Chronic kidney disease (CKD) is increasingly linked to environmental toxins, including the cyanobacterial toxin microcystin-LR (MC-LR), particularly in populations with pre-existing renal injury. We have previously demonstrated that MC-LR promotes CKD, however the full underlying mechanism remains poorly understood. This study investigated how MC-LR exacerbates adenine-induced kidney disease in animal models using an integrative multi-omics approach. Male Sprague-Dawley rats were assigned to four groups: control, MC-LR, adenine, and adenine + MC-LR. Histopathology showed that MC-LR alone caused only mild, focal interstitial inflammation and fibrosis, whereas adenine alone induced granulomatous interstitial nephritis with tubular atrophy and acute tubular necrosis. The most severe lesions were in the co-exposure group, with widespread tubular injury, dense granulomatous inflammation, and extensive interstitial fibrosis. Proteomic analysis revealed distinct clustering and overexpression of Ctss, Wipf3, and Hmgcs2 in kidney tissue from the co-exposure group, together with enrichment of pathways related to DNA repair, p53 signaling, and integrin-HMGB1 complexes. Urinary metabolomics and peptidomics revealed metabolic and peptide signatures associated with CAMKK2 signaling, Farnesyl CoQ10, ferroptosis, and immune activation. Integrative multi-omics analysis demonstrated strong cross-omics correlations, highlighting coordinated oxidative stress, mitochondrial dysfunction, ferroptosis, altered mitophagy, and fibrotic remodeling as key mechanisms of MC-LR-enhanced nephrotoxicity. Together, these findings show that even sub-toxic, environmentally relevant MC-LR exposure can amplify kidney injury through tightly interconnected metabolic and inflammatory networks. This work provides mechanistic insight into cyanotoxin-associated kidney disease and supports the need for stricter monitoring and prevention strategies in regions affected by harmful algal blooms.

Emphysematous pyelonephritis is a rare, life-threatening necrotizing infection that is typically characterized by classic urinary symptoms. However, it is exceptionally rare for emphysematous pyelonephritis to manifest with predominant gastrointestinal symptoms, a deceptive mimicry that often masks the underlying renal pathology and leads to significant diagnostic delays. We report the case of a woman in her 60s with type 2 diabetes whose initial presentation was limited to vomiting and diarrhea, suggesting acute gastroenteritis. In the absence of typical urological distress, her condition rapidly worsened, and she developed septic shock and altered mental status within 48 h. Computed tomography confirmed Huang-Tseng class 3B emphysematous pyelonephritis with extensive destruction of the right renal parenchyma. Recognizing the irreversible tissue necrosis and failure of medical therapy, a decisive transition to emergency nephrectomy was performed. This timely surgical intervention successfully arrested the fulminant progression, leading to hemodynamic stabilization and recovery. This case underscores that emphysematous pyelonephritis rarely masquerades as gastroenteritis; in diabetic patients, such atypical manifestations followed by rapid clinical deterioration necessitate immediate computed tomography evaluation. Furthermore, when imaging reveals extensive gas formation and clinical stability is lost, prompt and resolute surgical source control is a critical, life-saving measure for ensuring patient survival.

Legionnaires' disease is a rare cause of atypical pneumonia associated with a high mortality rate among untreated patients. In Romania, the disease has historically been underreported due to insufficient surveillance and limited diagnostic capacity. The aim of this study was to describe the characteristics of Legionnaires' disease cases admitted to a specialized infectious disease hospital between 2023 and 2024, with a particular focus on a cluster associated with travel to a spa resort. Most cases included in our study (31/36) were confirmed by urinary antigen testing, while one case was confirmed by a significant increase in the level of specific antibodies against Legionella pneumophila serogroup 1 in paired serum samples. The most frequently reported symptom was fever (28/32), followed by chills (24/32). Among the 32 confirmed cases, 3 patients died. Two cases were identified as part of a family cluster involving a father and son who had undergone physiotherapy at a balneary resort. Both patients presented with fever and gastrointestinal symptoms, and radiological investigations confirmed mixed pneumonia associated with an intense inflammatory syndrome. In the father's case, hepatic involvement and interstitial nephritis were also identified. Early diagnosis based on epidemiological data, clinical predictive scores, and laboratory investigations would allow timely administration of targeted antibiotic therapy and may contribute to reduced mortality.

Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD) is the third most common inherited monogenic kidney disorder. Mutations in UMOD and MUC1 account for most cases, with the disease characterized by progressive eGFR decline leading to kidney failure. No disease-modifying therapies exist, and transplantation is the only current option. Designing trials for ADTKD is hampered by small patient numbers, variable progression rates, and uncertainty around optimal endpoints. Building on natural history data from Wake Forest School of Medicine, nonlinear mixed-effects models were developed to describe eGFR decline in UMOD and MUC1 variants. These models formed the foundation for a web-based clinical trial simulation (CTS) tool (https://app.cop.ufl.edu/adtkd/) built in R Shiny. The tool allows users to define trial populations, configure design parameters, and estimate statistical power by simulating placebo vs. assumed treatment arms. Drug effects were modeled as percentage changes in key parameters of the developed disease progression models describing individual-level eGFR trajectory over age: DPT50 (age at which eGFR is half of its maximum decline), γ 1 $$ {\gamma}_1 $$ and γ 2 $$ {\gamma}_2 $$ (steepness before and after DPT50). Both slope-based eGFR change and end-of-trial eGFR measures functioned as effective surrogate endpoints. Herein, we present the model-based CTS tool developed for ADTKD and demonstrate its use in designing and evaluating clinical trial scenarios, illustrated by two representative case studies. The CTS tool provides a pragmatic framework for optimizing ADTKD trial design. By enabling scenario testing and highlighting genotype-specific considerations, it supports efficient, cost-effective planning and represents an example of model-informed drug development in rare kidney diseases.

Marsupials of the genus Didelphis are highly adapted to urban environments and are widely distributed in the Americas. Streptococcus didelphis is a bacterium that has been isolated from, and associated with disease, in the Virginia opossum (Didelphis virginiana) and the white-eared opossum (Didelphis albiventris). This study describes pathological changes associated with S. didelphis infection in white-eared opossums (Didelphis albiventris) and Brazilian common opossums (Didelphis aurita) as well as microbiological and genomic characterization of isolates. Ten opossums underwent necropsy and had ulcerative dermatitis of probable traumatic origin had S. didelphis was isolated from cutaneous lesions (n = 16) or systemic sites (n = 4). In contrast, 34 free-ranging opossums that were captured had negative culture results for S. didelphis from nasal swabs. Other lesions in opossums naturally infected with S. didelphihs included splenitis (7/10), myocarditis (6/10), interstitial nephritis and pyelonephritis (7/10), and myositis (4/10). Most isolates were susceptible to the antimicrobial drugs tested and none of them were able to form biofilm in vitro. Whole genome analysis of six isolates revealed no resistance determinants, virulence factors or plasmids, and the isolates showed high genomic similarity.

Necrotising pyelonephritis is an uncommon but severe renal infection that may lead to septic shock and thrombotic complications. Cardiac arrhythmias are recognised in sepsis; however, presentation with supraventricular tachycardia (SVT) is unusual and may obscure the underlying diagnosis. A previously healthy woman in her late teens presented with fever, flank pain and hypotension associated with SVT unresponsive to vagal manoeuvres and adenosine. Sinus rhythm was restored following fluid resuscitation. Further evaluation revealed septic shock due to right-sided necrotising pyelonephritis complicated by right renal vein thrombosis, with blood and urine cultures growing Escherichia coli Echocardiography demonstrated transient left ventricular systolic dysfunction consistent with sepsis-induced myocardial dysfunction. She was managed with early haemodynamic optimisation, broad-spectrum antibiotics, ureteric stenting and anticoagulation, resulting in full recovery. This case highlights that SVT may rarely represent a presenting feature of septic shock and underscores the importance of prompt source control and multidisciplinary management.

Hypertensive nephropathy (HN) is a leading cause of chronic kidney disease and end-stage renal disease worldwide and results from the long-term effects of hypertension on renal structure and function. The pathogenesis of HN is complex and involves haemodynamic disturbances, renal vascular injury, oxidative stress, chronic inflammation, and progressive interstitial fibrosis. In recent years, increasing attention has focused on the role of non-coding RNAs (ncRNAs)-including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs)-as key regulators of gene expression involved in these processes. This review summarises the current understanding of the molecular mechanisms underlying HN, with particular emphasis on the roles of oxidative stress, activation of the renin-angiotensin-aldosterone system, transforming growth factor beta signalling, and inflammatory and fibrogenic pathways. The contribution of dysregulated ncRNAs to endothelial dysfunction, inflammatory responses, apoptosis, angiogenesis, and renal remodelling and fibrosis is also discussed. Particular attention is given to miRNAs and lncRNAs as mediators of disease progression and potential biomarkers, as well as to the emerging role of circRNAs in hypertensive kidney injury, including their involvement in the regulation of redox balance and intercellular communication. Collectively, available evidence indicates that ncRNAs represent a critical link between haemodynamic stimuli and persistent molecular alterations in renal tissue, highlighting their potential as diagnostic markers and therapeutic targets in HN.