[Posted 28/Feb/2023]

AUDIENCE: Nephrology, Internal Medicine

KEY FINDINGS: PECs are thought to contribute to disease progression and severity, and the interdependence between these two cell-types during development and in various manifestations of kidney pathology is the primary focus of this review.

BACKGROUND: Podocytes and parietal epithelial cells (PECs) are among the few principal cell types within the kidney glomerulus, the former serving as a crucial constituent of the kidney filtration barrier and the latter representing a supporting epithelial layer that adorns the inner wall of Bowman's capsule.

DETAILS: Podocytes and PECs share a circumscript developmental lineage that only begins to diverge during the S-shaped body stage of nephron formation - occurring immediately before the emergence of the fully mature nephron. These two cell-types therefore share a highly conserved gene expression program, evidenced by recently discovered intermediate cell types occupying a distinct spatio-temporal gene expression zone between podocytes and PECs. In addition to their homeostatic functions, podocytes and PECs also have roles in kidney pathogenesis. Rapid podocyte loss in diseases such as Rapidly Progressive Glomerulonephritis (RPGN) and collapsing and cellular subtypes of Focal Segmental Glomerulosclerosis (FSGS) is closely allied with PEC proliferation and migration towards the capillary tuft - resulting in the formation of crescents and pseudo-crescents.

Copyright © American Society of Nephrology. All rights reserved.

Source: Bronstein, R., Pace, J., Gowthaman, Y., et al. (2023). Podocyte-Parietal Epithelial Cell Interdependence in Glomerular Development and Disease. Journal of the American Society of Nephrology . 2023; 10.1681/ASN.104. Published: February 16, 2023. DOI: 10.1681/ASN.0000000000000104.

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.

A Systematic Review and Individual Patient Data Meta-Analysis

[Posted 15/Sep/2025]

AUDIENCE: Infectious Disease, Pediatric

KEY FINDINGS: Regardless of malaria transmission intensity and age group, a single dose of 0.25 mg/kg primaquine is safe and efficacious for reducing P falciparum transmission. These findings underscore the need for primaquine formulations suitable for young children, and also provide supportive evidence to expand the use of single low-dose primaquine in regions with a moderate-to-high transmission rate that are threatened by artemisinin partial resistance.

BACKGROUND: Adding a single dose of primaquine to artemisinin-based combination therapy (ACT) for the treatment of falciparum malaria can reduce the transmission of Plasmodium falciparum and could limit the spread of artemisinin partial resistance, including in Africa, where the disease burden is greatest. Authors aimed to compare the safety and efficacy of single-dose primaquine plus ACT between young children (aged <5 years) and older children (aged 5 years to <15 years) and adults (aged >=15 years), and between low and moderate-to-high transmission areas.

DETAILS: For this systematic review and individual patient data meta-analysis, authors searched PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, WHO Global Index Medicus, OpenGrey.eu, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform, from database inception to April 3, 2024, with no language restrictions. Authors included prospective studies on efficacy against falciparum malaria that enrolled at least one child younger than 15 years and involved a study group given a single dose of primaquine (<=0.75 mg/kg) plus ACT. Studies involving mass drug administration, healthy volunteers, or patients with severe malaria or mixed (with non-falciparum) infections were excluded. For inclusion in the efficacy analysis, data on transmission potential (as determined by gametocytaemia, infectivity, or both) at enrolment and follow-up (day 3, day 7, or day 14) were required; the safety analysis required data on haemoglobin concentrations or haematocrit values at enrolment and at one or more follow-up visits by day 7, any data on adverse events, or both. After independent screening of the search results by two reviewers, the investigators of eligible studies were invited to contribute individual patient data. Authors quantified day 7 gametocyte carriage, probability of infecting a mosquito, decreases (>25%) in haemoglobin concentration associated with anaemia, and adverse events until day 28 using regression analyses, with random study-site intercepts to account for clustered data. These analyses were registered with PROSPERO, CRD42021279363 (safety) and CRD42021279369 (efficacy). Of 5697 records identified by the search, 30 studies were eligible for analysis. Of these, individual patient data were shared for 23 studies, including 6056 patients from 16 countries: 1171 (19.3%) young children (aged <5 years), 2827 (46.7%) older children (aged 5 years to <15 years), and 2058 (34.0%) adults (aged >=15 years). Adding a single low dose of primaquine (0.2-0.25 mg/kg) to ACTs reduced day 7 gametocyte positivity (adjusted odds ratio [aOR] 0.34, 95% CI 0.22-0.52; p<0.001) and infectivity to mosquitoes over time (aOR per day 0.02, 0.01-0.07, p<0.001). No difference was found in the effect of single low-dose primaquine both on gametocyte positivity in young children compared with older children (1.08, 0.52-2.23; p=0.84) and adults (0.50, 0.20-1.25; p=0.14) and between low-transmission and moderate-to-high transmission settings (1.07, 0.46-2.52; p=0.86), and on infectivity to mosquitoes in young children compared with older children (1.36, 0.07-27.71; p=0.84) and adults (0.31, 0.01-8.84; p=0.50) and between low-transmission and moderate-to-high transmission settings (0.18, 0.01-2.95; p=0.23). Gametocyte clearance was also similar for different ACTs (dihydroartemisinin-piperaquine vs artemether-lumefantrine) when combined with a primaquine target dose of 0.25 mg/kg (1.56, 0.65-3.79; p=0.32 at day 7). However, patients given a primaquine dose of less than 0.2 mg/kg with dihydroartemisinin-piperaquine were more likely to have gametocytaemia than those treated with artemether-lumefantrine (5.68, 1.38-23.48; p=0.016 at day 7). There was no increase in anaemia-associated declines in haemoglobin concentration (>25%) at a primaquine dose of 0.25 mg/kg, regardless of age group, transmission setting, and glucose-6-phosphate dehydrogenase status. The risks of adverse events of grade 2 or higher and of serious adverse events were similar between primaquine and no-primaquine groups, including in young children.

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

Source: Yilma, D., Stepniewska, K., Bousema, T., et al. (2024). Safety and Efficacy of Single-Dose Primaquine to Interrupt Plasmodium Falciparum Malaria Transmission in Children Compared With Adults: A Systematic Review and Individual Patient Data Meta-Analysis. The Lancet Infectious Diseases. 2025; 25(9): 965-976. Published: September, 2025. DOI: 10.1016/S1473-3099(25)00078-7.