Nephron最新文献

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.

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.

Introduction: Lysinuric protein intolerance (LPI) is a multisystemic inborn error of metabolism with a variable clinical expressivity that usually begins in childhood with growth failure and gastroenterological/neurological problems related to the altered urea cycle and, later, with complications involving the renal, pulmonary, and immunohematological systems.

Case report: We present the case of a 40-year-old woman suffering from chronic kidney disease in the context of a LPI, whose diagnosis was challenging because the signs of the disease were always blurred and the patient never manifested critical episodes typical of this multisystemic disease. In addition to renal disease, splenomegaly, thrombocytopenia, elevated lactate dehydrogenase (LDH), hyperferritinemia, and hypertriglyceridemia were also present. A thorough investigation of the patient's food preferences revealed her spontaneous aversion to protein-containing foods and excessive drowsiness during the occurrence of infectious episodes or on the rare occasions of excessive protein intake, although without ever coming to medical attention. These nuanced signs led us to suspect an impairment of the urea cycle and ultimately allowed us to narrow down the diagnosis to LPI through biochemical and genetic investigations.

Conclusion: Nephrologists should consider LPI in the differential diagnosis, whenever a patient presents with mixed proteinuria, tubular dysfunction, and/or chronic kidney disease of unknown origin. In these circumstances, we suggest looking for other signs such as growth failure, signs and symptoms ascribed to urea-cycle impairment, pulmonary involvement, hepatosplenomegaly, and laboratory alterations such as pancytopenia, hyperferritinemia, lipid abnormalities, and elevated LDH.

Objective: The aim of the study was to compare the direct healthcare cost and outcomes of a multidisciplinary care (MDC) program versus usual care for patients with advanced chronic kidney disease (CKD) in Singapore.

Methods: A retrospective study of patients with an estimated glomerular filtration rate (eGFR) less than 20 mL/min/1.73 m2, attending the MDC program or the usual care clinic in a tertiary hospital from 2016 to 2019. The usual care group was matched to the MDC group using propensity score matching based on age, gender, baseline eGFR, and diabetes mellitus. The primary outcome was the rate of emergent long-term kidney replacement therapy (KRT) initiation and the direct healthcare cost incurred from eGFR for less than 20 mL/min/1.73 m2 for the initiation of long-term KRT.

Results: There were 280 patients in each group. The MDC group had a lower rate of emergent KRT initiation than the usual care group (33.3 vs. 55.7 events per 100 patient-year, p = 0.003), shorter length of hospitalization stay (8.0 vs. 16.5 days per year, p = 0.004), lower number of emergency department visits (0.7 vs. 1.2 visits per year, p = 0.005), and higher number of renal clinic visits (14.5 vs. 13.0 visits per year, p = 0.009). The healthcare cost was lower in the MDC group than in the usual care group (SGD USD 18,408.83 (USD 13,664.51) vs. SGD USD 28,734.43 (USD 21,329.00) per patient-year, p = 0.016).

Conclusion: The MDC program for patients with advanced CKD in Singapore was associated with lower rate of emergent KRT initiation, shorter hospitalization stay, lower number of emergency department visit, and lower healthcare cost.