Renal Failure最新文献

As a pattern recognition receptor, Toll-like receptor 4 (TLR4) is crucial for the development and progression of acute kidney injury (AKI). This study aims to explore whether the deubiquitinase Usp9x influences the TLR4/NF-B pathway to cause sepsis-induced acute kidney injury (S-AKI). The model of AKI was established in Sprague-Dawley rats using the cecal ligation and puncture (CLP) method, while renal tubular epithelial cell NRK-52E was stimulated with lipopolysaccharide (LPS) in vitro. All plasmids were transfected into NRK-52E cells according to the indicated group. The deubiquitinase of TLR4 was predicted by the online prediction software Ubibrowser. Subsequently, Western blot and Pearson correlation analysis identified Usp9x protein as a potential candidate. Co-IP analysis verified the interaction between TLR4 and Usp9x. Further research revealed that overexpression of Usp9x inhibited degradation of TLR4 protein by downregulating its ubiquitination modification levels. Both in vivo and in vitro experiments observed that interference with Usp9x effectively alleviated the inflammatory response and apoptosis of renal tubular epithelial cells (RTECs) induced by CLP or LPS, whereas overexpression of TLR4 reversed this situation. Transfection with sh-Usp9x in NRK-52E cells suppressed the expression of proteins associated with the TLR4/NF-κB pathway induced by LPS. Moreover, the overexpression of TLR4 reversed the effect of sh-Usp9x transfection. Therefore, the deubiquitinase Usp9x interacts with TLR4, leading to the upregulation of its expression through deubiquitination modification, and the activation of the TLR4/NF-κB signaling pathway, thereby promoting inflammation and apoptosis in renal tubular epithelial cells and contributing to sepsis-induced acute kidney injury.

Background: While renal biopsy remains the preferred diagnostic method for assessing proteinuria, hematuria, or renal failure, laparoscopic renal biopsy (LRB) can serve as an alternative for high-risk patients when percutaneous kidney biopsy (PKB) is not recommended. This study was aimed to evaluate the safety of LRB.

Methods: In study 1, Fourteen patients from January 2021 to January 2023 had a LRB taken for various indications, such as morbid obesity, abnormal kidney construction, uncontrolled hypertension, and coagulopathy. We also conducted a Meta-analysis of the success rate and complication rate of previous LRB in study 2.

Results: All the patients completed biopsies and adequate renal tissues were obtained. The success rate was 100%. The median number of glomeruli obtained was 22.5 (range:12.0, 45.0). The complication rate was 7.1% (urinary tract infection). There were no significant differences between levels of hemoglobin, serum creatinine, and urinary NAGL before and after surgery. In the meta-analysis, the success rate of operation, satisfactory rate of sample, and complication rate of surgery were 99.9%, 99.1%, and 2.6% respectively.

Conclusion: LRB can achieve a good success rate and specimen retrieval and does not increase the risk of complications for high-risk patients. It can present as one of the alternative methods for patients with glomerular diseases.

Background: The association between proteinuria levels and cardiovascular disease (CVD) development and all-cause mortality in chronic kidney disease (CKD) patients remains controversial.

Methods: In this investigation, we conducted a retrospective analysis involving 1138 patients who were registered in the CKD-Research of Outcomes in Treatment and Epidemiology (ROUTE) study. The primary outcome of this study was the composite of cardiovascular events or all-cause death. Cox proportional hazards regression, smooth curve fitting, piecewise linear regression, and subgroup analyses were used.

Results: The mean age of the included individuals was 67.3 ± 13.6 years old. Adjusted hazard ratios (HRs) for UPCR in middle and high groups, compared to the low group, were 1.93 (95% CI: 1.28-2.91) and 4.12 (95% CI: 2.87-5.92), respectively, after multivariable adjustment. Further adjustments maintained significant associations; HRs for middle and high groups were 1.71 (95% CI: 1.12-2.61) and 3.07 (95% CI: 2.08-4.54). A nonlinear UPCR-primary outcome relationship was observed, with an inflection point at 3.93 g/gCr.

Conclusion: Among non-dialyzed patients with stage G2-G5 CKD, a nonlinear association between UPCR and the primary outcome was observed. A higher UPCR (when UPCR < 3.93 g/gCr) was an independent predictor of the primary outcome. Importantly, our study predates SGLT2 inhibitor use, showcasing outcomes achievable without these medications. Future research considerations will involve factors like SGLT-2 inhibitor utilization.

Background: This study aims to undertake a comprehensive assessment of the effectiveness and safety profile of Mahuang Fuzi and Shenzhuo Decoction (MFSD) in the management of primary membranous nephropathy (PMN), within the context of a prospective clinical investigation.

Methods: A multicenter, open-label clinical trial was executed on patients diagnosed with PMN. These individuals were subjected to MFSD therapy for a duration of at least 24 months, with primary outcome of clinical remission rates. The Cox regression analysis was employed to discern the pertinent risk factors exerting influence on the efficacy of MFSD treatment, with scrupulous monitoring of any adverse events.

Results: The study comprised 198 participants in total. Following 24 months of treatment, the remission rate was 58.6% (116/198). Among the subgroup of 130 participants subjected to a 36-month follow-up, the remission rate reached 70% (91/130). Subgroup analysis revealed that neither a history of immunosuppressive therapy (HIST) nor an age threshold of ≥60 years exhibited a statistically significant impact on the remission rate at the 24-month mark (p > .05). Multivariate Cox regression analyses elucidated HIST, nephrotic syndrome, or mass proteinuria, and a high-risk classification as noteworthy risk factors in the context of MFSD treatment. Remarkably, no fatalities resulting from side effects were documented throughout the study's duration.

Conclusions: This trial establishes the efficacy of MFSD as a treatment modality for membranous nephropathy. MFSD demonstrates a favorable side effect profile, and remission rates are consistent across patients, irrespective of HIST and age categories.

Nickel (Ni) is a common metal with a nephrotoxic effect, damaging the kidneys. This study investigated the mechanism by which gallic acid (GA) protects mice kidneys against renal damage induced by Nickel oxide nanoparticles (NiO-NPs). Forty male Swiss albino mice were randomly assigned into four groups, each consisting of ten mice (n = 10/group): Group I the control group, received no treatment; Group II, the GA group, was administrated GA at a dosage of 110 mg/kg/day body weight; Group III, the NiO-NPs group, received injection of NiO-NPs at a concentration of 20 mg/kg body weight for 10 consecutive days; Group IV, the GA + NiO-NPs group, underwent treatment with both GA and NiO-NPs. The results showed a significant increase in serum biochemical markers and a reduction in antioxidant activities. Moreover, levels of 8-hydroxy-2'-deoxyguanosine (8-OH-dG), phosphorylated nuclear factor kappa B (p65), and protein carbonyl (PC) were significantly elevated in group III compared with group I. Furthermore, the western blot analysis revealed significant high NF-κB p65 expression, immunohistochemistry of the NF-κB and caspase-1 expression levels were significantly increased in group III compared to group I. Additionally, the histopathological inspection of the kidney in group III exhibited a substantial increase in extensive necrosis features compared with group I. In contrast, the concomitant coadministration of GA and NiO-NPs in group IV showed significant biochemical, antioxidant activities, immunohistochemical and histopathological improvements compared with group III. Gallic acid has a protective role against kidney dysfunction and renal damage in Ni-nanoparticle toxicity.

Background: Patients receiving maintenance hemodialysis (MHD) frequently encounter a drop in blood pressure during dialysis, known as intradialytic hypotension (IDH). The AIP is associated with diseases such as diabetes and cardiovascular events. It remains unclear whether the AIP is associated with IDH. The present study aimed to explore the association between AIP and IDH in MHD patients.

Methods: In this multi-center cross-sectional study, we included 1946 adult hemodialysis patients from twenty dialysis centers. Patients were divided into four groups based on the AIP quartiles. Linear regression and multiple logistic regression models were used to analyze the relationship between AIP and IDH. Subgroup analyses were further conducted to assess the robustness of the association between the AIP and IDH.

Results: After adjusting for potential confounding variables, each 1-unit increase in AIP was associated with a 21% increase in the odds of IDH. The odds ratios (ORs) of IDH increased gradually with higher quartiles of AIP compared with the Q1 reference group (Q2: OR, 1.41, 95% CI: 0.91-2.18; Q3: OR, 1.63, 95% CI: 1.07-2.49; Q4: OR, 1.57, 95% CI: 1.01-2.42). No interaction was observed in the subgroup analysis stratified by age, sex, history of diabetes, heart failure, and myocardial infarction.

Conclusion: Elevated AIP levels are associated with a heightened risk of IDH in MHD patients.

To determine the relationship of hemodialysis access with vital sign variability and hemodialysis-related headache (HRH). Adult outpatients receiving maintenance hemodialysis (MHD) were prospectively recruited, and 12 consecutive dialysis sessions were monitored. Intradialysis (hour-to-hour) and interdialysis (dialysis day-to-day) vital sign variabilities were assessed via three metrics: the difference between the maximum and minimum values, average real variability (ARV), and residuals. Multivariate logistic regression analysis was used to explore the factors triggering HRH. A total of 91 Chinese MHD patients (60.4% male) aged 58.5 ± 17.2 years were included, with 59 patients using radiocephalic arteriovenous fistulas (RCAVFs) and 32 patients using tunneled cuffed catheters (TCCs) for dialysis. The median dialysis vintage was 26.8 (12.0-44.7) months. Compared with the RCAVF group, the TCC group had significantly greater urea reduction (71.1 ± 9.3% vs. 61.7 ± 10.5%, p < 0.001) and clearance (1.5 (1.2-1.8) vs. 1.1 (1.0-1.4), p < 0.001) rates, higher intradialysis pulse variability and lower intradialysis diastolic blood pressure variability. Some of interdialysis variability indexes in pulse, systolic blood pressure (SBP), and SpO2 were significantly greater in the TCC group than that in the RCAVF group. Age (OR = 0.880, 95% CI = 0.785-0.986, p = 0.028), TCC use (OR = 22.257, 95% CI = 1.190-416.399, p = 0.038), intradialysis SBP-ARV (OR = 2.768, 95% CI = 1.069-7.171, p = 0.036), and blood sodium level (OR = 0.400, 95% CI = 0.192-0.832, p = 0.014) were shown to be independent risk factors for HRH. In conclusion, the use of TCCs has multifaceted effects on intradialysis and interdialysis vital sign variabilities and is independently associated with an increased risk of HRH.

Objective: The incidence of acute kidney injury (AKI) in pediatric patients has been increasing over the years, and AKI significantly impacts children's health and quality of life. This article reviews the current epidemiological research on pediatric AKI.

Methods: The clinical data of hospitalized children aged 0 to 14 years from 20 different hospitals in Hunan Province, China, collected from December 2017 to February 2018, were analyzed. The incidence rate, misdiagnosis rate, main causes, and medical costs of AKI in hospitalized children were examined.

Results: A total of 29,639 patients were included, with an AKI incidence rate of 4.34% (1286/29,639). Among the 1286 AKI patients, 863 (67.11%) were classified as AKI stage 1324 (25.19%) as AKI stage 2, and 99 (7.7%) as AKI stage 3. AKI patients had significantly longer hospital stays [6.0 (4.0, 10) days vs. 6.0 (4.0, 8.0) days, p < 0.001] and higher hospitalization costs [3375.22 (1600, 6083.83) yuan vs. 2729.4 (1659.45, 8216.65) yuan, p = 0.003] than non-AKI patients. The mortality rate (1.2% vs. 0.1%, p < 0.001), intensive care unit (ICU) transfer rate (8.7% vs. 5.97%, p < 0.001), and use of invasive mechanical ventilation (3.6% vs. 1%, p < 0.001) were significantly greater in patients with AKI than in those without AKI patients. The etiology of AKI varied among different age groups, and dehydration, diarrhea, and shock were the main causes of pre-renal AKI.

Conclusion: The incidence and missed diagnosis rates of AKI in hospitalized children were high. AKI prolongs hospital stays, increases hospitalization costs, and increases the risk of mortality in children.

Background: Chronic kidney disease-associated pruritus (CKD-ap) is a common complication that negatively affects the quality of life. Difelikefalin has emerged as a novel FDA-approved drug to manage CKD-ap. This systematic review and meta-analysis will assess the efficacy and safety of Difelikefalin versus placebo to manage CKD-ap.

Methods: PubMed, Scopus, WOS, Central, and Embase were systematically searched until November 2023. RevMan was used to perform meta-analysis. Quality assessment was conducted using the Cochrane RoB 2.0 tool. Results were reported as risk ratio (RR) and mean difference (MD) with a 95% confidence interval (CI). PROSPERO ID: (CRD42023485979).

Results: Five RCTs with a total of 896 participants were included. Difelikefalin significantly decreased the weekly mean WI-NRS score (MD: -0.99 [-1.22, -0.75], p ˂ .00001), 5-D itch scale total score (MD: -1.51 [-2.26, -0.76], p > .0001), and Skindex-10 total score (MD: -7.39 [-12.51, -2.28], p = .005), but showed significantly higher adverse events (RR: 1.26 [1.03, 1.55], p = .03), versus placebo. However, there was no significant difference between both groups in serious adverse events (RR: 1.42 [0.78, 2.57], p = .25) or death (RR: 0.81 [0.19, 3.34], p = .77).

Conclusion: Difelikefalin appears to be a promising agent for the management of CKD-induced pruritus in patients with end-stage renal disease. However, evidence is still underpowered due to the paucity of the current data; therefore, more robust RCTs are required to confirm the benefit of Difelikefalin.

Background: Citrate dialysate (CD) has been successfully used in conventional hemodialysis and continuous renal replacement therapy; however, no study has compared pre- and post-dilution online hemodiafiltration (oL-HDF). Therefore, we aimed to investigate the efficacy of citrate anticoagulation for oL-HDF and the metabolic changes and quality of life of patients on hemodialysis treated using both modes.

Method: Eight dialysis patients were treated with CD containing 0.8 mmol of citric acid for 4 weeks in each phase. Visual clotting scores were investigated as the primary endpoints. Adequacy of dialysis, laboratory parameters, and quality of life were measured as secondary objectives.

Results: The mean clotting scores in the pre-dilution mode were significantly lower than those in the post-dilution mode and in all phases except the heparin-free phase (p < 0.001 in the baseline phase, p = 0.001 in phase 1, and p = 0.023 in phase 2). The values of Kt/V in both modalities were comparable except during the baseline phase, in which the values of pre-dilution were significantly greater than post-dilution (2.36 ± 0.52/week vs. 1.87 ± 0.33/week;95% CI -0.81 to -0.19, p = 0.002). The patient's quality of life regarding their physical activity level was significantly higher in the post-dilution mode than in the pre-dilution mode at baseline and in phase 1 (p = 0.014 and 0.004 at baseline and in phase 1, respectively). Metabolic changes did not differ between the two modes.

Conclusion: Citrate dialysate decreased or prevented anticoagulation in both pre- and post-dilution modes of oL-HDF without significant side effects and had comparable adequacy of dialysis.