[Posted 9/May/2024]

AUDIENCE: Nephrology, Internal Medicine

KEY FINDINGS: Kidney outcome in patients with biopsied IgA vasculitis nephritis treated with immunosuppression was determined by clinical risk factors and endocapillary hypercellularity (E1) and fibrous crescents, which are features that are not part of the International Study of Diseases of Children classification.

BACKGROUND: Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts.

DETAILS: Biopsies from 262 children and 99 adults with IgA vasculitis nephritis (N=361) from 23 centers in North America, Europe, and Asia were independently scored by three pathologists. MEST-C scores were assessed for correlation with eGFR/proteinuria at biopsy. Because most patients (N=309, 86%) received immunosuppression, risk factors for outcomes were evaluated in this group using latent class mixed models to identify classes of eGFR trajectories over a median follow-up of 2.7 years (interquartile range, 1.2-5.1). Clinical and histologic parameters associated with each class were determined using logistic regression. M, E, T, and C scores were correlated with either eGFR or proteinuria at biopsy. Two classes were identified by latent class mixed model, one with initial improvement in eGFR followed by a late decline (class 1, N=91) and another with stable eGFR (class 2, N=218). Class 1 was associated with a higher risk of an established kidney outcome (time to >= 30% decline in eGFR or kidney failure; hazard ratio, 5.84; 95% confidence interval, 2.37 to 14.4). Among MEST-C scores, only E1 was associated with class 1 by multivariable analysis. Other factors associated with class 1 were age 18 years and younger, male sex, lower eGFR at biopsy, and extrarenal noncutaneous disease. Fibrous crescents without active changes were associated with class 2.

Copyright © American Society of Nephrology. All rights reserved.

Source: Barbour, S., Coppo, R., Lee, E., et al. (2024). Histologic and Clinical Factors Associated with Kidney Outcomes in IgA Vasculitis Nephritis. Clinical Journal of the American Society of Nephrology . 2024; 19(4): 438-451. Published: May, 2024. DOI: 10.2215/CJN.0000000000000398.

[Posted 27/Oct/2025]

AUDIENCE: Infectious Disease, Microbiologists

KEY FINDINGS: Enhanced antibiotic performance observed in preclinical mouse models. Potential to improve treatment outcomes for multiple intracellular bacterial infections. Ongoing efforts include mechanism elucidation and patent development.

BACKGROUND: Antibiotic resistance has severely limited the effectiveness of conventional treatments against persistent bacterial infections. Some pathogens, such as Staphylococcus aureus, Mycobacterium tuberculosis, and Salmonella enterica, can survive inside immune cells, remaining dormant and shielded from antibiotic action. The increasing prevalence of such infections underscores an urgent need for alternative approaches that do not rely solely on developing stronger antibiotics.

DETAILS: Researchers at the University of North Carolina (UNC) School of Medicine, led by Dr. Brian Conlon and Dr. Kuan-Yi Lu, identified a novel small molecule that modifies immune cell behavior to enhance antibiotic performance. Instead of directly targeting bacteria, the molecule reprograms the host's immune cells to activate dormant pathogens, rendering them more susceptible to antibiotic killing.

The team screened approximately 5,000 small molecules through the UNC Small Molecule Screening Core. They used luminescent reporter strains of S. aureus to identify compounds that triggered bacterial activation. The most promising compound was subsequently tested in mouse models, where it significantly improved antibiotic efficacy when administered alongside standard treatments.

In animal models, the selected molecule substantially improved pathogen clearance for S. aureus, M. tuberculosis, and S. enterica when used in combination with existing antibiotics. This finding supports a new therapeutic concept: targeting the host cell environment can potentiate antibiotic activity and overcome intracellular bacterial persistence. The discovery presents an innovative direction for combating infections that evade standard therapy.

Copyright © UNC School of Medicine. All rights reserved.

Source: Conlon, B. and Kuan-Yi, L. UNC Researchers Discover Method to Combat Antibiotic Treatment Failure. UNC Health Newsroom. 2025; Published: October 14, 2025.

A Cohort Study Investigating Adherence of Dose and Duration to UK Clinical Guidelines

[Posted 14/Oct/2025]

AUDIENCE: Psychiatry, Family Medicine

KEY FINDINGS: This study highlights how antipsychotic prescribing in dementia is discordant with current NICE guidelines on both duration and dose. More than half of those who discontinued their treatment then restarted treatment. These findings emphasise a persistent gap between clinical guidelines and real-world prescribing, underscoring the need for interventions that prioritise safety and person-centred dementia care.

BACKGROUND: In the UK, it is recommended by the National Institute for Health and Care Excellence (NICE) that if antipsychotics are initiated in people living with dementia, treatment should be at the lowest dose for the shortest time possible (1-3 months). In this study, authors aimed to investigate how dose and duration of antipsychotic medication adhere to UK clinical guidelines and explore treatment restart details in those who stop treatment.

DETAILS: Authors did a retrospective cohort study using longitudinal UK primary care data from the IQVIA Medical Research Database. Authors included people living with dementia aged 60-85 years who received their first antipsychotic prescription between Jan 1, 2000, and Dec 31, 2023. Individuals with any previous antipsychotic prescriptions in their records more than 1 year before a dementia diagnosis and those who had missing social deprivation information were excluded from the study. Duration of first and subsequent antipsychotic treatment episodes, medication dosage, and treatment discontinuation and reinitiation rates were investigated. Duration and discontinuation were defined by grouping consecutive prescriptions into treatment episodes using the waiting time distribution method (80% inter-arrival density, 59 days). Daily doses were derived from strength and frequency information and categorised as low or moderate or high based on established minimum effective dose equivalences. People with lived experience of dementia care contributed throughout this project, shaping the research question and advising on interpretation and dissemination strategies. In the dataset search, authors identified 108,910 people with a record indicating dementia at any time. In total, 99,091 cases were excluded (ie, individuals with no antipsychotic prescription between the ages of 60 and 85 years between 2000 and 2023, a previous history of antipsychotics, missing deprivation information, or only one eligible prescription). Authors included 9819 people living with dementia aged 60-85 years who received their first antipsychotic prescription between 2000 and 2023 in the study. 5310 (54.1%) were female and 4509 (45.9%) were male, with a mean age of 77.1 years (SD 5.6 years), and ethnicity data were not available. The first treatment episode lasted a median of 7 months (IQR 6.6-8.7), exceeding NICE guidelines of 1-3 months and 18.1% [95% CI 17.4-18.9]) were initiated on a prescription above the minimum effective dose (ie, low dose). Of the 1781 participants who started on a moderate or high dose, 519 (29.1%) had a moderate or high dose in all quarters of the first year of treatment. 1 year after treatment initiation, 5136 (78.3%) of 6559 eligible individuals remained on medication (48.9% [95% CI 47.7-50.1] on low dose, 14.8% [13.9-15.6] on moderate or high dose of haloperidol, olanzapine, quetiapine or risperidone; and 14.6% [13.8-15.5] on other antipsychotics). Of the 5547 individuals eligible to restart treatment after initial discontinuation, 3106 (56%) restarted with a median treatment duration of 2.6 months (IQR 0.0-9.9).

Copyright © Elsevier Ltd. All rights reserved.

Source: Smsith, H. C., Petersen, I., Hayes, J. F., et al. (2024). Antipsychotic Prescriptions in People With Dementia in Primary Care: A Cohort Study Investigating Adherence of Dose and Duration to UK Clinical Guidelines. The Lancet Psychiatry. 2025; 12(10): 758-767. Published: October, 2025. DOI: 10.1016/S2215-0366(25)00261-5.

A Randomized Controlled Trial

[Posted 6/Oct/2025]

AUDIENCE: Nephrology, Cardiology, Internal Medicine

KEY FINDINGS:

• Physical exercise before hemodialysis is as cardioprotective as intradialytic exercise.
• Predialytic exercise potentially addresses several modality-specific barriers and challenges encountered by both health care providers and patients.
• These are likely mediated by mechanisms inherent to exercise itself, rather than by transient central and/or systemic hemodynamic alterations.

BACKGROUND: Hemodialysis induces left ventricular regional wall motion abnormalities (RWMAs) due to myocardial hypoperfusion. Although acute intradialytic exercise (IDE) has shown cardioprotective effects, its routine implementation faces feasibility challenges, and the potential of predialysis exercise as an alternative remains unexplored. This study aimed to compare the effect of predialysis exercise and IDE on hemodialysis-induced myocardial stunning.

DETAILS: In this open-label, randomized cross-over trial, 25 patients with ESKD underwent to each of three hemodialysis conditions, administrated in random order: standard hemodialysis (HD-_CONT), hemodialysis with IDE (HD-_PER), and hemodialysis preceded by exercise (HD-_PER). Two-dimensional echocardiography and whole blood viscosity (WBV) measurements were performed both immediately before hemodialysis onset (T₀) and at peak stress of hemodialysis (T_peak). Left ventricular longitudinal strain from an 18-segment model was used to assess the presence of RWMAs. Regular monitoring of cardiovascular hemodynamics was set up with measurements staggered every 30 minutes. Compared with HD-CONT, there was a significant reduction in RWMAs during both HD-_PER (estimated difference, 1.60 segments; 95% confidence interval, 0.09 to 3.10; P = 0.04) and HD-_PRE (estimated difference, 1.72 segments; 95% confidence interval, 0.21 to 3.22; P = 0.02). The magnitude of the exercise-induced reduction in myocardial stunning did not differ between HD-_PER and HD-_PRE (P = 0.86). Apart from the exercise period itself, kinetics of all hemodynamic variables were similar between HD-CONT and HD-_PER, whereas they were totally similar between HD-CONT and HD-_PRE. No associations of changes in RWMAs and hemodynamics variables between HD-CONT versus HD-_PRE or HD-_PER were found (P > 0.42). Comparing HD-CONT versus HD-_PER, WBV was preserved in HD-_PER and changes in RWMAs were associated with changes in WBV at high shear rates (225 s^-1: P = 0.006; 90 s^-1: P = 0.04).

Copyright © American Society of Nephrology. All rights reserved.

Source: Josse, M., Turc-Baron, C., Patrier, L., et al. (2025). Acute Exercise before Dialysis Is as Cardioprotective as during Dialysis: A Randomized Controlled Trial. Clinical Journal of the American Society of Nephrology. 2025; 20(9): 1236-1246. Published: September, 2025. DOI: 10.2215/CJN.0000000767.

A Retrospective Repeated Cross-Sectional Study

[Posted 3/Oct/2025]

AUDIENCE: Family Medicine, Infectious Disease

KEY FINDINGS: Medicare beneficiaries aged 65 years and older with HIV in the USA were more likely to receive opioid prescriptions and have OUD indicators than matched beneficiaries without HIV. Findings could help guide clinical opioid prescription guidelines and public health surveillance among this vulnerable ageing population.

BACKGROUND: There is longstanding concern that people with HIV receive prescription opioids at higher rates and have a disproportionate burden of opioid use disorder (OUD) compared with their counterparts without HIV. We aimed to evaluate trends of opioid prescriptions and indicators of OUD in an understudied but growing population of older adults with HIV.

DETAILS: For this retrospective repeated cross-sectional study, authors constructed annual cohorts through a nationally representative sample of fee-for-service Medicare beneficiaries aged 65 years and older in the USA with Part D coverage (ie, prescription drug) enrolled between Jan 1, 2008, and Dec 31, 2021. Beneficiaries were eligible for inclusion in each cross-sectional cohort if they had reached the age of 65 years by Jan 1 of the calendar year and had 1 year of continuous Medicare enrolment in Part A (inpatient hospital care), B (outpatient care), and D. Beneficiaries with HIV were matched in a 1:3 ratio to beneficiaries without HIV on age, sex, race or ethnicity, US state, and dual eligibility status (Medicare and Medicaid). The main outcomes were receipt of at least one opioid prescription and any indicator of OUD (ie, formal diagnosis, medication for OUD, or opioid-related or emergency department visits) during each calendar year. Generalised estimating equations were used to estimate odds ratios (ORs) of each outcome, comparing matched beneficiaries with or without HIV. Due to data availability, our analysis of indicators of OUD was restricted to 2008-16. Across all years, 163,429 beneficiaries with HIV and 490,287 beneficiaries without HIV were included (475,516 [72.7%] were male, 178,200 [27.3%] were female; 305,776 [46.8%] were non-Hispanic White, 238,172 [36.4%] were Black [or African American], 84,128 [12.9%] were Hispanic, 8964 [1.4%] were Asian or Pacific Islander, and 16,676 [2.6%] were other races or ethnicities). During 2008-21, 57,373 (35.1%) of 163,429 people with HIV and 138,547 (28.3%) of 490,287 people without HIV received at least one opioid prescription. During 2008-16, 2408 (3.1%) of 76,637 people with HIV and 2831 (1.2%) of 229,911 people without HIV had any indicator of OUD. Across all analysed years, beneficiaries with HIV had significantly increased odds of receiving at least one opioid prescription (OR 1.38, 95% CI 1.36-1.39) and having indicators of OUD (2.61, 2.47-2.76) compared with their matched counterparts without HIV.

Copyright © The Author(s). Elsevier Ltd. All rights reserved.

Source: Shiau, S., Drago, F., Kinkade, C. W., et al. (2024). Prescription Opioid Use and Opioid Use Disorder Among Older Adults With HIV in the USA From 2008 to 2021: A Retrospective Repeated Cross-Sectional Study. The Lancet Primary Care. 2025; 1(3): 100017. Published: September, 2025. DOI: 10.1016/j.lanprc.2025.100017.

[Posted 30/Sep/2025]

AUDIENCE: Internal Medicine, Nursing

KEY FINDINGS:

• DPP-4 inhibitors offer a safer alternative to meglitinides in T2D patients with Stage 5 CKD with lower severe renal outcomes and hypoglycemia risk.
• Hypoglycemia risk is lower with DPP-4i due to glucose-dependent insulinotropic action.
• DPP-4i are weight neutral, helpful in normal or lower BMI patients.
• Renoprotection mechanisms of DPP-4i may involve GLP-1 dependent pathways and antifibrotic effects but need further study.
• Observational data with residual confounding; randomized trials needed for conclusive evidence.
• Cost and access issues may influence DPP-4i use in some settings.

BACKGROUND: Managing hyperglycemia in type 2 diabetes (T2D) patients with advanced chronic kidney disease (CKD) is complex due to altered drug metabolism and risk of adverse events. Conventional treatments like metformin pose risks due to renal excretion; sulphonylureas and pioglitazone involve metabolites renally cleared raising hypoglycemia and fluid retention risks. Meglitinide repaglinide is preferred in this setting due to hepatic metabolism and flexible dosing. DPP-4 inhibitors (DPP-4i) offer a safer profile with low hypoglycemia risk and weight neutrality, but data on their safety and efficacy in Stage 5 CKD remain scarce.

DETAILS: Hung et al. conducted a nationwide Taiwanese cohort study (2012-2020) comparing renal outcomes in Stage 5 CKD patients with T2D starting either DPP-4i (n=5028) or meglitinides (n=2243). Stage 5 CKD was defined using erythropoiesis-stimulating agent (ESA) use as a surrogate for eGFR <15 mL/min/1.73 m². Propensity score matching adjusted for confounders. The primary composite outcome included renal replacement therapy (RRT), renal death, and kidney-related hospitalization. DPP-4i use was associated with a 14% lower risk of the primary composite renal outcome vs. meglitinides (HR 0.86; 95% CI 0.81-0.92), mainly through reduced need for RRT. Severe hypoglycemia risk was 41% lower in the DPP-4i group. The findings support the renal safety and possible benefits of DPP-4i over meglitinides in severe CKD. Limitations include observational design, ESA use as CKD surrogate, lack of clinical measurements, and limited generalizability due to homogeneous Taiwanese cohort.

Copyright © John Wiley & Sons, Inc. All rights reserved

Source: Ryden, M. (2025). Choosing Oral Antihyperglycaemic Drugs in People Living With Type 2 Diabetes and Severe Chronic Kidney Disease. Journal of Internal Medicine. 2025; 298(3): 149-151. Published: September, 2025. DOI: 10.1111/joim.70002.