Nephron最新文献

Introduction: The efficacy of telitacicept treatment in reducing proteinuria in patients with IgA nephropathy (IgAN) was indicated in a phase II clinical trial with small sample size. In this study, we conducted a large multicenter retrospective study to explore the efficacy and safety of telitacicept in patients with IgAN.

Methods: This study recruited patients with IgAN from 19 sites from China who were treated with telitacicept and had been followed up at least once or with side effect reported, since April 1, 2021, to April 1, 2023. The primary outcomes of the study were the changing in proteinuria and eGFR over time.

Results: A cohort of 97 patients with IgAN who were treated with telitacicept were recruited, with a median follow-up duration of 3 months. The median baseline proteinuria was 2.3 [1.3, 3.9] g/day and eGFR was 45.0 [26.8, 73.7] mL/min/1.73 m2. There was a significant reduction of proteinuria at 2, 4, 6 months when compared with baseline (2.3 [1.5, 4.1] vs. 1.5 [0.8, 2.3] g/day; 2.3 [1.1, 3.7] vs. 1.1 [0.6, 1.9] g/day; 2.1 [1.0, 2.7] vs. 0.9 [0.5, 1.7] g/day, all p values <0.01). The level of eGFR were comparable between at the baseline and 2, 4, 6 months of follow-up time (41.5 [29.7, 72.0] vs. 42.5 [28.8, 73.3] mL/min/1.73 m2; 41.0 [26.8, 67.7] vs. 44.7 [31.0, 67.8] mL/min/1.73 m2; 33.7 [24.0, 58.5] vs. 32.6 [27.8, 57.5] mL/min/1.73 m2, all p values >0.26). Telitacicept was well tolerated in the patients.

Conclusions: This study indicates that telitacicept alone or on top of steroids therapy can significantly and safely reduce proteinuria in patients with IgAN. The long-term kidney protection still needs to be confirmed in large phase III trial.

Introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent liver condition commonly associated with obesity, metabolic syndrome, and type 2 diabetes mellitus. It has also been linked to an increased risk of cardiovascular events and overall mortality. Recent studies have established pathophysiological connections between MAFLD and chronic kidney disease (CKD). This study aimed to determine the prevalence of MAFLD in patients with advanced chronic kidney disease (ACKD), identify associated factors, and evaluate its impact on patient survival.

Methods: A retrospective longitudinal cohort study was conducted with incident patients diagnosed with stage 4 or 5 CKD, not on dialysis, who initiated care for ACKD between 2011 and 2015. Clinical and laboratory data were collected, and the presence of MAFLD was estimated using the Fatty Liver Index (FLI). To assess the impact of FLI and other variables on survival, Kaplan-Meier univariate analysis and Cox regression multivariate analysis were performed, with follow-up through February 2024.

Results: Among 367 patients, 60.2% had diabetes, and 70.8% had an FLI ≥60. Age and diabetes mellitus were significant factors associated with a higher likelihood of FLI ≥60. FLI was identified as an independent risk factor for decreased survival in patients with diabetes, after adjusting for other variables (HR, 1.015; 95% CI 1.004-1.027; p = 0.009). However, in non-diabetic patients, FLI was not a significant predictor of lower survival in multivariate Cox regression analysis.

Conclusions: MAFLD is highly prevalent in patients with ACKD, particularly among those with diabetes, for whom it may represent an independent risk factor for reduced survival. This association was not observed in non-diabetic ACKD patients. These results suggest the need to design preventive and treatment strategies for MAFLD in this population.

Introduction: Acute kidney injury (AKI) is associated with adverse outcomes, including death and dialysis. The goal of this study was to identify prognostic biomarkers of AKI that could be used across multiple phenotypes of AKI and across different species.

Methods: Liquid chromatography/tandem mass spectrometry analysis of urine samples from three species (human, rat, and mouse) and four etiologies of AKI identified five potential biomarkers, of which two were validated, complement C3 and vitamin D-binding protein, in a cohort of 157 patients that developed AKI following cardiothoracic surgery. We studied the relationship between the biomarker's concentration in the urine and the development of a composite primary endpoint (stage 3 AKI within 10 days or death within 30 days).

Results: Of the 153 patients who developed AKI following cardiovascular surgery, 17 met the combined primary outcome. The median concentration of urine complement C3 adjusted to urine creatinine had the best predictive value and was significantly higher in the primary outcome group than in the controls. Similarly, the median concentration of vitamin D-binding protein was higher in the primary outcome group.

Conclusions: The studies provide proof in principle that cross-species discovery analyses could be a valuable tool for identifying novel prognostic biomarkers in AKI. Urine complement C3 and vitamin D-binding protein could be promising early predictors of adverse outcomes in patients who develop AKI after cardiac surgery.

The development of the human kidney leads to the establishment of nephron endowment through a process influenced by both genetic and environmental factors. There is individual variability regarding nephron endowment and factors including aging and pathological conditions contribute to the decline in the number of nephrons, impacting renal function. Genetic determinants, such as mutations in crucial developmental genes like Pax2, and epigenetic mechanisms mediated by key enzymes including sirtuin 3, play critical roles in the regulation of the number of nephrons, with implications for kidney disease susceptibility. Sexual dimorphism significantly influences kidney development and function, with the number of nephrons being significantly lower in females, consistent with lower female birth weight, which is considered a surrogate for nephron endowment. Also, although females have fewer nephrons, they experience a slower decline in GFR compared to males. Gender disparity in chronic kidney disease progression has been attributed to factors such as metabolism, oxidative stress, renal hemodynamics, and sex hormones. Understanding the complexities of nephron endowment variability, genetic determinants, and sexual dimorphism in kidney development and function is crucial for elucidating the mechanisms underlying individual kidney disease susceptibility and progression. Further research in this field holds promise for the development of personalized approaches to kidney disease prevention, management, and treatment.

Introduction: With the increasing prevalence of membranous nephropathy (MN), the gut microbiome (GM) is increasingly implicated in its cause, yet the intricate mechanisms remain unclear. Whether changes in the diversity and richness of gut microbial populations among MN patients contribute to disease prevalence is still unanswered, necessitating further exploration into the potential causative link between the GM and MN.

Methods: We conducted a comprehensive bidirectional mendelian randomization (MR) study. We selected 211 bacterial taxa using genome-wide association study (GWAS) data provided by the MiBioGen consortium, while GWAS data relevant to MN were obtained from ebi-a-GCST010005. The inverse-variance weighted (IVW) method was the primary technique used to delineate the causal relationship between exposures and outcomes. To confirm the robustness of our results, we used additional methods, including MR-Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses included tests for pleiotropy, heterogeneity, and leave-one-out sensitivity to ensure the integrity of our conclusions. Finally, reverse MR analyses were conducted to assess the likelihood of reverse causality.

Results: Using various analytical methods, including the IVW approach, MR-Egger, weighted median, simple mode, and weighted mode, our study identified six microbial taxa with a statistically significant causal link to MN, as indicated by p values <0.05. The implicated taxa are Butyrivibrio (OR = 1.25, 95% CI: 1.001-1.565, p = 0.048), Butyricicoccus (OR = 2.15, 95% CI: 1.005-4.621, p = 0.048), Catenibacterium (OR = 1.49, 95% CI: 1.043-2.134, p = 0.028), Ruminiclostridium 5 (OR = 1.78, 95% CI: 1.140-2.763, p = 0.03), Ruminococcaceae UCG-003 (OR = 1.78, 95% CI: 1.140-2.763, p = 0.011), and Bacillales (OR = 1.52, 95% CI: 1.135-2.025, p = 0.005). Each of these taxa has been established as a risk factor for MN. Notably, Ruminococcaceae UCG-003 and Bacillales were identified as having a bidirectional causal relationship with the disease.

Conclusion: Our MR study has revealed a causal link between six microbial taxa and MN, highlighting their potential involvement in the disease's development. These findings represent an initial step into this complex field and underscore the need for more in-depth research.

Background: Traditional biomarkers, such as estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (uACR), have long been central to chronic kidney disease (CKD) diagnosis and management, leading to a standardized CKD classification system. However, these biomarkers are non-specific and fail to capture the heterogeneity within CKD and the nuances of an individual's disease mechanism, limiting personalized treatment approaches. There is an increasing need for novel biomarkers that reflect the diverse pathophysiological processes underlying CKD progression, enabling more precise risk prediction and treatment strategies.

Summary: This review examines the limitations of current CKD biomarkers and classification systems, highlighting the need for a precision medicine approach. While traditional markers like eGFR and uACR are foundational, they inadequately capture CKD's complexity. Emerging biomarkers offer insights into specific disease processes, such as inflammation, oxidative stress, fibrosis, and tubular injury, which are crucial for personalized care. The article discusses the potential benefits of integrating these novel biomarkers into clinical practice, including more accurate risk prediction, tailored treatments, and personalized clinical trial designs, as well as the barriers to their implementation. Furthermore, advancements in multi-omics and high-throughput techniques offer opportunities to identify novel causative proteins with druggable targets, pushing CKD care towards greater precision.

Key messages: Current CKD classification systems, based on non-specific biomarkers, fail to capture CKD's heterogeneity. Incorporating biomarkers reflecting diverse pathophysiological mechanisms can enhance risk prediction, customized treatments, and personalized clinical trials. High-throughput multi-omic techniques present a promising path towards precision medicine in nephrology.

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: 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.

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.