Journal of Nephrology最新文献

Background: While electrical muscle stimulation during hemodialysis has been reported to improve physical performance in middle-aged patients, clinical evidence regarding its efficacy in older patients with frailty remains limited.

Methods: In this crossover trial, we randomly assigned 18 older patients (aged ≥ 65 years) with frailty receiving maintenance hemodialysis in a 1:1 ratio to the study intervention. Group 1 underwent electrical muscle stimulation first, followed by a five-week washout period, and then the control session without electrical muscle stimulation. Group 2 received the control session first, followed by the electrical muscle stimulation sessions. Eligible patients had physical frailty defined by a Short Physical Performance Battery (SPPB) score of 4-9 points. Electrical muscle stimulation was conducted for 30-40 min per day, 3 days a week, over 5 weeks, during hemodialysis sessions. The primary outcome was the difference in quadriceps isometric strength before and after the treatment period.

Results: Among 18 patients who were randomized, 16 patients were included in the intention-to-treat analysis (median age: 76 years [Q1 to Q3, 72 to 79]; men: 38%; median SPPB: 6 points [Q1 to Q3, 5 to 9]). The median change in quadriceps isometric strength (Q1 to Q3) was 1.5%dry weight (%DW) (0.2 to 4.2) during the electrical muscle stimulation intervention period and - 3.6%DW (- 7.7 to - 1.6) during the control period (P = 0.0027).

Conclusions: Our trial found that intradialytic electrical muscle stimulation was associated with improved quadriceps isometric strength in older patients with frailty, indicating a potential benefit of intradialytic electrical muscle stimulation intervention for physical performance, also in these subjects.

Trial registration: The study was registered in a public trial registry (UMIN-CTR, number: UMIN000032501).

Background: Acute kidney injury (AKI) is a common complication in patients affected by COVID-19 and has been strongly associated with increased mortality. However, its independent contribution remains debated. This study aimed to evaluate the independent association using a directed acyclic graph-based approach.

Methods: Retrospective, multicenter cohort study in Medellín, Colombia, from June 2020 to April 2022. AKI was defined according to KDIGO criteria. A directed acyclic graph was constructed to map the hypothesized causal relationship between AKI and mortality, integrating evidence from a comprehensive literature review and expert´s consensus. A Poisson regression model with robust variance was applied to estimate adjusted incidence rate ratios (IRRs) for mortality.

Results: A total of 1722 patients were included, of whom 30.7% developed AKI. Mortality was higher among patients with AKI (58.1% vs. 19.6%). A directed acyclic graph was used to identify a minimal sufficient adjustment set for confounding control. After adjustment, the IRRs for in-hospital mortality were 1.25 (95% CI: 1.09-1.43) for stage 1, 1.62 (95% CI: 1.35-1.93) for stage 2, and 1.64 (95% CI: 1.46-1.85) for stage 3.

Conclusions: AKI is independently and significantly associated with an increased risk of mortality in COVID-19 patients. This study makes a novel contribution by applying directed acyclic graphs to enhance causal inference. Directed acyclic graphs provide a rigorous framework for identifying true confounders and avoiding inappropriate adjustment for mediators, thereby reducing bias and improving the validity of causal estimates. In clinical settings where randomized controlled trials are not feasible, the use of directed acyclic graphs represents a robust alternative for exploring causal relationships.

Background: Kidney stone formation is driven by an imbalance between lithogenic substances and crystallization inhibitors. Current guidelines recommend a 24-h urine collection in patients with kidney stone disease to assess the risk of stone formation and monitor therapy compliance. However, real-world data on adherence to these guidelines remain limited and outdated.

Methods: We used the Health Search Database to examine laboratory test data of patients with kidney stone disease between 2013 and 2022 in Italy. Adults with at least one episode of kidney or ureteral stones during this period were included. We used the prescription of urinary calcium, oxalate, and citrate levels as a proxy for full metabolic testing.

Results: A total of 21,907 adult patients were identified (44.6% women). Only 4.8% (n = 1059) underwent 24-h urine testing, and just 0.6% had all three target measurements. Testing rates were slightly higher in recurrent stone formers (6.1%). The likelihood of receiving a test increased nearly sixfold after a nephrology visit (OR 6.09, 95% CI 5.27-7.05, p < 0.001), compared to a lower increase after urology visits (OR 1.95, 95% CI 1.71-2.23, p < 0.001). Nonetheless, fewer than 10% of kidney stone disease patients consulted a nephrologist, and only half of those with coexisting chronic kidney disease (CKD) had such a referral.

Conclusion: Awareness of 24-h urine testing and nephrology referral in stone formers remains low, despite their role in guiding personalized treatment. Promoting their use could enhance patient care by identifying urinary abnormalities and reducing the risk of recurrence and complications.

Nephrotic syndrome is a rare complication of allogeneic haematopoietic stem cell transplantation (alloHSCT). Its pathogenesis is not fully understood. Membranous nephropathy and minimal change disease are the most common causes of nephrotic syndrome. Nephrotic syndrome occurs more frequently in people with chronic graft-versus-host disease (GvHD). Glucocorticosteroids and cyclosporine are the most common treatments, but their use is associated with the risk of side effects and variable responses. We present a case of a patient after alloHSCT with advanced GvHD who developed nephrotic syndrome resistant to immunosuppressive treatment. Additionally, when her kidney function deteriorated, she required kidney replacement therapy. We would like to emphasise the importance of kidney biopsy as a tool for determining the extent of kidney damage and the possible response to therapy.

Background: Adenine phosphoribosyltransferase (APRT) deficiency is a rare, inherited metabolic disorder characterized by abundant urinary excretion of 2,8-dihydroxyadenine (DHA), causing urinary stones and chronic kidney disease. The aim of this study was to examine the effect of allopurinol and febuxostat on plasma levels and urinary excretion of DHA in individuals with APRT deficiency.

Methods: Adult individuals enrolled in the Icelandic APRT Deficiency Registry were invited to participate in a single-center, open-label, crossover, randomized clinical trial comparing the effect of allopurinol 400 mg/day and 800 mg/day and febuxostat 40 mg/day and 80 mg/day on plasma concentration and urinary excretion of DHA.

Results: Of 12 participants who initiated the study, 7 (3 females) completed the trial; median (range) age 57.7 (37.3-65.1) years. Off pharmacotherapy, the median plasma DHA was 300 (178-1315) ng/mL. In individuals taking allopurinol 400 mg/day and 800 mg/day, the median plasma DHA was 25 (below the limit of detection [LOD]-95) ng/mL and below the limit of detection (< LOD-92) ng/mL, respectively. On febuxostat 40 mg/day, the median plasma DHA was below the limit of detection (< LOD-35) ng/mL and on 80 mg/day DHA was below the limit of detection in all samples tested. The median urine DHA-to-creatinine ratio was 8.18 (6.21-18.69) mg/mmol off pharmacotherapy and 1.90 (< LOD-4.52) mg/mmol and 0.35 (< LOD-4.32) mg/mmol on allopurinol 400 mg/day and 800 mg/day, respectively. During treatment with febuxostat 40 mg/day and 80 mg/day, the urine DHA-to-creatinine ratio was 0.54 (< LOD-1.33) mg/mmol and below the limit of detection (< LOD-0.64) mg/mmol, respectively.

Conclusions: The plasma concentration and urinary excretion of DHA decreased markedly on treatment with both study drugs, although febuxostat was more efficacious than allopurinol in both prescribed doses. Trial registration number and date of registration. EudraCT No. 2021-002185-40; https://www.clinicaltrialsregister.eu/ctr-search/search?query=Research+Registry Date on which this record was first entered in the EudraCT database: 2019-03-19.

Background: Transplant arteriopathy involves a spectrum of Leukocyte Common Antigen-positive, hypoelastotic, foam cell intimal fibrosis. Transplant arteriopathy has been associated with both Chronic Active T Cell-Mediated Rejection and Antibody-Mediated Rejection chronicity. Aim of this study was to find clinicopathological correlates of transplant arteriopathy in a single centre retrospective cohort.

Methods: We retrieved 46 biopsies showing transplant arteriopathy from 33 patients, out of a total of 784 biopsies carried out between 2005 and 2014. We retrospectively evaluated Banff Lesion Scores and Additional Diagnostic Parameters as well as the transplant arteriopathy descriptors Leukocyte Common Antigen-positive, hypoelastotic, foam cell, and correlated these findings with clinical data and death-censored transplant survival.

Results: Transplant arteriopathy was frequently associated with antibody-mediated rejection-associated Banff Lesions Scores and Additional Diagnostic Parameters. Hypoelastotic, leukocyte common antigen-positive and foam cell lesions were often combined, with hypoelastotic lesion being the most frequent finding in transplant arteriopathy. Leukocyte common antigen-positive lesion appeared earlier and was associated with Banff Lesion Score v ≥ 1. About half were positive for donor-specific antibodies, about a third had concurrent transplant glomerulopathy, and about a sixth were C4d-positive. Twelve of thirty-three transplants were lost during follow-up, concurrent transplant glomerulopathy was associated with shorter transplant survival.

Conclusions: The frequent coincidence of transplant arteriopathy and indicators of antibody-mediated rejection suggests that this arterial remodelling could indeed be antibody-mediated rejection chronicity. The transplant community should re-examine transplant arteriopathy with an expanded definition including the previously ignored hypoelastotic lesion in order to re-confirm or reject with confidence transplant arteriopathy as Additional Diagnostic Parameter of Antibody-Mediated Rejection chronicity, and to learn about its prognostic and therapeutic implications.

Background: Sparsentan represents a major advancement in the treatment of proteinuric kidney diseases, offering a promising option to improve patient outcomes and slow disease progression. Evaluation of its safety profile is essential to support its long-term integration into clinical practice.

Methods: This study employed a retrospective descriptive analysis combined with four advanced statistical methods to evaluate adverse events related to sparsentan. The data, sourced from the WHO's VigiAccess database, was queried in November 2024 to retrieve adverse event reports associated with sparsentan. The Food and Drug Administration Adverse Event Reporting System (FAERS) database has also been utilized to conduct an in-depth analysis of adverse events associated with sparsentan.

Results: A total of 1476 adverse events associated with sparsentan were reported in VigiAccess until the end of November 2024. The analysis revealed that the ten most frequently reported adverse events included dizziness, fatigue, product use in unapproved indication, hypotension, nausea, peripheral swelling, headache, blood pressure decrease, pruritus, wrong technique in product usage process.

Conclusions: While the majority of adverse events were mild and self-limiting, there were instances of severe events that could have led to hospitalization or even fatalities. It is crucial to actively prioritize primary safety research on sparsentan, with a particular focus on cohort event monitoring, to better understand and establish causal relationships between the treatment and reported adverse events.

Background: This study explores vascular access complications in patients established on in-centre nocturnal haemodialysis (INHD) compared to conventional haemodialysis.

Methods: This was a retrospective cohort study; patients acted as their own control. Data were collected from three centres. Adults established on INHD (intervention) preceded by usual daytime haemodialysis (control) were eligible. Data were collected between 01/01/2009 and 12/31/2021. The data collection period was up to 12 months for both control and intervention periods. The primary outcome was a composite of outcomes related to vascular access complications: hospitalisation, intervention, change in vascular access modality, change in dialysis modality and death. The primary outcome was evaluated by time-to-event rate in days using Kaplan-Meier plots. Statistical significance was accepted at a P < 0.05.

Results: One hundred forty-five individuals were included: median age was 52.0 years (IQR 36.0-65.0), 71.0% (n = 103) were male, and 57.2% (n = 83) were White. The primary outcome occurred in 24.1% (n = 35) during the intervention and in 25.5% (n = 37) during the control period (P = 0.875). The 12-month vascular access survival probability was 73.4% (95%CI 65.8-81.0%) for the intervention and 70.6% (95%CI 62.4%-78.8%) for the control period. During the intervention period, arteriovenous grafts were associated with lower vascular access survival (P < 0.001). Regular vitamin K antagonist was associated with a lower 12-month vascular access survival for both the intervention (P = 0.044) and the control periods (P < 0.001).

Conclusion: There does not appear to be an increased risk to vascular access events for INHD compared to daytime haemodialysis. Vascular access type and regular anticoagulation were associated with a reduced vascular access survival probability.