Considering the low sensitivity of microalbuminuria and the increasing prevalence of diabetic nephropathy, biomarker discovery is a priority in diabetes research. We have previously reported increased urinary cubilin shedding preceding microalbuminuria in patients with Type 1 diabetes. In this study, we investigated the predictive value of urinary cubilin as a biomarker in diabetic nephropathy utilizing urine samples collected in one of the largest prospective cohort studies of Type 1 diabetes, Pittsburgh Epidemiology of Diabetes Complications. We measured urinary cubilin by ELISA in urine samples of the participants with normal kidney function and normoalbuminuria obtained at recruitment. Patients were stratified into three groups based on their disease course during a follow-up of > 20 years. Group 1 preserved normal kidney function and normoalbuminuria, Group 2 preserved kidney function but developed macroalbuminuria, and Group 3 progressed to have a > 40% decrease in kidney function during follow-up. We demonstrated that urinary cubilin normalized for creatinine predicted progressive diabetic nephropathy with an area under the receiver operating characteristic curve of 0.81. The urinary cubilin:creatinine ratio was marginally significant across the three groups evaluated by the Kruskal-Wallis test (p = 0.066). The adjusted p value for multiple comparisons of the urinary cubilin:creatinine ratio in comparing the group with > 40% decrease in kidney function and the other two groups was 0.05. The urine cubilin:creatinine ratio between the group with > 40% decrease in GFR and preserved kidney function was significant, with a p value of 0.017. We propose that urinary cubilin can be a promising biomarker to predict progressive diabetic nephropathy in patients with Type 1 diabetes. Studies involving larger patient populations are warranted to further validate urinary cubilin shedding as a novel biomarker in predicting progressive diabetic nephropathy.

Neurodevelopmental benefits of seafood consumption are inconclusive. In a Swedish mother-child cohort, seafood intake was assessed by food frequency questionnaires at gestational week (GW)34 and four years and by seafood biomarkers (methylmercury, arsenobetaine, long-chain polyunsaturated omega-3 fatty acids [n-3 LCPUFAs]) at GW29, birth, and four years. Maternal and child seafood intake (median: 184 and 138 g/week, respectively) was not associated with cognitive abilities (Wechsler Preschool and Primary Scale of Intelligence - Fourth Edition, WPSI-IV) or behavioral problems (Child Behavior Checklist, CBCL and Social Responsiveness Scale, Second Edition, SRS-2) at four years. However, maternal urinary arsenobetaine and erythrocyte arsenic, strongly correlated to each other, were associated with verbal abilities (B [95% CI] 0.5 [-0.0, 1.1] and 1.0 [-0.0, 2.0], per exposure doubling, respectively), as was children's erythrocyte arsenic (full-scale IQ: 1.4 [0.3, 2.5], verbal: 1.9 [0.5, 3.4]), and maternal and child erythrocyte mercury (verbal comprehension: 1.0 [-0.2, 2.2] and 1.0 [-0.3, 2.4], respectively). Maternal erythrocyte DHA and total n-3 LCPUFAs showed non-linear associations with verbal abilities (4.4 [1.0, 7.9] per IQR [1.73%, >4.2%] and 1.3 [0.1, 2.6] per 1% [>6.0%], respectively). Gestational erythrocyte and particularly newborn mercury were associated with less behavioral problems (total CBCL: B [95% CI] -0.5 [-1.3, 0.2] and -1.0 [-1.6, -0.4], per exposure doubling, respectively). In conclusion, seafood biomarkers, predominantly arsenobetaine and n-3 LCPUFAs, but not reported intake, confirmed neurodevelopmental benefits of seafood consumption in a population with below-recommended intake levels.

BACKGROUNDAntimicrobial resistance is highly correlated with inappropriate antimicrobial use. Urinary tract infections (UTIs) are the main infections treated with antibiotics in the population ≥ 70 years.AIMWe aimed to investigate antibiotic prescribing patterns for UTIs treatment among older people in Denmark and resistance trends to assess impact of antibiotic stewardship interventions and quality improvement strategies.METHODSThis national register-based surveillance study included people ≥ 70 years in Danish primary healthcare and assessed consumption of pivmecillinam, trimethoprim, nitrofurantoin and sulfamethizole from 1999 to 2023 and resistance levels from 2018 to 2023. Consumption data were obtained from the Register of Medicinal Product Statistics and resistance data from the Danish Microbiology Database. A review of quality improvement strategies from 2005 to 2020 was conducted to provide context for the study.RESULTSThe highest level of antibiotic consumption for UTIs in older people was in 2014 (447 prescriptions/1,000 people ≥ 70 years) and gradually decreased by 28.4% in 2023. Resistance to pivmecillinam, trimethoprim, sulfamethizole and nitrofurantoin in Escherichia coli and Klebsiella pneumoniae decreased significantly from 2018 to 2023, alongside the decline in antibiotic consumption. Focus on antibiotic stewardship was intensified after 2013, with several quality improvement initiatives and updated treatment guidelines aiming at improving diagnosis and antibiotic treatment.CONCLUSIONAntibiotic consumption for UTIs in people ≥ 70 years decreased notably, accompanied by a decrease in resistance levels, reflecting a positive impact of antibiotic stewardship programmes to improve diagnosis and treatment. However, a growing older population could place a strain on healthcare resources in the future.

This study provided a comprehensive analysis of 145 urinary bladder stone cases diagnosed in dogs and cats over a 5-year period at a private veterinary hospital. The aim was to evaluate demographic patterns, urolith composition, and species-specific trends to enhance understanding and improve management of urolithiasis in companion animals. A retrospective study was conducted on clinical records, including patient demographics (species, breed, age, sex), urolith composition, and stone size. Chemical composition of uroliths was determined using qualitative chemical analysis. Statistical analyses were performed to identify significant associations between patient demographics and urolith composition. Of the 145 cases, 80 were dogs (55.17%) and 65 were cats (44.82%). In dogs, calcium oxalate stones predominated (65.00%) followed by struvite stones (30.00%) and mixed compositions (5.00%). Conversely, cats exhibited a higher prevalence of struvite stones (55.00%), with calcium oxalate accounting for 40.00% and mixed stones for 5.00%. Larger stones (10.00 - 20.00 mm) were more common in female dogs, while cats generally presented with fewer and smaller stones. No statistically significant temporal trend in urolith composition was observed for either species during the study period. Stone color distribution varied by species including cream and brown stones being most common in dogs and cats, respectively. This study established baseline epidemiological data on urolithiasis for this region, revealing significant species-specific differences in stone composition. The high prevalence of calcium oxalate in dogs and struvite in cats highlighted the need for tailored clinical management and provides a crucial benchmark for future regional and global comparative studies.

Multidrug-resistant (MDR) bacterial infections are a major cause of morbidity, mortality, and graft loss in kidney transplant recipients, who are particularly vulnerable due to intensive immunosuppression, frequent healthcare exposure, and recurrent antibiotic use. The rising prevalence of resistance among key uropathogens and bloodstream isolates has outpaced the development and uptake of transplant-specific diagnostic and therapeutic strategies. This mini-review synthesizes contemporary evidence on MDR gram-negative and gram-positive infections in kidney allograft recipients, focusing on extended-spectrum beta-lactamase-producing Enterobacterales, carbapenem-resistant Enterobacterales, difficult-to-treat Pseudomonas aeruginosa, carbapenem-resistant Acinetobacter baumannii, vancomycin-resistant Enterococci, methicillin-resistant Staphylococcus aureus, and Clostridioides difficile infection. We outline epidemiology, risk factors, and clinical impacts on patient and graft outcomes, including the association of recurrent urinary tract infection and MDR bloodstream infection with reduced estimated glomerular filtration rate, increased hospitalization, and higher death-censored graft failure. The article highlights advances in rapid molecular diagnostics (such as polymerase chain reaction, matrix-assisted laser desorption/ionization-time of flight, and syndromic panels) that shorten time to organism and resistance detection, enabling earlier optimization and de-escalation of antimicrobial therapy. Emerging agents - including novel beta-lactam/beta-lactamase inhibitor combinations, siderophore cephalosporins, and investigational boronate beta-lactamase inhibitors - are discussed, emphasizing nephrotoxicity profiles, drug-drug interactions with calcineurin inhibitors, and evidence gaps in transplant populations. We also review the evolving roles of phage therapy, monoclonal antibodies, vaccines, and therapeutic drug monitoring (including area under the curve/minimum inhibitory concentration-guided vancomycin dosing and cautious reuse of aminoglycosides) in this high-risk cohort. Finally, we propose a pragmatic stewardship framework tailored to kidney transplant units, integrating individualized perioperative prophylaxis, avoidance of unnecessary treatment of asymptomatic bacteriuria, early device removal, and minimization of broad-spectrum exposure to limit MDR selection and Clostridioides difficile infection. A transplant-specific approach that combines rapid diagnostics, rational deployment of new antimicrobials, and rigorous stewardship is essential to improve survival and preserve allograft function in the era of MDR infections after kidney transplantation.

Chronic pelvic pain and lower urinary tract dysfunction are associated with a high prevalence of depression, anxiety, trauma history, and stress-related disorders, with worsening of symptoms in these groups. This review characterizes the mechanisms behind these associations and the benefits of intervention.