Nephron最新文献

Background: Sex differences exist in kidney physiology and disease which are underpinned by the biological actions of the sex hormones estrogen, progesterone and testosterone. In this review, we present an up-to-date discussion of the hormonal and molecular signalling pathways implicated in sex differences in kidney health and disease.

Summary: Estrogen and progesterone have protective effects on renal blood flow, glomerular filtration rate and nephron ion and water reabsorptive processes, whereas testosterone tends to compromise these functions. The biological effects of estrogen appear to be the most important in reinforcing kidney function and protecting against kidney diseases in females. The actions of estrogen are myriad but all tend to bolster kidney physiology to maintain a steady-state and adaptable extracellular fluid volume (ECFV) and blood pressure. Estrogen safeguards ECFV homeostasis by stimulating renal epithelial sodium channel (ENaC) and water channel (AQP2) expression and transport function. Renal maintenance of ECFV within narrow physiological limits is a first-line of defense against hypertension and lowers the risk of cardiovascular disease in women. The estrogenic and XX chromosome basis for a female advantage are evident in a wide range of kidney diseases including acute kidney injury, chronic kidney disease, end-stage kidney disease, diabetic kidney disease, and polycystic kidney disease. The molecular mechanisms involve estrogen regulation of nephron ion and water transport, genetic immunogenic responses, activation of the protective arm of the renin angiotensin-aldosterone system and XX chromosome reinforcement of immune responses. Kidney disease can also predispose patients to cancer and women are protected in renal cancer with lower incidence, morbidity, and mortality than age-matched men with the disease.

Key messages: This review underscores the importance of incorporating sex-specific considerations into clinical practice and basic research to bridge the gap in understanding and addressing biological sex disparities in kidney disease and renal cancer.

Introduction: Sepsis is the leading contributor to acute kidney injury (AKI), responsible for 45-70% of AKI occurrences. Despite this, septic AKI is a highly multifactorial and complex condition, and our grasp of its pathogenesis is still not fully developed. Consequently, there remains a significant gap in effective diagnostic and therapeutic strategies for septic AKI.

Methods: In the in vitro experiments, BUMPT cells were exposed to lipopolysaccharides (LPS). In vivo experiments involved inducing sepsis in mice through administration of LPS injections. Additionally, in certain experiments, either a miR-455-5p mimic or an anti-miR-455-5p LAN was administered to the mice via injections into the tail vein. The mice were then sacrificed 24 h following LPS administration for subsequent analysis.

Results: We observed a significant elevation in miR-455-5p levels within renal tubular cells following LPS-induced septic AKI. Our investigation revealed that NF-κB plays a crucial role in the upregulation of miR-455-5p. Inhibition of NF-κB using TPCA-1 prevented the rise in miR-455-5p levels in BUMPT cells (mouse proximal tubular cells from Boston University) cultured in vitro. Chromatin immunoprecipitation assays confirmed that NF-κB directly interacts with the promoter region of the miR-455-5p gene in response to LPS treatment. Functionally, introducing miR-455-5p mimics intensified cell apoptosis, kidney damage, and the production of inflammatory cytokines, while silencing miR-455-5p had protective effects in septic mice. Notably, administering anti-miR-455-5p enhanced SOCS3 expression, whereas miR-455-5p mimics reduced SOCS3 levels following LPS exposure. Furthermore, our luciferase reporter assays demonstrated that SOCS3 is a direct target of miR-455-5p.

Conclusion: This study indicates an NF-κB/miR-455-5p/SOCS3 axis which can exacerbate kidney damage by enhancing renal inflammation. This process highlights potential therapeutic targets for managing septic AKI.

Introduction: Serious outbreaks of Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) have been reported globally. In 2011, Germany experienced a significant outbreak of HUS caused by enteroaggregative E. coli (EAEC) O104:H4 strain. Since then, no other outbreaks of this strain have been reported. This study aims to evaluate pediatric patients affected by the second documented worldwide outbreak of STEC-HUS (EAEC O104:H4 serotype) contaminating local drinking water.

Methods: Medical records of patients hospitalized in five pediatric intensive care units (PICUs) diagnosed with STEC-HUS between July and September 2022 were evaluated retrospectively.

Results: Eighteen patients (14 girls and 4 boys) were enrolled in the study. The median age was 7.4 (Interquartile range [IQR] 1.3-17) years. Abdominal pain was the most common symptom (100%). The mean duration between symptom onset and development of STEC-HUS was 3 days (IQ 1-9). EAEC O104:H4 serotype was detected in the stool samples of 8 patients. Neurological involvement was observed in 3 patients, cardiac involvement in 2 patients, and both in 1 patient. Two patients required respiratory support and dialysis was performed in 16 (88.8%) patients. Plasmapheresis was administered to 2 patients, and eculizumab was given to four. No mortality was reported during follow-up; the mean durations of PICU and hospital stays were 11.3 and 31.6 days, respectively.

Conclusion: Outbreaks of HUS can have serious impacts on both mortality and morbidity. However, timely diagnosis and implementation of appropriate supportive care, including dialysis, respiratory support, and medical treatment for eligible patients, can lead to favorable outcomes.

Introduction: Advance care planning (ACP) is essential in managing patients with end-stage kidney disease (ESKD), yet its integration into clinical practice remains limited, particularly in low- and middle-income countries. This study explores the preferences, attitudes and perceived barriers of nephrology healthcare providers toward ACP for patients with ESKD in a tertiary care center in India.

Methods: A cross-sectional survey was conducted among nephrology healthcare providers at a tertiary care center in India. The survey, developed from literature reviews and pretested, covered demographics, ACP knowledge and attitudes, current practices, and perceived barriers and facilitators. Data collection occurred from September 2022 to March 2023. Quantitative data were analyzed descriptively, and qualitative data through thematic analysis.

Results: A total of 50 healthcare providers participated. While 36% acknowledged the importance of ACP, only 8% routinely engaged in ACP discussions. Major barriers included inadequate training (22%), lack of awareness about the importance of discussing ACP among stakeholders (20%), cultural barriers (18%), lack of time (14%), and the absence of institutional protocols for discussion on ACP (14%). Additional barriers included instances where families withhold health information from patients due to fear of losing hope (16%) and patient/family discomfort in discussing ACP (12%). Providers expressed a need for structured ACP protocols and educational programs.

Conclusion: Despite recognizing its importance, ACP is underutilized in the care of patients with ESKD in India. Addressing the identified barriers through targeted interventions may enhance ACP practices and improve patient outcomes.

The combination of nephrotic syndrome with mild histopathological lesions of IgA nephropathy is considered by some as a special form of IgA nephropathy with superimposed minimal change disease (MCD) while by others as a coincidental deposition of IgA in patients with MCD (MCD-IgAN). We present the first case of complete remission of nephrotic syndrome in a 55-year-old man with MCD-IgAN after the administration of a targeted-release formulation of budesonide (TRF-budesonide). The patient's treatment with TRF-budesonide, even though methylprednisolone, mycophenolate mofetil, and cyclophosphamide had been previously tried, is of particular importance because it not only suggests that TRF-budesonide appears to be a promising treatment for MCD-IgAN but may also provide a new therapeutic option for patients with podocytopathies.

Kidney transplantation (KT) is the treatment of choice for chronic kidney disease patients, but there is a continued loss of grafts in the long-term (50% at 10 years) due to either patient death or chronic allograft dysfunction. Metabolic syndrome (MS) is very prevalent after KT (30-40%) and its components contribute to the appearance of nonalcoholic fatty liver disease/metabolic dysfunction-associated fatty liver disease (NAFLD/MAFLD) and nonalcoholic steatohepatitis (NASH), which represent the hepatic component of MS. Furthermore, about 20-40% of KT recipients present early graft inflammation, including subclinical inflammation. Thus, the relationship between NAFLD-MAFLD/NASH and graft inflammation may be bidirectional, though no definite link between NAFLD-NASH and graft inflammation is currently known. Additionally, MS-related risk factors are associated with modern immunosuppressants and a negative synergistic effect on graft and patient survival seems plausible. Indeed, proinflammatory cytokines and adipokines released by adipose tissue can generate a low-grade inflammatory state and endothelial dysfunction, both involved in the appearance of CVD, and these disorders are associated with worsening liver lesions and subclinical and clinical atheromatosis. In this review, we discuss the recent clinical evidence regarding the prevalence and risk factors of MS and NAFLD/MAFLD following KT. Additionally, we propose the potential linking mechanism between NAFLD/MAFLD-NASH and post-KT graft inflammation, as well as alternative therapies for NAFLD after KT. Prevention of long-term life-threatening complications in this particular population rests upon better understanding and management of these severe clinical complications.

Introduction: Metabolic syndrome (MetS) and chronic kidney disease are both important risk factors for cardiovascular disease and are closely related to each other. We retrospectively investigated whether MetS or its components increase the risk of development of impaired kidney function in the Japanese general population.

Methods: This is a retrospective cohort study which enrolled 14,917 participants who visited our hospital for physical checkups from 2008 to 2018 and had normal estimated glomerular filtration rate (eGFR ≥60 mL/min/1.73 m2) during the baseline examination. Participants were followed up for the median of 1,847 days until 2019 with the development of impaired kidney function (eGFR <60 mL/min/1.73 m2) as the endpoint. The definition of MetS was based on Japanese diagnostic criteria (2005).

Results: Throughout the study, 2,150 participants (25.9 per 1,000 person-year) developed impaired kidney function after their baseline checkup. The incidence of impaired kidney function was more frequent in participants with MetS (39.3 per 1,000 person-year) than without (24.2 per 1,000 person-year, p < 0.001). Moreover, each MetS component was positively associated with the incidence of impaired kidney function, where the incidence of impaired kidney function increased with the number of MetS components at baseline (0, 1, 2, and ≥3 component(s); 17.3, 26.9, 32.9, and 39.7 per 1,000 person-year, respectively). Multivariate Cox hazard analysis revealed that MetS was an independent risk factor for impaired kidney function after adjusting for known risk factors (hazard ratio, 1.29; 95% confidence interval, 1.15-1.45).

Conclusions: Testing for MetS and its components can help evaluate the risk of developing impaired kidney function in the general population.

Introduction: Due to the chronic nature of kidney disease, the challenges of symptom burden, and reduced mortality and comorbidity, individuals living with the condition experience substantial anxiety and depression. Incorporating the arts into clinical practice is encouraged to promote and support mental health and well-being. The aim of the PAINT project was to undertake an international mapping exercise to identify the current provision of arts programmes in kidney centres for people living with kidney disease.

Methods: A multimethod approach was employed, involving a cross-sectional online survey and semi-structured qualitative interviews, which employed qualitative description research design. Healthcare staff working in kidney centres or organisations providing arts activities to individuals living with kidney disease were recruited into the study.

Results: One hundred and nineteen participants from 29 countries responded to the survey, with 39 of the respondents reporting arts activities in their renal unit. There was a wide range of respondents in terms of role, and the types of arts activities included visual arts activities, music, literature/creative writing, film, movement/dance, and craft. Individuals with chronic kidney disease who had taken part in arts activities were mostly adults (64%), and most were undergoing haemodialysis (82%). Sixteen respondents participated in the semi-structured interviews and encouraged the adoption of arts activities for people living with kidney disease. Three themes were identified: enhanced well-being and positive outcomes for individuals living with kidney disease; staff engagement and enthusiasm; and barriers to participation.

Conclusions: This overview of arts activities being offered globally to people living with kidney disease and experiences of renal healthcare staff who provide activities in their units are encouraging in terms of arts in healthcare. These practitioners have observed the benefits of this person-centred arts approach in action, predominantly in terms of the positive impact on the well-being of individuals with kidney disease and improved relationships with staff in dialysis units. Further attention and funding should be focused on arts activities within renal centres.