Kidney International Reports最新文献

Vascular calcification (VC) is a common complication of chronic kidney disease (CKD) and is closely associated with cardiovascular events. The transdifferentiation of vascular smooth muscles (VSMCs) into an osteogenic phenotype is hypothesized to be the primary cause underlying VC. However, there is currently no effective clinical treatment for VC. Growing evidence suggests that mitochondrial dysfunction accelerates the osteogenic differentiation of VSMCs and VC via multiple mechanisms. Therefore, elucidating the relationship between the osteogenic differentiation of VSMCs and mitochondrial dysfunction may assist in improving VC-related adverse clinical outcomes in patients with CKD. This review aimed to summarize the role of mitochondrial biogenesis, mitochondrial dynamics, mitophagy, and metabolic reprogramming, as well as mitochondria-associated oxidative stress (OS) and senescence in VC in patients with CKD to offer valuable insights into the clinical treatment of VC.

Introduction

Peritoneal dialysis (PD) shows promise for urgent-start dialysis in end-stage renal disease (ESRD), with automated PD (APD) having advantages. However, there is limited multicenter randomized controlled trial (RCT) evidence comparing APD with temporary hemodialysis (HD) for this indication in China.

Methods

This multicenter RCT enrolled 116 patients with ESRD requiring urgent dialysis from 11 hospitals, randomized to APD or HD. Patients underwent a 2-week treatment with APD or HD via a temporary central venous catheter (CVC), followed by a maintenance PD. Outcomes were assessed over 12 months during 8 visits. The primary outcome was dialysis-related complications.

Results

The 1-year incidence of dialysis-related complications was significantly lower in the APD group than in the HD group (25.9% vs. 56.9%, P = 0.001). No significant differences were found between the groups in terms of PD catheter survival rates (P = 0.388), peritonitis-free survival rates (P = 0.335), and patient survival rates (P = 0.329). In terms of health economics, the total direct medical cost of the initial hospitalization for patients with ESRD was significantly lower in the APD group (27,008.39 CNY) than in the HD group (42,597.54 CNY) (P = 0.001), whereas the duration of the first hospital stay showed no significant difference (P = 0.424).

Conclusion

For patients with ESRD needing urgent initiation of dialysis, APD was associated with a lower incidence of dialysis-related complications and lower initial hospitalization costs compared with HD, with no significant differences in PD catheter survival rate, peritonitis-free survival rates, or patient survival rates. These findings can guide clinical decision-making for the optimal dialysis modality for patients requiring urgent dialysis initiation.

Introduction

Apheresis allows the fast removal of autoantibodies in anti-glomerular basement membrane (anti-GBM) disease, and in severe antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis. The CINEVAS study tested whether immunoadsorption (IA) allowed a faster removal of ANCA and/or anti-GBM antibodies than plasma exchanges (PEx).

Methods

CINEVAS was a prospective multicenter study comparing IA to PEx in consecutive patients with ANCA and/or anti-GBM vasculitides. The primary objective was the reduction rate in autoantibody titers between the beginning of the first and the end of the seventh apheresis session. Secondary objectives were number of sessions needed to obtain desired reduction rates; reduction rates of total Ig levels; tolerance of sessions; and patients’ outcome.

Results

The results of 38 patients (16 treated with IA and 22 with PEx), and 43 autoantibodies, were analyzed. There was no difference in the reduction rates in autoantibody titers between IA and PEx over 7 sessions (respectively 98% vs. 96%, P = 0.39). The numbers of sessions needed to obtain undetectable autoantibodies, or 50%, 75%, or 90% reductions, did not differ between techniques. Greater reduction rates of autoantibodies were observed when plasma was separated by filtration compared to centrifugation, with IA and PEx. IA allowed a greater reduction in total IgG levels, and better preservation of total IgA and IgM levels than PEx. PEx sessions required higher volumes of plasma, IA sessions higher volumes of citrate; IA sessions were longer.

Conclusions

IA and PEx were comparable in ANCA or anti-GBM removal kinetics, despite a faster reduction in total IgG with IA.

Introduction

Immunoglobulin A vasculitis (IgAV) is related to chronic inflammation; however, little is known about the associations between IgAV and allergic rhinitis (AR) or chronic rhinosinusitis (CRS). We evaluated the relationships among IgAV, AR, and CRS in children.

Methods

The clinical data of children with IgAV who were hospitalized from January to December 2019 were analyzed retrospectively. Four groups were created, the simple AR, simple CRS, AR + CRS, and non-AR or non-CRS groups, to explore the relationships among IgAV, AR, and CRS.

Results

We included 504 children with IgAV; and 357 (70.8%) were combined with AR or CRS, including 51 with simple AR, 70 with simple CRS, and 236 with AR + CRS. The incidences of renal involvement and recurrent rash were significantly higher in the simple AR group than in the non-AR or non-CRS group (P < 0.001). The incidences of renal involvement and recurrent rash were significantly higher in the AR + CRS group than in the non-AR or non-CRS group (P < 0.001). The incidences of renal involvement between the simple CRS group and non-AR or non-CRS group did not differ significantly, but that of recurrent rash was significantly higher than that in the other groups (P < 0.001). Age, abdominal pain, recurrent rash, simple AR, and AR combined with CRS were risk factors for renal involvement (all odds ratio [OR] > 1, P < 0.05).

Conclusion

Chronic rhinitis may be related to the pathogenesis of IgAV, and AR or CRS may be the triggering factors of IgAV. AR may be a risk factor for renal involvement and recurrent rash in patients with IgAV.

Introduction

Internationally, peritoneal dialysis (PD) is increasingly being commenced within 2 weeks of catheter insertion. Studies are warranted to evaluate outcomes of this strategy.

Methods

This study examines outcomes of early-start PD (ESPD) and conventional-start PD (CSPD), commencing at ≤14 days and >14 days after catheter insertion, respectively. All adults with kidney failure within a large metropolitan PD unit initiating PD through a new catheter, inserted using laparoscopic or modified Seldinger technique, between August 2019 and August 2022, were included in this retrospective observational study. Demographic data and episodes of infectious and mechanical complications were collected using electronic medical records. Analysis was conducted using analysis of variance and Chi-square testing. A P-value < 0.05 was significant with Bonferroni correction performed where relevant. Kaplan-Meier and competing risks analyses were performed for time to PD-related peritonitis and transfer to hemodialysis.

Results

A total of 297 patients (70% male, mean age 58.7 years) were included, with 130 (43.8%) patients undertaking ESPD. Most patients had laparoscopically inserted catheters (65.3%) and 65 patients (22.0%) received prior hemodialysis. When compared to CSPD, ESPD was associated with a higher number of pericatheter leaks (6.9% vs. 0.6%, P = 0.003), with otherwise similar complication episodes and no significant difference with respect to time to PD-related peritonitis or transfer to hemodialysis. Catheter insertion technique or prior hemodialysis treatment did not significantly influence outcomes.

Conclusion

ESPD is associated with increased pericatheter leaks when compared to CSPD, with an otherwise similar complication profile.

Introduction

Genetic testing can reveal monogenic causes of kidney diseases, offering diagnostic, therapeutic, and prognostic benefits. Although single nucleotide variants (SNVs) and copy number variants (CNVs) can result in kidney disease, CNV analysis is not always included in genetic testing.

Methods

We investigated the diagnostic value of CNV analysis in 2432 patients with kidney disease genetically tested at the University Medical Centre Utrecht between 2014 and May 2022. We combined previous diagnostic testing results, encompassing SNVs and CNVs, with newly acquired results based on retrospective CNV analysis. The reported yield considers both the American College of Medical Genetics and Genomics (ACMG) classification and whether the genotype actually results in disease.

Results

We report a diagnostic yield of at least 23% for our complete diagnostic cohort. The total diagnostic yield based solely on CNVs was 2.4%. The overall contribution of CNV analysis, defined as the proportion of positive genetic tests requiring CNV analysis, was 10.5% and varied among different disease subcategories, with the highest impact seen in congenital anomalies of the kidney and urinary tract (CAKUT) and chronic kidney disease at a young age. We highlight the efficiency of exome-based CNV calling, which reduces the need for additional diagnostic tests. Furthermore, a complex structural variant, likely a COL4A4 founder variant, was identified. Additional findings unrelated to kidney diseases were reported in a small percentage of cases.

Conclusion

In summary, this study demonstrates the substantial diagnostic value of CNV analysis, providing insights into its contribution to the diagnostic yield and advocating for its routine inclusion in genetic testing of patients with kidney disease.

Introduction

Uremic toxins contributing to increased risk of death remain largely unknown. We used untargeted metabolomics to identify plasma metabolites associated with mortality in patients receiving maintenance hemodialysis.

Methods

We measured metabolites in serum samples from 522 Longitudinal US/Canada Incident Dialysis (LUCID) study participants. We assessed the association between metabolites and 1-year mortality, adjusting for age, sex, race, cardiovascular disease, diabetes, body mass index, serum albumin, Kt/Vurea, dialysis duration, and country. We modeled these associations using limma, a metabolite-wise linear model with empirical Bayesian inference, and 2 machine learning (ML) models: Least absolute shrinkage and selection operator (LASSO) and random forest (RF). We accounted for multiple testing using a false discovery rate (pFDR) adjustment. We defined significant mortality-metabolite associations as pFDR < 0.1 in the limma model and metabolites of at least medium importance in both ML models.

Results

The mean age of the participants was 64 years, the mean dialysis duration was 35 days, and there were 44 deaths (8.4%) during a 1-year follow-up period. Two metabolites were significantly associated with 1-year mortality. Quinolinate levels (a kynurenine pathway metabolite) were 1.72-fold higher in patients who died within year 1 compared with those who did not (pFDR, 0.009), wheras mesaconate levels (an emerging immunometabolite) were 1.57-fold higher (pFDR, 0.002). An additional 42 metabolites had high importance as per LASSO, 46 per RF, and 9 per both ML models but were not significant per limma.

Conclusion

Quinolinate and mesaconate were significantly associated with a 1-year risk of death in incident patients receiving maintenance hemodialysis. External validation of our findings is needed.

Thrombotic microangiopathy (TMA) represents a heterogeneous group of disorders characterized by microvascular thrombosis and end-organ damage. Pregnancy-associated thrombotic microangiopathy (p-TMA) has emerged as a distinct clinical entity with unique diagnostic challenges. Identifying the specific form of p-TMA is critical for appropriate and timely management. This review offers a comprehensive overview of the various forms of thrombotic microangiopathies associated with pregnancy, highlighting our current understanding of their pathophysiology and the evolving landscape of diagnosis and treatment for each.