Environmental exposures are increasingly associated with kidney and cardiometabolic disease in children. This review summarizes current understanding of the potentially hazardous effects of air pollution, chemical toxicants, and heavy metal contamination on pediatric kidney health and cardiometabolic risk factors for chronic kidney disease (CKD), as well as the potentially protective effect of green space. We highlight the critical windows of childhood development, during which the kidneys may have varying susceptibility to environmental exposures. We also discuss challenges and possible solutions to adequately powered studies at the intersection of environmental health and pediatric kidney disease. Environmental exposures are both ubiquitous and modifiable. Therefore, elucidating the contribution of environmental exposures to the increasing global burden of CKD will be crucial to informing strategies for kidney disease prevention, starting in childhood. IMPACT: We summarize current evidence on the associations between environmental exposures-including air pollution, chemical toxicants, and heavy metal contamination-and pediatric kidney disease and related cardiometabolic risk factors, as well as the potentially protective effect of green space. We highlight how the impact of environmental exposures on the kidneys may vary during different critical windows of childhood development. Lastly, we discuss methodological challenges and potential solutions, such as using novel technologies and approaches to adequately power studies toward the goal of environmental intervention for chronic kidney disease (CKD) prevention.
To visualize and characterize the five most common kidney stone types based on their magnetic susceptibilities in MRI using QSM. Three water-based agar phantoms were constructed, containing a total of 53 ex vivo kidney stones of varying types and sizes. Seven different MRI multi-echo gradient echo sequences were employed at field strengths of 1.5 T and 3 T. Each acquisition was repeated three times. Susceptibility maps were reconstructed and mean susceptibility values calculated for the individual kidney stones (normalized to the agar gel). Five of the most common kidney stone types-carbonate apatite, calcium oxalate, uric acid, cystine, and struvite-were investigated with respect to different sequence parameters and field strengths. All examined kidney stones were reliably visualized as diamagnetic using QSM. Overall, good repeatability was observed for the mean susceptibility values and standard deviations of the individual kidney stones. Mean susceptibility values were highly consistent across acquisitions at both field strengths for kidney stones belonging to the five major types with diameters larger than 3.0 mm (66% of all stones). The overall mean susceptibility values (± SD) were - 1.25 ± 0.16 ppm for carbonate apatite, -1.08 ± 0.13 ppm for calcium oxalate, -0.94 ± 0.17 ppm for uric acid, -1.32 ± 0.16 ppm for cystine, and -1.28 ± 0.28 ppm for struvite. Our data indicate that QSM is well-suited to reliably visualize kidney stones and distinguish certain types among the five most common kidney stone compositions using MRI. This represents a crucial step toward in vivo imaging of suspected urolithiasis in clinical practice.
Impaired memory function is a frequent yet understudied symptom in kidney transplant recipients. In part, this knowledge gap reflects the lack of scalable, sensitive, and low-burden tools for quantifying memory function in large clinical populations. The aim of this study is to evaluate a brief, remote memory assessment and to examine memory function and its clinical correlates in kidney transplant recipients compared with healthy controls. In this cross-sectional study, we demonstrate a remote, minimally burdensome memory screener, the Seattle-Groningen Memory Assessment, which estimates a patient's speed of forgetting from paired-associate learning. Participants aged 22-86 years from a large transplant cohort completed an eight-minute online memory test. Memory performance was compared between kidney transplant recipients (n = 556) and kidney donors (n = 408). Associations with demographic, clinical, and physiological variables were examined using regression analyses. Here, we show that the memory score derived from an eight-minute session is a reliable and accurate measure of an individual's ability for long-term retention. Kidney transplant recipients show more forgetting than donors. Memory scores are sensitive to demographic factors, including age and education level, and are associated with self-reported sleep quality, fatigue, and health-related quality of life. On the physiological level, more forgetting in recipients is linked to higher monocyte, neutrophil, reticulocyte, and white blood cell counts, as well as lower ferritin and greater iron deficiency. This work highlights the potential of computational memory assessment as a minimally burdensome and reliable tool for detecting cognitive impairment in complex clinical populations. Such tools may enable scalable monitoring of cognitive health and improve the detection of subtle cognitive changes relevant for disease progression and treatment evaluation. Memory problems are commonly reported by people who receive a kidney transplant, but they are often difficult to measure with traditional cognitive or neuropsychological tests. In this study, we evaluated a brief online memory task that can be completed at home in about eight minutes. The test measures how quickly newly learned information is forgotten over time. More than 500 kidney transplant recipients and about 400 kidney donors completed the assessment. We found that transplant recipients, on average, forgot information more quickly than donors. Memory performance was also related to factors such as age, education, sleep quality, fatigue, and several blood markers linked to inflammation and iron levels. Our findings suggest that short digital memory tests may offer a practical way to monitor cognitive health in people with complex medical conditions and could support future research and clinical care.
Organ transplantation is regarded as a lifesaving procedure, and a worldwide organ shortage has catalysed the market of illegal organ trade, especially for kidneys, due to high demand and need in low and middle-income countries like Pakistan. This process is often facilitated by sophisticated, organised crime networks acting within or parallel with licit healthcare systems, exploiting the vulnerable communities. Therefore, this study aims to explore the lived experiences of individuals who illegally donate their kidneys in Pakistan, with special focus on the whole process to map the findings on the crime script framework. The present study employs a qualitative, exploratory design using a semi-structured interview guide. Detailed in-depth interviews were conducted with five kidney donors using the snowball sampling technique. A thematic analysis approach was employed to interpret data, aided by crime script analysis to analyse the systemic organisation of the illegal kidney trade. Findings were divided into three major themes: Before Donation, During Donation, and After Donation. Participants explained that they were deceived by brokers, blindfolded, taken to hidden sites, and subjected to coercive surgery. Most suffered from health decline, psychological trauma, and economic instability after donation, with no long-term benefits. The crime script framework identified the sequential pattern of exploitation by brokers and collusive medical staff. Pakistan's illegal kidney trade is operated through an intricate yet predictable cycle based on poverty and poor regulation. Targeted policy change, institutional responsibility, and donor-focused protective measures are desperately needed to end exploitation.
Acute kidney injury (AKI) is a major clinical and economic challenge worldwide. Furthermore, early identification of AKI remains difficult given that traditional biomarkers like serum creatinine and urine output (UOP) have shown to have limitations since they reflect later stages of injury and are unable to detect the initial cellular damage in AKI. This issue creates an important gap in diagnosis given that early diagnosis could prevent worsening conditions. More research is focusing on non-invasive novel biomarkers options for early and accurate detection of AKI. Urinary exosomes are emerging as a valuable source of kidney-specific biomarkers. These nanovesicles come from all nephron segments, encapsulating intracellular components and providing a unique view of kidney health. Activating transcription factor 3 (ATF3), a transcriptional regulator induced by stress conditions, has emerged as a promising candidate for early detection of AKI. Studies in animals and humans have found that ATF3 is encapsulated and released in urinary exosomes in response to kidney injury, appearing much earlier than traditional biomarkers. This review mainly examines ATF3's role as a new biomarker for the early detection of AKI, it discusses the current understanding of ATF3's molecular role in kidney disease, evaluates the evidence for its use as a biomarker, and outlines a plan for future research and development to realize its full clinical potential.
BackgroundPure membranous lupus nephritis (MLN) generally has a better kidney prognosis than proliferative lupus nephritis (PLN), but comparative data from Latin America remain limited. We evaluated clinical features and kidney outcomes of MLN in a Colombian cohort and compared them with proliferative forms.MethodsWe retrospectively included adults (≥18 years) with first biopsy-proven MLN or PLN at a Colombian tertiary center. Clinical and histopathological features were compared between pure MLN (Class V) and PLN (Class III/IV ± V). Factors associated with MLN were analyzed using logistic regression. Kidney survival was estimated using Kaplan-Meier analysis, and predictors of end-stage kidney disease (ESKD) were assessed using Cox proportional hazards regression analyses. Because death could preclude observation of ESKD, competing-risks analyses were performed using cumulative incidence functions and Fine-Gray subdistribution hazard models with death treated as a competing event.ResultsOf 371 patients, 54 (14.6%) had MLN and 317 (85.4%) had PLN. Compared with PLN, patients with MLN have lower immunological activity, better kidney function, less active urinary sediment at biopsy, and lower modified NIH activity and chronicity indices scores. In multivariable logistic regression, higher eGFR was independently associated with MLN (OR 1.02, 95% CI 1.01-1.03), whereas anti-dsDNA positivity was inversely associated (OR 0.33, 95% CI 0.15-0.71). In univariable Cox analysis, MLN was associated with lower ESKD risk (HR 0.12, 95% CI 0.03-0.48); but this association was not confirmed in multivariable analysis, which was underpowered because only 2 ESKD events occurred in the MLN group. In competing-risks analysis, MLN was associated with a lower unadjusted subdistribution hazard of ESKD (SHR 0.13, 95% CI 0.03-0.51), but not after adjustment for baseline eGFR and modified NIH indices (adjusted SHR 0.46, 95% CI 0.11-2.00). Kaplan-Meier analysis showed higher crude renal survival in MLN than in PLN.ConclusionIn this Latin American cohort, MLN exhibited a distinct baseline profile characterized by lower inflammatory activity and better-preserved kidney function at presentation. Although crude and competing-risk analyses suggested a more favorable renal trajectory for MLN, the study was underpowered to confirm an independent effect of MLN on ESKD after adjustment.
Chronic kidney disease of uncertain aetiology (CKDu) is a regionally prevalent tropical disease whose pathogenesis is still unclear. Although kidney biopsies can help to characterize the disease, it is unclear whether histological analysis can also be used to make a prognosis. This retrospective study investigated kidney biopsy findings and progression factors in a 230 CKDu patients in Sri Lanka, with detailed follow-up of 62 participants for 4.2 ± 2.1 years. Participants were predominantly male farmers (93.3%), and 87.0% reported agrochemical exposure. Histology showed a wide range of tubulointerstitial injury. Most specimens exhibited tubular atrophy (90.9%), interstitial fibrosis (75.2%), and glomerulosclerosis (92.1%) to varying degrees. Unsupervised hierarchical clustering of eight activity and chronicity variables identified three groups: (1) mild chronic changes with minimal inflammation, (2) pronounced inflammation with chronic changes, and (3) chronic changes with low grade inflammation. Estimated glomerular filtration rate correlated negatively with seven histologic parameters. Baseline eGFR was significantly higher in cluster 1 than in clusters 2 and 3. In the follow up cohort, tubulitis and glomerulosclerosis were associated with faster eGFR decline and predicted progression. Progression was not explained by differences in reported risk exposures. This large-scale biopsy study revealed that patients with CKDu could be categorised into three subgroups based on their histological changes, with significantly different eGFR values observed between these subgroups. Tubulitis was associated with faster decline in kidney function in the follow-up subcohort. Further research is needed to determine whether the identified clusters represent different stages of the disease or different progression.
COVID-19 infection has been associated with significant morbidity and mortality across all age groups, yet data on pediatric kidney transplant outcomes associated with COVID-19 positive (COVID +) donors remain limited. Using the Scientific Registry of Transplant Recipients, we identified 143 pediatric kidney recipients (< 18 years) of COVID + donors transplanted between September 2020 and February 2025 and compared them with 1808 recipients of COVID-19 negative (COVID -) donors using propensity score weighting to account for transplant year, age at transplant, sex, race, human leukocyte antigen mismatch, prior transplant, and immunosuppression. Among 1940 pediatric recipients, 7.3% received kidneys from COVID + donors, with utilization increasing from 2.5% in 2020 to 10.5% in 2025. No statistically significant differences were observed in patient survival (HR 0.83, 95% CI 0.10-6.73, p = 0.86) and overall graft failure (HR 1.35, 95% CI 0.67-2.73, p = 0.41) between COVID + and COVID - groups over a median follow-up of 1.2 years. Delayed graft function (7.7% vs. 7.2%) and median initial hospital stay (8.0 vs. 8.0 days) were also comparable. The use of COVID + donors for pediatric kidney transplantation has increased over time. The posttransplant outcomes are similar between COVID + and COVID - pediatric recipients, supporting the use of COVID + donors in this population.
To characterize severe hemorrhage and determine its frequency, risk factors, and consequences in the perioperative period of pediatric kidney transplantation. Single-center retrospective study of children undergoing their first kidney transplant between 2008 and 2015. Severe hemorrhage was defined using a data-driven cluster analysis to identify patients with high perioperative bleeding volume and blood component requirements. Additionally, severe hemorrhage was defined by the need for reoperation or administration of activated factor VII or fibrinogen for bleeding related to transplant. Thirty-eight exposure variables were examined, including clinical and laboratory data, donor and recipient characteristics, surgical technical variables, and medications. Analysis of hemorrhage consequences considered the occurrence of delayed renal function, hospitalization length during transplantation, estimated glomerular filtration rate post-transplantation, and five-year graft and patient survival. Severe hemorrhage occurred in 16/218 cases (7.3%). In unadjusted logistic analyses, higher risk was observed among younger and smaller recipients, those receiving kidneys from older and living donors, and those exposed to a higher graft dose. Among laboratory markers, postoperative platelet count was associated with hemorrhage. Five-year graft survival was lower in children with severe hemorrhage compared with those without (62.5% vs. 91.5%, p < 0.001). The frequency of severe hemorrhage in children treated with kidney transplantation in our center was higher than reported in the literature. The type of donor and the combination of small recipients and large donors were the main risk factors. The need for a larger abdominal dissection area in small children receiving large grafts, contributing to the risk of bleeding, is a possible explanation for this finding.
Chronic kidney disease (CKD) is a major global health burden that disproportionately impacts people of recent African ancestry. The discovery of risk variants in the apolipoprotein L1 (APOL1) gene has transformed the understanding of racial disparities in CKD. In particular, APOL1 variants have been associated with increased risk of focal segmental glomerulosclerosis, virus-associated nephropathy, and other glomerular diseases in Black adults. While approximately 10-15% of Black Americans have a high-risk APOL1 genotype, disease penetrance is variable and is likely mediated by additional genetic and environmental "second hits." Variants in APOL1 have also been implicated in kidney transplant outcomes and pregnancy complications, underscoring its broad clinical relevance. Advances in therapeutic strategies, including small molecule inhibitors of APOL1 pore function, APOL1 antisense oligonucleotides, and JAK-STAT pathway modulation, offer promise for targeted interventions in adult populations. Emerging data in children highlight similar genotype-phenotype associations, with evidence of high-risk APOL1 genotype impacting steroid-resistant nephrotic syndrome and CKD progression. However, pediatric studies remain limited and underpowered, leaving critical gaps in the understanding of disease epidemiology, mechanisms, and long-term outcomes. This review will explore current knowledge of APOL1 kidney disease (AMKD) with a particular focus on pediatric populations and highlight the need for inclusion of children in future studies.
This study aims to determine the course of immunosuppressive medication adherence (MA) in individuals who have undergone kidney transplantation for over a decade and to identify the demographic and clinical factors affecting this adherence. This retrospective and cross-sectional descriptive study evaluated the biological adherence of 103 kidney transplant recipients (KTRs) at 12 different time points using tacrolimus and cyclosporine blood levels. Self-reported adherence was assessed via The Immunosuppressant Therapy Adherence Scale. Associations between adherence and demographic and clinical variables were also analyzed. The mean time since transplantation was 11.77 ± 1.46 years. Biologically, 43.3% of patients had low MA. In contrast, self-reported adherence was 82.52%. No statistically significant correlation was found between biological and self-reported adherence outcomes. Patients with low biological adherence presented increased blood urea nitrogen (BUN) levels at 6 months and 9 years post-transplant. Similarly, patients with low self-reported adherence had increased BUN levels at 10 years. Self-reported adherence scores were significantly lower among patients with a history of graft rejection (p < 0.001). No significant associations were found between MA and variables such as sex, donor type, or age (p > 0.05). This study identifies significant discrepancies between biological and self-reported methods for evaluating long-term adherence to immunosuppressive therapy. The results indicate that adherence fluctuates over time, highlighting the need for multidimensional assessment strategies. The implementation of standardized, and complementary tools is crucial to improving graft and patient survival. Future multicenter research should investigate pre-transplant predictors to optimize long-term medication adherence.
Cardiovascular-kidney-metabolic (CKM) syndrome has emerged as a major global health burden and driver of cardiovascular disease (CVD), the leading cause of death worldwide. Effective management of CKM depends on timely identification of underlying risk factors. Nevertheless, participation rates in primary care-based screenings are low. Consequently, CKM syndrome oftentimes remains undetected until organ damage is clinically present. Community pharmacies offer an accessible, yet underused, setting to enhance early detection. APOSCREEN-1 evaluates the feasibility and diagnostic yield of a pharmacy-based multi-parametric screening for cardiovascular-kidney-metabolic health. APOSCREEN-1 is a prospective single-arm clinical trial conducted in 20 community pharmacies in the German state of Schleswig-Holstein. Adults (n = 1000) aged ≥ 40 years with predefined risk criteria are included. Participants undergo standardized point-of-care testing (glycated hemoglobin, lipid profile, urinary albumin, blood pressure). Additionally, clinical history is assessed and results are transmitted to the study center via an online platform. Patients meeting pre-defined thresholds of the tested parameters are followed up by confirmatory laboratory testing at the study center or at the participants' general practitioner. Primary outcomes include completion rate, implementation metrics from the pharmacy perspective, and the number needed to screen to detect unknown or insufficiently managed cardiometabolic risk factors. Secondary outcomes comprise participant metrics, diagnostic metrics of the screening, evaluation of the clinical impact. This study aims to address the unmet need for scalable prevention of CVD by identification of CKM syndrome risk factors outside traditional primary care settings. Evidence on feasibility, acceptance, and diagnostic benefit may support the use of community pharmacies as an additional access point for early CKM syndrome detection. Future interventional studies will be required to evaluate structured follow-up pathways and long-term effectiveness. This study was registered with the German trial registry (Deutsches Register klinischer Studien) on 29.01.2026, under trial number DRKS00039149.
Cardiovascular-kidney-metabolic (CKM) syndrome represents a composite disease state driven by glucose and lipid metabolic dysregulation. The Cholesterol, High-density lipoprotein, and Glucose (CHG) index reflects the composite burden of these metabolic factors. However, its impact on the onset, stage-wise progression, and prognosis of CKM syndrome remains unclear. This study utilized data from two large-scale prospective cohorts. In the UK Biobank (UKB) cohort, Fine-Gray proportional subdistribution hazards models were employed to investigate associations between CHG levels and the risk of incident cardiovascular disease (CVD), chronic kidney disease (CKD), and type 2 diabetes mellitus (T2DM), as well as the risk of progression from CKM Stage 0-1 to 2-3 and Stage 1-3 to 4. In the Beijing Anzhen Hospital cohort, Cox regression models assessed the impact of CHG on major adverse cardiovascular and cerebrovascular events (MACCE) in patients with CKM Stage 4 (established coronary artery disease). A causal forest algorithm was used to identify high-value subpopulations, and restricted cubic splines (RCS) characterized dose-response relationships. Sensitivity analyses were conducted to verify result robustness. The study included 370,916 participants free of CKM diseases from UKB (median follow-up: 16.5 years) and 8,494 patients with CKM Stage 4 from Beijing Anzhen Hospital (median follow-up: 645 days). In the general population, each 1-SD increase in the CHG index was significantly associated with an increased risk of incident T2DM (HR: 1.47; 95% CI: 1.40-1.53), CVD (HR: 1.07; 1.06-1.09), and CKD (HR: 1.07; 1.04-1.10). Furthermore, elevated CHG significantly accelerated CKM progression from Stage 0-1 to 2-3 (HR: 1.16; 1.11-1.23) and from Stage 1-3 to 4 (HR: 1.06; 1.05-1.08) per 1-SD increase. In patients with established CAD (Stage 4), a 1-SD increase in CHG was associated with a higher risk of MACCE (HR: 1.12; 1.05-1.19). Machine learning analysis revealed that this prognostic impact was particularly pronounced in patients with low systemic inflammation and elevated HbA1c. The CHG index demonstrates significant predictive value for the onset of component diseases, stage-wise progression, and adverse prognosis across the entire CKM syndrome continuum.
Infections after kidney transplantation are a principal cause of morbidity, allograft failure and mortality. Paediatric recipients are less likely to have immunity through prior exposure to pathogens linked to graft failure such as CMV and EBV. This immunological naivety results in a need for meticulous donor screening, the deployment of strategies to minimise the risk of severe disease, and prompt treatment once infection is diagnosed. This review provides an up-to-date overview of major pathogens contributing to infection in paediatric kidney transplant recipients and we discuss prophylaxis, treatment and lifestyle modifications that can be employed to mitigate infection risk.
Early identification of acute kidney injury (AKI), including subclinical AKI, remains a critical challenge in septic patients undergoing major non-cardiac surgery. Exosomal microRNAs (miRNAs) represent emerging biomarkers capable of reflecting early renal cellular stress before detectable changes in serum creatinine occur. This prospective observational cohort study enrolled 120 adult septic patients undergoing major non-cardiac surgery (> 2 h) at Imam Sajjad Hospital, Tabriz, between early 2025 and August 2025 (Ethics Approval ID: IR.IAU.TABRIZ.REC.1404.179). Peripheral blood was obtained at three perioperative time points (preoperative, intraoperative, and 24 h postoperative) for exosome isolation and miRNA quantification. Clinical AKI was defined according to KDIGO criteria. Subclinical AKI was defined as urinary TIMP-2 × IGFBP7 > 0.3 in the absence of any rise in serum creatinine. Diagnostic performance of candidate miRNAs was assessed using receiver operating characteristic (ROC) analysis based on observed patient data. Among the 120 enrolled patients, a proportion developed AKI during the 24-hour postoperative observation period (final numbers provided in the Results section). Patients who developed AKI demonstrated distinct perioperative alterations in specific exosomal miRNAs compared with those who did not develop AKI. Several miRNAs showed measurable discriminatory ability for early AKI detection across different sampling time points, with areas under the ROC curve (AUCs) ranging within clinically relevant thresholds (AUC values reported in the Results and Tables following recalculation using observed data with 95% confidence intervals). These findings suggest that perioperative plasma exosomal miRNAs may serve as promising early indicators of acute kidney injury in septic patients undergoing major surgery. Their potential role in identifying subclinical AKI warrants further investigation in studies specifically powered for this endpoint.
We assessed the association between dolutegravir (DTG)-based antiretroviral therapy and kidney abnormalities among young people living with HIV in Kampala, Uganda. Cross-sectional albumin-creatinine ratio (ACR), proteinuria, and estimated glomerular filtration rate (eGFR) were measured. Among 483 participants, the mean serum creatinine was higher (0.68 vs. 0.59) and creatinine-based eGFR lower (118.8 vs. 113.9), among those on TDF/DTG. Cystatin C-based eGFR, prevalences of elevated ACR (9.6% vs. 13.0%), proteinuria (28.3% vs. 30.2%), and eGFR < 90 ml/min/1.73 m² (40.1% vs. 46.9%) were similar. Kidney abnormalities were not associated with regimen, supporting the need for longitudinal studies to clarify progression risk.
Long-term renal outcomes after ileostomy closure in patients undergoing curative colorectal tumor resection and diverting ileostomy remain unclear. We investigated renal outcomes and risk factors for chronic kidney disease (CKD) in this population. Patients who underwent colorectal tumor surgery after diverting ileostomy between January 2013 and December 2020 were analyzed. The serum creatinine (sCr) level and estimated glomerular filtration rate (eGFR) were monitored for up to three years after stoma closure. CKD progression was defined as an eGFR < 60 mL/min/1.73 m2. A multivariate analysis was used to identify independent risk factors for CKD. In total, 533 patients were included: 112 with preoperative CKD and 421 without CKD. Among patients without preoperative CKD, 322 were followed up for 3 years after stoma closure. sCr levels and the eGFR showed persistent worsening even after stoma closure. Based on the eGFR at three years, patients were grouped into CKD and non-CKD groups. A multivariate analysis revealed that age ≥ 70 years old, a preoperative eGFR < 90 mL/min/1.73 m2, and ileostomy-associated kidney injury were independent risk factors for CKD after stoma closure. The sCr levels and eGFR worsened up to three years after stoma closure, even without these risk factors. Diverting ileostomy poses a risk of a renal function decline even after stoma closure.
The Bone Morphogenetic Protein (BMP) family acts as a critical modulator of cellular plasticity and lineage commitment in oncogenesis. However, the systematic contribution of BMP-related mRNAs (BRMs) to the progression and immunophenotypic landscape of kidney renal clear cell carcinoma (KIRC) remains poorly defined. Integrating transcriptomic and clinical data, we established a BRM-based risk signature to refine KIRC prognosis. The model's robustness was validated using the E-MTAB-1980 cohort and a comprehensive nomogram. We employed advanced computational frameworks-including tumor mutation burden (TMB), tumor microenvironment (TME) deconvolution, and drug sensitivity profiling-to dissect biological heterogeneity between risk subgroups. A nine-BRM signature (comprising L1CAM, MPP7, CLIC5, TUBB2B, PLG, CA8, ITGAX, PADI3, and PRR15L) was identified as an independent prognostic factor. Kaplan-Meier analysis demonstrated significantly inferior survival in the high-risk group (HRG) compared to the low-risk group (LRG) (P < 0.001). The BRM-integrated nomogram exhibited superior predictive accuracy (AUC = 0.747) and strong calibration. Functional enrichment revealed that while the LRG was associated with physiological renal tubular secretion, the HRG was predominantly characterized by immunoglobulin production and B cell-mediated immune dysregulation. Furthermore, the HRG exhibited a significantly higher TMB and distinct sensitivity to Dactolisib and Podophyllotoxin, whereas the LRG favored Docetaxel. RT-qPCR successfully validated the differential expression of core BRMs in clinical samples. This nine-BRM prognostic model serves as a potential prognostic stratification tool that may complement existing clinical parameters in evaluating the outcomes of KIRC patients.
Human induced pluripotent stem cells (hiPSCs)-derived kidney organoids can resemble early stages of human kidney development, morphology and architecture. However, one of the main limitations of the organoids is the reduced vascularization, which limits differentiation and maturation. To increase the oxygen and nutrient supply, multiple vascularization strategies were proposed in literature, including organ-on-chip, hydrogels with angiogenetic cues, and co-culture with endothelial cells. In this work, we developed a three-dimensional (3D) printed chip by extruding sacrificial pluronic, in a fully automated and cost-effective way. By dissolving the pluronic, two circular cross-sectional channels, together with three separated central gel compartments, were created. Human umbilical vein endothelial cells (HUVECs) were seeded in the coated 3D printed chip, and after seven days kidney organoids were added in the central gel compartments, embedded in a partially digested decellularized extracellular matrix (ddECM) hydrogel, and co-cultured for five days under perfusion. At the end of the co-culture, capillary-like structures were formed towards the organoids both in the outer and central parts, colocalizing with LTL and PODXL positive stained areas. We were able to develop primitive capillary-like structures throughout the organoids, using an ad-hoc designed 3D printed chip. Our strategy provides new possibilities to investigate further organoid maturation, drug testing and disease modeling.
Acute kidney injury (AKI) represents a fatal complication of rhabdomyolysis, which is characterised by skeletal muscle damage and necrosis. Consequently, cell contents are released into the bloodstream, eventually obstructing renal tubules, which causes renal dysfunction due to elevated inflammation, oxidative stress, and apoptosis. Rosmanol (RM) is a phenolic diterpene compound isolated from Rosmarinus officinalis (Roary), which reveals antioxidative, anti-inflammatory, anti-apoptotic, and nephroprotective activities. Hence, we explore the nephroprotective efficacy of RM against glycerol-induced AKI in an in vivo model. Experimental rats were generally segregated into 4 sets. Group I: Normal control (NC); Group II: Glycerol alone; Group III-IV: Glycerol + RM (20 and 40 mg/kg bw); Group V: RM alone (40 mg/kg bw). Glycerol-induced rats revealed considerably increased (P < 0.05) renal toxicity markers, oxidative stress, caspase proteins, apoptosis, collagen deposition, and histopathological damages, while reduced antioxidative activity and PGC‑1α/SIRT3 signalling. Administration of RM (20 and 40 mg/kg bw) in the glycerol-stimulated rats remarkably diminished (P < 0.05) renal toxicity markers, oxidative stress, caspase proteins, apoptosis, histopathological damages, and collagen deposition, while markedly elevated (P < 0.05) antioxidant activity and mitochondrial function via enhancing PGC‑1α/SIRT3 pathway. These findings established that RM might be protective against rhabdomyolysis-triggered AKI by its antioxidative, anti-apoptotic, and nephroprotective properties.