BMC Nephrology最新文献

Background: Immunoglobulin A nephropathy (IgAN) is a major cause of chronic kidney disease (CKD) and kidney failure. Necroptosis is a novel type of programmed cell death that has been proved to be associated with the pathogenesis of infectious disease, cardiovascular disease, neurological disorders and so on. However, the role of necroptosis in IgAN remains unclear.

Methods: In this study, we explored the role of necroptosis-related genes in the pathogenesis of IgAN using a comprehensive bioinformatics method. Microarray datasets GSE93798 and GSE115857 were downloaded from Gene Expression Omnibus (GEO). "limma" package of R software was employed to identify necroptosis-related differentially expressed genes (NRDEGs) between IgAN and healthy controls. GO and KEGG functional enrichment analysis was performed by Clusterprofiler. Least absolute shrinkage and selection operator (LASSO) regression analysis identified hub NRDEGs. We further established a diagnostic model consisting of 7 diagnostic hub NRDEGs and validated the efficacy by an external dataset. The expression of hub genes was confirmed in sc-RNA dataset GSE171314. Immune infiltration, gene set enrichment analysis and transcription factor binding motifs enrichment analysis were conducted to further uncover their roles.

Results: 1076 differentially expressed genes were identified between healthy individuals and IgAN patients from RNA-seq dataset GSE9379. Then we cross-linked them with necroptosis-related genes to obtain 9 NRDEGs. LASSO regression analysis screened out 7 hub genes (JUN, CD274, SERTAD1, NFKBIA, H19, UCHL1 and EZH2) of IgAN. We further conducted functional enrichment analysis and constructed the diagnostic model based on dataset GSE93798. GSE115857 was used as the independent validation cohort and indicated a great predictive efficacy. Immune infiltration, gene set enrichment analysis and transcription factor binding motifs enrichment analysis revealed their potential function. Finally, we screened out four drugs that were predicted to have therapeutic value of IgAN.

Conclusions: In summary, we identified 7 hub necroptosis-associated genes, which can be used as potential genetic biomarkers for IgAN prediction and treatment. Four drugs were predicted as the potential therapeutic solutions. Collectively, we provided insights into the necroptosis-related mechanisms and treatment of IgAN at the transcriptome level.

Background: To analyze the relationship between endothelial activation and stress index (EASIX) and the occurrence of acute kidney injury (AKI) in critically ill cancer patients.

Methods: Critically ill cancer patients were selected from the Medical Information Mart for Intensive Care IV (MIMIC-IV). Multivariate logistic regression was used to analyze the association between EASIX and the occurrence of AKI in critically ill cancer patients.

Results: One thousand forty-one cancer patients were retrospectively included, including 607 men and 434 women with mean age of 64.86 ± 13.67 years. Univariate analysis showed that high EASIX levels were associated with an increased risk of AKI occurrence in intensive care unit (ICU) cancer patients (OR: 1.47,95% CI: 1.13-1.91, P < 0.05). After adjusting for other confounders, high EASIX levels remained an independent risk factor predicting the development of AKI (OR: 1.42,95% CI: 1.08-1.88, P < 0.05). Trends in effect sizes were generally consistent across all subgroups in the prespecified subgroup analyses.

Conclusion: EASIX is an independent risk factor for AKI in critically ill cancer patients. More prospective studies are needed to validate the effect of EASIX on the occurrence of AKI in critically ill cancer patients in the future.

Introduction: Chronic kidney disease is a significant public health issue. Dapagliflozin has been shown to improve the quality of life for patients with chronic kidney disease. This review aimed to systematically assess the cost-effectiveness of adding dapagliflozin to standard care compared with standard care alone for treating chronic kidney disease.

Methods: The relevant studies were searched in PubMed, Web of Science, Scopus, Embase, and Cochrane from the inception date to June 1, 2024. The titles, abstracts, and full texts were independently evaluated and screened by two authors. Additionally, the economic evaluation studies were assessed independently by two authors using the consolidated health economic evaluation reporting standards checklist.

Results: 14 studies were included which were about the economic evaluations of adding dapagliflozin in the treatment of chronic kidney disease. The minimum consolidated health economic evaluation reporting standards score for the studies was 0.77, indicating very good quality. Adding dapagliflozin to the standard of care would be more effective and cost-saving in Mexico, Malaysia, Canada, Thailand, and China. The highest incremental cost-effectiveness ratio of dapagliflozin ($67962.75/QALY) originated from the USA. According to the available studies, adding dapagliflozin to standard of care for the treatment of chronic kidney disease is considered cost-effectiveness from both the healthcare system and the payer's perspective.

Conclusion: Adding dapagliflozin to standard care in the treatment of chronic kidney disease is cost-effective from both the healthcare system and the payer's perspective in well-developed countries.

Background and objective: Critical bedside ultrasound is widely used in clinical practice, and it can monitor renal perfusion. The reduction of renal perfusion and inflammatory injury are two contributing factors to sepsis-associated acute kidney injury (SA-AKI).The aim of this study was to examine whether the oXiris filter was useful in the continuous renal replacement therapy(CRRT) treatment of SA-AKI patients.

Design, setting, participants, and measurements: We performed a retrospective single-center observational study and enrolled two hundred and forty-three SA-AKI patients from January 2022 to December 2023, who were divided into the oXiris group (n = 88) and the control group (n = 155). The primary endpoints were the 28-day recovery of renal function and 28-day all-cause mortality. The secondary endpoints included renal Doppler markers (RRI, RVSI, and PDU), SOFA, vasoactive-inotropic score (VIS), inflammatory markers (PCT, CRP, IL-10 and TNFα), lactate level, and length of stay in ICU and hospital.

Results: For the primary endpoint, the rates of complete recovery, partial recovery, and dialysis dependence were observed to be 60.3%, 13.6%, and 26.1% in the oXiris group, respectively, compared to 63.9%, 15.5%, and 20.6% in the control group. The 28-day all-cause mortality was not different in the two groups (22.7% vs. 27.1%). For the secondary endpoint, the oXiris group exhibited greater reductions in VIS scores compared to the control group within the first 24 h (p = 0.001) and 48 h (p < 0.001) of CRRT. Following 48-h of CRRT, lactate levels in the oXiris group were significantly lower than those in the control group (p = 0.014). Prior to CRRT, levels of IL-6 were higher in the oXiris group (p = 0.036), but these differences were not significant after CRRT (p > 0.05). The levels of RRI at T1 (p = 0.002) and T2 (p = 0.001) were lower in the oXiris group than in the control group. Even after adjusting for AKI stage, multivariable Cox regression analysis showed that SOFA and inflammatory factors (TNFα, IL-10, and IL-6), oXiris were significantly associated with a lower 28-day mortality among SA-AKI patients when compared to M150 [HR = 0.466, 95%CI 0.233-0.934, p = 0.031].

Conclusion: Our findings suggest that the use of the oXiris filter in CRRT is associated with reduced inflammatory injury and improvement in renal perfusion. However, it is not associated with improved 28-day recovery of renal function and 28-day all-cause mortality.

Background: Chronic kidney disease (CKD) is a progressive condition affecting more than 800 million individuals worldwide. Patient Reported Experience Measures (PREMs) are questionnaires aimed at evaluating patients' experiences with healthcare received. Given that CKD management often involves continuous treatments, capturing patient experiences can guide improvements in care that align with patients' preferences, making PREMS a relevant tool in CKD management. The Kidney PREM questionnaire was developed in the United Kingdom to measure patient experience across entire service provisions in patients with chronic kidney disease (CKD). This study aimed to adapt the English version to Spanish and Catalan and assess the face validity of the new language versions.

Methods: The translation process was guided by the International Society of Pharmacoeconomics and Outcome Research (ISPOR) Principles of Good Practice for the Translation and Cultural Adaptation of Patient‑Reported Outcomes Measures and included forward and back translation, cognitive debriefing, and harmonisation between the Spanish and Catalan versions. Face validity was assessed in a sample of Spanish- and Catalan-speaking health professionals.

Results: In the cognitive debriefing, 9 patients with CKD (4 in Catalan and 5 in Spanish) participated. Fourteen healthcare professionals (2 nurses and 12 nephrologists) assessed the face validity of the Catalan and Spanish versions. Overall, the language used in the original version of the questionnaire did not cause substantial problems for translation into Catalan or Spanish. Patients generally found the questionnaire to be relevant and relatively easy to complete but reported some difficulties with questionnaire design, including the use of 'skip' questions. Clinicians and nurses highly rated the questionnaire in terms of relevance (mean score of 8.7 on a 0-10 scale) and acceptability, indicating good face validity, but considered some elements to be lacking, such as the absence of an open-ended question or any queries regarding lifestyle.

Conclusions: It was feasible to produce culturally adapted Spanish and Catalan versions of the Kidney PREM questionnaire, and they showed acceptable face validity. They will be useful tools for furthering research and clinical practice in CKD patients in Spain.

Background: MUC1 and UMOD pathogenic variants cause autosomal dominant tubulointerstitial kidney disease (ADTKD). MUC1 is expressed in kidney, nasal mucosa and respiratory tract, while UMOD is expressed only in kidney. Due to haplo-insufficiency ADTKD-MUC1 patients produce approximately 50% of normal mucin-1.

Methods: To determine whether decreased mucin-1 production was associated with an increased COVID-19 risk, we sent a survey to members of an ADTKD registry in September 2021, after the initial, severe wave of COVID-19. We linked results to previously obtained ADTKD genotype and plasma CA15-3 (mucin-1) levels and created a longitudinal registry of COVID-19 related deaths.

Results: Surveys were emailed to 637 individuals, with responses from 89 ADTKD-MUC1 and 132 ADTKD-UMOD individuals. 19/83 (23%) ADTKD-MUC1 survey respondents reported a prior COVID-19 infection vs. 14/125 (11%) ADTKD-UMOD respondents (odds ratio (OR) 2.35 (95%CI 1.60-3.11, P = 0.0260). Including additional familial cases reported from survey respondents, 10/41 (24%) ADTKD-MUC1 individuals died of COVID-19 vs. 1/30 (3%) with ADTKD-UMOD, with OR 9.21 (95%CI 1.22-69.32), P = 0.03. The mean plasma mucin-1 level prior to infection in 14 infected and 27 uninfected ADTKD-MUC1 individuals was 7.06 ± 4.12 vs. 10.21 ± 4.02 U/mL (P = 0.035). Over three years duration, our longitudinal registry identified 19 COVID-19 deaths in 360 ADTKD-MUC1 individuals (5%) vs. 3 deaths in 478 ADTKD-UMOD individuals (0.6%) (P = 0.0007). Multivariate logistic regression revealed the following odds ratios (95% confidence interval) for COVID-19 deaths: ADTKD-MUC1 8.4 (2.9-29.5), kidney transplant 5.5 (1.6-9.1), body mass index (kg/m²) 1.1 (1.0-1.2), age (y) 1.04 (1.0-1.1).

Conclusions: Individuals with ADTKD-MUC1 are at an eight-fold increased risk of COVID-19 mortality vs. ADTKD-UMOD individuals. Haplo-insufficient production of mucin-1 may be responsible.

Background: Recently, the incidence of caffeine intoxication has been on an upward trend, with severe outcomes. However, acute kidney injury (AKI) resulting from renal pathologies secondary to caffeine intoxication is rare, and the pathophysiological mechanisms underlying AKI are unclear.

Case presentation: A female patient in her 20s ingested an over-the-counter drug containing caffeine. The patient was diagnosed with secondary non oliguric AKI caused by acute intoxication due to ingestion of a lethal dose of caffeine. On day 19 of hospitalization, a renal biopsy was performed to determine the etiology of her prolonged renal dysfunction. Light microscopy revealed normal glomeruli, mild inflammatory cell infiltration, and acute tubular damage. Myoglobin staining was positive within the tubules, with scattered myoglobin columns. Electron microscopy revealed loss of glomerular epithelial foot processes and inflated tubular mitochondria. After undergoing hemodialysis and continuous hemodiafiltration, the patient's overall condition stabilized. After a consultation with a psychiatrist, on her 34th day of hospitalization, she was discharged home.

Conclusions: Caffeine antagonizes adenosine receptors, stimulates ryanodine receptors, and elevates catecholamines. The onset of AKI is hypothesized to result from a combination of these mechanisms, resulting in tubular ischemia and injury, as well as renal artery constriction. The development of AKI was thought to be caused by the following factors: (1) disruption of the tubular oxygen supply-demand ratio and consequent ischemia due to adenosine receptor antagonism by caffeine, (2) tubular damage due to rhabdomyolysis and consequent ryanodine receptor stimulation, and (3) increased catecholamine levels and consequent renal artery constriction.

Maintaining optimal fluid balance is crucial for patients with end-stage renal disease on dialysis, as both fluid overload and excess removal can lead to poor outcomes. Traditional approaches such as physical exam and chest X-ray have limitations when assessing volume status. This review carefully examines the tools that provide more precise options, including lung ultrasound, echocardiography, Venous Excess Ultrasound (VEXUS), bioimpedance analysis (BIA), and passive leg raise (PLR). We discuss the principles, supporting evidence, and practical uses of these techniques differentiating between static and dynamic methods to evaluate ultrafiltration tolerance. By integrating these modern techniques with clinical judgment, nephrologists can optimize fluid management in dialysis patients. While these tools show promise, further research is needed to establish standardized protocols and evaluate their impact on patient-centered outcomes.

Background: The disability of patients with end-stage kidney disease (ESKD) and the possibility of reducing the ability to work for patients who are receiving hemodialysis require extensive investigations worldwide. In this regard, we aimed to investigate employment status and its effect on a large group of work ability-related factors in these patients.

Methods: A total of 191 patients with ESKD who were referred to the dialysis department of Guilan Educational and Medical Centers, Rasht, Iran, in 2023 participated. The demographic and occupational data, clinical characteristics, and laboratory findings of the patients were recorded. A work ability index questionnaire was used to record the ability to work.

Results: According to the results, 37.7% of people undergoing hemodialysis were employed, 45.4% of those who were not employed, lost their jobs before, and 54.6% lost their jobs after starting hemodialysis. Patients with lower values of work ability index found to be significantly older, illiterate, with lower job satisfaction and high frequency of absence from their job. Also, they were unemployed individuals with high rates of disability and no history of job change (P < 0.05 for all). Additionally, current unemployment, history of job changes, and packed red blood cell transfusion were predictive variables of the ability to work in hemodialysis patients (P < 0.001, P = 0.046, P = 0.046).

Conclusions: Our results illustrated that the employment rate is low among patients with ESKD even before starting hemodialysis. Patients with higher age, less education, disability and anemia are at higher risk of weak ability to work.

Background: The relationship between serum klotho level and albuminuria is unknown in middle-aged and elderly participants without diabetes mellitus (DM). Therefore, we will investigate the association between serum klotho level and albuminuria in middle-aged and elderly participants without DM.

Methods: Participants (aged 40-79) were from the five continuous cycles (2007-2016) of the National Health and Nutrition Examination Survey (NHANES). Multiple logistic regression was performed to investigate the association between serum klotho level and albuminuria.

Results: 9217 participants were included in the present study. 47.6% of the participants were male. The average age of the overall participants was 56.3 years (40-79 years). Overall, 823 participants with albuminuria were identified. After adjusted confounders (age, gender, marital status, ethnicity, family income to poverty ratio, education, body mass index, smoke, charlson comorbidity index, hypertension, hyperlipidemia, angiotensin converting enzyme inhibitor/angiotonin receptor blocker, and estimated glomerular filtration rate), participants with a high serum klotho level had a decreased risk for albuminuria. Compared with the lowest serum klotho level (Tertile 1), participants in Tertile 2 (odds ratio [OR] 0.83, 95% CI 0.70-0.99, P = 0.044) and Tertile 3 (OR 0.76, 95% CI 0.63-0.91, P = 0.003) had a lower risk of albuminuria (P for trend = 0.002). The stratified analysis showed that serum klotho level was still negatively associated with albuminuria in the subgroups, and statistically significant interactions were not observed in the subgroups (all P values for interactions > 0.05, except for the hypertension subgroup).

Conclusions: In middle-aged and elderly participants without DM, a high serum klotho level is associated with a decreased risk of albuminuria. In the future, the mechanism of the interaction between klotho and albuminuria needs to be elucidated to find new treatment targets for individuals without DM who suffer from albuminuria.