Nephron最新文献

Glomerular diseases with organized deposits can be classified into various etiologies. A diagnostic algorithm based on clinical and pathological findings has been proposed. However, some cases cannot be diagnosed using existing algorithms. Here, we report the case of a 77-year-old man diagnosed with membranoproliferative glomerulonephritis (MPGN) with striated ultrastructural deposits, micro-filament-like substructures with straight bands arranged in parallel in the subendothelial space by two sequential renal biopsies. His examinations and clinical findings were incompatible with known glomerular diseases with organized deposits. Dialysis was initiated 10 months after the second biopsy procedure. Furthermore, we report the first mass spectrometry analysis of laser micro-dissected glomeruli with striated ultrastructural deposits, which revealed significant levels of fibrinogen and fibronectin. Immunostaining was positive for fibrinogen, fibrin, and fibronectin in the subendothelial space. These findings suggest that the deposits were composed of a fibrin-fibronectin complex and that accumulation of these fibrin-fibronectin complexes possibly induced endothelial injury, leading to MPGN. We also reviewed the literature on the clinical and pathological characteristics of the four cases with striated ultrastructural deposits. Our investigation showed that all patients had the MPGN pattern and striated ultrastructural deposits in the subendothelial space, and all underwent hemodialysis within 3 years of renal biopsy. Clinicians should be aware of the findings of glomerulonephritis with striated ultrastructural deposits since this disease may be a new entity and has a poor prognosis.

Background: In contemporary kidney transplantation, the pathology is important for diagnosing various problems with an allograft. Striking a balance is essential to achieve accuracy and speed of a diagnosis. However, because of the distinctive characteristics of renal allograft pathology, there is a lack of pathologists with expertise in this specific domain.

Summary: A telepathology system using digital pathology can facilitate the delivery of diagnostic outcomes even in settings where pathologists with expertise may not be continuously available. This system is equivalent in diagnostic ability and superior in speed to the method using conventional diagnosis by light microscopy with glass slides. The pathology guidelines of various countries have emphasized the importance of ensuring the quality of digital pathology. Although maintaining the quality of diagnosis is necessary, telepathology in renal allograft pathology is an innovative tool that can shorten the time to diagnosis and address the shortage of pathologists. Unfortunately, the routine use of telepathology is currently limited to only a few institutions in Japan. One of the reasons for this limited use is the heavy burden on facilities requesting biopsies to set up infrastructure, such as slide scanners and servers.

Key message: Consequently, there is an urgent need for greater public support of telepathology.

Introduction: Atrophy of smooth muscle cells (SMCs) in the media of small arteries is occasionally observed, especially in long-term kidney allograft biopsies. The intima-media ratio is used as an index of arteriosclerosis in native kidneys, and medial SMC atrophy suggests severe arteriosclerosis. We aimed to investigate the clinicopathological significance of medial SMC atrophy in small arteries in biopsies from long-term kidney transplants.

Methods: Samples were obtained from kidney allograft biopsies carried out from January 2016 to December 2019, and biopsies obtained 10 years after transplantation were included in the study. The distal small arteries with the most atrophic SMCs in longitudinal sections in each biopsy specimen were selected (outer diameter <150 µm and ≥60 µm). The outer diameter and width of the media, intima, and lumen of each artery were measured. SMC atrophy was evaluated as the media-outer diameter ratio.

Results: Fifty biopsies were eligible. The mean media-outer diameter ratio was 0.27 ± 0.11. Donor age and allograft age were significantly inversely correlated with media-outer diameter ratio (rank correlation coefficient -0.3522, p = 0.0141 and -0.3700, p = 0.0096, respectively). After separation into two groups according to the media-outer diameter ratio, donor age and allograft age were both significantly higher and more focal segmental glomerular sclerosis (FSGS) lesions were observed in the low media-outer diameter ratio group. Multivariate analysis revealed that media-outer diameter ratio was significantly related to donor age, allograft age, and FSGS.

Conclusions: Medial SMC atrophy appears to be related to donor age, allograft age, and FSGS in kidney allografts. Disruption of vascular contraction as a result of medial SMC atrophy in aging allografts may lead to the development of FSGS.

In the article "Immunosuppressant Agents as Add-On Therapy Failed to Improve the Outcome of Immunoglobulin A Nephropathy with Crescent Score C1" [Nephron. 2024;148:587-600; https://doi.org/10.1159/000534788] by Bi et al., the funding grant (No. 82200836) from the Natural Science Foundation of China was mistakenly omitted from the funding statement of the published version.

Background: Patient and caregiver involvement in identifying and designing health interventions can enhance the acceptability and uptake of interventions for person-centered care and outcomes. Our aim was to describe the approaches used to involve patients and caregivers in the identification and design of interventions in chronic kidney disease (CKD).

Methods: Electronic databases were searched to April 2024 for articles that described the involvement of patients and caregivers in the identification and design of interventions for research in CKD. The findings were synthesized using a framework that addressed the type of intervention, purpose and reason of involvement, population involved, mode of involvement, and impacts of patient/caregiver involvement on the intervention.

Results: We identified 14 studies that involved patients with CKD (n = 238) and/or caregivers (n = 36). The types of interventions included psychosocial, educational, lifestyle, and navigator programs. Patients and caregivers were involved to identify and prioritize features of the intervention, describe their lived experience to inform the intervention, provide feedback on intervention design, and identify potential facilitators and barriers to the uptake of the intervention. Patients and caregivers were involved as members of steering committees and advisory groups, and participated through workshops, interviews, focus groups, meetings, and an online messaging forum. The input of patients and caregivers resulted in the addition and changes to intervention features (e.g., content, structure, delivery, and materials) to personalize the intervention and to improve its inclusivity, accessibility, and suitability.

Conclusion: Very few studies have described patient and caregiver involvement in the identification and design of interventions for research in CKD. Patients and caregivers were mostly involved in developing educational, lifestyle, and navigator interventions. Further efforts to involve patients and caregivers in developing interventions for research can help maximize the uptake and impact of person-centered interventions.

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.

Background: The lysosomal autophagic pathway plays a fundamental role in cellular and tissue homeostasis, and its deregulation is linked to human pathologies including kidney diseases. Autophagy can randomly degrade cytoplasmic components in a nonselective manner commonly referred to as bulk autophagy. In contrast, selective forms of autophagy specifically target cytoplasmic structures such as organelles and protein aggregates, thereby being important for cellular quality control and organelle homeostasis.

Summary: Research during the past decades has begun to elucidate the role of selective autophagy in kidney physiology and kidney diseases.

Key messages: In this review, we will summarize the knowledge on lipophagy and mitophagy, two forms of selective autophagy important in renal epithelium homeostasis, and discuss how their deregulations contribute to renal disease progression.

Background: This study aimed to assess the prognostic significance of serum ferritin levels in sepsis-associated acute kidney injury (SA-AKI) and their correlation with short-term mortality. Despite the established predictive value of serum ferritin in various serious diseases, its specific prognostic relevance in SA-AKI remains unexplored. Therefore, this study seeks to fill this research gap by investigating the association between serum ferritin levels and short-term mortality in patients with SA-AKI.

Methods: This retrospective cohort study utilized clinical data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database, including all patients with SA-AKI admitted to the intensive care unit for the first time. The relationship between serum ferritin levels and 28-day mortality was explored using restricted cubic splines. Kaplan-Meier curves and Cox regression models were employed to evaluate the association between serum ferritin levels and mortality. Subgroup and sensitivity analyses were performed to verify the robustness of the results.

Results: In this study, a total of 878 patients (486 males and 392 females) with a median age of 63.7 years were enrolled. The results indicated that increasing serum ferritin levels were linearly associated with a gradual increase in 28-day mortality rates. Specifically, patients in the highest quartile of serum ferritin had significantly higher 28-day mortality compared to those in the reference group (the first quartile of ferritin levels). After adjusting for various factors, the fully adjusted hazard ratio was 1.92 (95% CI: 1.24-2.96, p = 0.003).

Conclusion: In patients with SA-AKI, higher serum ferritin levels are associated with an increased 28-day mortality rate.

Background: Ferroptosis is a novel form of iron-dependent programmed cell death, characterized by lipid peroxidation and the accumulation of reactive oxygen species. Dysregulation of iron metabolism, lipid metabolism, or the antioxidant system can trigger this process. Emerging evidence suggests that ferroptosis is implicated in the pathogenesis and progression of various kidney diseases.

Summary: This review explores the pathophysiological mechanisms of ferroptosis, focusing on its role in cellular damage and disease progression in kidney diseases. The roles of iron homeostasis, lipid peroxidation, and antioxidant defenses in ferroptosis are discussed. Studies have demonstrated that inhibiting ferroptosis can protect against kidney injury, highlighting its potential as a therapeutic target. Additionally, current findings on ferroptosis-targeted therapies, including preclinical studies and potential clinical applications, are summarized.

Key messages: Ferroptosis plays a critical role in the development and progression of kidney diseases. Understanding the mechanisms governing ferroptosis and its relationship with kidney pathology provides a foundation for novel diagnostic and therapeutic strategies. Further research is needed to identify specific molecular mechanisms and advance clinical trials to translate ferroptosis-targeted therapies into practice, paving the way for innovative therapeutic interventions in kidney diseases.

Diabetic kidney disease is the most common driver of chronic kidney disease (CKD)-associated mortality and kidney replacement therapy. Despite recent therapeutic advances (sodium glucose co-transporter 2 [SGLT2] inhibitors, finerenone), the residual kidney and mortality risk remains high for patients already diagnosed of having CKD (i.e., estimated glomerular filtration rate <60 mL/min/1.73 m2 or urinary albumin:creatinine ratio >30 mg/g). The challenge for the near future is to identify patients at higher risk of developing CKD to initiate therapy before CKD develops (primary prevention of CKD) and to identify patients with CKD and high risk of progression or death, in order to intensify therapy. We now discuss recent advances in biomarkers that may contribute to the identification of such high-risk individuals for clinical trials of novel primary prevention or treatment approaches for CKD. The most advanced biomarker from a clinical development point of view is the urinary peptidomics classifier CKD273, that integrates prognostic information from 273 urinary peptides and identifies high-risk individuals before CKD develops.