Residents' learning and behavior about tool-guided clinical assessment of social determinants of health.

Background: The specific dimensions of learners that have been impacted by educational programs related to social determinants of health (SDoH) remain unknown. This study aims to elucidate how learners are affected by postgraduate education (a single 90-min educational session) regarding tool-guided clinical assessment of patients' social backgrounds. Methods: A pretest-posttest design was utilized in which residents (postgraduate year (PGY) 1 or 2) and fellows in family medicine (PGY over 3) were recruited. Likert-type questions were developed based on previous qualitative findings. Participants answered these questions before, immediately after, and 1.5 months after the educational session on tool-guided clinical SDoH assessment. Paired-sample t-tests were used, and effect size was measured using Cohen's d. Results: A total of 114 residents and fellows participated. After the session, participants expressed more interest in knowing their patients' social backgrounds when considering how to address their patients and were more open to embracing a pre-established assessment framework. Participants also considered clinical skills related to SDoH as learnable and improved their attitude toward patients. They reported that they did not perform specific interventions related to SDoH within 1.5 months after the session. Unlike previous qualitative findings, their concern about the implementation of SDoH-related practices did not increase significantly. Conclusion: An educational session on tool-guided SDoH assessment may have a positive impact on learners' attitudes related to addressing patients' social backgrounds without fostering concerns.

The Usage of the Term "Social" in Japanese Primary Care Literature.

INTRODUCTION: There has been a growing recognition of the importance of incorporating a "social" perspective in primary care practice. However, the specific meaning of the term "social" in the context of primary care is often not clearly defined or explained in the literature. This study aims to explore the usage and interpretation of the term "social" in primary care discourse in Japan. METHODS: We collected papers containing the term "social" ("shakai-teki" in Japanese) from 810 papers published between 2010 and 2022 in the Official Journal of the Japan Primary Care Association. Through abductive coding, we examined how the term was employed and the different meanings attributed to it. RESULTS: The instances of using the term "social" were classified into five distinct categories: (i) non-medical, (ii) emphasizing the importance of topics, (iii) public as an object, (iv) connections with people who support health and well-being, and (v) structural inequities that are detrimental to health.  Conclusion: The analysis revealed that the term "social" in the context of primary care discourse was multifaceted and characterized by ambiguity. To ensure effective communication and clarity in discussions, it is crucial for primary care professionals to have a clear understanding of the intended meaning and implications of the term "social."

The impact of patients' social backgrounds assessment on nursing care: Qualitative research.

Background: Although nurses are expected to address the social determinants of health (SDH) in clinical settings, the perspectives of front-line nurses on the integration of SDH into their clinical practice remain unclear. Understanding the dynamism of this integration and its outcomes can yield crucial insights into effective nursing care. This study aims to elucidate the integration and adoption of tool-based SDH assessment nursing programs and their impacts on daily nursing care. Methods: We conducted qualitative research at a small community-based hospital in Japan, where a tool-based program characterized by social background interviews and documentation was implemented. Nurses at the hospital were recruited via purposive and snowball sampling. After hypothesis generation, semi-constructed in-depth online interviews were conducted. Each interview lasted between 30 and 50 min. The data were analyzed via thematic analysis using the framework approach. Results: A total of 16 nurses participated. Participants' incorporation of the novel SDH assessment program was bolstered by prior learning and their recognition of its practical value. Institutional support and collaborative teamwork further facilitated the adoption of this innovation. Enhanced knowledge about the social contexts of their patients contributed to increased respect, empathy, and self-affirmation among participants, consequently enhancing the quality of nursing care. Conclusion: Through team-based learning, reflection, and support, nurses can integrate a tool-based SDH assessment program into their daily nursing practice. This program has the potential to empower nurses to deliver more holistic care and redefine their professional identity. Further research is warranted to assess patient-reported outcomes.

Development and assessment of a vaccine administration training course for medical students.

BACKGROUND: Vaccine administration skills are very important for physicians, especially in the era of global pandemics. However, medical students have reported that practical sessions to develop these skills are insufficient. Therefore, the aim of our study was to develop a vaccination training course for medical students. We also examined its educational effectiveness. METHODS: 5th- and 6th-year medical students at the University of Tokyo were recruited to attend the vaccine administration training course in 2021. These students were our study participants. Our course consisted of an orientation part, which included a lecture on the indications, adverse events, and vaccination techniques of flu vaccines and practice on a simulator, and a main part in which the staff of the University of Tokyo Hospital were actually vaccinated. Before and after the main part of the course, study participants completed an online questionnaire that assessed their confidence in vaccine administration technique through a five-point Likert scale. We also surveyed their feedback about the course content and process. At the beginning and end of the main part, their technical competence in vaccination was assessed by two independent doctors. These doctors used a validated checklist scale (ranging from 16 to 80) and a global rating scale (ranging from 0 to 10). We used their mean scores for analysis. The quantitative data were analyzed through the Wilcoxon signed-rank test. For the qualitative data of the questionnaire, thematic analysis was conducted. RESULTS: All 48 course participants participated in our study. Participants' confidence in vaccination technique (Z = -5.244, p < 0.05) and vaccination skill significantly improved (checklist rating: Z = -5.852, p < 0.05; global rating: Z = -5.868, p < 0.05). All participants rated the course as, "overall educational." Our thematic analysis identified four emerging themes: interest in medical procedures, efficacy of supervision and feedback, efficacy of "near-peer" learning, and very instructive course. CONCLUSIONS: In our study, we developed a vaccine administration course for medical students, assessed their vaccination techniques and confidence in those techniques, and investigated their perceptions of the course. Students' vaccination skills and confidence improved significantly after the course, and they positively evaluated the course based on a variety of factors. Our course will be effective in educating medical students about vaccination techniques.

Assessing Social Circumstances in Primary Care: Expert Consensus via Delphi Technique.

Background and Objective: In the Japanese primary care setting, a set of questions to screen patients' social circumstances has never been developed in a scientific manner. This project aimed to reach a consensus among diverse experts to develop a set of such questions, to meet the need for assessing patients' health-related social circumstances. Methods: We used a Delphi technique to generate expert consensus. The expert panel was composed of various clinical professionals, medical trainees, researchers, support members for marginalized people, and patients. We conducted multiple rounds of communication online. In round 1, the participants provided their opinions about what health care professionals should ask to assess patients' social circumstances in primary care settings. These data were analyzed into several themes. In round 2, all themes were confirmed by consensus. Results: Sixty-one people participated in the panel. All participants completed the rounds. Six themes were generated and confirmed: economic condition and employment, access to health care and other services, living in everyday life and leisure time, total physiological needs, tools and technology, and history of the patient's life. In addition, the panelists emphasized the importance of respecting the patient's preferences and values. Conclusion: A questionnaire, abbreviated by the acronym of HEALTH+P, was developed. Further research about its clinical feasibility and impact on patient outcomes is warranted.

Primary care physicians' perceptions of social determinants of health recommendations: a qualitative study.

BACKGROUND: Several organisations have called for primary care professionals to address social determinants of health (SDoH) in clinical settings. For primary care physicians to fulfill their community health responsibilities, the implications of the SDoH recommendations need to be clarified. AIM: To describe primary care physicians' views about being asked to address SDoH in clinical settings, from both positive and negative perspectives. DESIGN & SETTING: A qualitative study in Japan. Twenty-one physicians were purposively recruited. METHOD: 'Love and breakup letter' methodology was used to collect qualitative data that contained both positive and negative feelings. Participants wrote love and breakup letters about being asked to address SDoH in a clinical setting, then undertook an in-depth online interview. Data were analysed via thematic analysis using the framework approach. RESULTS: The following themes were identified: (i) primary care physicians take pride in being expected to address SDoH; (ii) primary care physicians rely on the recommendations as a partner, even in difficult situations; (iii) primary care physicians consider the recommendations to be bothersome, with unreasonable demands and challenges, especially when supportive surroundings are lacking; and (iv) primary care physicians reconstruct the recommendations on the basis of their experience. CONCLUSION: Primary care physicians felt both sympathy and antipathy towards recommendations asking them to address SDoH in their clinical practice. The recommendations were not followed literally, instead contributing to physicians' clinical mindlines. Professional organisations that plan to develop and publish recommendations about SDoH should consider how their recommendations might be perceived by their target audience.

Defining the observable processes of patient care related to social determinants of health.

INTRODUCTION: An understanding of social determinants of health (SDH) and patients' social circumstances is recommended to deliver contextualised care. However, the processes of patient care related to SDH in clinical settings have not been described in detail. Observable practice activities (OPAs) are a collection of learning objectives and activities that must be observed in daily practice and can be used to describe the precise processes for professionals to follow in specific situations (process OPA.) METHODS: We used a modified Delphi technique to generate expert consensus about the process OPA for patient care related to SDH in primary care settings. To reflect the opinions of various stakeholders, the expert panel comprised clinical professionals (physicians, nurses, public health nurses, social workers, pharmacists and medical clerks), residents, medical students, researchers (medical education, health care, sociology of marginalised people), support members for marginalised people and patients. The Delphi rounds were conducted online. In Round 1, a list of potentially important steps in the processes of care was distributed to panellists. The list was modified, and one new step was added. In Round 2, all steps were acknowledged with few modifications. RESULTS: Of 63 experts recruited, 61 participated, and all participants completed the Delphi rounds. A total of 14 observable steps were identified, which were divided into four components: communication, practice, maintenance and advocacy. The importance of ongoing patient-physician relationships and collaboration with professionals and stakeholders was emphasised for the whole process of care. DISCUSSION: This study presents the consensus of a variety of experts on the process OPA for patient care related to SDHs. Further research is warranted to investigate how this Communication-Practice-Maintenance-Advocacy framework could affect medical education, quality of patient care, and patient outcomes.

Insulin-induced mTOR signaling and gluconeogenesis in renal proximal tubules: A mini-review of current evidence and therapeutic potential.

Energy is continuously expended in the body, and gluconeogenesis maintains glucose homeostasis during starvation. Gluconeogenesis occurs in the liver and kidneys. The proximal tubule is the primary location for renal gluconeogenesis, accounting for up to 25% and 60% of endogenous glucose production during fasting and after a meal, respectively. The mechanistic target of rapamycin (mTOR), which exists downstream of the insulin pathway, plays an important role in regulating proximal tubular gluconeogenesis. mTOR is an atypical serine/threonine kinase present in two complexes. mTORC1 phosphorylates substrates that enhance anabolic processes such as mRNA translation and lipid synthesis and catabolic processes such as autophagy. mTORC2 regulates cytoskeletal dynamics and controls ion transport and proliferation via phosphorylation of SGK1. Therefore, mTOR signaling defects have been implicated in various pathological conditions, including cancer, cardiovascular disease, and diabetes. However, concrete elucidations of the associated mechanisms are still unclear. This review provides an overview of mTOR and describes the relationship between mTOR and renal.

Experience of residents learning about social determinants of health and an assessment tool: Mixed-methods research.

Background: Educating healthcare professionals about the social determinants of health is important in improving health outcomes of marginalized patients. Residents' experience of learning about the social determinants of health and a clinical assessment tool remains unclear. Methods: Residents participated in an online session about the social determinants of health and the assessment tool. Using the New World Kirkpatrick Model, we obtained data about participants' experience from various perspectives. The data were analyzed using a concurrent triangulation mixed-methods design. Results: The study included 20 out of 30 residents. Their response was good, and self-reported learning scores were increased by the session. They learned when to ask about patients' social conditions, what to ask, and how to coordinate medical care appropriately. Participants reported reflecting on their role as medical professionals and implementing new practices based on their learning, as well as concerns about addressing patients' social conditions. Conclusion: Through learning about the social determinants of health, and assessment tools, residents both acquired knowledge and skills, and reflected on their previous practice, accepted patients as they are, understood difficult patients better, and developed interprofessional collaboration. Medical education about the social determinants of health can trigger changes in residents' views.

Primary care nurses during the coronavirus disaster and their struggle: Qualitative research.

Background: Coronavirus disease 2019 (COVID-19) has substantially affected the health and lives of medical professionals. However, the experiences of nurses engaged in primary care remain unclear. We explored how nurses working in primary care were psychologically and socially affected by the COVID-19 disaster and how they overcame the difficulties experienced. Methods: We conducted a qualitative study of seven Japanese nurses working in primary care. Data collection was performed before, during, and after a workshop based on the Tojisha-Kenkyu (user-led research) framework to explore how the COVID-19 disaster affected the nurses and how they coped. Data were analyzed using inductive thematic analysis. Results: Three themes emerged from the analysis: effects of the COVID-19 disaster on nurses, nurses' newly found strength during the pandemic, and their changes and achievements through the Tojisha-Kenkyu framework. The first theme comprised four subthemes: fear of the unknown; difficulty in adaptation; dysfunction in patient care; and defilement and oppression. The second theme involved feeling in control and professionalism. The third theme, which was based on participants' discovery of "same and different" fellowships, showed work reconstruction and self-understanding, which alleviated their difficulties. Conclusions: The effect of the pandemic on nurses working in primary care ranges from work-related frustration to daily life issues. The Tojisha-Kenkyu method can help nurses to alleviate difficulties. Further research should be conducted to elucidate the constant burden on primary care professionals and establish appropriate occupational and daily life support during pandemics.

Oxidized alkyl phospholipids stimulate sodium transport in proximal tubules via a nongenomic PPARγ-dependent pathway.

Oxidized phospholipids have been shown to exhibit pleiotropic effects in numerous biological contexts. For example, 1-O-hexadecyl-2-azelaoyl-sn-glycero-3-phosphocholine (azPC), an oxidized phospholipid formed from alkyl phosphatidylcholines, is a peroxisome proliferator-activated receptor gamma (PPARγ) nuclear receptor agonist. Although it has been reported that PPARγ agonists including thiazolidinediones can induce plasma volume expansion by enhancing renal sodium and water retention, the role of azPC in renal transport functions is unknown. In the present study, we investigated the effect of azPC on renal proximal tubule (PT) transport using isolated PTs and kidney cortex tissues and also investigated the effect of azPC on renal sodium handling in vivo. We showed using a microperfusion technique that azPC rapidly stimulated Na+/HCO3- cotransporter 1 (NBCe1) and luminal Na+/H+ exchanger (NHE) activities in a dose-dependent manner at submicromolar concentrations in isolated PTs from rats and humans. The rapid effects (within a few minutes) suggest that azPC activates NBCe1 and NHE via nongenomic signaling. The stimulatory effects were completely blocked by specific PPARγ antagonist GW9662, ERK kinase inhibitor PD98059, and CD36 inhibitor sulfosuccinimidyl oleate. Treatment with an siRNA against PPAR gamma completely blocked the stimulation of both NBCe1 and NHE by azPC. Moreover, azPC induced ERK phosphorylation in rat and human kidney cortex tissues, which were completely suppressed by GW9662 and PD98059 treatments. These results suggest that azPC stimulates renal PT sodium-coupled bicarbonate transport via a CD36/PPARγ/mitogen-activated protein/ERK kinase/ERK pathway. We conclude that the stimulatory effects of azPC on PT transport may be partially involved in volume expansion.

Computer-based test (CBT) and OSCE scores predict residency matching and National Board assessment results in Japan.

CONTEXT: The Japan Residency Matching Program (JRMP) launched in 2003 and is now a significant event for graduating medical students and postgraduate residency hospitals. The environment surrounding JRMP changed due to Japanese health policy, resulting in an increase in the number of unsuccessfully-matched students in the JRMP. Beyond policy issues, we suspected there were also common characteristics among the students who do not get a match with residency hospitals. METHODS: In total 237 out of 321 students at The University of Tokyo Faculty of Medicine graduates from 2018 to 2020 participated in the study. The students answered to the questionnaire and gave written consent for using their personal information including the JRMP placement, scores of the pre-clinical clerkship (CC) Objective Structured Clinical Examinations (OSCE), the Computer-Based Test (CBT), the National Board Examination (NBE), and domestic scores for this study. The collected data were statistically analyzed. RESULTS: The JRMP placements were correlated with some of the pre-CC OSCE factors/stations and/or total scores/global scores. Above all, the result of neurological examination station had most significant correlation between the JRMP placements. On the other hand, the CBT result had no correlation with the JRMP results. The CBT results had significant correlation between the NBE results. CONCLUSIONS: Our data suggest that the pre-clinical clerkship OSCE score and the CBT score, both undertaken before the clinical clerkship, predict important outcomes including the JRMP and the NBE. These results also suggest that the educational resources should be intensively put on those who did not make good scores in the pre-clinical clerkship OSCE and the CBT to avoid the failure in the JRMP and the NBE.

Insulin promotes sodium transport but suppresses gluconeogenesis via distinct cellular pathways in human and rat renal proximal tubules.

Insulin is known to promote sodium transport and regulate gluconeogenesis in renal proximal tubules. Although protein kinase B (also known as Akt) and mammalian target of rapamycin complexes (mTORC) have been established as key regulators in the insulin signaling pathway, their roles in proximal tubules are poorly understood. To help define this, we examined the components of insulin signaling in sodium transport and gluconeogenesis in isolated human and rat proximal tubules, and also investigated the role of insulin in sodium handling and mTORC1 in insulin signaling in vivo. In isolated human and rat proximal tubules, Akt and mTORC1/2 inhibition suppressed insulin-stimulated sodium-bicarbonate co-transporter 1 (NBCe1) activity, whereas mTORC1 inhibition had no effect. Akt2 and mTORC2 gene silencing largely inhibited insulin-stimulated NBCe1 activity, whereas silencing of Akt1 and mTORC1 had no effect. Furthermore, insulin decreased sodium excretion, and this effect depended on phosphoinositide 3 kinase in vivo. Moreover, insulin reduced glucose production in rat proximal tubules and the expression of gluconeogenic genes in human and rat proximal tubules. Akt and mTORC1 inhibition largely abolished the observed insulin-mediated inhibitory effects. Gene silencing of insulin receptor substrate 1 (IRS1), Akt2, mTORC1, and mTORC2 also abolished insulin-mediated inhibition of gluconeogenesis. Additionally, in vivo, mTORC1 inhibition abolished insulin-mediated inhibitory effects in rat proximal tubules, although not in liver. These results indicate that insulin-stimulated proximal tubule sodium transport is mediated via the Akt2/mTORC2 pathway, whereas insulin-suppressed proximal tubule gluconeogenesis is mediated via the IRS1/Akt2/mTORC1/2 pathway. Thus, distinct pathways may play important roles in hypertension and hyperglycemia in metabolic syndrome and diabetes.

SLC4A4 compound heterozygous mutations in exon-intron boundary regions presenting with severe proximal renal tubular acidosis and extrarenal symptoms coexisting with Turner's syndrome: a case report.

BACKGROUND: Congenital NBCe1A deficiency with the SLC4A4 mutation causes severe proximal renal tubular acidosis, which often comprises extrarenal symptoms, such as intellectual disability and developmental delay, glaucoma, cataract and band keratopathy. To date, almost all mutations have been found to be homozygous mutations located in exons. CASE PRESENTATION: We performed direct nucleotide sequencing analysis of exons and exon-intron boundary regions of the SLC4A4 in a patient presenting with severe renal proximal tubule acidosis, glaucoma and intellectual disability and her parents without these signs. The examination revealed compound heterozygous mutations in exon-intron boundary regions, c.1076 + 3A > C and c.1772 - 2A > T, neither of which have been reported previously. While the former mutation was found in the mother, the latter was found in the father. The transcript of the SLC4A4 gene was almost undetectable, and the patient was also diagnosed with Turner's syndrome. CONCLUSIONS: We identified two novel SLC4A4 mutations, c.1076 + 3A > C and c.1772 - 2A > T. When presented in a compound heterozygous state, these mutations caused a phenotype of severe renal proximal tubular acidosis along with glaucoma and mental retardation. This is the first report of congenital proximal renal tubular acidosis carrying compound heterozygous SLC4A4 mutations in exon-intron boundary regions. We suggest that an mRNA surveillance mechanism, nonsense-mediated RNA decay, following aberrant splicing was the reason that the SLC4A4 transcript was almost undetectable in the proband.

Effects of Nitric Oxide on Renal Proximal Tubular Na+ Transport.

Nitric oxide (NO) has a wide variety of physiological functions in the kidney. Besides the regulatory effects in intrarenal haemodynamics and glomerular microcirculation, in vivo studies reported the diuretic and natriuretic effects of NO. However, opposite results showing the stimulatory effect of NO on Na+ reabsorption in the proximal tubule led to an intense debate on its physiological roles. Animal studies have showed the biphasic effect of angiotensin II (Ang II) and the overall inhibitory effect of NO on the activity of proximal tubular Na+ transporters, the apical Na+/H+ exchanger isoform 3, basolateral Na+/K+ ATPase, and the Na+/HCO3- cotransporter. However, whether these effects could be reproduced in humans remained unclear. Notably, our recent functional analysis of isolated proximal tubules demonstrated that Ang II dose-dependently stimulated human proximal tubular Na+ transport through the NO/guanosine 3',5'-cyclic monophosphate (cGMP) pathway, confirming the human-specific regulation of proximal tubular transport via NO and Ang II. Of particular importance for this newly identified pathway is its possibility of being a human-specific therapeutic target for hypertension. In this review, we focus on NO-mediated regulation of proximal tubular Na+ transport, with emphasis on the interaction with individual Na+ transporters and the crosstalk with Ang II signalling.

The role of renal proximal tubule transport in the regulation of blood pressure.

The electrogenic sodium/bicarbonate cotransporter 1 (NBCe1) on the basolateral side of the renal proximal tubule plays a pivotal role in systemic acid-base homeostasis. Mutations in the gene encoding NBCe1 cause severe proximal renal tubular acidosis accompanied by other extrarenal symptoms. The proximal tubule reabsorbs most of the sodium filtered in the glomerulus, contributing to the regulation of plasma volume and blood pressure. NBCe1 and other sodium transporters in the proximal tubule are regulated by hormones, such as angiotensin II and insulin. Angiotensin II is probably the most important stimulator of sodium reabsorption. Proximal tubule AT1A receptor is crucial for the systemic pressor effect of angiotensin II. In rodents and rabbits, the effect on proximal tubule NBCe1 is biphasic; at low concentration, angiotensin II stimulates NBCe1 via PKC/cAMP/ERK, whereas at high concentration, it inhibits NBCe1 via NO/cGMP/cGKII. In contrast, in human proximal tubule, angiotensin II has a dose-dependent monophasic stimulatory effect via NO/cGMP/ERK. Insulin stimulates the proximal tubule sodium transport, which is IRS2-dependent. We found that in insulin resistance and overt diabetic nephropathy, stimulatory effect of insulin on proximal tubule transport was preserved. Our results suggest that the preserved stimulation of the proximal tubule enhances sodium reabsorption, contributing to the pathogenesis of hypertension with metabolic syndrome. We describe recent findings regarding the role of proximal tubule transport in the regulation of blood pressure, focusing on the effects of angiotensin II and insulin.

Functional coupling of V-ATPase and CLC-5.

Dent's disease is an X-linked renal tubulopathy characterized by low molecular weight proteinuria, hypercalciuria and progressive renal failure. Disease aetiology is associated with mutations in the CLCN5 gene coding for the electrogenic 2Cl-/H+ antiporter chloride channel 5 (CLC-5), which is expressed in the apical endosomes of renal proximal tubules with the vacuolar type H+-ATPase (V-ATPase). Initially identified as a member of the CLC family of Cl- channels, CLC-5 was presumed to provide Cl- shunt into the endosomal lumen to dissipate H+ accumulation by V-ATPase, thereby facilitating efficient endosomal acidification. However, recent findings showing that CLC-5 is in fact not a Cl- channel but a 2Cl-/H+ antiporter challenged this classical shunt model, leading to a renewed and intense debate on its physiological roles. Cl- accumulation via CLC-5 is predicted to play a critical role in endocytosis, as illustrated in mice carrying an artificial Cl- channel mutation E211A that developed defective endocytosis but normal endosomal acidification. Conversely, a recent functional analysis of a newly identified disease-causing Cl- channel mutation E211Q in a patient with typical Dent's disease confirmed the functional coupling between V-ATPase and CLC-5 in endosomal acidification, lending support to the classical shunt model. In this editorial, we will address the current recognition of the physiological role of CLC-5 with a specific focus on the functional coupling of V-ATPase and CLC-5.

Bacteremia in hemodialysis patients.

Infection is a common complication and is the second leading cause of death in hemodialysis patients. The risk of bacteremia in hemodialysis patients is 26-fold higher than in the general population, and 1/2-3/4 of the causative organisms of bacteremia in hemodialysis patients are Gram-positive bacteria. The ratio of resistant bacteria in hemodialysis patients compared to the general population is unclear. Several reports have indicated that hemodialysis patients have a higher risk of methicillin-resistant Staphylococcus aureus infection. The most common site of infection causing bacteremia is internal prostheses; the use of a hemodialysis catheter is the most important risk factor for bacteremia. Although antibiotic lock of hemodialysis catheters and topical antibiotic ointment can reduce catheter-related blood stream infection (CRBSI), their use should be limited to necessary cases because of the emergence of resistant organisms. Systemic antibiotic administration and catheter removal is recommended for treating CRBSI, although a study indicated the advantages of antibiotic lock and guidewire exchange of catheters over systemic antibiotic therapy. An infection control bundle recommended by the Center for Disease Control and Prevention succeeded in reducing bacteremia in hemodialysis patients with either a catheter or arteriovenous fistula. Appropriate infection control can reduce bacteremia in hemodialysis patients.

Selective Insulin Resistance in the Kidney.

Insulin resistance has been characterized as attenuation of insulin sensitivity at target organs and tissues, such as muscle and fat tissues and the liver. The insulin signaling cascade is divided into major pathways such as the PI3K/Akt pathway and the MAPK/MEK pathway. In insulin resistance, however, these pathways are not equally impaired. For example, in the liver, inhibition of gluconeogenesis by the insulin receptor substrate (IRS) 2 pathway is impaired, while lipogenesis by the IRS1 pathway is preserved, thus causing hyperglycemia and hyperlipidemia. It has been recently suggested that selective impairment of insulin signaling cascades in insulin resistance also occurs in the kidney. In the renal proximal tubule, insulin signaling via IRS1 is inhibited, while insulin signaling via IRS2 is preserved. Insulin signaling via IRS2 continues to stimulate sodium reabsorption in the proximal tubule and causes sodium retention, edema, and hypertension. IRS1 signaling deficiency in the proximal tubule may impair IRS1-mediated inhibition of gluconeogenesis, which could induce hyperglycemia by preserving glucose production. In the glomerulus, the impairment of IRS1 signaling deteriorates the structure and function of podocyte and endothelial cells, possibly causing diabetic nephropathy. This paper mainly describes selective insulin resistance in the kidney, focusing on the proximal tubule.

A pure chloride channel mutant of CLC-5 causes Dent's disease via insufficient V-ATPase activation.

Dent's disease is characterized by defective endocytosis in renal proximal tubules (PTs) and caused by mutations in the 2Cl(-)/H(+) exchanger, CLC-5. However, the pathological role of endosomal acidification in endocytosis has recently come into question. To clarify the mechanism of pathogenesis for Dent's disease, we examined the effects of a novel gating glutamate mutation, E211Q, on CLC-5 functions and endosomal acidification. In Xenopus oocytes, wild-type (WT) CLC-5 showed outward-rectifying currents that were inhibited by extracellular acidosis, but E211Q and an artificial pure Cl(-) channel mutant, E211A, showed linear currents that were insensitive to extracellular acidosis. Moreover, depolarizing pulse trains induced a robust reduction in the surface pH of oocytes expressing WT CLC-5 but not E211Q or E211A, indicating that the E211Q mutant functions as a pure Cl(-) channel similar to E211A. In HEK293 cells, E211A and E211Q stimulated endosomal acidification and hypotonicity-inducible vacuolar-type H(+)-ATPase (V-ATPase) activation at the plasma membrane. However, the stimulatory effects of these mutants were reduced compared with WT CLC-5. Furthermore, gene silencing experiments confirmed the functional coupling between V-ATPase and CLC-5 at the plasma membrane of isolated mouse PTs. These results reveal for the first time that the conversion of CLC-5 from a 2Cl(-)/H(+) exchanger into a Cl(-) channel induces Dent's disease in humans. In addition, defective endosomal acidification as a result of insufficient V-ATPase activation may still be important in the pathogenesis of Dent's disease.