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Background The Agenda for Sustainable Development agenda prioritizes access to care for non-communicable diseases, including chronic kidney disease (CKD), and sustainable cities and communities. City-level health may impact local research capacity and subsequent participation in randomized controlled trials (RCTs). We identified city-level barriers to CKD RCT participation in the cities from the Global Observatory of Healthy and Sustainable Cities (GOHSC). Methods We conducted a cross-sectional study of 214 drug CKD RCTs (2003–2023) with participants spanning 146 GOHSC sites. We queried open datasets to retrieve relevant financial, urban, healthcare, and nephrology-related indicators. We designed a CKD research capacity scale incorporating six variables: population-weighted RCTs, sites per sqkm, funding, site span, facility type, RCTs per site. We classified research capacity as absent (0–1 points), insufficient (2–4), fair (6–7), good (7–8), or excellent (9–10) and compared indicators between research capacity categories. Results Of the included cities, Odense had the highest population-weighted RCT count (7.01 RCTs per 100,000 population), and Mexico City had the lowest (0.06 RCTs per 100,000 population). Cities with good or excellent research capacity had higher health expenditures, nephrologists, and dialysis centers per million population than cities with absent or insufficient research capacity . In cities with good or excellent research capacity , the most prevalent type of insurance coverage for CKD was public, whereas mixed financing was the most frequent type in cities with absent or insufficient research capacity . Among the identified non-traditional barriers to CKD RCT participation, daily living score, access to public transport, access to open spaces, and access to a fresh food market were higher in cities with good or excellent research capacity , compared to those with lower research capacity scores. Conclusions We found differences in CKD research capacity across the cities included in the GOHSC Study Collaboration, which may be affected by financial, socio-demographic, healthcare, and nephrology-related barriers. Local, regional, and international initiatives should address distinctive local variations to enhance CKD research capacity. Clinical trial number Not applicable

Systemic lupus erythematosus (SLE) frequently presents joint pain and stiffness, yet clinicians lack an objective, rapid method to quantify joint inflammation at the point of care. We introduce the Lupus Optical Tomography Imaging System (LOTIS), a wearable near-infrared (NIR) device that performs real-time three-dimensional tomographic imaging of hemodynamic changes in finger joints. LOTIS was developed to address key limitations of our earlier Flexible Optical Imaging System (FOIS), including mechanical fragility, high noise levels, single-joint acquisition, and slow reconstruction times. The new system integrates modular, mechanically robust optical patches with on-sensor digitization and a computationally efficient, non-iterative multispectral reconstruction algorithm to produce frame-by-frame maps of hemoglobin concentration. In a preliminary study using a standardized venous-occlusion protocol, LOTIS differentiated SLE-affected joints from those of healthy controls. Diseased joints exhibited blunted and spatially diffuse hemodynamic responses, whereas healthy joints showed localized and robust changes. These results demonstrate that LOTIS provides an operator-independent, patient-friendly method for quantifying joint-specific hemodynamic changes in real time, offering strong potential as a clinical tool for objective assessment and longitudinal monitoring of lupus arthritis.

ObjectiveWe performed a scoping review of randomised clinical trials (RCTs) assessing pharmacological therapies for the initial management of lupus nephritis (LN), focusing on study design, included populations and outcome definitions, to assess the generalisability of their results and identify gaps in the evidence.MethodsRCTs evaluating pharmacological interventions for the initial therapy of LN published between 2000 and 2024 were evaluated. Extracted variables included study design, selection criteria, outcome definitions, populations recruited and clinical characteristics of participants. Each study arm was included as intervention and segregated into guideline-recommended regimens (cyclophosphamide (CYC), mycophenolic acid analogues (MPAAs), calcineurin inhibitors and belimumab) or other regimens. Data were analysed by descriptive statistics, and Fragility Index (FI) was estimated to assess robustness of studies.ResultsWe included 124 intervention arms within 61 RCT, involving 7058 participants. Seventy-nine arms (63.7%) corresponded to guideline-recommended therapies: 33 (26.6%) MPAA, 28 (22.6%) NIH-CYC and 7 (5.6%) triple-drug therapies. While 100% of triple-drug therapies RCT were multinational, only 7.1% of NIH-CYC and 0% of tacrolimus RCTs were conducted in more than one country. Only 9 (14.8%) had follow-up ≥24 months. Ten (16.4%) RCTs exclusively included participants with severe or refractory LN. Only 29 (47.5%) reported serious adverse events, and few described patient-reported outcomes. Black and other race participants were under-represented, as well as participants from Middle East, North Africa, and the sub-Saharan African region. Response was variably defined and assessed at different intervals. Robustness of RCTs evaluating double-drug guideline-recommended therapies were mostly low, with FI ranging from 1 to 3.ConclusionsConsidering new recommendations for the management of LN, we call for broader inclusion of under-represented populations and homogenisation of study design. This study provides the rationale for evaluating unexplored treatment comparisons and conducting research on newer interventions in clinical settings where evidence is currently lacking.

Background Prognostication in glomerulonephritis with severe kidney function impairment is critical for evaluating the benefit-to-risk ratio of immunosuppression. We hypothesized that the urine biomarker epidermal growth factor (EGF) could have good discrimination power to identify subjects who might ultimately recover kidney function. Methods We included 82 subjects with glomerulonephritis and severe kidney function impairment at admission (estimated glomerular filtration rate [eGFR] ≤ 30 mL/min/1.73m 2 ): 58 with lupus nephritis (LN) and 24 with ANCA-associated vasculitis (AAV). Thirty-five subjects required kidney replacement therapy (KRT) at presentation. Urine epidermal growth factor was measured and corrected by urine creatinine (uEGF/Cr) and the population was analyzed by uEGF/Cr tertiles. The primary outcome was time to recovery of eGFR ≥ 30 mL/min/1.73m 2 and time to recovery of kidney function with dialysis independence in those with initial KRT. Results Forty-four (54%) participants met the primary outcome of recovery of eGFR ≥ 30 mL/min/1.73m 2 . The 6-month recovery rates were 93%, 57%, and 0% for participants in the highest, middle, and lowest uEGF/Cr tertile, respectively. Recovery of the kidney function was faster and led to a higher post-therapy eGFR in the highest uEGF/Cr tertile. In the ROC analysis, uEGF/Cr was a predictor of recovery with an area under the curve (AUC) of 0.92 (95% CI 0.87–0.98), and a cutoff of 2.60 ng/mg had 100% sensitivity to detect patients who recovered kidney function. In the subgroup of participants with initial KRT, the cut-off of uEGF/Cr of 2.0 ng/mg had 100% sensitivity to detect participants who recovered kidney function with dialysis independence by 6 months. Conclusions Urine EGF/Cr is a promising biomarker to aid in the prediction of recovery of kidney function in glomerulonephritis with severe kidney function impairment. Graphical abstract

Introduction/ObjectivesThe heterodimer exostosin-1/exostosin-2 (EXO-1/2) is a novel antigen observed in membranous nephropathy associated with systemic lupus erythematosus. This study aimed to evaluate the association between EXO-1/2 positivity in kidney biopsy and kidney outcomes.MethodsThe kidney biopsy tissue from 50 class 5 lupus nephritis (LN) and 55 mixed class 3/4 + 5 LN patients was stained for EXO-1/2. Baseline clinical and histological characteristics were compared between EXO-1/2 positive and EXO-1/2 negative patients. Time-to-event analyses were performed to compare rates of response to therapy, kidney flares, and progression to a 40% decline of the glomerular filtration rate (eGFR), doubling of serum creatinine, and kidney failure.ResultsFourteen out of 50 (28%) of class 5 and 5 out of 55 (9%) of mixed class 3/4 + 5 LN stained positive for EXO-1/2. Patients with class 5 LN and EXO-1/2 positive stain were younger, with better kidney function at presentation, and lower scarring in the kidney biopsy analysis. Over a median follow-up of 100 months, patients with positive EXO-1/2 staining had significantly lower rates of progression in the full cohort. When analyzed separately in class 5 and mixed class LN subgroups, there were significantly lower rates of progression to a 40% decline of the eGFR and non-statistically significant trends for doubling of serum creatinine and kidney failure.ConclusionEXO-1/2 is a novel antigen detected in class 5 LN and associated with a good prognosis of kidney function. The incorporation of EXO-1/2 staining in clinical practice can potentially modify the management of LN due to its prognostic implications. Key Points• Exostosin-1/exostosin-2 antigen has been found in cases of membranous nephropathy associated with autoimmune diseases such as systemic lupus erythematosus.• Exostosin-1/exostosin-2 staining in the kidney biopsy of class 5 or mixed class 3/4 + 5 lupus nephritis is associated with a good long-term prognosis of kidney function.• The incorporation of exostosin-1/exostosin-2 staining into clinical practice can potentially modify management due to its prognostic implications.