Journal of Nephrology最新文献

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.

Background: Stage 3 chronic kidney disease (CKD) often remains undiagnosed until more severe symptoms appear. This study assessed awareness and management of CKD among Italian general practitioners (GPs), focusing on early detection and current practices.

Methods: A nation-wide, retrospective observational study was conducted using data from The Health Improvement Network (THIN®) database. Each participant was required to have had at least one interaction with a GP for either medical or administrative purposes (considering the index date), and to have a minimum of three years of retrospective data available  from January 2021 to June 2022. The study evaluated the proportion of individuals aged ≥ 40 years who underwent a second serum creatinine test after ≥ 90 days, referrals to nephrologists, and CKD diagnosis confirmation and categorization. Multivariable Poisson regression models analyzed data to identify associations between patient characteristics and outcomes, in both the overall cohort and in the sub-group with available urine albumin-to-creatinine ratio (uACR) measurement.

Results: Among 347,548 adults aged ≥ 40 years, 18,002 (5.2%) had an initial estimated glomerular filtration rate (eGFR) indicating possible stage 3 CKD (30-59 mL/min/1.73 m²), and 1495 of these had a concomitant uACR assessment. Data concerning follow-up testing and specialist referrals were inconsistent, and available only for 53.0% and 9.0% of the patients, respectively. Overall, 15.3% met the criteria for KDIGO stage 3 CKD, yet CKD ICD-9-CM diagnostic codes were recorded for only 905 (5.0%) patients. Factors associated with these outcomes were analyzed, including age, comorbidities, treatments, and laboratory values.

Conclusions: Substantial gaps in GP awareness and adherence to CKD management guidelines were identified, particularly in follow-up testing, referral practices, and diagnostic coding. Targeted educational interventions and standardized care protocols are needed to enhance CKD detection and management in primary care, improving patient outcomes and healthcare system performance.

Background: Gout, a disease already described in the "Anonymus Parisinus Darembergii sive Fuchsii", one of the two surviving Greek medical manuscripts of the first century CE, is reviewed in an effort to trace the timeline of the knowledge of the disease between the Corpus Hippocraticum and the Renaissance.

Methods: The treatise exists in four manuscripts of varying lengths: two are located in Paris, one in Vienna, and one in London. The study was conducted using the 1997 Leiden critical edition by Ivan Garofalo, which unifies all four manuscripts ("Anonymi Medici. De Morbis acutis et chronicis"), and was translated into English by Brian Fuchs. The treatise consists of 51 sections (a capite ad calcem, head to heel), in which the description of sixteen acute diseases precede that of thirty-five chronic diseases. The chapter on diseases affecting the joints precedes the last chapter, that describes elephantiasis. The text on gout consists of 945 words covering causes (46 words), signs (138 words) and therapy.

Results: The causes of gout are attributed to bilious humors and phlegm, as described by the "Ancients". The signs include inflammation and severe pain, typically beginning in the great toe (later known as podagra), but can extend to affect the entire leg, hands (referred to as cheiragra), or other joints, indicating a broader condition of arthritis. Pain is more tolerable when swelling coexists. Therapy is based on immediate bloodletting, dietary restrictions, and abstention from meat, wine and venery.

Conclusions: Gout in the "Anonymus Parisinus" allows a full understanding of gout in the centuries between the Corpus Hippocraticum and Galen.

Background: Atypical haemolytic uraemic syndrome (aHUS) leads to acute kidney injury, necessitating dialysis in about half of patients. A certain proportion of patients treated with C5 inhibitors discontinue dialysis; however, little is known about the patient characteristics and clinical courses relating to discontinuation.

Methods: We compared the characteristics and clinical courses of patients with aHUS on dialysis at the initiation of eculizumab during post-marketing surveillance in Japan, stratified by those who did (Group A) and did not (Group B) discontinue dialysis within 26 weeks of eculizumab treatment.

Results: Of 38 included patients, 21 (55.3%) and 17 (44.7%) were placed in Groups A and B, respectively. No patient re-started dialysis. Hypertension was less frequent in Group A than in Group B (6/21 [28.6%] vs. 11/17 [64.7%], p = 0.022). Both the duration of dialysis before eculizumab initiation (6 vs. 17 days, p = 0.011) and the time from thrombotic microangiopathy onset to eculizumab initiation (9 vs. 25 days, p = 0.008) were shorter in Group A. A duration of less than 15 days from thrombotic microangiopathy onset to eculizumab initiation was associated with dialysis discontinuation. Kidney function improvement and normalisation of platelet count and lactate dehydrogenase levels were achieved earlier in Group A than in Group B (p = 0.050, 0.014, and < 0.001, respectively). Five (29.4%) of 17 patients in Group B discontinued dialysis after 27 weeks of eculizumab treatment, including one patient who underwent kidney transplantation.

Conclusions: Early initiation of eculizumab was significantly correlated with dialysis discontinuation.

Background: IgA nephropathy is a disease with a highly variable natural history, for which there is an increasing understanding of the role of complement activation in its pathogenesis and progression. We aimed to assess the clinical and prognostic implications of C4d staining in the kidney biopsy of IgA nephropathy patients.

Methods: This was a retrospective observational study wherein the medical records of IgA nephropathy patients were reviewed and baseline characteristics, kidney biopsy findings, treatment response and follow-up data were noted. We aimed to estimate the prevalence of C4d staining and assess its correlation with clinical presentation, MEST-C scoring as well as its predictive value on renal outcomes.

Results: A total of 131 kidney biopsies were studied in which the prevalence of C4d staining was 63.36%. C4d positivity was significantly associated with hypertension (P = 0.005), greater degree of proteinuria (P = 0.013) and lower estimated glomerular filtration rate (eGFR) (P = 0.04) at presentation. MEST-C score analysis revealed significant association of Segmental sclerosis (S1), Tubular atrophy and Interstitial Fibrosis (T1, T2) and a greater degree of glomerulosclerosis with C4d staining (P value < 0.001). On follow-up, lesser rates of complete remission, higher serum creatinine and lower eGFR were seen in the C4d positive group (P < 0.001). C4d positivity independently predicted progression to kidney failure [HR: 2.42; 95% CI:1.11-5.26 (P = 0.026)] with 5-year kidney survival of 58% (P < 0.001).

Conclusion: Mesangial C4d deposition is associated with adverse clinical and pathological characteristics and is an independent risk factor for progression to kidney failure in patients with IgA nephropathy. Thus, C4d staining could be integrated into routine kidney biopsy analysis as a potentially useful biomarker for prognostication and targeted complement-based therapies.

Background: Atypical hemolytic uremic syndrome (aHUS) usually results from an overactivation of the alternative complement pathway. As large clinical trials are scarce, patient registries can partially fill the knowledge gap on patient characteristics, management, and outcomes. We here describe the baseline clinical and genetic characteristics as well as the management of all Belgian patients enrolled in the Global aHUS Registry at data cut-off.

Methods: This observational study prospectively and retrospectively collected data (data cut-off: December 26, 2022) from patients of all ages with a clinical diagnosis of aHUS, irrespective of treatment.

Results: A total of 121 Belgian patients were registered in the Global aHUS Registry, resulting in a prevalence of 10.4 aHUS patients per million inhabitants, with a higher proportion of females affected (57.9% vs 42.1% of males). Among the 109 patients tested for at least one variant and/or anti-complement factor H (CFH) antibodies, 36 were positive for a pathogenic complement gene variant associated with aHUS (n = 29) and/or seropositive for anti-CFH antibodies (n = 14). The most common variants affected CFH, C3 and CD46. The higher proportion of complement gene variants in treated women versus men was not related to a specific gene.

Conclusions: This study strengthens the real-world evidence on aHUS and adds to previously published Global aHUS Registry data. In addition, it provides insights into the differential epidemiology of the disease in Belgium and demonstrates the increased susceptibility of women to aHUS across the whole spectrum of recognized complement gene variants.