Endothelial glycocalyx lines every blood vessel throughout the body, and has key roles in vascular biology, including vascular permeability and inflammation. Accumulated evidence from the past 15 years shows that the glomerular endothelial glycocalyx is a vital component of the glomerular filtration barrier, which limits the filtration of macromolecules such as albumin. However, the contribution of endothelial glycocalyx to the pathogenesis of proteinuria and its potential as a therapeutic target have not been fully explored. Experimental disruption of the glomerular endothelial glycocalyx increases glomerular albumin permeability, and loss of endothelial glycocalyx integrity has been observed in diseases that compromise the glomerular filtration barrier, including diabetic kidney disease and other glomerular diseases. Strategies to protect the endothelial glycocalyx have successfully reduced proteinuria in animal models of proteinuric kidney disease, indicating that therapeutic modification of the endothelial glycocalyx can achieve important functional benefits. Moreover, drugs with recognized roles in renal medicine (for example, mineralocorticoid receptor antagonists) reduce albuminuria at least in part by protecting theendothelial glycocalyx. Recognition of the glomerular endothelial glycocalyx as a therapeutic target could aid the development of drugs that specifically target theendothelial glycocalyx with potentially greater benefits than those that do so incidentally.

Emerging therapeutic strategies for acute kidney injury: a new dawn in renal medicine

Abstract Background and Aims Chronic kidney disease, particularly for those treated by haemodialysis (HD), contributes a heavy burden of increased mortality, multi-symptomatic morbidity and decreased quality of life. Intervention trials in HD therapy do not typically adhere to an agreed portfolio of defined outcomes, the relative importance of which may differ between different stakeholders (patients, carers, health care professionals (HCPs). The international Standardised Outcomes in Nephrology (SONG) initiative is a global project aiming to identify a standardised core outcome set to be reported in future clinical trials in kidney disease[1]. To date, there has not been a focused local investigation in Ireland of the proposed tiered system of outcomes. This study aims to determine the relative priorities accorded by Irish HD patients and HCPs to outcome measures in HD. It also aims to interrogate the degree of concordance with the 3-tiered hierarchical clusters of 15 biomedical and 19 patient related outcome measures (PROMs) identified, and previously tier-allocated, by the international SONG-HD group[2]. Method 144 participants (109 patients, 35 HCPs) from the Department of Renal Medicine, Cork University Hospital completed the survey, using convenience sampling techniques. Participants were aged ≥18 years and had ≥3 months experience in/of HD. Participants completed a survey listing the 34 outcome measures proposed by SONG-HD. Each outcome was ranked using a 9-point Likert scale. For each outcome mean, median and proportion rating as 7–9 was calculated. Outcomes were considered ‘critically important’ (Tier 1) if they met 2 of the following criteria: median score ≥8, mean score ≥7.5, and proportion rating the outcome as 7–9 ≥75%. Results 27 (79%) of outcomes were accorded the same Tier allocation by SONG-HD and by our group. Cardiovascular Disease, Vascular Access, Mortality and Fatigue were ranked as ‘critically important’ (Tier 1) by SONG-HD. The first two of these were also ranked in Tier 1 by our group, as was Blood Pressure. Mortality and Fatigue, by contrast, were ranked in Tier 2. For Tiers 2 and 3, our group ranked Ability to Work, Pain and Washed Out after Dialysis lower than did SONG-HD; Sleep was ranked higher. HD patients ranked the importance of six outcomes significantly higher (mean difference, 95% CI) than did HCPs. Ability to Travel (+2.2, 1.5, 2.9) was the most pronounced, followed by Mobility, Impact on Family/Friends, Drops in Blood Pressure, Sleep and Fatigue. HCP ranked 11 outcomes significantly higher than did patients. Dialysis Adequacy (+3.2, 2.3, 4.1), Potassium (+3.0, 2.1, 3.9], Hospitalisation (+2.7, 1.9, 3.5] and Anxiety/Stress (+2.2; (1.4, 2.9) being most prominent followed by Nausea/Vomiting, Restless Leg Syndrome, Pain, Cramps, Anaemia, Mortality and Infection/Immunity. For the Top 10 ranked outcomes, PROMs accounted for 7/10 in HD patients and 1/10 in HCPs. Conclusion The tiered hierarchy of outcomes proposed by SONG-HD aligns strongly with that generated by an Irish cohort of HD patients and nephrology HCPs. As with SONG-HD findings, patients generally prioritised PROMs over biomedical parameters, while HCPs prioritised the latter. This reinforces a mutual appreciation for the need to include both domains as core outcome measurements in future clinical trials in haemodialysis.

Abstract Background and Aims Peritoneal dialysis (PD) offers greater flexibility, a better quality of life, a lower risk of infections, better preservation of residual kidney function, and lower healthcare costs in comparison to in-centre hemodialysis (HD). Despite the known advantages associated with PD, over 35% of patients transition from PD to HD annually in the UK. The most common reasons for PD dropouts include mechanical failure, infection, inadequate clearance and death whilst receiving PD. We conducted a retrospective observational study at our centre investigating the characteristics of patients who dropped out of their PD regimens and the reasons for PD dropout over a 3-year follow-up period. Method There were 114 adult patients under the care of the renal medicine department at Northern Care Alliance NHS Foundation Trust who dropped out of PD between January 2022 and September 2024. Specific patient characteristics and the reasons for PD dropout were evaluated over this time period. Data collated include patient demographic characteristics, Charlson comorbidity index (CCI) scores prior to PD catheter insertion, issues identified during home visit assessments prior to PD initiation, and attendance to dialysis education visits. PD catheter-related information including the catheter insertion method (i.e. medical vs surgical insertion), whether an elective outpatient vs inpatient procedure was received, and the occurrence of acute complications post PD catheter insertion (e.g. catheter malposition) were recorded. In this study, continuous variables are expressed as median (interquartile range) with p values calculated via the Kruskal–Wallis H test or Mann–Whitney U test. Categorical variables are expressed as numbers (percentage) with p values calculated by the Chi-squared test. Comparisons were made between PD dropouts after catheter removal due to ’undesirable cause’ (UC) (i.e. infection and/or PD catheter dysfunction) versus ’natural causes’ (NC) (i.e. death, receipt of kidney transplantation or patient choice). Logistic regression statistics were applied to represent the findings of this comparative analysis. Results There were 43 patients in 2022, 42 patients in 2023, and 29 patients in 2024 who dropped out of PD. The cohort’s median age was 55.3 years, in which patients were predominantly male (69%) and of White ethnicity (81.3%). Patient characteristics relating to the pre-PD assessments—including CCI scores, issues identified during home visit assessments prior to PD initiation, and attendance to dialysis education visits—were similar between 2022 and 2024. The rates of medical PD catheter insertion (81.4% in 2022 vs 81% in 2023 vs 75.9% in 2024, P = 0.826) and elective outpatient catheter insertion (70% in 2022 vs 76.2% in 2023 vs 79.3% in 2024, P = 0.630) were similar across the 3 years. No differences were observed in terms of peri-operative characteristics relating to PD catheter insertion between 2022 and 2024, including constipation issues post-procedure, pre-procedure CCI scores or the number of medications received. There were an increased proportion of patients who dropped out of PD due to availability for kidney transplantation between 2022 and 2024 (21% in 2022 vs 28.6% in 2023 vs 48% in 2024, P = 0.005). Nevertheless, PD dropouts because of UC appeared similar over the years (35% in 2022 vs 43% in 2023 vs 31% in 2024, P = 0.564). Of the 114 patients, 42 had PD drop off due to UC and 72 had a NC. A comparison between the two groups showed a higher proportion of patients who had an emergency PD catheter insertion as inpatients eventually dropped off PD due to an UC (40.5% UC vs 16.7% NC, P = 0.005) (Table 1). Binary logistic regression analysis noted emergency inpatient catheter insertion as a significant predictor of UC for PD removal/drop out (OR 3.40, 95% CI 1.41–8.14, P = 0.006). Conclusion Our study highlights emergency inpatient PD catheter insertion as a risk factor that predicts for future ’undesirable‘ PD dropout. This study’s findings strengthen the stance that meticulous pre-procedure assessments in advanced kidney care services and dialysis preparation clinics are warranted to prevent ’undesirable‘ PD dropouts.

Introduction: Albeit comprising a small portion of the hospital population, persistent high utilisers (PHUs) contribute disproportionately to healthcare expenditures. Amid rising healthcare costs and an ageing population, this study examines factors associated with PHUs among residents in eastern Singapore. Method: This is a retrospective study of eligible patients at Changi General Hospital in Singapore between 1 January 2020 and 31 December 2022. The study included Singapore citizens who utilised any services offered by CGH. Patients were classified as PHUs if their annual healthcare expenditure exceeded SGD3700 for 3 consecutive years. Demographics, healthcare utilisation patterns and clinical profiles were compared, and multivariable analyses were conducted to identify factors associated with PHUs. Results: There were 267,838 eligible patients identified, with 5316 (2%) classified as PHUs. PHUs accounted for 18.4% of the total healthcare expenditure, with the highest costs attributed to inpatient services, followed by outpatient services. PHUs were more likely to be older, male, non-Chinese and of lower socioeconomic status. Conditions with the strongest association with PHUs were mental health disorders, chronic obstructive pulmonary disease, osteoporosis, asthma and renal diseases. Inpatient discharges from renal medicine, psychological medicine and general/geriatric medicine wards had the strongest association with PHUs. Utilisation of allied health services had the highest odds of being a PHU in outpatient care. Conclusion: This study identified key factors associated with PHUs, providing invaluable insights into the planning of population health services within the hospital’s geographical region. Targeted service development and process improvements of medical care can help mitigate persistent high utilisation.

Systematic reviews have become an essential foundation for evidence-based decision-making in nephrology, a specialty characterized by rapidly evolving therapeutic options, complex disease mechanisms, and diverse patient populations. High-quality systematic reviews offer clinicians, researchers, and policymakers a reliable synthesis of available literature, guiding clinical practice standards and shaping future research priorities. Producing robust systematic reviews requires a clear research question, rigorous methodology, transparent reporting, and critical appraisal of evidence. However, nephrology presents unique challenges for reviewers, including heterogeneity in patient characteristics, variability in disease classifications, inconsistent outcome definitions, and limited high-quality randomized controlled trials. This review provides an in-depth discussion of the essential elements involved in developing high-quality systematic reviews in nephrology, covering protocol development, literature search strategies, data extraction, bias assessment, evidence synthesis, and reporting standards. It also highlights common methodological pitfalls and explores how advancements such as automation tools, standardized registries, and improved statistical techniques can strengthen the quality of evidence synthesis in nephrology. The goal is to support researchers and clinicians in producing reviews that are methodologically sound, clinically meaningful, and capable of informing best practices in renal medicine.

BackgroundNeurofilament light chain (NfL) has emerged as a sensitive biomarker for neuronal injury across various neurological disorders. Recent studies suggest that its elevated serum levels are also associated with kidney disease, including chronic kidney disease, acute kidney injury, and diabetic nephropathy.Main bodyThis paper explores the potential of NfL as a diagnostic and prognostic tool in renal medicine, evaluates its clinical implications, and outlines future research directions. We reviewed recent literature on NfL dynamics, the neuro-renal axis, and the role of the neurofilament light chain in kidney disease across PubMed, Embase, Web of Science, Google Scholar, Cochrane Library, and Scopus. We then analyzed the current evidence on the diagnostic and prognostic value of serum NfL levels in various renal conditions and discussed potential therapeutic implications. Elevated serum NfL levels are associated with several kidney diseases, including chronic kidney disease, acute kidney disease, and diabetic nephropathy. Its increased serum level is related to impaired renal clearance, hormonal changes, and inflammatory processes. NfL levels correlate with traditional renal biomarkers, such as serum creatinine and estimated glomerular filtration rate, and offer additional insights into disease progression and patient prognosis.ConclusionNfL holds promise as a novel biomarker for kidney disease, offering potential advantages for early detection, risk stratification, and monitoring disease progression. Future studies should focus on longitudinal and mechanistic studies to elucidate the pathways linking NfL and kidney function, and clinical trials should be conducted to evaluate the effectiveness of NfL-targeted interventions.

Central venous dialysis catheters are the first line of choice to start on hemodialysis. They could be a bridge to establish another dialysis access. Dialysis catheters are essential of two types: temporary (non-tunnelled) and permanent (tunnelled). Insertion of a dialysis catheter is a ubiquitous procedure in renal medicine. One of the rare but serious complications is vascular erosion. We report on a case of a 68-year-old female patient with acute kidney injury who needed emergency hemodialysis. A permanent dialysis catheter was inserted into her right subclavian vein. There was not good flow in the dialysis catheter’s afferent and efferent lumens. The nephrologist performed a contrast chest roentgenoscopy, which showed that the dialysis catheter followed an abnormal course by passing into the ascending aorta. Emergency surgical extraction of the dialysis catheter was initiated using median sternotomy and supraclavicular incision to identify the entry point of the catheter into the subclavian artery. Due to the dissection of the subclavian artery, we performed an extra-anatomic aorto-subclavian bypass with a saphenous vein graft. The dialysis catheter was inserted through open access into the right subclavian vein.

Communication Strategizing Cardiovascular Management in Diabetic Patients: Insights and Advancements from the 2023 ESC Guidelines for the Management of Cardiovascular Disease in Patients with Diabetes Hongyuan Zhang 1, Darren Green 2 and Yanrong Liu 1,3,* 1 Michael Smith Building, Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M20 4BX, UK 2 Vascular Research Group, Department of Renal Medicine, Salford Royal NHS Foundation Trust, Stott Lane, Salford M6 8HD, UK. 3 The Department of Cardiology, the 1st Affiliated Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China * Correspondence: yanrong.liu@manchester.ac.uk Received: 12 October 2023; Revised: 26 November 2023; Accepted: 27 November 2023; Published: 13 February 2025 Abstract: Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in individuals with type 2 diabetes mellitus (T2DM). The 2023 European Society of Cardiology (ESC) guidelines represent a significant advancement in the management of CVD in T2DM, building on the 2019 recommendations. Unlike previous iterations, the updated guidelines focus exclusively on T2DM, excluding pre-diabetes due to limited evidence directly linking it to cardiovascular risk. A notable addition is the SCORE2-Diabetes algorithm, which integrates diabetes-specific factors with traditional risk determinants to estimate the 10-year cardiovascular risk. This personalized risk stratification tool underscores the importance of early identification and management of key contributors, such as hyperglycemia and insulin resistance. The guidelines advocate for a multidisciplinary approach, emphasizing collaboration among diabetes, cardiovascular, and chronic kidney disease specialists to address the complex interplay of these conditions effectively. Moreover, the 2023 ESC guidelines highlight the necessity of individualized treatment strategies to reduce cardiovascular complications in T2DM. By reflecting the heterogeneity of diabetic populations and the evolving pharmacological landscape, these recommendations aim to optimize cardiovascular outcomes. This comprehensive update marks a critical step toward reducing the burden of CVD and improving the quality of life for patients with diabetes.

Ferroptosis, a novel concept of programmed cell death proposed in 2012, in kidney disease, has garnered significant attention based on evidence of abnormal iron deposition and lipid peroxidation damage in the kidney. Our study aim to examine the trends and future research directions in the field of ferroptosis in kidney disease, so as to further explore the target or treatment strategy for clinical treatment of kidney disease. A thorough survey using the Web of Science Core Collection, focusing on literature published between 2012 and 2024 examining the interaction between kidney disease and ferroptosis was conducted. VOSviewer, CiteSpace, and Biblioshiny were used for in-depth scientometric and visualized analyses. From 2012 to 2024, a total of 2,244 articles met the inclusion criteria for final analysis. The number of annual publications in this area of study showed a steady pattern at the beginning of the decade. The top 3 journals with the highest publication output were Renal Failure, Oxidative Medicine And Cellular Longevity, and Biomedicine & Pharmacotherapy. China and the United States had the highest number of publications. Central South University and Guangzhou Medical University as the most active and influential institutions. Documents and citation analysis suggested that Andreas Linkermann, Jolanta Malyszko, and Alberto Ortiz are active researchers, and the research by Scott J. Dixon and Jose Pedro Friedmann Angeli, as the most cited article, are more important drivers in the development of the field. Keywords associated with glutathione, lipid peroxidation, and nitric oxide had high frequency in the early studies. In recent years, however, there has been a shift towards biomarkers, inflammation and necrosis, which indicate current and future research directions in this area. The global landscape of the ferroptosis research in kidney disease from 2012 to 2024 was presented. Basic research and mechanism exploration for renal fibrosis and chronic kidney disease may be a hot spot in the future.

BackgroundHealthcare contributes significantly to global carbon dioxide equivalent emissions, with kidney care contributing disproportionately to this. Renal medicine was one of the first specialities to actively develop a "green" community. This paper is a retrospective review of a series of comprehensive and impactful green initiatives across various aspects of kidney care delivery in a kidney unit from 2007 to 2024.MethodsThe interventions include using e-consultations and virtual clinics, online priming of haemodialysis machines, upgrade of water treatment systems, centralised dialysate acid delivery, use of 1:44 acid concentrate, use of dialysate autoflow function, installation of energy-efficient lighting, and incremental and decremental dialysis practices. Financial and environmental saving estimates for the haemodialysis-related interventions were calculated based on a 40-bed haemodialysis unit. A hybrid carbon footprinting approach was utilised to calculate the greenhouse gas and financial savings.ResultsThe cumulative estimated greenhouse gas and financial savings exceed 1,000 tonnes of carbon dioxide equivalent and £2.8 million, respectively. Among sustainable initiatives in haemodialysis, online priming, use of central acid delivery, dialysate autoflow facility, and incremental and decremental haemodialysis showed the most significant savings.ConclusionsInterventions to facilitate environmental sustainability may require upfront funding and staff investment of time and effort, but the dividend is long-term environmental protection, financial savings, enhanced quality of care, greater staff satisfaction and enhanced service resilience. Sharing these experiences may help other institutions to integrate green initiatives into everyday service planning.Graphical abstractSupplementary InformationThe online version contains supplementary material available at 10.1007/s40620-025-02354-x.

Background: This timely update in nephrology is based on the proceedings of The American Society of Nephrology (ASN) Kidney Week that was held in San Diego, California between October 23, and October 27, 2024. The meeting had 4 sessions dedicated to high-impact clinical trials and late-breaking science. Methods: This update will present 12 studies including 10 clinical trials. Each trial was published in a major peer reviewed journal on the day of the presentation. This will provide the reader with the opportunity to refer to the published study in its entirety. IgA nephropathy (IgAN) management was a major theme in the meeting, and 5 clinical Trials on that topic are included. Other topics included in this review cover kidney transplantation, sodium-glucose cotransporter 2 (SGLT2) inhibitors in chronic kidney disease (CKD), acute kidney injury (AKI), the role of APOL1 risk variants, semaglutide in non-diabetic CKD patients, potassium binders in hemodialysis patients, and blood pressure management strategies in non-cardiac surgery patients. Results: For each study a brief background will be provided, followed by the results of each individual study, then a conclusion and a statement about the study limitations. Conclusions: This update is a window into recent progress in renal medicine. Advances in basic science are propelling novel medications in the field of nephrology with the potential of impacting direct patient care. The excitement in the renal community is palpable.

To analyze the independent associations of the Kidney Failure Risk Equation (KFRE) and neutrophil gelatinase-associated lipocalin (NGAL) with end-stage renal disease (ESRD) among patients with chronic kidney disease (CKD) stages 3-5 in China and evaluate their predictive values for ESRD. A total of 716 patients with CKD stages 3-5 at the time of the initial renal medicine referral were retrospectively enrolled, and the study outcome was the observed incidence of ESRD at 2 years after the initial referral. Baseline characteristics were collected, and relevant laboratory indexes, including neutrophil gelatinase-associated lipocalin (NGAL), were detected. The binary logistic regression model was used to analyze the independent associations, and the receiver operating characteristic (ROC) curve was used to assess the predictive values. The 2-year incidence of ESRD was 20.5% (147/716). The 4-variable KFRE, 8-variable KFRE and NGAL were independently associated with ESRD after adjusting for potential confounding factors. The AUCs of the 4-variable KFRE, 8-variable KFRE and NGAL for predicting ESRD among patients with CKD stages 3-5 were 0.711 [standard error (SE): 0.026, 95% confidence interval (CI): 0.662-0.761], 0.725 (SE: 0.025, 95% CI: 0.677-0.774) and 0.736 (SE: 0.024, 95% CI: 0.686-0.785), respectively. The AUC of the 4-variable KFRE plus NGAL was significantly higher than those of the 4-variable KFRE and NGAL alone (0.900 vs 0.711, Z = 6.297, P < 0.001; 0.900 vs 0.736, Z = 5.795, P < 0.001), and the AUC of the 8-variable KFRE plus NGAL was also significantly higher than those of the 8-variable KFRE and NGAL alone (0.911 vs 0.725, Z = 6.491, P < 0.001; 0.911 vs 0.736, Z = 6.298, P < 0.001). The KFRE was able to independently predict progression of CKD stage 3-5 to ESRD in Chinese population. The addition of NGAL to the KFRE was able to elevate the predictive value when applied in predicting 2-year ESRD.

The kidney, an essential organ of the human body, can suffer pathological damage that can potentially have serious adverse consequences on the human body and even affect life. Furthermore, the majority of kidney-induced illnesses are frequently not readily identifiable in their early stages. Once they have progressed to a more advanced stage, they impact the individual's quality of life and burden the family and broader society. In recent years, to solve this challenge well, the application of machine learning techniques in renal medicine has received much attention from researchers, and many results have been achieved in disease diagnosis and prediction. Nevertheless, studies that have conducted a comprehensive bibliometric analysis of the field have yet to be identified. This study employs bibliometric and visualization analyses to assess the progress of the application of machine learning in the renal field and to explore research trends and hotspots in the field. A search was conducted using the Web of Science Core Collection database, which yielded articles and review articles published from the database's inception to May 12, 2024. The data extracted from these articles and review articles were then analyzed. A bibliometric and visualization analysis was conducted using the VOSviewer, CiteSpace, and Bibliometric (R-Tool of R-Studio) software. 2,358 papers were retrieved and analyzed for this topic. From 2013 to 2024, the number of publications and the frequency of citations in the relevant research areas have exhibited a consistent and notable increase annually. The data set comprises 3734 institutions in 91 countries and territories, with 799 journals publishing the results. The total number of authors contributing to the data set is 14,396. China and the United States have the highest number of published papers, with 721 and 525 papers, respectively. Harvard University and the University of California System exert the most significant influence at the institutional level. Regarding authors, Cheungpasitporn, Wisit, and Thongprayoon Charat of the Mayo Clinic organization were the most prolific researchers, with 23 publications each. It is noteworthy that researcher Breiman I had the highest co-citation frequency. The journal with the most published papers was "Scientific Reports," while "PLoS One" had the highest co-citation frequency. In this field of machine learning applied to renal medicine, the article "A Clinically Applicable Approach to Continuous Prediction of Future Acute Kidney Injury" by Tomasev N et al., published in NATURE in 2019, emerged as the most influential article with the highest co-citation frequency. A keyword and reference co-occurrence analysis reveals that current research trends and frontiers in nephrology are the management of patients with renal disease, prediction and diagnosis of renal disease, imaging of renal disease, and development of personalized treatment plans for patients with renal disease. "Acute kidney injury," "chronic kidney disease," and "kidney tumors" are the most discussed diseases in medical research. The field of renal medicine is witnessing a surge in the application of machine learning. On one hand, this study offers a novel perspective on applying machine learning techniques to kidney-related diseases based on bibliometric analysis. This analysis provides a comprehensive overview of the current status and emerging research areas in the field, as well as future trends and frontiers. Conversely, this study furnishes data on collaboration and exchange between countries, regions, institutions, journals, authors, keywords, and reference co-citations. This information can facilitate the advancement of future research endeavors, which aim to enhance interdisciplinary collaboration, optimize data sharing and quality, and further advance the application of machine learning in the renal field.

Kidneys play a crucial role in maintaining homeostasis within the body, and this function is intricately linked to the vascular structures within them. For vascular cells in the kidney to mature and function effectively, a well-coordinated spatial alignment between the nephrons and complex network of blood vessels is essential. This arrangement ensures efficient blood filtration and regulation of the electrolyte balance, blood pressure, and fluid levels. Additionally, the kidneys are vital in regulating the acid-base balance and producing hormones involved in erythropoiesis and blood pressure control. This article focuses on the vascular development of the kidneys, summarizing the current understanding of the origin and formation of the renal vasculature, and the key molecules involved. A comprehensive review of existing studies has been conducted to elucidate the cellular and molecular mechanisms governing renal vascular development. Specific molecules play a critical role in the development of renal vasculature, contributing to the spatial alignment between nephrons and blood vessels. By elucidating the cellular and molecular mechanisms involved in renal vascular development, this study aims to advance renal regenerative medicine and offer potential avenues for therapeutic interventions in kidney disease.

Noninvasive fluorescence imaging of renal function is a valuable technique for understanding kidney disease progression and the development of renal medicine. This technique requires sensitive imaging probes for reporting renal dysfunction accurately at early stage. Herein, a molecularly engineered imaging probe (800CW-PEG45-COOH) was synthesized by simply PEGylating conventional near-infrared fluorophore IRDye800CW with NH2-PEG45-COOH (molecular weight ∼2100 Da) for early detection and staging of renal dysfunction through noninvasive real-time kidney imaging. 800CW-PEG45-COOH not only cleared through the kidney efficiently (>90% injection dosage at 24 h postinjection) but was also found to be freely filtered by glomeruli without renal tubular reabsorption and secretion. Despite this simple construction strategy, the transport of 800CW-PEG45-COOH within the kidneys was extremely sensitive to the alteration of the glomerular filtration rate (GFR), which enabled it to detect renal dysfunction much earlier than commonly used serum biomarkers and stage kidney function impairments (mild vs severe dysfunction) via imaging-based kidney clearance kinetics. This work not only provides a promising optical imaging probe for the noninvasive evaluation of kidney function but also highlights the utility of PEGylation in enhancing the performance of conventional organic dyes in biomedical applications.

Abstract Background Written consent obtained for case report. A 59-year-old male who was 3-months post-EVAR repair under immunosuppression for kidney transplantation and anti-retroviral HIV treatment presented to ED in 2017 with abdominal pain and fever. CTAP revealed pyelonephritis in renal allograft. Blood cultures were positive for staphylococcus epidermidis. PETCT showed high-intensity uptake around endograft. Urgent explant of endograft and insitu biological aorto-biiliac graft reconstruction with bench prepared bilateral long saphenous veins were performed. Results The predicted challenges were locating source of infection, immunosuppressed state, and allograft preservation. Dacron graft was used as temporary perfusion shunt (left axillary artery to right superficial femoral artery) for renal allograft on right external iliac vessels. Endograft was removed via rooftop incision with visceral rotation. Supra-celiac and supra-superior mesenteric artery clamping times were 15 and 35 minutes. The source of infection was from infected appendix proximal to graft with erosion of right external iliac artery resulting in appendectomy in the same operation. Following 12-weeks of OPAT antibiotic-therapy, repeat PETCT revealed low-grade uptake around aortic graft and inflammatory markers were back to baseline. At 6 years in 2023, patient remains clinically well with ∼20% allograft function. Maintaining kidney allograft perfusion in the setting of elective non-infected aortic graft explant was previously reported, but with ENROUTE system (Rasheed et al., 2018). Conclusions The satisfactory long-term outcomes discussed here demonstrated with MDT planning involving vascular surgery, infectious diseases, renal medicine and patient, explant of infected graft with insitu biological graft reconstruction in renal transplant patients presenting with complex aortic-graft infection is feasible.

Renal physiology underpins renal nuclear medicine, both academic and clinical. Clearance, an important concept in renal physiology, comprises tissue uptake rate of tracer (tissue clearance), disappearance rate from plasma (plasma clearance), appearance rate in urine (urinary clearance) and disappearance rate from tissue. In clinical research, steady-state plasma clearances of para-amino-hippurate and inulin have been widely used to measure renal blood flow (RBF) and glomerular filtration rate (GFR), respectively. Routinely, GFR is measured at non-steady state as plasma clearance of a filtration agent, such as technetium-99m diethylenetriaminepentaacetic acid. Scaled to three-dimensional whole body metrics rather than body surface area, GFR in women is higher than in men but declines faster with age. Age-related decline is predominantly from nephron loss. Tubular function determines parenchymal transit time, which is important in renography, and the route of uptake of technetium-99m dimercaptosuccinic acid, which is via filtration. Resistance to flow is defined according to the pressure-flow relationship but in renography, only transit time can be measured, which, being equal to urine flow divided by collecting system volume, introduces further uncertainty because the volume is also unmeasurable. Tubuloglomerular feedback governs RBF and GFR, is regulated by the macula densa, mediated by adenosine and renin, and can be manipulated with proximal tubular sodium-glucose cotransporter-2 inhibitors. Other determinants of renal haemodynamics include prostaglandins, nitric oxide and dopamine, while protein meal and amino acid infusion are used to measure renal functional reserve. In conclusion, for measuring renal responses to exogenous agents, steady-state para-amino-hippurate and inulin clearances should be replaced with rubidium-82 and gallium-68 EDTA for measuring RBF and GFR.

To reaffirm the value of a joint obstetric and renal clinic on obstetric outcomes in patients with high-risk pregnancies due to chronic kidney disease (CKD). This was a retrospective cohort study of patients who attended the clinic between 2005 and December 2021. The hospital is a regional tertiary unit for renal medicine and a maternal medicine hub. The data included all women with pre-existing renal conditions who were cared for in a dedicated renal and obstetric clinic. Datasets were extracted from hospital notes, the renal database, clinical data and maternity electronic health records. The data analyzed included pre-existing renal conditions, biochemical parameters related to the renal condition, pregnancy outcomes included miscarriages, gestation, mode of delivery, postpartum hemorrhage (PPH), loss, birth weight and neonatal admission. The results were as follows: Lupus nephritis: four term deliveries; three had pre-eclampsia; two PPH and two miscarriages. Four estimated glomerular filtration rates (eGFRs) returned to baseline levels within 12 months. With regard to IgA nephropathy there were five live births, four term deliveries, two pre-eclampsia (PE) and five cesarean sections (CS). All eGFRs returned to baseline within 12 months. With regard to patients with adult polycystic kidney disease (APKD), there were six live births, two had pre-eclampsia and there were five term vaginal deliveries. Patients with lupus nephritis, APKD, and IgA demonstrated a higher incidence of adverse pregnancy outcomes as compared with our local pregnant population. Our findings reflect those of larger studies and support the role of combined renal/obstetric clinics. More research and larger scale studies are needed into specific CKD conditions and their outcomes.

Hyperkalaemia (HK) is prevalent among patients with chronic kidney disease (CKD) and chronic heart failure, especially if they are treated with renin-angiotensin-aldosterone system inhibitors (RAASi). This study evaluated the cost-effectiveness of a newly developed anti-HK therapy, sodium zirconium cyclosilicate (SZC), to the current standard of care for treating HK in advanced CKD patients from the Singapore health system perspective. We adapted a global microsimulation model to simulate individual patients' potassium level trajectories with baseline potassium ≥5.5 mmol/L, CKD progression, changes in treatment, and other fatal and non-fatal events. Effectiveness data was derived from ZS-004 and ZS-005 trials. Model parameters were localised using CKD patients' administrative and medical records at the Singapore General Hospital Department of Renal Medicine. We estimated the lifetime cost and quality-adjusted life years (QALYs) of each HK treatment, and the incremental cost-effectiveness ratio of SZC. SZC demonstrated cost-effectiveness with an incremental cost-effectiveness ratsio of SGD 45 068 per QALY over a lifetime horizon, below the willingness-to-pay threshold of SGD 90 000 per QALY. Notably, SZC proved most cost-effective for patients with less severe CKD who were concurrently using RAASi. Sensitivity analyses confirmed the robustness of the findings, accounting for alternative parameter values and statistical uncertainty. This study establishes the cost-effectiveness of SZC as a treatment for HK, highlighting its potential to mitigate the risk of hyperkalaemia and optimise RAASi therapy. These findings emphasise the value of integrating SZC into the Singapore health system for improved patient outcomes and resource allocation.