Pharmacists' perspectives and perceived barriers to counselling patients with kidney stones.

BACKGROUND: The global increase in kidney stone incidence and its complications emphasise the need for effective management. While pharmacists can play a significant role in counselling and guiding patients, their practices in managing patients with kidney stones remain unclear. OBJECTIVE(S): To explore counselling practices and experiences of pharmacists when dealing with patients with kidney stones and to identify the barriers they face while providing counselling. METHODS: A qualitative study was performed using semi-structured phone interviews with pharmacists practising in Jordan. Pharmacists were selected using quota sampling from those who took part in a previous study focused on pharmacists' knowledge of kidney stone aetiology and treatment. The COM-B Model of Behaviour Change was used to develop the interview guide and the analytical framework. Interviews were transcribed verbatim and analysed using a deductive thematic approach based on the pre-specified analytical framework. RESULTS: Seven pharmacists (85.7% female; 57.1% working in community pharmacies) were interviewed. Counselling practices of patients with kidney stones were categorised into five themes: (1) Pharmacists' beliefs about patient counselling: perceived importance and desire to improve health through counselling; (2) Most priority patients: Types of patients mostly counselled; (3) Content of kidney stones-specific counselling: patient assessment and recommendations about kidney stones management; (4) Duration of the counselling sessions: time offered and influencing factors; (5) Barriers to patient counselling: patient-related, and pharmacist- and doctor-related challenges. CONCLUSIONS: Pharmacists recognise the crucial role of kidney stones counselling but face gaps in their practices, including incomplete dietary education, limited knowledge of medication prescriptions, inconsistent patient-specific approaches, and potential communication challenges. These gaps can be overcome by enhancing training, standardising protocols of kidney stone treatment, promoting interprofessional communication, and improving communication strategies. Future research, including quantitative assessments, is needed to inform strategies that optimise patient counselling practices and facilitate improved outcomes.

A cross-sectional study confirms temporary post-COVID-19 vaccine menstrual irregularity and the associated physiological changes among vaccinated women in Jordan.

Background: COVID-19 vaccines continue to save people's lives around the world; however, some vaccine adverse events have been a major concern which slowed down vaccination campaigns. Anecdotal evidence pointed to the vaccine effect on menstruation but evidence from the adverse event reporting systems and the biomedical literature was lacking. This study aimed to investigate the physiological changes in women during menstruation amid the COVID-19 vaccination. Methods: A cross-sectional online survey was distributed to COVID-19 vaccinated women from Nov 2021 to Jan 2022. The results were analyzed using the SPSS software. Results: Among the 564 vaccinated women, 52% experienced significant menstrual irregularities post-vaccination compared to before regardless of the vaccine type. The kind of menstrual irregularity varied among the vaccinated women, for example, 33% had earlier menstruation, while 35% reported delayed menstruation. About 31% experienced heavier menstruation, whereas 24% had lighter menstrual flow. About 29% had menstruation last longer, but 13% had it shorter than usual. Noteworthy, the menstrual irregularities were more frequent after the second vaccine shot, and they disappeared within 3 months on average. Interestingly, 24% of the vaccinated women reported these irregularities to their gynecologist. Conclusion: The COVID-19 vaccine may cause physiological disturbances during menstruation. Luckily, these irregularities were short-termed and should not be a reason for vaccine hesitancy in women. Further studies are encouraged to unravel the COVID-19 vaccine adverse effect on women's health.

Evaluating kidney function and the associated risk factors among patients with type 2 diabetes mellitus: a cross-sectional study at a tertiary hospital in Jordan.

BACKGROUND: The diabetes prevalence is escalating in Jordan; as a consequence, the risk of developing diabetic kidney diseases is also increasing. OBJECTIVE: This study evaluated the effect of risk factors and comorbidities on kidney function in patients with type 2 diabetes mellitus (T2DM). DESIGN: A cross-sectional, survey-based study. SETTING: Participants were recruited from the endocrinology and cardiology clinics of a tertiary hospital in Jordan. PARTICIPANTS: Patients with T2DM aged 18 years and more who had undergone a kidney function test within a year before data collection. OUTCOME MEASURES: The estimated GFR (eGFR) mean values and proteinuria presence were used to evaluate the impact of risk factors on kidney function. Descriptive and analytical statistical approaches were used to calculate mean, prevalence and correlations. The SPSS software was used with a p value<0.05 for significance. RESULTS: Of the total 331 study participants, 54.1% were men and 45.9% were women. The mean age was 60 years. The eGFR mean values were significantly reduced in patients with T2DM with hypertension, hyperlipidaemia and proteinuria (p<0.01). The correlation analysis results showed that the eGFR was positively correlated with hypertension and hyperlipidaemia presence (rs=0.253, 0.220), and negatively correlated with age, body mass index and diabetes duration (rs=-0.395, -0.151, -0.221), respectively. However, the eGFR did not corelate with income, sex, smoking and anaemia. Of note, about 68% of the patients with T2DM had uncontrolled diabetes. CONCLUSIONS: Kidney function were severely affected in patients with T2DM in the presence of risk factors and comorbidities. It is highly recommended to control diabetes through medications and life style, and to regularly check for kidney function to halt the deteriorations in kidney function.

Both CLIC4 and CLIC5A activate ERM proteins in glomerular endothelium.

The chloride intracellular channel (CLIC) 5A is expressed at very high levels in renal glomeruli, in both endothelial cells (EC) and podocytes. CLIC5A stimulates Rac1- and phosphatidylinositol (4,5)-bisphosphate-dependent ERM (ezrin, radixin, moesin) activation. ERM proteins, in turn, function in lumen formation and in the development of actin-based cellular projections. In mice lacking CLIC5A, ERM phosphorylation is profoundly reduced in podocytes, but preserved in glomerular EC. Since glomerular EC also express CLIC4, we reasoned that, if CLIC4 activates ERM proteins like CLIC5A, then CLIC4 could compensate for the CLIC5A loss in glomerular EC. In glomeruli of CLIC5-deficient mice, CLIC4 expression was upregulated and colocalized with moesin and ezrin in glomerular EC, but not in podocytes. In cultured glomerular EC, CLIC4 silencing reduced ERM phosphorylation and cytoskeletal association, and expression of exogenous CLIC4 or CLIC5A rescued ERM de-phosphorylation due to CLIC4 silencing. In mice lacking either CLIC4 or CLIC5, ERM phosphorylation was retained in glomerular EC, but, in mice lacking both CLIC4 and CLIC5, glomerular EC ERM phosphorylation was profoundly reduced. Although glomerular EC fenestrae developed normally in dual CLIC4/CLIC5-deficient mice, the density of fenestrae declined substantially by 8 mo of age, along with the deposition of subendothelial electron-lucent material. The dual CLIC4/CLIC5-deficient mice developed spontaneous proteinuria, glomerular cell proliferation, and matrix deposition. Thus CLIC4 stimulates ERM activation and can compensate for CLIC5A in glomerular EC. The findings indicate that CLIC4/CLIC5A-mediated ERM activation is required for maintenance of the glomerular capillary architecture.

The chloride intracellular channel 5A stimulates podocyte Rac1, protecting against hypertension-induced glomerular injury.

Glomerular capillary hypertension elicits podocyte remodeling and is a risk factor for the progression of glomerular disease. Ezrin, which links podocalyxin to actin in podocytes, is activated through the chloride intracellular channel 5A (CLIC5A)-dependent phosphatidylinositol 4,5 bisphosphate (PI[4,5]P2) accumulation. Because Rac1 is involved in podocyte actin remodeling and can promote PI[4,5]P2 production we determined whether CLIC5A-dependent PI[4,5]P2 generation and ezrin activation are mediated by Rac1. In COS7 cells, CLIC5A expression stimulated Rac1 but not Cdc42 or Rho activity. CLIC5A also stimulated phosphorylation of the Rac1 effector Pak1 in COS7 cells and in cultured mouse podocytes. CLIC5A-induced PI[4,5]P2 accumulation and Pak1 and ezrin phosphorylation were all Rac1 dependent. In DOCA/Salt hypertension, phosphorylated Pak increased in podocytes of wild-type, but not CLIC5-deficient mice. In DOCA/salt hypertensive mice lacking CLIC5, glomerular capillary microaneurysms were more frequent and albuminuria was greater than in wild-type mice. Thus, augmented hypertension-induced glomerular capillary injury in mice lacking CLIC5 results from abrogation of Rac1-dependent Pak and ezrin activation, perhaps reducing the tensile strength of the podocyte actin cytoskeleton.

Clustered PI(4,5)P2 accumulation and ezrin phosphorylation in response to CLIC5A.

CLIC5A (encoded by CLIC5) is a component of the ezrin-NHERF2-podocalyxin complex in renal glomerular podocyte foot processes. We explored the mechanism(s) by which CLIC5A regulates ezrin function. In COS-7 cells, CLIC5A augmented ezrin phosphorylation without changing ezrin abundance, increased the association of ezrin with the cytoskeletal fraction and enhanced actin polymerization and the formation of cell surface projections. CLIC5A caused the phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] reporter RFP-PH-PLC to translocate from the cytosol to discrete plasma membrane clusters at the cell surface, where it colocalized with CLIC5A. Transiently expressed HA-PIP5Kα colocalized with GFP-CLIC5A and was pulled from cell lysates by GST-CLIC5A, and silencing of endogenous PIP5Kα abrogated CLIC5A-dependent ERM phosphorylation. N- and C-terminal deletion mutants of CLIC5A, which failed to associate with the plasma membrane, failed to colocalize with PIP5Kα, did not alter the abundance of PI(4,5)P2 plasma membrane clusters and failed to enhance ezrin phosphorylation. Relative to wild-type mice, in CLIC5-deficient mice, the phosphorylation of glomerular ezrin was diminished and the cytoskeletal association of both ezrin and NHERF2 was reduced. Therefore, the mechanism of CLIC5A action involves clustered plasma membrane PI(4,5)P2 accumulation through an interaction of CLIC5A with PI(4,5)P2-generating kinases, in turn facilitating ezrin activation and actin-dependent cell surface remodeling.

CLIC5A, a component of the ezrin-podocalyxin complex in glomeruli, is a determinant of podocyte integrity.

The chloride intracellular channel 5A (CLIC5A) protein, one of two isoforms produced by the CLIC5 gene, was isolated originally as part of a cytoskeletal protein complex containing ezrin from placental microvilli. Whether CLIC5A functions as a bona fide ion channel is controversial. We reported previously that a CLIC5 transcript is enriched approximately 800-fold in human renal glomeruli relative to most other tissues. Therefore, this study sought to explore CLIC5 expression and function in glomeruli. RT-PCR and Western blots show that CLIC5A is the predominant CLIC5 isoform expressed in glomeruli. Confocal immunofluorescence and immunogold electron microscopy reveal high levels of CLIC5A protein in glomerular endothelial cells and podocytes. In podocytes, CLIC5A localizes to the apical plasma membrane of foot processes, similar to the known distribution of podocalyxin and ezrin. Ezrin and podocalyxin colocalize with CLIC5A in glomeruli, and podocalyxin coimmunoprecipitates with CLIC5A from glomerular lysates. In glomeruli of jitterbug (jbg/jbg) mice, which lack the CLIC5A protein, ezrin and phospho-ERM levels in podocytes are markedly lower than in wild-type mice. Transmission electron microscopy reveals patchy broadening and effacement of podocyte foot processes as well as vacuolization of glomerular endothelial cells. These ultrastructural changes are associated with microalbuminuria at baseline and increased susceptibility to adriamycin-induced glomerular injury compared with wild-type mice. Together, the data suggest that CLIC5A is required for the development and/or maintenance of the proper glomerular endothelial cell and podocyte architecture. We postulate that the interaction between podocalyxin and subjacent filamentous actin, which requires ezrin, is compromised in podocytes of CLIC5A-deficient mice, leading to dysfunction under unfavorable genetic or environmental conditions.