwent three consecutive 7Li MRI scans and matched serum sampling over a 10-h period (0800, 1400, and 1800h). Whole-brain lithium measurements across timepoints were compared according to regimen using the brain observable lithium threshold region-of-interest approach. Secondary analyses modelled tissue-specific profiles, derived from the Newcastle lithium image voxel evaluation pipeline, and examined the relationship between serum lithium concentration and brain 7Li MRI signal intensity using repeated-measures ANOVA, linear mixed-effects models, and population pharmacokinetics. This study was informed by people with lived experience of bipolar disorder and long-term lithium treatment through patient and public involvement and engagement activities. Between April 19, 2022, and Dec 9, 2023, 44 eligible participants were recruited, of whom three withdrew before assessment. Therefore, 41 euthymic individuals (all White European; 21 [51%] female and 20 [49%] male; mean age 39&#xb7;2 years [SD 9&#xb7;8]) with bipolar disorder receiving stable lithium carbonate treatment (20 in the once-daily dosing group and 21 in the twice-daily dosing group) were evaluated. At 12 h post dose (0800 h), brain 7Li MRI signal intensity and serum lithium concentrations were equivalent across regimens. In the once-daily group, serum lithium declined across the day, whereas in the twice-daily group it increased after the morning dose and then decreased. Brain 7Li MRI signal intensity closely mirrored these regimen-specific serum profiles. Brain 7Li MRI signal intensity was higher in white matter than grey matter in both regimens and brain-to-serum ratios indicated more rapid equilibration in grey matter compared with cerebrospinal fluid and white matter. Brain lithium concentrations followed serum concentrations closely across the day but aligned between regimens at the standard 12-h post-dose sampling timepoint. These findings directly inform ongoing discussions about the applicability of a common reference range across regimens. The difference in brain and serum profiles of lithium with once-daily and twice-daily dosing might inform regimen selection and therapeutic monitoring strategies in clinical practice. Baszucki Brain Research Foundation and Deutsche Forschungsgemeinschaft (German Research Foundation).

Polymyxin B (PMB) is an antibiotic used to treat severe infections, but its use is associated with nephrotoxicity. Identifying risk factors for PMB-associated nephrotoxicity is essential for improving patient outcomes. This study aimed to identify risk factors for PMB-associated nephrotoxicity and evaluate their impact on renal function recovery. A retrospective analysis was conducted on patients who received PMB therapy at the Second Xiangya Hospital, Central South University, from August 2022 to August 2023. Univariable and multivariable logistic regression analyses were performed to assess risk factors for acute kidney injury (AKI) and factors influencing renal recovery. AKI was defined and staged according to the KDIGO criteria based on serum creatinine changes. Of the 325 patients treated with intravenous PMB, 112 (34.5%) developed AKI. Independent risk factors for PMB-associated AKI included use of vancomycin (RR=1.398, P=0.027), use of aminoglycosides (RR=2.047, P=0.018), use of amphotericin B (RR=1.834, P=0.006), use of furosemide (>20 mg/day) (RR=1.495, P=0.004), and a higher loading dose of PMB (RR=1.004, P=0.004). The median time to AKI onset was 7 days (IQR: 3-12). Renal recovery occurred in 41.1% of AKI patients, and the use of vasoactive agents was negatively associated with recovery, likely reflecting underlying hemodynamic instability rather than a direct nephrotoxic effect (OR=0.298, P=0.013). Key risk factors for PMB-associated AKI included the use of vancomycin, aminoglycosides, amphotericin B, high-dose furosemide (>20 mg/day), and the loading dose of PMB.&#xa0;Close monitoring of serum creatinine within the first week of PMB therapy is crucial for improving outcomes.&#xa0;Clinicians should minimize concurrent nephrotoxic agents where feasible and prioritizing rapid hemodynamic stabilization in patients with shock to optimize renal recovery.