Clinical Kidney Journal最新文献

Long-term peritoneal dialysis (PD) treatment can lead to the destruction of peritoneal structure and function, which can lead to PD failure or even a poor prognosis. However, validated early biomarkers for patients undergoing PD are lacking. PD effluent (PDE) is rich in various biological components, such as nucleic acids, proteins, and metabolites, and is now an important source of noninvasive biomarkers for the dynamic monitoring of disease progression. In recent studies, a variety of histological techniques have provided unprecedented depth and breadth to PD biomarker research, and are becoming key tools in the early diagnosis, prognosis, and therapeutic monitoring of PD patients. Correspondingly, artificial intelligence (AI) approaches, which can flexibly handle data and excel at mining nonlinear and high-dimensional relationships in multimodal data, have moved from theory to practice. AI-based multi-omics analysis has not only greatly improved the understanding of the pathophysiological mechanisms of PD-associated fibrosis (PF) but has also contributed to the development of new biomarkers and novel targets. This review provides a comprehensive summary of recent advances in the development of PDE biomarkers using AI-based multi-omics approaches. We highlight the application of AI-based multi-omics techniques for early diagnosis, evaluation of peritoneal injury, assessment of peritoneal function, and prediction of prognosis. Finally, we discuss the challenges and limitations of PDE biomarkers from the perspectives of multi-omics and AI. In conclusion, AI-based multi-omics analysis holds great promise for the development of PDE biomarkers, which are expected to significantly improve the prognosis of PD patients and ultimately facilitate precision medicine.

Nephrology has benefited from a growing body of high-quality clinical evidence, including clinical trials of pharmacological therapies and health service research on alternative care approaches. Consequently, there is an increasing need to perform economic evaluations in kidney disease to inform reimbursement decisions and optimise healthcare spending, thereby improving patient care within budget constraints. Cost-effectiveness assesses if the additional health gains are worth any additional costs by estimating differences in the quality and quantity of life, and the costs, from the point of intervention over observed but also longer (even lifetime) timelines, capturing the entire patient pathway through healthcare, e.g. from early-stage chronic kidney disease (CKD) through to dialysis or transplantation. Working with stakeholders to define the decision problem, merging evidence from a range of sources, including clinical trials complicated by limited follow-up and non-generalisable participants, surrogacy studies to estimate the intervention's impact on longer-term kidney failure risk, quality of life data collected ideally using instruments sensitive to kidney disease progression and other real-world data are required to make extrapolations sufficiently far into the patient's lifetime to capture kidney failure. Consideration of disadvantaged populations and how interventions may operate differently in certain groups may be indicated. Failure to capture competing risks of cardiovascular disease and death will bias estimates of kidney failure. Application of our tips, combined with an understanding of how decision-makers use cost-effectiveness results and information about factors like rarity and disease severity maximises the likelihood of new kidney treatments and care approaches being adopted.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a severe multisystem autoimmune disease in which renal involvement is common and often progresses, without timely intervention, to end-stage kidney disease. Standard remission induction therapy combines high-dose glucocorticoids (GCs) with cyclophosphamide or rituximab. While effective, cumulative GC exposure drives substantial treatment-related morbidity, including infection, diabetes, osteoporosis and cardiovascular complications, highlighting the urgent need for GC-sparing strategies. Avacopan, an oral selective C5a receptor antagonist, represents a novel therapeutic approach targeting the alternative complement pathway, a key mediator of neutrophil activation and vascular injury in AAV. The pivotal phase 3 ADVOCATE trial demonstrated that avacopan achieved non-inferior remission at 26 weeks and superior sustained remission at 52 weeks compared with a standard GC taper, while reducing GC-related toxicity and improving renal recovery, particularly in patients with advanced kidney impairment. Since approval in 2021, real-world studies and case series have given further confidence in avacopan's efficacy across diverse patient subgroups, including those with severe renal disease, diffuse alveolar haemorrhage and refractory manifestations. However, real-world data also highlight variability in GC tapering practices and safety signals, particularly hepatotoxicity in Japanese cohorts. Several unanswered questions remain, including the long-term safety, clinical benefit of treatment beyond 1 year and optimal GC concomitant use or even the feasibility of complete GC avoidance. Ongoing large-scale studies and international real-world evidence will be essential to define avacopan's optimal role in clinical practice, ensuring equitable access for patients with AAV.

Background: Sodium-glucose co-transporter 2 inhibitors have demonstrated renoprotective effects in patients with CKD. However, concerns remain regarding their potential effect on bone mineral metabolism. This study investigated the impact of dapagliflozin on bone health in non-diabetic patients with CKD.

Methods: This randomized, double-blind, placebo-controlled trial enrolled 100 non-diabetic adults with CKD and an estimated glomerular filtration rate (eGFR) of 25-75 ml/min/1.73 m². Participants were randomized 1:1 to receive either dapagliflozin 10 mg daily or placebo for 12 months and stratified by age and eGFR. Serum creatinine, eGFR, urinary protein:creatinine ratio, calcium:creatinine ratio and phosphorus:creatinine ratio were measured at baseline and after 12 months. Bone health was assessed at the same time points using bone formation markers [bone-specific alkaline phosphatase (BSAP), total procollagen type 1 N-terminal propeptide (P1NP)] and bone resorption markers [carboxy-terminal telopeptide of type I collagen (CTX-1), tartrate-resistant acid phosphatase 5b (TRAP-5b)]. Moreover, quantitative computed tomography (QCT) was used to assess volumetric bone mineral density (vBMD).

Results: Participants had a mean age of 53.5 ± 11.1 years, with no significant baseline differences between groups. Dapagliflozin significantly reduced proteinuria compared with placebo (P = .012) without significantly affecting eGFR. Both groups experienced significant decreases in BSAP and TRAP-5b levels (P < .001), with no intergroup differences. P1NP remained stable in both groups. CTX-1 levels increased significantly in the placebo group (P = 0.032) but not in the dapagliflozin group without significant intergroup differences. No significant differences in vBMD or T-scores at any lumbar or total lumbar spine were observed between groups after 1 year.

Conclusions: This exploratory randomized controlled trial did not demonstrate any meaningful impact of dapagliflozin on either bone turnover or QCT markers. While these findings provide reassuring preliminary evidence, larger studies are needed to definitively establish long-term bone safety of dapagliflozin in non-diabetic patients with CKD.

Background: Peritoneal dialysis (PD)-associated peritonitis remains a major complication affecting patient outcomes and modality survival. This study aims to evaluate temporal trends in pathogen distribution and antibiotic susceptibility over four decades as well as clinical outcomes in PD-associated peritonitis.

Methods: We retrospectively analyzed 832 peritonitis cultures of PD patients across four decades from 1979 to 2024 treated at Robert Bosch Hospital, Stuttgart (Germany). For longitudinal comparison of pathogen distribution and antibiotic susceptibility, the study period was divided into four time periods: P1 (1979-1992), P2 (1993-2003), P3 (2004-2014), and P4 (2015-2024). Clinical response and outcomes were assessed in P4.

Results: Gram-positive bacteria was the most frequent causative organisms (56%), followed by Gram-negative bacteria (30%) and culture-negative peritonitis (CNP, 13%). Gram-negative peritonitis increased significantly in P4 compared to P1-P3, while coagulase-negative staphylococci (CNS) declined from 31% in P1 to 14% in P4 (P = .0446). Vancomycin susceptibility among Gram-positive organisms remained high, whereas cefazolin susceptibility changed over time. In P4, the overall cure rate was 63%, with the highest in gram-positive (72%) and lowest in polymicrobial peritonitis (43%).Regarding clinical outcomes, transition to permanent hemodialysis (HD) was significantly more frequent in Gram-negative than Gram-positive peritonitis (27% vs. 12%; P = .03). Both catheter removal and transition to permanent HD occurred significantly more often in polymicrobial peritonitis (54% and 40%) compared with Gram-positive (24% and 12%; P = .001 and P = .0008) and CNP (30% and 17%; P = .01 and P = .04). Regarding individual pathogens, Staphylococcus aureus (MSSA) was associated with a significantly higher catheter removal rate compared to other Gram-positive organisms.

Conclusion: Our findings show temporal changes of microbiological spectrum of PD-associated peritonitis over four decades. Polymicrobial and Gram-negative peritonitis were associated with poorer outcomes, emphasizing the need for ongoing microbiological surveillance and antibiotic stewardship to optimize PD care.

Background: Despite the high suicide rates among patients with end-stage kidney disease (ESKD), there is no suicide prediction model specifically designed for this vulnerable population. Herein, we aimed to develop and validate a novel suicide risk score for ESKD patients.

Methods: We analyzed data from the National Health Insurance Service (NHIS) of South Korea, including 251 819 patients aged above 18 years diagnosed with ESKD between 2007 and 2022 in South Korea. The mean follow-up duration was 6.6 years. The cohort was randomly divided into derivation (70%) and validation (30%) sets. Using multivariate Cox proportional hazard regression, key variables were incorporated to develop the suicide risk score, which was converted into a 48-point scoring system, which is composed of easily identifiable clinical parameters.

Results: Among 176 273 patients in the derivation cohort, 1126 (0.64%) patients committed suicide. The suicide risk score demonstrated moderate discrimination in both the derivation (C-statistic, 0.694) and validation (C-statistic, 0.709) cohorts, with good calibration. In the validation cohort, patients scoring below 16, 17-32 and 33-48 had predicted 10-year suicide risk of 0.2%, 1.2% and 7.7%, respectively, while the observed 10-year risk were 0.3%, 0.8% and 3.9%. These findings highlight the model's ability to effectively stratify risk using routinely available clinical data.

Conclusions: The suicide risk score is a significant advancement in suicide risk prediction for ESKD patients. It is based on simple, routinely collected clinical indicators and provides an actionable tool for risk stratification and early intervention in daily practice.

Background: Diabetes is the leading cause of end-stage kidney disease (ESKD) worldwide. In particular, whether diabetes has a negative effect on the risk of transfer to haemodialysis (HD) remains controversial. This study was conducted to provide updated data on outcomes of patients with diabetes on peritoneal dialysis (PD).

Methods: This was a retrospective cohort study using data from the French Language Peritoneal Dialysis Registry, including patients starting PD between 2008 and 2018; the end of the study was 31 December 2021. Cox and Fine-Gray models examined associations between diabetes and mortality, transfer to HD, a composite outcome of death and HD transfer and kidney transplantation. In addition, the causes of transfer to HD were analysed separately. Mediation analyses were performed to assess the indirect effects of early peritonitis and assisted PD on HD transfer.

Results: Of 10 412 PD patients, 3473 (33%) were diabetics. Diabetes was associated with an increased risk of HD transfer {cause-specific hazard ratio [cs-HR] 1.69 [95% confidence interval (CI) 1.36-2.11]}, death [cs-HR 1.32 (95% CI 1.21-1.43)] and the composite outcome [cs-HR 1.23 (95% CI 1.15-1.31)] in Cox and Fine-Gray models [HD transfer subdistribution HR (sd-HR) 1.18 (95% CI 1.07-1.31); death sd-HR 1.25 (95% CI 1.15-1.35)]. Diabetic patients were less likely to receive a kidney transplant [cs-HR 0.52 (95% C: 0.41-0.66); sd-HR 0.44 (95% CI 0.35-0.56)]. At a 5% false discovery rate, diabetes was significantly associated with an increased risk of transfer to HD due to inadequate dialysis, other PD-related causes and non-PD-related causes. Mediation analyses showed no significant indirect effects via early peritonitis or assisted PD.

Conclusion: Diabetes has a higher risk of transfer to HD that was not explained by early peritonitis or not being assisted. Diabetic PD patients have a greater mortality risk and lower access to transplantation.

Background: The prevalence of depression is high among patients with end-stage kidney disease (ESKD). Recent studies have indicated under-recognition and -treatment of depression in this population, and little is known about how the specialty of the prescribing clinician may influence clinical outcomes. This study aimed to evaluate whether the prescribing clinician's specialty (psychiatrist vs. non-psychiatrist) is associated with clinical outcomes in patients with ESKD and comorbid depression who receive antidepressant treatment.

Methods: We extracted data from the Korean National Health Institute Database System from January 2004 to December 2022. Patients with ESKD and depression who underwent antidepressant therapy after their ESKD diagnosis were included. Patients were followed up for 4.7 ± 3.5 years.

Results: Among 16 756 patients with ESKD and depression [mean age, 67.3 years; 8614 (51.4%) men], 7841 (46.8%) patients were prescribed antidepressants by psychiatrists. After propensity score matching, the 5-year mortality was significantly lower in the psychiatrist (25.8%) than in the non-psychiatrist group (38.2%). After multivariable adjustment, prescription by a psychiatrist remained significantly associated with lower mortality (adjusted hazard ratio, 0.66; 95% confidence interval, 0.62-0.70; P < .001). All-cause mortality was consistent across various subgroups, such as age (above or below 75 years), sex, time from dialysis initiation to depression diagnosis, income level, region of residence, and comorbidity status. This trend remained in 6-month, 1-year, 2-year, and 3-year landmark analyses.

Conclusions: Our findings suggest a potential benefit of specialty psychiatric care for improving clinical outcomes in patients with ESKD and depression.

Despite advances and therapeutic progress, nephrotic syndrome (NS) in childhood remains challenging due to its heterogeneous presentation, variable response to treatment and the potential of adverse long-term kidney outcomes. The recently published KDIGO 2025 clinical practice guideline for the management of NS in children refines the definitions of relapse, infrequently- and frequently-relapsing NS and steroid-resistant NS. Herein we describe the revised definitions, summarize the key updates of the KDIGO 2025 guidelines and comment on the new treatment algorithm from a European viewpoint, highlighting the need for individualized approaches to minimize toxicity and optimize long-term kidney outcomes in NS in children.